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NBS SPECIAL PUBLICATION 601

U.S. DEPARTMENT OF COMMERCE / National Bureau of Standards

National Bureau of Standards

Library, E-01 Admin. Bldg.

OCT 1 1981

131093

/CO

QC

100

U57

no . 601

1981

V. ?

Implant Retrieval:

Material and Biological Analysis
NATIONAL BUREAU OF STANDARDS

The National Bureau of Standards' was established by an act of Congress on March 3, 1901. The Bureau's overall goal is to strengthen and advance the Nation's science and technology

and facilitate their effective application for public benefit. To this end, the Bureau conducts

research and provides: (1) a basis for the Nation's physical measurement system, (2) scientific and technological services for industry and government, (3) a technical basis for equity in trade, and (4) technical services to promote public safety. The Bureau's technical work is per- formed by the National Measurement Laboratory, the National Engineering Laboratory, and

the Institute for Computer Sciences and Technology.

THE NATIONAL MEASUREMENT LABORATORY provides the national system of

physical and chemical and materials measurement; coordinates the system with measurement

systems of other nations and furnishes essential services leading to accurate and uniform

physical and chemical measurement throughout the Nation's scientific community, industry,

and commerce; conducts materials research leading to improved methods of measurement,

standards, and data on the properties of materials needed by industry, commerce, educational

institutions, and Government; provides advisory and research services to other Government

agencies; develops, produces, and distributes Standard Reference Materials; and provides

calibration services. The Laboratory consists of the following centers:

Absolute Physical Quantities2 — Radiation Research — Thermodynamics and

Molecular Science — Analytical Chemistry — Materials Science. THE NATIONAL ENGINEERING LABORATORY provides technology and technical ser- vices to the public and private sectors to address national needs and to solve national problems; conducts research in engineering and applied science in support of these efforts; builds and maintains competence in the necessary disciplines required to carry out this research and technical service; develops engineering data and measurement capabilities;

provides engineering measurement traceability services; develops test methods and proposes

engineering standards and code changes; develops and proposes new engineering practices;

and develops and improves mechanisms to transfer results of its research to the ultimate user. The Laboratory consists of the following centers:

Applied Mathematics — Electronics and Electrical Engineering2 — Mechanical

Engineering and Process Technology2 — Building Technology — Fire Research —

Consumer Product Technology — Field Methods.

THE INSTITUTE FOR COMPUTER SCIENCES AND TECHNOLOGY conducts

research and provides scientific and technical services to aid Federal agencies in the selection, acquisition, application, and use of computer technology to improve effectiveness and

economy in Government operations in accordance with Public Law 89-306 (40 U.S.C. 759), relevant Executive Orders, and other directives; carries out this mission by managing the Federal Information Processing Standards Program, developing Federal ADP standards

guidelines, and managing Federal participation in ADP voluntary standardization activities; provides scientific and technological advisory services and assistance to Federal agencies; and

provides the technical foundation for computer-related policies o! the Federal Government.

The Institute consists of the following centers:

Programming Science and Technology — Computer Systems Engineering.

'Headquarters and Laboratories at Gaithersburg, MD, unless otherwise noted; mailing address Washington, DC 20234.

! Some divisions within the center are located at Boulder, CO 80303.
Implant Retrieval: Material and Biological Analysis

Proceedings of a Conference

Held at the National Bureau of Standards,

Gaithersburg, MD 20234, May 1-3, 1980

Editors:

Allan Weinstein

Tulane University

New Orleans, LA 70118

Donald Gibbons

Case Western Reserve University

Cleveland, OH 44106

Stanley Brown

University of California, Davis

Davis, CA 95616

William Ruff

National Bureau of Standards

Washington, DC 20234

National Bureau of Standard;

Library, E-01 Admin. Bldg.

MAR 3 0 1981

QOoo

Lite

Sponsored by:

National Bureau of Standards Food and Drug Administration

National Heart, Lung and Blood Institute National Institute for Arthritis, Metabolism and Digestive Diseases National Institute for Handicapped Research

Veterans Administration American Society for Testing and Materials

Si

U.S. DEPARTMENT OF COMMERCE, Philip M. Klutznick, Secretary

Jordan J. Baruch, Assistant Secretary for Productivity, Technology and Innovation

U NATIONAL BUREAU OF STANDARDS, Ernest Ambler, Director

Issued January 1981
Library of Congress Catalog Card Number: 80-600194

National Bureau of Standards Special Publication 601

Nat. Bur. Stand. (U.S.), Spec. Publ. 601, 772 pages (Jan. 1981) CODEN: XNBSAV

U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON: 1981

For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402

Price $12.

(Add 25 percent for other than U.S. mailing)
Foreword

Four years ago a symposium on retrieval and analysis of

implants was held at the National Bureau of Standards. That

symposium dealt exclusively with orthopaedic implants and was designed to bring together manufacturers, orthopaedic surgeons,

engineers and others interested in understanding and improving

the performance of orthopaedic implants. This second symposium

was developed with the same basic purpose but has been broadened

in scope to include cardiovascular as well as orthopaedic

implants. It is envisaged tha + the experiences of the one

clinical specialty can be translated to the other. The program

of this symposium deals mainly with the experience that has

been gained in understanding the performance of implants by

studying devices that have been removed from patients. However,

basic concepts and testing methods have also been included.

Their importance cannot be overs tressed in improving our understanding of host-implant interactions. The basic issue

to be addressed is still: "this is what happens, so let's try

to understand how and why." The benefits to be derived from

the evaluation of the performance of retrieved implants were

succinctly stated by Dr. Victor Frankel five years ago and they

are still true today: "The more reliable implant appliances can

be made, the greater security and safety the patient will

experience." Only through the study of retrieved implants will

it be possible to obtain the critical information that will

make devices more reliable.

Al lan Weinstein

Donald Gibbons

Stanl ey Brown

William Ruff

September 1 980

i i i
Preface

This publication contains the proceedings of a Conference

on Implant Retrieval: Material and Biological Analysis held at

the National Bureau of Standards, Gaithersburg, Maryland, on May 1 and 2, 1980. It also contains a summary of a workshop

held the following day in Washington, DC on the subject of

Implant Retrieval Programs in current use. The conference and

the workshop were sponsored by seven Federal agencies and groups:

The National Bureau of Standards; The Food and Drug Administration;

the National Institute for Arthritis, Metabolism and Digestive

Diseases; the National Heart, Lung and Blood Institute; the

Veterans Administration; the National Institute for Handicapped

Research; and the American Society for Testing and Materials.

The meeting was designed to bring together scientists and engineers

manufacturers, Federal Government representatives and others

concerned over the proper design and application of orthopaedic

and cardiovascular implants. The objective of the meeting was

to review the state-of-the-art in material and biological analysis

associated with implant retrieval. Topics considered at the

meeting included practices for obtaining and evaluating data

concerning implant retrieval as well as discussions of advances

in material and biological science relevant to implant retrieval.

The Conference was organized by a steering committee consisting

of A. Weinstein, Tulane University, Conference Chairman; J. Black,

University of Pennsylvania; P. Brown, ASTM; S. Brown, University of

Cal i form' a- Davis; R. Cohen, National Consumer League; A. Fraker,

NBS; D. Gibbons, Case Western Reserve University; S. Gordon, NIAMDD;

P. Laing, ASTM-F4; B. Morrissey, NBS; V. Nickel, VA; F. Pitlick,

NHLBI; W. Ruff, NBS; R. Stromberg, FDA; J. Traub, NIHR. The

Committee also acknowledges the very capable assistance of the

Conference arrangements staff at NBS, in particular Joanne Lorden

and Kathy Stang for their help in carrying out this meeting, as well as substantial contributions of typing and editing work on the part of Joan Marshall and the NML text editing staff.

i v
Abstract

This book contains the proceedings of a conference on implant retrieval and analysis as well as a report on a workshop concerned with implant retrieval systems.

Twenty-six invited papers that were presented at the

conference are included. Four subject areas are specifically

addressed: bulk phenomena, release phenomena, interface

phenomena, and information utilization. Implants of both

orthopaedic type and cardiovascular type were considered at

the conference. Data on the failure modes of implants were

presented. Specific consideration of biocompatability

problems was included. Several operating data/information

systems were described in detail. Recommendations were

made in the workshop concerned with uniformity and standardization of information systems dealing with implant retrieval

data.

Keywords: Analysis; biological; cardiovascular; implants;

metals; orthopaedic; polymers; retrieval.

Disclaimer

Certain trade names and company products are identified in

order to adequately specify the experimental procedure. In no case does such identification imply recommendation or endorsement

by the National Bureau of Standards, nor does it imply that the

products are necessarily the best available for the purpose.

Views expressed by the various authors are their own and do not

necessarily represent those of the National Bureau of Standards.

v
WELCOME

I am pleased to have this opportunity to welcome all of you to

the National Bureau of Standards and to this Conference on Implant

Retrieval: Material and Biological Analysis. As many of you may

recall, NBS also acted as host for the first Conference on Implant

Retrieval about four years ago. It is particularly pleasing to have

that opportunity again and to be able to learn of the growth and

developments in this important field.

This Conference is sponsored by a number of Federal agencies

and organizations. In addition to NBS these include the Bureau of

Medical Devices of the FDA, the Veterans Administration, the National

Institute of Handicapped Research, the National Heart, Lung and Blood

Institute, the National Institute of Arthritis, Metabolism and

Digestive Diseases and the American Society for Testing and Materials.

The potential importance of the work to be presented here can be

demonstrated in part through the recognition by these sponsoring

groups of the need for this conference. The Federal Government

investment in health-related activities is of course very large.

All of the agencies sponsoring this Conference are involved in

important aspects of those activities. The findings reported here

along with the conclusions you will reach will become an important

input to the plans and activities of these agencies and to the

entire effort directed toward safe and effective synthetic implants. >

I would like to briefly mention some of the involvements that

NBS has in its program concerning synthetic implants. Our contributions basically involve measurement methods, standards, and needed

data on materials used- in implant devices. This information will

become the central basis for improved performance and reliability

of implant devices. It will be used by implant manufacturers and

surgeons, and will benefit the public in many ways. It is our understanding that the lack of comprehensive and acceptable standards

for implants is one of the most significant barriers to progress in

this field. This is the area where contributions from NBS may form

a particularly useful response to the overall need.

The subject for these next two days will be implant retrieval

analysis. We all hope to hear of new techniques and new information

that have resulted from recent research efforts and studies of

retrieved devices. Clearly a unique opportunity is presented by

modern techniques of implant retrieval. Fundamentally this involves

the ability to learn of the performance and durability of implant

devices in actual service. This information can be one of the most

significant inputs to the further development of safe and effective

implants

.

vi
I am pleased that NBS has been instrumental in gathering

together the experts in physical and medical science that are involved in this conference. We have always regarded this

field of endeavor as a high scientific challenge with even

higher rewards in terms of human needs. You have my best wishes

for a very successful Conference.

John D. Hoffman

Director

National Measurements Laboratory

National Bureau of Standards

vii
WELCOME

I would like to welcome you to this Conference on Implant

Retrieval. We are pleased to be able to join other Federal

health agencies and the National Bureau of Standards in co- sponsoring this meeting. Many of the regulatory decisions that we at the FDA must make require sound technical information.

This is true, whether we are considering a new product for

approval, developing a standard, or attempting to determine if a device on the market is unsafe.

Medical devices can, of course, be tested in laboratories.

Nevertheless, the correlation between such examinations—no

matter how well one may try to simulate in vivo conditions--

to their performance in the body is often poor and always suspect.

This meeting, at which a variety of personal expertise and

experiences will be oriented toward an understanding of the

problems associated with the use of devices in humans, is of

critical importance to our Bureau. Development of consensus regarding the methods by which data are obtained would be

important to us as well as the entire field. In other words, we need the types of information that are included in this

program, in both the cardiovascular and orthopedic areas, in

order to carry out our mission more effectively. I hope that

all of you enjoy this meeting.

Victor Zafra

Acting Director

Bureau of Medical Devices

Food and Drug Administration

v i i i
CONTENTS

BULK PHENOMENA

The In- Vivo Performance of Polyethylene Components of Total

Joint Replacements

R. M. Rose, A. N. Crugnola, W. R. Cimino and M. D. Ries

A Biological and Structural Evaluation of Retrieved Dacron

Arterial Prostheses

R. Guidoin, M. King, P. Blais, M. Marois, C. Gosselin,

P. Roy, R. Courbier, M. David and H. P. Noel

Clinical, Hi sto-morphological and Material Related Observations on Removed Alumina- Ceramic Hip Joint Components

W. Plitz and P. Griss

Microscopic Analysis of Retrieved Polymethylmethacrylate

(PMMA) Bone Cement

D. F. Gibbons and K. A. Buran

Prosthetic Heart Valves: What Have We Learned From Our

Clinical Pathologic Experience

A. P. Yoganathan and E. C. Harrison

Examination of Orthopaedic Implant Failures

L. M. Taussig

A Study of Inclusions in Stainless Steel Implants and

Their Effect on Corrosion

R. Wilkinson and M. T. Shepherd

RELEASE PHENOMENA

Tissue Response to Wear Debris in Artificial Joints

H. G. Willert, G. Buchhorn and U. Buchhorn

Materials Degeneration Causing Late Failure of

Mechanical Heart Valve Prostheses: Problems and Promise

F. J. Schoen, J. L. Titus and G. M. Lawrie

Prosthetic Valve Wear Products — Embolization and

Systemic Presentation

J. M. Anderson, S. Barenberg and A. Hiltner

Metal Allergy and Metallurgy

S. A. Brown and K. Merritt

Techniques for the Examination of Tissues in Implant

Retrieval Analysis

D. F. Williams, A. McNamara and G. C. F. Clark

ix
INTERFACE PHENOMENA

Retrieval Analysis of Calcific Degeneration of Prosthetic

Tissue Valves: The Role of Vitamin K- Dependent Processes

and Other Regulatory Mechanisms

R. J. Levy, S. P. Sanders and J. B. Lian

Prosthesis - Related Infections

P. J. Parks

Study of 208 Explanted Bioprostheses : Distribution of

Dysfunction Patterns and Assessment of Durability at

1 0 Years of Use

R. C. Quijano

Retrieved Fracture Plates: Implant and Tissue Analysis

J. P. Simpson, V. Geret, S. A. Brown and K. Merritt

Corrosion, Materials Characteristics and Local Tissue

Reaction Associated with Osteosynthesis Devices

H. Skinner, A. M. Weinstein, A. J. T. Clemow,

M. McPhil 1 i ps-Meade, J. J. Klawitter, and G. French

The Evaluation of Explanted Umbilical Vein Grafts

S. Weinberg

Wear of Polymeric Prosthesis - Clinical Reality,

Retrieved Implants and Laboratory Predictions

I. C. Clarke

INFORMATION UTILIZATION

Considerations Concerning International Standards

for Accumulating and Reporting of Implant Experience

with Cardiac Pacemakers

R. C. Flink and W. Malette

An Analysis of 130 Removed Total Hips and Knees

R. Y. Hori, J. L. Lewis, R. L. Wixson

and G. M. Kramer

The Method of Implant Retrieval Analysis at the

Hospital for Special Surgery

T. M. Wright and A. H. Burstein

An Interactive Computer System for Implant Data

Retrieval /Analysis

S. D. Cook and A. M. Weinstein
A Data Retrieval System for Implant Failures

in Total Joint Replacement Surgery

D. J. Schurman, D. S. Burton, D. A. Nagel

and D. McShane

Predictions of Femoral Component Performance Through

Implant Retrieval Information

H. S. Dobbs

Legal and Regulatory Implications of Implant Retrieval

and Analysis

H. R. Piehler and L. E. Sloter, II

WORKSHOP ON IMPLANT RETRIEVAL PROGRAMS

xi

BULK PHENOMENA

THE IN-VIVO PERFORMANCE OF POLYETHYLENE

COMPONENTS OF TOTAL JOINT REPLACEMENTS

Robert M. Rose

Massachusetts Institute of Technology

Cambridge, MA 02139

Aldo N. Crugnola

University of Lowell

Lowell, MA 01854

William R. Cimino

Massachusetts Institute of Technology

Cambridge, MA 02139

Michael D. Ries

Dartmouth Medical School

Hanover, NH 03755

The polyethylene components of retrieved total joint

replacements are investigated with the scanning electron

microscope to assess the degree and causes of wear and other

deterioration in vivo . The highly variable performance of

the implants, ranging from no observable wear to disintegration of the articular surface, can be associated in some

cases with the presence of particles of acrylic cement or bone abrading the articular surface. Severe wear in the

absence of such abrasives may originate with the structure

of the polyethylene itself, and may be caused by molecular

weight degradation during processing: in such cases the

primary damage loci are fusion defects in the molded or extruded material.

1. Introduction

The magnitude of the problem posed by the wear of ultrahigh molecular weight polyethylene (UHMWPE) , a material used in total joint re- placements, has yet to be fully defined. In small volumes, wear debris

can be eliminated from the body via the lymph system. In larger amounts,

however, particles of UHMWPE wear debris are known to cause giant cell

foreign body reactions with a tendency toward scar tissue formation in

the articular capsule. [1, 2]

1 Scar tissue formation can severely reduce

joint mobility, which may result in the removal of the prosthesis; or

a strong resporptive reaction in the bone may loosen the prosthesis . [1, 2]

figures in brackets indicate the literature references at the end of

this paper.

J
Recent studies [3,4,5,6] both in vivo and in vitro , have demonstrated extreme variability in the wear of total joint prostheses. Variability is generally the greatest problem encountered when analyzing clinically failed prostheses since the physiological forces on joints are different for each patient depending on prosthesis design, patient physiognomy and activity. However, variability in the wear behavior of UHMWPE

was also observed for identical conditions in jln vitro simulations of

prostheses of similar design produced by different manufacturers. [7]

It is commonly believed that a three-body wear mechanism, involving

particles of the relatively harder polymethylmethacrylate (PMMA) cement

used to fix the prosthesis in the bone, is responsible for the catastrophic wear often observed on the polyethylene articular surface. Threebody abrasion is a problem primarily in knee prostheses. While three-body

abrasion is known to occur in hip prostheses, the geometry of the knee is more conducive to entrapping acrylic particles between the articulating

surfaces. While three-body wear is a major mode of failure, [1] recent

studies have suggested alternate mechanisms which do not involve abrasive

schemes yet which can account for the severe wear often observed in failed

prostheses. [6,8,9]

As of this date, we have examined 35 total knee prostheses and 15

total hip prostheses, all clinical retrievals, with the scanning electron

microscope. While such analysis cannot be, and is not intended to be,

exhaustive, it does provide useful insight into the mechanisms responsible for catastrophic material wear and failure of UHMWPE used in total

joint replacements.

2. Materials

Fifteen total hip and 35 total knee prostheses were obtained from the

Orthopaedics Associates Group of the Robert Breck Brigham Hospital in

Boston. The summary of the clinical information for the prostheses is

presented in tables 1 and 2. The UHMWPE articulating surfaces were ex- amined using Scanning Electron Microscopy.

3. A Note on Fabrication Techniques Used

in Total Joint Prostheses

The UHMWPE components of total joint prostheses are manufactured by

low temperature compression molding or extrusion of the powdered polymer.

The prostheses can be molded to the final shape or they can be machined

from a roughly-shaped block of polymer. This processing strategy is

necessary due to the high melt viscosity of UHMWPE. Also, it is commonly

thought that such processing minimized thermal and mechanical degradation

of the polymer. It has been found, however, that the high melt viscosity

of the polymer prevents total consolidation of the UHMWPE powder. Fusion

defects which appear as voids have been observed.

Previous scanning electron microscope studies have revealed that the

roughly-cylindrical polyethylene powder granules consist of aggregates of

smaller spherical particles. These aggregates are held together by virtue

of a network of tie chains or fibrils. When the polymer is molded at

temperatures low enough to avoid concomitant degradation of these fibrils

and of the molecular weight, the particles do not fuse completely.

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9
This produces a fusion defect as shown in figure 1.

4. Acrylic Cement and Abrasion

Scanning electron microscopy (SEM) examination of clinically-failed

total joint prostheses has revealed the presence of acrylic cement on the

UHMWPE articular surfaces. Particles becoming trapped between the articulating surfaces are ground into the surface and become embedded. The

embedded particles can be identified in various ways. Most conclusively,

X-ray fluorescence may indicate the presence of barium sulfate inclusions

which appear as white spots in the acrylic matrix. Fracture planes within

acrylic particles are also characteristic. In addition, cement particles

are usually found in an abraded region since acrylic is significantly

harder than polyethylene. A typical particle of cement embedded in the

polyethylene surface is shown in figure 2. The cement particle was identified using energy dispersive X-ray fluorescence analysis. The presence

of barium in an analyzed area yields characteristic fluorescence peaks

as shown in figure 3. A magnified view of the particle, figure 4, shows

the presence of white spots within the cement particle. These are the

barium sulfate inclusions in the acrylic.

In certain cases, particles embedded in the surface appear to be

acrylic cement yet X-ray fluorescence yields the absence of a barium

peak. One such example appears in figure 5. This is a close-up of the

particle of cement. The spherical cavities apparently were left when

incompletely-cured acrylic powder pulled out of the matrix. The questionable identity of this particle is confirmed by the clear fracture planes

shown in the general view of the particle, shown in figure 6. The identity

is again confirmed by the presence of abrasion in the material surrounding

the particle.

Acrylic cement is not the only abrasive influence found in joint replacements. In isolated cases particles of bone have been known to contribute to three-body abrasion. Such a particle is shown in figure 7, identified by strong calcium peaks in the EDAX spectrum.

Two-body abrasion is also observed to occur in joint prostheses, as asperities or defects in the femoral components of hip and knee prostheses

gouge and scrape material from the softer polyethylene surface. This

results in minor dimensional change of the polyethylene and generation of

particulate wear debris. However, given the current state-of-the-art of

surface finishing of the metal components, this process generally ceases

as the polyethylene surface smooths out and a transfer film builds up on the metal surface.

5. The Formation of Craters in UHMWPE Components

of Total Joint Replacements

When it is present at the articulating surface, debris is certainly

responsible for at least some of the observed abrasion. Cement particles

also are involved in the formation of craters. After a particle of cement

becomes embedded in the articular surface, local stresses begin to break

up and disintegrate the brittle cement. Figure 8 shows the appearance of

a particle in this stage of its lifetime. When the acrylic particle is

completely disintegrated and removed from the surface, a crater is left

I 0
behind. The resulting crater, as shown in figure 9, is typically flat-bottomed

and surrounded by abrasion.

Cement particles are not the only agency involved in crater production,

however. Craters also seem to form by a mechanism which is unrelated to the

presence of acrylic. The mechanism involves the presence of incompletelyfused UHMWPE powder granules at the articular surface. Such defects seem to

be formed during the low-temperature compression molding or extrusion operations .

Most prostheses in use presently are manufactured by the machining of

a block of UHMWPE which was compression-molded or extruded from powdered

UHMWPE. The migration of polymer chains to form fibrils between the powder

granules is responsible for the cohesion of the powder in the solid. Fibrils

bridging the gap between granules are shown in figure 10. The migration is

often impeded by the high melt viscosity of the polymer and it is often

observed that incomplete knitting of the powder granules occurs. A typically

incompletely-fused particle is shown in figure 11. The outline of the particle

is clearly visible. In addition to incompletely-fused granules, fusion defects

which are observed as voids, have also been detected. These can elevate local

stress levels by acting as stress concentrators. The tie chains, which maintain the mechanical integrity of the material, can fatigue and fracture when

exposed to these cyclical stresses. As a consequence, the powder particles

may be removed from the surface as debris. The fusion defects, therefore,

act to nucleate a process which can cause the release of debris within a local area. This mechanism can result in the formation of cracks and craters.

An example of a typical crater so formed is shown in figure 12. The floor

of the crater is dimpled. These indentations were left by the spherical

particles as they were released from the surface.

6. The Influence of Molecular Weight on Wear

The nature of the fatigue and failure mechanism indicates that several

factors may influence the catastrophic nonabrasive wear observed in the

study of clinically failed prostheses. These same factors will also effect

the length and number of intergranular fibrils. These fibrils probably re- present the highest molecular weight fraction in the polymer. Any degradation

in molecular weight will also degrade the fibrils which in turn reduces the wear resistance of the polymer.

It appears that the presence of a lower molecular weight fraction at

the surface may contribute significantly to the observed clinical wear. Figure 13 is a scanning electron micrograph of the surface of polyethylene

worn in vitro which has a molecular weight of 500,000. [9] Figure 14 shows

the articulating surface of a knee .prosthesis which was produced from UHMWPE

(molecular weight = 2 x 10^ to 6 x 10^). The severe deformation in both

surfaces is so strikingly similar that it suggests the presence of a low

molecular weight fraction on the articular surface of the polyethylene

component of the prosthesis. Such deformation was observed in several cases

of clinically failed prostheses. This fraction may have been formed by

degradation during processing through thermal, mechanical or chemical agencies.

S t
7. Conclusions and Recommendations

Scanning electron microscopic studies of the articulating surfaces

of the polyethylene components of 15 total hip and 35 total knee prostheses

revealed that catastrophic wear was caused both by the presence of acrylic

cement particles between the surfaces and by the fatigue and fracture of

molecular tie chains which maintain the mechanical integrity of the polymer.

The fatigue and failure of the tie chains is accelerated by fusion defects

in the material and is responsible for the formation of craters and cracks

which have been observed on severely worn clinically failed prostheses. While

the fusion defects seem to result from the high melt viscosity and the low

temperatures required to mold the UHMWPE, they are at present virtually

impossible to avoid.

Severe deformation observed in clinical failures suggests the presence

of a low molecular weight fraction at the articulating surface. It is assumed

that this fraction was formed by the degradation of UHMWPE, possibly during

forming operations. The degradation of the molecular weight of the polymer

at the surface may be difficult to avoid using present methods of manufacture.

The clinically failed prostheses used in this study were well preserved,

however dried serum on the surfaces often presented problems. Serum can coat

the prosthesis making microscopic wear studies difficult. Dried serum which

adheres to the prosthesis is extremely difficult to remove using conventional

solvents (e.g., isopropyl alcohol, acetone or alkyli) and cleaning apparatus

(e.g., ultrasonic cleaning). While the greatest success in removing the serum

was with acetone, this presents a problem since it is also a solvent for acryli<

cement. Consequently, prostheses which are cleaned with acetone will not be

expected to have acrylic particles embedded in the surface. This problem

would be alleviated if clinical failures which are to be analyzed in wear

studies were cleaned in saline or alkaline solutions immediately after

surgical removal.

We wish to acknowledge several sources of support for this work:

the Howmedica Corporation, via a grant-in-aid to M.I.T.; the National

Institutes of Health via Biomedical Research Support Grant NIH-5-507-RRO7047-

13; and the Hughes Scholarship which supported W. R. Cimino during part of

this research.

The gracious cooperation of the Orthopaedics Associates Group at the

Robert Breck Brigham Hospital in Boston, MA in providing the failed implants

is acknowledged, with gratitude and the hope that our labors will ultimately

lessen the availability of such material.

I 2
References

Willert, H.G., Reactions of the Articular Capsule to Plastic and

Metallic Wear Products from Joint Endoprostheses, Sulzer Technical

Review, 2:119-133, 1975.

Willert, H.G. and Semlitch, M. , Reactions of the Articular Capsule to

Wear Products of Artificial Joint Prostheses, J. Biomed. Mater. Res.

11:157-164, 1977.

Beckenbaugh, R.D., and Ilstrup, D.M., Total Hip Arthroplasty; A Review

of Three Hundred and Thirty-Three Cases with Long Term Follow-Up, J. Bone and Joint Surg., 60A:306-313, 1978.

Charnley, J. and Cupic, Z., The Nine and Ten Year Results of the Low

Friction Arthroplasty of the Hip, Clin, Orthop., 95:9-25, 1973.

Charnely, J. and Halley, D., Rate of Wear in Total Hip Replacement,

Clin. Orthop., 112:170-179, 1975.

Ries, M., "Wear Behavior of Polyethylene Components used in Total

Joint Prostheses," Masters Thesis, M.I.T., Department of Materials

Science and Engineering, June 1979.

Rose, R.M. , Nusbaum, H.J., Schneider, H., Ries, M., Paul, I., Crugnola,

A., Simon, S.R., and Radin, E.L., On the True Wear Rate of Ultrahigh

Molecular Weight Polyethylene in the Total Hip Prosthesis, J. Bone and

Joint Surg., in press.

Rose, R.M., Crugnola, A., Ries, M., Cimino, W.R., Paul, I., Radin, E.L.,

On the Origins of High In Vivo Wear Rates in Polyethylene Components

of Total Joint Prostheses, Clin. Orthop., 145:277-286, 1979.

Cimino, W.R., "The Comparative Wear Evaluation of Polyethylene for Total

Joint Arthroplasty," Masters Thesis, M.I.T., Department of Materials

Science and Engineering, June 1980.

Rostoker, W., Chao, E.Y.S. and Galante, J.O., The Appearance of Wear on Polyethylene—A Comparison of In Vivo and In Vitro Wear Surfaces, J.

Biomed. Mater. Res., 12:317-335, 1978.
Figure 1. A typical fusion defect in the molded surface of a total joint

replacement component made of ultrahigh molecular weight polyethylene (UHMWPE)

I 4

ML Z-5C * 4.4C KIM

US- 256 KEUEX 3X18*1

98 SEC

H8-1SKEU

Figure 3. The EDAX spectrum for the inclusion shown in figure 3. Peaks

for barium, gold (used to coat the specimen) and sulfur are

all in evidence.

1 6
Figure 4. A barium sulfate inclusion in the acrylic cement particle

shown in figure 2.

I 7
Figure 5. High magnification view of an acrylic cement particle, showing

pullout of acrylic globules due to incomplete curing.

I 8
Figure 6. Lower magnification view of the same particle as in figure 5,

showing fracture planes characteristic of embedded acrylic,

and heavily abraded UHMWPE surrounding the particle.

I 9
Figure 7. Bone fragments found embedded in the surface of an UHMWPE

tibial component of a total knee prosthesis.

20
21
Figure 9. A crater left by a departed acrylic particle, afer break up.

Figures 6, 8 and 9 constitute sequential pictures of the history of an

embedded acrylic particle.

22
Figure 10. Fibrils bridging two granules at a fusion defect in the UHMWPE

component of a total joint replacement.

23
Figure 11. An incompletely-fused UHMWPE granule, exposed at the articular

surface.

24
igure 12. An incompletely-fused UHMWPE granule delamina ting from the

articular surface. This process generates craters even in

the absence of acrylic cement debris

.

25
Figure 13. Surface of a polyethylene sample tested in vitro under simulated

total knee replacement conditions . [9]

The average molecular weight was 5 x 10 ,
Figure 14. Surface of a tibial component (clinical) produced from UHMWPE

(average molecular weight 2-6 x 106) , The similarity to

figure 13 suggests that the molecular weight at the articular

surface may have been degraded.

27
Discussion

Question (S. Barenberg, University of Michigan): What direct and/or

indirect evidence do you have that the bridging fibers are the high

molecular weight portion?

Answer : To the best of my knowledge there is no evidence, only

opinions, and these are controversial. On the one hand, the "high

molecular weight" school of thought maintains that the fibrils are indeed tie molecule agglomerations; on the other, the "low molecular

weight" school maintains that the fibrils are the result of turbulence in the reactor. As I have stated elsewhere, critical experiments to resolve this question remain to be done.

2 8
A BIOLOGICAL AND STRUCTURAL EVALUATION OF

RETRIEVED DACRON ARTERIAL PROSTHESES

3. b c d G

R. Guidoin , M. King , P. Blais , M. Marois , C. Gosselin , P. Roy, R. Courbier, M. David, H.P. NofeJl.

Pioneered in the 1950' s, reconstructive procedures involving the

implantation of synthetic blood conduits have become relatively common

since the early 1970' s. However, long term success is largely dependent on patient selection and surgical techniques as well as the design,

the dimensions and the material chosen to repair the nature conduit.

Polyethylene terephthalate(Dacron) tissue ingrowth fabric devices have

accounted for the larger portion of commercial devices and are currently implanted in a rapidly broadening spectrum of patients, many of whom

could potentially outlive the service lifetime of some of the newer

prostheses. "In-vitro" observations and studies on explanted prostheses

suggest that herefore unrecognized textile design and material biodeterioration considerations may have impact on long term prognostics

of success. In this work, the results of an ongoing prosthesis recovery

program encompassing more than 120 devices collected at autopsies and

reoperations are discussed. The evaluation protocol addresses healing,

textile geometry, product identification, dimensional stability of the

fabric, morphological changes of the yarns and fibres, mechanical properties and chemical changes in the material with "in-vivo" residency

time. The significance and the limitations of data derived from cardiovascular device recovery programs are also discussed.

a) Laval University, Laboratory of Experimental Surgery,

Dept. of Surgery, Quebec, Canada.

b) University of Manitoba, Dept. of Clothing and Textile, Winnipeg, Canada.

c) National Health and Welfare, Bureau of Medical Devices, Ottawa, Canada.

d) St-Francois d'Assise Hospital, Dept. of Pathology, Quebec, Canada.

e) St-Frangois d'Assise Hospital, Dept. of Surgery, Quebec, Canada.

f) See Table 1 for affiliation of other authors.

29
1. Introduction

From more than ten materials used clinically since 1954, polyethylene terephthalate (DacronR) has proven to be most desirable among

different porous fabric prostheses for cardiovascular replacement (1-4)

One style of device is currently available in more than twelve commercial

variations (5) . Superposed on the differences in design are the variations in porosity, weave style, fibre structure and fabric weight.

Over the last 20 years, emerging technology from the textile industry

has been adapted to medical fabrics and has enabled the routine production of low cost and relatively effective arterial prostheses for the re- placement of many types of blood vessels (6) . With the growing success of these prostheses as permanent arterial substitutes, research efforts

to refine surgical technics and develop new and improved products have

intensified.

Although a wide range of cardiovascular repair products have been

investigated and implanted in humans, a wholly satisfactory device of

universal applicability has not yet been found. This may, in fact, be an Utopian goal. Instead, specialized classes of products and technics,

each with specific merits and disadvantages, have emerged (3). Currently,

there are activities which aim at formulating standards for such products;

this suggests that the sector has reached maturity. Some properties such

as thickness, permeability to water (porosity), bursting strength, and

elongation are addressed in proposed standards for vascular prostheses

currently under development in the United Kingdom, Australia and the U.S.A.

(7-9) . Yet comparatively little is know of the mechanism of "healing",

the biodeterioration rate "in-vivo" and the impact of common pharmacologic

regimes for the management of related or concurrent clinical problems and

other factors which determine the clinical figures-of-merit for this

class of devices. The thickness and the nature of the ingrowth tissue,

the displacements and stresses due to limb movement as well as cyclic

tension and compression associated with pulsatile blood flow have implications with respect ot the useful lifetime of the prostheses "in-vivo" (10)

Premature mechanical failure, wear and deterioration of mechanical properties with extended post-implantation lifetimes are also becoming more

important considerations in view of the better prognosis fo many implanted

patients due to improved surgical techniques.

As a consequence, the use of Dacron fabric grafts in cardiovascular

surgery has become more clinically acceptable and more widespread over

the last decade. The introduction of superior and more easily implanted

devices has made the surgery very common (1 , 2) . Late trends in the

development of these prostheses have led to major reductions in the

fabric weight and tenacity in order to facilitate tissue ingrowth within

the fabric interstices (11). In 1976, several surgical centres in the

U.S.A. reported clinical difficulties with lightweight and other thin30
wall versions of these prostheses (12-16). Post operative dilation,

false aneurisms, suture line disruption and interstitial bleeding were

reported to occur shortly after the installation of the devices. Similar anecdotes involving thin-walled prostheses had also appeared earlier

(17-19) but had not attracted attention. As a result, use of "ultralightweight" prostheses was discontinued in the U.S. in spite of the

fact that the nature of the difficulty was not unequivocally established.

Of greater concern is the possibility that other synthetic prostheses

may be equally vulnerable over the long term because of insufficiently

large safety factors in the mechanical properties or excessive reactivity

of the constituent fibres towards the biological environment.

Some of these questions cannot be dealt with without the evaluation

of a reasonable number of devices which have been in clinical use;

although, well controlled experimental evaluation of implants on animal

models are indispensable, they do not simulate the realities of the

operating theatre or the condition of the average patient at the time

of surgery.

They have been relatively few implant recovery programs for cardiovascular prostheses. Although the literature has a considerable core

of "ad hoc" recovery of devices (10, 12-32) incidental to interesting

case histories, the overall aspect of explantation and analysis technology for this class of clinical material is more anecdotal than systematic. Instead, the emphasis has been placed on patient history follow-up

with minimal involvement in the pathology of the devices. Recent

examples include the work of Reichle and others where the discussion is

related to cardiovascular repair technics but do not address the issue

of failure analysis at the level of the prostheses or its materials (33-40)

.

It was the aim of this study to extend the present grasp of "in-vivo" fail- ure processes in fabric devices. This is needed in order to rationally

plan the necessary improvements to this class of implants and to identify

and correct possible deficiencies in the currently prevailing surgical

implantation technics.

This laboratory, heavily invested in the evaluation of cardiovascular

repair materials, has collected explanted vascular prostheses of various

classes from human patients for nearly four years. To date, more than

300 such devices have been analyzed and cataloged as part of an ongoing

program. Here, the results of work carried out on more than 120 Dacron

devices of comparable properties, collected from 10 surgical centres,

are presented with a summary of the case histories; autopsies and re- operations provided the major volume of clinical material to this study.
2. Materials and Methods

2.1 Clinical Material - Sources

Explanted prostheses were obtained at autopsy, reoperation or limb

amputation. Specimen size largely dictated the conditions under which

the analyses could be conducted. The retrieval program spans several

years and involved several centres from July 1975 to March 1979. It was made possible through the collaboration of many surgeons in Canada

and in France. Table 1 lists the principal participating centres and

their surgeons.

TABLE 1

Country

Canada

France

Surgeon

Camille Gosselin

Claude Rouleau

Jean-Frangois Girard

Paul Roy

Jacques Cote"

John Awad

Henry-Paul Noel

Robert Cote"

Robert Courbier

Jean-Marie J^tusseran

Michel David

Jacques Descotes

E. Chignier

Roger BSnichoux

Francis Godard

Gabriel Camel ot

Hospital or Centre City

Hopital St. Francois d 'Assise Quebec

Hopital de 1' Enfant Jesus Quebec

Centre Hospital ier de Quebec

L 'University Laval

Hopital du St. Sacrement Quebec

Hopital St. Joseph Marseille

Hopital du Bocage Dijon

Hopital Edouard Herri ot Lyon

CHU Nancy

Clinique St. Joseph Caen

CHU Besangon

Participating surgeons and centres in the retrieval program.

32
Since April 1979, several additional centres joined the retrieval

program from The Quebec City area, Winnipeg, Montreal (Canada), and

Bordeaux, La Rochelle and Metz (France) . These data will be discussed

in a subsequent work.

Grafts obtained at autopsy were explanted by local pathologists.

Autopsies were performed within a few hours after death. Grafts

obtained at reoperation were collected during the surgery with little

delay.

Explanted Dacron specimens included more than 200 grafts recovered

at autopsy, amputation or replacement reoperation and represented "invivo" residency times ranging from a few hours to nearly eleven years.

The collected prostheses included a typical assortment of tissue- ingrowth

cardiovascular textile products routinely used. Analysis of the first

120 grafts are reported here.

Unused grafts were commercial products indentical to those sold

for human implantation. Their origin is given in Table 2. Manufacturers

included: Meadox Medicals Inc., Oakland, N.J., U.S.A.; United States

Catheter and Instrument Co., (U.S.C.I.), Billerica, Mass., U.S.A.;

Goalski Laboratories Inc., Philadelphia, Pa, U.S.A.

2.2 Specimen preparation and method of analysis

In the event of death, the following procedures were followed:

autopsy is performed by the local pathologist within a few hours of

death after the family consent is obtained. The synthetic graft is

opened longitudinally and photographed. Post-mortem blood deposits are eliminated by gentle rinsing with heparinized saline. The graft is tben

divided into several specimens. Small samples (lxl cm) are taken

from different representative areas and identified. For example, for

aorto-femoral bifurcations, specimens are taken in the proximal anastomosis, in the middle of the body of the graft, at the bifurcation itself,

in the middle of both limbs and at both distal anastomoses. These

specimens are also divided into two sub-groups. The first one is

fixed in Bouin's solution (formaldehyde and picric acid) for twentyfour hours and thin sections (5 microns) are cut and stained following

routine pathological procedures. At the beginning, only hematoxylin

safran were used to differentiate fibrin from collagen. Later, other

staining techniques were added to identify other components of the

tissue - polymer composite sample. The second sub-group is fixed in a phosphate-buffered solution of 2% glutaraldehyde for up to one week,

followed by an overnight post-fixation using osmium tetroxide. The

specimens are then washed in distilled water. Drying is performed by

immersion in a graded series of ethanol-water solution terminating with

absolute ethanol. The specimens are then transferred to amyl acetate

prior to the final drying by critical point drying using CO2 as the

transfer medium. The specimens are finally mounted on SEM sample holders and coated with about lOOnm of gold-palladium in a sputter device

for viewing in a Cambridge S600 Scanning electron microscope at 10 or

15 kilovolts. More detailed pathological analysis procedures using

light microscopy and SEM are presented elsewhere (41)

.

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34
Grafts collected at reoperation are generally in a poorer condition

since they are often collected incidental to emergency surgery where

the patient is the primary concern. Normally, the useful size of the

graft is reduced. Such specimens are prepared in a way identical to

that of grafts collected at autopsy. When the size of sample is

sufficient, the remaining portions are assigned to mechanical and chemical evaluation. Specimen size largely dictates the conditions under

which the analyses can be conducted.

In such cases the remaining parts of the grafts must be stripped of

tissue prior to analysis. Tissue removal is achieved according to the

method of Hartigan (42) : grafts are boiled in a 5% sodium carbonate

solution, then immersed in commercial bleach and exhaustively washed

with distilled water and air dried. This treatment was shown not to be

deleterious to the Dacron fabrics; new prostheses treated with this

procedure are not significantly different with respect to the properties

of interest.

Virgin specimens were used as supplied for analysis and microscope

examination.

2.3 Analysis of Physical Properties

2.3.1 General Consideration

During "in-vivo" use, prostheses can suffer changes in dimension

and in shape. These are lateral dilation, loss of crimping and/or

longitudinal growth. The mechanical properties can also change concurrently. The aim of the analysis is to estimate these parameters

separately and to compare those of used prostheses to reference samples

of the product as supplied.

In some rare cases, prostheses cannot be unequivocally cross- matched to reference samples and their identity is uncertain. In other

cases remaining fabric samples are too small or severely damaged. Such

specimens are not assessed for mechanical properties.

Microscopy techniques can also be used as coarse methods for the

assessment of deterioration in mechanical properties. This approach is

based on flexing, stretching, or chemically etching used fabrics or

fibres and comparing their behaviour with virgin reference material

.

Such techniques reveal the depth ot which chemical attack has taken

place or the physical changes which have occurred in the polymer (fiber)

structure of filaments. These techniques were developed in the latter

phase of the program and will be reported elsewhere.

In order to understand the behaviour of the fabric under "in-vivo"

use, it is necessary to have some insight of prosthesis fabrication

technology. This aspect is covered under Appendix A.

Chemical analyses are generally laborious and a very limited number

of samples can be dealt with. In the present study, only samples with

exceptional experimental significance are subjected to chemical analysis

and molecular weight measurements.

35
Figure 1 : Pick Counter measuring crimp of explanted prosthesis in

reflected light.

2.3.2 Measurement of Crimp Retention

The fabric specimen were mounted in a relaxed state on a specially

made Crimp Tester. This device is shown in Figure 1. It is able to measure the length of the specimen to the nearest 0.2mm while extending

it sufficiently to remove all the crimp. The end point is readily

determined by ensuring that the fabric appears flat when viewed from

above in reflected light through an optical microscope. The amount of

crimp in the specimen is calculated from the difference between the

extended and relaxed length and is expressed as a percentage of the

original relaxed length.

2.3.3 Liquid Permeability

The measurement of liquid permeability (porosity) is carried out

according to techniques described by Buxton and Cooley (43, 44). It

gives an index of the intersticial leakage rate of the fabric prior to

surgical preclotting. It also has a relative index of fabric "openness". There, it only has meaning for clean fabrics without tissue.

3G
It was originally believed by us to be a useful measurement of "in-vivo"

fabric "growth" since changes in fibre geometry, fibre dimension and

fabric density affect the apparent porosity and the flow rate of liquid

through the network. In this work, however, its used is limited to

characterizing the prostheses according to established methodologies.

2.4 Bursting Strength

The measurement of bursting strength was carried out with a Mullen

Burst Tester (Mullen Model AH; B.F. Perkins and Sons Inc., Holyoke,

Mass. U.S.A.) fitted with a modified specimen holder suitable for a small circular (1 cm^) sample of fabric (Figure 2) . This instrument

requires the use of pressure equilizing membranes for porous samples

and is used widely in the textile, paper and rubber industries. It

amounts to a coarse biaxial tensile tensile test method which reflects

the coherence or the tenacity of films, webs and fabrics which cannot

be realistically assessed by uniaxial tensile tests. In all measurements,

identical compliant (latex rubber) pressure equalizing membranes of

0.014" were used (Triaxial Tyl4-WF 11090; Rubber Sleeves Inc.; 95 Montpellier St., Montreal, Canada). Appropriate corrections were applied

to compensate for the membrane contribution. All fabric samples were

preconditioned at 23° and at relative humidity of 65% for 24 hours

prior to testing. Samples were flattened prior to insertion in the

specimen holder in order to make the crimps disappear, but stretching

was avoided. Expansion and bursting of a graft is shown in Figure 3.

2.5 Stitch Density

This measurement is performed with the specimen mounted in the

extended state with its crimp removed by the Crimp Tester, the number

of stitches are counted in the warp and weft directions. A row of

stitches in the warp direction is called a wale, while a row of stitches

in the weft direction is called a course. When sufficient fabric is

available, determinations are made along 3 cm lengths in both directions

with the aid of an optical microscope in transmitted light. The stitch

density is the wales/cm multiplied by the courses/cm. The difference

between the stitch density of the graft and the explaned graft represents

the permanent deformation experienced by the fabric during implantation

due to distortion of the knitted loops and stretching of the yarns

(Figure 4)

.

37
38


2.3.6 Scanning Electron Microscopy of Fabrics

SEM study of samples was carried out with the aid of a Jeol JSM 35C

instrument after coating with carbon (50 nm) . A coating with goldpalladium (lOOnm) by evaporation was added for conductance improvement.

A silver paste was added on each corner of the graft to provide electrical continuity with the specimen mount. The microscope was fitted with

a backscattered electron detector of enhanced sensitivity and reduced

noise. Attempts to obtain satisfactory images with conventional secondary electron collector led to charging. This problem is common in many

synthetic textile products and is severe in polyethylene terephthalate

systems

.

2.3.7 Filament Diameter

Filament diameters are measured on individual yarns which are removed from the cleaned prostheses. The diameter of 20 filaments

selected at random from each yarn is measured using an optical microscope at 400 times magnification with a micrometer eyepiece. The eyepiece scale is calibrated against a stage micrometer and the average

diameter of the filaments is calculated for each prosthesis. Any

significant difference betweeen the average diameters of the unused

and the explanted filaments represents either longitudinal stretching,

lateral swelling, dissolution, abrasion of wear during "in-vivo"

residency of the prosthesis.

2.3.8 Chemical Analysis

In the case of prostheses showing visible damages with the unaided

eye, the mode and the cause of the damage is investigated. This is

supplemented by chemical analysis using mass spectrometry and infrared spectrophotometry. Mass spectrometry is used to determine the

amount and the type of volatile materials which can be removed at 205-

295°C. The ratio of peaks associated with volatiles molecular weight

corresponding to oligomeric species with two benzene nuclei is compared

to the peaks associated with fragments containing a single benzene

nucleus; this measurement allows an estimate of the ratio of very low

weight oligomers to dimeric species. For extensively degraded samples,

the quantity of oligomers containing a single benzene nucleus is expected to be larger. This technique still has to be refined and quantified

and will be the object of subsequent papers.

The infrared absorption of the polyester fabric has been measured

using conventional transmission infrared spectrophotometry, attenuated

total reflection infrared spectrometry (ART) and Fourrier Transform infrared spectrophotometry. The two former techniques did not of immediate

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42
usefulness and were abandoned early in the work. On the other hand,

Fourrier Transform spectrophotometry can be used to measure subtle

variations in the carboxy and hydroxyl end-group concentration in new

and explanted samples by comparing the absorption corresponding to

3,290 cm"! and 3,535 cm-~l respectively. These techniques are described

by Clark and Mickie (45)

.

The molecular weight of new and recovered prostheses material is

measured according to standard ASTM textile techniques (46, 47) . This

measurement is possible only in instances where substantial amounts of

material are available. For this purpose, specimens are weighed, dissolved in O-chlorophenol and serial dilutions are taken to generate

viscometric data at 25°C, according to conventional procedures.

Viscosity average molecular weight (Mv) can be calculated from

the intrinsic viscosity (»£) according the following equation from the

literature (48)

.

Mv

.81 x icr

1.9

3. Results

3.1 General Considerations

Specimen collected during this program numbered in excess of 300

including biological and PTFE grafts. However, analysis of 120 Dacron

grafts have been totally completed at the time of writing. Medical

histories were also available for almost all donor patients. The most

detailed examples came from reoperation cases. On the other hand, the

best specimens of prostheses originated from autopsies of patients who

died for a reason unrelated to the prosthesis.

Reference prostheses were available for most of the collected

samples and were characterized and cross-matched to explanted devices;

only very few could not be identified. The physical characteristics

of unused reference textiles are listed under Table 2 and 3. This list

includes only devides which were encountered in the recovery program;

it represents approximately 50% of the devices which have been marketed

over the last decade.

Table 4 is a compilation of devices received in a state such that

meaningfull physical properties measurements could be carried-out; it

includes less than 50 devices to date, the majority of which are in

the aorto-femoral bifurcation configuration. This is expected as this

43
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47

junction is the most common site of reconstruction in peripheral

vascular surgery. This table also includes other date of clinical

relevance such as the indication for implantation, durantion if implantation (residency time) , cause of death and site of implantation.

Patient-related information is presented in Tables 5.01-5.08 (reoperations and first surgery) and in Tables 6.01-6.07 (autopsies).

These summarize the age at which patients received their first device,

the type of device (s) implanted, the implantation site, the useful life

of the device "in-vivo" be'fore death or a second surgery, the indications for surgery of the cause of death, the aim of the subsequent

surgery, and the total number of device collected during specific phases

of the program. Such data were obtained from medical records and will

be the object of a separate publication. For the present need, the

following points are of value: the average of age of implantation

candidates is dropping rapidly and patients are, on average, several

years younger than a decade ago. More velour and lightweight devices

are now implanted; occlusive diseases affect the larger segment of

implanted patients while the resection of aneurisms is a much less

frequent indication of surgery; bilateral aorto-femoral replacement is

the most common procedure; almost a third of implanted patients require

additional surgery in the same field within 2 years of the first implantation; some patients may undergo as many as 4 related operations;

although, thrombus formation and degradation of the distal vascular bed

are the most common problems, device-related problems such as dilation,

false aneurism and stenosis are common; more patients fitted with

velour devices are reoperated upon; the primary cause of death is not

prosthesis-related.

3.2 Reoperations (Figures 5.01-5.08)

Prostheses collected incidental to reoperations were seldom of good

quality; most had suffered some damages during excision. A limited

number provided fragments which were suitable for mechanical properties;

these are listed in Table 4. Unlike devices collected at autopsies,

many prostheses issuing from reoperations were involved in problems intrinsic to the site of surgery, the distal vascular bed or the device

itself. Occlusive thrombosis was very common.

Dominant contributing factors to reoperation include the natural

progression of degenerative diseases such as atherosclerosis which

gradually increases the peripheral impedence of the circulatory system.

The probability of thrombosis is increased by any drop in arterial

pressure (flow velocity reduction), such phenomena can occur during an

infarct or during surgery; it is even present when the threshold blood

flow velocity is approached. Parallel pharmacological therapy may also

contribute to reducing or enhancing these effects by modifying blood

49
Table 5. 01

REOPERATIONS : IMPIANTATION SITE; (FIRST SURGERY )

IMPLANT SITE

PROSTHESIS TYPE TOTAL

WOVEN KNl'lTR) VELOURS

Aorto-Femoral

- (Bilateral) 1 30 9 40

Aorto-Femoral

(with 1 Fern. Popliteal) 2 2

Femoro-Popliteal 1 10 5 16

Axillo-Femoral 1 1

Others

(Upper extremities) 1 1

TOTAL 2 41 17 60

Table 5-02

AGE OF PATIENT AT SURGERY*

TYPE OF

PROSTHESES

MEN WOMEN TOTAL

PATIENTS

AVERAGE

AGE

NUM- RANGE

BER

AVERAGE RANGE NUMBER

AVERAGE RANGE

Woven 2 73 68-78 2 73-0 68-78

Knitted 35 55-5 28-73 6 57 41-67 41 55.7 28-73

Velours 15 53 42-67 2 53-5 53-54 17 53-1 42.67

TOTAL 52 55.8 28-78 8 56.1 41-67 60 55.8 28-78

* First surgery

50
Table 5-03

TYPE OF PROSTHESES

(FIRST PROSTHESIS IMPLANTED)

PROSTHESIS

BRAND

PATIENT

TOTAL

TYPE MALE FEMALF

Woven Woven de Bakey 2 2

Knitted Weavenlt 11 4 15

Knitted Cooley 4. 1 5

Mlcroknit Golaskl 1 1

Knitted de Bakey 11 11

ULW 4 4

Unidentified 4 1 5

Velours Mlcrovel 12 1 13

Vasculour D 2 2

Cooley Double Velour 1 1 2

TOTAL PATIENTS 52 8 60

5 I
Table 5-04

RATIONALE FOR FIRST SURGERY

DEVICE IMPLANTED

TOTAL

WOVEN KN1TIMJ VELOUR

Aneurism

(elective surgery)

0 4 1 5

Occlusive Disease 2 37 16 55

TOTAL 2 41 17 60

Table 5.05

REOPERATIONS

PATIENT STATUS SPECIMEN COLLECTED

First Reoperation 53

Second Reoperation 16

Third Reoperation 4

Fourth Reoperation 4

TOTAL REOPERATIONS* 77

TOTAL PATIENTS* 60

* Some patients provided two or more prostheses to the recovery program.
Table 5-06

NUMBER OF CASES AND INDICATION FOR REOPERATION

PC OPFJ)ST

NATIVE

1 1 WL

;o 6

WHS

(I5 to 2i ©NTHS

\ MDRE

24 K

THAT1 ONTffi

J

Patient status* 1 2 1 2 1 2 3 1 2 3

llitUIIIUUb q o X

7J c. 4

vascular bed 1 4 1 3 1 8 1

Prosthesis

Dilation 1

False aneurism 2 1 5 2

Infection 3 1 0 3 1 1

Aorta-enteric

fistulae 1 1 1

Hemorrhage 2 1 1

Stenosis 3 1 1 1 1 1

Number of related surgical acts in the area

53
Table 5-07

REOPERATIONS

pa

OPEFJ

>TITTVE1 1 MOt;o 6 JTHS

6 to 24

MONTHS

j ORE

24 M

IHAN

ONTHS

Patient status* 1 2 1 2 1 2 2 1 2 3 4

Thrombectomy 3 3 2 1 3 1 1 5

Replacement of

prosthesis 2 15 3 1 16 6 3

Addition of

supplemental

prosthesis

1 3 1 5 3

2 1 3

Amputation 1 1 1 1

* Number of related surgical acts in the area

Table 5-08

FABRIC CLASS OF PROSTHESES AND ELAPSED TIME COLLECTION ,—, (REOPERATION)

IN-VTVO RES3DENCTY TIME (MONTHS) TOTAL

PROSTHESES * Post- (or in

tra) operative

1 to 6

months

6 to 24

months more than24 months

Woven 0 0 1 1 2

Knitted k 12 31 51

Velours 5 5 11 6 27

* Includes devices issuing from reoperations.

** Samples of 2 kinds of grafts were occasionally collected at reoperation.
coagulation properties, local blood hemodynamics or altering blood

pressure. Many patients showed recurrence of the original underlying

cause which led to the first implantation. Reoperation does not necessarily precipitate replacement of the prosthesis. Successful thrombectomy could obviate the need for excision and reanastomosis of a new

device. However, any interruption in blood flow or a "reworking" of

the area greatly increased the prospects for replacement. Occasionally,

closely supervised patients gave evidence of dilation or stenosis of

the prosthesis and replacement of the device was elected. Some patients

underwent as many as four successive replacements of prosthesis, several

of which found their way into the recovery program. Occasionally a patient from this pool also provided a supplemental prosthesis at autopsy upon death.

False aneurism adjacent or contiguous to the anastomotic site were

also cited as indications for replacement of the prosthesis or supplemental surgery on adjacent areas. It is not uncommon to encounter

situations where reoperations aimed at thrombectomy or resection of

aneurism adjacent to a prosthesis did not require removal of the original

prosthesis. False aneurisms are common after more than six months postoperative; there were ten cases. The development of the condition

appears to take place over a protracted period of time and was generally

known for sometime before the planned surgery. Such prostheses sometimes

exhibited ruptured fibers or ruptured sutures as well as other local

mechanical damages to the anastomoses area. Arteries with friable walls

and inadequate mechanical properties do not securely anchor sutures and

increase the risks of hemorrhage. Such arteries were occasionally

encountered

.

Stenosis of the adjacent parts of the affected arterial network or of the prosthesis itself accounted for eight cases of reoperation leading to removal and replacement of the device. Fibrous hyperplasia was

a primary factor in the development of stenosis and was more commonly

encountered with double velour grafts and other devices with thick,

large surface area fabrics. In the case of double velours, spectacular

collagen ingrowth on the external wall was' found. Such devices had

highly organized and thick thrombotic deposits on the lumen wall; microvasculature (capillaries) were sometimes encountered within this mass. The full clinical implications of the inordinately thick wall are not

known. Nevertheless prostheses which show such features generally develop problems leading to replacement of the device. Fabric stretching

was observed in recovered samples. However, this was rarely evident

before surgery or at the time of explantation. Clinically obvious and

objectionable dilation in a prosthesis is cited only once as a cause

for prosthesis replacement. In this instance, a two-fold increase in

diameter of the device was noted over a distance of approximately 4 cm. Fiber damage was present in that area and appeared to be a consequence

as opposed to a cause of the observed dilation. There was little

evidence of healing and fibrin deposits were present. The problem was

further compounded by a mild bacterial colonization.

5-3
Figure 5-01 : Femoro- popliteal graft (FP08); SEM cross-section; 52 years

old patient; Milliknit ^9 months in situ. Section transverse to flow directiol

upper left hand segment shows dense organized concentric deposits and lower ri

hand corner shows disorganized occlusive thrombus in the lumen of the prosthesl

(x80).

Figure 5.02 : Aorto femoral bifurcated graft (BO^O implanted in a 65 years

old female for 28 months; graft of unknown origin; similar phenomenon to

figure 5-01 at higher magnification: A(x500) layers adjacent to the prosthesis wall, B(x500) lumen of the prosthesis.

5G
Figure 5«03 : Femoropopliteal graft, 1H months In situ (FP15) totally

thrombosed in the distal segment (A:x30) and well healed proximally,

SEM surface area shows an orderly layer of compacted fibrin (B:xl50).

Figure 5-0^ : B79; poorly healed internal surface of a prosthesis after 7 years in situ (standard knitted de Bakey). The patient was reoperated upon because of a false aneurism.

57
Figure 5-05 : Microvel aorto- femoral bifurcation (B05) inplanted in a 5^

years old male for one year; the patient was reoperated upon because of

stenosis at both anastomoses. Note thick capsule with amorphous neointima

and dense concentric layers of collagen surrounding the graft in Figure A

(x60); Figure B is a higher magnification of Figure A showing the structure

of capillaries in the internal capsule wall (xl200).

Figure 5.06 : Lightweight knitted graft of unknown origin implanted as a femoro -popliteal by-pass in a 5^ years old male (alcoholic) for 28 months;

note the presence of capillaries in the internal capsule (A: x 150; B: x 1200)

58
Figure 5. 07 : B52, aorto -femoral bifurcation implanted in a 56 years old

male; ^tn reoperation with incipient thrombosis and gangrene; uncharacterized

infection associated with absence of healing (A:x600; B:x2500).

Figure 5.08 : FP13, staphyloccocus aureus invasion after 6 months in situ

(Microvel); infection sites coincide with protruding fibers, bare areas and

zones of poor healing (A:150; Brx^OOO).

59
Figure 5. 09 : B^, device collected at the 4th reoperation for aorto

enteric fistula (Cooley Double Velour). Note the total absence of neointama and the presence of bacterial activity in the area of the fistula

(A: x 200; B: x 5000).

Infection sites were found on some prostheses. Common causes are: inadequate surface wound healing and pre-existing infections . The

problem is exacerbated by multiple reoperations. Staphiloccocus aureus was the most commonly encountered bacterial pathogen although other

organisms were occasionally found. It was noted that infected areas were generally devoid of coherent neoendothelium. Although it is possible that the infection pre-existed and forbade the development of a lumen lining, it is equally possible that a healthy lining formed first

and was then invaded by bacteria and destroyed by them. Although

bacterial activity would not be expected to damage polyester fibers,

it may still cause interstitial hemorrhage by eroding the deposit which

ensures the integrity of the capsule.

The recovery program received three prosthesis from patients with

aorto enteric fistulae. This included one Weavenit, one Cooley Double

Velour and one Microvel. Two of these patients died soon after the

second surgery. The noteworthy observation on such prostheses is that

healing and development of a neoendothelium does not take place on the

part which was in contact with the duedenum wall. The direct contact

between the duodenum and the fabric prosthesis promotes erosion of

the prosthesis lining in the lumen.

60
3.3 Prostheses Collected at Autopsy (Figures 6.01-6.06)

Samples originating from autopsies were generally in good condition

and included segments of the vascular tissue. This class of retrieved

specimen contained the largest number of "ideal" explants which provided insight on the morphology and the thickness of the neointima on

the lumen wall and the degree of external tissue encapsulation.

Newly deposited luminal surface linings (pseudo-neointima) were over- whelmingly acellular; endothelial -like cells suggestive of systematic

endothelialization beyond the anastomotic site were absent. Perhaps

extensive endothelialization of the luminal surface is not necessary for

long term patency of cardiovascular grafts ; also adhering microthrombi

and minor embolic structures were not uncommon and are perhaps normal

for most patients. Packed fibrin, collagen and fibroblasts seem sufficient to prevent leakage and contain the blood elements. Very thick

linings of blood products are not necessary to prevent interstitial

blood leakage through the fabric; a thin layer is sufficient. For

patients affected by systemic diseases , such as diabetes , it was not uncommon to find large areas of prostheses which were totally devoid of

any deposits. Such diseases may account for the considerable variations

in the extent of healing found on autopsy samples. The healing sequence

of a prosthesis consists of a rapid deposition of low density fibrin

which adheres loosely to the prosthesis. The second phase of the process

consists of a reorganization of this fibrin mat to constitute a much

denser and more hydrophobic luminal surface. Complete healing with the

development of pseudo-endothelial cells over the fibrin mat does not take

place extensively on the lumen. At best, only small islands of surface

cellular activity is evident even after many years post-implantation.

Thrombosis was one of the more frequent complications. Evidence

of infection and hemorrhage were seldom encountered. The degree of

fiber and fabric integrity in most explanted prostheses was surprisingly good. Nevertheless, prostheses with isolated areas of damaged fibers

could be found in many samples. The pattern of fabric damage was

occasionally suggestive of a vascular clamp or by abrasion by an other

surgical instrument, which may have taken place during the surgical procedure .

For most autopsies, it was possible to remove a portion of the pannus which included the interface with the artery as well as the suture.

For prostheses which had functioned for long periods of time the anastomotic area was well healed and appeared continuous with prosthesis.

Irregularities at that site generally lead to early problems due to

unfavorable haemodynamics and thrombosis becomes a more probable event.

Grafts exhibiting poor healing and incompletely covered luminal sur- faces were typical of those where patients had a diabetic history.

Fibrin deposits, in such cases, appeared irregular, sparse, and formed

rough luminal surfaces; distal embolization at or near the anastomosis

site was common. Much of the lumen surface remained uncoated but the

interstitial spaces between the fibres seemed adequately sealed to prevent blood leakage. Patches of uncoated yearns were readily found for

most prosthesis originating from patients who had been in a poor state

of health in the latter part of their life.

6 I
Sterile inflammatory reactions are not common in fabric cardiovascular implants. Nevertheless, one case was cited where such a reaction led to the mandatory replacement of a device. A Knitted de Bakey,

implanted at the sub-clavian position in a 71 years-old patient, developed this condition after 23 months and had to be replaced. It was

tentatively concluded that the patient developed an "allergy" to the

polyester material. Other than evidence of poor healing, the prosthesis

was unremarkable. Blood cultures for this patient proved negative and no bacterial development was noted by scanning electron microscopy;

bacterial invasion therefore does not appear to have been a factor.

Interstitial hemorrhages, in particular those near the anastomosis, were encountered and were sometimes related to the distention of prosthesis fibers and other fabric deformation phenomena. These led to

local interstitial leakage of blood; ruptured prosthesis fibers were

not found. Healing was relatively poor on such samples.

TABLE 6 - 01

SUMMARY OF PROSTHESES

OBTAINED AT AUTOPSIES

PROSTHESIS TYPES MALE FEMALE TOTAL

Woven Woven de Bakey 1 0 1 — 2 Unidentified 1 0 1y

Knitted Weavenit 17 0 17

ULW 4 0 4

Knitted de Bakey 4 0 4 -27

Milliknit Golaski 1 0 1

Unidentified 1 0 1

Velours Microvel 9 4 13

Vasculour D 0 1 1 -15

Sauvage Guideline 1 0 1y

TOTAL 39 5 44

62
TABLE 6.02

AVERAGE OF PATIENTS AT FIRST IMPLANTATION

(AUTOPSY CASES)

AGE AT

IMPLANTATION.

(RALE)

AGE AT

til rr\T A A FT1 A HT T T IMPLAnTAI ion

(FEMALE)

AVERAGE

AGE

Knitted Weavenit 58.625 58.625

ULW 60.33 66 61.75

Knitted de Bakey 59-25 59-25

Velours Mlcrovel 63.667 63-33 63-58

Excludes patients with traumatic and congenital indications for surgery.

TABLE 6.03

FUNCTIONAL IJFETTME OF PROSTHESIS

AS A FUNCTION OF AGE*

AGE POSTOPERATIVE

1-6

MONTHS

6-24

MONTHS

24 MONTHS

& ABOVE

TOTAL

30 - 40 1 1

40 - 50 1 2 3

50 - 60 3 2 2 8 15

60 - 70 5 3 2 8 18

70 - 80 3 2 2 7

TOTAL 13 7 6 18 44

Age at implantation.

63
TABLE 6.04

FUNCTIONAL LIFE OF PROSTHESES

WITH TYPE OF PROSTHESIS

(AUTOPSY CASES)

TYPE OF PROSTHESIS

POSTOP

1-6

MONTHS

6-24

MONTHS

MORE

THAN 24

MONTHS

TOTAL

W(J Vcl i WUV di LiTM JJCLn.",/ 1 _ 1

TTniiiprrf- i fi ptf - - 1 - 1

WcrcLVtrlJ-L U 4 o j 8 1 7

ULW 4 4

Knitted de Bakey 4 4

Mllllknit Golaski 1 1

Unidentified 1 1

Velours Microvel 7 6 0 13

Vasculour D 1 1

Sauvage Guideline 1 1

TOTAL 13 7 6 18 44

For aorto-femoral bifurcations, uncoated fibres are almost always

encountered in or near the bifurcation zone. The bifurcation zone appeared as a site of difficulty. It does not form a defined pseudointuna and most prostheses showed exposed yarns in that area, no matter

how long they had been implanted. It is noted that the bifurcation is

normally larger than the original artery which it replaces and that the

haemodynamics are not ideal; it is an area of turbulence. Recovered

samples confirmed this suspected inadequacy in current device designs.

64
TABLE 6.05

INDICATIONS FOR IMPLANTATION

WOVEN KNITi'ED VELOURS TOTAL

Aneurism 1

* 7

* 6

* 14

Claudication 21 *

7

* 28

Coarctation of the aorta 1 1

Congenital malformation 1 1

TOTAL 2 28 14 44

* Includes 5 ruptured aneurisms cases

The following anecdotal observations are worthy of mention in con- nection with the autopsy data. Neoendothelization with endotheliallike cell development was noted in only four cases. In all instances

it was confined to small patches on or near the anastomosis or on isolated areas not far from the anastomotic site: an aorto-femoral Weavenit after 17 months of implantation in a elective patient (48 years-old,

abdominal aorta aneurism, iliac stenosis) , a well healed Weavenit bifurcation implanted for 50 months in a 55 years-old patient treated for

claudication; a Knitted de Bakey implanted for 98 months after resection of an abdominal aneurism in a 64 years-old patient and a Knitted de

Bakey implanted for 84 months in two femoro-popliteal positions to bypass

bilateral blockage in a 58 years-old candidate. In summary, there are relatively few points in common for all these patients other than the

observation that they were somewhat younger and free of additional degenerative disease such as diabetes. Three Microvel prostheses (figure

6.06) implanted by the same surgeon and collected after two months,

showed radically different healing characteristics; the first, B16, was

the best in spite of the fact that it originated from a high risk

patient (75 years-old, emergency surgery for a ruptured aneurism, postoperative kidney failure) . All traces of healing were absent from a second prosthesis, B25, which originated from an elective patient (71

years old, diabetic) . This same patient had an uneventfull post-operative

recovery. The third device, B58, was also from an elective patient (59

years old, aneurism of the aorta). This device exhibited only a thin

coat of fibrin with a smooth surface but without densification or organ65
TABLE 6-06

CAUSE OF DEATH OF PATIENTS

(AUTOPSY CASES)

CAUSES POST OP.

1-6

MONTHS

6-24

MONTHS

MORE

THAN 24

MONTHS

TOTAL

Infarct 3 1 1 10 15

Post operative shock 2 1 3

Kidney failure 2 2 (1) (1) 4

Respiratory failure 3 (2) 1 (1) 1 (1) 2 7

Intestinal necrosis 1 1 2

Cancer l 1 3 5

niATthPT*! 01 i^i -X.wo^*.l.^x O^fl PTYT^I ^ i o i_; 1 2 (1) -)

Hemorrhage 2 1 3

Infection 1 1

Others 1 1

TOTAL 13 7 6 18 44

1 main cause

(1) associated cause

GG
TABLE 6.07

IMPLANTATION SITE OF PROSTHESES COLLECTED AT AUTOPSIES

Site Woven Knitted Velours Total

Aorto-femoral (bilateral) 1 24 U)

12 37

Ilio-femoral

Femoro-popliteal

1

x (b)

1 (C)

1

2

Coarctation of the aorta 1 1

Femoro femoral 1 1

Axil lo-femoral and

femoro -femoral 1 1

Abdominal 1 1

Total 2 28 14 44

(a) First surgery for unilateral by-pass followed by a replacement with a bilateral by-pass on a second surgical attempt.

(b) Bilateral

(c) Unilateral

ization; his death was primarily the end result of generalized atherosclerosis with terminal complications. Thus of all candidates, the one who appeared a poor risk prior to surgery and during post-operative re- covery showed the best healing characteristics thus illustrating the

impact of a patient's general state of health and the key role of associated degenerative diseases on healing processes.

Although no death can be attributed directly to failure of a prosthesis, the risk can be demonstrated for one patient. The patient who

provided prosthesis M015 (Vasculour D) , was exposed to a hemorrhagic

risk since many of the fibres of that device were broken at several sites.

Also, the external capsule to this prosthesis was particularly thin and

contained no elastin fibers, smooth muscle or connective tissue of any

king. M015 could be thus regarded as an incipient case of prosthesis

rupture

.

67
Figure 6.01 : Flow surface of a prosthesis after 6 weeks in-situ in a 67 years old poor risk patient (ruptured aneurism resection); note

dense network of fibrin and smooth surface. (Woven de Bakey, B66)

Several patients had prostheses with insecure anastomoses due to: disturbances in the suture line, tissue or prosthesis fabric tears or hyperplasic tissue proliferation in the area. Noteworthy examples of these effects are presented in Figures 6.01

to 6.07, with appropriate comments in the figure captions.

3.4 Fabric Properties

Prostheses which had sufficient amounts of fabric were evaluated

with respect to fabric properties. The results of these measurements

are shown in Table 7 and are presented graphically in Figure 7. Crimp,

stitch density and burst strength were all found to decay with "in-vivo"

residency (duration of implantation) . Only the filament diameter showed and initial increase; however, a decrease eventually took place

over a period of about 2-3 years of implantation.

66
Figure 6.02 ? Surface of a prosthesis after 3 days in-situ in ; old patient (elective aneurism resection); note mesh of fibrin

entrapped cells (Weavenit, B74).

Figure 6.03 : Flow surface of a prosthesis after 9 days in a 72 years

old diabetic; note bare fibres and pore filling debris. Such prostheses

in spite of their thin coating do not leak blood. (Weavenit, Bl)
70
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Figure 6.0.6 : Flow surface of a velour bifurcation (Microvel B56) in-situ

for 3 weeks in a 69 years old patient;

A: General view

B: Detail of surface of A, note irregular covering with wall thrombi and

protruding triloba! fibres (x 200)

3.5 Polymer Properties

The results of preliminary chemical analyses for the assessment of

chemical deterioration which were carried-out on fibres are presented

in the discussion.

3.6 Fibre Damage

A number of samples showed areas of macroscopic damage. Others gave

evidence of damage only at higher magnification under scanning electron

microscopy. Examples of damage, distorsion and deterioration are shown

in Figure 8. These separate into three classes: fabrication damage,

handling trauma and physico-chemical deterioration. Violent extension

and breakage of fibres yield characteristically thinned and "fibrillated"

structures whereas physico-chemical deterioration is more likely the cause of fibres with longitudinal cracks or splits and transverse crevices which do not extend across the fibre. Porous surfaces and sharply

broken fibres are other expressions of physico-chemical deterioration.

These types of damage are never found on new prostheses as supplied.

Fibres with regularly spaced features such as flats, depressions,

protuberances and other details suggestive of compressive deformation

are the characteristics of harsh shrinkage, compaction and crimping

processes and are found on new prostheses as well as on explanted ones. 72
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82
Figure 7-04A

CHANGE IN FILAMENT DIAMETER WITH DURATION OF IMPLANTATION
8<1
Figure 8.02 : (B^7) A. Externa] view of Weavenit prosthesis after 39 months

showing isolated filament failure and some variation in the loop length of

individual filaments. B. Circular cross-section filaments showing smooth and

undamaged surfaces.

85
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86
Figure 8- 0^ : (B55) A. External view of Knitted Cooley prosthesis explanted

after 48 months. B. Internal lumen side view of filaments at the crest of

a crimp showing flattened surfaces probably caused by contact of the mandrel

during crimping.

irigure : (ggg) A> External view of Woven De Bakey prosthesis after

explantation at 6 weeks. B. "Internal view of filaments at the crest of a crimp showing flattened surfaces probably caused by the contact of the

mandrel during crimping.

87
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88
Figure 8- 07 : (B73) Internal view of Standard Knitted De Bakey prosthesis

after 97 months showing yams ravelled from a damaged area.
Figure 3.09 : ( By 9 ) A> External view of a damaged Standard Knitted De Bakey

prosthesis in the area of the false aneurism showing fractured filaments and

ravelled yarns explanted after 8^ months. B. Ravelled filaments showing

smooth and damaged areas. C. Fractured filament containing many microfibrils and exhibiting extensive fibrillation, probably due to mechanical

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figure a. 11 : (FP26) A. View of damaged Weavenit prosthesis after 84 months

B. Yam failure. C. Non-circular filaments deformed pressure from adjacent

yarns during prosthesis manufacture. D. Transverse cracks and fracture

surfaces of embrittled filaments.

92
Figure 3.12 : (M015) A . View of damaged De Bakey Vasculourprosthesis after

iS^n-vivrB. Yam failure. C. ^iled filaments show^g fracture

surfaces. D. Cracks in filament showing axial splitting.

93
94
Figure 8.15 : (3113) A. External view of Microvel prosthesis after 2 days

implantation yarns. B. Velour trilobal cross-section filaments showing

axial cracking on the surface and between the lobes.

95
Figure 8.16 : (B75) A. External view of a Standard Knitted De Bakey prosthe

explanted after 72 months (inadequately cleaned). B. Filaments with adherin

tissue (residual) showing axial splitting.

4. Discussion

4.1 General Consideration

Cardiovascular reconstructive techniques which make use of fabrics

have progressed from the stage of surgical curiosities in the 1950'

to common management strategies in the 1970 's. Implantable fabrics

have also changed and are still evolving. The rationale for the evo- lutionary trends, however is not clear. At present, the life expectancy

of patients bearing implants is increasing since younger candidates are being accepted; elective operations take place earlier on the basis

that prognostics of success diminish rapidly with age and disease progression. Concurrently, the original concerns regarding the longevity

of the implants "in-vivo" has largely vanished from the list of preoccupations of the surgical team. In effect, the new generations of

prostheses are now taken for granted by many clinicians who view this

class of products as a "stock" surgical supply unlikely to undergo further major developments. In response, more recent develpments on these

prostheses have centered on production considerations in the absence of

clearly identifyable guiding criteria from the clinical sector. New

products released on the market are often re-issues of older styles of

devices superficially modified to accept different commercial yarns or more elegant production technologies.

9G
Once the gross anatomic configuration or the geometry of the needed

replacement device is established, it becomes very difficult to choose

one device over another on the basis of conventionally accepted performance criteria. Product literature reflects this dilemma.

This condition has prevailed over the last decade. However the

pool of implanted patients has increased enormously since 1970. Pre - 1970 devices are therefore more rarely recovered, not only because most

of these patients died before the start of one recovery program but

also because their relatively small numbers were overwhelmed by post - 1970

implantations. Considering that there were "fashion" cycles m tne populairty of certain devices, then the recovery distribution must also re- flect the degree of local commercial success and the fashions which

indirectly controlled the total number of devices of each king implanted

at different surgical centres.

In summary, the background against which thus recovery program was carried-out can be seen in the following way. Devices reported to be

clinically superior (or equivalent) were made by many manufacturers in a wide range of different configurations and fabric styles, sold and

implanted in different patients by different surgeons under different

conditions. Some of these patients subsequently returned to the general

population pool, but never reappeared into the health care delivery

system. Over a period of time which varied from a few month to a decade,

other patients, for one reason or another, suffered recurring circulatory

difficulties. Some died suddently outside of health care facilities and

the clinical performance of the implanted device or the value of the

replacement did not become known to the original surgeon. In other

instances, circumstances forced the patients to re-enter the health

care system where they were reoperated upon or else died of unrelated

causes. This last group constitutes the primary pool from which ex- planted cardiovascular prostheses originate.

In establishing the value of a recovery program and drawing conclusions from its statistics, it should be remembered that this pool was

not a normal population of patients; it was one tilted towards the

less healthy and less successful surgical candidates. There is, therefore, an apparent mismatch between the real device performance and that

perceived through an implant recovery program. In the present case,

there are other elements which further affect the result. For example,

many patients had degenerative diseases which brought on the condition.

Re-operation candidates tended to be "habitual"; patients with two

marginally successful attempts at reconstructive surgery had more chances of being reoperated upon than the ones who had a single successful

surgery and had been discharged from the hospital.

Experimental implantation of devices in animal models under closely

controlled conditions is essential in the evaluation of cardiovascular

implants. However, it is not sufficient; it does not accurately

simulate the conditions which will be met when such devices are used on

humans in large numbers. The first genuine insight on the clinical

performance of an implant in the field inevitably comes from the first

97
few recovered devices. Broad-based recovery programs, on the other hand,

provide knowledge regarding the long-term performance;, the possible

contraindications and the ultimate lifetime of the implant "in-vivo" as well as the limitations of the prevailing surgical technics and the

impact of other common parallel disease management procedure. They are also invaluable in directing evolutionary development of these devices.

Recovery programs need not recover only failed devices in order to forecast the ultimate lifetime of an implant. With current techniques of

"forensic" chemistry, pathology and other disciplines, it is possible to

ascertain the presence of subtle damages which have no clinical significance at the time of explantation but can eventually culminate in explicit

failure at a later date. Collected devices and their attached tissue,

the sutures and adhering thrombi are also good diagnostics with respect

to the compatibility of the device with the host organism under clinical

conditions. Complications related to parallel or complementary pharmacotherapeutic treatments can sometimes be forecast by the examination of

explants; the presence of sorbed pharmaceuticals, bacterial and fungal

invasion can often be detected. This is particularly important in the

cardiovascular sector where the average patient is in the later quarter

of his life and a variety of related or concurrent health problems may be

treated simultaneously and may assist or jeopardize the function of the

implant.

The general state of health of the patient is perhaps the most important factor in cardiovascular reconstructive surgery involving textile products since the living organism must provide the complementary part of

the prosthetic system through healing. A device recovery program does

not always give reliable information on the state of health of the

patient; case histories are needed to provide the etiologic context in

which such prostheses may be evaluated. From Table 4, it is readily

seen that most implantation candidates who provided explants had major

health difficulties at the time of implantation. Possible exceptions

included elective patients where aneurisms were the primary indications

for surgery. Also the causes of death (from autopsy specimens) suggested parallel development of other major health problems. Yet examination

of Tables 5A and 5B confirms that most patients were of a relatively

advances age and were affected with occlusive diseases.

The life expectancy of properly treated, implanted patients with

peripheral occlusive arterial diseases, not too uncomplicated by other

cardiovascular problems, is not significantly different from that of a healthy population of comparable age distribution (34, 38, 39); surgical

techniques which aim to correct or by-pass defective or occluded areas have merit primarily because, when successful, they can do much to the

patient's enjoyment of life. Their comfort is increased and their mobility is retained. Unfortunately, the underlying causes which led to the

first surgery generally remain and further surgical acts may be needed

at a later date. The implantation of a prosthesis into or near an area of blockage in order to irrigate the distal vascular bed does not, by

itself, arrest the progression of a degenerative disease: arteriosclerosis continues to increase. This is evident from Table 5.07 which

indicates that thrombus formation and degradation of the distal vascular

bed are amongst the primary cause of reoperations for patients with

occlusive diseases.

9 8
Tables 5 and 6 illustrate that over the last five years, three

devices dominated the sector and accounted for more than two thirds of

the products recovered; velours alone accounted for nearly a third.

Yet on considering tables 5.02 and 6.04, it seems that most of all

velours were recovered within two years of implantation where as almost

701 of knits were carried for more than three years "in-vivo" before re- operation or death. This, "a priori", suggests that the present popularity of velours is not fully justified on the basis of their long term

performance and that older styles of devices are at least as safe and

effective.

Functional cardiovascular fabric prostheses are composites of synthetic fibres and soft tissue at the moment of explantation. Their

performance assessment and their failure analysis are correspondingly

more difficult to carry out. "Healing" of the fabric and development

of pannus at the anastomoses are therefore crucial to the performance

of the implant "in-vivo".

Observations carried out on animal models and on recovered human

implants to compare the healing rate of fabric prostheses confirmed

that the healing process is identical for all Dacron prostheses ; it

depends primarily on the reorganization of the initial thrombotic matrix

which deposits on and within the fabric. Velour textiles appear to

provide a better encapsulation at a faster rate since a thicker lumen

wall deposit forms. However, the velour fibres are not fully incorporated in the neoendothelium and remain exposed to the flow of blood, in

particular near the anastomoses. The initial appearance of pseudoendothelial cells occurs within two to three weeks post-operative; these

are concentrated in the anastomotic area and develop along a continuous

front with the endothelium of the aorta and occasionally appear within

the folds of the crimps and in shielded or stagnant areas. However,

their clinical value is still debatable as they occupy only a minute

fraction of the total luminal wall area even after long "in-vivo" residency. During healing, the intrinsic thrombogenicity of the surface of

the endothelial izing prostheses diminishes rapidly and finally stabilizes

after two months post-operative. Porosity as measured by permeability,

a factor which is given considerable importance in the literature (2, 11,

43), does not seem to be a determining factor in the healing process, at

least in the range and types of porosities which are represented by

current commercial products.

A living organism fitted with a fabric prosthesis constitutes a new

system which behaves in a satisfactory fashion if the disturbance cause by the prosthesis can still be accomodated by natural adaptation of the

organism. This is strongly dependent on the general state of health of

the organism, even when considering only hemostasis blood coagulation

characteristics and connective tissue metabolism, factors which have

severe impact on the behavior of fabric cardiovascular devices. Adaptation is dependent on the general health and vitality of the organism.

In a patient, this is a difficult factor to define in which the medical

history of the patient, this genetic heritage and etiologic factors

specific to the site of the surgery contribute. Very large individual

99
healing rate differences can be found within a population. Such factors

affect endothelialization and healing of the anastomoses. In turn,

these same factors can indirectly affect ether performance determining

characteristics. Proper healing and endothelilization of the prosthesis

coincide with the return of normal platelet survival time and reduces

the consumption of fibrinogen. Well-healed anastomoses and endothelialized prostheses are no longer macroscopically porous and are thus less

exposed to bacterial invasion and growth.

Made up entirely of fibrin, collagen and fibroblasts, the primary

function of the internal capsula is to control the thrombogenecity of

the lumen wall. This is sufficient for a successful prosthesis. Complete

cellular neoendothelialization may contribute little to improve the

situation. Massive proliferative growth of perivascular collagen on

the exterior of the prosthesis appears as a net disadvantage; it con- straints the flexible prosthesis into an unstable matrix of tissue which

has a tendency to grow and eventually stenose the prosthesis or the

adjacent vessels.

The following sequence of events holds true for the healing of grafts

in healthy animal models; immediately following exposure to blood flow,

the surface of the prosthesis becomes covered with blood proteins, platelets, red cells and some fibrin. After about two days, this culminates

in a relatively thick layer of disorganized fibrin entrapping red blood

cells and other blood elements. Cells resembling fibroblasts or transitional form T cells appear between two and eight weeks post-operative and

the fibrin layer becomes dense and well organized; other blood debris

may act as cementing matrix. Some local cellular activity at the lumen

wall becomes visible between two to eight weeks and may culminate into a thin layer of pseudoendothelial cells on the anastomoses after several

months. Finally, the healing process reaches a plateau with the development of a patchy covering of thick, dense endothelium, with occasional

clusters of cells at the surface. Such complete healing is rarely observed in prostheses explanted from human patients. Such an effect may be

expected in young and healthy patients implanted as consequence of traumatic damage. Such patients, however, form a negligible minority of

implantation candidates amongst a pool of much older individuals with

various stages of degenerative or occlusive diseases; their healing

rates are slow and it is unrealistic to expect the development of autogenous tissue in sufficient quantities and of adequate mechanical properties to act as adequate blood vessels. Explanted devices examined to

date generally had very thin deposits of fibrin and other materials of

little cohesive strength. Even velours with their propensity for depositing thick linings with occasional microvasculature channels (capillaries)

rarely locked stable, coherent linings over much of the prosthesis area.

Some patients yielded devices almost devoid of surface lining after

considerable "in-vivo" residency periods; this was typical of diabetic

candidates. Contrary to previous beliefs, it now appears that the fabric

device is not just a scaffold or a model on which deposited blood elements

and other macromolecular substances can deposit and around which connective tissues grow; the fabric does not become redundant when the graft

reaches maturity. It is still needed to consolidate the weak neoendothelium. In addition, it may be called upon to protect it from the crushing and deforming forces generated by the developing perivascular tissue

in velours. Finally, this weak neoendothelium appears more vulnerable

to bacterial attack than normal vascular tissues.

I oo
Although some mechanical properties of the fabric, design features

of the prostheses and the geometry are secondary factors in healing,

they may nevertheless play a decisive role in the long term prognostics

of the patient. In the case of bifurcations, the junction of the legs

to the body is inevitably a poorly healed point for currently made devices

This fork remains a nearly bare fabric, uncovered by endothelium, and

remains thrombogenic for the duration of the prosthesis lifetime. Alterations in blood flow in that region may therefore present a major risk for

the patient, particularly with highly thrombogenic velours. Although

recent improvements in the haemodynamics of this area have taken place,

there is room for improvement, as turbulence and stagnation are undesirable factors. Yet there are severe technological limitations to improving

the geometry of that area with classical techniques of textile engineering; not only is the combination of a seamless branch points and crimping

difficult to achieve but it is also very unfavorable to laminar flow and

may preclude endothelialization. The ratio of cross sectional areas between the trunk and the tributaries is also of relevance. This issue

has been addressed by other authors (5) but wholly satisfactory solutions

have yet to be found.

A related issue is that of the mismatch between the prosthesis cross- section and that of the blood vessel to which it is anastomosed. A prosthesis, when pressurized, has a slightly larger diameter than the artery.

The result is a conduit with a larger blood volume per unit length than

the artery and a correspondingly lower blood velocity. Given the higher

thrombogenecity of the prosthesis as a whole, in particular if it has areas of bare fabric, thrombosis is therefore more probable as the thrombo

tic threshold velocity is reached sooner in the bifurcation area and at

the anastomoses.

The growth of stenosing perivascular tissue may also be stimulated

by a prosthesis with a weak, compliant fabric structure which expands

during the systole and contracts during the diastole. Sustained and

cyclic tension on collagen- forming tissues is known, empirically, to

stimulate growth of the tissue capsule and may further accelerate the

onset of stenosis.

In summary, the importance of the fabric component of prosthesis in

retaining the strength and the shape of the composite blood conduit

appears to have been neglected during the last decade.

4.2 Fabric Properties

All prostheses were found to lose stitch density. That is, the

fabric mesh opened-up gradually during "in-vivo" residency. The implications of this phenomenon is at the effective amount of material per unit area which held the prosthesis together diminished during use. Therefore, even if physical and chemical degradation of the fibres did not take

place, the strength of the prosthesis could still diminish with time.

i o I
A time -dependent diminishing stitch density suggests that the fabric,

initially compressed during fabrication, can somehow relax after implantation. As a consequence, the fabric structure inevitably suffers some form of irreversible dilation upon pressurization in the presence of lubricants and plasticizing liquids such as may be found in blood. Alternately,

the fabric can expand due to a distortion in shape and increase in tension

transfered to local portions of the knitted network; some fibres loops can tighten more in some areas than in others and thus allow dilation.

The rate of loss of stitch density depends on the type of fabric cons- truction and is not limited to medical textiles; it also takes place in consumer and industrial fabrics. Empirically, knitted fabrics such as the "two-bar warp knit" are more stable than the weft-knit devices.

Prostheses do not loose stitch density at the same rate; some fabrics

are more stable. Fabric structures differ in the amount of "free or loose" filaments which can tighten under pressure or tension. Cyclic

tension and pressurization facilitate and accelerate the process.

In addition, inherently unstable fabrics exhibit stitch density loss

and dilation in non-linear fashions. Some knitted configurations show

extremely rapid initial fabric relaxation with measurable reduction in

stitch density and distortion almost from the moment of blood pressurization. This explains the findings of other authors who demonstrated some knit configurations are particularly prone to dilation when pressurized

during surgery (35)

Prostheses were also found to lose the crimp geometry with time "invivo". Crimp is not lost in the same way for all types of fabric geometry. For example, very tight fabric structures with little interstitial

space between yarns and minimal excess interloop filaments length retain

crimp more readily unless there is a loss in the crease or "set" of individual fibres and yarn. On the other hand, more open fabrics allow rotation and displacement of fibres and rearrangement in the fabric which

culminate in loss of (macroscopic) crimp. However, the individual fibres can still retain the "set". A very rapid loss of macroscopic crimp in a fabric where individual fibres retain their "set" suggests an unsuitable

fabric construction.

Loss of crimp follows a similar pattern to the stitch density reduction and exhibits extremely rapid changes upon implantation for the circular crimp devices. This implies that the loss of crimp in such devices

may be primarily due to rearrangement of fibre geometry as opposed to

actual fibre fatigue and loss of "set". The helical crimp prostheses

examined were more crimp stable than circular crimp devices. The rate of

loss of crimp in helical crimp devices was much less severe initially and was gradual . The causes for the difference may not be intrinsic to the

geometry of crimping; they may simply reflect the different fabric styles or processes which are used to achieve crimping. However, this hypothesis

cannot be tested since the same fabric geometry is not available in both

crimping style. Different crimping techniques are found in the literature;

"a priori", these could have a large influence (for example, hot pressurization against a suitably shaped external mandrel or spiral winding of a thread with heat setting in a longitudinally compressed state) . NevertheI 02
less, it is apparent that different prostheses can have dramatically different degrees of crimp stability. The loss of crimp in a prostheses, as well as some currently available, do not have crimps, such devices appear

more subject to stenosis, suture disruption kinking and other forms of

haemodynamically unfavourable geometries, in particular at points where

there is substantial movement of flexing. For the need of the moment,

it is perhaps sufficient to say that a rapid loss of crimp, may it be

clinically important or not from the geometric or haemodynamic point of

view, is nevertheless a diagnostic of an unstable prosthesis fabric con- figuration and may forecast the occurence of more objectionable events

at a later date.

During this recovery program, random samplings of fibres were exa- mined by scanning electron microscopy. Prostheses showing evidence of

macorscopic damages received particular attention and various forms of

damage were encountered. Such damages separated into several categories

and by analogy with textile fibres subjected to controlled mechanical

abuse, it was possible to assign a probable cause of damage. Thus,

chemical deterioration with large losses in molecular weight produced

porous fibre surfaces, cracking and fibre cleavage perpendicular to the

fibre axis. Surface deterioration led to fibres with shallow crack on

the surface upon bending. Mechanically pulled or distended fibres fibrillated and cracked longitudinally and frequently "necked" to smaller diameters prior to failure. They also left dangling microfibres near the

break site.

Certain patterns of fibre damage indicate that surgical handling may

be the primary factor in failure or local damage. For example, the

application of unprotected vascular clamps can cause rupture of fibres

and perforation of prostheses. Yet in the prostheses examined where the

pattern of damage was suggestive of clamps, the morphology of the broken

fibre was not suggestive of mechanical abuse. Instead, it was concluded

that the clamp may have predisposed the fibres to an accelerated rate of

deterioration by modifying the physical structure (residual strain, cold

working, kinking) . The damage may therefore not have been evident at

the moment of the surgery. Over the subsequent "in-vivo" residency period,

deterioration preferentially took place in these areas of enhanced chemical reactivity and culminated in rupture of fibres and perforation of the

wall. In summary, the long-range impact of mechanical abuse during fabrication, crimpingm sterilization and surgical handling of such prostheses

have not been fully assessed. Retrieval shows that these are not negligible factors; they appear of considerable importance as they may control

the ultimate lifetime and the reliability index of prostheses "in-vivo".

The measurement of diameter and cross-section of filaments from

explanted prostheses confirmed that the polyester used in prostheses

sell measurably during the first 30 months of implantation. This swelling

is gradual and reaches a peak of about 5-6% . It may be associated with

the absorption of water or other blood components with a specific affinity

for the polyester. It may also be an indication of molecular weight breakI 03
down with the insertion of hydroxy and carboxy groups into the surface

layers of the fibre. Observations on prostheses with long "in-vivo"

residency confirmed that fibres can also suffer a reduction in diameter

with time. These observations are, at firts, contradictory. However, a possible interpretation is that fibres first swell, then degrade. Finally,

the molecular weight becomes so low that the surface material dissolves

or becomes or mechanically detached from the fibre core thus causing a decrease in diameter. Two discrete effects can be recognized: fibres

recovered from prosthesis with relatively short implantation times, in- crease in diameter are noted during the first 30 months while those with

long residency time show a gradual decrease in diameter which begins

after 30-50 months. Mechanical stretching of the weakened filaments can also cause a diameter reduction.

In summary, the polyester fibres used in existing prostheses are affected by the biological environment and the changes are suggestive of

multiple concurrent degradative processes with considerable short-term

and long-term impact on the over-all mechanical properties. Material is

lost from prostheses. This may ultimately enhance the risks in long-term

implantation candidates. Perhaps reformulation of improvements in the

polyester fibre, the spinning technology, the heat treatment and/or the

crimping procedures could lead to improvements in the chemical resistance

of existing fibres and the prostheses that are made from them. Conventional transmission infrared spectroscopy is not adequately sensitive to

establish the presence of chemical degradation in textile samples such as those used here. Conventional attenuated total reflection infrared spectroscopy ATR also yielded equivocal results. However, Fourier Transform

infrared spectroscopy confirmed the presence of an excess of hydroxy and

carboxy functions in yarns which had been "in-vivo" for more than 20 months

when compared to the unused reference products. By analogy with environmental deterioration of polyesters, it is tentatively concluded that hydrolysis takes place. Mass spectometry of thermally decomposed yarn also

suggested the presence of a larger quantity of very low molecular weight

fragments and a generally lower molecular weight measurements in samples

which had been implanted for several years.

Further work in these areas is necessary to establish the mechanism

of "in-vivo" degradation and the factors which contribute to it.

Bursting strength, as measured by the method chosen here, is an

insensitive parameter to detect subtle changes in mechanical properties.

Considerable scatter in data is noted. However, regression analysis of

the date showed a strong downward change in bursting strength with "invivo" residency time. This change amounted to about 10-15% after 2-3

years post- implantation, when all recovered prostheses were included.

Prostheses consisting of smaller diameter fibres generally showed

a larger drop in bursting strengths with time of residency. This is an expected result because the large surface area of the fine fibres gives

rise to a more rapid (volume) deterioration.

I 04
Figure 9

ESTIMTED RANGE OF ORIGINAL BURSTING STRENGTHS

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DATE OF IMPLANTATION

Of greater concern, however, is the actual bursting strength of

the prostheses at the moment of fabrication. These date are shown in

Figure 9, where the extrapolated original bursting strength of prostheses

are plotted against chronologic year of implantation. A severe decrease

in average reserve strength of prostheses is evident and reflects the

introduction and increasing popularity of the current velours and lightweight knits which can have as little as one fifth of the bursting

strength of earlier devices. In combination with the observable decay in

mechanical properties with implantation residency and the vulnerability

of low burst strength devices to intro-operative surgical damages, the

low initial burst strength devices appear less than ideal for patients

with long expected residual lifetimes.

I 05
5. Conclusions

5.1 Clinical and Technological Aspects

The pathology of recovered human cardiovascular implants constitutes

a key element in any device evaluation program. However, total reliance

on anecdotal observations is not justified. Ethical considerations in

surgery tend to bias the patient selection process towards the poorer implantation candidates. In addition, the haphazard recovery of implanted

materials embodies many uncontrollable variables which complicate the

assessment of the implant's performance. Early data derived from recovery

programs tend to originate preferentially from implanted patients who

suffer further complications leading to premature death or repeated cardiovascular surgery. Early data can therefore be deceptive as they frequently

originate from sedentary, debilitated patients. This may constitute an insufficiently stringent test on novel technology. Conversely, it may also

accentuate negative aspects in the implant performance. However, when

used devices are recovered in sufficient numbers, these programs establish

the clinical limits of that technology and of its therapeutic value. They

can also point the way to possible improvements.

The present work, even in its partly completed state, confirms that even after more than two decades of clinical use, polyester textile

prostheses are incompletely understood with respect to their "modus

operandi" in humans and that their performance in average diseased patients is not analogous to that in healthy animals. It also confirmed

that healing characteristics are not significantly different between the

various devices which have appeared on the market overt the last fifteen

years, except for the velours. This latter group encourages the development of excessive perivascular tissue and develops unnecessarily thick

lumen linings which has a repercussion on the service lifetime "in-vivo";

hyperplasia, stenosis and adhesion to adjacent tissue are more common. Sterile inflammatory reactions are also found and empirically, their

average "in-vivo" residency time, before the onset of difficulties, seems shorter than woven or knitted products.

Anecdotal evidence of other short-comings in various products was

also found and confirms isolated reports already present in the literature.

These include dilation, loss of crimp, loss of mechanical properties,

exceptional susceptibility to damage, embrittlement for lightweight knits

and velours (10, 12-20) and sterile inflammatory reactions for highsurface area velours (26, 50).

Noteworthy is the observation that the ultralightweight graft,

singled out for criticism because of its tendency to dilate soon after

^ being placed into service, has a bursting strength slightly under 15kg/cm

and that Table 2 shows five other types of prostheses with bursting

strength hear or below this value. Although strict correlation between

early post-operative dilation and bursting strength is not demonstrated,

it seems unwise to assume a large safety factor in the mechanical strength

and dimensional stability of prostheses which present low values for this

parameter. For these reasons, pre-operative manipulations and intraI OG
operative techniques may be more critical than for earlier devices of

stronger gauge. Additional work to fully assess the clinical risks in

the light of current surgical techniques will have to take into account

the limitations of the textile technology. Low fabric weight and high

porosity which benefit biocompatibility may be mutually exclusive with

large mechanical safety factors which are often strategic assets in

certain clinical circumstances. This is made even more important by the

observation that polyester fabric measurably with "in-vivo" residency

time.

It is presently necessary to establish design criteria for the forthcoming generation of cardiovascular prostheses. There is increasing

evidence that the current family of devices do not share the same characteristics of dimensional stability, biocompatibility with adjacent tissue,

resistance to mechanical significant biodeterioration and surgical con- venience as those used a decade ago. Yet quantification of the long-term

clinical value of individual devices is difficult since there appears to

be an insufficient number of "ex-vivo" test parameters available. The

burst test is a very coarse measurement which integrates many interrelated fabric design features into a single relatively insensitive number;

it is therefore not wholly satisfactory. Although efforts have been devoted to the establishment of "ex-vivo" design and performance criteria

for textile cardiovascular products (2, 11, 46, 47, 51, 53), it is becoming apparent that these parameters do not adequately predict the clinical merit and the service lifetime of the implants. Therefore the rational choice of prostheses for a given clinical situation remains difficult

in spite of more than twenty-five years of implantation experience.

Bursting strength of devices as a function of "in-vivo" residence

time indicate that there is measurable decay in the mechanical properties.

However, there is no basis, at this time, to fear early catastrophic

mechanical failure of these implants under normal physiology conditions

since they all exceed the bursting strength of average vascular tissue.

However, catastrophic rupture of the prosthesis "in-vivo" is not necessary

for a clinical failure. Deformation leading to interstitial bleeding or longitudinal tearing at the suture points is sufficient. The tenacity

of such fabrics and their resistance to fatigue is much worse under cyclic

pulsations and natural stresses caused by movement of the patient. An

inherently weak device with brittle fibres is also more vulnerable to

handling damage; local fibre scission, stretching and abrasions caused by

contact with surgical instruments and by cutting, suturing and occluding

procedures incidental to anastomosis accelerate the deterioration process.

Futhermore, these polyester fabrics suffer a significant loss of tensile

strength "in-vivo" over a period of several years, this corresponds to a decrease of about 4-7% annually. In addition, some constituent filaments

have been shown to "craze", split and cleave under "in-vivo" conditions.

On the basis of "ex-vivo" testing, the process is further accelerated

when fibres are under small sustained tension. Thus the newer generations

of thin lightweight grafts are potentially more vulnerable to trauma,

dimensional instability and embrittlement than the older devices.

I 07
At present, the newer prostheses are finding increased popularity

while the older, more robust ones, are falling into disuse. In turn, an increasingly large segment of cardiovascular surgery patients with widely varying prognoses are receiving fabric devices which may yet prove

less durable than anticipated. While congenital and traumatic cardiovascular defects in relatively young patients are now more frequently

repaired with fabric products which ideally should last several decades,

there are also many cases where concerns about long term durability are perhaps academic. At present, most of the new lightweight prostheses

appear satisfactory for the less stringent applications involving large

size blood vessels at unstressed locations.

As for fabrics such as velours which have a tendency to hyperplasia

and stenosis because of a stimulating influence on proliferative perivascular tissue growth, a more basic question of loss of patency must

be addresses in addition to the issue of marginal mechanical strength

inherent to the fabric construction. One may wonder however whether the new prostheses have sufficiently large safety factors and biocompatibility for all situation, regardless of patients' estimated residual lifetime and their degree of activity. Specific questions which remain to

be answered include the following. Should some versions of these devices

be contraindicated in surgery for certain patient classes (i.e. congenital defect repairs and traumatic damage in the young)? Should there be more stringent and meaningful "ex-vivo" criteria of performance on

general purpose device? Are they the best products which contemporary

biomedical and textile technology can provide?

Eventually, recovery programs such as are described here will provide answers.

5.2 On Retrieval Programs

An interdisciplinary, multicenter implant retrieval program can become an education for all participants. In this particular case, it

demonstrated that removed prostheses and associated tissue can contain

as much information as conventional pathology specimen. Although the

analysis of these complex systems appeared at first more difficult than

conventional pathology, it is now evident that this was primarily due to

inadequate collective knowledge in all of the disciplines which make-up

cardiovascular fabric technology.

Most surgeons participating in this program originally believed in

the immunity of polyester to the biological environment and to conventional surgical handling. Non-clinical workers in the research team were under the impression that implantation of prostheses follow the same ideal protocol and follow-up which take place in experimental sur- gery with animal models. Clinicians and non-clinicians believed that

materials and procedures associated with cardiovascular prosthesis

fabrication were specific to that sector. It is now recognized that

I 08
this is not so and that such products, no matter how refined, still have

much in common with consumer textiles. Perhaps the most useful result

derived from the recovery program is that it has underlined the realities

of industrial production, of practical surgery and of materials limitations .

Retrieval programs take a long time to become established, absorb

considerable amounts of resources and manpower and require long term

commitments. More often, they start as small, "ad hoc" "hobby" collections of failed devices given by colleagues in the same department.

This takes relatively little energy; conversely the information derived

is proportionnally smaller. The broadening of such implant collection

into significant retrieval and analysis programs inevitably require multicenter participation of several surgical groups. In addition, it requires

the cooperation of several pathology departments as well as access to

medical records. In the case of fabric cardiovascular devices, there is

the problem of prosthesis identification. It is only recently that manufacturers have begun to "label" prostheses directly with thermosol inks.

Presumably this will simplify identification in a few cases. However

prostheses are occasionally trimmed prior to surgery and there are strong

possibilities that the identification code is removed, discarded or obliterated during the preparation of the device or its explantation. Therefore, unequivocal identification of devices must be within the capability

of the research group. This is not as difficult as it appears at first

sight. However, it requires an in-depth knowledge of textile practices

and fiber identification techniques. It also requires an up-to-date

and complete retrospective bank of reference samples since it is not un- common for manufacturers to alter the production technology of a given

product after its introduction. Therefore, a certain degree of vigilance

over the commercial sector is necessary and timely purchase of new products

must be done. Furthermore, the introduction of new devices is often synchronized with the phasing out of older products which have lost popularity. Therefore, old samples can be extremely valuable as such devices

often reappear during recovery programs and may present cross -matching

difficulties if references are no longer manufactured. Some surgeons have

the habit of saving and filing the leftover prosthesis trimmings directly

in the patient records. The value of this procedure is obvious as it

gives a precise reference on the textile as it was at the time of implantation. Without this remnant, the material analyses are always subject

to uncertainties; prosthesis with long production lifetime are not always

made from the same materials by the same procedures, even if the fabric

geometry is not changed. Manufacturers depend on large fibre spinners

for their yarns and thus are at the mercy of the market and the goodwill

of the primary supplier when they deplete their first batch of yarn.

It is sometimes possible to estimate the original properties of a series of prostheses which were implanted at various times in the past.

For this purpose, the properties of devices implanted for different times

and originating from comparable families of products, can be extrapolated

I 09
to the moment of implantation. This is possible for burst tests and

molecular weight determinations which lend themselves to extrapolation

if enough different explanted samples are available. In summary, the

identification and characterization of textiles forms a key element in

recovery programs of this nature. This is in contrast with the simplicity

of identification in implants for total hip replacement of cardiac pacemakers; such devices have been engraved with serial numbers and commercial information almost from the moment of their introduction. At any

rate, their characteristics and appearance are so unique that misidentification is precluded. For fabrics, this demands more labor and may

require sophisticated microscopy and chemical analysis equipment.

Over the last five years, a number of manufacturers have introduced

patient reference cards for a number of implants. Pioneered for cardiac

pacemakers, this feature is slowly spreading to other sectors. Such

implant-patient cross reference file cards are enormously valuable during

any type of implant retrieval ; it is unfortunate that only a minority

of surgical centers make use of these cards. The filing of special information is very difficult and there is considerable resistance to the

introduction of any more "redtape" to the normal protocols. Perhaps a simplification of the card and or electronic data filing or processing

techniques could be of some help in order to minimize the clerical load

on. the surgical staff.

The fabric device is only one part of the prosthetic system. The

anastomoses, the ingrow tissue and the pathology of the patient at the

site of the operation, as well as the case history may have an equal, if

not superior information content. Much could be done to improve the re- cording, collection and processing of information of this nature. However, it is also labor intensive and is often clinically impractical.

The significance of some surgical details may also be unrecognized at the

time of the surgery. Therefore, recovery programs must still depend,

to a certain degree, on "forensic" sciences in order to extract certain

pathological information which are not available, recorded or obvious

from the explanted samples, or which have been partly obliterated during

the explantation step by a pathologist unfamiliar with all the peculiarities of the device which he excised; good liaison with pathology department yields valuable returns in any implant recovery program.

Since ingrowth tissue and pannus form integral parts of functional

prostheses, it is necessary to develop histo-pathologic techniques for

the preservation of the biologic component which are not deleterious to

the synthetic fibres. This problem may not be unique to cardiovascular

prostheses. This was done to some extent in this laboratory and the

technics are still being refined; it seems that it is always possible

to extract more information by the introduction of a new procedure. The

question is one of optimum returns for the invested labor. Tissue

staining methodologies were developed in house for this class of samples.

Originally, it was decided to differentiate only collagen from fibrin in

i i o
the soft tissue; it now appears important to locate and identify other

soft tissue components. For example, identification and the quantification of bacteria, elastin, smooth muscle, lipids, inorganics, the

location and severity of inflammatory reactions, the classification and

properties of pseudo-endothelial cells and their genesis are now interesting. Small implant recovery programs expose their staff to only a limited

range of phenomena of relevance. Thus as the recovery program becomes

larger, collective experience and insight builds up rapidly, efficiency

increases and success breeds more success. It is now apparent that protein analysis, high pressure liquid chromatography, x-ray diffraction,

electron probe microanalysis and neutron activation analysis will become

mandatory in order to elucidate some of the more subtle yet important

aspects of prosthesis biodegradation, tissue interaction, the impact of

common drugs and other features which are now know to be essential in

order to further improve the clinical value of these devices. Such work

however inevitably depends on the spontaneous and frequently unremunerated

participation of groups of workers in areas far removed from pathology,

surgery and textile physics.

Finally, the complexity of case histories which involve cardiovascular replacement surgery, in combination with the multiplicity of

participating centers and the large number of potentially recoverable

devices which contain important information make it imperative to develop standardized formats of data collection and storage. The existence

of unrelated embryonic recovery programs in different locations, the

sharing of clinical and pathological information and the statistical analysis of results from national and international programs will soon become

imperative in order to extract the maximum information from collected

cardiovascular implants. The further development of mathematical and

statistical analysis techniques also appears worthwhile at this juncture.

It would appear that some form of standardized electronic data processing

techniques where sample records are encoded in an internationally accepted

fashion would have much to offer in order to facilitate the retrieval of

clinical and technical informations. Finally, it must be emphasized that

information or experimental details which seemed unimportant yesterday,

all of a sudden acquire importance in the light of new knowledge. For

these reasons, the cataloguing and the preservation of samples according

to standardized techniques would be most beneficial, as it would allow

retrospective investigations for missed information.

i I i
6 . Ackna«7ledgments

The gift of reference prostheses samples from Meadox, (Brent Surgical, Canada), U.S. C.I. (Medico-Tech. Ltd., Canada), Golaski Laboratories

(Medtronic, Canada) and Rhone-Poulenc (Hospal, Canada) and the participation of staff from the Centre de la Recherche Industrielle du Quebec,

is acknowledged. We are indebbed for technical assistance to Suzanne

Bourassa and Denise Lafreniere-Gagnon and to all those nurses and techni

cians who participated in this project. The guidance of Dr Gerard Roy

and Dr Louis Levasseur is also acknowledged.

This work was supported in part by grants from the Quebec Heart

Foundation, the Department of National Health and Welfare (Canada)

through its National Health Research and Development Program and the

Mrs. Richardson Foundation.

The opinions expressed therein are solely those of the authors and

do not necessarily represent existing or forthcoming policies of the

affiliated or sponsoring agencies.

i i 2
References

(1) Wesolowski, S.A., Fries, C.C., Martinez, A. and McMahon, J.D.;

Arterial prosthetic materials; Ann. N.Y. Acad. Sc. 146, 325-344

(1968).

(2) Wesolowski, S.A.; Performance of Materials as Prosthetic Blood

Vessels; Bull. N.Y. Acad. Med. 48, 331-356 (1972).

(3) Sawyer, P.N. and Kaplitt, M.J., editors; Vascular Grafts,

Appleton-Century-Croft Publishers N.Y. (1978).

(4) Reichle, F.A.; Criteria for evaluation of new arterial prostheses

by comparing vein with Dacron femoropopl iteal bypasses; Surg.

Gyn. Obst. 16, 714-720 (1978).

(5) Sauvage, L.R., Robel , S.B., Wood, S.J., Yates, S.G., O'Brien, M.A

Smith, J.C., Davis, C.C., Hall, D.G. and Masfield, P.B.;

Geometric comparison of aortic bifurcation prostheses to the

normal and atherosclerotic human aorta and clinical trial of a vertical seamed bifurcation prosthesis; Surg. 8J_, 22-32 (1977).

(6) De Bakey, M.; The development of vascular 'surgery; Am. J. Surg.

137 , 697-738 (1979).

(7) Working draft for implantable vascular prostheses. Document

79/63 966, British Standards Institution (Sept. 1979).

(8) Proposed 150 working draft standard for vascular prostheses.

Document ISO/TC 150/SC 2/ WG 3/-X submitted by Australia

(March 1979).

(9) Draft standard for vascular graft prostheses. Document AAMI VPD 8/79 (1979).

(10) Berguer, R. and Higgins, R.F.; Deterioration of grafts and

prostheses; J. Cardiovasc. Surg. 1_7, 493-501 (1976).

(11) Golaski, W.M.; Engineering design factors in the construction and

evaluation of knitted arterial prostheses; presented at the

Symposium on Bio-Chemical Engineering Materials, Part II,

March 31 -April 4, 1968, Philadelphia, Penn. (1968).

(12) Lynn, R.B.; Knitted Dacron Ultra-Lightweight Grafts - A Warning;

Canadian J. Surg., 22, No. 6, 593 (Nov. 1979).

(13) Hayward, R.H. and Korompai , F.L.; Degeneration of knitted Dacron

grafts; Surg. 79, 581 (1976).

(14) Ottinger, L.W., Darling, C, Wirthlin, L.S. and Linton, R.R.;

Failure of ul tral ightweight knitted Dacron grafts in arterial

reconstruction, Arch. Surg. Ill , 146-149 (1976).

I I 3
Hussey, H.H.; Arterial replacement - Failure of synthetic prostheses. J. A.M. A. 235, 848 (1976).

Blumemberg, R.M. and Gelfand, M.L. (1977); Failure of knitted

Dacron as an arterial prosthesis; Surg. 8]_ } 493-496 (1977).

Deterling, R.A.; Failure of Dacron arterial prostheses, Arch.

Surg. 108, 13-14 (1974).

Cooke, P. A., Nobis, P. A. and Stoney, R.J.; Dacron aortic graft

failure; Arch. Surg. 108, 101-103 (1974).

Perry, M.O.; Early failure of Dacron prosthetic grafts; J. Cardiovasc. Surg. 16, 318-321 (1975).

Yashar J.J., Richman M.H., Dyckman, J., Witoszka, M. , Burnard,

J., Wyman, A.K. and Yashar, J.; Failure of Dacron prostheses

caused by structural defect; Surg. 84, 659-663 (1978).

Blum, L., Tiefenbrun, J.; Giant pseudoaneurysm. Late

complication of aortoiliac synthetic grafts; New York J. Med.

78, 1925-1927 (1978).

Kim, G.-E., Imparato, M. , Nathan, I. and Riles, T.; Dilation

of synthetic grafts and junctional aneurysms; Arch. Surg. 114 , 1296-1303 (1979).

Komoto, U., Uchida, H. and Teramoto, S.; Anastomotic rupture of

aortic grafts; Angiology, 30, 75-80 (1979).

Agrifoglio, G. , Constantini, S. , Zanetta, M. and Castelli, P.;

Infections and anastomotic false aneurysms in reconstructive

vascular surgery; J. Cardiovasc. Surg. 2£, 25-32 (1979).

Kennedy, J.H., Hwang, N.H.C., Leoffler, R. , Von Koch, L.,

Swan, J. A. and Henly, W.S.; Possible femoral "Steal" Syndrome

following femoral -femoral bypass; J. Cardiovas. Surg., 1_8, 373-378 (1971).

Kaupp, H.A., Matulewicz, T.J., and Lottimer, G.L.; Graft

infection or graft reaction? Proc. 27th Sci. Mtg. International

cardiovascular society, Nashville, Tenn., June 28, 48-49 (1979).

Wilson, S.E., Jabour, A., Stone, R.T. and Stanley, T.M.,

Patency of biologic and prosthetic inferior vena cava grafts

with distal limb fistula; Arch. Surg., 1]3_, 1174-1179 (1978).

Perry, Mo.0., Melichar, R. and Heimbach, D.M., Duodenal erosion

by aortorenal Dacron graft; J. Cardiovas. Surg. 1_8, 77 (1977).

0'Mara, C. and Imbenbo, A.L.; Paraprosthetic-enteric fistula;

Surg. 8J_, 556-566 (1977).

I i a
Pinkerton, J. A.; Erosion of Dacron graft by atherosclerotic

Plaque; J. Cardiovasc. Surg. 20, 385-387 (1979).

Seymou, E.Q.; Aortoesophageal fistula as a complication of

aortic prosthetic graft; Am. J. Roentgen. 131 , 160-161 (1978).

Rals, 0., Lundstrom, B., Anqvist, K.A. and Hallmans, G; Bilateral aneurism of Dacron grafts following aorto-femoral

graft operation; Acta. Chir. Scand. 142 , 479-487 (1976).

Taylor, R.S. and Fox, N.D.; Ultrasonic prediction of graft

failure; J. Cardiovas. Surg. j_8, 309-316 (1977).

Reichle, F.A., Rankin, K.P. and Tyson, R.R.; Long term results

of 474 arterial reconstructions for severely ischemic limbs:

a fourteen year follow-up; Surg. 85, 93-100 (1979).

Nunn, D.B., Freeman, M.H., Hudgins, P.D.; Post-operative

alterations in size of Dacron aortic grafts. An ultrasonic

evaluation; Ann. Surg. 189, 741-745 (1979).

Wukasch, D.C., Cooley, D.A., Bennett, J.G., Gontijo, B. and

Bongiorno, F.P.; Results of a new Meadox-Coo ley double velour

Dacron graft for arterial reconstruction; J. Cardiovasc. Surg.

20, 249-260 (1980).

Goldstone, J. and Moore, W.S.; Infection in vascular prostheses;

Am. J. Surg. 128, 225-233 (1974).

Christensen, J.T., Einarsson, E., Eklof, B. and Norgren, L.;

Synthetic arterial grafts; Scand. J. Thor. Cardiovasc. Surg. 1J_,

37-42 (1977), ibid. 12, 121-124 (1978).

Malone, J.M., Moore, W.S. and Goldstone, J.; Life Expectancy

following aortofemoral arterial grafting; Surg. 81_, 551-555

(1977).

Stephen, M. , Loewenthal , J., Little, M.J., May, J. and Sheil,

A.G.R.: Autogenous vein and velour Dacron in femoropopl iteal

arterial bypass-, Surg. 81_, 318 (1977).

Guidoin, R. , Gosselin, C, Marois, M. , Roy, P., Domurado, D.,

Rouleau, C, Blais, P., Cote\ J. and Awad, J.; Surface

characteristics of Dacron vascular prostheses implanted in human - A scanning electron microscope study; Sc. Elect. Microsc. Symp. 2_; 597-602 (1978).

Hartigan, J.M.; Meadox Medical Cor., personal communication (1977).
(43) Buxton, B.F., Wukash, D.C., Martin, C, Liebig, W.J., Hallman,

G.L. and Cooley, D.A.; Practical considerations in fabric

vascular grafts; Am. J. Surg. 125 : 288-293 (1973).

(44) Cooley, D.A., Wukasch, D.C., Bennett, J.G. and Truno, R.;

Double velours knitted Dacron grafts for aorta-iliac replacements. Chapter 18 in Vascular Grafts edited by Sawyer, P.N.

and Kaplitt, M.J., Appleton Century Croft, N.Y.

(45) Clark, M.J. and Hickie, T.S.; The quantitative analysis of some binary mixtures of fibers by methods of infra-red

spectroscopy; J. Textile Inst. 66: 243-248 (1975).

(46) American Society for Testing Materials. "Annual Book of ASTM

Standards, Parts 32 and 35" D2857-70, Philadelphia (1977).

(47) Norme Nationale du Canada; Mgthodes pour epreuves textiles;

CAN2-42-M77; Methode 7 (1977).

(48) Moore, W.R. and Sanderson, D.; Viscosities of dilute solutions

of polyethylene terephtalate; Polymer 9: 153-158 (1968).

0*9) Miller, D.C., Grlepp R.B. and Oyer P.E.. Initial clinical performance and histopathological evaluation of a new porous velour

knitted Dacron prosthesis. Europ. Symp. Cardiovasc. Surg.

Tel-Aviv Israel, June (1977).

(50) Kaupp N.A., Matulewicz T.J., Lattimer G.L., Kremen J.E. and

Celani V.J.. Graft infection or graft reaction?

Arch. Surg. 114, 1419 - 1^22 (1979).

(51) Abbott, W.M. , Bouchier-Hayes, D.J.

The role of mechanical properties in graft design, in "Graft

materials in Vascular Surgery" edited by H. Dardik. Symposia

Specialists Miami, P. 59-78 (1978).

(52) Hasegawa, M. and Azuma, T.. Mechanical Properties of Synthetic

Arterial Grafts. J. Biomechanics, 12, 509-517 (1979).

(53) Hoffman, H.L. and Turner, R.J.. A New Method for Testing Burst

Strength of Vascular Materials. Personal Communication, Meadox

Medical Corp. (1979).

I I 6
APPENDIX A

PROSTHESIS PROPERTIES AND FABRICATION TECHNOLOGY

1. Yarn

Current polyethylene terephthalate (PET) vascular prostheses

consist of continuous multifilament yarns. Each yarn is composed of

20-100 fine filaments which measure between 10-20 urn in diameter. The

number of filaments per yarn is called the "filament count" and the

width of the filaments is called the "filament diameter". The filament

diameter is controlled by the size of the holes in the spineret, the

degree of filament stretching as well as lateral shrinkage that takes

place during subsequent drawing, texturizing, compacting, crimping and

cleaning stages. A great variety of yarns can be produced by combining

identical or separately spun filaments.

The total size or "coarseness" of a yarn is measured in terms of

its linear density (weight per unit length). It can be seen from table

2 and 3 that the woven and the early knitted prostheses (Cooley, De

Bakey Standard, Milliknit) are constructed of heavier yarns; they have

bursting strengths above 19 kg/cm^. Recent designs of lightweight

prostheses have used finer yarns in order to provide more flexible, more

'porous and more easily sutured grafts. However, finer yarns, and

particularly fine filaments entail a higher surface area of material and

are more susceptible to damage from chemical treatments and handling as

well as from biodegration after implantation. Consequently the values

for the linear density of yarns may not be reduced without a penalty in

strength. There is a relationship between prosthesis diameter and

linear density value for a given fabric configuration which ensures

that the bursting strength of the resulting prosthesis is in excess of

12 kg/cm^. This value corresponds to a proposed minimum requirement

in the Draft British Standard and aims to provide an adequate safety

factor for long term implantation (7).

The first generation of densely woven and knitted grafts were

originally critized because of poor adhesion between the fabric and the

neointima. This disadvantage could be circumvented by using "texturized"

multi-filament yarns instead of "flat", non-texturized yarns. Texturizing involves heat setting the flat yarn in deformed states so that the

individual filaments are not densely packed.

Such yarns may show evidence of random or periodic local damage or

other filament characteristics which reflect the severety of the treatment (flattened surfaces, cross section and diameter irregularities,

sharp kinks and dents); texturizing processes may be applied to separate

filaments which are subsequently assembled or to preassembled yarns.

Both processes generate yarns with increased bulk and more open structures.

The methods used include forcing filaments or yarns, into a hot compartment to induce random kinks (stuffing box), shock cooling, crimping,

twisting, heating or stretching periodically, kinking with hot loosely

meshed gear wheels and asymmetrically heating the fibres on hot bars.

Such processes generally enhance the reactivity of the filaments and, on

I I 7
average, reduce the tenacity of the yarns. With the increased volume

occupancy and stretch of texturized yarns, thicker and more porous

grafts can be fabricated. Stiffness can also be reduced and surgical

handling characteristics may be improved by texturizing. Because of

the increased exposed surface area of filament, blood interaction and

thrombogenicity of the yarn is enhanced thus facilitating pre-clotting.

On the other hand texturizing reduces dimensional stability.

Most prostheses have used yarns consisting of filaments with

circular cross sections. However, some recent prostheses use yarns

with triloba! cross-section filaments. Such yarns have optical,

mechanical and tactile properties which differ subtly from conventional

ones. They scatter more light for a given opacifier (filler) concentration and can be textured more easily. The reasons for their

inclusion in medical fabrics is not clear at present although it has

been suggested that trilobal filaments increase the porosity and

facilitate the clotting process; superior adhesion and more efficient

entrapment of blood components are claimed (49). Trilobal filaments

exhibit fatigue damage under in vitro and in vivo conditions and their

larger surface area, the filament may be more susceptible to physicochemical and biochemical deterioration.

2. The Fabric

All commercial PET devices currently in use are woven or knitted

as seamless cylinders and may subsequently be processed to give circular or helical crimped tubes. Thermal and chemical treatments may

be used to achieve crimping. Prostheses fall under three classes.

These are the woven, the knitted and the "velour" fabric configurations. However, in effect, there are only two types of fabric

construction, the woven and the knitted; the latter class comprises

the velour as a variant.

Early experimental and commercial vascular prostheses were woven;

some made use of stock consumer or industrial fabrics. Later versions

had custom-woven textiles. Yarns production however, is a high

capital cost operation. Therefore custom-made yarns are seldom used;

instead suitable stock consumer or industrial yarns are selected and

given supplemental treatments

Woven fabrics consist of two sets of yarns, called the warp and

the weft, which are interlaced at right angles to each other. This is

the type of construction found in the Woven de Bakey and Cooley Grafts.

The warp yarn lie alternately over and under each of the weft yarns.

Consequently this fabric is designated a 1/1 plain weave and is called

a "taffeta". This is the strongest construction; it has the best

dimensional stability, the highest fabric density and the lowest

permeability to water. These and other characteristics, such as thickness and fabric weight (mass per unit area) are controlled by the size

(linear density) and number of yarns interlaced together. The number

of yarns per centimeter called wales/cm and courses/cm in table 2

gives the fabric count in each direction. Woven prostheses are less

prone to kink and collapse than knits. However, the construction has

poor compliance, limited elongation, limited water permeability and a tendency to fray. These properties confer notoriously difficult

I I 6
handling characteristics. The limited degree of compliance to longitudinal deformation can lead to high stresses at the anastomoses

and eventual failure of the suture or anchoring natural tissue for

devices implanted in the "stretched" state. Fraying must be guarded

against. Woven prostheses are particularly suited to emergency

surgical situations, for example in the resection of aortic aneurysms,

where large grafts are needed.

Knitted constructions were introduced with the aim of circumventing

the problems of traditional weaves. Knitted constructions contain sets

of yarns which are interlooped around each other instead of being interlaced. The compliance behaviour of knitted fabrics depends on the

direction in which the yarns are interlooped. If the yarns lie predominantly in the lengthwise direction then the fabric is a "warp knit",

whereas if they lie in the transverse direction, it is a "weft knit".

Figures A and B illustrate the difference in construction between a single "jersey weft knit" and a "2-bar locknit warp knit" when viewed

from the frontal plane.

All commercial knitted grafts have either "regular" or "reverse"

constructions. The advantage of the reverse jersey knit over the

normal orientation is that the wales on the inside of the fabric cause

less turbulence in the blood flow. The black yarns are included in

the diagrams for clarity.

Figures C and D show the external and internal views respectively of a De BakeyR Standard weft knit graft with single jersey

construction. Figures E and F show external and internal views,

respectively of a warp knitted Cooley Graft with reverse "2-bar

locknit" stitch. A significant difference between these two types of

knit is that weft knit fabrics unravel, whereas warp knits do not.

Knitted fabrics have much more open constructions than wovens.

This is illustrated by the water permeability values of table 3. Table 3 shows values of permeability to water for knitted grafts in

the range of 2,300 to 5,300 ml min*"2 cm

-2

. These values were obtained

in our laboratories using an applied pressure of 120 mm of Hg according to the test method described by Buxton & Cooley (43). Water

permeability values ranging from 2,000 to 5,000 ml min"' cm" 2 are believed to be an optimum figure (2). The more porous knitted grafts

require elaborate preclotting prior to implantation; thus the fabric

walls are rendered impervious by the accumulation of blood debris (2).

The increased stretch of knits provides better pulsatile compliance and mechanical compatibility with the host vessels. A disadvantage is the lack of dimensional stability; when exposed to cyclic

stresses, as experienced in the arterial system, such structure do

not behave perfectly elastically and tend to fatigue or "grow" over a period of time. This has been confirmed in-vivo on recovered

prostheses. Growth or dilation takes place with concurrent loss in

stitch density and the concentration of bending stresses on the loops.

This implies a decay in the tenacity of the fabric even in the absence

of chemical deterioration.

I;

I I 9
External surface of a de Bakey standard weft D: Internal surface of a de Bakey standa

knit prosthesis knit prosthesis

I 20
External surface of a warp-kitted Cooley

)rosthesis with reverse two-bar locknit F: Internal surface of a warp-knitted Cooley

prosthesis with reverse two-bar locknit.

I 2 I
So-called lightweight constructions were attempts at further

improving compliance and surgical handling characteristics as well

as healing properties by further reducing fabric density and thickness

Recent clinical experience suggest that such devices have inadequate

stability and mechanical strength for most applications (12-19) and

that healing is not significantly better than other constructions.

Catastrophic rupture is not necessary for failure. Dilation, fabric

growth and deformation leading to interstitial bleeding, suture line

disruption or stretching at the suture anchoring sites are sufficient.

Light weight devices appear more vulnerable to deformation and stretch

ing resulting from cyclic blood pulsations.

All commercial velour grafts have knitted constructions; they are

a late evolutionary variant o'f the knitted prosthesis. Except for

Microvel, they are all knitted from the same type of jersey weft knit or "2 bar bocknit" (warp knit) described previously. They differ from

the earlier knits by a much thicker fabric construction, a greater

porosity, a low fabric density and/or lower stitch density (table 2).

The "velour characteristic" is incorporated by the use of a finer and

lower linear density texturized yarn (Cooley Double Velour, Microvel),

a lower stitch density (vasculour D), napping the fabric with wire

brushes to give a raised, disorderly pile and/or laying an additional

set of texturized yarns under low tension so that they form a looped

pile above the base fabric (Microvel).

Velours aimed at improved adhesion of the initial thrombus layer

and the neointima to the lumen wall and minimum hemorrhagic blood loss

during and after the surgery. With a rougher and more porous surface

internally and externally, neointimal and perigraft tissue is expected

to grow more extensively into the device. The graft acts as a porous

trellis which provides an improved hypothrombogenic surface, accelerates preclotting by trapping fibrin and retains the cellular blood

constituents within the fabric so as to promote interstitial growth of

a fibrin matrix.

It is generally believed that the porosity of a fabric, as measured by permeability to water, reflect potential for tissue

adhesion. This is misleading because the permeability to water is a property that depends more on the porosity of the non-velour component

of the fabric. It is on the size and shape of the interstitial and

interf ilamentary pores in the flow controlling layer of the fabric and

the surface tension of the material with reference to water which

dominate. Tissue adhesion, on the other hand, is controlled principally by the porosity near the fabric's surface. It may be preferable

to measure the internal lumen wall surface porosity in terms of an "internal velour index" which measures the total amount of "cilia"

or accessible yarn extending into the lumen.

Since velour grafts have highly porous constructions with little

substance, their bursting strengths are not related to fabric thickness, but are influenced primarily by the linear density of their

yarns and filaments in the base component of the fabric. The "fill"

or velour component contributes little to the tenacity or the stability.

I 22
Microvel's low burst strength is also a consequence of its unique

construction. It is the only graft where the base fabric is knitted

with a half-tricot stitch with only one set of yarns. Two sets are

used in the locknit construction of all other warp knit grafts.

Microvel^ does contain a second set of yarns but they are used exlusively to form the loose looped pile and are therefore unable to contribute

to strength and dimensional stability.

On removal from the knitting machine, the water permeability of

the knitted and velour fabric is too high. Shrinkage of the knitted

construction is necessary to bring the fabric porosity within acceptable limits. This can be accomplished by chemical or thermal treatments.

The Chemical process consists of an immersion in swelling agents

(e.g. methylene chloride) and acid solvents (e.g. trichloroacetic

acid). The thermal process uses dry heat or a heat transfer medium at

120 - 155°C. In either case, the molecular structure of the PET is

given such mobility that the filaments can experience considerable

diameter increase and longitudinal shrinkage thus reversing the structural changes incorporated during the drawing of fibres and yarns. So

forceful is the swelling that individual filaments in a multifilament

yarn bundle are often crowded against each other while soft and develop

periodic flattened surfaces at the contact points.

These macroscopic changes are visible evidence of major alterations

in the macrolecular order. Thus compaction processes are accompanied by

significant changes in molecular orientation, crystall inity and surface

Concurrently or subsequently to compaction, most grafts are crimped

to radially stiffen the structure and increase the potential elongation.

This feature inhibits collapse, stenosis, wrinkling and kinking after

' implantation. This can be done by winding a thread spirally around the

graft after fitting it on a mandrel and heating it after compressing

the fabric tube from both ends. This produces a helical crimp. Such

methods, however, are not suitable for velours and high bulk texturized

yarn since the thread pressure will permanently flatten the pile. An

alternative crimping method using internal steam pressure in a mold is

preferred for velour grafts; the technique can produce circular as well

as helical crimps. The depth and frequency periodicy of the crimps in

a prosthesis (table 3) therefore depend either on the pitch of thread

windings or on the form and shape of the steam pressure mold.

It has been suggested that the helically crimped grafts have

better blood flow characteristics than the grafts with circular crimps.

A priori, a differences between flow characteristics of circularly

crimped and helically crimped devices of the same periodicity would be,

at best, marginal. Instead, the depth of the crimp in relation to the

average lumen diameter, the crimp frequency and the shape of the crest

on the crimp overshadow helicity or circularity insofar as the haemorheological characteristics of the devices are concerned.

3. Compaction and Shrinkage

chemistry of the PET fibres.

4. Crimping

I 23
The crimped configuration increases the longitudinal and radial

compliance of a graft. The presence of crimps provides a longitudinal

and volume compliance which are believed to facilitate maintenance of

patency of the graft, reduce the stresses and likelihood of stricture

and thrombosis at the anastomosis line and buffer the local blood

pressure pulse (water hammer effect) that results from an unmatched

graft/arterial compliance. However, the compliance and flexibility

of crimped grafts are severely limited when the graft becomes extensively encapsulated with new perivascular collagenous tissue; external

velours and double velours are known to develop abundant external

perivascular tissue.

The processes through which the prosthesis and its intermediates

must pass are not unlike those which lead to consumer products; the

melting, compounding, handling, spinning, weaving, knitting, crimping

and shrinking introduce contamination which cannot be tolerated on the

finished product and must be removed prior to packaging and sterilization.

5. Final Cleaning

Proprietary cleaning techniques for prostheses issue from conventional textile cleaning technology. They include hydrocarbon washes,

mechanical or ultrasonic agitation, countercurrent or continuous

solvent refluxing, caustic scouring, chemical bleaching and other

harsh treatments. Such treatments therefore have impact on the physical

properties and the surface chemistry of the device.

In many cases, yarns intended for wearing apparel or industrial

textiles must also be used for medical applications for lack of suitable alternatives. Occasionally, such yarns are already contaminated

to a level where they are difficult to process without jeopardizing

the knitting machinery; they must therefore be pre-cleaned on arrival.

These treatments may impose further penalties on the performance of

the finished product.

It is occasionally claimed that "medical grades" of yarn are used

for some prostheses. The only significant difference between the PET

used in vascular prostheses and that used in regular apparel, furnishing and industrial applications is that the "medical grade" appears to

have received an extra scour and bleach treatments to remove surface

impurities. Inevitably, the internal impurities and additives remain.

Thus, traces of initiators, ol igomers, anti-oxidants, stabilizers,

delusterant and pigment particles will be found in the yarns even after several years in-vivo.

Porous vascular prostheses must be free of pathogens. It is noted

that, if infected at implantation, prostheses and their neointima

have poor antibiotic accessibility and control of infection is

difficult. Therefore implants must be freed of micro-organisms by

post-manufacturing sterilization. This must destroy both bacteria and

spores and may be achieved by the use of dry heat, moist heat, gamma

irradiation or chemical agents according to established practices. Such

treatments are often deleterious to PET fibres and the changes which

I 2 4
occur in the material and the fabric must therefore be taken into

account.

6. Sterilization

Today, almost all prostheses are sold pre-steril ized in porous

envelopes or other similar packaging systems suitable for autoclaving

or gas sterilization. Some prostheses are claimed to be resteril izable

by steam according to traditional hospital practices. Other manufacturers advise against resteril ization under any circumstances.

Heat sterilization is most common. In dry heat sterilization,

pathogens are thermally oxidized at temperatures between 160° and 190°.

Moist heat sterilization is effective atlower temperatures (120-140°C)

but the presence of superheated water vapor is a potential plasticizer

for certain PET formulations. Predictably, such treatments can oxidize

the surface of PET and cause other physical and chemical damages to the

fibre.

Some hospitals resteril ize whole grafts or portions of grafts left over from previous surgeries. Multiple sterilization cycles in steam

cause some grafts to lose mechanical compliance and make them more

difficult to handle. Experiments in this laboratory do not support

the contention that repeated steam sterilization causes significant

changes in the gross permeability to water and in the bursting strength

of grafts. However, such thermal treatments, in combination with liquid

or reactive gas plasticization may sufficiently alter the surface

morphology and chemistry of the fibres to affect in vivo biocompatibility or accelerate biodeterioration.

Amongst chemical sterilization processes, only ethylene oxide is now used for prostheses; the reactive gas is normally diluted with other

gases such as Freons, carbon dioxide and water vapour. Ethylene oxide

can polymerize to oligomeric polyethylene glycols and remain sorbed in

the PET and act as a plasticizer or else change the surface properties

of fibres so as to influence the pre-coagulation step.

At present, it appears that only minimal physico-chemical changes

occur in spun and drawn yarns and in some of the woven devices as a consequence of sterilization. This is not necessarily the case for

knitted prostheses after compaction, crimping and finishing. Work in our laboratories suggest that changes occur to the chemistry and microstructure of compacted and crimped yarns when exposed to ethylene

oxide sterilization conditions.

Gamma radiation sterilization is becoming more popular. However,

conventionally accepted dosage for sterilization near 2-3 mrad and is

harsh on polyester molecules; it can cause chain scission, cross-linking, oxidation and other undesirable chemical changes. One manufacturer

uses this steri lization process, it is not unequivocally established

that cardiovascular fabric devices can sustain this treatment without

changes in properties.

I 2 5
In summary, polyester devices, once believed unaffected by sterilization treatment, are emerging as subtly vulnerable systems.

Their in-vivo performance and durability are controlled by many

factors, some of which are integral parts of the sterilization treatment. Even too mild sterilization processes which have no obvious

chemical repercussions on the chemistry of the fibre, there are still

many unanswered questions regarding changes in the physics of the

textil es.

I 2b
Di scussion

Question (R. Leininger, Battel le-Col umbus Laboratories): Your presentation indicates that there is a change in burst strength of cardiovascular prostheses with j_n vivo residency time but the correlation

coefficient of the data is not stated. Can the statistics of measured

burst strength be quantified or defined more precisely?

Answer : The nature of our recovery program is such that a remnant of

prosthesis of the same type and batch as that was originally implanted

in the patient is seldom available. Therefore, it is necessary to

depend on average properties of prostheses fabricated when the original

device was implanted. However, even that is not always available.

Also, our samples are not numerous. For these reasons, strict mathematical correlation is difficult if not impossible for many types of

early devices. It is noteworthy that a severe decrease in burst

strength is noted for some families of devices whereas others such as the Standard Knitted DeDakey appear to be as tenacious after 10 years

in vivo residency as the products which are commercially produced

today.

I Question (R. Leininger, Battel 1 e-Col umbus Laboratories): Are there

plans to do further fiber characterization work such as tenacity,

molecular weight and molecular weight distribution of the polyester

in the fibre?

Answer : This type of study has been considered and some portions of

it are currently in progress. However, there are severe difficulties

in conducting polymer characterization work on such small samples

which are contaminated by absorbed and adhering biological products.

Question (S. Bruck, Stephen Bruck Associates, Inc.): The biological

performance, as opposed to physical performance of grafts is influenced

amongst others by the post-surgical anticoagulation regime of the

j patient. Since there is no data presented on this factor, could you

please comment on anticoagulation in these patients?

Answer : Such information is occasionally included in patient records.

However, more often, it is omitted along with many other elements

which, in retrospect, appear very important in establishing the

performance of prostheses in individual patients. More detailed

medical and surgical records are necessary for any comprehensive

study on implant performance; these at present are not available

except in rare cases.

Question (S. Bruck, Stephen Bruck Associates, Inc.): There is need

for appropriate statistical analysis of performance data. Although

there is data presented on approximately 150 arterial grafts, there

I 27
were some of different construction and from different manufacturers.

There may not have been enough samples in various categories to reach

definite conclusion. Please comment?

Answer : In order to carry out comprehensive retrospective studies on the prosthesis' performance, many thousands of protheses would be

needed. However, for reasons which are outlined in the paper, collection of samples in a pathological study is dictated by factors over which there is no control. In fact, we should be grateful to have

had that many prostheses collected in conditions such that they could

be studied. Ultimately, there will be sufficient autopsy and recovery

data to make the statistical analysis on graft properties more meaningful. Until that time, however, the results presented in this paper

can only be regarded as qualitative. Nevertheless, trends towards

reduction in burst strength with i_n vivo residency are clearly shown.

Question (James Anderson, Case-Western Reserve University): Porous

vascular grafts in animals have been shown to undergo complete endothelial ization of the blood contact surface. However, this has not been

seen in human vascular grafts. Have you evaluated the degree of

endothel ial ization in your retrieved grafts? If there is not complete

endothelial coverage, is it possible to explain? Could the endothelial

layer, which is extremely fragile, be lost in the specimen work-up

procedure or is the luminal surface not completely endothel ial ized?

Answer : Endothel ial ization of tissue ingrowth devices is still

controversial and has been so for approximately 10 years in the

clinical and scientific literature. Studies on healthy animals

carried-out in our laboratories confirm there is some endothelialization on the luminal surface in particular near the

anastomoses. This occurs more readily in some classes of prostheses

in certain experimental animals. Chemical fixation treatment do not

destroy the morphology. Such structures readily service the specimen

work-up techniques and can be clearly seen even at low magnification

in some cases. However, it is noteworthy that endothel ial ization

with cellular development appears to proceed with great difficult

even in healthy animals. In the case of recovered prostheses used in

humans, cellular endothel ial ization is virtually absent or at best

sparse. Perhaps this reflects simply the age and the overall vitality

of the patient. This point is discussed further in the paper.

Question (Walter L. Scott, Food and Drug Administration): From the

data presented, the number of samples examined at each point in time

appears to be low. Therefore, the exact geometric location of each

sample could be an important variable when comparing prosthesisartery

morphology. Has this consideration been taken into account in sample

selection?

Answer : These factors have been taken into consideration when possible

Details of explanation sites and even parts of sample are often lost

I 28
between the operating room and the pathological laboratory. However,

the work is continuing and the protocol of collection is being refined.

Such considerations are now being taken more closely into consideration

for currently collected prostheses.

Question (U. M. Gross, Free University, Berlin, Germany): You use

the statements "healing" and "no healing" to describe the state of

the imolantation bed and the luminal surface of the Dacron arterial

prostheses. Please elaborate on the meaning of this terminology?

Answer : "Healing" in this context implies a healthy and well irrigated

tissue capsule of uniform and reasonable thickness throughout the

length of the prosthesis. This generally consists of new tissue

approximately 100 microns in thickness. Morphologically, this translates

as a smooth, glistening interior wall which has little obvious porosity

even when seen under high magnification. Absence of "healing", on the other hand, implies the lack of an internal capsule or the existence

of a porous, disorganized mass of fibrin and/or blood components even

after several months. This situation normally correlates with patients

afflicted by several concurrent diseases such as diabetes and/or

atheroselerosis. Such prostheses also have greater probabilities of

showing irregular thrombotic structures on the lumen and will generally

show many totally exposed Dacron fibers and sutures.

I 23

Clinical, histo-morphological and material

related observations on removed aluminaceramic hip joint components.

W. PLITZ

+

P. GRISS

++

+ Orthopadische Klinik und Poliklinik der

Universitat (Direktor: Professor Dr. A.N. Witt),

Labor fur Biomechanik

Harlachinger Str. 51

D - 8000 Munchen 90 / West-Germany

++Orthopadische Klinik Lindenhof

(kommissarischer Direktor: Privat-Dozent

Dr. P. Griss) Fakultat fiir Klinische Medizin

Mannheim der Universitat Heidelberg,

MeerfeldstraBe 69

D - 6800 Mannheim 1 / West-Germany

These investigations were supported by the German

Federal Minister of Research and Technology under

contract No. MT 02 34 and MT 267.

I 3 I
1 . Introduction

Every new biomaterial has to stand its test of

time in clinical practice after a period of extensive experimental testing. In the case of

high density alumina ceramic 5 years of clinical

experience as a bearing surface for artificial

hip joints have recently been completed in

Western Germany. During this clinical test

period some 3.000 hip endoprostheses with A^O^/

A1

2

C>3 ceramic bearing surfaces for socket and

ball have been implanted. Besides considerable

success reports (GRISS et al., 1977; MITTELMEIER

et al., 1980) material specific complications

appeared (Fig. 1). This paper deals with investigations of now 15 cases of removed endoprostheses with bearing surfaces of high density,

high purity alumina ceramic.

The report will be subdivided into the following

sectors of investigation.

- Clinical observations

- Histo-morphological results from the tissue

surrounding alumina hip endoprostheses

- Complete or partial fractures of alumina

ceramic components with special reference

to the self-locking taper for ball fixation

to the metallic stem.

- Wear behaviour of the ceramic bearing

surfaces

I 32
Clinical results

The one of us (P.G.) has recently reviewed his

own 129 cases of A^O^/A^O^ ceramic endoprostheses

implanted since 1974. An overall clinical success

rate of 84.2 p.c. (Fig. 2) is contrasted by

15.8 p.c. of fair and poor results, the latter

being caused by mainly individual clinical reasons

not directly related to the material and prosthesis

design. Most of the patients are very satisfied

with the endoprosthesis function.

Two prostheses had to be reoperated for cemented

stem loosening, 7 patients sustained a ceramic

ball fracture in the body requiring reintervention

(Fig. 3 and 4) . Loosening of a non-cemented screwsocket (GRISS et al., 1976; 1977) was not observed

in this series. This part of the ceramic hip

prosthesis concept therefore proved to be very

satisfactory in clinical practice.

Histo-morphological observations

.

Human material for histo-morphological examination

was obtained from 15 reinterventions in ceramic on

ceramic hip joint replacements. The prostheses were

in function between 2 weeks and 3 years. Both,

joints with a macroscopically visible high wear

rate and those with minimal visible wear of the

retrieved ceramic parts could be investigated.

The size of most of the ceramic wear particles

(crystals) stored in the neocapsular tissue around

A^O^/A^O^ ceramic hips was below 2|im. However,

some large grains "pulled out" in toto from the

I 33
articulating surface were in the range of up to

20 |im. All small particles were stored intracellular^ within histiocytes or accumulated

superficially in a layer of amorphous fibrincollagen separating the underlying scar tissue

from the joint surface. Macrophages overloaded

with phagocytized ceramic wear material tend to

form clusters or islands within the scar tissue

(Fig. 5a) . In deeper layers they concentrate

around small blood vessels (Fig. 5b). This

indicates transport of the wear material in

macrophages via perivascular lymphatic vessels

to local lymph nods. Observations in experimental

animals support this view (GRISS et al., 1973;

1974; HARMS and MAUSLE, 1980). Within crystal

accumulations only a small number of round cells

are scattered in between. More pronounced inflammatory cell reactions are seen in areas where

ceramic and metal wear (from the naked metal

taper articulating to the ceramic socket after

ball fracture) are deposited together. In cases

of stem loosening foreign body giant cells may be

seen storing PMMA particles freed from the cement

cuff by fretting of the metallic stem against the

cement. In conclusion the morphologic reaction to

ceramic wear debris in the human body is well in

line with the experimentally established good

tissue compatibility of particulate A^O^ ceramic

material

I 34
Ceramic ball / socket fractures in vivo.

Fig. 1 collected the ball / socket fractures

reported in the literature since 1974 in

Western Germany. This includes components of

3 different designs and manufacturers

(Fa. Feldmiihle, Friedrichsfeld , Rosenthal).

Fig. 3a/b shows typical X-ray examples of

ball fractures. Fig. 4 is a collection of

ball fragments removed from the body at reintervention after ball fracture in vivo . To explain these ball fractures a number of

hypotheses have been developed. From a clinical point of view extremely high strains

occuring during a "short term" subluxation of

the joint and the following hard rebounding

into the normal position, a non ideal fitting

of the male and female taper, "inborn" frozen

strains within the ball created during its

production, cement or bone fragments caught

between taper and ball during insertion or

even only a blood coated taper may produce

extremely high stresses at the ball metal

interface during accidentally high loading

and cause ball fracture.

A too vigorous blow with a mallet onto the ball

during its fixation to the metal stem at insertion can as well produce "frozen" stresses

in the ball itself. A wet "slippery" cone

during fixation of the ball causes unfavourable

friction-conditions in the ball / self-locking

cone system and creates a "frozen" stress

condition in the system.

I 35
In cases of socket fractures besides design

dependant reasons (large ceramic neck) an

unfavourable steep position of the socket

may induce a levering of the ball over the

sockets rim. This levering may occur during

routine movements of the leg and produce

local stress concentration in the socket

and the ball thus creating local implant

damage and fracture of ball and/or socket

in vivo .

Impaired strength of the high quality

; high

density, high purity A^O^ ceramic may be

another reason for ceramic component failure

in vivo . The strength of this material

depends among other characteristics on grain

size and grain homogeneity. Coarse grains as

seen in some removed cases can reduce the

local strength and initiate a material

fracture

In laboratory investigations HINTERBERGER and

UNGETHUEM (1978) have produced ceramic ball

fractures under static loading conditions by

means of the test equipment shown in Fig. 6.

At an average constant load of 40.000 N

(min. 19.000 N, max. 56.000 N) fractures of

ceramic balls (diameter 26 - 32 mm,

3 manufacturers) occured. In dynamic tests

several metal stems with ceramic balls have

been tested in "physiological position"

without corresponding socket (Fig. 7) . No

ball fractures were observed using this test

assembly under sinus load of 5.000 +_ 4.000 N.

I 36
Wear phenomena in ceramic hip joints.

As substantiated by WILLERT et al. (1976;

1978) basically every wear particle of a

given material for artificial joint replacement may have a detrimental effect on long

term function. The amount of wear per unit

of time and the morphology - in other words

form and size - of the wear particles are

considered to be a decisive criterion in

the functional failure of the artificial

joint system. One of the main causes fully

recognized only recently is the overflow

of wear particles within the joint space.

This results in overstressing of the body's

capacities to deal with this debris, that

means to store and to eliminate it.

Granulation tissue, bone resorption and

loosening of the implant are common features

in this process of particle "incorporation

and elimination".

We have observed one singular case of extreme

wear of a ceramic ball in a correctly implanted

endoprosthesis (Fig. 8) . This component had to

be removed 3 years after implantation for stem

loosening. The maximum loss of material in the

center of the load transmitting area amounts

of about 0.9 mm. The worn area comprises

approximately 650 mir£ , representing almost two

third of the available ball surface. A scanning

electron microscopic surface analysis of this

ball (Fig. 9) demonstrates massive destruction

of the surface.

I 37
Picture E in Fig. 9 on bottom left documents

the frequently observed phenomenon of grain

excavation which is probably the initial phase

of the whole destruction process. The arrow in

E points to a crack in the material which may

be recognized as a starting point for a

future grain excavation mechanism. It has to

be emphasized again that in this case correct

socket orientation and slight valgus position

of the prosthetic stem as well as two and a

half years of good function could not contribute

to explain this wear phenomenon. Studying the

cases in total all showed areas of wear in a

more or less impressive amount. Therefore,

besides mere defective surgical technique

(subluxation) further individual not yet fully

defined factors are involved in the process of

wear in ceramic total joint replacement.

Essentially the same manifestations of destruction occur both in sockets and balls. In

the cases investigated the destroyed surface

area of the socket is always smaller than that of

corresponding ball. Fig. 10 shows the worn out

sections of surface area as an informative

example? Fig. 11 shows the clinical aspect of

the removed implant.

I 36
6. Proposed mechanism of alumina ceramic wear in vivo.

Instead of discussing the cases in more extensive

detail (they almost exclusively show the same

basic wear phenomena) the authors present their

hypothesis of wear mechanism in A^O^/A^O^ ceramic

hip endoprostheses in vivo (Fig. 12). The starting

point in surface destruction of alumina on alumina

gliding partners is in our opinion always a grain

excavation. Fig. 13 represents such a grain excavation in the ball surface of object F / 10 shown

in Fig. 11. Following our hypothesis such a sharp

edged hard particle is caught between both gliding

surfaces moving one against the other under load.

This causes the crystal to change position and

consequently create further damage to the areas

being passed through the gliding way. This may

create further grain loosening and thus sustain a

snow ball effect (Fig. 14). As a consequence an

avalanch -like acceleration of further grain excavations and finally the destruction of the whole

bearing surface can result. Fig. 15 compares a

polished surface above with a worn out surface

below to support our observations and interpretations

more drastically.

In summing up these observations it can be stated

that material quality, design and implant finish

as well as adequate surgical technique are the

challenging factors for minimizing wear of A^O^/

A^O-j ceramic hip components (Fig. 16). Newer developments are aimed at further reducing the

average grain size of the material, improving

density, surface roughness, matching of socket and

I 39
ball (sphericity) as well as the technique of

the self-locking taper or other anchoring

techniques between ceramic balls and metal

components. Presently running and future

experiments however have to prove the

efficiency and relevance of these new developments for clinical practice.

Summary

All of the stated possible causes for component

fractures and/or surface wear do not generally

occur isolated from one another but exist quite

simultaneously, whereby they can reciprocally

influence each other adversely. Concerning the

virtual connection between the component loosening factors and the observed wear we can only

record that the tissue reaction onto wear-particles

as it is shown in section 3 may be supported by

the increase of the friction-moment between ball

and socket which is remarkable in case of destroyed surfaces. We have by clear mind not made

a statistical evaluation and classification of

individual cases because the total picture is

still too inconsistent.

In conclusion we would like to confirm the following

Based on the total number of implanted hip endoprostheses with ceramic-ceramic bearing surfaces,

the number of failures we have experienced appears

to be minimal. After an implantation period of now

5 years in Western Germany we consider it premature

to calculate a general percentage failure rate at

I 40
this time especially because reliable complete

figures are not available for either of the

implanted or removed designs. Despite the

constant manufacturer's claims alumina ceramic

has proved to be not absolutely free of wear

or the danger of component fracture. Therefore

alumina ceramic components deserve further

critical observation.

I 4 I
Literature

1. GRISS, P. , B. Krempien,

H . v . Andrian-Werburg

,

G.Heimke, R.Fleiner:

2. GRISS, P., R. Silber,

B. Merkle, K. Haehner,

G. Heimke, B. Krempien:

3. GRISS, P., E. Werner,

R. Buchinger, G. Heimke

4. HARMS, J., E. Mausle

5. HARMS, J. and

H. Mittelmeier:

6. HINTERBERGER, J.,

M. Ungethum:

Experimentelle Untersuchung

zur Gewebevertraglichkeit

oxidkeramischer (A^O^)

Abriebteilchen

Arch. Orthop. Unfall-Chir . 76

,

270 - 279, 1973.

Biomechanically induced tissue

reactions after A^O^-ceramic

hip joint replacement.

Experimental and early clinica

results

J. Biomed. Mater. Res. Symp.7,

519 - 528, 1976.

Die Mannheimer OxidkeramikMetall-Verbundendoprothesen

Eine kritische Wertung unserer

bisherigen klinischen Erfahrungen

Arch. Orthop. Unfall-Chir. 87,

73 - 84, 1977.

Biokompatibilitat von Implantaten in der Orthopadie.

Hefte zur Unfallheilkunde

,

Springer Verlag,

Berlin - Heidelberg - New York

1980.

Statistische Auswertung von

4 Jahren klinischer Prufung

der Hiif t-Alloarthroplastik

mit Keramik-Tragrippen-Endoprothesen

Med. Orthop. Technik 100,

25 - 29, 1980.

Untersuchungen zur Tribologie

und Festigkeit von Aluminiumoxidkeramik-Huftendoprothesen

Z . Orthop . 116,

294 - 303, 1978.

I 42
7 . MITTELMEIER, H.

:

8. WILLERT, H.G.,

M. Semlitsch,

G. Buchhorn, U. Kriete:

9. WILLERT, H.G.,

M. Semlitsch:

4 Jahre Erfahrung mit

Autophor-Keramik-Hiiftendoprothesen. Bericht iiber ein

Symposium am 18.11.1978.

Med. Orthop. Technik (MOT) 100,

19 - 25, 1980.

MaterialverschleiB und Gewebereaktion bei kunstlichen Gelenken.

(Histopathologic, Biokompatibilitat, biologische und klinische Probleme)

.

Orthopade 1, 62 - 83, 1978.

Tissue reactions to plastic

and metallic wear products

of joint endoprostheses.

In: Total Hip Prosthesis

N. GSCHWEND and

H.U. DEBRUNNER,

Hans Huber Verlag Bern,

Stuttgart, Wien, 1976.

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X-rays of Alumina /Alumina hip endoprostheses after ball fracture

(two different designs and

manufacturers)

I 4 6
X-rays of Mumira/Mumina hip endoprostheses after ball fracture

(two different designs and

manufacturers)

.

I 47
Macroscopic appearance of broken

parts of a 26 mm ceramic ball.

I 4 8
Fig. 5: a/b: Histo-morphologic picture of ceramic

wear deposits in human periarticular

scar tissue.

a) Cluster of macrophages loaded with

phagocytized A^Cs ceramic wear

particles

.

b) Peri-vascular concentration of

macrophages with Al^O^ wear

particles. Note only minimal

round cell reaction!

I 49
Line drawing of equipment for static

cone test (after HINTERBERGER and

UNGETHUM)

Fig. 7: Line drawing of equipment for dynamic

cone testing.

I 50

Fig. 9: SEM analysis of the ball surface

in Fig. 8.

A undamaged surface

B same area as in A magnified 800 x

C Boarder zone between damaged and

undamaged area. Arrow indicates area

of very high surface roughness.

D Damaged surface area (grain

excavation with average 10 - 15 |im

diameter)

E Grain excavation hole,

higher magnification.

I 52
I 53
Schematic draft of Al7Qfbearing-surface destruction

toad

destruction of bearing-surface

motion

grain excavation

t ~

| material quality | 1 excessive surface load] [ fault strain]

Fig. 12: Schematic representation of proposed

destruction mechanism.

Fi9* 13

Grain Excavation in the ball-surface

of the removed object shown in

Fig. 1 1 (magn. 6300 x)

I 54
Schematic destruction-mechanism

Destruction-mechanism of A^O^ bearing

surfaces in hip joints.

Comparison of "as delivered" surface

(above) with worn surface (below)

.

I 55
AlXXbeannq-surface destructbn factors

material quality

gran size av < 7^

purity Aipp>99.5%

excessive surface load

WW

fault strain

surface finish cia<o.o5yum

•-sphericity fd < 5/jm

luxation too short neck

length I ?

»~ position of stem or cup

<x<45°

Fig. 16: Possible destruction-factors of A^O.,

on AH^O^ surfaces.

I 5G
MICROSCOPIC ANALYSIS OF RETRIEVED

POLYMETHYLMETHACRYLATE (PMMA) BONE CEMENT

D.F. Gibbons* and K.A. Buran

+ Case Western Reserve University, Cleveland, Ohio 44106

Metallographicaly prepared sections from retrieved bone

cement were examined with reflected light microscopy. Gross

plastic deformation was observed in the femoral collar region

and interdigitating bone regions. Deformation strain lines are also observed frequently associated with cracks in the

cement. Plastic deformation of the bone cement under physiological stress states can therefore account for femoral com- ponent loosening. Cracks are also observed radiating from

the corners of the medial edge of the femoral stem. The

bone-trabeculae interface was observed to be closely adapted

with no fibrous capsule interposed. The surface morphology

of the cement with bone was demonstrated to range from smooth

to porous. These data correlate well with previous scanning

electron microscopic evidence. Bone debris from the surgical

procedure was also observed. Abrasive wear of the bone cement

at the prosthesis interface was observed which can account for

the small PMMA particles observed in the tissues of the joint

capsule.

Introduction

The successful implementation of an in situ polymerizing polymethylmethacrylate (PMMA) cement by Charnley [1] for the stabilization of the

components in total hip replacement (THR) caused a dramatic increase in

the total number of joint prostheses implanted in both Europe and the USA

[2]. The objective of the cement was to uniformly distribute the transfer of stress from the femoral component to the surrounding bone and thus

avoid bone resorbtion in regions which were unloaded, due to lack of direct

contact with the prosthesis. Until that time bone resorbtion had usually

produced disasterous loosening of the femoral component and thus severely

compromised the clinical efficacy of joint replacement.

Although the use of the PMMA cement for fixation of the components

has made total joint replacement an acceptable surgical procedure, a significant number of the joint components become loose with time. The

loosening mainfests itself clinically as pain and may subsequently lead

to fracture of the femoral stem, either of which require surgical revision,

A number of explanations for the loosening of the components of the prostheses, particularly of the femoral component of total hip replacements,

*Departments of Biomedical Engineering and Pathology

tDepartment of Biomedical Engineering

I 57
have been suggested. Mechanical failure of the PMMA cement, as a re- sult of the stresses applied during walking and other normal activities

has been implicated. Excessive wear debris, produced at the acetabularfemoral head articulating interface, has also been suggested as being

responsible for local bone resorption [3].

Many factors which influence the mechanical and physical properties

of bone cement have been investigated in vitro . The cement [4] consists

of spherical particles of PMMA, or a copolymer with -2% styrene, powder

produced by suspension polymerization. The powder also contains a catalyst, benzoyl peroxide. The bone cement is prepared by mixing the powder

with a liquid which consists primarily of the monomer, methylmethacrylate

(MMA), together with an accelerator, N,N-dimethyl -p-toluidene, and an inhibitor, typically hydroquinone. After mixing the liquid MMA swells

and starts to dissolve the PMMA powder, however polymerization of the

MMA is also initiated and the mixture increases in viscosity and eventually becomes a hard solid as total polymerization is achieved. The

final product is a two phase material consisting of the original spherical particles of the powder embedded in a martix of in situ polymerized

MMA. The matrix may contain either BaSCL or ZrCL powder (-10%) to make

the final cement radiopaque. The mechanical properties and heat evolved

during the exothermic polymerization reaction have been shown to depend

upon the ratio of liquid to powder [5], presence and amount of BaSO- or

ZrCL [6,7,8] and amount of catalyst [8]. The effect of the mixing rate,

which influences the volume percentage and size of air voids incorporated

in the cement, has also been demonstrated to affect the mechanical properties [9,10].

This study was undertaken to analyze the PMMA bone cement recovered

at surgical revision or autopsy and evaluate evidence for mechanical deterioration of the cement. Polished and etched sections were prepared

from the retrieved PMMA bone cement [11,12]. This method allows the

visualization of deformation and cracks in the cement as well as the

structure, including void content. A previous study of retrieved bone

cement [13] examined the surface with Scanning Electron Microscopy (SEM)

with the object of correlating the surface morphology with the surrounding

tissue. As a result of this study the authors speculated that the

irregular surface, in which the individual spheres of powder were observed

to be in an apparently "porous" array, could initiate cracks.

Materials and Methods

The series of retrieved bone cement samples which we analyzed were obtained from 9 cases of THR, 8 obtained at surgical revision and one at

autopsy. This analysis is part of the Implant Retrieval and Analysis

program of the Department of Pathology at CWRU. Table 1 summarizes the

pertinent data from these cases. The time of implantation ranges from

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I 50
15 months £o^5 years and 4 months* and the cement was either Simplex-P**

or Zimmer.

The sections for examination were selected from regions which were anticipated to provide potentially significant information e.g. the medial

and lateral collar region, medial and lateral borders of the stem (proximal

and distal), regions exhibiting cement interdigitation with bone, acetabular 5

, cup, areas showing defects, such as voids, folds and debris visible by eye or under 20x power with a binocular dissecting microscope.

The sections were cut from the specimens by hand with a jewelers saw. They were secured in a metallurgical mounting ring with Hysol epoxy cement

and polished by a standard metallographic technique to a 0.03ym finish.

After polishing the specimens were etched with nitric acid fumes for periods of from 2-5 min [14]. The metallographic specimens were then examined

with reflected light by a Zeiss Universal Microscope using Nomarski differential interference - contrast optics,

Results

a) Deformation : Figures 1-3 illustrate examples of gross deformation

of the bone cement. The spherical powder phase is highly deformed and the cross sections are no longer circular but tend to be elliptical with major:

minor axis ratios ranging up to 5:1, The deformed regions also exhibit a high density of deformation strain lines indicating regions of concentrated

flow in both the powder and matrix phases. The regions of gross deformation

were located

i) at the bone-PMMA interface, beneath the collar of the

femoral component, in the medial, mediolateral region,

Fig. 4(a),

ii) regions of PMMA which had penetrated into and were surrounded by the bone bed, Fig. 4(b),

iii) occasionally at the prosthesis-PMMA interface, the medial

border, at the junction between collar and stem, Fig. 4(a),

*We wish to greatfully acknowledge the three specimens included in this

series received from Dr. CO.. Townley (Port Huron, Michigan), the re- maining specimens were received from Drs. C. Herndon and V. Goldberg of

the Department of Orthopaedics, CWRU.

**Howmedica Inc., Medical Division, Rutherford, N.J.

***Zimmer USA, Warsaw, Indiana

i so
Figure 4. Areas of observed gross deformation, A

a) collar region

b) interdigitating cement-bone

Figure 5 illustrates an example of deformation strain lines. These

regions of plastic deformation may also be associated with cracks, Fig,

6. The regions where deformation strain lines are frequently observed

are the same as those described in i) and ii) for gross plastic deformation. They are, however, quite frequently observed in regions which

exhibit no gross deformation.

Figures 7-9 illustrate examples of crack propagation in the bone

cement. The cracks are most frequently associated with the intersection

of the medial and lateral faces of the stem. The general appearance of

the cracks, which are ascribed to failure of the bone cement - in vivo , is quite different to those produced in the cement during removal of the

cement at surgical revision, Fig, 10. Cracks are also observed in bone

cement which interdigitates with the bone bed,

b) Wear : Abrasive wear of the bone cement at the prosthesis interface,

whenever present, is readily visible on sections. Figures 11 and 12 show

the interface of the cement with the proximal medial surface of the femoral

stem; the originally spherical powder phase exhibits flat abraded facets

produced by the relative motion between cement and femoral stem. Figure

13 illustrates a typical example of the cement-prosthesis interface where

no relative motion occurred.

c) Cement-Bone interface : Figures 14-16 illustrate the range of morphologies observed at the surface of the cement. The morphology ranges

from a relatively smooth surface, no interdigitation with the bone bed

where the spherical powder phase rarely protrudes above the surface (Fig,

15) to a highly porous surface with some spherical powder particles barely

attached to the body of the cement by slender filaments of matrix phase.

Figures 17 and 18 show examples of the close adaptation of bone trabeculae to the cement surface. This adaptation may occur with viable bone

I 6 I
trabeculae either completely surrounded by cement (Fig. 17) or con- tiguous with a smooth surface of cement (Fig. 18).

d) Cement Morphology : Figure 19 (a) and (b) illustrate the structure

of Simplex-P and Zimmer bone cement respectively; these sections were

from cement mixed and polymerized in air in vitro at an ambient temperature of 23°C. The Zimmer cement contains non spherical particles of powder, typical of comminuted PMMA. Figures 20 and 21 illustrate examples

of bone debris incorporated into the cement; the bone chips appear to be

nonviable.

Discussion

Figures 1-3 clearly demonstrate that in vivo there are locations where

the bone cement is subjected to a predominantly compressive stress and that

the cement is capable of substantial plastic defromation, Presumably the

plastic deformation occurs slowly and may be characterized as creep deformation. The creep rate of bone cement at 24°C and subjected to compressive

stresses 62.0 N/mm (9,000 psi) has been measured [8] and shown to be

markedly increased by the plasticizing effect of water; Ringers solution

was used to simulate the biological environment, The lower stress range

for significant creep rates at 37°C in an aqueous environment has, to the

best of our knowledge, not been determined. It is, therefore, not possible

to estimate the probable stress to which the regions illustrated were subjected.

The observation of gross plastic deformation correlated with those of

Willert et al. [13] who demonstrated with SEM, the presence of highly deformed spheres at the surface of retrieved cement. However, they speculated

that the deformation occurred at the time of insertion, when the spherical

particles were softened by swelling of the MMA monomer. We consider that

this explanation is not consistent with the observations we have presented.

At the time of insertion the matrix is still viscous and in order to produce

the observed degree of deformation the matrix would be extruded from between the particles in order to produce sphere-sphere contacts. This is

not observed, the matrix phase still separates the powder phase particles. ' In addition the presence of deformation strain lines in both phases strongly

suggests that the deformation occurred in the fully polymerized state.

The deformation strain lines (Fig, 6) suggest that creep deformation of

both phases may also occur under a predominantly shear stress state. These

strain lines propogate through both the spheres and matrix indicating no major difference between the mechanical properties of either phase. This

is not unexpected since the powder is produced by suspension polymerization

rather than thermal polymerization under pressure, used in the mechanically

stronger commercial PMMA (Lucite^). The deformation strain lines may provide a nucleus for the initiation of a crack (Fig. 6) however, with the data

available we are not able to substantiate such a relationship.

The abrasion of the bone cement at the interface with a loose prosthesis

I 62
is of interest since the abraided debris presents a significant source for

the very small particles of PMMA which can be observed in the tissues of

the joint capsule [3]. Because the comminuted debris is restrained at the

cement/prosthesis interface it can accelerate the abrasive wear process

and induce highly non-uniform wear, with crater formations, which is

observed at the cement-prosthesis interface, particularly in the proximal

region near the collar.

The close adaptation of viable bone trabeculae to the bone cement has

been unambiguously demonstrated at both smooth surfaces (Fig, 18) and interdigitating surfaces (Fig. 17). This is of considerable improtance in understanding the mechanical aspects of fixation. Charnley [15] had demonstrated

that thermal necrosis occurred in the tissue adjacent to the polymerizing

cement and that fibrous tissue was then formed at the interface. The data

presented by our examination of retrieved cement, many months after surgery,

show that either viable bone can be maintained at the initial interface or that stress transfer to the bone is sufficient to induce new bone formation

which grows into the intersticies of the cement or up to a smooth surface..

Growth up to a smooth surface strongly supports the later hypothesis, since

it is unlikely that a smooth trabecular bone surface would exist at the

reamed surface produced at surgery to receive the implant and cement..

Analysis of retrieved bone cement using standard reflected light metal

lographic techniques has provided a useful method for exploring the mechanical behavior of PMMA bone cement, which has been subjected to the stress

states experienced in humans with partial or total joint replacements. The

technique has demonstrated that considerable plastic deformation, by creep,

can occur in the cement under certain physiological loading conditions.

These data suggest that these stresses may cause sufficient plastic deformation to the cement so that the stem becomes loose within the cement bed; a situation frequently confirmed by clinical observation at revision of the

prosthesis. The direct interaction of plastically deforming cement with the

bone bed is also of significance in that it represents another contribution

to the factors influencing the bone remodeling and/or resorbtion,

The authors wish to acknowledge that this investigation was carried

out as part of The Implant Retrieval and Analysis Program of the Department

of Pathology, CWRU.

References

1. J. Charnley, "Acrylic Cement in Orthopaedic Surgery", E and S Livingstone Publishers (Edin) 1970.

2. R.Y. Hon", J.L. Lewis, J.R. Zimmerman and C.L. Compere, Clin. Orthop.

and Rel. Res., ]32, 46 (1978).

3. H.-G. Willert and M. Semlitsch, "Total Hip Prosthesis", Edited by N. Gschwend and H.U. Debrunner, Williams and E i 1 kins Co, (Baltimore)

p. 205, (1976).

I 63
4. G.M. Brauer, D,J. Termini and G, Dickson, J, Biomed,. Mater, Res,, Vj_t 577 (1977),

5. E.P. Lautenschlager , B.K. Moore and CM, Schoenfeld, J, Biomed, Mater,

Res. Symposium No, 5, 185 (1974).

6. T. A. Feitag and S.L. Cannon, J. Biomed. Mater. Res,, 1J_, 609 (1977).

7. P.W.R. Beaumont and R.J. Young, J. Biomed. Mater. Res,, 9, 423 (1975),

8. R.W. Treharne and N. Brown, J. Biomed. Mater. Res. Symposium No, 6. !3, 81 (1975),

9. A.J.C. Lee, R.S.M. Ling and J.D. Wrighton, Clin. Orthop, and Rel . Res.,

95, 281 (1973).

10. R.M. Fumick and D.F. Gibbons, Orthop, Rev,, 8, 41 (1979).

11. R.P, Kusy and D.T. Turner, J. Biomed. Mater. Res. Symposium No, 6. 9_, 89 (1975).

12. R.P. Kusy, J.R. Mahan and D.T. Turner, J. Biomed. Mater. Res., 10, 77

(1976).

13. H.-G. Willert, K. Mueller and M, Semlitsch, Arch. Orthop, Traumat,

Surg. 94, 265 (1979),

14. D.C. Smith, Brit, Dent, J., Ill, 9 (1961).

15. J. Charnley, J. Bone and Joint Surg., 46B , 518 (1964),

I 64
I 65
Figure 6, Cement-Bone Interface:

Sample D - medial collar region

x 75

Figure 7, Cement-Prosthesis Interface: proximal stem region, trans< verse section.

I 66
Figure 8, Cement-Prosthesis Interface: Sample D - proximal medial

stem region x 75

Figure 9 9 Cement-Prosthesis Interface: Sample J - proximal medial

stem region x 75

Figure 10, Cement-Prosthesis Interface; Sample C - cracks produced

during removal x 75

I G7
Figure 11, Cement-Prosthesis Interface: Sample B - wear in medial

collar region x 100

Figure 12, Cement-Prosthesis Inter

face: Sample J - wear and cracks

proximal medial stem region x 75

Figure 13, Cement-Prosthesis Interface: Sample A - "normal" interface

x 75

l-4

*s If V : t

I 66
Figure 16, Cement-Bone Interface:

Sample H - central lateral region

x 75

I 69
Figure 19, Bone Cement: (a) SimplexP in vitro polymerized x 75

I 70
* - m

>To c < y

Figure 19, Bone Cement: (b) Zimmer

in vitro polymerized x 75

Figure 20, Bone Cement: Sample F - bone debris x 75 »^ • \ ?

'' ^ ^ % "3^ r

***

* m *

* 9 w* * . TP Mir , **~

*4 * m

Figure 21, Bone Cement: Sample J bone debris x 275

I 7 I
Discussion

Question (Anthony K. Hedley, University of California at Los Angeles):

I would like to address the comments about the intimate contact

between cement and bone. Have you any histology to show that there

are no cellular elements at the interface? Where did the cement come

from with respect to the prosthesis and what was the implantation

period? What was the mode of failure which lead to the retrieval?

What was the size of the trabeculae present? How do you know the

bone was viable? We believe that there is always a cellular response

at the interface which may only be a single cell thick. Under con- ditions of prosthetic instability metaplasia and bone resorption may occur with formation of the fibrous capsule. A bone to be viable

within acrylic nutrients must reach the deepest parts. If the trabeculae

are small (less than lOOp), the blood supply is peripheral so capillaries

must exist at the interface. With larger trabeculae (more than

lOOp), the blood vessels are contained inside the trabeculum, much

like an haversian canal, so a more intimate contact between bone and

cement is feasible. Thus, there are several factors involved in

attaining close contact between bone and cement and I would welcome

your observations with respect to these.

Answer : In the series examined so far and reported in the paper, we

have no histopathology data because the retrieval protocol did not

include formalin fixation. With the resolution available on specimens

prepared for reflected light microscopy it is not possible to resolve

details within less than ~ lOp of the interface. It is possible in

principle therefore to have a single cell layer between the cement

and bone. We have observed "viable" bone trabeculae in specimens

retrieved after 4 years and 4 years 6 months. The samples originated

from the central and proximal, lateral regions. The size of trabeculae

ranged from 600 to 300 nm and contained more than one haversian

system. The failure mode in one case was loosening in the cement and

the other was an autopsy case. The only case where the bone was unambiguously surrounded by cement the haversian structure is readily

observed (fig. 17). However, in other cases trabeculae were observed

at or near a surface where indeed one might anticipate that the

nutrient artery supply is superficial. Because of the retrieval

protocol we do not have standard histopathology evidence of viability;

future retrieval will include recovery in formalin.

We have data from a series of implant experiments in canine

femora which demonstrates that a rough or textured surface, such as occurs at an interdigitated PMMA surface, does allow direct apposition

between a foreign implant surface and bone, with no cellular or fibrous capsule interposed. It thus appears that the stress pattern

at an interface can markedly influence the nature and morphology of

the cellular response.

I 72
Question (Darrel W. Haynes, University of Arkansas Medical Sciences):

Can you be sure, using reflected light microscopy or transmitted

light, that the osteocytes are viable and are not just encapsulated

or entombed thus not enabling cell lysis to occur? Could the differences in sphere sizes be due to the possible differing polymerization

rates due to the warm bone and a cooler metal stem? Charnley has

stated that thin cement fails. Did you look at thin cement? What in

your opinion is the minimum and optimum cement thickness?

Answer : With the data presently available, we cannot categorically

establish that the bone is viable. However, in regions where we have

observed nonviable bone debris, there is a significant loss of lamellar

detai 1

.

The spheres are prepolymerized PMMA, it is only the matrix which

is polymerized i_n situ . There exists of course a range of diameters

for the spherical powder particles in the unmixed state.

We do not have sufficient data to answer the question of optimal

cement thickness. We would anticipate that it would vary with position

along the stem, since the interface stresses vary with location.

Question (Vimal Desai , Johns Hopkins University): In your study, did

you take any bone cement samples from the lateral side of an artificial

hip which experiences lesser load as compared to the medial side?

Did the samples from the lateral side show a lesser degree of gross

deformation?

Answer : We have examined samples from all positions, proximal,

distal, lateral and medical, etc. As indicated in figure 4, samples

where gross deformation was observed originated from the proximalmedial aspect.

Question (D. C. Richardson, Food and Drug Administration): In the

series of retrievals you have had the opportunity to examine, a) were

clinical parameters such as the time delay between mixing and the means of cement insertion (finger pressure, syringe injection)

retrieved as well, and if so, b) do your optical microscopic observations confirm published reports that good initial filling of the

extremely reamed-out medullary cavity with low-viscosity "dough" at

moderate-to-high injection pressures insures better interdigi tation

into bone than the older Charnley-recommended technique?

Answer : The study was retrospective and so no data was available

regarding the elapsed time between mixing and insertion. In all

samples retrieved so far the cement was manually inserted. However,

in all cases the degree of interdigi tation of the PMMA with bone

varied widely in any single case. Typically, all retrieved samples

had regions of good i nterdigi tation as well as areas which were completely smooth.

I 73
Question (Pei Sung, Food and Drug Administration): The failure of

bone cement caused either by brittle fracture or plastic deformation

is probably very sensitive to the polymerization induced stress

(internal microstress) , shrinkage and porosity generated from the

mixing procedures. I wonder is there any nontoxic, ionic polymerized,

zero shrinkage (during curing) bone cement available? Is anyone

performing research in this area yet?

Answer (D. F. Gibbons): To the best of my knowledge no cement, such

as you describe, exists at the present time. I believe that a few

groups are attempting to develop a more effective "cement", including

Dr. D. C. Smith, who played an important role in the early development

of the PMMA cement with Dr. Charnley.

Questi on (I. C. Clarke, University of Southern California, Los Angeles):

You referred to viablbone in DIRECT contact with cement. Other

detailed histological studies (e.g. Hedley, HIP Society, San Francisco,

1979) have described 1 i ve bone always separated by a fibrous membrane

from the acrylic cement. In other words, if the bone is dead, there

can be no reaction to the cement; if it is viable, a membrane forms.

Your data appears to contradict this argument and raises questions

about when is bone dead and how careful was the preparation protocol?

(i.e., preservation of soft tissue interfaces?)

Answer : As I indicated in my response to Dr. Hedley, the data on retrieved bone cement cannot rule out the presence of a single cell

layer; certainly no fibrous capsule is observable with the resolution

available. However, the surface roughness or "texture" caused by

i nterdigi tation with bone, is known in other systems, to allow direct

apposition between a foreign surface and viable bone.

I 74
PROSTHETIC HEART VALVES: WHAT HAVE

WE LEARNED FROM OUR CLINICAL

PATHOLOGIC EXPERIENCE

* + Ajit P. Yoganathan and Earl C. Harrison

* School of Chemical Engineering

Georgia Institute of Technology, Atlanta, GA 30332

+Cardiology Section

USC-LA County Medical Center

Los Angeles, CA 90033

Some of our clinical and pathologic observations, and

in vitro hemodynamic experiences with the Bjork-Shiley , StarrEdwards (ball valves), Smeloff -Cutter , St. Jude, Kay-Shiley and

tissue bio-prostheses are discussed. It is quite clear that at

present there is no ideal prosthetic heart valve. The major

problems that affect the mechanical valves are thromboembolism

and tissue overgrowth, while the porcine valves are affected

by structural degradation and poor hemodynamic performance in

the small sizes.

The observed problems of thrombus formation, tissue

overgrowth, red-cell destruction and damage to the endothelial

lining of vessel walls adjacent to the valve prosthesis are directly related to the hemodynamics of the respective prostheses.

It is our experience that all prosthetic heart valves that

are presently commercially available are liable to thrombus

formation and tissue overgrowth. Therefore, correlative

studies such as described in this article should be conducted

with all heart valve prostheses. Detailed pathologic studies

on approximately 150 to 200 recovered prosthetic heart valves

of different types are presently in progress.

1 . Introduction

Heart valve prostheses have been used successfully since 1960. As

stated by Roberts [l] the decade of 1960 will probably be remembered most

Figures in brackets indicate the literature references at the end of this

paper

.

I 75
in the annals of cardiology as the decade during which cardiac-valve

replacement became a successful reality. Of the nearly 50 or more different cardiac valves introduced over the past 20 years, many have been

discarded due to their lajk of success, and of those remaining several

modifications have been made or are being made. In addition, the next

few years will see the introduction of new designs of cardiac valves. The

most commonly used basic types of prosthetic valves at present are: (a)

the caged ball, (b) tilting or pivoting disc, (c) tissue bioprostheses

,

and (d) caged-disc valves. At present over 90,000 prosthetic valves of

different designs are used annually throughout the world.

Even after 20 years of clinical and pathologic experience the problems associated with heart valve prostheses have not been totally eliminated

The most serious problems associated with them are: (a) thrombus formation, (b) red-cell destruction, (c) damage to the endothelial lining of

the vessel wall adjacent to the valve, (d) excessive tissue overgrowth,

(e) valve failure due to material fatigue and/or chemical change, (f)

tearing of sewing sutures [1-10] . The current status of prosthetic heart

valves has been recently reviewed in some excellent articles and books

[1,5,6,7]. Problems (a)-(d) are directly related to the hemodynamics

associated with the various heart valves. The other problems are indirectly

related to the hemodynamics.

In vitro physical and hemodynamic characteristics of prosthetic heart

valves strongly influence their initial use. They are eventually, however,

judged clinically by the frequency and severity of the complications they

engender. Ideally, a prosthetic cardiac valve should not be degraded by

its biological environment nor cause any adverse effects on surrounding

tissues or blood.

(1) It should ideally have a durability equaling or exceeding the normal

life expectancy of the patient.

(2) The valve design should be such that it produces minimal restriction

(and therefore pressure drop) to forward flow for the tissue annulus

area that it occupies.

(3) Its size and shape should be such that it does not interfere with the

normal function of the surrounding tissues.

(4) It should be made as radiographically visible as possible without

significantly compromising its function or durability, or without

making it thrombogenic

(5) It should not be so loud that it distracts the patient; yet ideally

its opening and closing sounds should be distinctive enough to allow

detection of significant alterations.

(6) The physical and hemodynamic characteristics of the prosthesis should

be such that it produces minimal damage to red blood cells, platelets

and the surrounding tissues. It should not create large regions of

flow stagnation or separation which cause thrombus formation and/or

excess tissue overgrowth on the valve super -strueture

Heliums and his co-workers [11,12] and Hung et al. [13] have studied

the effects of shear stress on blood cell damage, while Fry [14,15] has

studied the effects of shear stress on the vascular endothelium. Damage

to platelets has been produced in a cylindrical viscometer at shear stresses

as low as 100-500 dynes/cm2 with ~100 second exposure times. Damage to

I 7G
normal red blood cells can occur at 1500 dynes/cm2

, yet sickle cells can be lysed at shear stresses of 500 dynes/cm2 . Fry has conducted two studies

of the effects of wall shear stresses on canine aortic walls with variable

exposure time. He found that endothelial cells on the vessel wall could

be damaged at wall shear stresses of about 400 dynes/cm2 and could be eroded

off the vessel wall at shear stresses of about 950 dynes/cm^. Blackshear

[16,17] and Mohandas, et al. [18] have suggested that red blood cells which

adhere to a damaged vessel wall or the super-structure of the valve (such as the cloth fabric) could be damaged at shear stresses as low as 10-100

dynes/cm2

.

2 . Experimental Methodology

During the past 15-20 years one of the authors (E.C.H.) has had the

opportunity to follow hundreds of valve patients and also to study approximately 100-200 recovered heart valve prostheses of different designs. In

this paper we will discuss briefly some of these clinical and pathologic

experiences with the Bjork-Shiley, Starr-Edwards (ball valves) , Kay-Shiley,

Smeloff -Cutter , St. Jude and tissue bio-prostheses

.

In addition, we have studied the in vitro hydrodynamics of these valves.

Such studies included the measurements of pressure drop, velocity and shear

stress, and the opening and closing motion of the valve. Velocity and shear

stress measurements were made using laser-Doppler anemometry. Detailed

descriptions of the experimental apparatus and techniques have been previously published [19-22]. We will also attempt to correlate the in vitro

hydrodynamic results with some of the clinical pathologic observations made

on recovered heart valve prostheses.

3. Results & Discussion

3.1. Bjork-Shiley aortic prosthesis

The Bjork-Shiley tilting disc aortic prosthesis has been in clinical

use since January 1969. Approximately 95,000 of the standard (flat disc)

prostheses have been implanted in the aortic position. The prosthesis has

undergone various modifications in design and materials since its initial

use. The original Bjork-Shiley aortic valve had a Delrin disc. The Delrin

disc, however, caused auto-claving and handling problems during surgery.

Therefore, since the spring of 1971 the disc has been made out of pyrolytic

carbon manufactured by General Atomic Company, San Diego. Over tne past

few years it has been observed that thrombus formation on the aortic face

of the disc could lead to impaired or abolished mobility of the tilting

disc. Unfortunately, it was not possible to monitor the disc movement

by radiographic techniques. In order to overcome this drawback valves

manufactured after September 1975, have a radio opaque Tantalum hoop

incorporated in the aortic well of the disc.

In our clinical use of the Bjork-Shiley aortic prosthesis we have

found that its major advantages are (1) low pressure drop, (2) low level

of hemolysis, (3) low profile and (4) structural durability. The majority

of patients achieve significant functional improvement after replacement

of their aortic valves with this prosthesis.

I 77
^REGION OF Mllfe)

TISSUE OVERGROWTR

MODERATE

THROMBUS

Figure 1. Recovered Bjork-Shiley aortic valve. Moderate

thrombus formation on aortic face of disc and marked tissue

overgrowth along the perimeter of the valve adjacent to the

minor outflow region.

REGION OF MILD^ISSUE

LVERGROWTI

Figure 2. Recovered Bjork-Shiley aortic valve. Thin layer

of thrombus on aortic face of disc and mild tissue overgrowth

along the perimeter of the valve adjacent to the minor outflow

region

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Unfortunatley , we have also observed thrombus formation and tissue

overgrowth in ten aortic prostheses recovered six months or longer after

implantation as shown in figures 1 and 2 . Such thrombus formation and

tissue overgrowth have also been observed by others [23-26]

These pathologic findings may be attributed to the flow characteristics

of the prosthesis. The open disc of the valve separates the flow into two

unequal regions. Varying degrees of thrombus formation were observed in

the minor outflow region, including the depression in the aortic face of

the disc and the metal strut bridging this area. Tissue overgrowth was noted along the perimeter of the prosthesis adjacent to the minor outflow

region. That overgrowth further reduced the available cross section for

flow in this already constrained area. Ill vitro measurements with a laserDoppler anemometer identified a zone of stagnation about 20 mm wide near

the aortic face of the disc (fig. 3) of a size #27 Bjork-Shiley valve. The

average velocities in the major and minor outflow regions were around 100

and 25 cm/sec, respectively, and the corresponding peak-shear stresses were approximately 700 and 150 dynes /cm^ (fig. 4) . There is reason, then, to

attribute the thrombus formation and tissue overgrowth to the stagnation

zone and the low shear in the minor outflow region [23].

Figure 5 shows the upstream aspect of a Bjork-Shiley aortic valve.

The valve had been implanted 23 months earlier. This case demonstrates

accumulation of thrombus between the upstream hinge and the base ring of

the prosthesis. A portion of the native aortic valve not removed at the

time of surgery probably produced flow stagnation and encouraged thrombus

formation. Figure 6 shows another consequence of undebrided tissue on a Bjork-Shiley tilting disc aortic valve. In this case the tissue impeded

the complete opening of the tilting disc.

In the hope of reducing the pathologic conditions of thrombus formation on the aortic face of the disc and tissue overgrowth along the sewing

ring adjacent to minor outflow region, the new convexo-concave Bjork-Shiley

prosthesis was developed. In_ vitro velocity measurements made with a laserDoppler anemometer in the immediate downstream vicinity of the convexo- concave Bjork-Shiley aortic valve indicate that the design changes have

decreased the size of the stagnation zone and have increased flow and shear

in the minor outflow region. We conclude that the problems of thrombus

formation and tissue overgrowth may be reduced in the new convexo-concave Bjork-Shiley aortic valve.

3.2 Starr-Edwards ball valve prostheses

The Starr-Edwards 1260 valves are closed caged silastic ball valves.

They are comprised of a polished Stellite alloy 21 cage with a combination

of Teflon and polypropylene cloth sewing ring. The cloth on the sewing

ring extends to the orifice, leaving no exposed metal on the in-flow face

of the valve. The ball is made of silicone rubber and contains 2 percentby-weight barium sulfate for radiopacity. The radiopacity aids visualization

of the ball motion on cinefluoroscopy . The 1260 model was first made generally available in July 1969 as a modification of the model 1200 aortic

prosthesis. Approximately 30,000 have been implanted in the aortic position.

It has an excellent record of durability.

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The Starr-Edwards Model 2320 closed caged ball valve prosthesis is

comprised of a Stellite alloy 21 cage with completely cloth covered struts

and a composite orifice consisting of metal and cloth to form the poppet

seating surface. The metallic stops project through the knitted orifice

at regular intervals. The cloth covering which is made of Teflon and

polypropylene is intended to promote tissue invasion and encapsulation of

the valve cage and its orifice. The ball is hollow and made of Stellite

alloy 21. It has potentially greater resistance to biodegradation as compared with silicone rubber. This model has been on the market since

1968.

The Starr-Edwards 2400 closed caged ball valve is known as a com- posite track valve prosthesis. " It is comprised of a partially cloth

covered Stellite alloy 21 and a hollow poppet made of the same material.

The cage legs are covered with a porous knit polypropylene cloth except

for an exposed metal track on the inner aspect which protects the strut

cloth and metal stops which protrude through the cloth at regular intervals

and protect the orifice cloth from poppet impact. All other surfaces which

do not come into contact with the poppet are completely cloth covered.

Examinations were made at the USC - Los Angeles County Medical Center

of 15 Starr-Edwards aortic ball valve prostheses recovered during autopsy

and/or surgery. Thrombus formation and tissue overgrowth were observed

at various locations on the recovered as illustrated schematically by

figure 7. Figures 8-11 show examples of some of the recovered ball valves.

Varying amounts of thrombus formation were observed predominantly at the

base of the struts and the apex of the cage, while varying degrees of

tissue overgrowth were predominantly observed on the aortic side of the

sewing ring and on the struts of the cloth covered valves. In some cases

the thrombus had grown along the struts, probably starting either at the

apex or the base of the struts. In addition, examination of the vessel

walls immediately downstream of the valve sewing rings indicated varying

degrees of endothelial damage and fibrous tissue proliferation in some of

the specimens. Detailed pathologic studies on the recovered valves are in

progress at the present time.

Clinical and pathologic studies on recovered Starr-Edwards aortic ball

valves by other investigators have also identified: (a) thrombus formation

on the apex of the cage, at the base of the three struts and occasionally

along the struts, (b) tissue overgrowth on the aortic side of the sewing

ring and on the struts of the cloth covered models, (c) endothelial damage

and tissue proliferation of the proximal ascending aorta, and (d) increased

hemolysis with the cloth covered strut models [1,3,4,27-31].

Clinical experience with the cloth covered Starr-Edwards aortic ball

valves indicated an increase in hemolysis as opposed to the non-cloth

covered valves. There was also excess tissue overgrowth along the cloth

covered struts. This seriously affected the motion of the poppet (ball)

Another frequent problem with the cloth covered valves was deterioration of

the cloth on the struts (probably due to ball impact) as shown in figure

11. This figure shows a 2320 Starr-Edwards aortic prosthesis which had

to be removed due to severe mechanical hemolytic anemia.

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Our in vitro studies on a 1260-12A valve (sewing ring: 27 mm)

,

indicate that the Starr-Edwards ball valves have major fluid dynamic

drawbacks [32] such as: (a) relatively large pressure drop (17.3 to 31.0 mm Hg at a flow rate of 417 cm3 /sec) , (b) hydrodynamically unstable poppet,

(c) regions of flow separation at the base of each of the three struts, (d)

region of flow stagnation at the apex of the cage CW to 15 mm in diameter)

(see fig. 12) , (e) large wall-shear stresses (^500-2000 dynes/cm2

) and bulk

turbulent shear stresses (on the order of 100-5000 dynes/cm2 ) in the immediate downstream vicinity of the valve, and (f) large shear stresses

adjacent to the poppet surface and struts (on the order of 10 2 - 10 3 dynes/

cm2

) .

The observed stagnation zone could encourage thrombus formation on the

apex of the cage, while the observed regions of flow separation could lead

to thrombus formation and tissue overgrowth at the base and upwards along

the struts. The observed wall shear could lead to damage of endothelial

tissue in the proximal ascending aorta, to hemolysis, and to thrombus

formation. In addition, the elevated shears adjacent to the struts and

the surface of the poppet could lead to increased hemolysis with those

Starr-Edwards ball valves having cloth covered struts.

3.3. Smeloff -Cutter ball valve

The Smeloff-Cutter prosthesis is a double-cage full orifice ball valve.

It consists of a double open-ended cage which is machined as one unit from

commercially pure titanium and a poppet made from solid silicone rubber.

The suture ring is made of non-reactive Teflon and loops of heavy Dacron

suture embedded inside the metal ring, with multiple knots for maximum

security. This valve has been on the market since 1966 and has a proven

record of durability. Approximately 20,000 valves have been implanted,

mostly in the aortic position. The valve is presently being manufactured

by Sutter-Biomedical , Inc. (San Diego, CA) .

Our clinical experience with this valve has been very satisfactory

[33]. Of a total of 46 patients followed over a period of 8 years, two

patients had pulmonary embolism and only one had a case of bland systemic

embolism. Fifteen of sixteen patients had mild hemolysis as evidenced

by increased serum lactic dehydrogenase or decreased haptoglogin or presence

of urinary hemosiderin. No ball variance or other types of material failure were detected in eight valves that were recovered at autopsy. Most of the

recovered Smeloff-Cutter aortic valves showed no regions of thrombus formation and/or tissue overgrowth on the valve superstructure. A few (2 or 3)

of the recovered valves showed small amounts of thrombus formation at the

base of the aortic side of the struts as shown by figure 13. In addition,

examination of the vessel walls immediately downstream of the valve sewing

rings indicated varying degrees of endothelial damage and fibrous tissue

proliferation in some of the specimens.

Our in vitro flow studies on a A5 Smeloff-Cutter valve (sewing ring:

26 mm) indicated that this peripheral flow valve creates relatively high

wall shear stresses (^ 1670 dynes/cm2 ) . As shown in figure 14 the velocities

near the apex of the cage were negative and on the order of -10 to -20 cm/s.

This may produce a mild "washing" effect and tend to prevent material adherin

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to the apex of the cage. A region of flow separation was observed near

the base of the aortic side of the struts. Such a region of flow separation

could lead to thrombus formation at the base of the aortic side of the struts

as shown in figure 13.

3.4. St. Jude bi-leaflet valve

Since July 1976, St. Jude Medical Inc. has been testing a new bileaflet prosthetic valve made of pyrolytic carbon. At present this valve

is undergoing clinical testing and evaluation at selected medical centers

throughout the world. As of April 1980, approximately 3000 implants have

been made in the aortic, mitral and/or tricuspid positions.

Velocity measurements [34] made in the immediate downstream vicinity

of a #27 St. Jude valve show that the flow field that emerges from the

valve is centralized (see fig. 15) . The velocity measurements also indicated

that there was a region of flow separation adjacent to the vessel wall and

immediately downstream from the sewing ring as can be seen in figure 16.

Such a region of flow separation could lead to tissue overgrowth along the

aortic side of the sewing ring. The wall shear stress (500 dynes/cm^) and

pressure drops across the St. Jude valve were lower than other valves tested.

Our clinical experience with the St. Jude valve indicates that postoperatively this valve creates relatively low pressure drops and the patients

seem to achieve significant functional improvement after surgery. The

mechanical durability of the St. Jude valve is not yet proven. One of the

major clinical disadvantages of this valve is that the motion of the valve

leaflets cannot be seen properly in cine-fluoroscopy . If viewed in the same projection during fluoroscopy the St. Jude valve is not properly

visible until the leaflets are in the fully open position as shown in fig- ure 16.

3.5. Tissue bio-prostheses

Tissue bioprostheses have been in clinical use since about 1968. However, it is only during the past five to seven years have they gained widespread use throughout the world. Their main advantage compared to the rigid

prosthetic heart valves is that they have a lower incidence of thromboembolic

complications [6,35].

At the present time the Hancock, Carpentier-Edwards and Angell-Shiley

porcine valves, and the Ionescu-Shiley calf pericardial valve are the most

widely used tissue heart valve prostheses. As of January 1980 approximately

50,000 Hancock valves and 25,000 Carpentier-Edwards valves had been implanted throughtout the world. Numbers for the other two valves are not

available

Our clinical experience with the tissue valves is that they have a lower incidence of thromboembolic complications as compared to mechanical

prostheses. Of a group of 34 recipients of single Hancock mitral valves

the incidence of atrial thromboembolic events was 7.0/1000 patient months.

Death due to thromboembolism occurred in one patient. Considering the

multiple factors involved in production of thrombi, it is unlikely that the

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placement of any prosthetic valve (even tissue valves) , especially in the

mitral position, will allow a patient to be totally free of the complications of thromboembolism.

The tissue bio-prostheses in general do unfortunately have the following clinical disadvantages: (a) relatively large pressure drops compared to some of the rigid prostheses, especially in the smaller sizes, (b) jet-like

flow through the valve leaflets, (c) poor opening and closing characteristics,

(d) material fatigue or wear of the valve leaflets, and (e) valve leaflets

are subject to changes that affect the natural valves, namely, lipid deposition and calcification. Figures 17-20 show examples of recovered porcine

tissue valves. Figures 17 and 18 show a Hancock porcine aortic prosthesis

(sewing ring: 24 mm) which had been implanted approximately 6 months earlier.

Figure 18 is the downstream aspect of the prosthesis trans-illuminated by

back lighting. The valve demonstrates heavy calcification. There was near complete immobilization of two of the cusps. The valve has a 79 mm Hg pressure drop at a steady flow rate of 20 £/min. Figures 19 and 20 show a Hancock porcine mitral (27 mm) and an aortic (19 mm) valve which had been

implanted approximately 2 years ago and were recovered during surgery. As

shown in figure 19 the mitral valve has large tear in one of the leaflets.

There was also calcification and prolapse of the leaflets. The aortic

porcine valve did not exhibit any obvious stiffening of the valve leaflets.

It, however, exhibited a pressure drop of about 60 mm Hg at steady flow

rate of 10 £/min. During cardiac catheterization a mean systolic pressure

drop of 55 mm Hg was observed across this valve. The foregoing example

illustrates quite clearly the fact, that in the smaller sizes the porcine

tissue valves are indeed stenotic. Figure 20 illustrates the phenomena of

"creep" in the valve stents. The above clinical pathologic problems have

also been observed by other investigators [8,9,36].

Even though the above examples discussed pertian to the Hancock prosthesis it is felt similar problems will be observed with the other types of

bioprostheses especially porcine valves. Detailed pathologic studies on the recovered bioprostheses are presently in progress. Our experience

indicates that of the tissue valves in current clinical use the IonescuShiley pericardial valves is hemodynamically the best.

3.6. Kay-Shiley disc valve

The Kay-Shiley prosthesis has been in clinical use since 1967. It

has been used exclusively in the mitral and tricuspid positions. It is a low profile valve. It has a Delrin disc poppet, bare Stellite 21 struts

and a Teflon cloth sewing ring.

Our clinical experience with this valve stems from the study of 82

Kay-Shiley mitral valve recipients [37]. Of a group of 63 patients

followed in the clinic the incidence of arterial thromboembolic events was 10.3/1000 patient months. Death due to thromboebolism occurred in seven

of the 63 patients. Figures 21 and 22 show examples of recovered KayShiley valves. Of the 20 Kay-Shiley valves examined at autopsy eleven

had thrombus formation and/or tissue overgrowth on the valve superstructure.

The thrombus formation mainly occurred at the base of the valve struts as shown in figure 21. Tissue overgrowth occurred along the ventricular side

of the sewing ring. The thrombus formation and tissue overgrowth in some instances prevented the disc from seating properly and thereby causing the

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(right) valves. The mitral valve has large tear in one of the

leaflets. Calcification was also observed.

Figure 20. Same two recovered valves. This figure shows

the phenomena of "creep" (drooping inwards) of the stents

of the mitral valve.

I 92
Figure 21. Recovered Kay-Shiley mitral valve. Thrombus formation at the base of the struts.

Figure 22. Recovered Kay-Shiley mitral valves. Thrombus formation at the base of the struts and tissue overgrowth along

sewing ring prevented proper motion of the discs. Figure also

shows clearly grooving and notching of the discs.

I 93
valve to leak during ventricular systole. The thrombus formation and/or

tissue overgrowth could be attributed to flow separation at the base of

the struts

Another problem observed with this valve was the grooving and

notching of the Delrin disc as shown in figure 22. The grooving and

notching of the disc was due to the prevention of proper disc motion

because of thrombus and/or tissue overgrowth on the valve superstructure.

Proper disc motion includes movement up and down the cage during the

cardiac cycle as well as rotation.

4. General Comments and Conclusions

An important aspect to the clinical evaluation of valve prostheses is

to determine how effectively the valve prostheses utilize the available

space in the aortic or mitral root. The space occupied by the valve in

the root can be estimated by knowing the mounting or sewing ring diameter.

However, because the primary orifice area of the valve is further obstructed

by the valve occluder or leaflets and the hinge or strut mechanisms, an effective valve orifice area must be estimated. The method for estimating

the effective orifice area described by Aaslid [38] was used in our in

vitro studies where peak volume flow and peak flow gradients were known.

The effective area indicies of the valves we studied were then calculated

by the following formula:

EOA = 0.32 PF

/Ap

where 0.32 is a constant determined by the units used and the density of

blood

EOA = effective orifice area

PF = peak volume flow (£/min)

Ap = peak flow pressure drop (mm Hg)

The effective area index as suggested by the pressure drop data showed that

the St. Jude valve allows the most forward flow for the space it occupies.

The other valves in descending order are: Bjork-Shiley , Ionescu-Shiley

,

Smeloff-Cutter, Starr-Edwards (ball valves) , and Carpentier-Edwards and

Hancock porcine valves.

A further important clinical consideration is a comparison of valve

profile heights as they relate to mounting diameters as shown in figure

23. The ball valves tend to have the greatest profile height while the

St. Jude valve has the lowest. There is a good deal of variation in

profile height between the smallest and the larger valves of each valve

type. The size and shape of a prosthetic heart valve should be such that

it does not interfere with the normal function of the surrounding tissues.

Pathology specimens shown in figure 24 suggest very strongly why all valve

prostheses should and must have radiographically visible components. More

advanced cases of poppet variance and partial obstruction to motion can be

» 94
COMPARISON OF VALVE PROFILE HEIGHTS (millimeters)

STARR EDWARDS

* I 260

SMELOFF CUTTER \

A"23/35

HANCOCK «242

IONESCU SHILEY

BJORK SHILEY

ST JUDE

"J

' 2 1

19 2 1 29 3 1 MOUNTING DIAMETER (millimutcrs)

Figure 23. Comparison of profile heights of different valve

types

.

Figure 24. Pathology specimens of various types of recovered

valves indicating the need for radiographically visible heart

valves

.

I 95
determined fluorscopically if the poppet is opaque. In the case of tilting disc valves it is important to be able to assess both the opening and

closing angle of the disc. It is also important to have a visible base

ring in all valve types in order to assist in diagnosing valve dehiscence.

Not only is it important to evaluate proper opening and closing of disc

valves but it is advantageous to know if they are able to rotate. The

Bjbrk-Shiley valve can be readily seen radiographically . A tantallum loop

has been implanted in the disc to assist in calculation of its opening and

closing angle. The model 1260 Starr-Edwards ball valve can also be readily

seen radiographically. Two-percent-by-weight barium sulfate in the silastic

poppet allows an examiner to determine the completeness of both the opening

and closing of the valve. The silastic poppet of the Smeloff-Cutter valve

contains no barium and its motion can not be easily visualized fluoroscopically. The titanium stent of the Ionescu-Shiley valve and the stellite metal

ring of the Hancock valve allow ready visualizaiton of the base ring motion

f louroscopically . The leaflet motion, however, can not be visualized. As

stated previously if viewed in the same projection during fluoroscopy the

St. Jude valve can not be properly seen until the leaflets are in the open

position.

HAUI UUHAHHI U V I SI BI L IT Y

OF HEART VALVE PROSTHESES

BJORK-SHILfEY

Stellite cage

Tantalum loop

in disc

IONESCU-SHILEY

b

Titanium stent

STARR-EDWARDS

(1260)

Stellite cage

Ball (2% barium)

HANCOCK

Stellite metal ring

SMELOFF-CUTTER

Titanium cage

Ball (no barium)

ST. JUDE

Cage/leaflets

Figure 25. Radiographic visibility of various types of heart

valve prostheses.

Everything else being equal the patient would prefer a quiet valve.

The bioprostheses are clearly the "quietest" valves while valves made of

pyrolytic carbon and hard durable metals are the loudest.

Some of the clinical, pathological, physical and hemodynamic characteristics of prosthetic heart valves which influence their use have been

considered. Our experience is that all valve types are liable to thrombus

I 9G
formation and tissue overgrowth. The "ideal" prosthetic heart valve has

yet to be developed. Accelerated fatigue testing and clinical experience

indicate that the Starr-Edwards 1260, Smeloff-Cutter and Bjb'rk-Shiley valves

are the most durable. The St. Jude valve produced the least restriction to

forward flow for the mounting area it occupied. It also had the smallest

profile height. X-ray visibility of the Bjork-Shiley and Starr-Edwards ball

valves was the best. The tissue bioprostheses were the quitest and probably

the least thrombogenic of the valves studied.

5 m Acknowledgment

The work was supported by the American Heart Association, Georgia Tech

Bio-Medical Research Grant, Donald E. Baxter Foundation and the Childrens

Heart Foundation of Southern California. We also wish to acknowledge the

help and co-operation of Professor W. H. Corcoran, Drs. W. A. Edmiston, A. Chaus, R. H. Franch, I. A. Shulman and W. Parnassus.

I 97
References

[1] Roberts, W. C. Choosing a substitute cardiac valve: type, size,

surgeon. Am. J. Cardiol. 38./ 633-644 (1976) .

[2] Roberts, W. C. and Hammer, H. J. Cardiac pathology after replacement

with a tilting disc prosthesis (Bjork-Shiley type) . Am. J. Cardiol.

37, 1024-1033. (1976)

[3] Roberts, W. C. and Morrow, A. G. Anatomic studies of hearts containing

caged-ball prosthetic valves. Johns Hopkins Med. J. 121 , 271-295.

(1967)

[4] Roberts, W. C. and Morrow, A. G. Late post-operative pathological

findings after cardiac valve replacement. Circ. Suppl. (I) 35-36 , 271-295. (1967).

[5] Lefrak, E. A. and Starr, A. Cardiac Valve Prostheses . (AppletonCentury-Crofts , New York, 1979).

[6] Ionescu, M. T. Tissue Heart Valves . (Butterworths , London, 1979).

[7] Prosthetic Heart Valves . Proceeding of a symposium at the 14th Annual

AAMI Meeting, Las Vegas, Nevada, May 21, 1979. Editors: Yoganathan,

A. P., Harrison, E. C. and Corcoran, W. H. (Caltech, Pasadena, CA,

March 1980)

[8] Spray, T. L. , and Roberts, W. C. Structural changes in porcine xenografts used as substitute cardiac valves, Am. J. Cardiol. 40, 319-

330. (1977).

[9] Ferrans, V. J., Spray, T. L. , Billingham, M. E. , and Roberts.. W. C.

Structural changes in gluteraldehyde- treated porcine hetrografts

used as substitute cardiac valves, Am. J. Cardiol. _41, 1159-1184

(1978)

[10] Chin, H. P., Harrison, E. C. Blankehorn, D. H. and Moaccnin, J.

Lipids in silicone rubber valve prostheses after human implantation.

Circ. Suppl. (I) 43-44 , 51-56 (1971).

[11] Heliums, J. D. and Brown III, C. H. Blood cell damage by mechanical

forces. Cardiovascular Fluid Dynamics (Edited by Hwang, N. H. C. and

Normann, N. A.) pp. 799-823. (University Park Press, Baltimore, 1977).

[12] Nevaril, C. G. , Heliums, J. D., Alfey Jr., C. P. and Lynch, E. C. Physical effects in red blood cell trauma. AIChE J. 15_, 707-711

(1969)

[13] Hung, T. C. , Hochmuth, R. M. , Joist, J. H. and Sutera, S. P. Shearinduced aggregation and lysis of platelets. Trans. Am. Soc. Artif.

Intern. Organs 22_, 285-290 (1976).

( 98
[14] Fry, D. L. Acute vascular endothelial changes associated with

increased blood velocity gradients. Circ. Res. 22.' 165-197 (1968) .

[15] Fry, D. L. Certain histological and chemical responses of the

vascular interface to acutely induce mechanical stress in the aorta

of the dog. Circ. Res. 2j4, 93-108 (1969).

[16] Blackshear, P. L. Hemolysis at prosthetic surfaces. Chemistry of

Biosurfaces (Edited by Hair, M. L.) Vol. 2. pp. 523-561. (Marcel

Dekker, New York, 1972).

[17] Blackshear, P. L. Mechanical hemolysis in flowing blood. Biomechanics - Its Foundations and Objectives (Edited by Fung, Y. C. , Perrone, N.

and Anliker, M.) pp. 501-528. (Prentice - Hall, Englewood Cliffs,

1972)

.

[18] Mohandas, N., Hochmuth, R. M. and Spaeth, E. E. Adhesion of red

cells to foreign surfaces in the presence of flow. J. Biomech. Mat.

Res. 8, 119-136 (1974)

.

[19] Yoganathan, A. P. Cardiovascular Fluid Mechanics . Ph.D. thesis,

(California Institute of Technology, Passadena, 1978)

.

[20] Yoganathan, A. P., Reamer, H. H. , Corcoran, W. H. and Harrison, E. C. A laser-Doppler anemometer to study velocity fields in the vicinity

of prosthetic heart valves. Med. Biol. Engng. Computing 17_, 38-44

(1979).

[21] Yoganathan, A. P., Corcoran, W. H. and Harrison, E. C. In vitro

velocity measurements in the vicinity of aortic prostheses. J.

Biomech. _12, 135-152 (1979) .

[22] Yoganathan, A. P., Corcoran, W. H. and Harrison, E. C. Pressure

drop across prosthetic heart aortic heart valves under steady

and pulsatile flow - in vitro measurements. J. Biomech. 12_, 153-164

(1979) .

[23] Yoganathan, A. P., Corcoran, W. H. , Harrison, E. C. and Carl, J. R. The Bjork-Shiley aortic prosthesis: flow characteristics, thrombus

formation and tissue overgrowth. Circulation 58_, 70-76 (1978) .

[24] Ben-Zvi, J., Hildner, F. J., Chandraratne , P. A. and Samet, P. Thrombosis on Bjork-Shiley aortic valve prosthesis. Am. J. Cardiol.,

34, 538-544 (1974)

.

[25] Bozer, A. Y. and Karamehmetoglu, A. Thrombosis encountered with

Bjork-Shiley prosthesis. J. Cardiovasc. Surg., 13_, 141-143 (1972).

[26] Chandraratne, P. A., Lopez, J. M. Hildner, F. J., Samet, P. and BenZvi, J. Diagnosis of Bjork-Shiley valve dysfunction by echocardiography

Am. Heart J., 91, 318-329 (1976).

I 99
[27] Smithwick III, W. , Kouchoukos, N. T. , Karp, R. B., Pacifico, D. and

Kirklin, J. W. Late stenosis of Starr-Edwards cloth-covered prostheses.

20, 249-255 (1975).

[28] Stein, D. W. , Rahimtoola, S. H. , Kloster, F. E. , Selden, R. and Starr,

A. J. Thorac. Cardiovasc. Sugg. 7X, 680-684 (1976).

[29] Crawford, F. A., Sethi, G. K. , Scott, S. M. and Takaro, T. Systemic

emboli due to cloth wear in a Starr-Edwards model 2320 aortic prosthesis.

Ann. Thorac. Surg. 16, 614-619 (1973).

[30] Lamberti, J. J., Das Gupta, D. D. , Falicov, R. and Anagnostopoulos,

C. E. An unusual form of- late stenosis after aortic valve replacement

with cloth-covered Starr-Edwards aortic prosthesis. Chest 71, 680-684

(1977)

[31] Davila, J. C. , Palmer, T. E., Sethi, R. S., DeLaurentis, D. A.,

Enriquez, F., Rincorn, N. and Lautsch, E. V. The problem of thrombosis

in artificial cardiac valves. Heart Substitutes: Mechanical and Transplant (Edited by Brest, A. N.), pp. 25-36. (Charles C. Thomas, Springfield, 1966)

[32] Yoganathan, A. P., Reamer, H. H. , Corcoran, W. H. , Harrison, E. C.

,

Shulman, I. A. and Parnassus, W. The Starr-Edwards aortic ball valve:

flow characteristics, thrombus formation and tissue overgrowth. BioFluid Mechanics 2, 267-294 (1980)

[33] Sarma, R. , Roschke, E. J., Harrison, E. C. , Edmiston, W. A. and Lau,

F. Y. K. Clinical experience with the Smeloff-Cutter aortic valve

prosthesis: an 8-year follow-up study. Am. J. Cardiol. 40_, 338-344

(1977)

[34] Yoganathan, A. P., Corcoran, W. H. , Harrison E. C. and Chaux, A. In

vitro fluid dynamics of the St. Jude, Ionescu-Shiley and CarpentierEdwards aortic valve prostheses. Bio-Fluid Mechanics 2_, 295-316 (1980) .

[35] Stinson, E. B., Griepp, R. B. , Oyer, P. E., and Shumway, N. E. Long

term experience with porcine aortic valve xenografts. J. Throac.

Cardiovasc. Surg. 7_3, 54-63 (1977).

[36] Broom, N. D. Fatigue induced damage in glutaraldehyde-preserved heart

valve tissue. J. Thorac. Cardiovasc. Surg. 76_, 202-211 (1978).

[37] Edmiston, W. A., Harrison, E. C. , Parnassus, W. , Mitani, G. and Sarma,

R. Thromboembolism in aortic and mitral prosthetic valve recipeints.

Prosthetic Heart Valves (Edited by Yoganathan, A. P., Harrison, E. C.

and Corcoran, W. H.) pp. 357-367 (Caltech, Pasadena, CA, March 1980).

[38] Aaslid, R. , Levang, 0. , Frosaker, T. , Skagseth, E. and Hall, K. V.

In situ evaluation of the aortic pivoting disc valve prosthesis.

Scand. J. Thorac. Cardiovasc. Surg. 9_, 81-84 (1975).

200
EXAMINATION OF ORTHOPAEDIC IMPLANT FAILURES

Leonard M. Taussig

Taussig Associates, Inc.

6955 North Hamlin Avenue

Chicago, Illinois 60645

A study of 110 removed metal prostheses and internal fixation devices was conducted over a 26 year period. The case histories accompanying each implant allowed the correlation

of the metallurgical analyses with possible causes of failure.

Statistical tables provide information regarding classifications of the implants by cause for removal, anatomical location, type of implant, fabrication method and alloy, fracture

mode and location for various implants, and general patient

information relative to the implants. The reguired metallurgical analysis (designed to comply with all ASTM specifications),

consisting of non-destructive testing, semi-destructive testing,

and in certain cases mechanical tests, is briefly described.

The characteristics of different fracture modes, such as due

to mechanical fatigue and fatigue corrosion, are discussed

and illustrated by photomicrographs, and the origins of the

failures presented when possible. The difference between

stress corrosion and fatigue corrosion is also explained. The

study utilizing metallurgical analysis, patient histories,

and the physiological aspects surrounding the events prior

to and after failure, indicates correlations between implant

fractures and lack of bony union, fatigue forces, design deficiencies, surgical implantation technigues, and improper

use of the implants. Experience in metallurgy and its application to the implant and its environment reguired for acceptable and proper retrieval analysis is emphasized.

1. Introduction

The 110 fractured metal prostheses and fixation devices included in

this study were chosen from more than 500 submitted for analysis over the

last 26 years. The implants selected were accompanied by sufficient

patient medical information to make it feasible to correlate the conclusions of the metallurgical analyses with other conditions possibly

causing or contributing to the failures. Tabulations of statistical

information derived from these case histories and specific examples of

failures are presented.

In the context of this article "failure" is defined to mean that the

implant did not accomplish its intended function and/or actually fractured,

and had to be retrieved.

The implants examined were manufactured by nine competitive companies,

both U.S. and foreign. Their distributors, several hospitals, numerous

doctors, and legal firms also became involved when litigation resulted

from the failure of an implant.

20 I
During the period 1954-59 establishing development and testing

procedures in the laboratories of implant manufacturers, investigating

heat treatment methods for improving implant properties, and determining specifications for materials and fabricating techniques were the

most significant problems to be solved. Since then, due greatly to the

impact of the American Society for Testing Materials F-4 Committee for

Medical and Surgical Materials and Devices, formed in 1962, the effort

has concentrated on the evaluation of failures (1).-'-

The failed implants were subjected to appropriate metallurgical

tests such as chemical analysis, light and electron microscopy, mechanical testing and other procedures depending on the nature of the

problem. All testing conformed to applicable ASTM F-4 Committee

specifications.

2. Procedures

The first phase of testing is non-destructive, and after visual

and macroscopic inspection, may involve light and electron microscopy,

radiography, fluorescent penetrant examination and energy dispersive

x-ray analysis. After the non-destructive phase has been completed,

semi-destructive testing including chemical analysis, determination of

grain size, inclusion content, and hardness and other metallurgical

properties is conducted. Then, depending on the sample size, mechanical tests such as tensile or deflection tests may be performed. (See

section 4. Metallurgical analysis.)

"''Figures in () at the end of a sentence indicate the literature refer- ences at the end of this article.

202
3. Statistical Summaries

The following information presented in tabular form was compiled

from written statements, hospital records, manufacturing information, and

various other documents, and is limited to information extracted from

case histories in file.

Table I is a general classification of the investigations performed

on 110 implants retrieved from patients, and divided into three categories of reported causes.

TABLE I

Classification by Reported Cause for Removal

Reported Cause No. of Implants 3

Fractured implant 105

Suspicion of tissue reaction 2

Bending without fracture 3

TOTAL 110

Selection of implants for metallurgical analysis reguired that

pre-op and post-op data was available for inclusion in the

evaluation

.

Table II indicates the general classification, by anatomical location, and reveals that the majority of the failed implants in this

group were removed from femoral head, neck and shaft areas.

TABLE II

Classification of Removed Implants by Anatomical Location

General Location No. of Implants

Femoral head and neck 80

Femoral shaft and condyle 23

Tibial 4

Humeral 1

Mandibular 2

TOTAL 110

203
Table III presents a more detailed classification of the implants

by general type, and the sub-type under each group. Again, the majority of investigations relate to the hip and femoral area.

TABLE III

Classification of Examined Implants by General Type

Type Totals

Intertrochanteric Nail/Plate Combinations

One piece 19

Two piece 11

Sliding nail 9

39

Hip Prostheses

Proximal femoral prosthesis 3

Total hip-femoral component 23

26

Intramedullary Nails

Solid cross-section 13

Cloverleaf type 4

17

Fixation Pins 7 7

Bone Screws 5 5

Bone Plates

Slotted 4

Standard 6

Compression type 6

16

TOTAL 110

204
Table IV summarizes the implants by fabrication method and alloy

type. Most of the devices are in the stainless steel category \i/hich, in

all probability, correlates with the number of stainless steel implants

in current use and being marketed. The larger number of failed stainless steel implants should not be interpreted to mean that stainless

steel is more prone to failure than other materials.

TABLE IV

Classification of Implants by Fabrication Method and Alloy Type

Type No. of Implants Examined

Stainless Steel (ASTM F-55, 56, 138

Forged

Wrought

Cast

Cobalt Base Alloy (ASTM F-75)

Cast

Titanium (ASTM F-67)

Wrought

TOTAL

ASTM specifications apply only to wrought and forged classes

of stainless steel.

, 139)

a

30

59

8

97

ii ~Tl

2 2 Ho

200
Table \l concerns the distribution, by location, of the fractures

of nail/plate intertrochanteric combinations. It is apparent that the

majority of the failures occur at the first hole of the plate. The

second portion of Table V correlates the fracture mode with the percentage of occurrence and shows the other phenomena associated with the

fracture mode (2,3,4,5). Of particular interest is the predominance of

mechanical fatigue compared to fatigue corrosion, and the high incidence

of crevice/fretting corrosion.

TABLE V

Location of Implant Fracture Mode Identification

(By per cent approximation)

Intertrochanteric Nail/plate Combination

Location of Metal Fracture Per cent

1st Screw 2nd Screw

Nail Junction Hole Hole

One piece 20 25 45 10

Two piece 10 20 55 15

Sliding nail 25 5 60 10

g Failure Mode

Mechanical fatigue*3 56

Fatigue corrosion 40

Bending 4

Crevice and/or fretting corrosion of bone screw holes detected in

75?o of the implants examined.

The cross section penetrated by the fatigue crack is larger in

the fatigue corrosion mode than mechanical fatigue.

206
Table VI presents the distribution, by location of fractures in

femoral hip prostheses, and the percentage of fracture modes and re- lated phenomena. It is evident that the majority of failures involving

femoral hip prostheses occur approximately 2 in. (5 cm) from the distal

tip, and that the largest number of these fractures are created by mech

anical fatigue, predominantly in a torsional fatigue mode. Based not

only on these case histories, but also evidence presented by other investigators, there is a correlation between the stress concentration

zone created by the anatomical stresses applied to the femur and the

fracture point of the hip prosthesis (6,7,8,9). Also there is a definite contribution by the support, or non-support, of any polymeric

material used to secure the stem in the femur. It is interesting to

note that beyond 3 in. (7.6 cm), there is evidence that all fractures

are associated with inherent metallurgical defects or weld repairs of

the casting.

TABLE VI

Location of Implant Fracture and Identification

of Fracture Mode for Hip Prosthesis

Implant Fracture Location

Location (Approx.) of Fracture

Zone from Distal Stem Tip Per cent

1 in. (2.5 cm) 4

2 in. (5.0 cm) 66

2k in. (6.4 cm) 8

3 in. (7.6 cm) 6

3% in. (8.9 cm) 16

a

Fracture Mode'

3

Mechanical fatigue 87

Corrosion fatigue 13

Fracture associated with weld repair or serious casting defects.

Fracture origin predominately at the lateral surface and with a bending- torsional vector.

Limited to stainless steel.

207
Table VII relates to the distribution of the fractures and the

fracture modes for intramedullary nails. Of particular interest is the

location of the majority of the fractures at the one-third quadrant

from the proximal tip of the intramedullary nail. Also, mechanical

fatigue predominates with some correlation to bending prior to failure.

It was noted, generally, that the fatigue corrosion cracking progressed

through a larger area of the implant prior to the final failure than

did mechanical fatigue cracking. It is not surprising that such a correlation exists since there is definite evidence relating to corrosion assisted fatiaue fractures and their selected paths of fracture

progression. Also, generally, the fatigue stresses required to initiate and propagate the fatigue "corrosion cracking are at a lower level,

thus causing the critical length of the crack to be longer prior to

catastrophic failure (10).

TABLE VII

Location of Implant Fracture and Identification of

Fracture Mode for Intramedullary Nails

Implant Fracture Location (Approx. zone) Per cent

1/3 length from proximal tip 75

1/2 length from proximal tip 17

At threads or broach area 8

Fracture Mode

Mechanical fatigue

Fatigue corrosion

45

55

Approximately 17% of fractured nails possessed detectable

bending prior to fracture.

b Limited to stainless steel.

208
Studies by other investigators have revealed that trauma at the

bone fracture may be accompanied by a lowering of the pH in the area

as well as the possibility of oxygen starvation (11). It is shown by

the tables that fatique corrosion fractures are limited, according to

the study, to the stainless steel alloys.

Table VIII, which shows the distribution of bone plate fractures

and the fracture mode, indicates that 95% of the failures occurred at

the first screw hole or slot from the center of the plate, and that the

fracture modes were mechanical fatigue and fatigue corrosion. It is

logical to conclude that the high stress point would be at the first

stress concentration from the center since the bone plates are normally

placed with their center portion over the bone fracture. Further evaluation indicated that the lack of bony union, or early weight bearing,

is directly related to bone plate fractures, as indicated in subsequent

tables.

TABLE VIII

Location of Implant Fracture and Identification of

Fracture Mode for Bone Plate

Implant Fracture Location Per cent

1st screw hole or slot

from center of plate 95

2nd screw hole or slot

from center of plate 5

Fracture Mode

Mechanical fatigue 40

Fatigue corrosion 60

Limited to stainless steel.

209
Tables IX and X are related to the correlation of patient information based on case histories.

Table IX simply shows the percentage of male and female patients

and their age distribution, based on the relatively small sampling.

TABLE IX

General Patient Information Relating to Removed

Surgical Implants

Sex and Age

Distribution Per cent

Male 37

Female 63

Age

66 - 86 years 55

8-44 years 5 45 - 65 years 40

Table X is a classification of the implant type and the average

lenqth of time the devices were in service. Of probably the most significance is the evidence of non-union of the bone related to the various categories. As can be seen, failed intramedullary nails have,

almost always, a relation to non-union. Bone plates and intertrochanter

ic nail plates also have a predominance of non-union case histories.

TABLE X

General Patient Information Relating to Removed Implants

(By insertion-to-removal-time and evidence of non-union of bone)

g

T

, . T Time in Months Evidence of Non-union Implant Type : r D , J Range Average Per cent

Intertrochanteric

nail/plate 2 - 11 eh 60

Bone plates 6 - 11 9 75

Intramedullary nails 6 - 19 11 92

Femoral hip prostheses 19 - 36 28

Based on time of operation to time of implant removal.

2 I 0
Table XI presents additional patient history information regarding

the non-union of bones and implant failures.

TABLE XI

Patient History Related to Evidence of Non-Union

and Implant fracture

History with Non-union Evidence Per cent

No unusual case history 56

Report of falls or accidents

prior to implant fracture 19

Early weight bearing 14

Miscellaneous 11

4. Metallurgical analysis

The metallurgical examination and analysis of failed implants, as briefly described in section 2, consists of non-destructive testing

followed by semi-destructive testing and then, if the sample allows, by

mechanical tests. (The tests are carefully designed to comply with all

ASTM specifications.)

Visual and macroscopic examination, that is inspection of the fractured surface at magnifications of less than approximately 50X, reveals

a considerable amount of information to a trained metallurgist. Of

course, some information has been effaced by the abrasion and peening

which occurred during and after the fracture of the implant, and as a result of its surgical removal.

An example of the information that can be retrieved from visual and

macroscopic examination is illustrated by figure 1. This is a photomacrograph of the fractured surface of a cobalt base (P-75) total hip femoral component. Note that the origin of the fatigue failure can be

traced by the macro-fatigue striation lines, and is illustrated by the arrow. This evaluation also indicated that probably torsional components were involved in the fatigue loading.

Non-destructive tests such as fluorescent penetrant examination

and radiography are common methods of quality control for surgical implant products. In fact, a vast majority of the metal surgical implant

manufacturers have achieved 100% non-destructive testing by using one

or both of these methods, further, specifications have been promulgated

by the ASTM f-4 Committee relating specifically to the procedures for

both fluorescent penetrant and radiographic examinations of surgical implants (1).

2 I t
Figure 1. Photomacrograph (15X) of fatigue origin on the femoral stem

portion of total hip prosthesis (ASTM F-75). The macro-fatigue

striation emanates from the portion indicated by the arrow.

In retrieval analysis, it is advisable to apply non-destructive

testing to determine if there are any defects, voids, cracks, etc., adjacent to or near the zone of failure. Many times these areas of defects are sub-surface and/or cannot be detected by visual and macro- scopic examination. Fluorescent penetrant inspection becomes very

valuable in revealing cracks adjacent to fatigue failures in plates,

pins, and nails, since these implants usually have a high luster and

cracks cannot easily be viewed by visual or macroscopic examination.

The scanning electron microscope (SEM) is basically employed to

determine the mode of fracture, its origin, its continuity, and any

evidence of inherent or service defects. For example, high magnification photomicrographs with the SEM show the differences between various

fracture modes such as a typical mechanical fatigue fracture (illustrated by figure 2 which represents a mechanical fatigue fracture of a bone plate), a fatigue corrosion progression (which is shown by figure

3), a fatigue failure assisted by corrosion through the plate portion

of an intramedullary nail, and a ductile overload failure (illustrated

by figure 4) of a bone screw.

2 I 2
Figure 2. Scanning electron microscope photomicrograph (2100X)

illustrating mechanical fatigue failure of a stainless steel

(ASTM F-55) bone plate.

Figure 3. Scanning electron microscope photomicrograph (2500X)

illustrating a fatigue corrosion fracture through a stainless

steel (ASTM F-55) intramedullary nail.

2 I 3
Figure 4. Scanning electron microscope photomicrograph (500X)

illustrating a ductile overload fracture of a stainless steel

(ASTM F-138) bone screw.

When warranted, and dependent upon the amount of material available, chemical analyses should be performed using ASTM Methods and used

for comparison with ASTM Specifications for Surgical Implant Materials.

In many cases, when inadeguate sample is available for identifying the materials by other tests (such as with small bone screws), the use of energy dispersion x-ray analysis is valuable. This technigue,

or other similar techniques, is also valuable in identifying corrosion

residue or unusual surface characteristics.

Metallographic analysis reguires the removal of a cross section of

material and preparation of the surface for study with a metallographic

microscope (metallograph) . This type of examination reveals information

concerning the fabrication, heat treatment (if any), fracture progression, associated cracking and a general history of the material. Metallography is also a guantitative tool used to determine grain size,

ferrite content, presence of carbides and other characteristics of the

samples (as reguired by many ASTM F-4 Standards). A skilled metallographer can also perform a qualitative evaluation of the material and its

type by his examination.

2 I A
Examples of some of the information that can be retrieved

through metalloqraohic examination are illustrated in fiqures 5 and 6.

Figure 5 shows a fatigue corrosion crack emanating from a thread notch.

The progression, of a transgranular nature, and the emanation from an initiating corrosion pit lead the experienced metalloqrapher to the

identification of the mechanism as fatigue corrosion. Figure 6 shows a series of fatigue corrosion cracks which are located immediately adjacent to and parallel to the primary fatigue failure. In cases where a broad zone of stress concentration is involved in the fatigue loading,

it is common for a group of fatigue corrosion cracks to form.

Figure 5. Photomicrograph (100X) of a metallographic cross section through a stainless steel (ASTM F-138) bone screw.

The transgranular fatigue corrosion crack progression emanates from the thread root and a corrosion pit. (Etchant:

10?o Ammonium Persulfate Electrolytic)

Figure 6. Photomicrograph (250X) illustrating an unetched

metallographic cross section adjacent to a bone plate fracture of stainless steel (ASTM F-138) with a group of fatigue

corrosion cracks adjacent to the primary fracture.

2 I 5
The identification of fatigue corrosion in stainless steel is

made from the microscopic crack geometry, and the way it progresses

through the grain structure. Many times stress corrosion and fatigue

corrosion cracking of stainless steel surgical implants are confused,

in that some aspects of the crack progression are similar. However,

on the basis of the investigations performed, a literature search,

and the reports of other authoritative investigators, it is apparent

that stress corrosion cracking, in the true sense, cannot occur in

stainless steel implants (12,13,14,15,16,17,18). One of the factors

is the temperature dependence necessary to create the stress corrosion

cracking process in a saline solution. Also fracture mechanics

studies have shown that fatigue corrosion cracking may proceed in

both intergranular and transgranular progressions similar to that of

stress corrosion cracking. (Lacking the specific background, and not

having studied surgical implants in their environment, some investigators mistakenly identify a fatigue corrosion crack as stress corrosion in stainless steel.)

5. Conclusions

The retrieval analysis of failed surgical orthopaedic implants

employs metallurgical analysis which applies scientific methods of

testing and evaluation to the failure, but the patient background,

history, and when possible, the physiological conditions surrounding

the events prior to and after the failure must also be utilized.

This paper not only presents some of the procedures of metallurgical analysis used in failure examination, but also a statistical

analysis of the information pertinent to the fractured implants. The

26 year long study of approximately 500 fractured orthopaedic implants,

of which 110 failures accompanied by patient information are considered

in this paper, suggests that only a relatively small number of implants

fracture as a result of inherent or metallurgical defects.

Most implants, other than prostheses, are not designed to be

weight-bearing for any extended period of time. They are intended

primarily to keep the fracture reduced and allow the bone to form a callous, and subsequently a strong union.

As a prime example of the retrieval analysis concept of failure

analysis, experience has shown that the fracture of bone plates or intramedullary nails are almost always related to the lack of a bony

union of the femur. However, an investigator without this knowledge

would tend to blame the design or material of the implant for failure

to resist the fatigue forces when, in fact, unusual fatigue forces were applied to the implant due to the non-united bone.

This paper also attempts to point out that experience, not only

in metallurgy is required, but the application of this knowledge to

the implant environment and the parameters affecting implant failures

is necessary to reach valid conclusions. Unfortunately, many metallurgists assume the attitude that "if the implant failed, it therefore

was defective," which is not in accordance with acceptable and proper

retrieval analysis.

2 I 6
Further, knowledge of the various fracture mechanisms is essential

when human body environments are involved. A common error of inexperienced investigators is to identify fatigue corrosion fractures of

stainless steels as stress corrosion. It has been proved, not only by

this investigator, but by many others, that stress corrosion cracking

does not occur within the parameters (particularly temperature),

acting on surgical orthopaedic implants.

The ultimate function of the metallurgical failure analysis of

implants is to focus on needed improvements, whether they exist in

manufacturing methods, design, or surgical techniques. The analysis

of failed surgical implants should not be relegated to only areas of

product liability investigations and malpractice litigation, but be

used to improve implants with the sole purpose of helping the patient.

REFERENCES

(1) Annual Book of ASTM Standards, Part 46.

(2) Frankel, \l . H., Mechanical fixation of unstable fractures about the

proximal end of the femur, Bui. of the Hospital for Joint Disease,

24, (1), 75-84 (April, 1963).

(3) Hicks, J. H., The fixation of fractures using plates, Engineering in

Medicine, 2, (3), 60-63 (Unknown).

(4) Sloter, L. E., and Piehler, H. R., Corrosion-fatigue performance of

stainless steel hip nails - Jewett type, Corrosion and Degradation

of Implant Materials, Amer. Soc. for Testing and Materials, 173-195

(Unknown)

.

(5) Williams, D. F., Retrieval and analysis of orthopaedic implants,

Nat. Bur. Stand., Spec. Publ. 472, A review of metallurgical failure

modes in orthopedic implants, 11-21, U. S. Dept. of Commerce (Unknown).

(6) Dobbs, H. S. and Scales, J. T., Fracture and corrosion in stainless

steel total hip replacement stems, Corrosion and Degradation of

Implant Materials, Amer. Soc. for Testing and Materials, 245-258

(Unknown)

.

(7) Ducheyne, P., DeMeester, P., Aernoudt, E., Martens, M. , and Mulier,

J. C, Fatigue fractures of the femoral component of Charnley and

Charnley-Muller type total hip prostheses, J. Biomed. Materials

Research Symposium, (6), 99-219 (1925).

(8) Galante, J., Rostoker, W., Doyle, J. M. , Failed femoral stems in total

hip prostheses, Clinical Orthopaedics and Related Research, 86_, 3. B. Lippincott Co. (Unknown).

(9) Weinstein, A., Amstutz, H., Pavon, C, Franceschini, V . , Orthopedic

implants - a clinical and metallurgical analysis, J. Biomed. Materials

Research Symposium, (4), 297-325 (1973).

2 I 7
(10) Tu, L. K. L., and Seth, B. B., Threshold corrosion fatigue crack

growth in steels, J. Testing and Evaluation, Amer. Soc. for Testing

and Materials, 6, (l), 66-74 (Jan. 1978).

(11) Galante, J., and Rostoker, W. , Corrosion-related failures in metallic implants, Clinical Orthopedics and Related Research, 86_, 237-

244 (July - Aug., 1972).

(12) Jones, R. L., Wing, S. S., and Syrett, B. C, Stress corrosion

cracking and corrosion fatigue of some surgical implant materials in

a physiological saline environment, Corrosion-Nace, 226-236, National

Association of Corrosion Engineers (1978).

(13) Truman, J. E., The influence of chloride content, pH and temperature

of test solution on the occurrence of stress corrosion cracking with

austenitic stainless steel, Corrosion Science, _17, 737-746, Pergamon f Press (1977).

(14) Truman, J. E., Methods available for avoiding stress corrosion

cracking of austenitic stainless steels in potentially dangerous

environments, Stainless Steels, 101-109, The Iron and Steel Institute)

London (Unknown).

(15) Uhlig, H. H., Corrosion and corrosion control, 117-120 and 280-281,

John Wiley & Sons, Inc. (1965). p(

si (16) Wallen, B., and Olsson, J., Corrosion resistance in agueous media,

Handbook of Stainless Steels, 16-89, McGraw-Hill Book Company

(Unknown)

(17) Zucchi, E. G., Tranbanelli, A., Erignani, M., and Zucchine, M., The

inhibition of stress corrosion cracking of stainless steels in

chloride solutions, Corrosion Science, 18_, 87-95, Pergamon Press

(1978).

(18) Resistance of type 316 stainless steel to stress corrosion cracking

in human serum, Armco Research Laboratories Memorandum No. 982,

Collision Surgical Engineering Company (1961).

2 I 8
Di scussion

Question (D. F. Williams, University of Liverpool, U.K.): Could you

explain how you differentiate between fatigue and corrosion fatigue

mechanisms?

Have you performed any control experiments in which stainless

steel specimens have been tested under fatigue conditions in air and

then in a saline environment to determine the difference in morphology

or the fracture surfaces in these two modes?

Assuming you can differentiate between the two, can you explain

why some samples of stainless steel should be susceptible to corrosion

fatigue rather than fatigue, whereas others suffer fatigue only.

Answer : The difference between the mechanism of fatigue or fatigue

corrosion of stainless steel surgical implants has been determined

not only be our personal examination but by research of other investigators concerning this subject.

We, that is Taussig Associates, Inc. , have not performed any

controlled experiments in our laboratory personally? however, we have

performed examination of stainless steel specimens which have been

subjected to fatigue conditions in other laboratories (primarily

manufacturers). The analysis concerns not only fatigue fracture in

air but also in such solutions as Ringers and similar saline solutions

known to be comparable to body fluids i_n situ .

The SEM examination of the fracture mechanisms, based on fracture

analysis of actual implants fractured i_n vivo and the samples supplied

from controlled conditions have led to a differentiation of the

fracture pattern as follows:

Mechanical Fatigue :

Mechanical fatigue of stainless steel surgical implants is

characterized by a continuous striation pattern passing

primarily in a transgranular manner. The photomicrograph

in our paper is typical of mechanical fatigue. The effects

of inclusions, grain boundary materials and changes in

hardness many times can be detected in the striation pattern.

The evaluation of fatigue in ASTM F-75 castings does present

a problem in that only macro-striations are normally detectable by laboratory techniques. We have not been able to

substantiate micro-striations by SEM techniques in F-75

material --this has been confirmed by Dr. Donald Cox of

Failure Analysis, Inc., Los Angeles, California in his

doctoral dissertation of 1977.

2 i 9
Fatigue Corrosion :

Fatigue corrosion exhibits a different f ractographic appear- ance than mechanical fatigue as found in surgical implants.

The two (2) photomicrographs in this paper are typical of

the differences.

Fatigue corrosion is more difficult to identify since the

striation pattern is somewhat masked by the corrosion

reactions—additional ly , the fracture can progress by both

intergranular and transgranular paths. Another factor that

may confuse investigators is the appearance of slip planes

in stainless steel which can be mistaken for fatigue striations. The photomicrograph shown in this paper illustrates

the fatigue striations progressing normal to the crystal lographic pattern of the stainless steel --this is the type of

fatigue corrosion evidence that we look for in our SEM

exami nation.

Also, we have noted a separate artifact which is common to

fatigue corrosion f ractures--that is the presence of sec- ondary cracks sometimes appearing as branch cracking—this

should not be confused with stress corrosion cracking.

We cannot answer, with authority, as to why some implants fracture

by mechanical fatigue and others by fatigue corrosion. It is our current opinion that those appliances such as intramedullary nails,

bone plates and intertrochanteric implants are subject to failure in

conjunction with and caused by the lack of a bony union. When the

bone does not unite, it is our opinion that a concentrated area of

trauma and subsequent corrosion potential is created thus increasing

the factor of corrosion in the fracture mechanism. It may be possible

that only the stage I fracture is created by mechanical fatigue while

the state II fracture progresses by fatigue aided by corrosion.

Question (D. F. Gibbons, Case Western Reserve University): The

observation that chemical analysis of trace elements, particularly

nitrogen concentrations which are high, in 316 LVM stainless steel

could well account for cases of corrosion fatigue. The stability of

the austenitic transformation, allowing "galvanic" type corrosion to occur within the crack!

Answer : We believe that some of the trace elements may have an effect on the initiation or retardation of corrosion fatigue. We do

not normally analyze the stainless steel implants for % nitrogen?

however, based on the metallurgy of stabilization, it would follow

that nitrogen could certainly affect the mechanism of corrosion

fatigue.

220
We are planning to address this subject in the future based on a review of previous findings and future analyses of fractured stainless

steel implants.

We do, routinely, analyze the stainless steel composition for %

copper. We intend to review our records to determine if there may be

any relation between % copper and the occurrence of mechanical fatigue

and/or fatigue corrosion.

Question (P. Sung, Food and Drug Administration): You mentioned that

316 stainless steel will not go through the stress corrosion process

during fracture. Your detailed explanation with experimental confirmation of your claims would be of interest.

Answer : This paper does present our opinion concerning the temperature

dependence of stress corrosion and its relation to the fracture

process of stainless steel implants. We have included some pertinent

references which substantiate this finding--we hope in time, to

publish a supplementary paper specifically related to stress corrosion

verses fatigue fracture of stainless steel implants.

Aside from the references shown in this paper, we can provide

many additional references concerning the mechanism of stainless

steel cracking and the dependency not only on temperature and concen- tration of solution, Ph and oxygen content. Only recently have

investigators concerned themselves with temperature dependence. Most

investigators used boiling MgCl 2 solutions as their test criteria

this criteria does not relate to conditions found in vivo .

Question (R. Wilkinson, Strathclyde, U.K.): Did you measure the

concentration of the elements or the implant components? If you did,

how many failed to meet specification?

Answer : If we have permission to perform semi-destructive testing,

we do routinely analyze the components for chemical composition.

Of the stainless steel implants analyzed, all manufactured

within the last 10 years have fallen within the composition requirements of F55, F56, F138, or F139.

Cobalt-chromium cast alloys for ASTM F75 have had some deviation

in compliance to ASTM composition requirements and are usually manu- factured in Switzerland—their specifications have slight variances

from ASTM.

Therefore, we find no trend nor any significant findings of

elemental analysis beyond specifications of the applicable surgical

implants.

i
Question (Allan Weinstein, Tulane University): Have you tried to

correlate the chemical composition as regards the percentage of the

minor constituents with the propensity towards corrosion-fatigue vs. mechanical fatigue.

Answer : Our answer to Dr. Donald F. Gibbons of Case Western Reserve

University essentially addresses itself to Dr. Weinstein 1 s suggestion.

We do intend in future investigations to attempt a correlation

between the trace elements and fatigue corrosion and/or mechanical

fatigue.

Question (Kirk J. Bundy, Johns Hopkins University): Did you examine

fracture surfaces with energy dispersive analysis in order to differentiate between mechanical fatigue and corrosion fatigue?

Answer : We have examined the fractured surfaces of surgical implants

by Energy Dispersion X-ray Analysis (EDX). Our findings did not show

or indicate a differentiation between those fractures which were classified as mechanical fatigue or fatigue corrosion.

We doubt that we would ever find a correlation since most samples

when received in our laboratory have been cleaned in some manner;

however, there may be some symptomatic residue which is on the surface

that has been cleaned by some pathologist or some intermediary.

22 2
A STUDY OF INCLUSIONS IN STAINLESS

STEEL IMPLANTS AND THEIR EFFECT ON CORROSION

R. Wilkinson, M.T. Shepherd, * Bioengineering Unit, University of Strathclyde,

Wolfson Centre, 106 Rottenrow, Glasgow G4 ONW

A study of stainless steel implants nominally conforming

to BS 3531 has been undertaken. Corroded areas have been

examined using the SEM and inclusions visible in the corroded

areas identified using energy dispersive X-ray analysis.

Inclusions present in a polished section of the component

were also identified and measured to produce inclusion ratings

which were then compared with the estimated corrosion. Some

components were analysed using wavelength dispersive X-ray

analysis and 5 screws were found deficient in nickel. Screws

having low nickel were then compared with the others. The

interrelationships of the different inclusions and relationships

with corrosion are discussed and the case for more stringent metallurgical control considered.

1. Introduction

Inclusions are non-metallic particles embedded in a metal matrix

which may affect both chemical and mechanical properties (1 ,2 ] In steels,

they arise from a number of different sources and these will be

considered in turn. Modern steel making reduces the carbon content of

steels using oxygen which must be removed in its turn. This is accom- plished by the use of deoxidants, commonly aluminium and silicon, but

elements such as titanium and vanadium have been used [3]. The kinetics of

deoxidation are extremely complex [4,5] and the details are not well

understood.

After the original addition of aluminium to the melt the aluminium

and oxygen react to form A1 2 0 3 which then floats to the surface. To

produce a clean steel it is necessary to produce melt conditions which

will facilitate this 'float off. A low concentration of aluminium and

oxygen remains dissolved in the melt but cannot remain in solution after

solidification. As the temperature falls and solidification begins, a supersaturation of aluminium and oxygen builds up ahead of the solidification front and a number of small inclusions are produced [5]. The

concentration falls and then builds up again as solidification proceeds,

leading to an inhomogeneous distribution of small nuclei [6].

If silicon is used as well as aluminium the situation becomes even more complex since Si O2 , Al 2 0 3 or various silicates can be produced

* present address Deloro Surgical, Swindon, England.

223
depending on the way the two elements are added. The oxygen content

of steel is said to be more uniform if silicon is used [41. Complex

oxides may also be produced involving deoxidants and components of the

melt [7]. Components of the melt such as manganese and chromium are strong oxide formers and if conditions are right, simple and complex

oxides of these metals may be formed. This reduces the quantities of

these materials in solid solution but not necessarily the total amount

in the melt.

Inclusions from deoxidation are almost impossible to eliminate in

a single stage process. Thus various forms of re-melting have been

developed in an effort to reduce impurities. The most common are Vacuum

Arc Remelting (VAR) and Electro-Slag Refining (ESR). VAR seems more

effective for oxides and ESR for sulphides [8]. When considering effects

of inclusions it is therefore necessary to consider effects due to the

different types of inclusions.

Other sources of inclusions are the refractories lining a steelmaking plant, chemical reactions of impurities in the raw materials and

pre-formed inclusions from scrap if the temperature of the melt was too

low to bring them into solid solution. More careful selection of raw materials will obviously reduce inclusions due to impurities but will

lead to increased costs. Improved refractories and better control of

pouring and casting procedures will reduce refractory wear.

1.1 Formation of complex inclusions

As has already been indicated, the kinetics of inclusion formation

are complex. In the melt, nucleation, growth and inhibition must be

considered as well as 'float off. In the solid state nucleation,

diffusion and growth are important. Homogeneous nucleation requires a degree of supersaturation, at least on a local scale, and even then may

be delayed in static conditions [4]. In commercial steel making there

are normally adequate nuclei for heterogeneous nucleation in the melt [4],

but homogeneous may be necessary in the solid state.

Heterogeneous nucleation may lead to the growth of 'onion' like

inclusions where layers of materials deposit around a central core. Deposition of distinct crystals of one phase on crystals of a second

phase is also observed [7]. Aggregation of inclusions may also be

important as this affects 'float off [5]. But if solidification has

occurred retaining the inclusion within the ingot then different spots

of an apparently single inclusion may contain very different elements.

In solid solution diffusion plays a dominant role in the kinetics

of growth. Because of greater ease of nucleation and increased diffusion

rates many inclusions nucleate at grain boundaries. The most notorious

of these in stainless steels is probably chromium carbide which leads to

intergranular corrosion by chromium depletion of the adjacent grain [9].

1.2 Inclusions and mechanical properties

Inclusions may affect mechanical properties. Because inclusions are discontinuities they affect dislocation and grain boundary migration and

224
may act as sites for crack initiation, This last effect is most

important in fatigue strength [1,10], The likelihood of crack initiation depends on the stress field around the inclusion which depends on

its size, the difference in modulus between inclusion and matrix, the

shape of the inclusion in relation to the applied stress, and the

strength of the interfacial bond, In general, large, hard inclusions

with sharp edges are the most damaging [11] . Examination of ductile

fractures often reveals inclusions at the base of the 'dimples' showing

that failure has initiated at the relatively weak interface [1]. Grain

boundary inclusions may also be implicated in some cases of intergranular

fracture although this is often due to precipitation of a second phase [12].

The subject will not be pursued further in this paper but reviews may be

found in ISI Special Report 134.

1.3 Inclusions and corrosion

Inclusions may affect the corrosion resistance of metals because of

local galvanic cells set up between the inclusion and its matrix [2].

Poor interfacial bonding may lead to the production of crevices, possibly

forming concentration cells [13] or matrix depletion of a particular

component may affect protective oxide formation [14].

Residual elements in the matrix may also affect corrosion resistance

and these effects may be complex, for example low concentrations of

copper increase the resistance of stainless steels except in the presence

of molybdenum when it is reduced [9]. It should be borne in mind that in

quenched steels residual elements may be found in greater than

equilibrium concentrations because of the kinetics of nucleation.

Most studies have concentrated on particular inclusions e.g. A1 2 0 3 under a condition relevant to industrial needs or on looking at oxides,

sulphides, nitrides and carbides as classes [6]. The latter studies

have tended to use the optical microscope where identification of the

metallic component is often not possible. Laboratory studies tend to use

special small melts where conditions have been adjusted to affect the

concentration of a particular class of inclusions [15].

2. Method

Stainless steel implants removed in the course of surgery were collected from two Glasgow hospitals. Where possible, swabs were obtained

and the implants themselves cultured. A sample form was provided for

the theatre staff to complete (fig. 1); if information was missing,

where possible the patient was traced and the missing information

obtained from medical records. Staff were also requested to mark the

proximal end of bone plates with a loop of thread.

After culture and sterilisation, the implants were thoroughly

washed and dried then stored in labelled polythene bags. Hardness of

all components was measured using a Vickers Pyramid Diamond Indentor.

Screw heads were removed and mounted for examination in the SEM. The

remainder of each screw was mounted for metal! ographic examination.

Corrosion was assessed using a scale developed for this study[l6,17]

225
A series of standard SEM micrographs of corroded areas was assembled

representing minimal to severe corrosion (fig. 2). These were ranked,

choosing photographs which represented as linear a scale of metal loss

as possible. A corrosion rating was then obtained by estimating the area of corrosion corresponding to a particular grade and using the

equation

n CORR =

I A1G1 + . . . + A G L 1 1 n n

l

where A = area in vm and G = grade. The numbers were felt to be

extremely large and so for final analysis all the earlier ratings were divided by 10 yielding the final equation

n CORR = 0.1 Y AiG, + . . . + A G L 1 1 n n

l

Polished, unetched sections were carefully mounted for SEM examination with the top face parallel to the stub. The plastic mount was painted with either colloidal carbon or colloidal silver to reduce

charging. Inclusions were identified using energy dispersive X-ray

microanalysis and the area of the inclusion estimated. An inclusion

rating, consisting of the area occluded by inclusions of a given type

in a specimen area of 0.5 mm sq, was produced for each section examined.

Attempts were made to analyse the matrix but the simultaneous presence

of molybdenum and sulphur led to unreliable results. A few samples were mounted for examination in an electron probe microanalyser at

Edinburgh which used wavelength dispersion. This is slower but has

better discrimination. A wavelength dispersive system is being

commissioned at Strathclyde and this aspect of the work will be

extended shortly.

Inclusions in the corroded areas of the screw heads were identified

using the energy dispersive system. Attention was confined to screws

in this study except for measuring the hardness difference between

screw and plate.

The partly commissioned wavelength dispersive unit was used to

examine inclusions on the polished sections in order to detect the low

atomic number elements. The energy dispersive system identified the

metallic elements although if carbon was sought it was necessary to use

12 KV to excite the metallic elements while 6 KV gave better detection

of carbon. Approximate peak to background ratios were determined

although these should be interpreted with caution because the system was

not fully calibrated.

Results were analysed using the SPSS statistical package on an IBM 2980 computer.

226
3. Results

3.1 Bacteriology

Three implants from the series were found to be infected although

not all the implants could be cultured. One case produced pathogenic

organisms (staph, aureus) and two organisms often considered non- pathogenic (diptheroid; 2 types of strep, viridans and 2 types of staph,

epidermidus) . In addition 4 cases of infection were reported in the case notes (coagulase +ve staph and diptheroids; staph aureus; E-coli

and* unspecified) where swabs were not provided nor the implant placed in

sterile jars

.

3.2 Comparison of screws having low nickel content

Table 1 shows the means of different variables for the two groups.

Despite the low numbers certain statistically significant differences

are apparent. Because this work is in an early stage significances

as low as 0.10 will be considered and further investigations made. The

first difference is in corrosion where the low nickel group showed

increased corrosion although the variance is high. However, the time

of implantation was longer for this group. Inclusions found in the two

groups are also different, titanium, mixed metal-aluminium containing,

and silicon inclusions all being higher in the low nickel group.

Aluminium inclusions (presumed A1 2 0 3 ) were not found in the low nickel

group at all although the absence is not statistically significant.

None of the other variables showed significant differences, including

the amounts of other alloying elements.

Table 1. Comparison of screws with low

and normal nickel contents

*A1 cont

Corr Time *Ti Inc Inc *Si Inc

No. 5 3 5 5 5 Low Ni Mean 389 68 152 213 63

St. dev. 548 55 292 299 83

No. 31 26 28 28 27

Normal M , N i Mean 144 27 67 15

St. dev. 203 26 4 87 45

Significance 0.10 0.05 0,02 0.05 0,10

* Ti Inc - titanium inclusion rating. Al cont Inc - rating for

all aluminium containing inclusions. Si Inc - silicon inclusion

rati ng

.
3,3 Comparison of corroded screws containing chromium inclusions

in the corroded areas with corroded screws without corrosion

associated chromium inclusions

Table 2 shows there were no significant differences in either the

estimated corrosion or the time of implantation. Inclusions present in

the polished sections showed no significant differences, the high Ti

rating in the chromium present group was caused by one very 'dirty' screw containing massive amounts of titanium. However the amounts of

alloying elements did differ significantly. Measured chromium was less,

possibly reflecting loss of chromium to the inclusions which then floated

off, although chromium containing inclusions in the area analysed would

have contributed to the chromium signal.

Nickel was lower in the chromium present group, the significance is

not clear since the quantities present should be adequate to stabilise

the austenitic phase. The higher value for manganese may reflect the

tendency for chromium inclusions to also contain manganese, possibly as a spinel type mixed oxide. A chromium inclusion rating was not considered

since it proved extremely difficult to separate chromium and manganese

except in the case of manganese sulphide.

Table 2. Comparison of corroded screws having chromium inclusions

present in corrosion with those having no such inclusions

Corr Time Ti Inc %Ni %Mn %Cr

No. 22 21 10 8 8 8

Cr Inc M

present

Mean 119 49 68 10.8 1.9 17.8

St. dev. 286 42 212 0.9 0.2 0.3

No. 57 49 25 24 24 24

No Cr

I nc Mean 104 33 6 12.2 1.7 18.2

present

St. dev. 183 27 18 1.5 0.16 0.4

Significance NS NS NS 0.025 0.01 0.02

3.4 Comparison of corroded screws having aluminium containing

inclusions in the corroded areas with corroded screws without corrosion associated aluminium inclusions

Table 3 shows that there were no significant differences in either

corrosion or time of implantation. A significant difference in screw

and plate hardness difference was detected but this was felt to be random

chance since their values for hardness of the two sets of screws were

similar. The only other significant difference was in titanium inclusions

where those screws with the aluminium inclusions did not contain much

titanium, this may reflect deoxidation practice since both elements have

been used as deoxidisers.

228
Table 3, Comparison of corroded screws having aluminium

inclusions present in corrosion with those

without such inclusions

Corr Time VH diff Ti Inc*

No

ai inc

present

Mean

O L • UcV

68

96

I / U

61

36

o I

65

42

OH

30

5

1 /

No

No Al Inc 11

. Mean

present

St.dev

11 182

398

9

50

41

8

108

40

5 136

299

Significance NS NS 0.01 0.05

3.5 Other types of inclusions

No significant differences were found for subjects produced by

considering silicon, manganese sulphide, sulphur, calcium and aluminium

without other metals in the same way.

3.6 Relationship of inclusions in the corroded areas to those in

polished sections

No attempt was made to quantitate inclusions present in corroded

areas but merely to report their presence and relative abundance. The

first and striking difference was that aluminium, presumed to be A1 2 0 3 was frequently detected in corroded areas but relatively rarely in

polished sections. Also Al/Si combinations were found in corroded

areas but hardly ever in polished sections without other elements

e.g. Al/Si /Ti or even more complex agglomerated.

The other striking difference was in the presence of obviously

incidental inclusions (those whose presence was due to contamination

rather than deliberate additions). Silver, copper, mercury, tin, zinc

and gold have all been found. Very few have been found in polished

sections. This may be due to sampling but in the case of silver a number of silver inclusions are usually detected within the corrosion

if one is found. Silver has been found on a number of occasions in

corrosion but only once in a polished section. Because of the

relative rarity more screws will have to be studied before the effects

of these inclusions can be assessed.

3.7 Oxygen content of inclusions

As expected the aluminium inclusions produce relatively high

oxygen peaks. Inclusions containing chromium and manganese also show

reasonably high oxygen peaks indicating that the chromium in these steels

229
is probably participating in oxide rather than carbide formation.

As expected, sulphur containing inclusions rarely revealed significant

oxygen concentrations unless in a mixed inclusion with a strong oxide

former such as aluminium. Silicon inclusions have variable oxygen

concentrations, most of them on the low side, indicating that the Si

2 range of minerals is relatively rare.

3.8 Carbon content of inclusions

As expected, the carbon content of inclusions containing oxide

formers is usually low. Four chromium containing inclusions with

significant amounts of carbon have been found; two inclusions in each

of two screws. Only 10 screws have been studied in this way, seven of

which contained chromium bearing inclusions. Even in the two screws with chromium and carbon containing inclusions there were more inclusions containing low to negligible amounts of carbon than containing significant amounts.

Only 3 silicon inclusions were studied all of which contained

measurable amounts of carbon (lower than the chromium but higher than

most aluminium and sulphur ones). One inclusion containing aluminium

had a very high carbon peak which was puzzling. In certain areas a 'dark stain' with diffuse edges appeared. The metallic signal was indistinguishable from that of the matrix but the carbon content was relatively high. This has been observed on 10 occasions, the explanation is not clear but this may represent a carbon rich second phase.

Further studies are planned.

4. Discussion

4.1 Nickel content

Although the numbers are low, nickel was found to be out of

specification in over 10% of components (6/43, 5 of which were screws).

All other constituents analysed (carbon was not measured) were within

specification. The low nickel components tended to have higher

corrosion. The duration of implantation was longer but in a multivariate regression analysis time could not be shown to have any

significant correlation with corrosion [16, 17] .

Chromium and aluminium containing inclusions all showed higher

ratings in the low nickel group but in the larger series they were not

shown to have any significant effect on corrosion resistance. Poor

control of the melt may be. indicated by the simultaneous occurrence of

low nickel and high inclusion ratings.

In the absence of other evidence the nickel content should be more carefully controlled, both because of its austenite stabilising

effect and also because of its possible effect on corrosion resistance.

Further investigations are planned, first to establish the incidence of

failure to meet specification on a larger sample and then to establish

any effect on corrosion resistance.

230
4.2 Instrumental problems in the analysis of inclusions

Inclusions may be analysed either in situ or extracted from the

matrix. Both conditions have their advantages but in this study only

in situ analysis was undertaken because removal from the matrix is

essentially a destructive process and the amount of material from a screw available for analysis is relatively small and destructive testing was avoided. Composition analysis is difficult in situ because of matrix

contributions to the signal. With small inclusions, even using the spot

mode, X-rays are generated outside the inclusion. The volume of

excitation can be reduced by reducing the voltage and spot size but both

may reduce the signal. Reducing the voltage from 25 KV to 12 KV has

little effect on the lower atomic number elements e.g. Al , but reduces

the signal and broadens the peaks for elements such as chromium and

manganese. Reducing the voltage is required for very low atomic number

elements such as oxygen and carbon but sacrifice at the higher AN end of

the spectrum is then necessary. Reducing the spot size reduces the

number of exciting electrons which worsens the signal to noise ratio.

True quantitation is only possible for flat (or at least geometrically defined) surfaces and so only inclusions in polished sections could

be analysed quantitatively. Polishing however cuts through the complex

structure of many inclusions [7] and creates its own problems in interpretation. This cutting may explain the greater number of multi-element

inclusions in polished sections. An inclusion such as that in fig. 3,

embedded in matrix, may only produce recognisable signals from its outer

component while a polished section may allow all the components to be

excited.

A restriction on this type of study is the time taken to acquire

the information. Energy dispersive analysis is relatively fast and an inclusion assessment takes about 30 min/sample. Wavelength dispersion

is much slower, particularly if the crystal settings have to be changed.

The present analysis was done by analysing for oxygen and then going back

and analysing the same specimens for carbon on different days.

Wavelength dispersion does not cope well with alloys where molybdenum and sulphur co-exist. Confidence in the results obtained was insufficient to allow definite statements on conformity with BS3531 to

be made. The results obtained with a borrowed instrument indicate that

such studies should be pursued despite the longer times involved.

4.3 The role of chromium

Austenitic stainless steels owe their corrosion resistance to an adherent oxide film in which chromium plays a major part [18]. If

chromium is bound in inclusions it is not available to form the oxide

film even though chemical analysis would include bound chromium in the

total chromium content. Carbides are more significant than oxides

because many oxides form while the steel is still molten, allowing a homogeneous distribution of free chromium while carbides form in the

solid state and precipitation tends to occur at grain boundaries and

leads to depletion in the surrounding grain.

23 I
The formation of chromium oxides is governed by deoxidation

practice 5 and can be reduced but probably not eliminated. It

would seem that lower manganese and higher nickel concentrations

might help.

4.4 Implications of the results

Results from this study seem to indicate that improvements in

corrosion resistance of stainless steel could be obtained by better

metallurgical control. This would obviously increase the cost of

the implant. This increase could only be justified on economic

grounds if it could be demonstrated that such a reduction in corrosion

or associated improvement in mechanical reliability would lead to

less morbidity and a lower rate of medically necessary removal. The

cost of the implant is a relatively small proportion of the total cost

of the initial treatment, the cost of failure is also high and so a relatively large percentage increase in the cost of the implant might

still be cost effective. Possibilities of producing small to medium

sized special melts of steel should be explored and the increased

costs calculated.

This study could not have been undertaken without the provision

of implants by Glasgow Royal Infirmary and Gartnavel General Hospital

Orthopaedic Departments. A grant from the SRC towards purchase of

the SEM and research studentships from SRC and MRC are gratefully

acknowledged. Special thanks are due to Mrs. R. Cuthbert for her

patience and help in the preparation of the manuscript.

232
References

Pomey, G„ and Trentini b. Introductory address: some aspects of

cleanness in steels (Production and application of clean steels,

Balatonfured, Hungary, 1970) Book, Special report 134,

Production and Application of Clean Steels , p. 1-14, Iron and

Steel Institute (1972)

Smialowska, Z.S. Influence of sulphide inclusions on the pitting

corrosion of steel s. Corr 28, 388-96 (1972)

Samarin, A.M. Physical chemistry of the deoxidation of metal

alloys (Production and Application of Clean Steels, Balatonfured,

Hungary 1970) Book, Special report 134, Production and

Application of Clean Steels pp 17-23, Iron and Steel Institute

(1972)

Forster, E. and Richter, H c Kinetics of the deoxidation of steels

(Production and Application of Clean Steels, Balatonfured,

Hungary 1970) Book, Special report 134, Production and

Application of Clean Steels , pp 24-28, Iron and Steel Institute

(1972)

Grethen, E. and Philippe, U Kinetics of deoxidation reactions

(Production and Application of Clean Steels, Balatonfured,

Hungary 1970) Book, Special report 134. Production and

Application of Clean Steels

pp 29-34, Iron and Steel Institute

(1972)

Case, S.L. and Van Horn, K.R. Aluminium in Iron and Steel , p 21-56 (John Wiley and Sons Inc. 1953).

Golikov, IoN. Certain peculiarities in the formation of oxide

inclusions revealed by complex analysis (Production and

Application of Clean Steels, Balatonfured, Hungary 1970) Book,

Special report 134 Production and Application of Clean Steels,

pp 35-41, Iron and Steel Institute (1972).

Muller-Aue, H.J. and Bardenheuer, P.W. Comparison of the ESR

process with others (Proceedings of Conf. on Electroslag Refining,

Sheffield 1973) Book, Electroslag Refining pp 163-8, Iron and Steel

Institute (1973)

Scharfstein, L.R. Effects of residual elements on the general

corrosion resistance of austenitic stainless steels (Symp 0 at 69th

Annual Meeting of ASTM, Atlantic City, N.J. 1966) Book, Effects of

Residual Elements on Properties of Austenitic Stainless Steel

pp 90-104, ASTM special technical publication 418 (1967)

233
Castagne, J.U, Davidson, J,H,, Duffaut, F., Marlet, J. Influence of inclusions on the fatigue resistance of high strength

steels (Production and application of Clean Steels, Balatonfured,

Hungary 1970) Book, Special report 134, Production and

Application of Clean Steels , pp 221-6, Iron and Steel Institute

(1972)

Tricot, Rc, Relative detrimental effect of inclusions on service

properties of bearing steels (Production and Application of Clean

Steels, Balatonfured, Hungary 1970) Book, Special report 134

Production and Application of Clean Steels, pp 199-204* Iron and

Steel Institute (1972)

Tetelman, A.S., McEvily, A.J. Jr 0 Fracture of structural materials,

pp 418-24 John Wiley & Sons (1967)

Kinoshita, N„, Ohashi, N., Takeda, M. Effect of the composition of

non-metallic inclusions on the rusting of ferritic stainless steels.

Trans Iron Steel Inst. Japan ]£, 251-7 (1976),

Jordan, B.A. The characteristics of fretting and fretting corrosion

damage in surgical implant materials, AWRE 44/83/181 DHSS project

A129 (1976)

Kozakevitch, P., Olette, M. Role of surface phenomena in the

mechanism of removal of solid inclusions (Production and Application

of Clean Steels, Balatonfured, Hungary 197Q) Book, Special' report

134 Production and Application of Clean Steels , pp 42-49

(1972)

Shepherd, M C T 0 Corrosion of surgical implants and debris

progression through adjacent tissue,, Ph.D. Thesis, University of

Strathclyde, Glasgow, UK (1979)

Shepherd, M.T., Wilkinson, R. Factors affecting the corrosion of

surgical implants, presented at the 1st World Biomaterials

Congress, Baden, Vienna (1980).

Colombier, L, Hochmann, J„ Stainless and heat resisting steels

p 135-6, Arnold (1967)
Fi g o 1 Form supplied to theatre staff for

use with retrieved implants

Age and Name of Patient

Patient Hospital Number

Date of Implantation Date of Removal

Antibiotics used: Yes/No» If yes, time administered

Quantity and make

Reason for removal

Figure 2. An example of a grade 7 Figure 3. Inclusion in matrix^

corroded area*

RELEASE PHENOMENA

237

TISSUE RESPONSE TO WEAR DEBRIS

IN ARTIFICIAL JOINTS

Willert, H.G*, Buchhorn, G., Buchhorn, U.

Orthopaedic University Hospital Gottingen

D - 3400 Gottingen, Robert-Koch-StraBe 40

Semlitsch, M.

Dept. of Medical Engineering, Sulzer Brothers Limited

CH - 84 01 Winterthur

Macroscopic and microscopic examinations of

the tissue from the joint capsule and the bone /

cement - border of revised artificial joints are

carried out. The tissue response to wear products

of the biomaterials ( CoCrMo - cast alloy, stainless steel - AISI 316 L, Polyester, Polyethylene,

silicone rubber and bone cement on acrylate base)

is described and its connection with implant

loosening is demonstrated. The particles are characterised and some clinical measurements of the

wear rate of polyethylene are reported.

Looking at the state of art in artificial joint

replacement one can say that within the last ten years

important improvements have been made on the technical

aspect, for example in the design of implants, the quality and combination of biomaterials, the implantation

technique and so on. /1/*

On the other hand, the biological aspect has not

changed very much, and we must admit, that we still do

not know very much about it and that there are still

more questions than answers.

The living tissue responds to the material, the

artificial joints are made of, as to a foreign body.

This reaction is modified by the type of the implant,

the type of the material, as well as by the size and the

shape of the 'foreign bodies'. Basically, however, the

pattern of the tissue reaction is always the same.

The subject of this paper is the interaction between wear particles of biomaterials used for artificial

joints and the surrounding tissue.

1 . Material and Methods

*Figures in brackets indicate the literature references

at the end of this paper.

233
The results I am going to present were obtained

by investigating tissue specimen, taken at reoperations

from the capsule surrounding the moving parts of the

artificial joints and from the bone in which the implant

had been anchored (in the majority of cases by means of

bone cement) (table 1.).

Up to now we studied and collected data on 552 tissue

samples. The majority of them came from revisions of

hip endoprostheses (73.5%) others from second operations of knee-, elbow-, wrist- and finger joint endoprostheses of different types.

Table 1 . Origin of the Tissue Samples studied in the time period January, 1970 - December , 1 979

ORIGIN NUMBER

Capsule 236

Bone/Cement border 154

not specified 44

of the pelvis 54

of the leg 56

Bone 59

not specified 21

of the pelvis 9

of the leg 29

Debris of tissue 23

Fibrous tissue, not specified 63

Patella 8

Interposition 4

Fistula 2

Zone of Osteolysis 2

Lymphnode 1 total number of tissue samples 552

The materials included metals, polymers, ceramic

and X-ray contrast medium of the bone cement.

The metals were CoCrMo-cast alloy, FeNiCrMo steel

(AISI 316L) and CoNiCrMo-forged alloy.

The CoNiCrMo-forged alloy is now used only

for the anchoring parts of the prostheses; in

some types of joints also the moving parts had

been made out of CoNiCrMo-forged alloy, but in

those cases the articular surfaces were especially chromium plated.

The polymer materials were Teflon (Tetraf luorethylene) , Ultra High Molecular Weight Polyethylene (RCH

1000 type), Polyester (polyethyleneterephthalate , Hosta240
dur KVP - 4022/AP4) , Polyacetal (polyoxymethylene

homopolymer, Ertacetal) and Silicone Rubber. As bone

cement on the basis of Methylmethacrylate mainly PALACOS , seldom CMW-Bone Cement, was used. The contrast

medium of PALACOS is Z irconiumdioxide (Zr02), the contrast medium of CMW-Bone Cement is Bar iumsulphate

if.BaSOj . The ceramic material was High Density Aluminium

Oxide

The materials of the articulating surfaces were

used in different combinations, as metal to metal, metal to polymer, ceramic to ceramic and ceramic to polymer coupling.

The causes, which made a surgical revision of the

artificial joint necessary were loosening, evtl . with

fracture of the implants, paraarticular calcifications,

complications due to malposition or technical errors

during implantation as well as complaints of the patient without any visible fault in the function of the

prosthesis.

Cases with deep infection were excluded

from this study.

The tissue material subjected to investigation

consequently originated chiefly from joint replacement

failures that means it represents a negative selection. Such cases, however, are most suitable to illustrate the whole range of problems connected with

tissue reactions to wear particles.

Immediately after excision from the patients'

bodies, the pieces of tissue were fixed in neutral

formalin and representative samples were selected for

analysis and histology. The analytical methods used

were spectral analysis, atomic absorption spectrophotometry and electron microprobe analysis 12/ . For histological examination, serial sections prepared

from paraffin embedded tissue material were used;

where necessary, decalcified material and frozen sections were also employed. The preparations were studied by light microscopy, polarized-light microscopy

and - after special preparation - by scanning electron microscopy as well.

2 . Results

The presentation of our findings is subdivided

into a synoptic description of the processes taking

24 I
place in the tissus and a special discussion of the tissue reactions associated with the respective implant materials used. The identification of particles of the

different materials by microscopic and analytic investigations we described in detail elsewhere /3/.

2.1 Tissue Reactions in General

After an endoprosthesis has been implanted, a new

capsule of connective tissue is formed in the wound

cavity around the artificial joint. This replaces the

original capsule, if it has been excised. The new capsule resembles a normal synovium. However the architecture of the tissue is rather rough and sometimes it is

hard to identify the different layers, expecially if regenerative processes are combined with reactions to

foreign bodies /4 , 5 , 6 /. These foreign bodies consist of particles produced

by wear either from the moving surfaces of the joint,

from the bone cement within the implant bed or from broken prosthetic parts. Like every other material even

polymer plastics, metal and ceramic materials especially

selected for articulating joint surfaces are subjected

to abrasion. The worn off particles, which accumulate in

the joint cavity are incorporated into the capsule mainly by direct phagocytosis.

The continuous production of wear particles necessitates a constant supply of cells capable of phagocytosis.

Thus a foreign body granulation tissue is formed within

the capsule. Depending on the worn off foreign material

it may consist almost entirely of histiocytes or it may

contain predominantly multinucleated giant cells. Small

particles are usually stored by mononuclear histiocytes,

whereas foreign body giant cells accumulate around bigger particles.

All of these cells may agglomerate and form nodules

which tend to become necrotic in the center. Also superficial layers of the capsule can become necrotic. When

the necroses are rejected into the joint cavity, they

accumulate there as caseous, paste like masses, intermingled with foreign body particles. This joint content

permanently irritates the capsular tissue and promotes

further organization, which leads to the production of

even more granulation tissue.

Another feature of the foreign body granulation

tissue is its tendency towards fibrosis and scar formation. In this process more and more collagen fibres are

differentiated. The capsule is growing thicker and the

cells are perished with increasing fibrosis . Lymphocytic and plasmacellular infiltrations may

occur even without bacterial inflammation. This may be a

2<1 2
sign of a humoral defense process or of a hypersensitivity to the incorporated material respectively.

The capsular tissue is able to transport the phagocytized particles away and to eliminate them. This

transprt is accomplished through the lymphatic system

via perivascular lymph spaces.

It seems to be proved, that a certain amount of

wear particles can be eliminated in this way by the capsular tissue. This mechanism can establish an equilibrium between the abrasion, phagocytosis and elimination of wear particles. This equilibrium has to be

looked upon as the optimum state as long as wear cannot

be avoided totally (fig. 1).

An increasing release of wear particles induces

an increased formation of foreign body granulation

tissue. But the bigger the granulomas, the greater is

their tendency to become necrotic. The necroses, accumulating in the joint cavity, cover most of the inner

surface of the capsule. Such a capsule is no longer

able to eliminate wear products. At this point, the

foreign body reaction in the surrounding of the artificial joint decompensates (fig. 2). Now, in addition to

the joint capsule, other tissues become involved in the

phagocytosis, storage and transport of wear debris.

These tissues are

-the connective tissue at the interface between bone

and implant,

-the bone marrow.

With a development of a typical foreign body granulation

tissue in the neighbourhood of bone, bony trabeculae

are subjected to resorption too. This results in a loss of bony anchors, required for the fixation of the

implant (i.e. the bone cement) and loosening of the

implant develops.

2.2 Tissue Reactions in Relation

to Different Materials

2.2.3 Metal

The amount of metallic wear particles, stored in

the adjacent tissue varied from case to case and there

was also a great variation with the different types of

endoprostheses. 83% of visible particles measure less

or equal 1 . 1 3pm^ . Fig. 3 shows the size distribution of

metal wear particles measured by television image analysis of unstained histological sections.

The smallest amount and the smallest sizes of me243
Figure 1. Equilibrium between the abrasion, phagocytosis and elimination of wear particles.

244
transport

perivascular lymph spaces

granulation tissue

$S#lymphocyt«s

' histiocytes SCOW

C> a foreign m

body giant cells

ranulation tissue

bone resorption

Figure 2. Decompensation of the foreign body reaction

The bone / cement - border of the femur as well as of

the acetabulum is involved in the storage of wear

particles

245
tallic wear particles were detected when the artificial

joint consisted of a metal and a polyethylene component,

and the prosthetic parts had been intact. The tiny particles were phagocytozed by histiocytes as well as by

foreign body giant cells, together with plastic and PMMA

debris. One" cannot see that the tiny metal particles do

any har to these cells.

Greater amount of metallic wear products and bigger sizes of particles we sometimes found in the surrounding of joints with plastic and metal components

when they were in function for a longer period of time

(more than 6 years) , or when the femoral stem had become loose and was broken. Furthermore around metal to

metal joints, like the McKee-Farrar-type , greater

amount of metallic wear products could be seen. The

particles were stored mainly in histiocytes. In those

cases the newly formed joint capsule showed a stronger

tendency towards fibrosis and necrosis.

Excessive amounts of metallic wear debris were produced by hinged, all metal knee- and elbow-prostheses

.

In those types also the size of the particles was considerably larger.

In these cases, macroscopically the capsular tissue had

a more or less intense black colour, in particular at

the inner layer facing the joint cavity. The metallic

particles mainly were to be found in histiocytes whose

cytoplasm often was completely packed with black particles. The phagocytes were mostly arranged perivascular ly in strings or foci, so that they appeared to form

granulomas. A strongly marked lymphoplasmacellular infiltration was sometimes notable without any evidence

of bacterial infection. The tissue shows a strong tendency to form collagenous fibres, i.e. fibrosis and

scar formation. On the other hand we found together

with an above the average amount of metallic wear a considerable tendency of the capsular tissue to become

necrotic. Then, in the joint cavity masses of fibrin

and necrotic debris were found, aggregated on the inner

surface of the capsule. They also contained large

amount of black, metallic particles. This indicates a decompensation of the foreign body reaction in the

joint capsule. The tissue at the interface between bone

and cement-implant as well as the RHS of the bone marrow had already become involved in the storage of metallic wear particles. This could be recognized macroscopically by the black colouring of the tissue. By help

of the microscope, a foreign body granulation tissue

with phagocytes containing the metal particles and with

resorption of the adjacent bone trabeculae could also

be seen at the bone / cement - interface and in the

marrow spaces. Clinically most of these endoprostheses

had been loose (fig. 4). A comparative survey is given

24B
Size Distribution of Metal Wear Particles

100-t average number I %l

CoCrMo -cast alloy / CoCrMo -cast alloy CoCrMo - cast alloy / polyester AISI-316 L - stainless steel /polyethelene CoCrMo-cast alloy /polyethelene

Inil 0.0- V3' -2.26' - 3.39'XU

>i>52> - 5.65' .ATM

area of particles

Figure J. Size distribution of metal wear particles

stored in tissue surrounding total hip replacements

of different material combination. The average number

( % ) of particles measured to ly in a certain range

of size is given. Metal-on-metal total endoprostheses

produced the most, metal-on-polymer less amount of

metallic wear. The material combination CoCrl'Io-cast

alloy on Polyethylene proved to cause the least

metallic wear.

24 7
Figure 4. Micro-photographs , 800 magnification,

a) bright light, b) polarized light show a tissue

section, stained H&E, of capsular tissue surrounding

a total elbow-joint replacement after two years of

function, material combination: metal on metal.

Diffraction of the polarized light on orientated

particle borders causes changes of the rotatoinal

plane of polarisation. Thus the particles produce

bright light effects.

24 8
in table 2.

2.2.4 Polymer Materials

2.2.4.1 Teflon (Tetraf luorethylene ) and Fluorosint (Tetraf luoiethylene filled with mica)

Acetabular cups made out of Teflon or Fluorosint

were subjected to a high rate of wear. The metallic

head of the femoral component shifted on an average of

2.5mm pa. into the cup, producing an enormous amount of

wear particles in a wide range of size. They caused a foreign body reaction in the joint capsule which was

characterized by formation of large granulomas, containing numerous giant cells and a strong tendency to

necrosis. That means the foreign body reaction of the

capsule decompensated soon. In the joint cavity masses

of caseous, necrotic tissue debris accumulated, containing the wear particles. The tissue at the cement /

bone - interface always had become involved in the response to the wear products, forming a foreign body granulation tissue which caused resorption of the adjacent

bone. The osteolysis markedly occured at the calcar

femoris and in the depth of the acetabulum. Loosening

or fracture of the prosthetic components most often led

to a failure of the artificial joint.

Since Teflon and Fluorosint are no longer used as

materials for artificial joints we will not go into

further details.

2.2.4.2 Polyester (Polyethyleneterephthalate)

In artificial joints, having a metal component for

the femoral head and a polyester socket, the production

of wear debris resembles in somewhat those hip replacements with metal and polyethylene combination, showing

an increased rate of abrasion. In other words: the polyester sockets were subjected to a greater amount of

wear than polyethylene sockets. In some instances the

polyester sockets broke after some years of function.

In artificial hip joints with trunnion bearing # where the ball was made out of polyester and the femoral

stem and the socket out of metal, an excessive amount

of wear occured with the polyester. The polymer was

abraded mainly at the bore of the cylinder of the ball.

The size of the abraded particles ranged from 0.5 up

to 20 jam (seldom up to 100 jam) in diameter. 34 % of the

visable particles ranged from 1.1 up to 2.2 jam^ . Figure

249
5 shows size distribution of polymer wear particles

measured by means of television image analysis. In such

cases the joint capsule was considerably increased in

thickness and consisted, expecially in the inner layers,

of a granulation tissue in which mono- and binuclear

histiocytes of epitheloid appearance predominated,

whereas multinucleated foreign body giant cells were

less frequent. The small and medium sized polyester

particles were stored in the plasm of the histiocytes

while larger polyester particles were either surrounded

by giant cells or were situated extracellular ly in the

tissue (fig. 6). The foreign body granulation tissue

formed large nodules with necroses in the center and a palisade-like arrangement of cells as well as lymphoplasmacellular infiltration in the periphery. Together

with the appearance of giant cells the picture resembled

tuberculosis. The tendency to necrosis was highly pronounced in these capsules. The capsular tissue furthermore showed a strong tendency to fibrosis and hyalinisation and consequently to scar formation. Decompensation of the foreign body reaction was indicated by the

accumulation of large amounts of pasty masses (histologically recognizable as fibrin and necrotic tissue)

in the joint cavity, covering the inner surface of the

capsule and filling deep crypts between course capsular

villi. The necrotic masses are intermingled with polyester particles similar to those incorporated in the

capsule. In all of these cases a typical foreign body

reaction additionally developed at the bone - cement - interface and within the marrow spaces of the adjacent

spongious bone (see comparative survey given in table 2).

Again, here the bone trabeculae were resorbed and the

prosthetic implants loosened. The loosening clinically

occured on average after a relatively short period of

3 to 4 years of function of the joints in the human

body

.

2.2.4.3 Polyacetal (Polyoxymethylene , homopolymer)

The changes of the histological response to the

implant evoced by wear particles released from polyacetal resemble very much those observed with polyester.

2.2.4.4 Polyethylene

(Ultra-High-Molecular-Weight Polyethylene)

In artificial hip joints we found that the material

combination of polyethylene (socket) and CoCrMo-cast

alloy or chromium-plated CoNiCrMo-forged alloy (femoral

head) showed the smallest rate of wear. In the surroun250
average number I %1

Size Distribution of Polymer Wear Par tides

area of particles [ jum?]

Figure 5- Size distribution of polymer wear particles

gained by television image analysis of tissue sections

surrounding total hip replacements. The average number

( % ) of particles measured to ly in a certain range

of size is given. The polyester particles are on

average twice as much stored in the tissue as polyethylene particles.

25 I
Figure 6. Microphotograph of tissue section, stained

H&E, of capsular tissue surrounding a Weber-Huggler

total hip replacement after three years of function,

material combination: CoCrMo-cast alloy on Polyester,

a) bright light, b) polarized light, note double

diffraction of the polymer particles.

252
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w-t I t h-H I 1 EH Pd 03 1^1 O EH

Ph <j

Ph S ++

Fh + + o + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

EH pq

\si Ph P H pq \03 EH tu & O CO EH

O Ph

p

O Ph pq 1 pq o pq P o >H M p pq

EH pq !=> P P p pq pq p o o H P>

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253
ding tissues of these joints only very few polyethylene

particles were to be seen, mainly situated in the vicinity of vessels, where they apparently were transported

away via the perivascular lymph spaces (fig. 7). Here,

obviously an equilibrium had been established between

the release of wear particles and the tissue reaction,

and had been maintained even after a long lasting function period of the endoprostheses. Their size ranged

from 0.5 to 50 jam in diameter, some even up to 100 _um.

Most of the polyethylene particles were found to be in

the same range of size as those from polyester when

measured by television analysis (fig. 5). But in the

range of 4.4 up to 15.6 jum2 greater amounts polyethylene particles were found.

The wear of the polyethylene sockets in dependanoe

of time can be determind by measuring the X-raypictures of the hip prosthesis, taken during the

follow-up period. Using the method of SCHEIER and

SANDEL HI we measured the wear of polyethylene

sockets of 254 hip prostheses with an implantation period of 6 to 96 months. The measuring

method based on the determination of the position

of the prosthetic head in the socket. If wear

occurs at the articular surface of the cup, the

head migrates in the direction of abrasion which

lies in the main bearing area of the joint. The

metal wire marker of the polyethylene socket runs

equatorially around the socket and appears on

radiographs as an ellipse. The displacement of

the head can be estimated by measuring the distances 1 . between the margin of the head and the

vertices of the ellipse and 2. between the center

of the head and the main axis of the ellipse.

During the first year after operation the shift

of the head was about 0.3 mm on average but decreased in the following years to an average

value of 0.14 mm per year / 8 , 9 , 10 / (fig. 8) . Most of the measured hip prostheses clinically

showed good functional results and a normal

weight bearing of the artificial joints was possible. There were no hints of imminent failures

of the endoprosthesis, neither signs of loosening nor other complaints (except some typical

pain when starting to walk)

.

Basing on these results it can be considered

that the capsular tissue is able to incorporate

and transport continuously wear particles, originating from the articular surface of a polyethylene socket with a rate of wear of 0.1 mm per

year. This amount of wear can be taken as a limit

for the ability of the tissue to cope with wear

particles and maintain the postulated "equilibrium";

254
b)

Figure 7- Microphotograph of tissue section, stained

H&E, of capsular tissue surrounding a Hiiller total

hip prosthesis after four years of function, material

combination: CoCrKo-cast alloy on UHMW Polyethylene,

400 magnification, a) bright light, b) polarized

light. Particles are visible by means of their

birefringence

255
oc

Q) £1.0

•5 OS

r o.& w0,7

0,6

OJS OA

03

0.2

0.1

,x average shift

.x »y

9

x^ —. Q—. _

Q_ . . _g Q shift per year

0.5 1 2 3 U 5 6 7 8time [years]

Figure 8. Evaluation of the shift of the prosthetic

head into the hip socket measured from radiographs.

The hip prostheses were of the Miiller type with a metal stem and head ( CoCrMo-cast resp. CoNiCrMoforged alloy ) and a polyethylene socket. The average

values of the shift and the yearly rate of shift are

shown in dependance of the time period after

operation

.

25G
An increase of the amount of wear particles

of polyethylene can occur if unfavourable conditions exist in addition to the functional stress

of the joints. For example high abrasion of polymer material can be caused by

- scratches at the highly polished joint surface

of the metallic head,

- bone fragments being entrapped between the artucular surfaces,

- a design of the prosthesis not corresponding

to the material' s properties.

This was true, for example, when polyethylene

had been used as material for the ball of a total hip endoprosthesis. An enormous abrasion of

the polyethylene took place at the convex surface

of the ball which finally caused loosening of the

prosthetic parts (11),

Extremely worn-out polyethylene sockets can cause

wedging of the metal head and, because of an overstress of the cement anchors, loosening of the

implants can be induced.

In cases with a relatively high wear of polyethylene, a massive storage of polyethylene particles could

be found in the capsular tissue, often in connection

with small amounts of metallic debris. The smaller polyethylene particles are stored in histiocytes , the larger ones in multinucleated giant cells. If histiocytes

and giant cells accumulate, they form a foreign body

granulation tissue, which is typical for the storage of

polyethylene wear debris. Furthermore there is a more

or less strongly marked formation of collagenous fibres,

resulting in fibrosis and scar formation. On the other

hand, the capsular tissue shows little tendency to

hyalinization and necrosis. Lymphoplasmacellular infiltrates, if at all , were observed on a very small

amount only (see table 2)

Under circumstances of a higher wear rate we found

even in joints with polyethylene bearings a decompensation of the foreign body reaction. Then, the tissue

at the cement / bone - interface also showed the development of a foreign body granulation tissue which contained polyethylene wear products, and which initiated

bone resorption, finally leading to loosening of the

implants. Thus, in principle, loosening due to excessive wear even can occur with polyethylene bearings.

2.2.4.5 Polymethylmethacrylate Bone Cement

and Contrast Medium Zr0 2 and BaSO^

Deposits of Polymethylmethacrylate (PMMA) and

257
contrast medium could always be found in the tissue of

the implant-bed and in the joint capsule.

PMMA is soluble in conventional solvents used in

histology-preparations. Consequently it is dissolved in histological sections prepared from

paraffin-embedded tissue material. On the other

hand, in frozen sections polymethylmethacrylate

remains preserved without any changes. It stains

red-orange with SUDAN III (fig. 9)

.

The contrast medium (ZrC^ or BaSO^) which is

usually added to the bone cement is not soluble

in conventional solvents. It therefore remains

in place even after paraffin-embedding and can

therefore be used as a tracer to detect or to

prove inclusions of bone cement particles in the

tissue

.

Within fragments of bone cement the contrast medium shows the same distribution as in the cured bone

cement mass : The particles lie between the pearls.

In the neighbourhood of smaller PMMA- inclusions often

the particles of contrast medium can be found in histicytes as well as in giant cells. Sometimes the foreign

body granulation tissue contains relatively large

amount of particles of the contrast medium. From this

finding one might conclude that bigger bone cement

fragments had been disintegrated by cellular activity

so that the particles of the contrast medium could

become liberated an phagocytosed by the cells.

Larger Polymethylmethacrylate particles (up to

1 and 2 mm) were surrounded by numerous foreign body

giant cells. Frequently, a cell-containing notwork

could be seen extending between the beads of the polymer. Medium sized and small fragments (only few Jim)

are completely incorporated in the plasm of multinucleated foreign body giant cells. The very small, dustlike PMMA-particles were stored in mononuclear histiocytes; the plasm of these cells became granular and

foamy. The PMMA-containing cells accumulated and formed

granulomas (compare with table 2).

Depending on whether large or small particles

preponderate, foreign body giant cells or histocytes

dominate the histological picture. When only a few

acrylate inclusions are present, they are distributed

irregularly within the capsular tissue and are mostly

enveloped by foreign body giant cells. The tendency

to fibrosis of the tissue containing PMMA-particles

is weak, especially in areas abounding with giant

cells. Necroses and hyalinization were observed sometimes; lymphoplasmacellular infiltrates were rare.

Frequently PMMA particles were observed in the peri258
Figure 9- Microphotograph of frozen tissue section,

stained Sudan III, of the bone - cement border from

a Miiller total hip replacement after five months of

function, material combination: CoCrlio-cast alloy on

Polyethylene. 560 magnification, a)bright light,

b) polarized light. Note that non dissolved PMHA-beads

show little if any double diffraction.

253
vascular lymph spaces, even in a great distance from

the inner surface of the capsule. This finding suggests that a transport of bone cement fragments too

via the perivascular lymph spaces occours.

Like the other biomaterials , also particles of

the PMMA-bone cement can cause a loosening of the

implants due to the development of a foreign body

reaction at the bone / cement - interface. The only

difference is that the particles of PMMA originate

not at the joint surfaces but directly at the bone /

cement - interface. This occurs if the bone cement

cuff breaks or if single pearls or clusters thereof

are abraded or broken out of the surface of the

cement implant, for example due to micromovements

during weight bearing. These fragments are incorporated or surrounded by histiocytes and foreign body

giant cells, which again are forming a granulation

tissue capable to resorb the bone from the inside

( fig. 10 ).

2.2.4.6 Silicone Rubber

This material is used for implants which are

called ' interpositional arthroplasties' in finger-,

wrist- and elbow joints. These implants are not firmly anchored to the bone but become fixed by an

encapsulation process due to the formation of a functionally adapted fibrous capsule /12/. Under movement of the joint, a shifting and rubbing of the

implant against the bone can occour which sometimes

causes a considerable abrasion of silicone rubber

particles ( size of a wide range: 1 - 50 - 100 nw ) from the surface of the implant. These particles are

phagocytosed by the surrounding tissue, which is the

abovementioned fibrous capsule ( see table 2 ).

The tissue develops a foreign body reaction with the

appearance of foreign body giant cells and histiocytes which incorporate the silicone particles and

form granulomas of considerable dimensions ( fig. 11)

Not only in the fibrous capsule but also in the

marrow spaces of the adjacent bone this foreign body

granulation tissue occurs and gives rise to bone

resorption, resulting in a more or less pronounced

osteolysis /13A

2.2.5 Ceramic

In contrast to the initial hope, the combination

of ceramic material in artificial joints will not pro

duce a substantial amount of wear particles, one had

to learn in the meantime that even the highly wear

260
Figure 10. Formation of a foreign body granulation

tissue and "bone resorption induced by scattered bone

cement

26 I
Figure 1*1. Tissue sample, stained H&E, surrounding a

Swanson hand interponent, completely made out of

silicone rubber after 1.75 years of function. Abraded

particles are hardly visible in normal transmitted

light. Stored in foreign body giant cells and histiocytes as well as extracellularly the round and oval

particles show a slight dark-lined border. Microphotograph, 800 magnification, normal transmitted

light

.

262
resistant High Density Aluminum Oxide Ceramic (14)

is subjected to abrasion (15) (fig. 12).

The ceramic particles released from 1 he articluar

surfaces were incorporated in phagocytes of a foreign

body granulation tissue which appeared in the joint

capsule as well as at the bone / cement - interface

(comperative table 2).

3. Discussion and Conclusions

Investigating the biological response to wear debris in total joint replacement we came to the following

conclusions

- the presence of a foreign body reaction in the

surrounding of an implant at all indicates, that

constituants of the implant's material are released

into the tissue.

- The intensity of the foreign body reaction and the

amount of particles incorporated in the tissue can

be taken as measure for the mater ials 'wear resistance

under use in the human body.

- The biocompatibility of implant materials can be

estimated from the character of the foreign body

reaction

- Judging the effects which biomaterials may have on the

living tissue one should keep in mind that tissue

necroses can appear not only as a result of toxicity

but also as a consequence of excessive proliferation

of a foreign body granulation tissue.

- The occurence of lymphocytes and plasma cells in the

tissue in connection with a foreign body reaction

does not necessarily indicate a bacterial inflammation . It might be supposed that these infiltrates have

something to do with a hypersensitive response. Besides an accumulation of lymphocytes and plasmacells

especially adjacent to metallic wear debris, we did

not find any changes which could be designated as

characteristic for an allergic reaction to materials

of the implants. Thus we could not confirm the statement of EVANS et al. /16/ or Jones et al . /17/ that

loosening of the implants can be a result of tissue

changes due to metall allergy.

A certain amount of wear particles even of bigger

sizes can be eliminated by the capsule tissue. This

mechanism allows to achieve an equilibrium between

abrasion, phagocytosis and elimination of wear particles. This equilibrium we have to look upon as optimal as long as it is not possible to avoid wear totality

263
b)

Figure 12. Microphotograph of ceramic particles out

of capsular tissue of an all-ceramic total joint re

placement, J 20 magnification, a)normal bright light

b) polarized light. Birefringence of particles

depending on their orientation to the optical axis.

264
The release of excessive amounts of wear particles

causes a decompensation of the foreign body reaction in the joint capsule recognizable by the incidence of large areas of necroses in the foreign body

granulation tissue. These necroses impede the phagocytic activity of the capsular tissue. Then in addition to the capsule, the tissue of the bone / implantinterface becomes involved into the foreign body reaction, resulting in the formation of a foreign body

reaction, resulting in the formation of a foreign

body granulation tissue, resorption of the adjacent

bone and finally loosening of the implant. The relationship between excessive wear, bone resorption of

the implant bed and loosening of the implant has been

proved now for 7 different materials. The connecting

link of these phenomena is the foreign body reaction

to wear produces. For this mechanism the chemical

structures of the implant materials seem to be much

less important than the amount of wear products.

If larger amounts of tissue necroses accumulate within

the joint cavity, they can interfere with the lubrication of the articulating surfaces.

The tendency to thickening and fibrosis of the joint

capsule can result in an increasing loss of mobility

of the artificial joint. This is most important in

particular for the finger joints /13/.

For the moment, we found, that the material combination of polyethylene with metal still seems to be the

best, because it showed the smallest quantity of wear

and the slightest foreign body reaction of the surrounding tissues.

2G5
References

1* Semlitsch, M. , Technical progress in artificial

joints, in Total Hip Prosthesis , Gschwend, N. and

Debrunner, H.U. eds., pp. 256 - 278 (Hans Huber

Publishers, Bern Stuttgart Vienna, 1976)

2. Semlitsch, M. , Vogel, A. and Willert, H.G., Kombination moderner Mikroanalysemethoden zur Untersuchung von Gelenkendoprothesen-Abr ieb im

Bindegewebe der Gelenkkapsel , Medizinalmarkt/

Acta Mediotechnica, _1_9, (6/7), 38-41 and 49-52,

(1971

)

3. Willert, H.G., Buchhorn, G. and Semlitsch, M.

,

Recognition and differentiation of wear products

in the surrounding tissues of joint endoprostheses, in The Tribology Of The Natural And Artificial Joints , Dubleton, J.H. ed. (Elsevier Publishers,

Amsterdam, 1980, in press)

4. Willert, H.G. , Tissue reactions around joint

implants and bone cement, in Arthroplasty Of The

Hip

,

Chapchal, G. ed. , pp. 11-21 (Georg Thieme

Publishers, Stuttgart, 1973

5o Willert, H.G. and Semlitsch, M. , Reaction of the

articular capsule to plastic and metallic wear

products from joint endoprostheses, Congress of

Dutch-Swiss Orthopaedic Societies, Lausanne,

(1974), reprint from Sulzer Technical Rev.

2, (1975)

6.- Willert, H.G. and Semlitsch, M. , Reactions of the

articular capsule to wear products of artificial

joint prostheses, J. Biomed. Mater. Res., 1

1

, 157-164, (1977)

7. Scheier, H. and Sandel, J., Wear affecting the

plastic cup in metal-plastic endoprostheses,

in Total Hip Prosthesis , N. , Debrunner, H.U. eds., pp. 186-190, (Hans Gschwend,

Huber Publishers, Bern Stuttgart Vienna, 1976)

8* Willert, H.G., Semlitsch, M. , Buchhorn, G. and

Kriete, U., Mater ialver schleiB und Gewebereaktion bei kiinstlichen Gelenken, Orthopade , 1_, 62-83 (1978)

9* Buchhorn, U. , Willert, H.G., Semlitsch, M.

,

Weber, H., Lehmann, M. , Niederer, P.G. and

Dorre, E., Wear behaviour of total hip prosthesis components made of different bearing

materials - a clinical and laboratory study

2S6
(Proc. 3rd Internat. Conference: Plastics in

medicine and surgery), pp. 11.1-11.6 (The

Plastic and Rubber Institute, London, 1979)

10. new own measurements, unpublished data

11. Dahl, E. and Mikkelsen, O.A. , Wear of the

polyethylene head of the oscobal prosthesis,

Acta orthop. scand. , <47 , 643-647 ( 1 976)

12. Swanson, A.B., Flexible Implant arthroplasty for

arthritic finger joints, J. Bone Jt. Surg.,

54-A ,/3/, 435-455 (1972)

1

j Willert, H.G., Buchhorn, G. and Semlitsch, M.

Die Reaktion des Gewebes auf Verschlei Bprodukte von Gelenk-Endoprothesen der oberen

Extremitaten, Orthopade, 9, pp. 94-107 (1980)

14, Heimke, G., Griss, P. and Krempien, B.,

Ceramic endoprostheses, Powder Metallurgy

International, 8,/2/, pp. 77-81 (1976)

15; Plitz, W. , Clinical and tribological aspects of

the damage analysis of A^O^ ceramic hip-joints

(First World Biomaterials Congress, Baden,

1980) Book of Abstracts, p. 3.3.6

16* Evans, E.M. , Freeman, M.A.R. , Miller, A.J., and

Vernon-Roberts, B., Metal sensitivity as a course of bone necrosis and loosening of the

prosthesis in total joint replacements,

J. Bone Jt. Surg., 56-B , 626-642 (1974)

17, Jones, D.A., Lucas, H.K., 0

1 Driscoll, M.

Price, C.H.G. and Wibberley, B., Cobalt

toxicity after Mc Kee hip arthroplasty,

J. Bone Jt. Surg., 57-B, 289-258 (1975)

This work was partly supported by the

Deutsche For schungsgemeinschaf t (Wi 346/6).

2S7
I I I)!fI
MATERIALS DEGENERATION CAUSING LATE FAILURE OF MECHANICAL HEART

VALVE PROSTHESES: PROBLEMS AND PROMISE

Frederick J. Schoen 1 , Jack L. Titus and Gerald M. Lawrie

Department of Pathology

University of Florida College of Medicine

Gainesville, Florida 32610

and

Departments of Pathology and Surgery

The Methodist Hospital

Baylor College of Medicine

Houston, Texas 77030

Materials degradation with resultant clinically significant valvular dysfunction has been an important late

complication of cardiac valvular replacement with mechanical

prostheses. Major mechanisms of failure are primarily re- lated to either lipid absorption by silicone elastomers or abrasive wear of polymers. In a review of the necropsies of

99 patients dying late after cardiac valvular replacement,

we encountered two cases of fatal valve deterioration, one involving each of the above failure modes. We examined by

scanning electron microscopy and analytical surface profilometry seven contemporary heart valve prostheses recovered

from this series, all of which had no clinical or pathological evidence of degeneration/dysfunction, and all of which

contained pyrolytic carbon components and had been in-situ

for 30 months or longer. Results of this analysis suggest

that progressive deterioration by abrasive wear of pyrolytic

carbon heart valves will not be a significant problem.

1. Introduction

Prosthetic valve malfunction resulting from materials degeneration

has been an important late complication after cardiac valvular replacement. Reoperation with replacement of the prosthetic valve for degeneration/dysfunction was required in 2.5% of 891 patients undergoing valve

replacement from 1962 to -1977 in one study [I]

2 and 1.5% of 799 in

another [2]. Mortality for reoperation has been high — 36% and 42% in

the above studies. In a necropsy study of patients having a variety of

Present mailing address: Department of Pathology, Peter Bent Brigham

Hospital, 721 Huntington Avenue, Boston, MA 02115.

2 Figures in brackets indicate the literature references at the end of

this paper.
mechanical prostheses, prosthetic valve deterioration was the cause of

death in 19% of 134 patients dying more than 60 days after valve re- placement [3]. The significance of dysfunction among specific prosthetic

valve designs varied widely.

In this report we examine the problem of mechanical prosthetic valve

dysfunction due to materials degeneration from three approaches. First, we review the various modes of failure that have been identified for the

wide variety of mechanical heart valve prostheses in past and current

use. Secondly, we examine fatal valve degeneration among 99 patients

dying late (up to ten years) after receiving prosthetic heart valves.

Lastly, we summarize our analysis of abrasive wear in eight pyrolytic

carbon-containing heart valve prostheses recovered from patients who died

or required reoperation, seven of these after implantation times of

greater than two-and-a-half years.

2. The Problem: Materials Degeneration and Valve Durability

The silicone ball occluder in early models of the Starr-Edwards 3 and

Smel off-Cutter caged ball prostheses was subject to lipid infiltration

and subsequent swelling, distortion, grooving, cracking, embolization of

poppet material or abnormal movement of the poppet due to sticking [5,6].

This phenomenon, known a ball variance, often led to acute valvular malfunction and death. In one large series, 16 of 25 (64%) of deaths of

patients who survived more than two years (average 43 months) after aortic

valve replacement with caged ball prostheses were caused by ball variance

[7]. Mitral ball variance (fig. 1) has been less common than aortic, suggesting that hemodynamic factors play a role [7,8]. For valves produced

since 1964, changes in the fabrication of the silicone elastomer have

almost eliminated ball variance as a problem. However, there have been

occasional reports of severe poppet wear in some cloth-covered silicone

ball containing valve prostheses that were implanted during 1971-74 [9].

The mechanism of this complication is abrasive wear and is not related to

lipid infiltration. Use of a hollow ball fabricated from metal (chromiumcobalt alloy) has now virtually eliminated post-implantation changes in

the poppets of caged ball valvular prostheses.

Cloth-covered caged ball valves with silicone and metal poppets do

suffer problems related to cloth wear (fig. 2) and attendant hemolysis [9-

11]. Although the exact incidence is not known, evidence of cloth wear in areas of abrasion by the metal poppet was seen in 10 patients reoperated

for prosthesis-related complications in one study [10], and in another

series, 5 of 204 (2.5%) patients with cloth-covered metal ball Starr-Edwards prostheses were reoperated for consequences of cloth wear [11].

Symptomatic embolism of the cloth covering the cage struts has been reported as a secondary problem. A recently introduced modification of the

cloth-covered ball valve prosthesis incorporating a metal track is designed to eliminate direct contact of the metal ball with the cloth-covered

cage [10], but the long term fate of this prosthesis is not yet certain.

Wear of the caged disk valves has been a significant problem and

descriptions of the specific prosthetic cardiac valve designs discussed

are available [4].

270
abnormalities in the disks of a variety of caged disk valves have been

reported [12,13]. Abrasion in this design may be concentrated at critical

points. When extensive material loss occurs disk motion may become irregular. Although it is intended that the disk rotate over time and

abrasive action be distributed symmetrically around its circumference,

this is not always the case, and notching as well as severe decrease in

diameter of the disk may occur. In designs which have a plastic disk and

plastic-coated metallic struts, the struts may also be a localized site

of wear, to the extent that underlying metal may be exposed (fig. 3).

The functional results of disk wear include partial tilting of the

disk in a fixed position that may lead to acute valvular dysfunction with

mixed obstructive and regurgitant components, chronic valvular regurgitation accelerating cardiac decompensation, hemolytic anemia and systemic

embolization of valve material. In one series in which thirteen Beall

valves (Teflon disk and strut coating) implanted for periods greater than

29 months were recovered and analyzed, twelve valves had notching of the

disk and focally complete denudation of the plastic coating on the struts,

always worse on the dependent struts [13]. Nine of these 12 patients (75%)

had hemolysis with anemia. Excessive mechanical destruction of the formed

elements of blood (particularly red blood cells) may lead to iron deposits

in the kidneys, with potential clinical significance (fig. 4a). A consequence of the degeneration of the materials of construction of such prostheses is the systemic embolization of plastic fragments. In such cases,

polymeric fragments are often seen in the small arteries of the heart

(fig. 4b) and other organs with a surrounding foreign body giant cell inflammatory reaction.

Tilting disk valves in general have had a good record with regard to

durability. The design of both the Bjork-Shiley and Lillehei-Kaster valve

prostheses allows for disk rotation and minimal stress, so that progressive

mechanical failure is unlikely [3,14,15]. The design of the Wada-Cutter

valve, on the other hand, does not allow for disk rotation and thus localized wear and its consequences may occur [16].

Trileaflet polymeric aortic valve prostheses, exemplified by the Hufnagel prosthesis, showed severe fatigue degeneration and were discontinued

[17].

The long term durability of the glutaraldehyde-stabilized porcine

heterograft remains uncertain, despite favorable clinical experience of

over six years [18,19], Recent evidence indicates that degeneration with

dysfunction is a common late occurrence; a particularly high incidence of

calcification of the valve leaflets is seen in children receiving this

prosthesis [20].

3. Fatal Valve Malfunction Due to Degeneration

From April, 1962, to June, 1979, 99 patients died and underwent necropsy at The Methodist Hospital of Houston, Texas, 30 days to ten years

after cardiac valvular replacement. From analysis of pertinent clinical

and pathological data, the causes of death in these patients could be

grouped into three categories: (1) residual or associated cardiovascular

defects or complications of operation; (2) prosthesis-associated complica27 I
tions; and (3) conditions unrelated to the cardiovascular problem (fig.

5)

1*. The prosthesis-associated complications, which were responsible for

40% of late deaths were thromboembolic catastrophies (including thrombotic occlusion, systemic thromboembolism and antocoagulation-related hemorrhage) in 24%, prosthetic valvular infection in 14% and materials degeneration with dysfunction in 2%. The lattermost two cases are of major interest in this paper.

In one of the two cases of fatal dysfunction, a 44 year old woman had

undergone aortic and mitral valve replacement for rheumatic heart disease

in 1964. The mitral prosthesis was a Starr-Edwards caged ball valve with

a silicone occluder and the aortic was a Smeloff-Cutter ball valve with a silicone poppet. Nine years later she died of congestive heart failure.

The aortic valve poppet was markedly discolored, swollen and virtually immobile in the cage (fig. 6a). The poppet of the mitral prosthesis was slightly discolored but there was no apparent distortion of shape or

function. In the other case, a 48 year old man with rheumatic mitral valve

disease received a DeBakey mitral prosthesis with a Teflon disk in 1969 and

died sixty-nine months later of congestive heart failure caused by prosthesis incompetence. The disk occluder was markedly notched and reduced in

size (fig. 6b). A striking finding in this case was the presence of intense foreign body giant cell reaction to fragments of plastic in the

heart and kidneys.

4. Valves without Malfunction

In an effort to assess the significance of abrasive wear occurring on components of mechanical heart valve prostheses utilizing pyrolytic carbon

components, we recovered 9 prostheses for detailed analysis (table 1).

Eight were from the necropsy series described above and one was recovered

from a patient requiring reoperation for a minute thrombus occluding valve

motion. Eight of these valves had carbon occluders or both carbon occluders and cages; seven of the eight valves had duration in-situ of greater

than thirty months. A Teflon Beall disk valve implanted for thirty-four

days and a DeBakey disk valve with a carbon disk implanted for forty-four

days served for comparison to the valves of longer function. No clinically

significant wear was apparent on any of these prostheses.

After retrieval, the valves were carefully cut so that that the occluders could be removed and sent for analytical surface prof ilometry and the

cage struts oriented and prepared for scanning electron microscope examination. A detailed description of this study will be reported in a separate

communication.

A cage strut from a Teflon Beall valve implanted for thirty-four

days is compared with that from a pyrolytic carbon Beall valve implanted

for four years in figure 7. More abrasive wear occurred on the Teflon cage

strut than on the carbon cage strut, even though the latter had been in

service more than ten times as long as the former. Little difference in

Tor the purposes of this report we consider late separation of the valve

prosthesis from the tissue annulus (dehiscence) to be a complication of

the operation rather than a complication of the prosthesis per se.

272
wear was seen among the four vertical components of the struts of each of

the carbon valves examined; in contrast, there was a large difference in

the degree of wear among the four Teflon struts, as previously reported

after longer periods of function [4],

The DeBakey caged ball valves with carbon occluders and titanium cage

struts had noticeable wear on the struts (fig. 8), but this was not of

clinical significance. This contrasts with the report of extensive titanium abrasion in an unusual case where proper excursion of the ball of

this aortic prosthesis was prevented by anatomical constraints [21]. The

markings on the titanium cage struts of a DeBakey carbon disk valve after

only forty-four days of implantation (fig. 9) are somewhat similar to

those of the carbon Beall valve after considerably longer duration of implantation (fig. 7).

Representative traces obtained by surface profilometry 5 of the carbon

disks from a Beall valve, a Cooley-Cutter valve, a Bjork-Shiley valve and

a Lil lehei-Kaster valve are shown in figure 10. The traces were selected

from those areas of the disk known to have contact with the cages. The

only disk having any localized abnormal ity was from a Lillehei-Kaster prosthesis in which a circumferential groove of minimal depth (<0.5y) was

noted, as reported by Lillehei [15].

Materials degeneration of prosthetic heart valves with dysfunction,

either fatal or significant enough to require reoperation, has been an important late complication of heart valve replacement. There is evidence

from both clinical and pathological studies that this complication is decreasing with improvements in prosthesis design and materials.

Despite the significant advantage offered by tissue prostheses not

requiring chronic anticoagulation of the patient, tissue prostheses have

not been shown to have reliable lifetimes exceeding those of currently

available mechanical prostheses. Therefore, further consideration and

development of mechanical heart valve prostheses is critical.

Traditionally, analysis of implanted medical devices in general has

concentrated on those devices that failed in service. Little attention

has been paid to those serving the patient well until death or removal

for reasons other than device malfunction. The present study is additional

verification that detailed analysis of functional prostheses removed from

patients after long durations of implantation may yield worthwhile data

regarding the insidious development of complications. As an increasing

fraction of patients with prostheses die of causes other than complications

of their devices, such studies will continue to be an important source

of information not obtainable in-vitro or in pre-clinical animal investigations.

Pyrolytic carbon is a material that has found wide application in car- diovascular prostheses, especially prosthetic heart valves [22]. It is

Analytical surface profilometry was done by Dr. H.S, Shim of CarboMedics,

Inc. , San Diego, CA.

5. Concluding Comments

273
well to keep in mind, however, that although pyrolytic carbon is extremely

strong and abrasion resistant, under certain conditions the material has

brittle characteristics which render it sensitive to cracks and notches,

particularly those induced during pre-implantation manipulation. Rare

reports of catastrophic failure of carbon valve components have appeared

[23,24]. Nevertheless, the use of pyrolytic carbon as an occluder and

strut material for mechanical heart valve prostheses appears to have

eliminated abrasive wear as a long term complication of cardiac valvular

replacement.

The authors wish to thank the American Lung Association for partial

support of this study through a Clinical Training Fellowship awarded to one of us (FJS).

Table 1

Valves Examined, Sites and Implantation Times

Prosthesis type Site3 Duration inDeBakey (PYC

bdisk) M 44 days

Lillehei-Kaster (PYC disk) T 30 mos

Beall (PYC disk) M 32 mos DeBakey (PYC ball) A 48 mos

Beall (PYC disk) M 48 mos Cooley (PYC disk) M 48 mos Bjork (PYC disk) A 60 mos DeBakey (PYC ball) A 85 mos

Beall (Teflon disk) M 34 days

aT=tricuspid valve, M=mitral valve, A=aortic valve

kpYC=pyrolytic carbon

274
Figure 1. Ball variance in a Starr-Edwards mitral valve

prosthesis. The silicone ball

occluder is markedly swollen

and fixed in position.

Figure 2. Cloth wear in a Braunwald-Cutter clothcovered aortic prosthesis

with a silicone ball

occl uder

Figure 3. Beall mitral prosthesis

with a Teflon disk and Tefloncoated cage struts. Notching of

the disk and complete focal denudation of the Teflon coating

exposing the underlying metal of

one of the struts is apparent.

275
Figure 4. Distant effects of prosthetic cardiac valve degeneration,

a) Renal hemosiderosis. Large deposits of granular iron-containing

material are seen in the epithelial cells of the renal tubules (T)

of a patient with extensive valve-related hemolysis. There is a glomerulus at upper left (190X). b) Multiorgan plastic embolization.

Large foci of foreign body reaction are seen in the heart of this

patient with a deteriorating prosthesis. Fragments of valve material

eliciting this inflammatory response are marked by arrows (300X).

Figure 5. Causes of death in 99 patients dying late after cardiac

valvular replacement. Forty patients (40%) died of prosthesisassociated complications, including thromboembolic catastrophies

(24 patients), prosthetic valve endocarditis (14 patients) and

degeneration of materials with dysfunction (2 patients).

276
I Figure 6. Fatal valve degeneration with dysfunction, a) SmeloffCutter aortic prosthesis (left) with ball variance after 9 years.

This patient also had a mitral Starr-Edwards (right) which had a slightly discolored ball but normal function, b) DeBakey mitral

disk prosthesis after 69 months. The disk is severely notched

leading to incompetent valve function and congestive heart failure.

277
Figure 7. Comparison of strut wear on carbon and Teflon Beall valves,

a) Beall carbon valve, gross photograph, b) Scanning electron micrograph of wear on cage strut from valve shown in (a) indicating thin

superficial abrasion after 48 months service (9X). c) Teflon Beall

valve, gross photograph, d) Scanning electron micrograph of strut of

valve shown in (c). The wear mark at the site of disk/cage contact

is evident. In each micrograph, the wear marks are deliniated by arrows.

278
Figure 8. DeBakey ball valve, a) Implant of 7 years duration, gross

photograph, b) Scanning electron micrograph of wear on metallic cage

struts by pyrolytic carbon ball of valve similar to that shown in (a),

implanted for 48 months (11X). c) Scanning electron micrograph of

strut wear on valve shown in (a) (11X). d) Higher magnification of area within box in (c) (33X). In both (b) and (c) the wear marks on the struts are emphasized by arrowheads.

279
Figure 9. DeBakey carbon disk valve implanted for 44 days, a) Gross

photograph, b) Scanning electron micrograph of wear on cage struts

by pyrolytic carbon disk of valve shown in (a). A superficial area

of wear is marked by arrowheads (11X).

D

Horizontal distance

Figure 10. Surface profile analyses of pyrolytic carbon occluders after

long durations of implantation, taken over critical wear areas,

a) Beall mitral disk, 32 months, b) Cooley mitral disk, 48 months,

c) Bjork-Shiley aortic disk, 60 months, d) Lillehei-Kaster tricuspid

disk, 30 months.

260
References

Sandzeu J.G., Clark, R.E., Ferguson, T.B., et aJL_, Replacement of

prosthetic heart valves, J. Thorac. Cardiovasc. Surg. 74, [6], 864-

874 (Dec. 1977).

Stewart, S. and DeWeese, J. A., The determinants of survival following

reoperation on prosthetic heart valves, Ann. Thorac. Surg. 25_, [6],

555-557 (June 1978).

Roberts, W,C. and Hammer, W.O., Cardiac pathology after valve re- placement with a tilting-disc prosthesis (Bjork-Shiley type): A

study of 46 necropsy patients and 49 Bjork-Shiley prostheses, Am. J. Cardiol. 37, [6], 1024-1033 (June 1976).

Silver, M.D., Datta, B.N. and Bowes, V.F., A key to identify heart

valve prostheses, Arch. Path. 99, [3], 132-138 (March 1975).

McHenry, M.M., Smeloff, E.A., Fong, W.Y., et al

, Critical obstruction of prosthetic heart valves due to lipid absorption by Silastic,

J. Thorac. Cardiovasc. Surg. 59, [3], 413-425 (March 1970).

Hylen, J.C., Durability of prosthetic heart valves, Am. Heart J. 8J_,

[3], 299-303 (March 1971).

Roberts, W.C., Bulkley, B.H. and Morrow, A.G., Pathologic anatomy of

cardiac valve replacement: A study of 224 necropsy patients, Prog.

Cardiovasc. Dis. 1_5, [6], 539-587 (May/June 1973).

Joyce, L.D., Emery, R.W. and Nicoloff, D.M., Ball variance and fracture of mitral valve prosthesis causing recurrent thromboembol i , J. Thorac. Cardiovasc. Surg. 75, [2], 309-312 (Feb. 1978).

Pluth, J.R., Broadbent, J.C., Barnhorst, D.A., et al

, Aortic and

mitral valve replacement with cloth-covered Braunwald-Cutter prosthesis: A three-year follow-up, Ann. Thorac. Surg. 20, [3] 239-247

(Sept. 1975).

Bonchek, L.I. and Starr, A., Ball valve prostheses: Current appraisal

of late results, Am. J. Cardiol. 35, [6], 843-854 (June 1975).

Shah, A., Dolgin, M., Tice, D.A., et al

, Complications due to cloth wear in cloth-covered Starr-Edwards aortic and mitral prostheses —

and their management, Am. Heart J. 96, [3], 407-414 (Sept. 1978).

Roberts, W.C., Fishbein, M.C. and Golden, A., Cardiac pathology after

valve replacement by disc prosthesis: A study of 61 necropsy patients,

Am. J. Cardiol. 35, [5], 740-760 (May 1975).

Silver, M.D. and Wilson, G.J., The pathology of wear in the Beall

model 104 heart valve prosthesis, Circulation 56, [4], 617-622

(Oct. 1977).

28 I
Bjork, V.O., The history of the Bjork-Shiley tilting disc valve,

Med. Instrum. [2], 80-81 (March/Apr. 1977).

Lillehei, C.W., Heart valve replacement with the pivoting disc

prosthesis: Appraisal of results and description of a new allcarbon model, Med. Instrum. £2], 85-94 (March/Apr. 1977).

DuPriest, R.W., Semler, H.J,, Oyama, A. A., et aJL_, Sudden death due

to dislodgement of disc occluder of Wada-Cutter prosthesis, J. Thorac. Cardiovasc. Surg. 66, [1], 93-95 (July 1973).

Fishbein, M.C., Roberts, W.C., Golden, A., et_ aJL_, Cardiac pathology

after aortic valve replacement using Hufnagel trileaflet prostheses:

A study of 20 necropsy patients, Am. Heart J. 89, [4], 443-448 (Apr.

1975).

Cohn, L.H., Koster, J.K. , Mee, R.B.B., et aj^, Long-term follow-up

of the Hancock bioprosthetic heart valve: A 6-year review, Circulation 60 (Suppl. 1), [2], 187-192 (Aug. 1979).

'

Oyer, P.E., Stinson, E.B., Reitz, B.A., et a_L , Long-term evaluation

of the porcine xenograft bioprosthesis, J. Thorac. Cardiovasc. Surg.

78, [3], 343-350 (Sept. 1979).

Geha, A.S., Laks, H., Stansel , H.C., et aJL_, Late failure of porcine

valve heterografts in children, J. Thorac. Cardiovasc. Surg. 78, [3],

351-361 (Sept. 1979).

Paton, B.C. and Pine, M.B., Aortic valve replacement with the DeBakey

valve, J. Thorac. Cardiovasc. Surg. 72, [4], 652-656 (Oct. 1976).

Bokros, J.C., LaGrange, L.D. and Schoen, F.J., Control of structure

of carbon for use in bioengineering, in Chemistry and Physics of

Carbon , Vol. 9, P.L. Walker, ed., pp. 103-171 (Marcel Dekker, New

York, N.Y., 1973).

Gold, H. and Hertz, L., Death caused by fracture of a Beall mitral

prosthesis: Report of a case, Am. J. Cardiol. 34, [3], 371-375

(Sept. 1974).

Norenberg, D.D., Evans, R.W., Gunderson, A.E., et al^, Fracture and

embolization of a Bjork-Shiley disc: Fatal failure of a prosthetic

mitral valve, J. Thorac. Cardiovasc. Surg. 74, [6], 924-927 (Dec.

1977).

282
PROSTHETIC VALVE WEAR PRODUCTS- -EMBOLIZATION AND SYSTEMIC PRESENTATION

J. M. Anderson, S. Barenberg* and A. Hiltner

Departments of Pathology and Macromol ecular Science

Case Western Reserve University

Cleveland, Ohio 44106

An uncommon but potentially catastrophic mode of prosthetic heart valve failure is related to the inadequate

durability of the materials used in the construction of the

heart valve. The inadequate durability of these materials

results in wear of the disc or ball occluders, the polymeric

fabric covering the seat and struts and the metallic frame.

This paper presents some of the common modes of wear of

prosthetic heart valves with an emphasis on the embolization

and systemic presentation of wear products. In particular,

the identification in organs of ball occluder fragments

from the Braunwald-Cutter aortic prosthesis will be

presented.

1. Introduction

Since the advent of surgical replacement of diseased cardiac valves

by prostheses and prosthetic materials in the early 1950's, the clinical success of these devices has been modulated by the incidence of serious

complications. These serious complications include thromboembolism,

infective prosthetic valve endocarditis, prosthetic structural dysfunction, suture dehiscence, hemolysis, hemolytic anemia and sudden death.

[1,2,3]!. Excluding those causes of prosthetic valve failure related

to surgical judgement and procedure, the majority of failures of prosthetic heart valves are related to their respective design and structural characteristics. For example, caged-ball or disc valves are all obstructive to varying degrees. This obstruction to flow may lead to

turbulence and stasis and predispose to thrombus formation and thromboembolism. Thrombogenicity is primarily related to the materials used in

the constuction of the blood contacting components of the valve. It is

not the purpose of this paper to discuss those modes and mechanisms of

failure related to inappropriate blood/materials interactions or design,

but rather, to discuss those failures which result due to inadequate

durability of the materials used in the construction of the respective

prosthetic valves. Moreover, this discussion will be limited to the

systemic findings in selected surgical pathology and autopsy pathology

cases from the Implant Retrieval and Evaluation Program at Case Western

Reserve University.

It must be emphasized that prosthetic valve failures resulting from

^Department of Chemical Engineering, University of Michigan, Ann Arbor,

Michigan.

figures in brackets indicate the literature references at the end of

this paper.

283
inadequate durability of the component materials range from common to uncommon to rare, depending on the specific type of valve and the respec

tive materials under consideration. Thus, this review will deal with

the principal failure modes with little emphasis being placed on the incidence* of specific types of failure modes as they relate to each type

of valve. The reasons for this approach are that the real numbers of

such cases are small and that many cases are probably not documented

through surgical or autopsy follow-up.

In general, the cause of prosthetic valve failure due to durability

problems can be related to one or more of the valve components. These

components are the disc or ball occluder, the polymeric fabric covering

the seat (and in some cases, the struts) and the metallic frame, including the seat and struts. Over the past two decades, numerous combinations of metallic and polymeric materials have been used in the construe

tion of prosthetic valves. These materials are listed in table I for

the sewing ring (fabric covering the valve seat), the cage or cage and

strut, and the occluder or poppet.

Table I. Materials Used in the Construction of Prosthetic Heart Valves.

Sewing Ring

Dacron

Teflon

Polypropylene

Occluder/Poppet

Silicone Rubber

Polytetraf 1 uoroethyl ene Polyethylene

Del rin

Pyrolytic Carbon

Stellite 21 Titanium or Alloy

Cage/Strut

Dacron over Titanium

Dacron over Stellite 21 Teflon over Stellite 21 Teflon over Titanium Al loy

Polypropylene over Stellite 21 Titanium Alloy

Stellite 21 Pyrolytic Carbon

(Coated)

Dacron over Del rin

(Stent)

Teflon over Elgiloy

(Stent)

Polypropylene (Stent)

Wear and embolization of wear products from prosthetic heart valves

may involve any combination of the valve components; the disc or ball

occluder, the valve seat or fabric covering the seat and the struts.

Embolization of valve fragments may occur following catastrophic failure

via a fracture mechanism and in some cases this has been preceded by wear.

Ball or disc occluder variance is the most commonly found example

of wear phenomenon in prosthetic heart valves. The first case of this

problem was reported by Krosnick and Ablaza in 1965 [4,5]. In these

cases, wear and ball variance occurred in a Starr-Edwards model 1000

aortic valve to the point where the silicone poppet embolized and caused

the death of the patient. In addition to wear, the use of the StarrEdwards Model 1000 valve identified another mechanism by which the

284
silicone ball could develop ball variance with the end result being ball

fragmentation, embolization of the fragments and the death of the patient

due to acute aortic insufficiency. This mechanism involves physical

chemical changes brought about by the inappropriate interaction between

the blood and the silastic ball, and results in the loss of the structural integrity of the ball occluder by fatty infiltration, swelling, lobulation and cracking or fissuring [6,7,8,9]. Starr has estimated that

this phenomenon occurred in approximately 75% of the patients receiving

the Starr-Edwards model 1000 valve between 1962 and 1964. [10]. These

results led to the improved design and development of the models 1200

and 1260 series of valves with a change in the fabrication techniques

for the silastic ball. The incidence of swelling, fatty infiltration,

lobulation and cracking or fissuring has been markedly reduced, but the

problem of silastic ball wear remains a problem. For this reason, the

Braunwald-Cutter aortic prosthesis has been removed from clinical use [11,12,13]. The problem of poppet wear and embolization of wear fragments in the Braunwald-Cutter aortic prosthesis will be presented in

detail in the discussion.

Disc wear has been observed in those valves which employ a plastic

occluder: Beall-Surgitool models 103 and 104 (Teflon), Bjork-Shiley

(Delrin) and Kay-Shiley (silicone rubber) [14,15,16,17,18,19]. Edge wear of the disc is commonly seen with the Beall-Surgitool models 103

and 104 and this clinical observation has lead to the use of a Pyrolitic

carbon coated disc. The disc material has also been changed for the

Bjork-Shiley and Kay-Shiley valves.

Disc variance due to edge wear may lead to subluxation of the disc

with the disc being cocked between the struts and the valve seat. Edge wear may also limit rotation of the disc and exacerbate erosion and wear. This wear occurs on both the disc edge and the Dacron fabric covering

the valve seat, and fiber embolization may result if the fabric wear is severe. Clark and coworkers have correlated the disc variance as measured radiological ly by the disc-cage ratio with hemolysis and coagulation deficits in patients with Beall-Surgitool model 103 and 104 valves

[20]. Anemia, marked elevations of LDH and large urinary iron losses

are important clinical indicators of disc variance in these valves.

Strut wear may be observed in valves where there is a mismatch in

the hardness properties of the occluder material and the strut material.

This has been seen in the Bjork-Shiley, DeBakey-Surgitool and CooleyCutter valves, and the latter two examples result from the hard carbon

occluder eroding the soft titanium struts [18,21,22,23]. This may re- sult in strut fracture. Wear is also commonly seen on the Teflon coated

struts of the Beall-Surgitool models 103 and 104 valves. In general,

embolic wear particles are too fine to be identified in the peripheral

organs in cases of strut wear.

The success of an implant retrieval and evaluation program hinges

upon the correct identification of the type of prosthesis, device or biomaterial under consideration. In regard to prosthetic heart valves,

the type of valve must be known since different valves have different

failure modes. Indeed, various models within the same group of valves

285
may have different design and structural characteristics which

can lead to different modes of failure. The identification of the

valve type and model has been facilitated by the manufacturers by providing patients with implant identification cards. If the identification card is not available, the investigator may make use of the original operative report in identifying the prosthetic valve. If neither

of these means of identification are available, the investigator may

turn to several reports which are available in the literature and permit

the identification of the specific type of prosthetic valve based on their respective structural characteristics.

In 1975, Silver and coworkers published "A Key to Identifying Heart

Valve Prostheses" [24]. They have provided schemes for identifying the

various types of caged-ball and disc valves based on the structural characteristics of the cage and struts. Chun and Nelson have published on the radiologic features of prosthetic heart valves, [25]. Morse and

Steiner have provided an atlas which provides for each type of valve,

the photographic and radiological appearance, the physical characteristics and materials used, size range and available dimensions, and

orifice area [26]. Finally, the definitive work by Lefrak and Starr

provides information on the clinical performance of each type of valve

in addition to an excellent review of the literature [1].

2. Results and discussion

2.1. Sewing ring fabric wear

Tearing, fraying and deterioration of the fabric covering the sewing ring (valve seat) may occur due to the trauma of the occluder disc

or ball striking the valve seat. This phenomenon has been observed for

nearly all valves which employ a cloth covering of the valve seat and

has been seen most commonly in the Beal 1 -Surgi tool mitral valve. Fabric

covered prosthetic heart valves were developed to reduce the incidence

of postoperative thromboembolic complications. Braunwald and her associates carried out studies which showed that the rate of thromboembol

i

formation could be reduced by a neointima which formed over and was adherent to the fabric over the inflow surface of the valve. This con- cept coupled with an appreciation of the wear phenomenon lead Starr and

his associates to design the Starr-Edwards Model 2310 valve, which made

use of the fabric orifice covering with metal studs on which the Stellite

21 ball occluder could seat. Accelerated test studies have shown that even this design may be susceptible to fabric wear [27].

An example of sewing ring fabric wear is shown in figures 1 and 2. This Beall-Surgitool 104 mitral valve had been implanted for 6.5 years

and was surgically replaced following the clinical diagnosis of valve

malfunction. It can be seen that the Dacron covering over the valve

seat has worn away, causing the fabric to extend into the inflow tract

and reduce the inflow surface area. In this case, the inflow surface

area has been reduced by ca_ 35%. This reduction in inflow tract surface

area can lead to a compromise in the patient's hemodynamics and increased

turbulence and blood trauma. This extent of sewing ring fabric wear is

usually accompanied by disc variance and strut wear.

28G
Figure 1. Ventricular view of a Beall model 104 mitral valve with

marked sewing ring fabric wear. Implanted for 6.5 years,

note exposed metallic frame.

Figure 2. Atrial view of a Beall model 104 mitral valve with marked

sewing ring fabric wear. Implanted for 6.5 years, note

loss of neointima from frayed fabric in the inflow tract.

2.2. Fabric embolization

The diagnosis of fabric embolization from worn prosthetic heart

valves is rare. This phenomenon is occult and with the Beal 1 -Surgi tool

287
104 valve it is associated with disc variance. The clinical diagnosis of

disc variance (valve malfunction) is usually made and appropriate surgical measures taken to replace the valve. These circumstances obviously

do not permit microscopic examination of the organs and obviously, the

diagnosis of prosthetic valve embolization cannot be made. Thus, this

diagnosis can only be made in autopsy cases which have a worn valve or which have had surgical replacement of a worn valve. The exception to

the preceding discussion may be the diagnosis of wear particle embolization from Braunwald-Cutter prosthetic heart«valves and this will be

presented in the following discussion.

This case involved a 54-year-old white female with a long history

of rheumatic heart disease. At 50 years of age, she underwent an aortic

valvulotomy and mitral valve replacement with a Beall-Surgitool 104

valve. Four years following these procedures, the diagnosis of valve

malfunction was made on the basis of increasing congestive heart failure

and hemolytic anemia, and she underwent a valve replacement procedure.

Two days postoperatively she expired following pulmonary arrest. The

pertinent autopsy findings relative to this discussion were the pre- sence of numerous foreign body giant cells in the arterial walls of

blood vessels in the brain and heart.

0

*

i

• 4

* •4

I

* *

*

Figure 3. Cerebral cortex with foreign body giant cells containing

birefringent fibers (original 200X). Beall model 104

mitral valve implanted for 4 years.

Microscopic examination of routine sections of the cerebral cortex,

figure 3, the basal ganglia, figure 4, and the cerebellum, figures 5 and

6, revealed numerous foreign body giant cells. Polarized light examination showed birefringent fibers present in the cytoplasm of the multinucleated giant cells. These are consistent with fiber emboli from the worn Dacron fabric of the sewing ring. The presence of anoxic neurons adjacent to the perivascular foreign body giant cells in the basal gang288
Figure 4. Basal ganglia with foreign body giant cells containing

birefringent fibers (original 120X). Beall model 104

mitral valve implanted for 4 years.

lia (fig. 4) are suggestive of ischemia. In the cerebellum (figs. 5 and

6), neurons show eosinophilic nuclei suggestive of early microinfarction

by the cellular reaction to the fiber emboli. Older microinfarcts would

show more tissue damage with astrocytic proliferation and activated

microglia. As these features are not seen, the microinfarcts may be

early (days) or only partial, leading to the observed ischemic changes.

Fiber embolization leading to vasculitis has also been observed in

patients who have undergone intracardiac operations or cardiac catheterization. While fiber embolization is more commonly seen in small vessels, this process may involve larger vessels with associated morbidity

and mortality. Dimmick et al_. have observed this phenomenon in two

cases, one involving the death of a patient and the second requiring

amputation of an extremity. [28]. They described the presence of fibers

within a thrombus which had occluded a major pulmonary artery resulting

in pulmonary infarction. This patient subsequently died shortly after

a corrective procedure for tetralogy of Fallot. Their other case involv

ed the cannulation of the radial artery in a patient undergoing an intra

cardiac operative procedure. This patient subsequently developed gangrenous necrosis of the hand requiring amputation. Fibers were observed

in the thrombus which had occluded the radial artery leading to ischemia

of the extremity and subsequent gangrenous necrosis.

2.3. Disc occluder variance

As previously described in the introduction, disc variance usually

arises due to the use of a relatively soft material such as Teflon for

the disc. Edge wear can be autoaccelerating as the rotational motion of

the disc is inhibited. Edge wear as well as focal grooving of the disc

283
Figure 5. Cerebellum with foreign body giant cells containing

birefringent fibers (original 120X). Beall model 104

mitral valve implanted for 4 years.

Figure 6. Cerebellum with foreign body giant cells containing

birefringent fibers (original 120X). Beall model 104

mitral valve implanted for 4 years.

can also increase the wear and deterioration of the sewing ring fabric

An example of extensive variance is shown in figure 7. This BeallSurgitool mitral valve had been implanted 6.5 years previously and at

the time of reoperation, the patient had developed a severe chronic

290
Figure 7. Beall model 104 mitral valve implanted for 6.5 years.

Note marked disc variance with grooving and the exposure

of the metallic frame.

anemia. The disc/cage ratio for this valve is approximately 0.89 indicating moderately severe wear [20].

2.4. Ball occluder variance

While ball occluder variance due to wear has been noted for all

types of prosthetic valves, this phenomenon has led to disastrous re- sults with the Braunwald-Cutter aortic prosthesis [12,13]. This valve

makes use of a Dacron fabric over the struts to promote neointima formation. Unfortunately, cloth fragmentation due to the trauma of the

ball impacting on the cloth-covered struts occurs first. Fragmentation

of the cloth on the struts causes the cloth to slide down the struts

where it can disturb the normal seating of the ball. In addition, the

ball then continues to impact on the bare metal struts, increasing the wear rate on the silicone rubber ball. The loss of fabric from the

struts increases the distance from the struts and thus the potential

for ball embolization. Figure 8 shows a typical example of a BraunwaldCutter aortic valve with ball variance and cloth fragmentation from the

struts. This valve had been implanted for 6.5 years and when removed

at surgical replacement, the ball could slide easily between the struts.

Note the marked variance of the ball leading to "flat" portions on the

surface of the ball occluder. Wear particles from these valves, either

in the form of silicone rubber and/or silicon dioxide, embolize to various organs, in particular the liver, where a characteristic foreign body

granuloma results. This will be discussed in the following section.

2.5. Embolization of ball occluder wear products

At the present time, our implant retrieval and evaluation program

29 I
Figure 8. Braunwald-Cutter aortic valve implanted for 6.5 years.

Note "flat" portions over the surface of the ball

occluder.

has identified three cases in which occluder embolization has occurred

from Braunwald-Cutter aortic valves. The following case report is a brief description of one of these cases and, in general, describes the

events leading to the patients' demise and the autopsy findings in cases involving Braunwald-Cutter occluder embolization.

A 59-year-old white female had previously received a BraunwaldCutter prosthetic valve of the aortic type for severe aortic insufficiency. She was admitted for her last hospital admission following a two-week period of urinary frequency, pyuria, dysuria and hemoglobinuria

Her hematocrit had dropped five points over this two-week period and was 27. On physical examination, her blood pressure was 130/65 with a pulse of 68. There was a grade 5/6 holosystolic murmur over the entire

precordium. Workup procedures were instituted, however, two days following her admission she was found on her bed breathing but unresponsive

Ten minutes prior to this she had been observed in the halls of the ward

walking and alert. Her pulse was 50 but no measurement of the blood

pressure could be obtained. In a few seconds the pulse was lost and

cardiac resusci tative measures failed and the patient died.

At autopsy, it was readily observed that the silicone occluder ball

from her Braunwald-Cutter aortic valve prosthesis had embolized and was found lodged in the abdominal aorta at the level of the renal arteries.

The occluder ball was grossly intact and there were no fracture lines or cracks over the surface; it was smooth and without missing fragments.

The struts of the valve prosthesis were bare, exposing the metallic

struts and the dacron fabric had been partially pushed to the base of

the struts. The liver, spleen, kidneys and lungs showed acute and

chronic passive congestion and edema. Microscopic examination of the

292
liver and spleen showed occasional periportal foreign body giant cells

containing a foreign material which was not birefringent and could not

be stained with hematoxylin and eosin, PAS or tri chrome stains.

In recent years, there have been several reports describing the

erosion and subsequent embolization of ball occluders from caged-ball

cardiac valve prostheses. Associated with these findings has been the

presence of foreign body giant cells in the liver, spleen and kidneys

[29]. It has been suggested that the foreign particles within these

giant cells are fragments of the occluder ball and that the wide dissemination in several organs represents the systemic embolization of wear

particles. We have made use of KEVEX X-ray dispersion analysis to identify the particles within the foreign body giant cells as containing

silicon and thus provide the first direct identification of the material

within these foreign body giant cells.

In the three cases, the metallic struts of the cage were exposed to

varying degrees and the occluder balls were absent from the cages. In the two complete autospy cases, the occluder balls were found in the abdominal aorta. In both cases, they were spherical and could easily

slide between the struts of the valve cage. No grooving, cracking or other macroscopic signs of variance in the occluder balls were seen. Histologic examination of the liver, spleen and kidneys in these two cases revealed the characteristic perivascular foreign body granulomas;

and within the liver foreign body giant cells were present in the periportal areas with variable degrees of inflammation and fibrosis (figures

9 and 10). The foreign material within these foreign body giant cells

consisted of refractile irregular clumps which were not birefringent and

could not be stained with hematoxylin and eosin, PAS or trichrome stains.

' i i Jv \ - ; :

3 o 0 -a •

0 o \ f - \

• G . V Q © . - O

o

r* ad

>*1 O

s (1 «» * •*

_ k» TV! Figure 9. Periportal foreign body giant cells in the liver; BraunwaldCutter aortic valve implanted for 3 years (original 200X).

293
0

4^

5 • %

^ V • . \* -

f >

I

'"lit *

Figure 10. Periportal foreign body giant cells in the liver;

Braunwal d-Cutter aortic valve implanted for 3 years

(original 320X):

Infrared spectral analysis and atomic absorption spectrophotometry

have been previously used to identify silicon-containing materials in

tissues. Unfortunately, neither of these techniques allows a direct

appreciation of the cellular-material interaction. For this reason,

we turned to the use of KEVEX X-ray dispersion analysis coupled with

scanning transmission electron microscopy using a JEOL 100-B instrument

with 100 kV accelerating voltage. Appropriate stained and unstained

50 nm thin sections were prepared in our electron microscopy laboratory

and mounted on copper grids. Simultaneous characterization using scanning transmission electron microscopy and KEVEX X-ray dispersion analysis

was carried out. Figure 11 shows the general type of inclusion (white

arrow) which was analyzed and Figure 12 is a photograph of the KEVEX

video display showing the presence of the Ka and Kg peaks of silicon.

3. Conclusion

With the increasing effort directed toward the development of non- thrombogenic materials for cardiovascular applications and the continued

improvement in surgical techniques, it is anticipated that the long term

durability of materials used in valve prostheses will play an increasing

role in determining the life-time of the respective valve prostheses.

If the modes and mechanisms of valve failure due to durability problems are to be recognized, evaluated and used as a basis for future design

of valve prostheses, it is important that retrieval and evaluation programs be developed in which the participating individuals not only have

a knowledge of the clinical aspects of valve prostheses, but also a knowledge of the physiological and biomaterials aspects of valve

prostheses.

294
Figure 11. Scanning transmission electron micrograph of a typical

inclusion in the foreign body giant cells in the liver.

Braunwald-Cutter aortic valve implanted for 3 years.

In closing, we would like to make one further statement regarding

the retrieval and evaluation of valve prostheses. While the BraunwaldCutter aortic prosthesis is no longer in clinical use today, having

been removed from the market in 1974; there are patients who still have

this prosthesis and are at risk for the problems presented in the preceding discussion. The problem of long-term durability cannot neces- sarily be judged from animal studies and accelerated in vitro tests.

Therefore, implant retrieval and evaluation programs are necessary if we are to appropriately determine the clinical efficacy of prostheses,

implants and other devices.

The authors wish to thank the various agencies (NIH, NIAMD, NHLBI,

NBS, FDA and VA) and the ASTM for their sponsorship. The authors also

extend their appreciation to Drs. J. Ankeney, R. Nash, B. Schumann and

C. Colenda for their assistance.

295
438-8 - MK K 2*14 SI

2X18*2$ 8.48 KEU 288 SEC

MS" 2K 1A+B M HS- 28EM IAB

Figure 12. KEVEX video display with Ka and KB peaks of silicon from

the inclusion pictured in figure 11.

References

[1] Lefrak, E.A. and Starr, A., Cardiac Valve Prostheses , AppletonCentury-Crofts, New York, N.Y., 1979.

[2] Brewer, L.A., editor, Prosthetic Heart Valves , Charles C. Thomas,

Inc., Springfield, Illinois, 1969.

[3] Hylen, J.C., Mechanical malfunction and thrombosis of prosthetic

heart valves, Amer. J. Cardiol., 30, 396-404 (1972).

[4] Krosnick, A., Death due to migration of the ball from an aorticvalve prosthesis, JAMA, 191_, 1083-1084 (1965).

[5] Ablaza, S.6.G. e_t al_. , Fatal extrusion of the ball from a StarrEdwards aortic valve prosthesis: report of a case, J. Thorac,

Cardiovasc. Surg., 50, 409-409 (1965).

[6] Roberts, W.C. and Morrow, A.G., Fatal degeneration of the silicon

rubber ball of the Starr-Edwards prosthetic aortic valve,

Amer. J. Cardiol., 22, 614-620 (1968).

296
Hameed, K. , Ashfaq, S., and Waugh, D.O.W., Ball fracture and extrusion in Starr-Edwards aortic valve prosthesis with dissemination of ball material, Arch. Path., 86, 520-524 (1968).

Fiegenberg, D.S., DeColli, J. A., and Lisan, P.R., Fracture of a Starr-Edwards aortic ball valve with systemic embolism of ball

fragments, Amer. J. Cardiol., 23, 458-563 (1969).

Joyce, L.D., Emery, R.W., and Nicoloff, D.M., Ball variance and

fracture of mitral valve prosthesis causing recurrent thromboemboli, J. Thorac. Cardiovasc. Surg., 75, 309-312 (1978).

Starr, A., in Cardiac Valve Prostheses , p. 387, Appleton-CenturyCrofts, New York, N.Y. , 1979.

Pluth, J.R. and Danielson, G.K., Poppet embolization in clothcovered Silastic poppet valves, Mayo Clin. Proc, 49, 811-

814 (1974).

Pluth, J.R., Broadbent, J.C., and Danielson, G.K., Aortic and

mitral valve replacement with the cloth-covered BraunwaldCutter valve, Mayo Clin. Proc, 48, 722-727 (1973).

Blackstone, E.H. et al_. , The performance of the Braunwald-Cutter

aortic prosthetic valve, Ann. Thorac. Surg., 2_3, 302-318

(1977).

Robinson, M.J., Hildner, F.J., and Greenberg, J.J., Disc variance

of Beall mitral valve, Ann. Thorac. Surg., 1J_, 11-17 (1971).

Sandza, J.G. et al_. , Replacement of prosthetic heart valves, J. Thorac. Cardiovasc. Surg., 74, 864-873 (1977).

Jost, R.G., McKnight, R.C., and Roper, C.L., Failure of Beall

mitral valve prosthesis, J. Thorac. Cardiovasc. Surg., 7£,

163-165 (1975).

Montoya, A., Sullivan, H.J., and Pifarre, R., Disc variance: a potentially lethal complication of the Beall mitral valve

prosthesis, J. Thorac. Cardiovasc. Surg., 71_, 904-906 (1976).

Elliott, R.A., Bjork-Shiley prosthesis recall, Circulation, S3,

206 (1976).

Paton, B.C., Vogel , J.H.K., Ovary, H. , and Blount, S.G., Follow-up

results on the Kay-Shiley valve, in Brewer, L.A., editor,

Prosthetic Heart Valves , C.C. Thomas, Springfield, Illinois,

1969, pp. 598-608.

Clark, R.E. et al_. , Quantification of wear, hemolysis and coagulation deficits in patients with Beall mitral valves, Circulation,

56, Supp. 2 [3], 139-143 (1977).

237
[21] Paton, B.C. and Pine, M.D., Aortic valve replacement with the

DeBakey valve, J. Thorac. Cardiovasc. Surg., 72, 652-656 (1976).

[22] Scott, S.M. et al_. , Insidious strut fractures in a DeBakeySurgitool aortic valve prosthesis, Ann. Thorac, Surg., 25_,

382-384 (1978).

[23] Ansbro, J., Clark, R., and Gerbode, F. , Successful surgical correction of an embolized prosthetic valve poppet, J. Thorac. Cardiovasc. Surg., 72, 130-132 (1976).

[24] Silver, M.D., Datta, B.N., and Bowes, V.F., A key to identify

heart valve prostheses, Arch. Path., 99, 132-138 (1975).

[25] Chun, P.K.C. and Nelson, W.P., Common cardiac prosthetic valves:

radiologic identification and associated complications, JAMA,

238 , 401-403 (1977).

[26] Morse, D. and Steiner, R.M., The Pacemaker and Valve Identification

Guide , Medical Examination Publishing Co., Inc., Garden City,

N.Y., 1978.

[27] Hodam, R. , Anderson, R., and Starr, A. et al_. , Further evaluation

of the composite-seat cloth-covered aortic prosthesis, Ann.

Thorac. Surg., 12!, 621-635 (1971 ).

[28] Dimmick, J.E. e_t al_. , Fiber embolization - a hazard of cardiac

surgery and catheterization, New Engl. J. Med., 292 , 685-687

(1975).

[29] Ridolfi, R.L. and Hutchins, G.M., Detection of ball variance in

prosthetic heart valves by liver biopsy, Johns Hopkins Med. J.,

134, 131-140 (1974).

238
METAL ALLERGY AND METALLURGY

Stanley A. Brown* D. Eng. , and Katharine Merritt* Ph.D.

University of California

Davis, CA 95616

Metal allergy reactions result from sensitization

of T-lymphocytes to metal ion-protein complexes. In the case of reactions to implants it is presumed that the

metal ions as corrosion products complex with local

tissue proteins. An in vitro test for metal sensitivity

is described in which lymphocytes are challenged with

metal chlorides in the presence of plasma proteins. The

test can differentiate between patients with no sensitivity to nickel, cobalt, or chromium, sensitivity to one or more of the metals, and patients with allergic

reactions to implants. The test results performed on 164 patients at the time of implant removal show that

37% of the patients in this group were reacting to their

implants. The results of implant analysis and the blood

test results are presented for cobalt-chrome hip hemiarthroplasties, stainless steel plates, and stainless

steel nail -plates. Specific cases are presented in

which metal lographic and SEM analysis of the implants

are used to demonstrate correlations between implant

degradation and the immune response.

1. Introduction

When an implant made of surgical grade stainless steel or cobalt-chromium alloy is placed in tissue, the implant surface will

quickly passivate due to the self passivating nature of these alloys.

However, as has been shown by Laing et al . [I] 1

, there will be a release of some alloy constituents into the surrounding tissues, even when the passive metal is in an unstressed condition as with a cylinder in the muscle of an animal. In more challenging situations,

such as orthopaedic implants, the release of metal ions into the

tissue is accelerated due to mechanisms of fretting and crevice corrosion. As has been published previously by others, and is presented

in other papers in this volume, the tissue levels of implant con- stituents can reach disturbingly high levels.

figures in brackets indicate the literature references at the end of

this paper.

*Current address: Orthopaedic Research Laboratory, TBI 39,

University of California Davis, Davis, CA 95616

299
In reviewing the literature, one finds occasional references to

adverse tissue reactions to metallic implants, which are attributed

to metal sensitivity to corrosion products. Barranco and Soloman [2]

reported a case of an eczematous dermatitis reaction to a stainless

steel screw in a patient with sensitivity to nickel, McKenzie et al

.

[3] reported a case of urticaria after insertion of a cobalt-chromium

Smith-Peterson nail. While there have been other reports concerning

fracture fixation devices, the most convincing literature has been in

the area of tissue reactions to metal -metal total joint prostheses,

which have shown a positive correlation between pain and prosthesis

loosening and metal sensitivity [4, 5, 6]. For more complete discussions of the literature, the reader is referred to recent publications by the authors [7, 8]. The objectives of this report are to

discuss the effects of metal ions on the human immune system, and to

look at the relationships between implant degradation and the development of immune reactions in the form of metal sensitivity.

2. Immunology and Metal Sensitivity

In the ionic state, metallic implant corrosion products,

although foreign to the body's immune system, are too small to be

recognized by the immune system. However, when complexed with protein carriers, the metals can stimulate an immune response. Thus,

metal ions are haptens which, when complexed with protein carriers,

are immunogenic. From an orthopaedic implant viewpoint, the haptens

of importance are nickel, cobalt, and chromium.

There are two branches of the immune system which must be discussed if one is to understand the possible immune reactions to

metallic implants [9]. Both branches stem from lymphocytes which are made in bone marrow and differentiate in other organs. Lymphocytes

are the memory cells of the immune system, in that they carry binding

sites on their cell membranes which allow the cells to recognize that

"which is not self." The B-lymphocyte will, when stimulated, undergo

blastogenesis and produce plasma cells. These plasma cells will produce and release antibody against the specific antigen that stimulated the B-lymphocyte. The T-lymphocyte , when stimulated, will

undergo blastogenesis to produce more T-lymphocytes , all of which

will release a number of soluble substances known as lymphokines.

There are also B-cell T-cell interactions which are beyond the scope

of this presentation. Concerning allergic or hypersensitivity reac- tions, it is the B-cell reaction that causes allergy to dust and

pollen. The T-cell is responsible for what is known as delayed or

eel 1 -medi ated immunity, and it is the T-cell reaction that is of

primary importance in a discussion of metal sensitivity reactions.

T-lymphocytes are capable of becoming sensitized to metal -protein complexes. The sensitivity can be acquired by repeated exposure to metals or metal salts on the skin, by metal salts injected in

muscle, and presumably by repeated exposure to corrosion products.

Once sensitized, the T-cells will react whenever they are challenged

300
by (exposed to) the metal ion-protein complex to which they are sensitive. The reaction in vitro results in the production of a number

of substances known as lymphokines , which can be used for sensitivity

testing, and which are responsible for the symptoms associated with

in vivo hypersensitivity reactions.

The classic test for metal sensitivity is the skin test [10].

The method involves placing a salt of the metal in question on the

patient's skin and observing the skin reaction 24 and 48 hours later.

If the patient's T-cells are sensitive, they will react to the com- plexes formed between the metal ions and the skin proteins. There

are a number of concerns about using skin testing for metal sensitivity in orthopaedic patients. First the reaction is only to skin

protein complexes which may be antigenical ly different from deep

tissue-metal ion complexes. Second, the method only tests for T-cell

mediated reactions and does not determine if there is any B-cell

dependent sensitivity. But perhaps most importantly, the method of

skin testing is the same as the method of sensitivity induction. A

patient (or animal) can be made sensitive by repeated skin testing

[11]. Thus we feel that skin testing may not be sensitive nor safe

enough to be used routinely in implant sensitivity studies. There

are, however, in vitro tests for metal sensitivity.

When T-lymphocytes from a patient's blood sample are challenged

with metal-protein complexes in vitro , they will respond by releasing

lymphokines. The two that are most commonly used for in vitro

testing of cell -mediated immunity are blastogenic factor and migration inhibition factor. The assay for blastogenic factor involves

the use of radioactive labels and takes five to seven days. The

assays for migration inhibition are faster, easier, and less expensive. While doing both in our laboratory studies, we have selected

and modified the migration inhibition test [12] for our clinical

study of implants and metal allergy [7, 8, 13].

When incubated in agarose in vitro , leukocytes such as polymorphonuclear leukocytes and macrophages will migrate in an ameboid

fashion. This migration is inhibited by migration inhibition factor

released by T-lymphocytes. There are probably two factors, one which

inhibits macrophages ( MI F) and one which inhibits the monocytes and

polymorphonuclear leukocytes in peripheral blood (LIF). For the purposes of this paper we will simply refer to LIF. It is important in

these in vitro studies to test for normal T-cell function as a control. We use phytohemaggl utinin (PHA) to test for normal T-cell

function. Normal T-cells should produce LIF when stimulated with PHA,

and the response to the metal salts in question can be compared. To

provide a source of protein for metal salt complexing, we incubate

the metal salts with plasma and then the cells. As a normal migration control, we incubate the cells in plasma alone. Thus, there are three test conditions: serum for migration control, PHA for T-cell

function, no migration control, and incubation with the metal salt(s)

in question.

3 0 I
We have found in the clinical and animal studies that there are three results from the test [7, 13, 14]. A patient with no sensitivity will show normal cell migration with serum, no migration with

PHA, and normal migration in the presence of the metal salts. A patient with metal sensitivity will show normal migration in serum, no migration with PHA, and no migration in the presence of the specific

metal salt to which the T-cells are sensitive. The third condition

is that of no cell migration in any of the test conditions. Patients

in this third condition are referred to as "nonmi grators .

The condition of no cell migration has only been observed with

blood samples taken from patients bearing metallic implants. In all cases where blood samples have been obtained after implant removal,

the test has shown normal cell migration in serum and a specific sen- sitivity to one or more of the metals tested (nickel, cobalt, and

chromium). We interpret this no migration condition to mean that the

T-cells have been stimulated in vivo by metal ion corrosion products

released by the implant. In animal studies, we have shown this con- dition to be associated with very severe tissue reactions at metal

implant sites [14]. Thus, we consider the condition of no migration

to be diagnostic for the presence of allergic reaction.

The problem of diagnosis of a metal sensitivity reaction to an implant is probably one of the most critical clinical issues. If the

reaction results in a skin rash, then sensitivity is suspected. However, if the symptoms are pain, swelling, or loosening of the implant,

there are many more probable causes, with infection being the most

probable. In cases of contact dermatitis reactions to watches or jewelry, the diagnosis is comparatively easy: there is a rash under

the metal item; one cannot see rashes around implants. Thus, we con- sider the diagnostic nature of the condition of no migration to be

important and have been studying these patients in some detail. While

the immunological details of the nonmigrators are not the subject of

this presentation, it is worthwhile discussing them briefly.

The observation of the existence of the condition of nonmigration in some of our patients with metallic implants raised a number

of fundamental questions. Theoretically the situation where there

was no migration in the cell control would indicate an invalid test.

However, this nonmigration occurred only in patients who were cur- rently bearing metallic implants. In addition, tests set up at the same time or using the same reagents showed excellent migration in

the control wells. Furthermore, within a few weeks of removal of

the implant, the nonmigrators returned to the situation of good

migration in the control well. Thus, the error did not seem to be

with the test method. The question then focused on what was wrong

with the patient cells. Cell viability studies were done using the

method of exclusion of trypan blue according to the protocol described by 6IBC0 (Grand Island, NY) with their reagent. Cell

viability was similar with migrators and nonmigrators with viability

of 90% or greater.

302
The next question was what was the capacity for lymphocyte

function. In order to assay for this, we chose to test for the production of blastogenic factor using PHA (Difco) as the stimulating

lectin. The data on the human patients and on rabbits indicated that

the lymphocytes of the nonmigrators were fully capable of responding

to PHA. The data is insufficient at this time and thus has not been

analyzed to determine if there is a small but definite difference in

the degree of division in the unstimulated control cultures between

migrators and nonmigrators or during the progression to the situation

of nonmigration. However, the conclusion can be drawn that the

lymphocytes do respond to PHA.

The next question was what about the function of the ameboid

polys and monocytes which are the nonmigrators in this situation. It

is evident that these cells are incapable of responding to chemotactic factor: either to C5a generated by zymosan and serum or to n- formyl peptides from bacteria. We are currently evaluating the

binding and cleaving of the peptide which seems impaired and phagocytosis and killing of bacteria which do not seem impaired in the

nonmigrator cells [15]. Thus, at the moment we feel that the defect

resides on the ameboid leukocytes. It is possible that the lymphocyte has produced a factor which is bound to and inhibiting these

cells. Attempts to cleave it off with trypsin and neuraminidase have

been unsuccessful to date.

Another question would be whether or not there is a factor in

the serum of nonmigrators which would inhibit migration. Serum from

nonmigrators was concentrated 5x, diluted in increments to 1/100, and

was used undiluted. There was no evident inhibition of migration of

normal cells.

Similarly, the buffy coat leukocytes from nonmigrators were mixed at the starting concentration for the test and at dilutions of

1/2, 1/5, and 1/10 with normal migrating cells. There was no inhibition of normal migration.

Thus, at this time we have not found a factor that is soluble

or a factor on cells that inhibits other cells. We also have not

been successful in turning nonmigrating cells into migrating cells

in vitro . This conversion requires the removal of the metallic implant from the patient or animal i_n vivo and then a recovery period

of a few weeks for normal migration to be evident in the in vitro

test.

The effect of the situation of nonmigration on various immune

functions and nonspecific defense mechanisms remains an important

aspect of this study and is under active investigation.

On the other side of the tissue-implant interaction leading to

metal sensitivity and sensitivity reactions is the role of the implant

and mechanisms of implant degradation leading to release of sensitizing ion haptens. To this end we are examining all implants

303
retrieved from patients whose blood has been tested for LIF. The objectives are to determine if there is any correlation between the

immune response and the macro- and microscopic appearance of the

implants; i.e., is there anything about the implant that suggests

accelerated rates of corrosion that would result in elevated levels

of alloy constituents in the tissues?

3. Methods

The patients presented in this study were all admitted to the

Orthopaedic Service at Mary Hitchcock Memorial Hospital for surgical

removal of a metallic appliance. The reasons for removal were primarily pain, implant revision, or routine removal after fracture

healing. The blood samples and implants were contributed with informed consent. Pertinent clinical information was gathered using

ASTM F-561 [16].

3.1. LIF test

To perform the LIF test, 10 cc of venous blood was withdrawn

into a heparinized vacutainer and allowed to settle. After the red

cells had settled, the white cell buffy coat on the top of the tube was removed and the cells washed, centrifuged, and resuspended in 100

yl of saline. The lymphocytes in the buffy coat were then subjected

to five test conditions by pipetting 20 yl of the resuspended cells

into each of five test tubes which contained 10 yl of the patient's

plasma and 10 yl of the test solution. The test solutions were

saline for normal cell migration control, PHA for T-cell function

control, 0.2% NiCl 2 for nickel sensitivity testing, 0.2% CoCl 2 for

cobalt sensitivity, and 0.2% CrCl 3 for chromium sensitivity. The

tubes were then incubated at 37°C for thirty minutes to allow the

metal ions to complex with the serum proteins and challenge the

lymphocytes

.

The migration of leukocytes was determined using 60 x 15 mm

petri dishes containing 5 ml of a mixture of agarose and Click's

growth medium [17]. Two sets of five 3 mm diameter holes were

punched out of the medium, and 10 yl of the test solutions placed in

duplicate in the wells. The plates were then incubated overnight at

37°C in 5% C02 (in a candle jar). The cells were then fixed with

methanol, the agarose dried and stained with methylene blue or Giemsa,

and examined for migration with a microscope. The distance the cells

had migrated from the edge of the well was determined for each of the

five test conditions. If the cell migration in the presence of a metal salt was less than 50% of the cell control, then the patient

was said to be sensitive to that metal. There should be no migration

with PHA.

3 04
3.2. Implant analysis

The method of implant analysis depended to some extent on the

type of implant and the alloy used for manufacture. In all cases

the implants were first examined with a dissecting microscope for

evidence of surface damage in the form of wear, burnishing, or cor- rosion as per ASTM F-561 [16]. Interactions between screw heads and

plates were described using the forms and contact area code described

in this volume in the paper by Simpson et al . [18]. Implants were

then sectioned with a carbide cutoff wheel with water cooling and the

sections embedded for metal lographic examination using standard techniques. After sanding to 600 grit, and polishing to 0.05 y alumina,

samples were examined for evidence of gas porosity. They were then

electro-etched to reveal inclusions and microstructure and described

using ASTM E-45 and ASTM E-112 [19, 20]. Stainless steel was etched

for 20 seconds in 50% HN0 3 at 1.5 volts; cobalt alloy was etched for

2 seconds in 2% HC1 at 3.5 volts. Rockwell hardness of cobalt alloy

implants was determined using ASTM E-18 [21] and converted according

to ASTM E-140 [22].

4. Results

The results of LIF testing of 164 patients at the time of implant removal are shown in table 1. The data are subdivided according to implant type and implant material. In the first column, the

total number of patients with a given implant type is shown; the numbers in the "#" columns are the number of patients with implants of

the particular alloy. The results of the LIF test are listed as "GOOD" meaning good cell migration with no metal sensitivity, "SENS"

meaning sensitivity to one or more metals, and "N0M" meaning no migration in any of the test conditions.

NUMBER FOR EACH

TYPE OF DEVICE

COBALT -CHROME STAINLESS STEEL

# GOOD SENS NOM # GOOD SENS NOM

45 SCREWS 29 10 5 14 16 4 5 7 20 HEMI-HIPS 19 7 2 10 1 1 17 PLATES 4 2 2 13 8 1 4 24 NAIL PLATES 11 2 4 5 17 7 2 4 20 I ,M. RODS 3 3 17 4 9 4

9 STAPLES 7 2 2 3 2 2 29 PINS; WIRE 29 8 13 8 164 TOTAL 73 21 18 34 91 34 30 27

29% 24% 47% 37% 33% 30%

Table 1 . Breakdown

of patients according to LIF test

results, implant

type, and implant

alloy.

305
The patients in this group include those whose implants were

removed as part of routine postoperative care, as in tibular-fibular

screws and fracture plates, as well as those who presented with symptoms such as pain or skin rash, and thus removal was not routine in

the strict sense of the word. The time of implantation ranged from 6

weeks to 16 years. Thus, it is difficult to draw many specific

conclusions from this table.

Taking the 164 patients as a group, we find 55 (34%) with no sensitivity, 48 (29%) with a sensitivity, and 61 (37%) nonmigrators

.

In comparison, blood tests performed on 159 patients at the time of

implantation (some of whom had previously had implants) revealed 72%

with no sensitivity and 28% with sensitivity to one or more metals,

with sensitivity to nickel (19%) being the most common.

In looking at table 1, one must be careful about drawing any con- clusions about the differences between the two alloys, because of the

wide range of implant type and duration. One group within the table

that is relatively comparable is the bone screw group. These 45

patients had single or multiple screws which were removed routinely

or because of pain. The incidence of allergic reactions as evidenced

by no cell migration was 48% for cobalt-chrome, 43% for steel, and

47% overall. It is doubtful if this difference is statistically significant. As for differences in symptoms, there were several patients

with cobalt screws presenting with skin reactions, while no patients

with steel screws had obvious reactions. Complaints of pain were

reported with both materials. At the time of this writing, there can

be no statements concerning differences between the alloys used for screws. Unfortunately, our metallurgical analysis has not revealed

any correlation either.

Because of the variation of implants, we do not feel detailed

further analysis of table 1 is appropriate. However, detailed

analyses of implants are appropriate, and there are some findings of

interest in the analyses of specific implant groups. To look at cor- relations between implants and the immune response, we will discuss

three implant groups: cast cobalt-chromium hemi hip arthroplasties,

stainless steel fracture plates, and stainless steel nail-plates.

4.1. Hemi hip arthroplasties

Table 1 lists 19 patients with cobalt-chrome hemi hip arthroplasties. Of these, 14 were of the Moore or Thompson variety and were available for metal 1 urgical analysis. Being large, weightbearing devices with significant surface areas with direct bone-metal

contact, it is not surprising that this class of implant had the

highest incidence of allergic reactions (53% when another nonmigrator

whose implant was lost is included). Because of the bone-metal con- tact in the stem and collar area, both microstructure and hardness were considered important material properties for corrosion and wear

resistance. Similarly, the stems were examined for evidence of wear

306
and burnishing. The results of implant analysis, LIF testing, and

the pertinent clinical findings are listed in table 2.

HEMI HIPS

M YRS RHA VOID G . B

BURN LIF CLINICAL

1 1 0/ U

n r U~L u GOOD PAIN, INF 2 1.8 66 0 o-c 2 GOOD PAIN, INF, MIG

3 3 66 0 0 4 GOOD PAIN

4 5 63 2 o-c 6 GOOD LATE INF

5 5 67 0 o-c 6 GOOD PAIN

6 0.7 62* >3 I 1 SENS PAIN

7 3.7 60* >3 c 2 SENS INF, PMMA

8 0.5 60* 2.5 c 1 NOM PAIN, MIG!

9 3 59* »3 I 2 NOM PAIN

10 4 65 0 0 6 NOM PAIN, MIG!

11 4.7 62* 1.5 I 6 NOM PAIN, MIG 1., ASTHMA

12 5 60* 2.5 c 5 NOM PAIN, LOOSE

13 11 66 0 0 7 NOM PAIN, MIG

in 16 65 0 o-c 5 NOM PAIN, ASTHMA

Table 2. Patients

with hemi hip, Moore

or Thompson implant

prostheses

G.B. = grain

boundaries

0 = indistinct

C = clean

1 = precipitates or

incl usions

RHA = Rockwell hardness A

*means below ASTM

F-75 specifications

In looking at the clinical symptoms listed, one sees that

virtually all the patients complained of pain, whereas roentgenographs evidence of implant migration in the absence of infection was only seen in the no cell migration group. Three patients had severe

implant migration as indicated by the exclamation mark "!". The two

patients with asthma are discussed subsequently.

The implants were examined grossly for signs of wear and burnishing of the collar and stems, and graded on an arbitrary scale.

Table 2 would suggest that burnishing had a stronger correlation with

time than with the immune response. Sections were cut from the stem

portion of the implants and hardness determined using the Rockwell A

scale. ASTM F-75 Standard Specification for Cast Cobalt-ChromiumMolybdenum Alloy for Surgical Implant Applications [23] specifies

that the hardness shall be Rockwell C 25 to 34, which when converted

by ASTM E-140 [22] gives a Rockwell A range of 63 to 67. Those implants which were below specifications for hardness are indicated

with an asterisk "*". It can be seen in the table that the hardness

of the implants in the good migrator group were all within specifications, that the implants in the patients with sensitivity were below

specifications, and four of the five implants from patients with no

cell migration and implantation times of five or fewer years were

below specifications. The two long-term (11 and 16 year) implantation times were implants within specifications. From this we can begin to draw a conclusion that hardness correlates with the LIF

test.

Sections were also cut from the stems and embedded for metal lographic examination of void content and grain boundary prominence.

ASTM chart E-45 was used to attach a number to the void content. It

307
can be seen that void content has the same correlation as hardness,

which is not surprising. Grain boundaries "G.B." were rated as being

indistinct "0", distinct but clean "C", or containing precipitates of

non-metallic inclusions or eutectoid blocky carbides "I". Here we

see a weak correlation between grain boundary structure and LIF

results. The significance of grain boundaries and the objectives of

the investigation are seen in the following comparison [13].

(a) (b)

Figure 1 Roentgenographs of patient #11 in table 2 at the time of

implantation (a) and 4 years later (b), demonstrating

migration of the prosthesis down the femoral canal and

into the acetabulum.

The roentgenographs in figure 1 demonstrate a significant amount

of migration of the Thompson prosthesis both down the femoral canal

and into the acetabulum during the four years between films. After

about two years implantation, the patient began to complain of pain

and symptoms of respiratory asthma. Patient #14 in table 2 also

developed symptoms of pain and asthma, but in this case the symptoms

developed 14 years after implantation of the Moore prosthesis. In this second case, there was no roentgenographs evidence of migration

or loosening. Thus, the question is posed: why was the time course

so different in these two cases?

308
(a) (b)

Figure 2 Comparative metal lographic sections of hemi hip patients

#11 (a) and #14 (b), with outer surface of implants on left sides of the figures. Original magnification xlOO.

The transverse metal lographic sections of figure 2 were taken to

reveal the microstructure and grain boundary pattern of the stems of

the prostheses of these two patients. The section in figure 2a

reveals a significant amount of grain boundary inclusions and voids

due to gas porosity. In contrast, the grain boundary in figure 2b is

free of precipitates, and the microstructure is that of interdendritic carbides. The differences in these identically etched sections suggested that there might be a difference in the response of

the actual prosthesis stem surfaces in the corrosive in vivo

environments.

The scanning electron microscope photographs in figure 3 are of

the actual outer surfaces of the stems of patient #11 (a) and patient

#14 (b). Both pictures were taken at the same magnification. Figure

3a reveals a severely pitted surface with some deep cracks or slots

which are suggestive of corrosive attack of intersecting grain

boundaries. Figure 3b reveals a rough surface typical of a cast

implant, with slight evidence of corrosive attack. It must be

remembered that the corrosion attack seen in figure 3a was after 4.7

years in vivo , while that in figure 3b was after 16 years in vivo .

309
(b) hemi hip patient

#14

original magnification x680

The hypothesis is that the grain boundary sensitization of the first

case resulted in more rapid implant attack and tissue exposure to

alloy constituents, and thus the development of a metal sensitivity

reaction in two years, whereas the cleaner metal of the second case resulted in greater implant stability in vivo .

Another interesting finding in these two cases is that both

patients complained of asthma, with onset of symptoms coincident with

the onset of pain. After implant removal and replacement with

cemented THR prostheses, both patients were relieved of their asthma,

and LIF tests in both cases showed normal cell migration with sen- sitivity to cobalt and chromium in the first case, and to cobalt,

nickel, and chromium in the second case.

3 I 0
4.2. Steel plates for fracture fixation

Thirteen patients tested for LIF production were admitted for

removal of stainless steel fracture fixation plates. The plates from

these patients were analyzed using the contact area code and plate

analysis form described by Simpson et al . in another paper in this

volume [18]. The results of the analysis and review of pertinent

clinical findings are summarized in table 3. It will be noted that

most of the plates were 4- or 5-hole plates used for forearm

fractures.

STEEL PLATES

SCREW PLATE CORR.

# YRS PLATE AVERAGE TOTAL LIF CLINICAL

1 0.6 4h 0/0 0/0 GOOD ROUTINE

2 0.6 8h 0/0 1/1 GOOD PAIN (SHOULDER)

3 1 5h l/l 2/2 GOOD ROUTINE

4 1.2 5h, 4h 1.7/1, 1.7/1.7 7/4, 7/7 GOOD ROUTINE

5 1.2 4h 1/1 2/5 GOOD ROUTINE 6 2.7 4h, 4h 1/0, 1/0 4/1, 4/1 GOOD PAIN

7 3 5h 1/1.3 7/8 GOOD INF

8 6 4h 1.7/2 7/8 GOOD PAIN

9 0.7 10h 3.7/3.1 34/31 SENS PLATE FX 10 0.5 7h 1/1 10/9 NOM RASH, SCREW LOOSE 11 1.2 4h 0 2/0 NOM PAIN 12 1.5 4h 3/2 11/8 NOM ROUTINE

13 2 4h 3.2/3 13/12 NOM ROUTINE, MILD PAIN

Table 3. Summary of

implant analysis and

clinical findings of

patients with stainless steel plates.

Corrosion ratings

are given as "plate/

screw.

In looking at table 3, one can see that the average ratings for

corrosion of the plates and screws from the patients with no metal

sensitivity were all very low. In contrast the sensitive patient and

two of the nonmigrators had average corrosion values higher than the

first group. The table also shows that the total corrosion is higher

in the sensitive and nonmigrator groups than in the first. While the

numbers in this study are too low to draw definitive conclusions,

there is a suggestion of correlation between corrosion and the

development of metal sensitivity.

One of the patients, #10, who at first glance appears to be a glitch in the data, is in fact a very interesting case, and points to

the question of what is more important, total corrosion or local

corrosion. This patient had a 7-hole plate on the tibia, which was removed at 6 months, primarily because the proximal most screw came

loose. The average corrosion was 1/1, which is very low, yet the

total was 10/9. Two of the distal plate/screw contact areas showed

significant attack, especially in position d2. Position d2 showed

three 2/1/6 (medium size/minimal depth/corrosion) contact areas on the plate, similar contact areas on the screw head, and a rainbow

pattern indicative of corrosion products on the upper plate surface.

The patient also presented with an itchy rash on his shin over this screw position. The plate and screw d2 from this patient were

examined with the scanning electron microscope and examined

metal lographical ly.

3 I I
Figure 4

SEM photograph of

contact area on plate

position d2 from

patient #10 in plate

study. Contact area

is in upper right,

with edge running

diagonally. Pitting

is outside of primary

contact area.

original magnification x500

Figure 4 is a SEM photograph of the contact area on the plate in

position d2. The plate contact shows a parallel line pattern in the

upper right portion of the figure, while significant pitting is seen outside of the primary contacting area in the lower left of the

figure. The parallel line pattern in this round hole plate contact

area is suggestive of the cold rolling cold work pattern of this

class of metal. This and other SEM pictures of this plate hole and

position d4 showed significant corrosive attack.

At low power the corresponding contact area of the screw d2

showed a superficial attack with a crack-like structure in the middle

The SEM photograph of figure 5a shows that the crack was a result of

corrosive attack, possibly by crevice corrosion. Surrounding the

crack was a region with superficial pitting. Elsewhere in the middle

of the contact area, a structure similar to that seen in metallographic etching of a cold worked steel was seen, as shown in figure

5b. Near the edge of this screw contact area, figure 5c, the metal

showed crystallographic pitting suggestive of low pH corrosive attack

The significant amount of corrosive attack and hence metal re- moval from the contact area in position d2 correlated with the

allergic skin reaction seen over this screw, and is consistent with

the nonmigration status of this patient in the LIF test. However,

this seems like a significant amount of corrosion for only 5 months

in vivo . Thus, the question of metal quality was raised.

Longitudinal and transverse metal lographic sections of the plate

and screw d2 are shown in figure 6. The four sections were etched

and photographed under identical conditions. So as not to over-etch

the transverse section of the screw, the other sections are somewhat

under-etched. Both plate and screw show a comparatively clean, finegrained structure, with elongated grains in the longitudinal sections

3 I 2
Figure 5 SEM examination of screw

d2 from plate patient #10.

(a) crack and corrosion

near center of contact

area

original magnification

x!200

(b) corrosion revealing

cold work microstructure from middle of

contact area

original magnification

x600

(c) crystallographic cor- rosion pitting near

edge of contact area

original magnification

xl200

3 1 3
(a) Plate (b)

Figure 6

Metal lographic sections of plate (a, b) and screw d2 (c,

d) from patient #10 in the plate study. Figures on the

left (a, c) are longitudinal sections; figures on the

right (b, d) are transverse sections. Original magnifications x320.

3 I 4
The longitudinal sections, especially that of the screw, show a stringy sort of cold working pattern related to cold working during

rolling. It is hypothesized that this cold forming structure cor- responds to the parallel line pattern seen in the plate contact area of figure 4. Aside from these observations, the metal lographic

examination did not reveal anything unusual about the metal used for

manufacture of this plate and screw.

4.3. Stainless steel nail plates

Thirteen patients in the LIF and implant removal study were admitted for removal of nail plates or angle blade plates. The implants were analyzed using the same contact area code [18] and a variation of the analysis form as depicted in figure 7. The plate

holes were numbered as though all were distal, and the contact area

code was used to describe the plate/screw interaction and the interaction between the various components of the nails, bolts, and

sleeves

Hospital Series Name Plate

Birth Date Screws

Date Impt rem. Bone

Date Analysis SEM?

Figure 7 Form used for recording

results of implant analysis

of nail plates.

'03

The implants, implantation times and the results of implant

analysis, LIF testing, and patient history review are listed in table

4. The description of corrosion lists the screw positions where

plate/screw interaction was seen and where interaction of the bolt

3 I 5
and washer was observed. The most striking observation one can make

about this table is the wide variation of implants used. There is some suggestion of more significant corrosion in the sensitive and

nonmigrator patients, although the correlation is not strong.

STEEL NAIL PLATES

# IMPL YRS CORROSION LIF CLINICAL

1 N 2 MO MIN GOOD THR

2 J4 2 MO d2 (2/1/6) GOOD BAD POSITION

3 C3 5 MO MIN GOOD MIG

1 J5 9 MO d2, d5 (2/2/6) GOOD ROUTINE

5 H 10 MO d2 (2/2/6) GOOD AVASC. N. THR

6 M 2 NAIL-SLEEVE GOOD PAIN, N,U.

7 M 9 MIN C.W. N=S GOOD THR

8 SP+M 1 WASH, Dl, D5 (3/3/6) SENS PAIN

9 SP+M d2, d5, d6 (2/2/6) SENS

10 C3 5 MO d2 (3/1/6), n-s (3/2) NOM INF. AVASC. N.

11 2 A5 11 MO d5 (3/1/3) NOM ROUTINE

5 MO d4 (3/2/6, 7) 12 E 1.2 BURNISHING NOM NONU,

13 2 SP+T 9 wash, Dl (3/2/6) NOM PAIN BURSA

12 Dl (2/1/6) NOM PAIN, BOLT MIG

Table 4. Steel

plate study.

nai 1

M = Massie nail

J4 = Jewett with 4 screws

C = compression screw

SP+M = Smith-Peterson

+ McLaughlin

SP+T = + Thornton

plate

A = angle blade plate

E = Elliot blade plate

If we are to hypothesize that time and corrosion will lead to

elevated tissue levels of alloy constituents and thus the possibility

of metal sensitivity, one might ask why the patient #7, with a multicomponent Massie nail had no sensitivity after 9 years implantation.

In examination of the implant, there was virtually no evidence of

degradation between plate and screws, nor between nail and sleeve.

It is proposed that one reason for the lack of nail-sleeve interaction

is that, unlike most similar implants, there were no microstructural

differences between the nail and sleeve. As is shown in figure 8,

the grain size and degree of cold working of these two identically

etched and photographed sections was virtually the same. While hard- ness testing would be a better method for differentiating degrees of

cold work, the issue here is electrochemical differences which might

lead to galvanic corrosion. The response of these two sections to

the electrochemical etch was the same, and thus their response to the

corrosive in vivo milieu could be expected to be the same. In contrast, most sliding nail-plate implants show a significant difference in cold working. Such was the case in the implant from

patient #6, which showed large areas of superficial corrosive attack

in nail-sleeve contact areas.

3 1 G
(a) (b)

Figure 8

Metallographic sections of identically etched and photographed sections of the nail (a) and sleeve (b) of the

Massie nail-plate implant from patient #7 in table 4.

5. Discussion

In considering the clinical significance and the role of implant corrosion in metal sensitivity reactions to metallic implants,

we must bear in mind that there is a very significant patient

variable in this subject: genetics. Some patients have or can develop metal allergy while others will not. Most people can go

through life wearing jewelry and stainless steel watch bands with

impunity, while others will develop contact dermatitis. It has been

reported that the incidence of metal allergy in the "normal" population is 13% for nickel, and 7.8% for chromium [24]. Thus, our

studies looking at correlations between the results of implant analysis and LIF testing are skewed by patient genetics.

Another issue to be raised is the sensitivity and specificity

of the LIF test. It is well known that some of these metallic

elements are toxic, and thus their presence in the LIF cell culture

could have a toxic effect on the leukocytes rather than a stimulatory effect on the T-lymphocytes . We have conficence that toxic

effects are minimal since most patients show good migration in the

presence of the metals in the concentrations used. However, the

issue still remains as to differences in individual patient sensitivities to the toxicity of the metals. Since T-cells will only

respond to metal ion haptens complexed with proteins, the immunogenic!" ty of the specific protein complex may play a role in the

3 I 7
sensitivity and specificity of the test results. We have been

critical of the skin test since only skin proteins are involved, and

yet use plasma rather than tissue proteins in the test. Nevertheless,

the plasma proteins are certainly available at the implant site for

hapten binding. Another disadvantage of the skin test is that it

does not assay for sensitivities involving T-cell, B-cell and antibody interactions, as does LIF test. However, these interactions may

result in the LIF test being too sensitive.

In looking at the LIF test results for specific implant types, one sees a surprising number of nonmigrators in the bone screw group.

While these are comparatively small implants, they are in a mechanically stressed situation, with direct bone-metal abrasion

possible, and the implants themselves tend to have surface defects

such as small casting defects or machine tool chatter marks. In comparison, the much larger intramedullary rods tend to be much

smoother and more highly polished. One interesting patient with a Lottes tibial nail was a nonmigrator until the rod failed in fatigue.

Some months later he had good migration with a nickel sensitivity.

Analysis of the retrieved rod revealed significant burnishing of the

distal stem of the rod. Presumably the burnishing was occurring prior

to failure, and after failure and re-casting of the leg, the bonemetal abrasion was reduced to the point where presence of the otherwise polished rod was no longer producing tissue levels sufficient to

stimulate an immune response.

This hypothesis of wear between bone and metal being a causative

factor in metal sensitivity reactions has been applied in the discussion of hemi hip arthroplasties in section 4.1. One of the difficulties of the implant analysis was determining how much metal had been worn off the stems. The burnishing code numbers in table 2 were more

an estimation of the area of burnishing than of the depth of the worn

area. Thus, the numbers do not truly reflect the amount of metal

lost. On the other hand, the hardness of a metal is related to its wear resistance. Table 2 shows a good correlation between soft

metals and patients developing early complications associated with

metal sensitivity. The process of wear would also lead to fretting

accelerated corrosion [25], and set up a crevice corrosion environment. This mechanism is also proposed for the severe attack seen in screw and plate d2 of patient #10 in the plate study.

With this discussion of bone-metal wear, it is of interest to

observe that the treatment for the hemi hip patients, and some of the

hip-nail plate patients was total hip arthroplasty with cemented

femoral components. These devices have been well tolerated, presumably by isolation of the metal component with PMMA bone cement and

articulation with UHMWPE acetabular cups. The polished prosthesis

neck seems to be sufficiently passive to avoid immune reactions. However, some patients have had allergic complications when stainless

steel wire (bone-metal contact) was used for reattachment of a trochanteric osteotomy [8].

3 I 8
As for the two patients with asthma, prior to implant removal

both were well controlled with medication, and both discontinued

using medication after prosthesis removal and total hip replacement.

Whether the implant allergies actually caused the asthma is still a subject for debate at our institution. Asthma is a complex clinical

syndrome with many endogenous and exogenous causes. It may have been

coincidence in these two cases. However, these patients were among

the few in our and other studies with allergy to chromium, and asthma

is known to occur in chromium workers.

6. Conclusions

It can be concluded from this study of 164 patients at the time

of implant removal that metal sensitivity reactions can be a cause of

patient morbidity associated with metallic implants. However, sen- sitivity is probably not a major cause of complications; e.g., all the

hip arthroplasties hurt. In reviewing a patient's symptoms, sensitivity should be considered. If the patient is reacting to the

device, the symptoms probably will not improve, and if appropriate,

removal of the device should be considered.

Cases have been presented where evidence of implant degradation

due to wear and corrosion do correlate with the immune response. The

study is still too limited in size to make any definitive conclusion

concerning specific alloys or implant types. It does suggest that

implants subjected to situations conducive to wear and fretting cor- rosion are likely to stimulate an immune response. The question of

whether implants can cause metal sensitivity and sensitivity reactions

is the subject of an ongoing prospective study in which sensitivity

testing is performed prior to and during the implantation period and

at the time of removal. The retrieved implants are also analyzed.

We believe that such prospective studies are essential for the

development of a better understanding of the relationships between

metal implants, metallurgy and metal allergy. We do not recommend

skin testing for such prospective studies.

The authors wish to acknowledge the orthopaedic section of Mary

Hitchcock Memorial Hospital, especially Drs. Michael Mayor and Leland

Hall, for providing the patient material discussed in this report.

The technical assistance of Mr. Leo Dauphinais and Mrs. Helene Klein

is gratefully acknowledged. The authors are indebted to Mrs. Normalie

Barton, without whose assistance in editing and typing, this manuscript

would be only a collection of scribbled notes.

This study was funded by a grant from the Educational Foundation

of America, Encino, California, and from USPHS grants AM 17749 and

AMA I 20271.

3 I 9
References

1. Laing, P. 6., Ferguson, A. B., Jr., and Hodge, E. S., Tissue

reaction in rabbit muscle exposed to metallic implants,

J. Biomed. Mater. Res. ]_, 135-149 (1967).

2. Barranco, V. P., and Soloman, H., Eczema tous dermatitis from

nickel, JAMA 220_, 1244 (1972).

3. McKenzie, A. W. , Aitken, C. V. E., and Risdi 11 -Smith, R.,

Urticaria after insertion of Smi th-Petersen vital! ium nail,

Br. Med. J. 4, 36 (1967).

4. Benson, M. K. D., Goodwin, P. G., and Boostoff, J., Metal sensitivity in patients with joint replacement arthroplasties,

Br. Med. J. 4, 374-375 (1975).

5. Elves, M. W. , Wilson, J. N., Scales, J. T., and Kemp, H. B. S.,

Incidence of metal sensitivity in patients with total joint

replacements, Br. Med. J. 4, 376-378 (1975).

6. Evans, E. M., Freeman, M. A. R., Miller, A. J., and VernonRoberts, B., Metal sensitivity as a cause of bone necrosis and

loosening of the prosthesis in total joint replacement,

J. Bone and Joint Surg. 56B, 626-642 (1974).

7. Merritt, K. , Mayor, M. B., and Brown, S. A., Metal allergy and

implants: concepts and clinical significance, in Current Concepts of Internal Fixation of Fractures , H. K. Uhthoff, ed.,

pp. 165-173 (Springer-Verlag, Berlin, 1980 )

.

8. Merritt, K. , and Brown, S. A., Hypersensitivity to metallic biomaterials, in Systemic Aspects of Biocompatibi 1 ity , D. F. Williams, ed., Chapter 21 (C.R.C. Press, in press).

9. Eisen, H. N., Immunology (Harper and Row, Hagerstown, 1974).

10. Fisher, A. A., Contact Dermatitis , 2nd Edition (Lea and Febiger,

1973).

11. Meneghini, C. L., and Angelini, G., Behavior of contact allergy

and new sensitivities on subsequent patch tests, Contact

Dermatitis 3, 138-142 (1977).

12. Clausen, J. E., Leukocyte migration inhibitory factor, in Manual

of Clinical Immunology , N. R. Rose and H. Friedman, eds.,

Chapter 11 (American Society for Microbiology, Washington, 1976).

13. Brown, S. A., Shafer, J. W., Mayor, M. B., and Merritt, K.

,

Metal allergy and its role in the biocompatibil ity of orthopaedic implants, in Proc. N. E. Bioeng. Conf. 5_, 6-10 (1977).

320
14. Merritt, K., and Brown, S. A., Tissue reaction and metal sensitivity: an animal study, Acta Orthop. Scand. (in press).

15. Merritt, K., and Brown, S. A., Loss of random and chemotactic

cell migration in humans and rabbits, Abstracts 80th A.S.M.,

68 (1980).

16. ASTM F-561 Standard practice for retrieval and analysis of

metallic orthopaedic implants, ASTM Annual Book of Standards , part 46 (Philadelphia, 1979).

17. Click, R. E., Benck, L., and Alter, B. J., Immune responses in

vitro 1 . culture conditions for antibody synthesis, Cell

Immunol. 3, 264-276 (1972).

18. Simpson, J. P., Geret, V., Brown, S. A., and Merritt, K.

Retrieved fracture plates: implant and tissue analysis (in this

volume)

19. ASTM E-45 Recommended practice for determining the inclusion

content of steel, ASTM Annual Book of Standards , part 11 (Philadelphia, 1979T

20. ASTM E-112 Estimating the average grain size of metals, ASTM

Annual Book of Standards , part 11 (Philadelphia, 1979).

21. ASTM E-18 Tests for Rockwell hardness and Rockwell superficial

hardness of metallic materials, ASTM Annual Book of Standards , part 10 (Philadelphia, 1979).

22. ASTM E-140 Standard hardness conversion tables for metals, ASTM

Annual Book of Standards , part 10 (Philadelphia, 1979).

23. ASTM F-75 Specification for cast cobalt-chromium-molybdenum alloy

for surgical implant applications, ASTM Annual Book of Standards , part 46 (Philadelphia, 1979).

24. Rudner, E. J., et al . , The frequency of contact sensitivity in

North America, 1972-1974, Contact Dermatitis 1_, 227-280 (1975).

25. Simpson, J. P., Merritt, K. , Brown, S. A., Fretting corrosion of

steel plates and screws, presented at First World Congress of

Biomaterials , Baden-near-Vienna (April 1980).

32 I

TECHNIQUES FOR THE EXAMINATION OF

TISSUES IN IMPLANT RETRIEVAL ANALYSIS

D. F. Williams, A. McNamara and G. C. F. Clark

Department of Dental Sciences

School of Dental Surgery

University of Liverpool

P. 0. Box lk7

Liverpool, L69 England

A detailed examination of the tissue response to

implanted high purity metals has been undertaken. The

methods used include conventional histology, enzyme histochemistry, transmission and scanning electron microscopy,

EDAX analysis and elemental analysis by flame and flameless

atomic absorption spectrophotometry and polarography

Details of these techniques are given in this paper with a summary of some of the results obtained in experiments and

the applicability of the methods to the examination of

tissue samples taken at implant retrieval.

1. Introduction

It has long been recognised that the greatest value in implant

retrieval analysis is obtained when the examination involves the

biopsy (or autopsy) tissue samples and clinical data in addition to

the materials of the device. A full understanding of the reasons

for failure, or conversely of the conditions predisposing to success, can only be achieved when all the factors are considered. This point was emphasised in earlier work from our laboratory. [1,2]^" The significance of metallic corrosion, for example, can only be assessed by

an examination of the tissues adjacent to the implant and with reference to the clinical observations leading to implant removal.

In most of the reports of the tissue examination subsequent to

implant removal, reference is only made to haematoxylin and eosin

stained sections of tissue, studied by light microscopy. Whilst giving a reasonable amount of information, and being quite adequate in

many circumstances, such an examination cannot always determine the

extent or significance of the implant-tissue interaction and it may

be desirable to use other methods.

Figures in brackets indicate the literature references at the end of

this paper.

323
In view of this situation, attempts have been made to utilise a variety of microscopical and analytical techniques in the assessment

of the biological response to orthopaedic implants and these are discussed in this paper. It must be recognised that there are other

aspects of the biological response that are not included here, such

as the immunological and microbiological aspects, their ommission

being due solely to the constraints of the present experimental programme, without any reflection on their importance.

Because of the difficulties involved with standardising data

from retrieval specimens, and the absence of controls, the experimental

work described has been carried out with animal models, with a view to

gaining a greater understanding of the fundamental aspects of biocompatibility and to developing techniques for later use in a programme

of device retrieval.

2. Animal Model

All of the experimental work has been performed with black and

white hooded Lister rats of the Liverpool strain. These are usually

three months old at the time of operation. Two types of experiment

are relevant to the present discussion. In the first, metallic discs

are implanted intramuscularly, bilaterally in the paravertebral muscles,

where they are retained for varying periods of time. After sacrifice

the tissues and discs are prepared for examination by one of the methods

described below. In the second type of experiment the distribution of

metal ions in the animal tissues is determined following the intramuscular or intraperitoneal implantation of powders. In this case, one of several types of analytical method may be used on the dissected

tissues. The methods described are those found to be most suitable in our laboratory, although naturally there are alternatives which other

workers may prefer.

3. Materials

Since this programme of work is primarily aimed at providing a better understanding of the biocompatibi 1 ity of metals, only pure

metals have been used. It is difficult enough evaluating the tissue

response to one metal without introducing the complexities of alloy

systems, where there may be three, four or even more elements of

significant concentration, each being released at a different rate

and each with a different potential for cytotoxic behaviour. Nevertheless, the techniques used, which are the main concern of this

paper, are equally applicable to pure metals or alloys.

The metals used in the study include nickel, cobalt, copper,

aluminium, titanium and lead. Table 1 indicates the purity of each

metal. The implanted discs were 5mm i n diameter and the powders were

of 20 mesh particle size.

324
Table 1 Pure Metals Used

Disc Powder

Nickel 99.999/o 99-995%

Cobalt 99.998% 99.995%

Copper 99-999% 99.999%

Aluminium 99.998% 99.98%

Lead 99.999%

Titanium 99.8% 99.8%

h- Microscopical Technique

Conventional histological methods involving either paraffin wax

embedded or frozen blocks stained by haematoxylin and eosin give a considerable amount of information about the morphology of the tissue.

For example, detailed studies of the fibrous tissue capsule around the

implanted discs of the pure metals have been undertaken using frozen

section techniques, representative areas being shown in figure 1 (a-e). These techniques are standard and need no further comment

here. They may, however, be supplemented by other techniques to give more detail about the effects in the tissue.

Histochemical methods

The response of tissue to the implantation of a foreign body

usually involves a considerable cellular infiltration. These cells

will be continuously synthesising and releasing enzymes for specific

functions, associated with, for example, phagocytosis. Each type of

cell has associated with it a variety of lysosomal enzymes such that

the presence of enzymes in tissue is indicative of the types of cell

that are present and, more importantly, the quantity of the enzyme

reflects cellular activity and, by implication, the extent of the

effect of the foreign body on the tissue. Salthouse [_J>-^1 was the

first to demonstrate the relationship between lysosomal enzyme ac- tivity in the tissue with the toxicity of implants, in this case plastics and has refined the techniques to allow a quantitative analysis of the response [6]. The techniques presented here are those

used in our laboratory for the study of the soft tissue response to

metals.

The principle of the technique is that if enzymes in tissue are presented with their own specific substrate, a reaction will take

place, yielding a well defined product which may be possible to detect. Often this primary reaction product is invisible and so it is

coupled with another substrate that is insoluble but visible. Thus,

the tissue is stained according to the enzymes which are present.

1 Metals Research Ltd., Cambridge, U.K.
The coupling substrate used varies with different enzymes, diazonium

salts being used for phosphatases and tetrazolium salts for dehydrogenases for example. It is important to note that pH control is

very critical in this process.

It is also important that controls are performed, since substrates deteriorate and may give false negatives. A positive control should always be included which will confirm the activity of

the chemicals used whilst negative controls, produced for example

by deliberate omission of the substrate from the incubation medium

or inclusion of specific enzyme inhibitors, should indicate that

any positive results obtained with test samples are not artefact and

exclude non-specific background staining.

For this work, frozen sections are necessary and rapid freezing

is essential to avoid ice crystal artefacts. Isopentane suspended

in liquid nitrogen is suitable and the tissue sample is placed in

the liquid while held between two metal discs to give faster heat

conduction. Approximately 7'p.m thick sections are prepared at -15° C

in a cryostat and placed on glass coverslips.

The following is a brief outline of the methods used for selected enzymes.

If. 1.1. Phosphatases

The hydrolysis of organic phosphate esters provides the basis

for the reactions. After reaction with the enzyme, the alcoholic

residue of the substrate is allowed to react with a diazonium salt

to give a highly coloured insoluble azo dye.

(1) Alkaline phosphatase. The substrate used here is

naphthol AS-B1 phosphate which is hydrolysed by the

enzyme producing an insoluble naphthol derivative.

This is reacted with a diazonium salt such as fast

red TR, which yields an insoluble azo dye at a final

pH of 9.0.

(2) Acid phophatase. A substituted napthol is also used

here to yield an insoluble naphthol derivative, which

is reacted with hexazonium pararasaniline at a pH of

h.7 to 5*0. An example is given in figure 2a.

if. 1.2. Dehydrogenases

The coupling substrates used for dehydrogenases are tetrazolium

salts which are water soluble and almost colourless and accept H

+ released from the substrate after reaction with the enzyme, giving

an insoluble highly coloured deposit of a formazan compound.

(l) Succinate dehydrogenase. The substrate is sodium suc- cinate and the coupling substance a monotetrazolium salt

(MTT). Formazan is then chelated with Co^+ ions to give

a coloured insoluble granular deposit. The pH is 7»0«

326
(2) Lactate dehydrogenase. The technique is essentially the same

but uses sodium lactate as the substrate. In addition, NAD

is required as a hydrogen acceptor before the tetrazolium

salt can be converted into a formazan compound (Fig. 2b).

4.1»3» Leucine aminopeptidase

The substrate is 1-leucyl-^-methoxy-p-naphthylamine, which is split

by the enzyme. A diazonium salt, fast blue B is used to react with this

yielding an insoluble azo dye which can in turn be treated with CuSO^

when the copper ions form a chelate with the azo dye. An example of a section stained in this way is seen in figure 2c.

^.2. Electron Microscopy

The electron microscope, with all its analytical facilities, provides

a very useful tool for the analysis of biological tissue. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Energy

Dispersive X-ray Analysis (EDAX) have all been used.

^f.2.1. Scanning electron microscopy

Critical point drying is used in the preparation of specimens for

scanning electron microscopy. This involves the following sequence of

solutions.

50% ethanol/water 10 mins

70% ethanol/water 10 mins

90% ethanol/water 10 mins

95% ethanol/water 10 mins

100% ethanol/water 15 mins

3'i ethanol/acetone 15 mins

1:1 ethanol/acetone 15 mins

1?3 ethanol/acetone 15 mins

100% acetone 2 x 20 min

The tissue previously fixed in formal saline, is placed in mesh

baskets and covered with acetone, which is then flushed with C02 until

the acetone layer is removed. It is left for 1 hour in liquid CO2 before the CO2 is sublimed off, which should occur at J>8° C. The speci- mens are mounted on aluminium stubs and coated in the normal way prior

to examination in the microscope."'"

Interesting observations have been made on the tissue adherent to

implanted metal surfaces using this technique, some examples being

shown in figure 3»

^Jeol JSM-3SC

327
if. 2. 2. Transmission electron microscopy

Transmission electron microscopy is carried out on specimens

prepared in the following way.

1 l/2 hours in glutaraldehyde (cacodylate

buffered at 6.25%).

1 1/2 hours in cacodylate buffer (with

changes.

1 1/2 hours in osmium 1% (2% in water

diluted to 1% in cacodylate buffer).

Cacodylate buffer, pH 7«4.

10 mins 70% methanol

30 mins 90% methanol

2 hours 100% methanol, with changes

15 mins propylene oxide

overnight ^0/^0 araldite^/propylene

oxide at 60° C.

Transfer to araldite containing accelerator, with 2-3 changes before final

embedding in gelatine capsule.

4.2.3. EDAX

The same method may be used for the preparation of specimens for

EDAX investigations, although it may be preferable to use a non- aqueous process to avoid any problem of leaching of metal ions. In

this case, the procedure is as follows:

12 hours in glycol

2h hours in Cellusolve

48 hours in 5O/5O Cellusolve/Spurr resin.

2k hours in 100% Spurr resin. The specimens are preferably

mounted on aluminium grids rather than copper to prevent masting.

5. Analytical Methods

When examining the tissue adjacent to metallic implants, it is

desirable to determine the concentration and if possible, the distribution of metal in that tissue. It would also considerably increase

our knowledge of the effects of metallic prostheses on patients if

samples of organs could be taken at post mortem examination for analy

sis. There are several methods available for this analysis, two of

the more important, atomic absorption spectrophotometry (AAS) and

polarography being discussed in this paper.

JE0L, JEM 100c X

Ciba-Geigy

Fixation:

Wash:

Dehydrate:

Embedding:

326
5.1. Ashing techniques

The traditional method of preparing biological tissue for elemental analysis involves digestion in acid. The method used in our laboratory is as follows. The sample is weighed, dried at 110° C and

reweighed. Approximately 0.2^ cm^ of a solution comprising 1 part

cone. HNO-z, and 3 parts F^SO^ is added per lOOmg wet weight. This is

heated until it becomes clear, with no further brown fumes evolved,

or until no further clarification occurs. Heating is carried out

at 8o° C in polypropylene vessels. The product is usually a brown

liquid, fully miscible with water and quite suitable for AAS. However, it is not entirely successful with fatty tissue, which tends

not to dissolve, and bone which may give a precipitate of calcium

sulphate.

This technique has the advantage that many samples can be processed at the same time. If complete digestion can be achieved and

the solution is clear, then all metals and anions are accessible to

any of the analytical techniques. With solutions that do not clear,

complexing agents may be present leading to interference with ionselective electrodes, polarography and other methods. The main disadvantage of the technique is that the concentrated acids used can be a source of contamination, especially for the lighter elements

such as aluminium, and ultimately controls the sensitivity. All

solutions are made up in cone. H2S0^ which makes dilution difficult

and implies all standards have to be in H2S0/

+ as well. In flameless

AAS the signal tends to be very noisy.

An alternative technique is now used exclusively in our laboratory since it is less susceptible to contamination. This involves

subjecting the sample to a low temperature discharge in an instrument referred to as a Plasma Asher."*" The sample is weighed, dried

in vacuo and reweighed. Dry samples, contained in glass or quartz

vessels are placed in the chamber of the instrument which is then

operated for about l8 hours with an oxygen flow rate of 2-3 cm-^ min-

^, at a pressure of 1 torr and 100 watts power. For most materials, the sample should be stirred to disturb the upper layer of

ash which would otherwise obstruct the access of the plasma to the

sample. After ashing the sample is dissolved in diluted HC1 at,

for example, 0.1 cm-5 O.^M per 100 mg wet weight. The technique is

slow since a limited number of samples can be ashed at any one time

and there is a possibility of contamination from the glass vessels,

although this has not been detected so far. Hydrochloric acid is

the purest of acids and hence gives rise to considerably less con- tamination than the acids used in wet digestion. The solutions are dilute and so no problems occur with standards or dilutions.

IPlasmaprep 100: Nanotech (Thin Films) Ltd., Manchester.

329
5.2. Atomic Absorption Spectrophotometry (AAS)

This technique is based on the absorption of light by atoms of

the element to be analysed. A lamp specific to the element in

question is used (i.e. giving radiation of a specific wavelength)

and noise can be reduced by chopping this with a continuous source

(e.g. Dp) which envelops the chosen wavelength, typically to +. 0.2nm.

There are two basic types of AAS, the difference lying with the

method of atomisation of the sample and the sensitivity. With flame

AAS^ a solution containing the element is sprayed into a flame,

either acetylene-air or acetylene-nitrous oxide, where it atomises.

The nitrous oxide flame gives a higher temperature and hence a higher atomisation rate. With flameless AAS^ a small volume of the

sample is injected into a graphite tube. Here automatic temperature programming will dry the sample, volatilise unwanted material,

especially organic substances, and then vaporise the sample. The

atomisation temperature may be as high as 3000° C« An inert gas is

used as a blanket to prevent oxidation of the tube. This may be

nitrogen, but for metals which form stable nitrides, such as aluminium or titanium, argon is preferable.

It is necessary in all cases to prepare a series of standard

solutions covering the expected sample concentration. Each is analysed to prepare a calibration curve. Since the atomisation process

is very fast with the flameless AAS, only single values can be obtained so that replication of injections is essential.

Generally the flameless AAS is more sensitive than the flame

AAS, their use being optimum in the ranges ^>-^>00 p.p.b. and O.5-

100 p. p.m. respectively. The flame AAS technique is fast ( 10 sec

per sample) and precise as sample spraying is not under operator

control, but has limited sensitivity and requires relatively large

volumes (71 «5 cm^). Flameless AAS is slower (2 mins per injection)

and its accuracy is controlled by the precision of injection.

However, it is 100 to 1000 times more sensitive and there is less

risk of interference because of the ashing stage and the high temperature attained.

5»3« Polarography

This technique involves conversion of the metal from an ionic

form to a lower oxidation state, which may be the metal itself.

The rate of this reaction is a function of the standard electrode

potential, the diffusion coefficients for the reactants and products

and the concentration of the reactants and products. The rate is

measured as the electrical current that flows and by the use of

standards this can be converted to a concentration of the metal.

iSP 192 Pye Unicam Ltd.

SP 9-01 Digital Flameless Atomiser, Pye Unicam Ltd.

330
The apparatus required is a reproducible anode at which the reactions

may occur, a current carrying cathode, a reference electrode, an accurate scanning potentiometer and a very sensitive ammeter suitable for currents less than 0.02pA.^

There are several different varieties of polarographic technique available which primarily reflect electrical refinements to

eliminate background contributions to the current and to avoid electrochemical effects which reduce the sensitivity. The conditions

of pH, redox potential and chelating species must be selected to

separate the metal of interest from others that may be present.

Anode stripping voltammetry is one variation of polarography

that can increase the sensitivity by almost 1000-fold, giving a detection limit in the region of 0.01 p.p.b. If the metal forms an amalgam with mercury and is reducible at a mercury electrode, then

it may be concentrated by electrolysis into the mercury drop. On

scanning the potential in a positive direction the metal is oxidised,

giving a large current peak. The technique is restricted to a few

metals, chiefly lead, cadmium, thallium, copper, zinc and antimony,

although other metals can be included by use of various esoteric

refinements.

One problem with polarographic techniques is the sensitivity

to contamination due to either chelating or surface active species,

which places a greater emphasis on the digestion procedures.

5.4. Comparison of Polarography and AAS

Table 2 illustrates the technique most suitable for a range

of metals and the sensitivity that can normally be achieved.

Table 2 Analytical methods

Metal Technique Sensitivity

Aluminium, Al AAS (flameless) 0.2 ppb

Cobalt

Co AAS (flameless) O.5 ppb

Chromium, Cr AAS (flameless) 1.0 ppb

Copper, Cu Polarography 0.01 ppb

Iron, Fe AAS (flame) 0.2 ppm

Molybdenum, Mo AAS (flameless) 0.3 ppm

Nickel, Ni AAS (flameless) 1.0 ppb

Titanium, Ti Polarography 1.0 ppb

Vanadium, V Polarography 2.0 ppb

Tungsten, Tu Polarography 2.0 ppb

PAR 17ifA: Brookdeal Electronics Ltd.

33 I
An example of the results obtained with these techniques is

shown in Table 3i which compares the cobalt levels in various tis- sues and organs of rats which were maintained either on a standard

diet or a diet supplemented with a ten-fold increase in cobalt

content, or were implanted with cobalt powder, either intraperitoneally or intramuscularly. Analyses were performed by flameless

AAS.

Table 3 Cobalt Levels in Rats (ppm)

-L lOOUU Control Cobalt V1 \y KJ OA. -L 10 wk 10 wk 26 wk 26 wk

Supplel.M. l.P. l.M. l.P. mented

Diet

Adrenals 0.23 O.5I 1.28 5.68 1.10 0.18

Kidney o.Mf 1.86 kz.o 30.9 G.7k 3.07

Liver 0.25 1.16 5.28 25.4 0.86 1.02

Blood 0.11 0.11 0.9^ 0.71 0.26 0.50

Heart 0.18 0.60 1-7 2.5O 3.23 2.62

Brain 0.21 0.32 0.28 O.33

Spleen 0.18 0.53 1.48 1.11 0.21 0.17

Muscle 0.16 0.60 0.06 I.05 0.28 0.1k

Implant Site i.8xio5 8xio^ 2.2k 2.5x10^

Peritoneal Wall 0.10 3-24 1.96

Bone 0.81 0.17 1.13

It can clearly be seen from these results that there is a significant increase in the level of cobalt in the kidneys at 10 weeks

but this level is reduced by 26 weeks. Most tissues have slightly

raised cobalt levels following implantation.

6. Discussion

The techniques reported in this paper are those which have

been found to be the most suitable in our laboratory for tissue

examination. Although representing a personal preference in many

cases, where quite adequate alternatives exist (with enzyme histochemistry, for example) , in other cases they represent what are considered ideal conditions after extensive investigations of the

alternative methods (for example, with the digestion of tissues).

These techniques have been fully utilised in the animal experiments

discussed and should be readily applicable to any tissue samples

obtained at implant retrieval. Detailed results of the specific

experiments mentioned are to be reported elsewhere.

332
Figure 1 Haematoxylin and eosin stained sections of tissue adjacent

to pure metals, implanted intramuscularly,

a) Ni x 100? b) Co x I5O?

c) Cu x 50,'

d) Al x 50; e) Pb x 50

333
c

Figure 2 Enzyme activity in tissue adjacent to intramuscular

implants of pure metals.

a) Acid phosphatase, aluminium implant x ^>0. b) Lactate dehydrogenase, nickel implant x ^0.

c) Leucine aminopeptidase, nickel implant x 1^0.

334
Figure 3 Scanning electron micrographs of metal surfaces and

adherent tissue after intramuscular implantation,

a) Ni x 600 ,• b) Co x 750,*

c) Cu x

d) Al x 5000; e) Pb x 5OOO.

335
The authors wish to thank both the Science Research Council

and the Medical Research Council for support of parts of the

research reported in this paper.

References

[l] Williams, D. F. and Meachim, G. A combined metallurgical and

histological study of tissue-prosthesis interactions in orthopaedic patients, J. Biomed. Mater. Res. Symp. No. 5* 1-9 (197*0 •

[2] Meachim, G. and Williams, D. F. Changes in non-osseous tissue

adjacent to titanium implants, J. Biomed. Mater. Res. 2.1 555"

572 (1973).

[3] Salthouse, T. N. and Matlaga, B. F. Enzyme histochemistry of

the cellular response to implants. In Fundamental Aspects of

Biocompatibility, D. F. Williams, ed. (CRC Press, Boca Raton,

FL, 1980, in press).

[if] Salthouse, T. N. and Williams, J. A. Histochemical observations

of enzyme activity at suture implant sites. J. Surg. Res. 2., 481-/+86 (1969).

[5] Salthouse, T. N. and Williams, D. A. An enzyme histochemical

approach to the evaluation of polymers for tissue compatibility.

J. Biomed. Mater. Res. 6, IO5-II3 (l9?2).

[6] Salthouse, T. N., Matlaga, B. F. and O'Leary, R. K. Microspectrophotometry of necrophage lysosomes enzyme activity: a measure of polymer implant tissue toxicity, Toxicol. Appl.

Pharmacol. 2$., 201-211 (1973).

336
INTERFACE PHENOMENA

337
!
RETRIEVAL ANALYSIS OF CALCIFIC DEGENERATION OF PROSTHETIC

TISSUE VALVES: THE ROLE OF VITAMIN K-DEPENDENT PROCESSES

AND OTHER REGULATORY MECHANISMS

Robert J. Levy, Stephen P. Sanders, Jane B. Lian

Children's Hospital Medical Center

300 Longwood Avenue

Boston, Ma. 02115

Calcification of glutaraldehyde preserved porcine xenograft valves represents a major clinical problem affecting

the use of these prostheses. Currently, there is no satisfactory explanation for this pathologic process. The

present work explores the inter-relationships of both

clinical parameters and biochemical changes in the

affected valve tissue. The results of the present study

show that the prosthesis failure in our patient population

was always associated with calcification, and this com- plication was noted to occur only in those patients under

15 years of age at the time of valve replacement. Amino

acid analysis of calcified leaflet tissue revealed the

presence of high levels of proteins containing the

vitamin K-dependent, Ca++ binding amino acid, gammacarboxyglutamic acid (Gla) , in mineralized specimens,

with no Gla present in non-calcified valve tissue. In

addition, the Ca++ binding amino acid O-phosphoserine was detected in relatively greater amounts in the mineralized

specimens, compared to control. Calcified xenografts also

demonstrated a relative reduction in collagen content

(as evidenced by hydroxyproline analysis) . The implications that vitamin K-antagonism could be of benefit in

treating or preventing prosthesis calcification is discussed.

1. Introduction

Calcification of glutaraldehyde preserved porcine xenograft

valves has emerged as a major problem affecting these prostheses.

Precise data on the incidence of this complication is not as yet

available, but work to date suggests that the problem is more frequent

in children EL,2jl and that increased mineralization occurs with time

[1,2,3]. Clinically, calcific degeneration of the xenograft valves

can produce either valvar stenosis or regurgitation depending upon

the presence of mineral associated tears in the leaflets [1,2,3].

Pathologic studies of xenograft mineralization reveal dystrophic

calcium deposits to be present either as superficial nodules, or associated with the collagen fibrils in the valve stroma [3,4].

^"Figures in brackets indicate the literature references at end of this

paper.

339
The pathogenesis of porcine xenograft valve calcification is poorlyunderstood. However, recent work has indicated that proteins containing

the vitamin K-dependent Ca++ binding amino acid, gammacarboxyglutamic acid

(Gla) occur in a wide variety of pathologic calcifications including

calcified atherosclerotic plaque and calcified cardiac valves [5,6,7].

Gla was first discovered by Stenflo to occur in the Ca++ binding sites

of the prothrombin molecule 18 ] . Subsequent work demonstrated that Gla

synthesis occurs in the vitamin K-dependent coagulation factors as a vitamin K-dependent, post-translational enzymatic carboxylation [9] of

specific glutamic acid residues. In fact, warfarin therapy (fig. 1)

results in inhibition of Gla synthesis, with loss of Ca++ binding and

anticoagulation [9].

Ca++

COO

I CH2 CH2

Glutamic Acid

in Protein

Vitamin K Dependent

Carboxylase

Warfarin Inhibition

COO^

/

COO

CH

I CH2

f- Carboxyglutamic Acid

in Protein

Figure 1. Post-translational Gla synthesis

In 1975 Hauschka, Lian and Gallop demonstrated the presence of a unique Gla containing protein in normal bone, which they named osteocalcin [10] . Following this, Lian and her colleagues demonstrated

Gla containing proteins to be present in pathologic calcifications

including calcium containing renal stones [5,6], calcified skin

deposits occurring in dermatomyositis and scleroderma [5] , and

calcified atherosclerotic plaque [5] . Following this, Levy, Lian

and Gallop [ 11] isolated and have partially characterized a unique Gla

containing protein from atherosclerotic plaque which they have named

atherocalcin. In addition, Levy, Zenker and Lian [7] have recently

demonstrated the presence of Gla containing proteins in calcified

aortic valves including several cases of porcine xenograft calcificattion.

In the present paper, we will present further evidence linking

vitamin K-dependent processes involving proteins containing Gla to

340
porcine xenograft valve mineralization. In addition, data will be

presented indicating that relative diminution of collagen content is

also associated with xenograft calcification, and that phosphoproteins

containing the Ca++ binding amino acid, O-phosphoserine also occur

at high levels in porcine xenograft valvar calcification.

2. Methods

2.1 Clinical Material

Stent-mounted porcine xenograft valves were retrieved at cardiac

surgery for prosthesis failure. In addition, clinical and physiologic

data on all patients with this type of prosthesis were compiled to

compare those patients with valve failure to those with xenografts

still in place.

The xenograft specimens obtained at surgery were subjected to a brief pathological exam and then frozen at -20°C. Control tissue

analyzed consisted of porcine aortic valves obtained fresh at slaughter

and commercially prepared glutaraldehyde preserved porcine aortic

valves. In addition, human aortic valve tissue obtained at surgery

for aortic stenosis was also examined, as was tissue from a non- preserved, calcified aortic valve homograft. Control human aortic

valve tissue was obtained at autopsy.

2.2 Biochemical analyses

Individual valve leaflets were rinsed with normal saline to remove adherent blood and thrombus; the leaflets were then freeze dried.

Lyophillized tissue specimens were ground to a coarse powder over

liquid nitrogen. 2N KOH hydrolysis (which circumvents decarboxylation

of Gla to glutamic acid) of the powder aliquots was carried out at

110°C for 24 hours for the detection of Gla as previously published [12]

The presence of Gla was confirmed by 6 N HC1 decarboxylation of the

apparent Gla peak, with resultant formation of glutamic acid. 6 N HC1

hydrolysis of separate powder aliquots was performed at 110°C for 24

hours for total amino acid analysis (using a Beckman Spinco 12 1M amino

acid analyzer) , and for calcium content by atomic absorption spectroscopy (using a Perkin Elmer Model 603) . Tissue protein content

was computed from total amino acid content. O-phosphoserine amino

acid analysis was performed and calculated as previously described for

bone extracts [ 13] . The lower limit of sensitivity for amino acid

analysis in our laboratory is 10 picomoles with ninhydrin peak

variation (in triplicate) of less than 2% [12].

3. Results

3.1 Clinical aspects

At our institution, porcine xenograft failure was always

associated with valvar mineralization. As presented in Table I, a marked age effect was noted with all cases of calcific valve

failure occurring in patients receiving prostheses before the age of

15 years (8 of 14 cases). Of the 11 patients over the age of 15 at
prothesis insertion, none have calcified xenografts (follow up range

21 to 50 months). Clinical data presented in table I indicate that

valve size in general was more than adequate and probably not a factor in valve calcification. Furthermore, valve mineralization

resulted in valvar stenosis or regurgitation, regardless of valve

size or age.

Table I

Calcific Xenograft Failure - Clinical Parameters

Case

No.

Age at

Implant (y

)

Body

Surface

Area (m^)

vaive

Size

(mm)

oite Duration

in Place

(mos)

Diagnosis at

Retrieval

1 3 7/12 . 6 23 Mitral 22 regurgitation

(Mi)

2 6 3/12 .6 27 Mi 42 stenosis

3 10 7/12 1.0 31 Mi 36 regurgitation

4 10 8/12 1.0 27 Mi 34 stenosis

5 10 9/12 0.9 27 Mi 34 regurgitation

6 12 4/12 1.1 29 Mi 49 regurgitation

7 14 3/12 1.4 25 Aortic 32 stenosis

8 14 6/12 1.2 29 Mi 64 stenosis

Complete analysis of our clinical data also indicated that the sex of the patients was not a determinant of valve failure, and that

those patients without valvar mineralization at the time of the study

had valves in the same size range as patients with calcific valvar

degeneration.

3.2 Biochemical aspects

Gla was present in all calcified porcine xenografts suitable for

analysis (N=6) and was not present in fresh porcine aortic valves and

in nonimplanted glutaraldehyde preserved porcine aortic valves

(table II and figure 2). As Figure 2 indicates, Gla content appears

to be related to valvar calcium, and the relative amounts of protein

bound Gla present were comparable to those found in calcific aortic

stenosis and in a case of aortic valve homograft calcification. No

Gla was detectable in normal human aortic valves, or in noncalcified

valve tissue from patients with congenital aortic stenosis.

342
20

GLA

nmol/mg Protein

10-

o

o

0 10,000 20,000 30,000

Ca++ (nmol/mg Protein)

© Calcific Aortic Stenosis

it Aortic Homograft * Porcine Xenograft

Figure 2 . Aortic valve Gla and Ca++ content

Amino acid analysis for hydroxyproline (Hyp) as well as specialized O-phosphoserine (P-Ser) determinations are also presented

in table II. As evidenced by the hydroxyproline level [14], calcified

glutaraldehyde preserved porcine xenograft valves exhibited markedly

lower relative collagen content than does either the fresh prosthetic

material or human valves. Furthermore, high levels of O-phosphoserine

also occurred in the calcifed xenografts at levels comparable to those

found in calcified human aortic stenosis leaflets.

343
Table II

Comparative Amino Acid Analysis and Calcium Content

in Human and Porcine-Xenograft Valves

Tissue No. of Ca++ (NM/mg Gla (NM/mg P-Ser (res/ Hyp (res/

Diagnosis Valves Protein) Protein) lOOOaa)* lOOOaa)

Fresh Porcine 1 146 0.0 - 94

Aortic Valve

Nonimplanted 2 108-133 0.0 .35-. 60 94-99

Xenograft

Normal Human 2 36-164 0.0 .40-. 59 44-92

Aortic Valve

Calcific Aortic Stenosis2080-16197 2.0-10.6 3.9-5.9 42-88

Calcified Aor- 1 tic Valve

Homograf

t

9180 4.2 66

Calcified

Porcine

Xenograft

7527-30441 4.3-18.3 4.0-9.3 14.1-36.7

* res/lOOOaa = residues/ 1000 amino acids

4. Discussion

The results of the present study indicate that proteins containing

the vitamin K-dependent calcium binding amino acid, Gla, occur at high

levels in the pathologic calcifications associated with porcine xenograft

valve failure. The role of vitamin K-dependent processes in mineralization, both normal and pathologic, is currently being elucidated.

In bone, a unique Gla containing protein, known as osteocalcin,

has been discovered [10] . The function of osteocalcin is not as yet

clear., but work to date suggests that this protein serves as a regulator of normal mineralization [15,16]. Osteocalcin biosynthesis in

bone has been shown to occur i_n situ as a vitamin K-dependent process

[15] . Warfarin anticoagulant therapy has been shown in experimental

animals to result in suppression of Gla synthesis in osteocalcin with

resulting associated diminished bone density! 16]. Levy, Lian, and Gallop

have recently isolated a new Gla containing protein called atherocalcin from calcified human atherosclerotic plaque [J.1] . Partial

characterization of atherocalcin indicates that it has a molecular

weight of about 80, 000,and an amino acid composition and charge

distinctly different from other known Gla containing proteins of

human origin. Furthermore, increased levels of Gla and hence

344
atherocalcin occurred in atherosclerotic lesions of increasing severity

[11]; these results suggest that atherocalcin may play a role in the

pathologic progression of atherosclerotic lesions. It may be that

atherocalcin or related proteins occur in the mineralizing xenografts

and work is in progress to establish the functional role of Gla

containing proteins in this type of cardiovacular calcification.

The clinical observation that age at implantation is a crucial

determinant of subsequent xenograft mineralization may be interrelated to a number of developmental considerations concerning

normal vitamin K metabolism and other endocrinologic factors.

Gundberg et al [17] have shown that Gla metabolism as evidenced

by urinary Gla excretion is markedly elevated in younger children

and decreases with age to adult levels by age 14 to 16 years. This

observation together with the present data suggests that younger

children may be more prone to the induction of vitamin K-dependent

pathologic mineralization since their vitamin K metabolism is

normally occurring at a higher level. Furthermore, serum phosphorus

is also significantly higher in younger children and decreases steadily

to adult levels by about age 15 years [18] . It may be that there is some increased mineral deposition secondary to the higher phosphate

in the younger children, making them more prone to precipitate mineral

at nucleating sites. Work is now in progress to evaluate possible age

dependent effects in those patients at risk for porcine xenograft

calcification.

The presence of proteins containing O-phosphoserine in the

calcified xenograft leaflets and the associated observation of

diminished collagen content are of importance with respect to considerations of both valve mineralization, and ultimate durability.

O-phosphoserine occurs in phosphoproteins of dentin and bone, and has

been thought to occur at nucleating sites of hydroxyappatite deposition [13] » O-phosphoserine may serve a similar function in xenograft

mineralization. In fact, the levels of O-phosphoserine found in the

calcified valves reported in the present work are comparable to what

one finds in bone [13] , and suggest that mineral deposition occurring

in cardiac valves takes place as an ordered process with some important

similarities to bone mineralization. Unlike bone, however, relative

amounts of collagen in the mineralizing xenograft valves are diminished compared to normal porcine aortic leaflets. This biochemical observation agrees well with the ultrastructural observations

of Ferrans et al [4] of marked disruption of collagen fibrils with

time, occurring in glutaraldehyde preserved porcine xenograft valves.

These findings, plus the present data, suggest that associated with

valvar calcium depositions, there may be significant deterioration in

the tensile strength of the xenograft due to collagen degradation.

In conclusion, the present study has provided evidence that

the mineralization of glutaraldehyde preserved porcine xenograft valves

occurs in association with the deposition of vitamin K-dependent,

calcium binding proteins in the valve leaflets. We have also demonstrated the associated presence of protein bound O-phosphoserine,

which may serve as a nucleating site. Finally, there is also associated

345
a marked diminution of valvar collagen in the mineralizing leaflets , indicating a probable deterioration in strength due to reduction of

this principle structural protein of valves. Furthermore, there is an overriding age effect, with calcific valve failure occurring only in

recipients younger than 15 years, suggesting an age dependent endocrine

interaction.lt may be that Gla protein synthesis is a crucial regulator

for the entire pathologic process, and that the use of vitamin Kantagonists such as warfarin or related drugs, either in valve

preparation or therapeutically, could be of benefit.

This work was supported by NIH grants, HL05606, HL24463, and DE0461.

The authors wish to thank John A. Zenker for his expert technical

assistance, and Barbara Cesaro for the preparation of the manuscript.

We also wish to thank Drs. Judith Levy, Paul Gallop and William Bernhard

for valuable discussions.
References

[ I] Sanders, S.P., Levy, R. J. , Freed, M.D. , Norwood, W.I. , and

Castaneda, A.R. , Use of Hancock porcine xenografts in children and adolescents, Am. J. Cardiol, (in press)

[2] Kutsche, L. , Oyer, P., Shumway, N. , Baum, D. , An important

complication of Hancock mitral valve replacement in children

Circ. 60 (Suppl I), 98-103 (1979).

[3] Fishbein, M. , Gissen, S.A., Collins, J., Barsamian, G.M.

and Cohn, L.H. , Pathology in patients with glutaraldehydefixed porcine cardiac valves, Am. J. Cardiol. _39_, 331-337

(1977)

[4] Ferrans, V.J. , Spray, T.L. , Billingham, M.E., and Roberts,

W.C. , Structural changes in glutaraldehyde-treated porcine

heterografts used as substitute cardiac valves, Am. J.

Cardiol. 41, 1159-1184 (1978).

[5] Lian, J.B., Skinner, M. , Glimcher, M.J., and Gallop, P.M.,

The presence of X -carboxyglutamic acid in the proteins

associated with ectopic calcification, Biochem. Biophys.

Res. Commun. 71, 349-355 (1976)

t6] Lian, J.B. , Prien, E.L. , Glimcher, M.J., and Gallop, P.M.,

The presence of protein bound ^"carboxyglutamic acid in

calcium containing renal calculi, J. Clin. Invest. 59 , 1151-1157 (1977) .

[7] Levy, R. J. , Zenker, J. A., and Lian, J.B., Vitamin K-dependent calcium binding proteins in aortic valve calcification,

J. Clin. Invest. 65, 563-566 (1980)

[3] Stenflo, J., Fernlund, P., Egan, W. , and Roepstorf, F.

Vitamin K-dependent modifications of glutamic acid residues

in prothrombin, Proc. Natl. Acad. Sci . U.S.A. 71, 2730-

2733 (1974)

[9] Suttie, J.W. , and Jackson, CM., Prothrombin structure,

activation, and biosynthesis, Physiol. Rev. 5_7, 1-70 (1977).

[ 10] Hauschka, P.V. , Lian, J.B. , and Gallop, P.M., Direct identification of the calcium binding amino acid, -carboxyglutamate in mineralized tissue, Proc. Natl. Acad. Sci. U.S.A.

7j2, 3925-3929 (1975) .

[II] Levy, R. J. , Lian, J.B., and Gallop, P.M., Atherocalcin , a Y -carboxyglutamic acid containing protein from atheroscler

otic plaque, Biochem. Biophys. Res. Commun. 91 , 41-49 (1979)

347
[12 ] Hauschka, P.V. , Quantitative determination of ){ -carboxyglutamic

acid in proteins, Anal. Biochem. 8(3, 212-223 (1977).

[13 ] Cohen-Solal, L. , Lian, J.B. , Kossiva, D. , and Glimcher, M.J.

,

The identification of O-phosphothreonine in the soluble non- collagenous bone matrix, F.E.B.S. Letters 89_, 107-110 (1978).

[14] Jackson, D.S., and Cleary, E.G., The determination of collagen

and elastin, Methods Biochem. Anal. 50_:25-76 (1967).

[15] Lian, J.B. , and Friedman, P.M., The vitamin K-dependent synthesis of q -carboxyglutamic acid by bone microsomes, J. Biol.

Chem. 253, 6623-6626 (1978)

.

[16] Lian, J.B. , Reit, B. , Roufousse, A.H., Glimcher M. J. , and

Gallop, P.M., Osteocalcin content in normal, rachitic, and

vitamin K-antagonized bone, Book, Vitamin K Metabolism and

Vitamin K-Dependent Proteins , J. W. Suttie, ed. , pp. 237-244

(University Park Press, Baltimore, MD, 1979).

[17] Gundberg, C.M. , Lian, J.B. , and Gallop, P.M., A new method for

the detection of -carboxyglutamic acid at the nanomole level.

Ibid , 153-156 .

[18] Harrison, H.E., The structural system: bone, Book, The Biologic

Basis of Pediatric Practice , R. E. Cooke, ed. , p. 136 (McGrawHill Inc., New York, NY, 1968).

348
PROSTHESIS - RELATED INFECTIONS

Patrick J. Parks, PhD. , M.D.

Case Western Reserve University

Department of Pathology

2085 Adelbert Road

Cleveland, Ohio 44106

Thirty-one patients with prosthesis related infections

have been identified. Seventeen patients treated for hydrocephalus with ventriculojugular, ventriculoatrial and

ventriculoperitoneal shunts exhibited bronchopneumonia and/

or evidence of septic emboli. An additional fourteen

patients had evidence of direct infection of prostheses.

In the latter group, histological examinations in con- junction with positive bacterial or fungal cultures was superior to either technique alone in confirming an infectious process. The causative organisms were similar

to those reported in other series on device-related infection, and are similar to those seen in immunosuppressed

patients.

1. Introduction

The significance of infections of indwelling devices, and the peculiarities associated with them, were demonstrated convincingly approximately 25 years ago by Elek and Conen (10) in their studies of Staphylococcal infections of sutures. Numerous reports document the role

of catheters on the development of bacterial disease, with more recent

studies considering their influence on the development of fungal

disease (14). The majority of studies relate to temporarily implanted

vascular catheters. The present study deals with retrieved implants

designed to be permanent and is part of The Implant Retrieval and

Analysis Program of The Institute of Pathology and Case Western Reserve

University.

2. Materials and Methods

The problem of prosthesis related infections has been divided into

two categories: (1) infections of target organs associated with devices

and (2) direct infections of the prostheses. The first category of

infection was approached by a retrospective analysis of polyethylene

ventriculojugular, ventriculoatrial, and ventriculoperitoneal shunts

used in the treatment of hydrocephalus.

The autopsy records of University Hospitals of Cleveland, Ohio

from 1954 to the present were reviewed, and 28 patients with ventricular

shunts of all types were recovered. The histopathology of the central

nervous system findings in the same group of patients has been the

subject of a separate report (19).
Additional prospective analyses were carried out on implants removed

at surgery or autopsy beginning circa 1976. In both groups of patients,

prosthesis-related infections were defined as present when (1) the tentative clinical diagnosis of prosthesis-related infection was made (e.g.

prosthetic valve endocarditis) and was verified by a positive bacterial

or fungal culture or (2) there were classical signs of infection (e.g.

fever) in the absence of positive bacterial or fungal cultures.

Histopathology was carried out using routine sectioning, preparation

and staining, with additional standard special stains used to detect

bacteria, fungi or parasites.

3. Results

3.1. Ventriculojugular, Ventriculoatrial and

Ventriculoperitoneal Shunts

The single greatest problem with ventriculojugular and ventriculoatrial shunts is continued thrombosis and thromboembolism with subsequent pulmonary infarction, pulmonary hypertension (6) and cor pulmonale.

Bronchopneumonia secondary to septic thromboembol i is an additional complicating factor. Seventeen of 28 patients with a ventriculojugular, ventriculoatrial, or ventriculoperitoneal shunt had bronchopneumonia (Table 1).

Of the 15 with pneumonia and a ventriculojugular or ventriculoatrial shunt,

two had cor pulmonale (Cases 11 and 17). Of the entire group of 17

patients with bronchopneumonia five had an associated ventriculitis, implying that the pulmonary infectious complications of ventriculojugular,

ventriculoatrial and ventriculoperitoneal shunts are independent of those

of the central nervous system. In only one case, Case 3, was there simultaneously obtained positive cultures made premortem on cerebrospinal fluid

and blood.

Case Time in Situ Months Type of Shunt Causative Organism

1 h V-J (1) * (2)

2 1 V-J *

3 \h V-P E. coli

4 1% V-J Nocardia Asteroides

5 2 V-J E. coli and Candida sp.

6 2H. V-J S. aureus, B-Hemolytic strep

7 3h V-J *

8 % V-J Proteus Mirabilis

9 7 V-J Proteus Mirabilis

10 14 V-J *

11 17 V-J * 12 24 V-J * 13 29 V-J Micro coccus sp.

14 39 V-P *

15 43 V-J E. coli

16 48 V-J *

17 72 V-J S. aureus

(1) V-J = Ventriculojugular, V-P = Ventriculoperitoneal

(2) * = No growth or mixed growth

Table 1. Pulmonary Infections Secondary to Ventricular Shunts

350
In eight of 17 patients there were either no positive cultures postmortem or there was a mixed growth of organisms. Failure to obtain a positive culture postmortem is most frequently the result of premortem

therapy with antibiotics. Such therapy may either eradicate the causative organism or prevent its growth postmortem. Mixed growths have been

attributed to the overgrowth of the normal gut flora.

In the remaining nine patients where either one or two organisms

grew in large numbers postmortem, four had their ventricular shunts in

place because of hydrocephalus secondary to a malignant process (Cases 4,

5,6,8). Since treatment of their malignancies included immunosuppressive

agents, it is unclear whether the shunt or the therapy predisposed to

infections by such unusual pathogens as Nocardia asteroides . In the

remaining five patients, (Cases 3,9,13,15,17) pneumonia was secondary to

the less frequently encountered lung pathogens such as Staphylococcu s aureus , Proteus mirabil is , E. col

as well as micrococcus sp. , usually

a nonpathogen.

3.2. Direct prosthesis infection

Definitive, positive bacteriological cultures were obtained in seven of 14 patients whose prostheses were removed since 1976 (Table 2).

Twelve of the 14 had a definitive diagnosis of an infectious process

when histological examination was coupled with isolates recovered on culture (Table 2).

3.3 Histopathology of infections

The histopathology within the lungs reflected the pneumonia superimposed on recurrent thromboembolism in all patients with ventriculojugular

shunts. Vegetations were present at the site of the fibrous capsule,

where the shunt entered the jugular vein or right atrium (figure la)*.

In several cases, septic embolization obviously had occurred, as indicated

by multiple, peripheral, pleural based abscesses (figure lb) and necrotizing bronchopneumonia foci (figure 1c). While septic emboli could not be

illustrated definitively in every case, the finding of pneumonia with

pulmonary emboli and/or vegetations was uniformly observed in all patients

with ventriculojugular shunts.

The bronchopneumonia secondary to Nocardia asteroides was unique, in as much as the organism is a fungus-like bacterium with a filamentous

structure (figure Id).

The histopathological changes observed in cases of direct infection

of prosthesis were of greater variability. In vascular prostheses the

causative bacterial organisms were in the lumens (figure 2a) and formed

septic thrombi (figure 2b). Fungal infections of vascular devices, on the

other hand, were located near the anastomoses with the natural blood

vessels, and tended to be on the adventitial surface rather than the

luminal surface.

* All figures appear at the end of the text.

35 1
Table 2

Type of Graft

Case

18 Vascular,

Expanded PTFE

19 Vascular,

Expanded PTFE

20 Total Hip

Replacement

21 Total Hip

Replacement

22 Total Knee

Replacement

23 V-P Shunt

24 Total Hip

Replacement

25 Prosthetic heart

valve, aortic

26 Vascular, dacron

27 Prosthetic Heart

valve, aortic

28 Prosthetic Heart

valve, mitral

29 Vascular, Expanded

PTFE

30 Vascular, dacron

31 Vascular, dacron

Direct Prosthesis Infections

Time in

Situ

7 Days

11 Days

2 Mos.

1 Yr.

2 Yrs.

2 Yrs.

4 Yrs.

4 Yrs.

6 Yrs.

9 Yrs.

10 Yrs.

Organisms

Isolated

(2)

E.Coli (5)

E. Col i (5)

Micrococcus

sp. (6)

S. Aureus (7)

S. Epidermidis

(7)

Streptococcus

Sal ivarius(7)

Organisms by

Histology

Mixed GM+ (1) Isolated budding

yeast

GM+ Cocci (3)

(4)

Aspergillus species

(4)

GM+ Cocci

Budding yeast

GM+ Cocci

Budding yeast

Bacteria in

Thrombus

(1) Culture from swab of adventitial tissue

(2) * = No growth

(3) GM+ = Positive on Gram stain

(4) No sections submitted

(5) Culture from hip aspirate

(6) Culture from valve vegetation

(7) Blood culture

352
In the two cases of orthopedic appliance infections where tissue sections

were submitted, only 1 case of fungal infection demonstrated an organism

(figures 2c and 2d). The presence of mycelial forms with septate hyphae,

with no apparent yeast forms, strongly implicates Aspergillus species

as the infecting agent.

The histopathology seen in the cases of prosthetic heart valves was

similar to that seen with infected ventriculojugular or ventriculoatrial

shunts. Friable microscopic vegetations consisted of disorganized

necrotic material, fibrin and occasional organisms.

4. Discussion

Although the numbers of patients with prosthesis-related or direct

prosthetic infections are small, the findings are of significance with

regard to the nature of the infecting organism and the detection of

infection. The frequent isolation of opportunistic organisms, such as Aspergillus , Nocardia , Micrococcus , and S. epidermidis suggests an underlying altered immune response in these individuals. The observed organisms,

as well as Proteus mirabilis may also be expected in patients that are severely immunocompromised (29).

Fungal infections, for example, have been observed in dialysis

patients (18), and in patients who are leukopenic secondary to immunosuppressive therapy. None of these patients, however, were leukopenic*

(White blood cell count less than 5000 cells per cubic millimeter), and

only four were on immunosuppressive therapy, thereby excluding an a priori

deficiency of immunocompetent cells. It is postulated that the prosthesis,

possibly through the induction of the fibrous capsule that is ubiquitous

in soft tissue interactions, leads to a "localized immunosuppression" at

the site of implantation. The absence of macrophages in the peri-prosthetic

inflammatory infiltrate suggests suppression of this population. The

absence of macrophages further suggests that suppression of this cell

population may partially account for the bacteriological findings.

Infections of prostheses have been divided into "early" and "late"

stages. The exact definition of early and late has been related to the

nature of the prosthesis. Early infections of prosthetic heart valves

are those occurring within three months of replacement, late infections

are those occurring beyond three months (9). Most (70%) infections of

ventriculoatrial, ventriculojugular and ventriculoperitoneal shunts were

apparent within two months (24) while a large fraction of orthopedic

prostheses infections occurred within the first year (11). Other clinical

studies have indicated that the types of organisms responsible are related

temporally to the time of prosthesis placement. In all types of prostheses,

Staphylococcus aureus or S_. epidermidis were the organisms most commonly

encountered in early infections. Late infections of prosthetic heart

valves were caused by streptococcal species, staphylococcal organisms,

and less frequently by other gram negative bacteria and fungal organisms

(2,9). The incidence of streptococcal infection reflects the condition

seen in the endocarditis of natural tissue heart valves. Staphylococcus

353
aureus was also the most frequent cause of early infection of prosthetic

hips and of ventricular shunts (24) while late infections of prosthetic

hips and ventricular shunts involved gram negative bacteria, anaerobes

and aerobes of low virulence. Anaerobic bacteria present a major

technical problem of isolation. To date, anaerobic infection has been

rare, (possibly reflecting the technical difficulties!) and in prosthetic hip replacements has included gram positive organisms (15) in

contrast to the usual clinical anaerobic infection (27).

The early infections correspond to the early phase of wound healing.

The difference in organisms causing late infections implies a difference

in innate reactivity of the material (12) or in a conditioning of the

protein coat adherent to devices placed within the blood stream and soft

tissues (4,22). Such conditioning has been implicated in experimental

studies of bacterial adherence to various solid substrates (8,26) and

in experimental vascular graft infections where the "protein coat" forms

the neointima (23).

In the present study the organisms responsible for infection did

not fit easily into the prescribed pattern of "early" or "late"

infections. It is unclear why this occurred, but may reflect a sampling

bias or may be the result of too few cases.

In addition to temporal considerations, there appears to be at

least two mechanisms of prosthesis infection. The first mechanism is

the direct ingress of the organisms onto the prosthesis at the time of

surgery. The direct introduction of organisms has been used to explain

early endocarditis caused by Staphylococcal species (9,11) and late

"delayed" infections of prosthetic hip replacements (11). Direct invasion

would appear to be the mechanism of Aspergillus sp. infection in Case 21 (25). A second route of importance, especially in orthopedic appliances,

is the hematogenous spread of organisms from another site. Staphylococcus

aureus infection of decubitus ulcers in Case 17 preceded the septic pulmonary infarcts. Similarly in Cases 20 and 24 an E. col

i

urinary tract

infection preceded E. col

i

infection of the total Fip replacement.

Hematogenously carried organisms have been responsible for infections

caused by S. epidermidis (3), and for infections of orthopedic devices by

Mycobacterium fortuitum (7), M. tuberculosis (17), among others (1,16).

Affirmation of direct prosthesis infection by bacteriological means

was encumbered by the manner in which the prosthesis was infected. Routine

swabs of the peri prosthetic regions and/or wound sites were made. However, as evidenced by the infections of the expanded polytetrafluoroethylene grafts, the process began on the luminal surface. Although the

bacteria were observed "percolating" through the pores, apparently none made it to the adventitial surface where the culture was taken. Similarly,

small colonies of yeast at the junction of the prosthesis and natural

vessel would be unlikely isolates of a random swab of the periprosthetic

area.

354
Further complicating the assessment of infection was the paucity

of clinical signs and symptoms. Fever was present only in five of 14

patients with direct prosthesis infection. Two of these, Cases 20 and

24, had urinary tract infections prior to the onset of prosthesis

infections and in two others, Cases 22 and 23,-^0 positive cultures were

made. Leukocytosis (more than 10,000 cells mm ) was present in less

than half of the patients with direct prosthesis infection. In several

cases, the erythrocyte sedimentation rate (ESR) was measured, and was elevated above the range of normal in all cases where it was recorded.

The ESR is a useful indicator of acute inflammation, reflecting the

levels of fibrinogen as an acute phase reactant. The ESR is subject

to many variables, and in future studies, quantitative levels of

C-reactive protein (4) may provide better clues regarding prosthesisrelated infections.

In summary, infections of prosthetic devices cause disease by

direct infection, leading to failure of the device, and in the case of

intravascular devices, to dissemination of the organisms throughout

the body. The infections in the present study are similar to previous

reports in as much as usually avirulent or low virulence organisms were

responsible. Studies on the effect of material on bacterial growth and

bacterial inhibiting properties of cells and serum are indicated and

have apparently begun (20). An associated problem of isolation and

confirmation of infection may require new culture techniques and new

ancillary tests (13,28).

Acknowledgments

The author would like to acknowledge first the continued interactions with Dr. Donald F. Gibbons, Director of the Implant Retrieval

Service at Case Western Reserve University, Institute of Pathology and

second, useful conversations and the critical review of the manuscript

by Dr. Joseph F. Tomashefski, Jr.

The author would like to thank Ms. Mary E. Johnson for typing the

manuscript.

355
References

(1) Ahlberg, A., Carlsson, A.S. and Lindberg, L. Hematogenous Infection in Total Joint Replacement.

Clin. Orthop. Rel . Res. 137:69, 1978

(2) Alexander, W. J., Mowry, R.W., Cobbs, C.6. and Disnukes, W.E.

Prosthetic Valve Endocarditis Caused by Histoplasma Capsulatum . J. Amer. Med. Assoc. 242:1399, 1979

(3) Archer, 6. L. , Tenenbaum, M.J., and Haywood, H. B., Rifampin

Therapy of Staphylococcus Epidermidis. Use in Infections from

Indwelling Artificial Devices. J. Amer. Med. Assoc. 240: 751,

1978

(4) Aronsen, K.F. , Ekelund, G. , Kindmark, CO., and Lauren, C.B.

Sequential changes of plasma proteins after surgical trauma.

Scand. J. Clin. Lab. Invest. 29: Suppl 124, 127, 1972

(5) Bagnall , R.D., An Approach to the Soft Tissue/Synthetic Material

Interface. J. Biomed. Mater. Res. 11:939, 1977

(6) Barnard, P. J., Pulmonary Arteriosclerosis and Cor Pulmonale Due

to Recurrent Thromboembolism. Circulation 10: 343, 1954

(7) Booth, J.E., Jacobson, J. A., Kurrus, T.A., and Edwards, T.W.

Infection of Prosthetic Arthroplasty by Mycobacterium Fortuitum

J. Bone Joint Surg. 61A:300, 1979

(8) Dexter, S.C., Influence of Substratum Critical Surface Tension on Bacterial Adhesion-in-Situ Studies. J. Colloid Interface Sci

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70:346, 1979

(9) Dismukes, W.E., Karchmer, A.W., Buckley, M.J., Austen, W.G. and

Swartz, M.N., Prosthetic Valve Endocarditis, Analysis of 38 Cases.

Circulation 48: 365, 1973

(10) Elek, S.D. and Conen, P.E., The Virulence of Staphylococcus Pyogenes

for Man. A Study of the Problems of Wound Infection. Br. J. Exp.

Pathol. 38: 573, 1957

(11) Fitzgerald, R.H. and Kelly, P.J., Total Joint Arthroplasty. Biologic

Causes of Failure. Mayo Clin. Proc. 54: 590, 1979

(12) Gristina, A.G., Rovere, G.D., Shoji, H., and Nicastro, J.F.

An in Vitro Study of Bacterial Response to Inert and Reactive Metals

and to Methyl Methacrylate. J. Biomed. Mater. Res. 10:273, 1976

(13) Kagan, R.L., Scheutte, W.H., Ziendt, C.H., and MacLowry, J.D.

Rapid Automated Diagnosis of Bacteremia by Impedance Detection.

J. Clin. Microbiol. 5: 51, 1977

356
Klein, J.J. and Watanakunakorn, C. , Hospital-Acquired Fungemia.

Its Natural Course and Clinical Significance. Am. J. Med. 67:

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Kaumme, C, Lidgren, L. , and Mardh, P. A., Anaerobic Bacteria in

Late Infections After Total Hip Arthroplasty. Scand. J. Infect.

Dis. 6:161 , 1974

Lattimer, G.L., Keblish, P. A., Dickson, T.B., Vernick, C.G. and

Finnegan, W.J., Hematogenous Infection in Total Joint Replacement.

Recommendations for Prophylactic Antibiotics. J. Amer. Med.

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McCullough, C.J., Tuberculosis as a Late Complication of Total

Hip Replacement. Acta Orthop. Scand. 48: 508, 1977

Onorato, I.M. , Axelrod, J.L., Lorch, J. A., Brensilver, J.M. and

Bokkenheuser, V. Fungal Infections of Dialysis Fistulae

Ann. Intern. Med. 91: 50, 1979

Parks, P.J. and Roessmann, U., to be published

Petty, W., The Effect of Methylmethacryl ate on the Bacterial

Inhibiting Properties of Normal Human Serum. Clin. Orthop.

Rel. Res. 132: 266, 1978

Rao, P.S., Molthan, M.E. and Lipow, H.W., Cor pulmonale as a com- plication of ventriculoatrial shunts. J. Neurosurg. 33: 221, 1970

Rigdon, R.H., Plastics and Inflammation: An in vivo Experimental

Study. J. Biomed. Mater. Res. 8: 97, 1974

Poon, A.J.,Malone, J.M., Moore, W.S., Bean, B. and Campagna, G. Bacteremic Infectabil ity : A Function of Vascular Graft Material

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cerebrospinal fluid shunts: Epidemiology, clinical manifestations,

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Opportunistic Myocotic Osteomyelitis: Bone Infections Due to

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(28) Wheat, L.J., Luft, F.C., Tabbarah, Z. , Kohler, R.B. and White, A. Serologic Diagnosis of Access Device - Related Staphylococcal

Bacteremia. Am. J. Med. 67: 603, 1979

(29) Winston, D.J., Gale, R.P., Meyer, D.V., Young, L.S., and UCLA

Bone Marrow Transplantation Group. Infections Complications of

Human Bone Marrow Transplantation. Medicine 58: 1, 1979

35 8
Figure la. Pulmonary infections complications of ventricular shunts

Micrococcal vegetation on fibrous capsule surrounding

jugular portion of V-J shunt. H&E, 100X.

359
Figure lc. Pulmonary infections complications of ventricular shunts

Necrotizing bronchopneumonia, H&E, 40X.

360
Figure 2a. Direct prosthesis infections.

Septic thrombus, H&E, 40X.

Figure 2b. Direct prosthesis infections.

Septic thrombus of expanded PTFE, B&B, 100X.

361
Figure 2c. Direct prosthesis infections.

Aspergillus species in necrotic tissue adjacent to

prosthetic hip replacement, GMS, 40X.

362
STUDY OF 208 EXPLANTED BIOPROSTHESIS

DISTRIBUTION OF DYSFUNCTION PATTERNS AND ASSESSMENT

OF DURABILITY AT 10 YEARS OF USE

R. C. QUIJANO

HANCOCK Laboratories Incorporated

4633 E. La Palma

Anaheim, Ca. 92807

As the HANCOCK* bioprosthesis completed 10 years of clinical use

as a human valvular substitute, specific dysfunction patterns have

become evident in a very small percentage of the xenografts. Simultaneously, the durability or longevity of this porcine derived material

extending over this period has been questioned. Studies at this

laboratory have addressed both phenomena: dysfunction and durability of

these bioprostheses. An explanted valve retrieval program has been

ongoing at HANCOCK Laboratories Inc. for the past eight years and the

observations and studies generated are the subject of this paper. A

total of 208 explanted valves are analyzed and reported. The distribution of the modes of dysfunction show they may be due mainly to:

1) two distinct forms of mineralization, 2) unhealed prosthetic valvular endocarditis, 3) early uncomplicated thrombosis, and other minor

reasons. A statistical breakdown for each occurrence is given.

Physical and biochemical studies on excised valves returned in nonfixative solutions give clues as to the nature of interstitium material

reported elsewhere to be products of valve material degeneration. Together the findings indicate that the HANCOCK* bioprosthesis demonstrates

conservation of intrinsic pre-implant characteristics for up to 100

months in vivo , and a longer projected prosthetic durability in the

absence of extrinsic factors.

1. Introduction

Over the past decade, continuous research and development and the

support of a unique technology at HANCOCK Laboratories Inc., has re- sulted in a clinically proven widely accepted bioprosthesis, the

HANCOCK* Stabilized Gl utaral dehyde Process porcine aortic heart valve

mounted on a flexible stent ft] 1. Clinical acceptance is evidenced by

the nearly exponential increase of its use as a human valvular substititute and the long term clinical experience at numerous institutions

throughout the world where it has become the valve of choice. Estimates at present (fig. 1), conservative as they may be, set the number

of these valves used in replacement at well over 60,000.

1. Figures in brackets indicate the literature references at the end

of this paper.

TRADEMARK

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This estimate is presented only to provide context and perspective while examining the explanted valve population reviewed in this

report.

Three types of prostheses: aortic valves, atrioventricular valves

and valved conduits (figs. 2A, B, C) have been used, though the process

is chemically the same in all cases and starts from the same material:

the porcine aortic valve.

It must be realized that while a large number of implant-patient

years and impressive actuarial outlook C2 ,3,4,5,6,7,8,9,10,11 J , for

patient survival are important in determining the benefits of a tissue

bioprosthesi s , the surgeon, cardiologist and patient need and deserve

to be made aware of the individual outlook or predictability with

respect to implant duration and possible dysfunction. Thus, this

report presents information obtained from the Clinical Valve Explant

Retrieval Program conducted in this laboratory since 1974. It is felt

that clinical users of this bioprosthesi s will derive important information concerning the efficacy and predictability of the valve,

especially with regard to its dysfunction and durability.

2. The Explanted Valve Retrieval Protocol

When released from the manufacturing laboratory, the clinical grade

valve possesses characteristics designed towards proper functionality

and durability in its intended position. Care is taken during the

Stabilized Gl utaraldehyde Process to preserve collagenous components as well as the elastic lamina which forms the blood contact interphase, as it is believed that this preservation results in the reported low

thrombogenic potential of this bioprosthesi s.

2.1 The explanted bioprosthesis

The explanted bioprosthesis represents an invaluable source of

research material. Only through an objective comparison is the ex- planted valve with characteristics present before implant which are docu

mented photographically through the manufacturing process, coupled

with patient parameters received from implanting and retrieving centers

can valuable information be derived. Patient history includes 1) reason

for initial valvular replacement, 2) intra- and postoperative course,

3) reason for extirpation and 4) patient age, sex, valve position,

physiological profile, etc. Additionally, a complete analysis of the

explanted bioprosthesis will include physical, biochemical, structural

and ultrastructural and microbiological observations in this laboratory.

The information thus obtained may be used to begin assessment of the

possible causes of dysfunction as well as of the projected durability

or longevity of this bioprosthesis.

To date about 300 explanted bioprostheses have been received at

HANCOCK Laboratories. While this does not represent the entire pop3G4
ulation of expl anted HANCOCK valves, discussions with various major

centers throughout the world suggest that this represents a substantial fraction of the total explanted valve population.

2.2 Methods

Explanted valves are received in two types of sterile solutions.

The majority of valves implanted for less than five years may be re- turned in 10% buffered formalin or any other buffered fixative. Those

valves having implant duration longer than five years are preferably

received in cold, sterile saline or balanced electrolyte (5-15°C) sealed

container packed in ice (not frozen). The latter are not exposed to

fixative since some of our studies require that the valve be in as close

a condition as it was in the physiological environment, and that it

arrives within 18 hours from the time of excision. Valves in fixative

may be mailed. This protocol is also used for valves explanted from

animal studies (canine MVR).

When the valve is received in the laboratory, it is assigned a study number for identification, and a file is opened for each individual bioprosthesis.

If it arrived in saline, it is routed immediately through the

Microbiological Laboratory where seals and solution are carefully

studied to determine if contamination or infection is present. In some instances its hydrodynamic characteristics are determined in the

Flow Testing Laboratory. All explants proceed through the Histopathology and Electron Microscopy Laboratories. The Chemistry Laboratory

will qualify and quantify the nature and concentration of the shipping

solution. Routing of the valve is illustrated in figure 3.

Following gross anatomical description of valve and components, as well as gross photography of both inflow and outflow aspects of the

valve, the pathologist indicates the plane and morphological location

of sections for study in the map in figure 4, indicated by the gross

morphology. Sections are stained by various techniques always including

hematoxylin-eosin (HE), von Kossa (vK) Gramm (G) and Acid-Fast (AF)

stains. In many instances, tissue may be processed for transmission

electron microscopy.

Complete light microscopic description of each section is obtained and light micrographs of representative sections are included

in the bioprosthesis file.

The explanted bioprosthesis file is considered complete only when

all observations and descriptions are gathered and a final report is

generated. This report may be used to provide periodic information

to those centers retrieving the valves.
3, Results

The entire explanted valve population, intitally consisting of

180 valves and later updated to 208 valves was categorized principally by etiology of the dysfunction involved necessitating extirpation.

This analysis made use of the patient's medical and surgical history

and all observations on the bioprosthesis as outlined above.

A summary of the number of these bioprostheses by position and

implant duration is shown in figure 5. Each vertical bar represents

the number of valves retrieved within the interval, i.e. the first bar

represents valves retrieved from a few hours after operation up to the

end of the first twelve months, etc.

This figure indicates that nearly 40% of all valves in the study were removed within one year of implant time. The first three categories will indicate that most of these bioprostheses were removed

for truly non-dysfunctional or non-valve related reasons.

3.1 Non-valvular related removal

Thirty five of 180 (19.4%) explants were removed for reasons not

directly related to valve dysfunction. Chief reasons for this category

were: patient death not due to valve dysfunction, outgrown by the

patient of non growing valve as happens with youngsters, missizing,

degenerative aortic roots, peri valvular leaks, and disease other than

valvular disease, i.e. carcinoma, death, etc. In nearly all cases,

valve characteristics were almost identical to preimplant specimens.

Figure 6 A shows the time course of removal category, and figure 6 B shows a gross photograph of a 92 month (7 years, 8 months) explant ex- cised because of a degenerative aortic root. Examination showed this

valve was well conserved in all aspects.

3.2 Unknown etiology

In this category are grouped valves which were removed and sent to our laboratory with no more data than implant and explant dates. No

obvious defects were noticed and all these bioprostheses had characteristics similar to preimplant valves and could not be assigned to any

other category. The time course of retrieval is illustrated in figure

7 A and an example of this type valve received within the heart sent to

us is shown in figure 7 B.

3.3 Endocarditis

Seventeen percent of the explanted population (31/180) were re- moved at the time the patient was experiencing acute, subacute or chronic infective endocarditis without healing. In some instances there

was involvement of the bioprostheses. Figure 8 A shows the chronology

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of removal and figure 8 B is a photograph of a valve removed at 6 months

because of this occurrence.

3.4 Mineralization

One major alteration in the functional morphology of the porcine

heterograft is associated with mineralization or calcification. Of

the explants reported here, 83 valves (46%) were removed at some stage

of mineralization. Careful analysis of all these explants indicates

that functionally significant calcification occurs as a result of

various phenomena categorized by two rather distinct patterns of salt

deposition.

3.4.1 Extrinsic mineralization

This form of calcification appears to be usually associated with

a previous episode of infective bacterial or thrombotic endocarditis.

This pattern represents 23% (42/180) of the entire explanted valve population discussed here. For this population, the time course of re- moval is illustrated in figure 9 A. No distinction can be made by

sex, age, or position of valve implantation and the frequency of this occurrence.

Leaflet surfaces are commonly filled with dense mineralized

verrucous deposits (fig. 9 B) which can often be peeled off, leaving

underneath a leaflet which, in crossection, appears histologically and

architecturally intact (fig. 9 C), the fibrinous material on the surface showing positive von Kossa (black) material indicative of calcific

deposits.

3.4.2 Intrinsic mineralization

We have observed a totally distinct form of mineralization which,

by its mode of occurrence, we have termed "intrinsic mineralization" or fibrocalcification. Intrinsic mineralization is characterized by

calcific deposits WITHIN the valvular or leaflet structures. Of the

total calcific population, one-half appears to occur in this manner re- presenting 23% (41) of the total explants studied. The time frame of

extirpation is shown in figure 10. A. This form of calcific deposition

exhibits differences in rate of occurrence related to the age of the

recipient. In children at-risk, (patients under 20 years of age) if it

happens, it will do so early. For adults at-risk, there is no specific

chronology, but it seems that in those prone to calcify the bioprosthesis

in this manner, the occurrence may be related to length of implantation;

the probability thus, being higher the longer the implant duration.

However, no all patients, children or adults, will calcify the porcine

heterograft.

3G7
Figure 10 B illustrates the typical picture of this occurrence in

its intermediate stages. Subsurface nodules are evident which resulted

from the idiopathic calcification of the fibrous collagenous bundles near the attachment of the leaflet to the aortic wall. With time, this

calcification may proceed from initial nidi to disruption of leaflet

collagenous tissue, though the surfaces may not be initially affected

(figs. 10 C, D, E).

3.5 Thrombus

A significant benefit of the HANCOCK* bioprosthesis is its low

thrombogenic potential, the management of the majority of patients

without long term anticoagulation or embolic penalty. Valves removed

because of thrombotic episodes represent 4.5% (8) of the expl anted

valve population in this report and their removal chronology is given

in figure 11 A. None of these demonstrated obvious etiology in terms

of alterations to histological architecture or leaflet surface appearance at both LM or EM levels. Figure 11 B shows a histological

section of a leaflet on whose surface a massive thrombus can be observed.

3.6 Primary tissue dysfunction

This phenomenon, tears of unknown etiology, represents less than

27o of the explanted valve population (fig. 12 A). Valves in this category typically have one or more leaflet tears or punctures which, at

present, appear to show no correlation with implant duration or any

other cause. With the exception of this fact, the bioprostheses present

excellent histological architecture and grossly normal appearance

(fig. 12 B). Light microscopy (fig. 12 C) at and near the tear site

presents well defined tissue discontinuities with total absence of degeneration of surrounding collagenous tissue. Iatrogenic tears were excluded on the basis of surgical notes; tears secondary to calcification or bacterial activity were likewise excluded.

4. Summary

The data described above is summarized in figure 13. Late update

from 180 to 208 explanted valves indicates that there are no drastic

changes in the distribution of dysfunction patterns found for the

bioprostheses retrieved and accumulated in this laboratory. Table I illustrates the results obtained after the addition of 28 explants.

5. Durability of the HANCOCK* Bioprosthesis

The long term success of glutaraldehyde process porcine aortic

valves utilized for human valvular replacement depends upon various

368
extrinsic and intrinsic factors. The former, as described aboye,

are primarily associated with phenomena related to cardiac function,

sepsis, healing, and metabolic conditions. The latter are closely

associated with conservation of the underlying constituents as a consequence of preservation by processes and resistance to continued

deleterious host-graft interactions.

In the native condition, the functionally significant anatomic

regions of the various valvular structures are composed primarily of

collagen in association with non-fibrous components consisting mainly

of mucopolysaccharides and glycoproteins. The HANCOCK process, eliminates the majority of non-fibrous components along with much of the

cellular constituents. Except for the aortic wall and some regions

of the inflow aspect, which exhibit a rather significant elastic com- ponent, the resulting bioprosthesis is mainly composed of collagen.

Collagen is one of the few biological entities whose molecular

structure both explains and is reflected by its observable ultrastructure. Maintenance of the fiber structure, either by turnover,

repair or inherent stability most certainly is requisite for biologic

or functional competency, and continued conservation of the fiber con- figuration would also seem logical exigencies for in vivo prosthetic

function

Recently studies have investigated the fate of gl utaraldehyde

processed collagen in vivo T28 1 . Moreover, the studies were concerned

with durability of tissue prostheses as a function of collagen fiber degeneration. The authors indicate that shortly after prosthetic implantations in humans, valvular collagen begins to undergo morphologic degradative alterations. They further indicate that these changes relate

to durability and, therefore, potentiate prosthetic dysfunction. That

is, the ultimate fate of tissue prostheses must be intimately associated with the rate and chronology of these events.

Their conclusions are partially dependent on the appearance shortly

after implantation (as early as 28 days) of a granular electron dense

material associated with collagen fibers and permeating the interstitium.

This phenomenon is interpreted as representing the onset and, with time,

continued collagen disintegration. A blurring or focal loss of the

characteristic crossbanding pattern of collagen was also noted accompanying or preceding fiber disruption.

Should these precipitous changes occur, degradation of glutaraldehyde fixed collagen must certainly be related to the efficacy of the

tanning process. The exact mechanism of gl utaraldehyde preservation

has not yet been elucidated, but it is reasonable to assume that ultrastructural conservation is dependent upon "mechanical" cross! inking by

single or polymerized gl utaraldehyde molecules. Thus, the loss or preservation would be reflected in the results from various physiochemical

studies designed to evaluate their failure or diminution.

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5,1 Studies on long-term implants

The preservation of the tissue components of HANCOCK valves implanted for extended periods of time has been the subject of continuous

study by this laboratory since the early stages of success of this

bioprosthesi s. Analysis of these components by various physical, biochemical and microscopical means is used to partially asses the durability and to begin projection of the longevity of this bioprosthesi s.

5.1.1 Histological comparisons

Careful observations of diverse areas of valvular tissues obtained

from explants ranging from 2 years to 5 years, 10 months, compared to

preimplant specimens showed that no difference in morphology is observable at the light microscopic level. Figures 14 A and B are photographs of a valve implanted for 5 years, 10 months from inflow and outflow aspects. The sections in figure 14 C represent regions of the

valve known to be under continuous physiological stress. No significant

alterations were noted at gross histological levels when these tissues were compared with tissue from preimplant valves.

5.1.2 Shrinkage temperature

Shrinkage temperature has been shown to reflect the degree of collagen crossl inking by aldehydes [j?7]. The shrinkage temperatures of

explanted valves returned in cold sterile saline and having no contact

with any fixative solution, were determined. Figure 15 shows the distribution of temperatures observed and the best fit curve obtained from

these results. More data is being incorporated to extend this line to

encompass valves retrieved up to nine years implantation time.

5.1.3 Disruption, enzyme and electron microscopy studies

Tissue for the various studies was obtained from three Hancock

porcine heterograft valve prostheses (three patients) explanted at re- operation for valvular replacement. Implant duration for the three

prostheses was 34, 92, and 100 months. The 92 month implant was re- placed because of a degenerative aortic root; the other two valves were explanted because of intrinsic prosthetic mineralization. The explants

were received in cold saline and had not been exposed to any form of

fixation subsequent to explantation. Pieces of tissues (1 mm x 1 mm) were removed from the valve leaflets, rinsed in saline, and either in

2.5% .1 M cacodvlate buffered glutaraldehyde (untreated controls) or retained for enzyme and disruption studies.

5.1.3.1

Pieces of leaflet tissue were incubated with continuous shaking

370
in 5 ml of a 4 M guanidine HC1 solution adjusted to pH 7,5 with Tris

base. Similarly treated unfixed and gl utaraldehyde processed unimplanted leaflet tissues served as controls.

Up to four pieces of tissue were incubated for 24 hours at 25°C

with constant orbital shaking in a 50 mM Tris buffered (pH 7.5) trypsin

solution containing 10 mM CaCl2- Pieces of explant tissue were also

incubated in the buffer CaCl2 solution without enzyme. When collagenase

was used the concentration of enzyme was 1 mg/ml in the same buffer

system containing 0.004% CaCl2-

After incubation the pieces of tissue were rinsed (x3) for 10

minutes in .1 M cacodylate buffer (pH 7.4) and transferred to cold (3°C)

0.1 M cacodylate buffered (pH 7.4) 2.0% gl utaraldehyde for 24 hours.

After fixation the samples were postfixed with cold 1% OSO4 in 0.1 M

cacodylate buffer (pH 7.4), dehydrated in 2, 2-Dimethoxypropane and embedded in Maraglas. Half-micron and ultrathin sections were cut with

an LKB Ultratome IV, stained with uranyl acetate and lead citrate,

and examined with a Philips EM 400 electron microscope.

5.2.1 Ultrastructural morphology of explanted valvular heterografts

Comparison of collagen from leaflets of the explanted valves (fig.

16 A) with that from comparable regions of the unimplanted controls

(fig. 16 B) revealed (1) a variable loss of contrast or blurring of the

collagen fiber crossbanding pattern, (2) electron dense granular matj erial associated with the collagen fiber surface, and (3) an accumulation of similar material in the interfiber spaces. Close examination of individual fibers showed associated granular and filamentous

material which appeared to be attached to the fiber surface and possibly within the fiber intermolecular interstices (fig. 16 C).

5.2.2 Effects of guanidine HC1 on leaflet ultrastructure

Fresh, unfixed porcine aortic leaflet tissue exposed to 4 M guanidine HC1 showed collagen fiber alterations ranging from fiber "unwindj ing" to almost complete disruption into microfibrillar components

(fig. 17 A). Gl utaraldehyde processed unimplanted tissue appeared re- sistant to dissociative treatment and showed no significant ultrastructural changes (fig. 17 B). Collagen from the explanted valves

(figs. 18 & 19) also exhibited no morphologically significant changes

when compared to either the unimplanted or untreated controls. It should also be noted that guanidine HC1 treatment did not appear to

have a significant effect on the presence or appearance of the granular

5.1.3.2 Enzyme studies

5.1.3.3 Electron microscopy

37 1
material in the explanted samples.

5.2.3 Effects of trypsin on leaflet ultrastructure

Exposure to trypsin (fig. 20) resulted in rather striking changes

in the explanted tissue when compared to the untreated controls. The

most apparent effect was a significant decrease of the amount of material

associated with both the fibers and the interfiber regions. The paucity

of the granular material was accompanied by a more distinct fiber surface and crossbanding pattern resulting in an overall collagen ultrastructural profile comparable to unimplanted controls.

6. Discussion

The results obtained from these analyses suggest that distinction

should be made when areas of critical importance to the long term functionality of tissue prostheses are reviewed. Specifically, the dysfunction patterns of the bioprosthesis should be viewed separate from a seemingly distinct issue, that of its durability and longevity. However,

that the former may in some way be contributory in some instances to the

latter may not be excluded.

6. 1 Dysfunction

As pointed out earlier, the majority of factors related to dysfunction of tissue bioprostheses appear to be extrinsic in nature.

These factors seem to be primarily associated with phenomena related

to cardiac function, sepsis and healing, and metabolic conditions.

While the population described perhaps represents only a fraction

of all valves explanted to date, it is substantial in that no other

group has reported numbers comparable to these. Also the distribution

of dysfunction patterns appear to be plausible, and communications with numerous users of the HANCOCK* bioprosthesis reflect agreement with our

findings.

Non valvular problems (18.2%) active infective and bioprosthesis

endocarditis (17.3%) as causes for removal account for nearly half of the

dysfunction patterns reported in the explant population. Both are ex- trinsic factors to the dysfunction of the bioprosthesis. Magilligan

ejt al_ C 12 3 in relating their experience with the Hancock valve concluded

that: 1) it is as resistant to infection when inserted in the face of

active infective endocarditis as are rigid prostheses; 2) is resistant to

early post operative bacteremias; and 3) it is easier to sterilize than

rigid prosthesis as well as being more durable than other tissue valves

in the face of prosthetic valve endocarditis. The review of the Stanford

group experience by Rossiter and associates Q.3] concluded that heterograft aortic endocarditis was more easily cured by medical treatment

than a mechanical valve endocarditis, if treated before annular abscesses

372
occurred. They also showed agreement with Magilligan in regards to the

advantages of medical over surgical treatment of the condition. However,

failure of medical therapy must be identified without delay and reoperation undertaken promptly to avoid excessive operative mortality,

A survey of the experience of various authors with endocarditis

and porcine valves [143 reveals that with nearly 5000 valves, in a comparable number of patients, the percentage of cases was substantially less than 1%.

Forty six percent of the dysfunctions observed in this explanted

valve population was secondary to calcification. Reports on this type

of valve related complication have been uncommon Q 15,16,17,18,19]]

While generally calcification of the valve is considered overall

as a single process, the data in this report points to a dual phenomenon characterized by rather different patterns of initiation and proliferation.

The sequence of events in extrinsic mineralization (23%) bears

similarity to those occurring in human valvular endocarditis, where

Extensive fibrinous and cellular deposits occur. These deposits are associated with previously infected regions of the valve as a consequence

of host mechanisms. The susceptibility to salt deposition demonstrated

by these deposits is, in our estimation, most likely associated with

specific molecular conformations of organized or unorganized fibrin. The

orobable sequence of events is illustrated in figure' 21, where it is seen that as mineralization progresses, leaflet function is compromised.

Eventually the erosive effects of salt deposits may result in leaflet

fraying and tearing.

This form of mineralization does not seem to occur as a result of

iny intrinsic or inherent characteristics of tissue valvular prostheses,

lor does it show to occur with preferential dependency for age or sex of

:he valve recipient.

Another 23% of the explanted population was observed to occur by a :otally different pattern we have termed intrinsic mineralization and

/hi ch other authors [[17,18,193 have referred to as idiopathic, or fibro-

:alcifi cation. This form of calcification by contrast, rare as it must

»e considered, appears to occur with a chronology dependent on the age

hough not on the sex of the valve recipient. The chronology as well as

he age dependency is shown in figure 10 A. For this analysis, patents under the age of 20 years are grouped separately from the remaining

dult patients.

Thus, it can be deduced that when this form of mineralization occurs

n children, it does so early after implantation of the bioprosthesi s

e have observed this as early as six months and as late as six years,

report on a similar bioprosthesi s to the Hancock valve, described its ccurrence within 19 days of implantation Q23 "]

. In adults, there is no

pparent chronology associated with its occurrence.

373
Only specific individuals, adults and children are at risk, and the

factors which increase this risk are still poorly understood.

For adults with a propensity for calcification, a time relation is

suggested, the probability of occurrence may increase with duration of

implant.

Some factors which have been considered influential in precipitating the onset of calcification are associated with metabolic and

electrolyte disturbances [6,18, 193 such as may be found in patients

under chronic hemodyalysis L 6 >3l3 > sickle cell disease [15 J elevated

alkaline phosphatase levels, secondary hyperparathyroidism and increased

calcium turnover. Levy and associates [ 20,21 J have explored the possible

role of a newly found calcium binding amino acid, y-carboxygl utamic acid

in valvar and tissue prostheses calcification. Their results suggest a possible relationship of vitamin K-dependent processes to the pathogenesis of these diseases.

An extension of their results can be envisioned in the possibility

of correlating excretion levels of this amino acid and heterograft

status in patients at risk of fibrocalcification.

One possible mechanism for the salt deposition within valvular

structures is illustrated in figure 22. The intraleaflet regions affected seem to exhibit host protein infiltration as a consequence of voids

produced by process variables which remove porcine proteins and muco- polysaccharides. This may be a desirable interaction as these viscous

fluids may provide internal lubricity necessary to decrease shear stresses provided to the valve by the human hemodynamic environment. In certain patients extensive protein inundation of the interfiber spaces

may promote salt deposition with progressive leaflet stiffening, and as there is crystalline growth, cusp tears, dehiscence, and total leaflet

disruption as the final outcome.

However, it must be emphasized that the fibrocalcification process

becomes a chronic process and an intrinsically calcified valve may con- tinue to function for extended periods of time, gives ample warning of

malfunction and in most cases allows elective rather than emergency

surgery £22 ,23 ].

Seemingly this form of calcification is generic to all glutaraldehyde fixed tissue valves. It suggests there are heterograft sites

which, in the presence of certain factors, may elicit the initiation of

f ibrocalcific deposits. This clearly introduces the possibility that

additional treatments to block the potential nidi may help to delay or arrest the processes in the implanted valve.

In our experience, intrinsic calcification is an uncommon event.

Our current estimate puts it in the neighborhood of 0.5% of all implanted valves. Certainly this is comparable to reports in the literature

which show numbers in the same order; Cohn[V): 0.3%; Lambert i [l5l: less

than 1%; 0yer[7]: 0.45%, showing in children 50% rate and Thandroyen

374
0?3U: less than It, encompassing experience of these authors with over

3000 patients.

Numerous reports attest to the advantages of the HANCOCK*

bioprosthesis over its mechanical counterparts with regards to its low

thrombogenic potential Q3, 4, 5, 6, 7, 24, lb} Hetzer and associates 24

have identified patient related factors associated with increased risk

of thromboembolism after mitral valve replacement with this bioprosthesis

and described specific anticoagulant regimens for patient subgroups with

various thrombogenic factors. Cevese[4]in a series of 629 xenografts

reports a total incidence of embolization for the entire group of patients as 2.3%. Oyer et ajX 7 J re ports over-all rates in 1118 patients at

risk ranging from 1.7% to 2.6% with a maximum follow up of 7.3 years.

Thus, the 4.3% rate we find in the population of explanted valves does

not seem inordinately large.

Exposure to antibiotics during the rinsing sequence has been

thought to be related to subsequent thrombosis due to electrochemical

potential changes of the valve surface induced by these drugs (fig. 23).

Cohnr25.Jhas described thromboembolic phenomena in patients with

chronic valvular heart disease resulting from decreased cardiac output

as a consequence of myocardial dysfunction, increased atrial chamber

size, supraventricular arrythmias, and obstruction of flow. Thus, he

concludes, any condition leading to decreased blood flow across the

valve orifice, stagnation, or obstruction of blood flow may predispose

to thromboembol i

Patients with chronic atrial fibrillation, or decreased myocardial

performance, following mitral replacement specially, are predisposed to

thromboembolic episodes whether or not a tissue valve is inserted. It

is interesting to note that a survey of 19 major cardiovascular centers

L 25 J showed a wide variation in anticoagulation regimens for patients

receiving tissue heart valves. It has become general practive to require long-term anticoagulation on patients showing poor hemodynamic

performance, and for all patients in the perioperative period for 6 to

12 weeks.

Tears of unknown etiology, often referred to as primary tissue dysfunction represents about 2% of the explanted valve population £

26"}.

Explanation for the causes of this dysfuntion at this time can only be

speculative. Natural variations in porcine collagen may exist from

animal to animal, differences which could result in potentially less

durable areas. The possibility of leaflet trauma during retrograde

catheterization, discussed with various users of this bioprosthesis

leaves open a possibility for the initiation of events which could lead

to eventual leaflet tears.

To date there has been no pattern to this occurrence, nor has the

frequency increased in proportion to the explanted or implanted valve

population C 63.

375
In summary, the dysfunction patterns of this bioprosthesis. , as assessed by examination of the explanted valve population accumulated

in this laboratory and in relation to the total implant population, indicate that a small percentage of the xenografts are at risk of calcification and thromboembolic complications. Similarly, a fraction of the

population may necessitate removal in the face of active infective endocarditis without healing or prosthetic valvular endocarditis.

6.2 Durability

No other tissue heterograft enjoys, at the present time, a decade

long clinical experience. This fact affords the HANCOCK* bioprosthesis

a unique opportunity to evaluate critical post implantation follow-up

beyond five years. The explanted valve program has afforded the opportunity to evaluate bioprosthesis structural condition after extended

in vivo functional periods of time.

As was stated above, the long term success of these bioprostheses

depend on various extrinsic as well as intrinsic factors. Their durability, in the absence of all extrinsic factors, described in the

section of dysfunction, depends solely on the durability of the underlying network of collagen constituting most of the functional aspects

of the valves.

The shrinkage temperature of explanted valves indicated that valvular tissue maintained a relatively unaltered degree of collagen cross- linking after seven years of implantation. Histological observations

did not reflect tissue degeneration in the absence of the extrinsic

factors mentioned. However, electron microscopical examination of

leaflets from clinically explanted prosthetic heart valve heterografts

revealed post implant changes characterized by apparent collagen fiber

alterations concommitant with the accumulation of a fine granular material. The latter appeared to coat the fibers and reside within the

interfiber and valvular spaces previously occupied by nonfibrous proteincarbohydrate complexes eliminated during heterograft processing. The

studies by Ferrans et al_ [28j indicate that the initial appearance and

subsequent accumulation of the material occur as a result of progressive

collagen disruption, and if the granulation does represent collagen degradative products it would seem reasonable to assume that the material

originates as a consequence of fixation deterioration, host mediated

enzymatic action, or a combination of both.

The first purpose of the study was to determine whether the glutaraldehyde crosslinks induced during initial fixation of the prostheses

were conserved.

The mode of action of guanidinium dissociation appears to be based

on the ability of the denaturant to disrupt or break hydrogen bonds with

the loss of bonding resulting in the progressive disaggregation of collagen fiber into microfibrillar components £29 J . The almost total disruption of the fresh unfixed valvular collagen (fig. 17A) indicates that

376
covalent lysyl -derived crosslinks only partially stabilize the fiber

structure. The rather remarkable resistance of the unimplanted glutaraldehyde treated collagen to denaturation (fig. 17B) shows that the

glutaraldehyde derived crosslinks significantly increase fiber stability.

The results obtained with the expl anted tissue, which also exhibited a comparable resistance, demonstrate that the aldehyde crosslinks are apparently conserved after implantation (figs. 18, 19, 20).

In a study examining the consequences of experimentally induced

corneal immune injury Mohos and Wagner fjo] have described the progressive dissolution of collagen fibers as a result of the injection of proteolytic and hydrolytic enzymes into intact, healthy rabbit cornea. Among the enzymes utilized trypsin was shown to be an effective proteolytic agent against collagen resulting in a superficial peeling of

the fiber followed by a more complete dissolution into fragmented microfibrils. These changes were reported after only 2 hours of exposure of

the tissue to enzyme. In the present study the effects of trypsin on unfixed and fixed unimplanted tissue were not examined but the resistance of expl anted prosthetic collagen to 24 hours of enzyme exposure

(fig. 20) further supports the stabilizing effect of the glutaraldehyde

crosslinks as well as a conservation of that effect after extended prosthetic implantation. Studies designed to examine the effects of other

proteolytic enzymes with both specific and general bond affinities are presently being performed.

The second purpose of the present study was to attempt to determine

to what extent, if any, the post implant granular material observed

coating collagen fibers and accumulating within interfiber spaces re- presents the consequences of fiber degradative alterations. It would

seem reasonable to assume that if prosthetic collagen degradation does occur the granular material could be wholly collagenous in origin or consist of a combination of collagen and host material. In their studies

concerning corneal immune injury Mohos and Wagner concluded that in the

case of an immunological response associated with collagenous tissue

the resulting fibrinoid was composed of an immune precipitate with en- trapped fragmented collagen. Since glutaraldehyde processed prostheses

[do not appear to elicit any significant localized cell mediated immune

response it seems doubtful that this would be the mechanism by which

'the material forms. Circulating immunologically derived components

could, with time, infiltrate the prosthesis and possible contribute to

the observed phenomenon but it would seem unlikely that an immune component in the absence of any localized cellular response could account

j for a significant breakdown of the collagen.

Even though the previously discussed findings indicate that prosthetic collagen fixation is conserved the possibility exists that over

an extended time period there is, in the absence of any host mediated

mechanism, a slow yet progressive fiber degradation with the resulting

products accumulating as collagen fragments or as a complex involving

host components. Such a mechanism or any involving a significant contribution of the prosthetic collagen to the formation of the material

would be expected though to result in irreversible fiber ul trastructural
alterations. That treatment of explanted tissues with trypsin results

in the elimination of the granular material, and the apparent "restoration" of the preimplant collagen ultrastructural profile, strongly

supports the hypothesis that prosthetic collagen is not a significant

component of the material. For example, even though close examination

of the explanted collagen fibers reveals what appears to be focal disruption (fig. 19) fibers from the same region after enzyme exposure

appear comparable to those of preimplant tissue (fig. 20). Alternatively

the granular material could be wholly host in origin. We have observed

that within days after prosthetic implant an electron dense granular

material accumulates in association with the remaining basement membrane

components at the leaflet surfaces and with the more superficial fiber

bundles. The electron microscopic appearance of this material is virtually undistinguishable from that observed after extended implant time

and appears to almost certainly result from the infiltration of host

material. While the present study is primarily concerned with the

collagenous component it should be noted that the trypsin exposure also

results in the removal of the basement membrane associated material

leaving behind an intact basement membrane with an electron lucent background. The generally accepted specificity of trypsin toward peptide

bonds involving the carboxyl groups of lysine and arginine may have significance with regard to identity of the material especially since the

latter is characteristic of fibrinogen. Studies concerned with the isolation and characterization of the material are suggested with special

emphasis on amino acid profiles.

In summary, the results of this study indicate that the glutaraldehyde crosslinks induced at initial fixation of the prosthetic tissues

are conserved and apparently effectual after extended prosthetic implant duration. The absence of a significant amount of the post implant

granular material and the restoration of the collagen ultrastructural

profile comparable to that of preimplant tissues as a result of enzyme

exposure strongly suggests a noncollagenous host origin of the material.

Together these findings offer evidence that gl utaraldehyde processed

valvular prostheses may not be subject to progressive intrinsic deterioration.

7. Comment

A population of HANCOCK* bioprostheses retrieved for various rea- sons after extended implantation, and their modes of dysfunction have

been analyzed. The results we believe will be of interest to the medical

community in evaluating the performance of this valve in terms of functionality and longevity. We believe that the durability of any tissue

bioprosthesis can only be realized through extensive clinical evaluation

and thorough examination of retrieved specimens.

Acknowledgments

I wish to thank Mr. David Ott and Ms. Lots Goughnour for their fine

technical assistance and Ms. Barbara Evans for preparing the manuscript.

378
1

379
PLANE

OF

Figure 4. Map of plane

and morphologic location

of valve histologic

sections.

SUMMARY OF VALVE REMOVAL

ACCORDING TO IMPLANT DURATION

1 2 3 4 8 6 7 t 8 10

Duration of Implant (Years)

Figure 6. A. Non valvular reason for retrieval.

B. Outflow aspect of 92 month implant removed because of patient

degenerative aortic root disease. Valve showed well conserved tissue

at gross and microscopic levels.

380

.i
Figure 7. A. Time course of valve retrieval for unknown reasons

B. Valve in situ, removed for unknown reasons.

1

VALVE REMOVAL ACCORDING TO

IMPLANT DURATION AND ETIOLOGY

ENDOCARDITIS (Inlective & Thrombotic)

J14567««» Duration of Implants (Yews)

Figure 8. A. Chronology of retrieval in the face of active infective

endocarditis or bioprosthetic endocarditis.

B. Valve removed at 6 months because of unhealed infective

endocarditis. Histological sections revealed abundant

aggregates of coccal organisms.

38 !
Figure 9. A. Extrinsic mineralization as reason for valve removal.

B. Gross photograph of extrinsical^ calcified valve. Note mineralized verrucous deposits along

commissural edges of valve leaflet.

The remaining tissue is smooth and

glistening. C. Fibrin accumulated on surface of valve demonstrates positive von Kossa (black)

material indicative of calcific deposit. The architecture of the leaflet is well conserved.

I .t

i III

Duration of Impionto (Yooral P

Figure 10. A. Removal due to INTRINSIC mineralization of valves. Distribution between children and adults demonstrate different chronology.

B. Pictorial gross review of calcified "strut" and calcific modules

under surface.

302
Figure 10.C. Crossection normal to the

direction of collagenous bundle showing

von Kossa positive material.

D. Intrinsic mineralization of collagenous

bundles.

E. Subsurface mineralization of leaflet

fibrosa . Notice that leaflet surface is

not yet affected.

Figure 11. A. Idiopathic thrombosis requiring

retrieval

B. Histological section of well -conserved

leaflet demonstrating massive thrombotic

desposition.

303
VALVE REMOVAL ACCORDING TO

IMPLANT DURATION AND ETIOLOGY

PRIMARY TISSUE DYSFUNCTION

1 2 1 4 S • 7 g 10

Duration of Implant* (Yaara)

rigure 12. Tears of unknown etiology.

B. Gross vi ev/ of the phenomenon.

C. Histological sections of leaflet at site of rupture. Notice

good conservation of collagenous

material throughout leaflet.

EXPLANTED VALVE POPULATION

Percent Exhibiting Specific

Pathology- 180Specimens

BACTERIAL ENDOCARDITIS 17 %

("UNHEALED")

NON VALVULAR / ^EXTRINSIC

PeLvutarteak . 19%M ITMINERALIZATION

Degenerative mB^SbhbBB^ [& 23%

•Outgrew valve -Other

UNKNOWN ETIOLOGY

11%

EARLY THROMBUS

5%

DYSFUNC

Figure 13. Summary of dysfunction (180 valves).

384
Table I

DYSFUNCTION

208 Excised HANCOCK Valves

Hon Mineralization Leaflet Valvular Endocarditis Extrinsic Intrinsic Failure Thrombus Unknown

Number •» se 47 51 a » 22

% mj nja 22.0 2*,* 2* 4.3 io.6

llllfli

1 ||Li. 5

Figure 14. A and B. Inflow (A) and outflow (B) aspects of valve explanted 5 years 10 months (70 mos.). Exhuberant host fibrotic ingrowth into the sewing ring stops at points of leaflet flexure.

385
5yr 10mo Explant

I

Figure 14 C. Cusp elastica showing elastin fibers. 2. Shows good con- servation of collagenous bundles. 3. Near node of Arantius, point of

high stress. 4 and 6. Ground substance from the elastic triangle which

serves as an infinitely rolling hinge. 5. Cusp material. All com- parable to preimplant tissue.

Figure 15. Shrinkage temp of

valves retrieved in cold saline.

After the initial drop of less

than a degree, there are no changes in this temperature.

This figure at present extends over 1\ years.

SHRINK TEMPERATURE VS

IMPLANTATION TIME FOR

EXPLANTED CLINICAL VALVES

386
Figure 16 A. Ultra structural view of collagen from leaflet of valve

explanted at 92 months. Notice blurring of collagen fiber crossbanding and ubiquotous adherent material. B. Ul trastructure of preimplant

collagen. C. Adherence of granular material to single elastin fiber

(arrow). All X47,000

Figure 17 A & B. Effect of 4 M guanidine hydrochloride on unfixed and

glutaraldehyde processed porcine valvular collagen. A. Unfixed collagen from various regions of leaflet. The dissociating effect is seen

in both longitudinal and transverse aspects of fibers. Uncoiling

or unwinding is evidenced after exposure of tissue to the agent.

B. Glutaraldehyde fixed, unimplanted collagen. Stabilization of collagenic structure by glutaraldehyde crosslinks evidenced under the same condition as A. Crossbanding is sharp, fiber integrity conserved

(X225,000).

387
Figure 18. Ill trastructural section of collagen fibers from leaf

let of 92 month explant treated

with 4 M guanidine hydrochloride.

Notice the blurring of typical

periodic pattern and granular mat

erial everywhere. (X47,000)

Figure 19. Electron micrographs of clinically explanted Hancock

valves. A. After 100 months of implantation. Interstitium of the

individual fibers, bundles of the fibrosa are occupied by electron

dense material (X9,000). B.& C. (X175,000) Higher magnification of

longitdunal (C) and transverse sectioned collagen show the fine

granular nature of the electron dense material in A. D. (92mos.

X225,000), E (34 mos. X225,000) and F (34,000 X71,000) show the

intimate association of the material with the individual fibers.

388
9 0 0

0 0-, 9

®w m & & mm*

Figure 20. Electron micrographs of explanted Hancock valves after

exposure to trypsin. A. 34 month explant illustrating the re- storation of the lucent interstitium (X25,000). B, C and D. Higher

magnification of 34, 92 and 100 month valves respectively showing

the absence of electron dense granules and collagen ultrastructure

comparable to unimplanted tissue ( B X91,000, C X145,000, D X91,000,

E X225,000).

389
SEQUENCE OF EVENTS FOR

EXTRINSIC MINERALIZATION

A. ORGANISMS COLONIZE ON

VALVE SURFACE

SEQUENCE OF EVENTS FOR

INTRINSIC MINERALIZATION

: >. ;'/

: ":

. - Leaflet tissue Is Infiltrated by

host plasma proteins

Figure 21. Probable sequence of Figure 22. One possible mechanevents in extrinsic ism leading to biomineralization, prosthetic mineralization .

Figure 23. Scanning electron micrograph of the surface of a bioprosthesis which was rinsed in antibiotic solution.

Notice massive thrombocyte deposition. (X5,000)

390
REFERENCES

Cll Reis, R.L., Hancock, W.D., Yarborough, J.W. Glancy, D.L., Morrow,

A.G., The flexible stent; a new concept in the fabrication of

tissue heart valve prostheses, J. Thorac. Cardiovasc. Surg. 62,

[5l , 683-689 (1971 ).

L*2l Hannah, H., Reis, R.L., Current status of porcine heterograft

prostheses: A 5-year appraisal, Circulation 5_2, [Supp. 1 1 , 11-30

(1975).

[3] Mcintosh, C.L., Michaeles, L.L., Morrow, A.G., Itscoitz, S.B.,

Redwood, D.R., Epstein, S.E., Atrio-ventricular valve replacement

with the Hancock porcine xenograft. A five-year clinical experience, Surgery 78, 768-775 (1975).

C41 Cevese, P.G., Callucci, V., Morea, M. , Volta, S.D., Fasoli, G.,

Casarotto, D., Heart valve replacement with the Hancock bioprosthesis. Analysis of long-term results, Circulation 56_, [Supp. Ill,

111-116 (1977).

[5l Hancock, W.D., The porcine heart valve prosthesis. Med. Instrum.

11, £23, 102-103 (1977).

[62 Cohn, L.H., Koster, J.K., Mee, R.B.B., Collins, J.J., Long-term

follow-up of the Hancock bioprosthetic heart valve. A 6-year

review. Circulation 60, CSupp. Il , 87-92 (1979)

[7l Oyer, P.E., Stinson, E.B., Reitz, B.A., Miller, D.C., Rossi ter,

S.J., Shumway, N.E., Long term evaluation of the porcine xenograft

bioprosthesis, J. Thorac. Cardiovasc. Surg. 78, Dl , 343-361

(1979)

[81 Davila, J.C., Magilligan D.J., Lewis, J.W., Is the Hancock valve

the best cardiac valve substitute today? Ann. Thorac. Surg. 26_,

[41 , 303-316 (1978).

[9} Struck, E., Meisner, H., Schmidt-Habelmann, P., Sebening, F.,

Cardiac valve replacement with Hancock and Carpentier-Edwards

biopros theses, Book, Proceedings of the Symposium on "Bioprostheti c Cardiac Valves , Munich, Apr. 5-7, 1979, F. Sebening, W.P. Klovekorn,

H. Heisner and E. Struck, eds. pp. 61-67 (Ebert GmgH, Germany 1979).

[101 Cohn, L.H., Collins, J.J., The glutaraldehyde stabilized porcine

xenograft valve, Chapter 5, Tissue Heart Valves , M.I, Ionescu, ed.

pp. 173-200, (Butterworth & Co. Ltd., London, UK, 1979).

DTI Hancock Laboratories, Inc. Durability assessment of the Hancock

porcine bioprosthesis. A multicenter retrospective analysis of

patients operated prior to 1975. Special publication, April, 1980.

39 I
[12 Magilligan, D.J., Quinn, E.L., Davila, J.C., Bacteremia, endocarditis and the Hancock valve, Ann. Thorac. Surg. 24, U6l , 508-518

(1977).

DH Rossiter, S.J., Stinson, E.B., Oyer, P.E., Miller, D.C., Schapira,

J.N., Martin, R.P., Shumway, N.E., Prosthetic valve endocarditis,

J. Thorac. Cardiovasc. Surg. 76, C6] , 795-803 (1978).

[14] Drexler, L., Rytel , M., Keelan M., Bonchek, L.I., Olinger, G.N.,

Aspergillus terreus infective endocarditis on a porcine heterograft

valve, J. Thorac. Cardiovasc. Surg. 79, £21 , 269-274 (1980).

D5] Lamberti, J.J., Wainer, B.H., Fisher, K.A., Karunaratne, H.B.,

Al-Sadir, J., Calcific Stenosis of the porcine heterograft, Ann.

Thorac. Surg. 28, 1X1 , 28-32 (1979).

D 63 Ashraf, M., Bloor, CM., Structural alterations of the porcine

heterograft after various durations of implantation, Am. J. Cardiol.

41_, 05J , 1185-1190 (1978).

[17] Spray, T.L., Roberts, W.C., Structural changes in porcine xenografts

used as substitute cardiac valves, Am. J. Cardiol. 40, C3] , 319-330

(1977).

D81 Geha, A.S., Laks, H., Stansel , H.C., Cornhill, J.F., Kilman, J.W.,

Buckley, M.J., Roberts, W.C., Late failure of porcine valve heterografts in children, J. Thorac. Cardiovasc. Surg. 78_, L3] , 351-364

(1979).

L"19] Kutsche, L.M., Oyer, P., Shumway, N., Baum, D., An important com- plication of Hancock mitral valve replacement in children,

Circulation, 60, CSupp. 13, 98-103 (1979).

[2QI Levy, R.J., Zenker, J. A., Lian, J.B., Vitamin K-dependent calcium

binding proteins in aortic valve calcification, J. Clin. Invest.

65, 563-566, 1980.

[21] Levy, R.J., Lian, J.B., Gallop, P., Atherocalcin, a y-carboxyglutamic acid containing protein from atherosclerotic plaque,

Biochem. Biophys. Res. Comm. 91, CO , 41-49 (1979).

[22 Silver, M.M., Pollock, J., Silver, M.D., Williams, W.G., Trusler,

G.A., Calcification in porcine xenograft valves in children, Am.

J. Cardiol. 45, 685-689 (1980).

[23) Thandroyen, F.T., Whitton, I.N., Pine, D., Rogers, M.A., Mitha,

A.S., Severe calcification of glutaraldehyde-preserved porcine

xenografts in children, Am. J. Cardiol. 45, 690-696 (1980).

392
[243 Hetzer, R. , Hill, J.D., Kerth, W.J., Ansbro, J., Adappa, M.G.,

Rodvien, R., Kamm, B., Gerbode, R. s Thromboembolic complications

after mitral valve replacement with Hancock xenografts, J. Thorac.

Cardiovasc. Surg. 75, C5l , 651-658 (1978).

[253 Cohn, L.H., Bioprosthetic cardiac valves - anticoagulation or not?

Book, Proceedings of the Symposium on "Bioprosthetic Cardiac

Valves", Munich, Apr. 5-7, 1979, F. Sebening, W.P. Klovekorn,

H. Meisner and E. Struck, eds. pp. 107-120 (Eberl GmbH, Germany

1979).

[E6] Housman, L.B., Pitt, W.A., Mazur, J.H., Lichtford B., Gross, S.A.,

Mechanical failure (leaflet failure) of a porcine aortic heterograft: Rare cause of acute aortic insufficiency, J. Thorac.

Cardiovasc. Surg. 76, T2J , 212-213 (1978).

[273 Strawick, E., Hancock, W.D., Nimni, M., Chemical composition and

biophysical properties of porcine cardiovascular tissues, Biomat.

Med. Dev. Art. Org. 3, DH , 309-319 (1975).

[283 Ferrans, V.J., Spray T.L., Billingham, M.E., Roberts, W.C.,

Structural changes in glutaraldehyde-treated porcine heterografts

used as substitute cardiac valves, Am. J. Cardiol. 41_, 1159-1184

(1978).

[293 Lillie, J.H., MacCallum, D.K., Scalleta, S.J., Occhino, J.C.,

Collagen structure: Evidence for a helical organization of the

collagen fibril, J. Untrastruc. Res. 58, 134-143, (1977).

DO] Mohos, S.C., Wagner, B.M., Damage to collagen in corneal immune

injury. Observation of connective tissue structure, Arch. Path.

88, 3-20, (1969).

Dl] Fishbein, M.D., Gissen, S.A., Collins, J.J., Pathologic findings

after cardiac valve replacement with glutaral dehyde fixed porcine

valves. Am. J. Cardiol. 40, 331-337 (1977).

393

RETRIEVED FRACTURE PLATES: IMPLANT AND TISSUE ANALYSIS

James P. Simpson, Ph.D.

Institut Straumann A.G.

CH-4437 Waldenburg

Switzerland

Verena Geret

Swiss Research Institute

CH-7270 Davos Platz

Switzerland

Stanley A. Brown,* D. Eng. , and Katharine Merritt* Ph.D.

University of California

Davis, CA 9561 6

A study was undertaken by AO/ASIF to investigate the

suitability of different materials for bone plates for

osteosynthesis. A total of 80 plates were retrieved

together with clinical data, histologic data, and chemical

analysis. The materials used were stainless steel 316

LVM, commercially pure titanium, titanium (Ti-6A1-4V)

alloy, and a cobalt-chrome-nickel-tungsten-iron alloy as AO/ASIF compression plates and screws. The protocols

used and the results of these first 80 cases are presented. The histologic analysis revealed the greatest

differences occurring in the accumulation of lymphocytes,

macrophages, and giant cells which were greatest with

the cobalt alloy. The quantity of debris in the tissue

was greatest with titanium. The chemical analysis

revealed a wide scattering of values and the results

are discussed. The examination of plates and screws revealed that stainless steel suffers fretting corrosion

and that the amount of metal loss is less on the cobalt

alloy, titanium, and the titanium alloy although significant corrosion was observed at the plate screw contact area for the cobalt alloy.

1. Introduction

The bulk of osteosynthesis implants in use today are stainless

steel, implant grade 316 LVM. This alloy has often been criticized

for its susceptibility to crevice and pitting corrosion [1, 2] 1

. Cobalt base alloys and titanium and its alloys have been considered

figures in brackets indicate the literature references at the end

of this paper.

Current address: Orthopaedic Research Laboratory, TB 139,

University of California Davis, Davis, CA 95616.

395
as suitable alternatives. However, these materials must not impair

fracture healing or initiate an adverse host response. An AO/ASIF

(Arbeitsgemeinschaft fur Osteosynthesefragen/Association for the

Study of Internal Fixation) study was undertaken to investigate the

effects of different materials on fracture healing in patients.

Clinical data was collected and the plates and screws retrieved for

analysis along with a tissue sample taken at removal for histology

and chemical analysis. The protocol is presented here as an example

of how reliable and usable data from this type of multi-institutional

study can be obtained for analysis of the suitability of implant

material in fracture fixation. The results of this limited study are presented and indicate the trends in clinical acceptability and

tissue reaction observed with the different implant types.

2. Methods: Collection of Material

2.1. Implants

Plates of 316 LVM stainless steel (ASTM F-138) [3], cobalt alloy

(Co-Ni-Cr-Mo-W-Fe) (ASTM F-563) [4], titanium (ASTM F-67) [5], and

titanium alloy (Ti-6A1-4V) (ASTM F-136) [6] were distributed for

implantation. The materials were used in the following plate/screw

combinations: stainless steel/stainless steel, titanium/titanium,

titanium al 1 oy/ titanium alloy, titanium/ti tan i urn alloy, titanium/

stainless steel, cobalt alloy/cobalt alloy. There were no cobalt

alloy cancellous bone screws available; when required, stainless

steel screws were substituted.

2.2. Patient selection

Three hospitals: Spital Davos, Kreuzspital Chur, and Kantonspital Basel, Switzerland, provided the material analyzed in this

study. Patients who presented with fractures suitable for plating

with the size plate distributed in this study received the test

plate. The study was limited to fractures of the lower limb.

2.3. Plate removal

Plates were usually removed as part of the routine care of the

patient. The duration of the implantation is considered in the

evaluation of this study.

2.4. Clinical data

At the time of removal of the plate, the clinical form (fig. 1) was completed. This is a slightly modified translation of the

original AO/ASIF form. This included questions on symptoms and

evaluation of the general appearance of the tissue. The numerical

data on the clinical performance of the test plate was allocated as indicated on the form. Higher values are regarded as less acceptable

responses.

33G
AO/AS IF PLATE REMOVAL

Pat. No. Name

Bone Address

Date Implanted

Date Removed

Surgeon

Plate

Hospital

Screws

First Name

Weight

Date of Birth

Phone

Clinical Results at Metal Removal

Pain in fracture area Weather sensitivity

Swelling tendency

Inflammation, redness

Infection

Function of limb

Range of motion

in the two adjacent joints

0 - no

0 - no

0 - no

0 - no

0 - no normal

normal

seldom 2 - yes

seldom 2 - yes

seldom 2 - always

yes, when

- superficial 2 - deep

ightly

impaired

heavily

impaired

contraction

degree of flexion

Fracture healing: roentgenographs

0 - primary 1 - light callus 2 - heavy callus 3 - delayed

4 - pseudoarthrosis 5 - infection

Other complications

Local findings at metal removal:

Scar: 0 - inconspicuous 1 - distinct 2 - red 3 - eczematous

Tissue over plate: 0 - soft 1 - thickened 2 - bony

Coloration: 0 - none 1(+), 2(++); color: white, gray, brown, black

Tissue contacting plate: 0 - intimate 1 - cavity 2 - serum

Collar around screw head: 0 - connective 1 - bony 1/2 - combination

Plate bed: 0 - vascularized 1 - avascular 1/2 - combination

Biopsy of plate capsule: proximal distal

Others:

Figure 1

397
2.5 Tissue sample

At explantation, the tissue over the plate and the first two screws at the proximal end (unless otherwise indicated) was obtained

for chemical and histological analysis. The protocol was that depicted in figure 2. The proximal ends were tagged with sutures. The

tissue was split longitudinally down the middle. Both pieces were

placed on a small piece of plastic and held in place with rubber bands

to prevent curling of the tissue. One piece was placed in absolute

alcohol for chemical analysis. The second half was placed in formalin

for embedding, sectioning, and staining for histological analysis.

ALCOHOL

PROXIMAL

( Chemical Analyses

)

suture

^^^^^^^ jan pet Men

FORMALIN -7- suture

( Histology

)

Figure 2 Procedure for

tissue sampling

for histology and

chemical analysis,

3. Methods of Analysis

3.1. Histology

The tissue was embedded in poly (methyl methacryl ate) [7] and

positioned so that the sectioning plane was normal to the fracture

plate, thus revealing contact and overlying tissue. The tissue was sectioned with a Zeiss Cutall to obtain 5 y sections, and the

sections were stained with hematoxylin and eosin, or with Giemsa.

The slides were examined by a single observer without knowledge

of the plate material. A grading scale of 0 to 5 was used. The

tissue was examined for the presence of bone, muscle, and connective

tissue. The majority of the tissue samples were composed of con- nective tissue (fig. 3). The tissue was also examined for the

presence of lymphocytes. A grade of 1 was given when occasional

scattered lymphocytes were seen. A grade of 2 indicated a cluster of

lymphocytes or many scattered lymphocytes. A grade of 3 indicated

398
more than one cluster or a cluster and extensive scattering of lymphocytes. Figure 4 depicts a cluster of lymphocytes with some scattered

lymphocytes and some perivascular cuffing. A grade of 4 indicated

several clusters of lymphocytes with lymphocytes scattered in the

tissue. A grade of 5 indicated extensive lymphocyte accumulation

with many large clusters and lymphocytes throughout the tissue.

The tissue was also examined for the presence of macrophages and

giant cells. These cells were generally found in association with

lymphocyte accumulations. A grade of 1 indicated a few macrophages

or giant cells in the clusters of lymphocytes or scattered in the

tissue. The grade increased with increasing numbers of these cells

in the lymphocytic nodules or associated with debris or with perivascular cuffing. A grade of 5 indicated that there were large

accumulations of macrophages or giant cells in the lymphocytic nodules

and in the tissue. Figure 5 shows extensive accumulation of macrophages in a necrotic center of a lymphocytic nodule, and figures 6

and 7 depict giant cells and macrophages in a nodule.

The accumulation of debris was scored in two separate ways. One

involved a scan of the tissue section at low power, and the deposition of debris in the tissue was scored. A few areas of debris were

scored as a grade of 1 with the grade increasing through 5 when

massive accumulations were seen in several areas (fig. 8, 9). Then

the tissue was examined at a higher power to disclose the amount of

debris that was actually engulfed by cells. Again, a few cells with

debris were scored as 1 with many cells having engulfed debris being

scored as 5. Figure 10 shows debris in cells with no other cellular

reaction

The tissue was also examined for the presence of blood vessels.

A grade of 1 indicated the presence of some capillaries. A grade of

2 indicated a rich capillary bed. The grade increased to a score of

5 which indicated the presence of capillaries and arterioles and

venules. Figure 11 shows a section classified as 5 for blood vessels.

The final examination was a rough score of the thickness of the

capsule. A score of 1 indicated a small thread of tissue. A score

of 2 indicated a section that filled 1/3 to 1/2 the field with a lx

objective (4x magnification). A score of 3 indicated a section that

filled 1/2 to 3/4 of the field. A score of 4 indicated a section

that was just within the field, and a score of 5 indicated a tissue

section that more than filled the field with the lx objective.

3.2. Chemical analysis

The size of the tissue samples received was variable, and the

sampling technique did not allow an evaluation of the total metal in

the tissue. It was thus decided to further divide the tissue in an attempt to find the range of metal concentration in the various areas

of the tissue above the plates.

399
Figure 3 Typical connective

tissue observed in

sections

.

Figure 4

Cluster of lymphocytes

and lymphocytes

scattered with some perivascular cuffing.

Figure 5 Macrophages in center

of lymphocytic nodule.

4 00
Figure 6

Giant cells and

macrophages in a nodule.

Figure 7 Lymphocytic nodule

with giant cells and

macrophages

Figure 8

Grade 5 deposition of

debris with no cellular reaction.

4 o i
Figure 9

Grade 5 deposition of

debris with cellular

reaction and necrosis

Figure 10

Debris engulfed by

eel Is.

Figure 11 Grade 5 blood and

lymphatic vessels.

4 0 2
The tissue was subdivided into different portions on the basis

of discoloration intensity, or if the tissue was of a uniform color,

the tissue from the immediate vicinity of the screw holes was separated from the remainder and analyzed separately. The discoloration normally coincided with the screw hole impression. The tissue

sample was dried overnight at 70°C, allowed to cool for 1 hour ex- posed to the atmosphere, and weighed, and then in 1 hour heating and

cooling cycles until the weight was constant. The samples were then

dissolved in spectroscopic grade mineral acids using the following

procedure.

A few drops of concentrated nitric acid - the smallest volume

sufficient to cover the tissue - were added and the test tube immersed in boiling water. If after 1 hour the specimens had not dissolved completely, one or two drops of concentrated hydrochloric acid were added. Any residues still present after a further hour could

normally be dissolved by a very small amount of concentrated sulfuric

acid. A blank solution - without tissue but containing the same quantities of mineral acids - was prepared along with the test sample.

The dissolved samples were diluted to 3 ml with double distilled

water and analyzed by flame atomic absorption spectroscopy. The

elements analyzed were selected on the basis of the implant the

patient had received.

i) stainless steel implants - Cr, Ni

ii) stainless steel with titanium - Cr, Ti , Ni

iii) titanium implants - Cr, Ti

iv) syntacoben implants - Cr, Co, Ni

The results were expressed as micrograms of element per gram of

dried tissue (yg/g). In addition the color of the tissue and the

detection limit for each sample were recorded.

3.3. Implant analysis

The retrieved implants were examined for fretting and corrosion

damage which took place while in the body. It was necessary to

quantify the degree of damage suffered by each screw or plate hole

in order to differentiate between the materials. The form used is

shown in figure 12 and will be described in detail here.

The contact damage evaluation method presented here was developed for compression hole plates as this study consists exclusively

of this type of straight bone plate. The evaluation form, however,

can be used for round hole plates and has been suitably adapted for

other types of plates, e.g., compression hip screw plate, angle blade

plate, etc. (See paper by Brown and Merritt in this proceedings

[8].) The compression hole and its corresponding screw normally have

two distinct contact areas, and the method for producing a numerical

value for degree of damage used in this study is most suited to this

type of plate hole.

403
Figure 12

Hospital Series Recovered implant

Name Plate examination form.

Birth Date Screws

Date Impl. rem. Bone

Date Analysis SEM?

©

CP

(Da

Holes Area Code Area CodeScrew Remarks

The plate hole or screw was examined under a low power binocular

microscope at 8-1 6x magnification. Both the area and the depth of

each of the two contact areas for each screw head or plate hole were evaluated using the following scheme:

Size Depth

0 no contact 0 minimal

1 small 1 superficial

2 medium 2 significant

3 large 3 severe

The degree of damage was then obtained by summing the two size

numbers and the two depth numbers for each screw head or plate hole

and subtracting 3 (i.e., degree of damage = [size + depth] - 3).

This gave a damage scale of 0 negligible to 9 severe. If only one contact area was found, that is, size and degree for one of the

two expected contact areas were zero, then the two remaining numbers

404
were summed and 1-1/2 subtracted. Such holes or screws were then

identifiable by their fractional damage number.

Occasionally on one side of the screw two separate areas were

seen, one on the head and one on the shaft, just under the head.

These were always on one "side" of the screw, and the areas were

"totalled" to make a size for this side of the screws. The size,

shape, and position of the contact areas were also sketched on the

implant evaluation form.

In this scheme for implant analysis, the damage to the screw or

plate from implantation or removal was excluded. It was easy to

identify on the plates when the inside of the plate hole had been

drilled or tapped and when there was damage to the screw head from

tightening or removing the screw. Unfortunately the damage to the

plate hole on tightening and removal of the screw coincides with the

contact site during the implantation period, and it was less easy to

separate out this artifact on the plate hole.

In addition to the degree of damage, it is also possible to

classify the type of damage observed under the binocular microscope.

To date, we have identified nine surface morphologies, and these are

given classification numbers which are not implied to be in order of

severity.

1. Plastic deformation - burrs of material or brows ploughed

into the material

2. Burnished - bright featureless contact area in the case of

stainless steel or the cobalt-chrome-nickel alloy, matt but

smooth for titanium.

3. Rough - the contact area is rough. This is common on titanium, and for the other two alloys when corrosion

features were not positively identified (fig. 13a).

4. Parallel lines - the contact area shows parallel linear

features

5. Cracks, crevices - the contact area appears to have a crack

in the surface although when this is further investigated on

the SEM (fig. 14), it is a deep long corroded region, or the

edge of the contact area is corroded in depth, a crevice.

6. Corrosion - the area appears corroded (fig. 13b, c).

7. Needle pitting - small holes in the surface indicating

pitting in depth.

8. Gross pitting - large pits in the contact area (fig. 15).

9. Rainbow - a rainbow pattern may be present on the polished

unattacked surface next to a corroded area.

These numbers are entered into the implant evaluation form. It

is common for a contact area to exhibit more than one of these

features. The reader is referred to the completed implant form shown

in figure 16.

4 05
Figure 13

a. Contact area on

a titanium screw,

size 2, degree 2,

nature 3.

b. Contact area on a cobalt alloy screw,

size 3, degree 2,

nature 6.

c. Contact area on a stainless steel screw,

size 2, degree 3,

nature 5, 6.
Figure 14

Scanning electron micrograph

of a contact

area containing

a feature which

appears to be a semi -ci rcul ar crack under the

bi nocul ar microscope.

Figure 15

Scanning electron micrograph

of deep pits on

a stainless

steel screw. These are easily identified under the

binocular

microscope as large black

hoi es

Figure 16

An example of

a completed

implant analysis

form.

4 07
4. Results

The numbers of cases for each metal and the average implantation

times are listed in table 1. The titanium alloy cases were grouped

with the commercially pure titanium as insufficient numbers were available to make a separate analysis for these two alloys. First

impressions are, however, that there is no large difference between

titanium and its alloy; the alloy is randomly distributed in the

group. It is anticipated that as more cases are added to the study

we will be able to treat titanium and its alloy separately. In the

series there are only four femurs, one each in the steel and cobalt

alloy groups and two in the titanium steel group.

Table 1. The number of cases and implantation times are listed for the different materials.

Plate Screws Cases

Average Implantation

Time (Months)

Steel

Co alloy

Titanium

Ti alloy

Titanium

Steel

Co alloy

Titanium]

Ti alloy

j

Steel

16

25

16

23

18.0

18.0

15.0

15.9

TOTAL 80 16.9

4.1. Clinical performance

The values recorded for the clinical observations were averaged

for the series of 80 and for each of the plate/screw combinations.

These are recorded in table 2. It becomes evident throughout this

study that the series is too small to attach statistical significance

to more than a few observations. However, the trends observed are worth presenting and discussing. There was no pain or swelling

reported by patients with the titanium plates, whereas with the other

groups the pain reported was similar. Those patients with steel

plates had the greatest amount of swelling recorded. When the values

for these three clinical symptoms were combined, those patients with

titanium plates had a much lower incidence of symptoms. There was more scar formation with the use of cobalt alloy plates. There was more tissue discoloration reported with steel and the cobalt alloy.

These plate removals were for the most part routine removals, and the

general clinical progression was similar and satisfactory for the

four groups with good healing of the fractures.

4 08
Table 2. Clinical observations.

Weather 3 Values

Pain Sens. Swelling Combined Inf. Heal. Scar. Cap. Color

Range 0-2 0-2 0-2 0-6 0-2 0-5 0-3 0-2 0-2

16 STEEL .13 .43 .64 1.5 .07 .75 .15 .88 1 25 COBALT

ALLOY

.42 .58 ,i)5 1.45 .08 .43 .42 .78 .93

16 Ti 0 .29 0 0.29 0 .3 .14 .5 .6

23 Ti/S .43 .7 .19 1.32 0 .58 .07 .7 .7

80 SERIES .35 .54 .32 1.21 .04 .52 .20 .72 .81

4.2. Histologic analysis

The histologic analysis was treated in a similar manner with the

values for each category averaged for the series and for the different

types of implants. The data for connective tissue, bone, and muscle

was about the same for the groups. The tissue was predominantly a connective tissue with occasionally some bone and muscle. The types

of connective tissue have not been subclassif ied at this time. The

data for the remaining histologic evaluations are recorded in Table 3.

The biggest difference is seen in the values recorded for lymphocytes.

The tissue from patients with cobalt alloy plates had a statistically

significant elevation of lymphocytes. When the gradings for lymphocytes, macrophages, and giant cells were added together the cobalt

alloy tissue was still significantly higher. Titanium and titanium

with steel screws had the lowest combined scores. The tissues in

general were quite rich in vascular and lymphatic supply with titanium

having the highest score. The presence of debris in tissue and in

cells was also highest for titanium. These high values for debris

associated with titanium plates with titanium screws are not quite

statistically significant compared to the others. Finally, the

estimated thickness of the tissue averaged about the same for all

four groups.

Table 3. Average values of the histologic grading

Blood + Debris Debris

Macro- Giant 3 Values Lymph in in Plate Lymphs phage Cell Combined Vessels Tissue Cells Thick. Steel 1.9 1.15 0.54 3.36 2.23 1 1.08 2.08 Cobalt Alloy 2.82 1.3 0.3 4.29 2.5 0.73 0.73 2.78 Titanium 1.36 0.35 0.21 1.92 3.64 1.4 2.14 2.0 Ti/Steel 1.25 0.5 0.04 1.78 2.67 1.1 0.89 2.6

Series 1.8 0.82 0.24 2.84 2.73 1.04 1.1 2.4

4 09
4.3. Chemical analysis

The other piece of tissue was analyzed for the presence of metal

and the data on these chemical analyses are presented in Table

4. In all groups there were some tissue samples with no detectable

metal and thus the minimum in all groups is zero. The maximum

values found and the average values for each group are presented in

Table 4. The range is thus zero to the maximum. The highest values

for nickel were recorded with stainless steel plates; the highest

values for cobalt were found with the cobalt alloy plates; the

highest values for chromium were found with the steel plates; the

highest values for titanium were found with the titanium plates. There

is no statistical significance in the data. The data on chemical

analysis needs to be considered carefully and discussed in relation to

other findings.

Table 4. Chemical analysis of tissue over the plates (yg/gm tissue)

Plate

Nickel

Ave (Max)

Cobalt

Ave (Max)

Chromium

Ave (Max)

Titanium

Ave (Max)

Steel

Co alloy

Titanium

Ti/steel

157 (910)

85 (786)

ND*

99 (640)

ND*

371 (2510)

ND*

ND*

1595 (10464)

806 (10219)

14.5 (150)

1129 (9727)

ND*

ND*

1308 (9960)

66 (255)

*ND = not done

4.4. Implant analysis

The examination of the recovered implant produced a degree of

damage number for each platehole and screw head. The degree of damage

scale runs from 0-9, and the histograms in figures 17-19 show the distribution of these scores. Figure 17 compares steel screws and plates

and cobalt alloy screws and plates. Figure 18 shows the distribution

for titanium alloy plates and screws compared with steel plates and screws. Figure 19 shows the distribution for steel screws and plates

and steel screws on titanium plates. For the purposes of constructing

these histograms, the values containing 1/2 points were rounded down.

The mean value of the degree of damage is the value in the top

right of the figures and is also presented in table 5 with the number

of entries for that combination.

Since stainless steel is the most common construction material

for orthopaedic bone plates, it was taken as the reference material

against which the cobalt alloy and titanium were compared.

Figure 17 shows the distribution of the degree of damage for the

cobalt against that for steel. The mean value and the histogram both

indicate that the cobalt alloy suffered less material loss. The x

2 test showed the two distributions to be significantly different, as

4 I O
were all three of the distributions presented (fig. 17-19). Qualitatively the cobalt alloy showed severe metal loss with a score of 5-9

in 17% of all entries compared with steel which had 39% in this range

Table 5. Degree of damage on plate hole and screws.

Plates + Screws

Screws Only Ave. Degree No. of

Plate/Screw Counted Counted of Damage Entries

Series X 3.1 1246

Steel/Steel X 4.1 252

Co alloy/Co alloy X 2.5 387

Titanium/Titanium X 2.6 229

Steel/Steel X 3.9 124

Titanium/Steel X 3.4 184

The picture is similar for steel compared with titanium and its

alloy which had only 15% in the 5-9 range and a lower average. However, the implantation time was on average shorter, at 15 months com- pared with 18 months for steel.

The average degree of damage on the cobalt alloy and titanium

were about equal, 2.5 and 2.6 respectively, although there was one possibly important difference. Very severe damage (7-9) was found on only one plate hole for titanium but on 6% of the cobalt alloy plate

holes and screws. The cause of this will be discussed later.

The performance of steel screws against titanium plates in com- parison to steel screws against steel plates seems to support the con elusion of Riiedi [9] that the behavior of steel is not modified by

the presence of titanium. The average degree of damage on steel screws is improved slightly from 3.9 to 3.4 when used on titanium

plates, although the improvement in the heavy damage range is slight

(fig. 19).

Figure 20 is another way of presenting the implant examination

data. The degree of damage was first averaged for each patient, i.e.

total degree of damage on holes plus screws divided by the number of

holes and screws. The mean and standard deviation for each metal

combination was calculated and the range indicated in figure 20 is one standard deviation either side of the mean. Steel screws with

steel plates have the most severe metal loss. As expected, the steel

screw, titanium plate combination falls midway between all steel and

all titanium, again suggesting that the damage to either is independent of the presence of the other. The cobalt alloy and titanium had

virtually the same mean, but the range of values for the cobalt alloy

was greater.

4 I I
STEEL 4.1

Co-Cr-Ni 2.5 [

3 4 5 6 DEGREE OF DAMAGE

Figure 17

Distribution

of degree of

damage for

stainless steel

holes and screws compared

with cobalt

alloy holes and screws

.

STEEL 41

TITANIUM 2.6 AND TI-6AL-AV 1=1

3 4 5 6 DEGREE OF DAMAGE

Figure 18

Distribution

of degree of

damage for

stainless steel

holes and screws compared

with titanium

and titanium

alloy holes and screws

.

STEEL SCREWS

v STEEL PLATES

39

STEEL SCREWS 3 4

v Ti AND Ti-6AL-4V

3 4 5 DEGREE OF DAMAGE

Figure 19

Distribution

of degree of

damage for

stainless steel screws on stainless steel

plates compared

to stainless

steel screws on titanium plates.

4 I 2
TITANIUM SCREWS

TITANIUM PLATES

Figure 20

Damage (patient

range) for the

four metal groups

Co-Cr-Ni SCREWS

Co-Cr-Ni PLATES

STEEL SCREWS

TITANIUM PLATES

STEEL SCREWS

STEEL PLATES

0 2 3 4 5 DAMAGE (PATIENT RANGE)

6

As mentioned in the methods section, damage to the plate and

screws caused by insertion or removal was, if possible, excluded from

the degree of damage number. Thus the metal loss graded occurred

while in the patient. The low power light microscope observations

gave the following picture concerning the nature of the attack.

Corrosion was commonly observed at the contact area between

steel and steel and on the steel screws in contact with titanium.

This corrosion was in many cases severe and was the reason for the

higher degree of damage scores for steel, as corrosion produces deep

damage areas and thus large damage scores. The mechanism has been

reported to be fretting induced crevice corrosion [10].

The cobalt alloy also corroded, although a lower proportion of

screws and plate holes were corroded. Burnishing, probably produced

by micromovement between the two components, was more common. This

accounts for the high proportion of 0 and 1 scores (fig. 17) for this

Titanium and titanium alloy screws and holes had almost exclusively 2's and 3 ' s in the damage nature code. The contact surface was either a dull matt gray and smooth or a dark gray and rough.

Examples of these contact areas were also looked at under the

scanning electron microscope. The figures 15, 21, and 22 are SEM pictures of contact areas of steel (fig. 15), cobalt alloy (fig. 21), and

titanium (fig. 22a and 22b). Corrosion of the steel and cobalt alloys

was confirmed by the presence of typical corrosion surface morphologies. The rough surface on titanium is shown to have no depth. This

accounts for the lack of high degree of damage ratings, and metal loss

appears to be via a gall and tear mechanism.

metal

4 I 3
Figure 21 Crystal lographic

corrosion pattern on

a cobalt alloy screw

head.

Scanning electron

micrograph.

Figure 22

a. Contact area of

figure 13a as a scan- ning electron micrograph. The contact

damage has no depth.

b. Detail of figure

22a. Metal loss from

titanium by a gal 1 and tear mechanism.

4 ! 4
4.5. Cross correlations

The data was subjected to correlation analysis and the r coefficient determined, and the 95% level taken to indicate a correlation.

It must be pointed out again that the series is small, and statistical

differences are generally not found. However, there were some correlations of special interest.

It might be expected that time is one of the important factors

involved. The length of time the implant was in place should correlate with the amount of corrosion of plate and screw. The findings on these 80 patients do not support this hypothesis. Similarly, the

amount of metal in the tissue should be affected by time, and this

data does not support this hypothesis. Similarly, we saw no correlation between time and debris. However, when one compares time with

the lymphocyte accumulation there is a negative correlation for the

series, steel plates, cobalt alloy plates, and titanium plates with

steel screws. There is no correlation between time and lymphocyte

accumulation with titanium plates.

In the histologic analysis, it is of interest that the debris in

the tissue and the debris in the cells shows a strong correlation with

steel plates, cobalt alloy plates, and titanium plates with steel screws. The correlation between debris in the tissue and debris in

the cells was not found with titanium plates and titanium screws.

When combined histology (lymphocytes, macrophages, and giant

cells) was compared with corrosion values for the respective pair

(values for damage to plate holes and screws under the position of the

tissue biopsy), a strong correlation was observed with only the cobalt

alloy plates. When the lymphocytes were considered alone, there was

no correlation.

When chemical analysis was correlated with various other factors,

the only strong correlation found was the concentration of titanium in

the tissue and damage to the respective pair of plate holes and screws.

5. Discussion

In this paper a scheme for the evaluation of bone plates and

i screws for osteosynthesis has been presented. The object of this

particular study was to investigate the differences between four

different alloys.

It is not easy to demonstrate an advantage over a material

(stainless steel) which has proven satisfactory in millions of cases

and causes truly material related problems only in a very small

percentage of them. Most important is clinical success, but this is

very difficult to define. What is acceptable to one surgeon or patient may not be to another. Thus, it could be impossible and

would certainly require a very large number of cases to prove an

4 I 5
improvement on an already good success rate due to the material

change alone, solely on the basis of the success rate.

In this study it was hoped that this problem could be overcome

by demonstrating that certain disadvantageous phenomena were on balance less severe for a particular material or materials. For

instance, a reduction of pain or swelling during treatment; a reduction in the amount of material released to the host by corrosion or fretting; and a minimal histologic response could all be regarded as desirable improvements.

It is important to collect the maximum amount of data on each case in this type of study. The methods described here were designed

to ensure this. Much of the type of data used in this study have

previously been purely qualitative evaluations and thus not amenable

to statistical methods. A grading scheme was established for each

section, which although somewhat arbitrary, provided usable information. The histologic and degree of damage data were each generated

by a single observer, whereas the clinical data stemmed from three

different hospitals and many individuals. The biases and inaccuracies

introduced by these evaluation methods are, by the nature of the data,

undoubtedly large.

The implant examination part of this study will be considered

first. The authors feel that the method outlined in this paper

proved to be a satisfactory method for investigating the metal loss

from the bone plates and screws used in this study; The data demonstrated that the metal loss is greatest from stainless steel and

that the volume of metal released to the host can be reduced by substituting titanium or cobalt alloy. However, this is certainly insufficient evidence to come to the conclusion that this substitution

should be recommended. The corrosion or wear products from titanium

or the cobalt alloy could elicit less favorable healing or tissue

responses compared to the steel. There is to date insufficient data

to support or refute these possibilities.

A discussion of the method used for chemical analysis is

necessary. When the study was planned, this was thought to be a useful input. However, it has become clear that there are some difficulties when interpreting these results. The method used - acid

digestion of the removed tissue for atomic absorption spectroscopy - does not differentiate between solid particle contamination of the

tissue and metal bound to tissue from metal ions released by cor- rosion. The solid particles are the problem. These may be the

result of fretting, or they could be generated during implantation by

mechanical action on the screw-plate interface when tightening down

the screw (fig. 23). A further source is that some screws are inserted at such an angle that the bone tap or drill goes through the

side of the plate hole. The large particles produced by the latter

mechanism in particular, if included in the tissue analyzed, could

produce misleadingly high metal concentrations. An illustration of

this point is provided by the titanium group where chromium was found

4 I 6
in three cases of the 16 in the group. This presumably comes from the

instruments used to insert or remove the implants. The authors doubt

if these measurements will produce any useful information and are of

the opinion that this total metal content analysis could well be of

minor value and that an analysis method which separates solid wear

particles from metal ions would be of more value.

Figure 23

Scratch and tear

marks on a stainless steel screw

caused by tightening of screw. This is a possible

source of sol id

metal debris.

The histologic analysis also raises a number of questions. The

tissue type was similar in all groups. The tissue is mostly connective tissue, and the description of how much bone or muscle was

present is not contributory. The connective tissue was not subdivided as to loose connective tissue, dense connective tissue, and

the amount of adipose tissue found. This might possibly turn up some differences

The biggest variations were found in the accumulation of lymphocytes, macrophages, and giant cells. The method of analysis is quite

crude; however, detailed analysis including cell counting seems unwarranted. The tissue samples were not of the same size and, therefore, the cells should be counted per unit area. However, the lymphocytes tend to cluster, and the clusters might be missed in setting up

grids for unit area measurements. Rough determination of number and

size of clusters as well as scattered lymphocytes in the tissue sample

seems less time consuming and, although crude, probably more accurate.

A ratio of size of nucleus to cytoplasm as reported by Riede et al

[11] seems unwarranted because of the normal variability in nucleus to

cytoplasm ratio of these cell types.

4 I 7
The correlation of lymphocyte accumulation with other factors was disappointing. There was a negative correlation with time; that is,

the plates removed early had higher quantities of lymphocytes. However, the implant times cluster around the mean, but should this trend

be confirmed, then the question whether or not they were removed early

for subtle reasons not reflected in the clinical report forms must be

addressed.

Of special interest is the strong correlation between the com- bined score of lymphocytes, macrophages, and giant cells with the

degree of damage of the respective pair (plate and screws under the

biopsy) for the cobalt alloy.

The question of metal sensitivity must be considered when a histologic reaction of this type is observed. The issue of metal sen- sitivity in relation to implant analysis is discussed in detail in

another paper in this volume [8], and the reader is referred there for

the details. It is the hypothesis that it is the damage to the implant

in the tissue that will lead to metal ion release and that the metal

ions may complex with proteins and stimulate a sensitivity reaction in some patients. A few of the patients in this series with the cobalt

alloy plate were tested for LIF production [8]. There was one patient

who was a nonmigrator (sensitive and reacting to the implant) who had

a large accumulation of lymphocytes, macrophages, and giant cells.

However, one patient with large accumulations of these cells did not

have any sensitivity on testing. This series is too small to draw

conclusions, but this may be an example that some patients develop

sensitivities and others do not regardless of the metal ion concentration and the accumulation of these cells to remove the ion-protein

complex.

There was also no correlation of debris in the tissue with the

chemical analysis and corrosion. However, the debris ratings did

produce one interesting correlation. The highest grading values for

debris were found in the tissue from the patients with titanium plates.

When the debris in the tissue was correlated with the grading scores for the debris in the cells, there was strong correlation with all

groups except titanium. It was noted on the histology sections that some had large deposits of debris as in figure 10 with no cellular

reaction. This was a feature of titanium plates. The debris produced by the other plate-screw combinations was being engulfed by

cells and stimulating a cellular reaction. The only correlation between debris in the tissue and corrosion of the respective pair was found for the titanium group.

There were many histology sections suggestive of very bad tissue

reactions with large areas of lymphocytes, macrophages, giant cells,

inflammation, and slight necrosis. When the type of implant was checked against these specimens, all four groups were represented.

Once again, more cases are required to identify a trend.

4 I 8
The ultimate test of an implant is its clinical acceptance.

Thus, the clinical data in this type of study requires the care,

understanding and enthusiasm of the physician. It is important to

remind the physician, especially the intern and the resident, that

decisions on compatibility of implants require careful attention to

detail in completing a clinical evaluation from.

6. Summary

In this paper, a protocol for the evaluation of metal osteosynthesis plates has been presented along with a scheme for analyzing

tissue responses and obtaining clinical data. The number of cases

at present available for analysis does not permit any definite con- clusions as to the advantages of one of the alloys tested over another

It is hoped that with the addition of more cases this will be possible

We recommend that the type of protocol we have described here be used

so that comparisons can be made between different studies.

We would like to thank the entire AO/ASIF for undertaking this

study with special thanks to Drs. Allgbwer, Matter, Perren, and Ruedi

for their diligence in collecting the clinical data and supplying the

plates and tissues used in this paper. The histology group at the

Swiss Research Institute, Davos, especially Katie Reusser, are thanked

for their beautiful work and superb records. We are grateful to Fredy

Schmidli in Walderburg for performing the chemical analysis and

finding one or two metal turnings in the tissue samples. Thanks go

to Carrie Green, Dartmouth Medical School, for the computer analysis

of this data.

This work was supported in part by the Educational Foundation of

America and USPHS AMAI 20271.

4 I 9
References

1. Williams, D. F., and Roaf, R., in Implants in Surgery (Saunders,

London, 1973).

2. Colangelo, V. J., and Greene, N. D., Corrosion and fracture of

Type 316 SMO orthopedic implants, J. Biomed. Mater. Res. 3,

247-265 (1969).

3. ASTM F-138 Standard specification for stainless steel bar and

wire for surgical implants (special quality), ASTM Annual Book of

Standards , part 46 (Philadelphia, 1979).

4. ASTM F-563 Standard specification for wrought cobal t-nickelchromium-molybdenum- tungsten-iron alloy for surgical implant

applications, ASTM Annual Book of Standards , part 46

(Philadelphia, 1979).

5. ASTM F-67 Standard specification for unalloyed titanium for

surgical implant applications, ASTM Annual Book of Standards , part 46 (Philadelphia, 1979).

6. ASTM F-136 Standard specifications for titanium-6Al-4V ELI alloy

for use as surgical applications, ASTM Annual Book of Standards , part 46 (Philadelphia, 1979).

7. Perren, S. M., and Geret, V., Technique and results of evaluation

of early tissue reaction to implantation of metals, in Evaluation

of Biomaterials , G. D. Winter, J. Leray, K. deGroot, eds. (John

Wiley, London, 1980 in press).

8. Brown, S. A., and Merritt, K. , Metal allergy and metallurgy (in

this volume).

9. Ruedi , T. P., Titan und Stahl in der Knochenchirurgie, Supplement

123, Mschr. Unfallheik, (Springer-Verlag, Berlin-Heidelberg-New

York, 1975).

10. Simpson, J. P., Merritt, K. , and Brown, S. A., Fretting corrosion

of steel plates and screws, presented at World Biomaterials Congress, Baden near Vienna (1980).

11. Riede, U. N. , Ruedi, Th., Rohner, V. L. E., Perren, S., and

Guggenheim, R., Quantitative und morphologische Erfassung der

Gewebereaktion auf Metal 1 implantate (Osteosynthesematerial )

,

Arch. Orthop. Unfall-Chir. 78, 199-215 (1974).

420
Di scussion

Question (D. F. Williams, University of Liverpool, U.K.): Could it

be made clear exactly what you are saying about titanium deposits in

the tissue?

Are you saying that the presence of titanium in the tissue is

solely due to mechanical damage?

Answer : In our opinion the bulk of the material we saw in the tissue

samples is due to fretting i.e., mechanical wear due to micromovements

between the bone plate and the screw head.

Question (William Ruff, National Bureau of Standards): Was there

evidence for fatigue cracks in the specimens and if so, were there

differences between the materials?

It would seem that the differences in the number density of

surface cracks among materials might have a role in overall response

differences.

Answer : There were no fatigue cracks observed during the macroscopic

examination of the plates.

The use of the word cracks in the examination code is perhaps

misleading. These features (fig. 14 in text) all turned out to be

long narrow corrosion pits on examination in the scanning electron

microscope. Furthermore, they were normally in the center of the

contact area and not, as would be expected for a fatigue crack, at

the top edge of the hole.

Question (Anthony K. Hedley, University of California at Los Angeles):

The authors have shown very beautifully how titanium produces a much

lesser reaction than steel and cobalt chrome alloy. Their phagocyte

count is significantly less in local tissues with titanium than the

latter two metals, yet there is more debris seen in the tissues with

titanium. I am wondering if this is related to a diminished transport

of the ions which therefore must accumulate rather than to the suggestion that to the suggestion that titanium produces more debris than

the other metals described.

I would be interested to know if the authors have been able to

show decreased or suppressed migration and phagocytosis by histocytes

with titanium. This could have important clinical implications when

infection or metal sensitivity are considered.

Answer : It seems from the data so far that titanium suffers less

total metal loss from the implants than stainless steel and a similar

amount compared to the cobalt alloy. In the authors' opinion the

metal loss from titanium is mechanical by fretting but from the other

42 I
two materials a larger percentage of the loss is electrochemical.

The first mechanism produces metal particles the second metal ions in

solution. In the case of corrosion the metal ions are available for

further reactions and may well bind to proteins etc. and trigger

various biological responses.

On the other hand this route is not available to titanium, as the titanium debris is a purely mechanical product.

Our observation is that the titanium debris was not phagocytized

to such a large extent as debris from the other materials, but whether

this is due to a suppression of migration and phagocytosis or that

these responses were just not triggered by the products from titanium

is a question this study cannot answer.

Question (L. M. Taussig, Taussig Associates, Inc.): Can you clarify

any data relating to the reasons for explantation (i.e., fracture,

infection, routine removal).

Answer : In all but one of the cases (pseudoarthrosis) bony union of

the fracture was achieved. There were no broken plates, but three

screws failed on removal.

Infection was reported in three cases and although this may have

resulted in removal earlier than normal; bone healing in these cases was also satisfactory.

Implant removal is recommended AO/ASIF practice and thus the

majority of implants received came from routine removals.

Comment (L. M. Taussig, Taussig Associates, Inc.): On Dr. Ruff's

question on the relation between implant fracture and bone screw corrosion reaction.

We at Taussig Associates have found no correlation between the

incidence and position of bone plate corrosion and fatigue fracture

of the plate.

422
Corrosion, Materials Characteristics and Local Tissue

Reaction Associated with Osteosynthesis Devices

1 2 2 H. Skinner , A.M. Weinstein , A.J.T. Clemow , 2 2 1 M. McPhillips-Meade , J.J. Klawitter , and G. French

Tulane University

New Orleans, Louisiana

Abstract

A series of 112 internal fixation devices, comprising

75 bone plates and 37 hip nails, have been retrieved and

subjected to mechanical bend tests. In addition, the

severity of any corrosion of these devices was measured,

together with their metallurgical condition.

Further, in seven cases, the reaction of the tissue

adjacent to the removed implant was examined and graded

upon an arbitrary scale. Results from these tests are presented and discussed.

1. Introduction

The use of metallic implants to achieve internal fixation in the

treatment of bone fractures is standard orthopaedic practice and for

many year surgeons have achieved excellent results using such devices.

A number of well-documented cases have been reported, however, in which

an implant causing pain may be associated with an excessive degree of

corrosion (1)3. Similarly, it is important that these devices have sufficient mechanical strength so that they do not fracture in service,

and many cases of such an occurrence may be found in the literature (2-7)

The present study is concerned with the relationship between the

material characteristics of internal fixation devices, the extent of

Department of Orthopaedic Surgery, Tulane University Medical School

2 Biomaterials Laboratory, Tulane University School of Engineering

3Figures in parentheses indicate the literature references at the end

of this paper.

423

i
any corrosion associated with them, the local tissue reaction observed

around these implants, and their clinical performance.

2. Corrosion of surgical implants

A number of authors have reported the apparent incidence of cor- rosion in fracture fixation devices (1-12). It is important to recognize, however, that many of these studies were concerned only with the

examination of those implants which had either mechanically failed in

service, or were removed for clinical cause and consequently are not

representative of the population of internal fixation devices as a whole.

In addition, two of the earlier studies of retrieved implants, namely

that by Scales et al. in 1959 (8) and again by the same authors in

1961 (9) , were concerned with examining the relative corrosion resistance "in vivo" of different stainless steels. Since this point is no longer contentious and a standard of ASTM F 139 stainless steel has

been agreed upon, these particular results will be excluded from further discussion.

Once these distinctions have been made, the number of studies

which may be used to indicate the extent of corrosion in surgical implants becomes limited. Between 1967 and 1972, Meachim and Williams

(1) collected a total of 190 orthopaedic implants which were then subjected to a number of metallurgical tests, including a close examination for evidence of any corrosion. Of the 190 implants, 119 were made

of stainless steel, 49 of titanium, and 9 of Co- Cr alloy. Of the stainless steel implants, a total of 64 (54%) exhibited corrosion to some

degree. Of the titanium implants, corrosion was not found to have

occurred in any of the devices.

Weinstein et al. (10) have reported upon the incidence of corro- sion in a total of 133 retrieved prostheses and internal fixation devices, collected as part of an earlier implant retrieval program.

Of particular importance is the finding that corrosion was limited almost exclusively to the stainless steel devices compared to those manu- factured from Co-Cr alloy. Ninety-six percent (96%) of the multicomponent stainless steel devices exhibited interfacial corrosion, whereas in none of the single component stainless steel devices could any

evidence of corrosion be observed. By comparison, corrosion was identified in 5.7% of the Co-Cr alloy implants.

In a similar implant retrieval study, Weinstein et al. (11) studied

the incidence of corrosion in a total of 17 multi-component stainless

steel implants, principally bone plates and hip nails. In all of the

17 implants, corrosion was observed at the interface between screw and

plate. No relationship could be derived, however, between the severity

of corrosion and the length of implantation time. This latter feature

contradicts a finding of Colangelo and Green (12) who reported that both

the incidence and severity of corrosion increased with time in situ for

their series of stainless steel implants examined. However, Colangelo

and Green found that 91% of the multi-component stainless steel devices

exhibited some extent of corrosion compared to only 10% of the single

component implants.

424
In summary, it is apparent that of the metallic biomaterials in use today for the manufacture of internal fixation devices, a very much

higher incidence of corrosion may be expected from those made from stainless steel than from either Co-Cr alloy or titanium. Such a conclusion

is consistent with the "in vitro" corrosion measurements conducted upon

these alloys. In addition, the previous implant retrieval studies have

demonstrated that in those stainless steel devices in which more than one component is present, typically bone plates, the incidence of interfacial

corrosion may approach one hundred per cent of the cases.

3. Tissue reactions associated with internal fixation devices

As important as it is to understand the reaction of surgical implants

to the body environment, it is equally clear that the reaction of the

body to the degradation products of those implants must be appreciated.

It is generally agreed that when present in bulk form, the primary

alloys used provoke a minimal response aside from the formation of

a fibrous membrane which serves to encapsulate the implant. In this

case, a steady state condition may be envisaged between the rate of general dissolution of the alloy and the ability of the host environment to

respond to the dissolution products.

The situation becomes more complicated, however, when either localized corrosion, wear, or a conjoint process occurs. In these cases, the

quantity of dissolution products increases by orders of magnitude and the

severity of the tissue reaction changes. The exact mature of the reactions differs according to the implant alloy involved and therefore will

be considered separately.

3.1. Co-Cr alloy

As mentioned in the previou;: section, Co-Cr alloy exhibits good

corrosion resistance, even within crevices around. screw holes. This

alloy, however, was used for many years in McKee-Farrar hip prostheses,

having metal upon metal bearing surfaces, and most metal knee joints.

In such cases, large numbers of wear particles were produced and the

effect that these have upon adjacent tissue has been reported by Winter

(14) and Willert and Semlitsch (15). These authors agree that the

particles within the tissues in which the various constituents of the

Co-Cr alloy may be identified are phagocytosed by macrophages. Evans

et al. (16) have shown that those patients who had received an allmetal Co-Cr, alloy total hip prosthesis were more sensitive to cobalt,

chromium, and nickel than those who had received a metal-plastic joint.

They concluded that the release of metal ions from the large quantities

of wear particles generated by these prostheses may produce changes in

the local blood supply and thereby lead to necrosis of bone and soft

tissue. It should be emphasized that these reactions have only been

observed for all-metal prostheses where the quantity of metal release

is significantly greater than that found around internal fixation devices .

4 25
3.2. Stainless steel

Due to the lower corrosion resistance of 316 type stainless steel

compared to either the Ti-6A1-4V or Co-Cr alloys, the problems of tissue

reactions are inevitably more severe. This situation is further aggravated by the large number of stainless steel devices inserted for the

internal fixation of fractures each year.

Meachim (17) has reported upon the examination of 120 tissue sam- ples removed during surgery from areas adjacent to orthopaedic implants.

It was found that the release of corrosion products was capable of causing a number of reactions in the surrounding tissue, ranging from the

formation of a fibrous membrane when only mild corrosion occurred to

the appearance of what were labelled "microplates . " These latter particles, having a very similar appearance to haemosiderin were believed,

however, to be extracellular in origin. Meachim and Williams (1) have

reported that in four out of fifteen cases examined, where the removal

of an implant was necessitated due to pain in its locality, severe cor- rosion of an internal fixation plate was accompanied by the presence

of these microplates in the surrounding tissue.

Winter (14) in a similar type of study has categorized the types

of foreign material found within tissue adjacent to stainless steel

implants in the following manner:

Type I deposit: opaque, small irregular shaped particles , 0 . 3mm-0 . lum.

Type II deposit: large, platy, sometimes green particles, 5.0mm-0.1;im.

Type III deposit: yellow brown granules, mainly spherical, 3mm-0.1pm.

The Type I deposit was found to consist of small fragments of

stainless steel and was more associated with the wear of stainless steel

than with its corrosion. Type II and Type III particles were frequently

found together. In a later report Winter (15) demonstrated that the

Type II deposit consisted of a compound rich in chromium, iron and phosphorous. It was also observed that the Type II deposit was associated

with tissue which was either acellular collagen or necrotic.

The Type III deposit would appear to correspond to the "microplates"

reported by Meachim (17) in that close similarity to haemosiderin was

noted. Winter performed selected area electron diffraction upon these

Typo III deposits and found the presence of the iron oxides aFe^-j and

yFe^O^ together with the hydrated iron oxide raFe^O^ . H^O (geolite) and

yFe^O^ . H 9 0 (lepidocrocite) . A. to whether this indicates that the

Type III deposits are haemosiderin produced as a result of excessive

ferrous iron in the body or whether they are a simple corrosion product

remains uncertain. It would be expected, however, that if the latter were the case, then the simultaneous presence of chromium oxide, C^O.^

would have been detected. The reaction of these particles to the

tissue was found to be minimal when present in small quantities. Where

contamination was heavy, however, a similar reaction to the Type II deposit was observed.

4 26
3.3. Titanium

Since, as mentioned previously, titanium and its major alloy Ti-6A1-

4V, exhibits an extremely low incidence of crevice corrosion in vivo, the

only alternative mechanism of titanium release is by uniform corrosion.

Meachim and Williams (1 ) used neutron activation analysis to measure the

titanium concentration in tissue adjacent to 19 titanium implants. They

found that the concentrations varied from patient to patient, with no apparent influence of the duration of implantation. In three of the 19

cases, titanium concentrations of greater than 2000 ppm were measured

compared to an average of 22 ppm around a control series of Co-Cr alloy

implants

Two types of particulate material were observed in the histological

sections: Type "A" giving a positive Perls' stain and having the appearance of normal haemosiderin, and Type "B" which gave a negative Perls'

stain. These latter particles were found in regions of reactive fibrosis

and often within the cytoplasm of fibrocytes, perivascular cells and

macrophages. Meachim and Williams concluded that the release of titanium

from the implant was likely, though not proven to have necessitated the

removal of the implant in five cases.

A. Correlation and conclusion

The insertion of an implant into the human body starts a series of

reactions which may or may not influence the success of the procedure.

Two of these reactions have been discussed here, namely, corrosion and

the severity of any associated tissue reaction.

With regard to the extent of corrosion, it is clear that a certain

degree of interfacial corrosion must be expected from multi-component

stainless steel devices. It remains to be investigated, however, to

what extent this corrosion is significant in determining the clinical

success of these implants. The extent of this corrosion is sufficient

to induce a variety of reactions ranging from a minimal encapsulation

of the device by fibrous tissue to necrosis of adjacent tissue. In such

cases the extent of the tissue reaction would appear to be related to

the extent of the corrosion though this point is by no means certain

since other variables such as patient sensitivity may influence the

result

The Co-Cr alloy implants would appear to exhibit interfacial corrosion at a very much lower rate than equivalent stainless steel devices. It is difficult, however, to determine what tissue reaction

this provokes since the use of this alloy in internal fixation devices

is restricted. Certainly, the presence of large wear particles of this

alloy does induce a severe tissue response, but it is extremely unlikely

that such a situation would ever occur around an internal fixation device .

Of the three alloys used for the manufacture of bone plates, titanium and its major alloy Ti-6A1-4V, possess the best corrosion resistance.

Of greater concern is the observation of extremely high levels of titanium in the tissue surrounding titanium implants.

427
5. Methods of procedure

5.1. Retrieval of implants

A total of 112 internal fixation devices, 75 bone plates and

37 hip devices, obtained from the Moore Clinic in South Carolina,

the V.A. hospitals in San Francisco and New Orleans, and the Children's

Hospital in New Orleans, were studied. Of the bone plates, one was fabricated from Ti , one from a Co-Cr alloy and the remainder from

stainless steel. Of the hip nails, 32 were fabricated from stainless

steel and 5 from Co-Cr alloys.

Upon receipt, all of the implants were thoroughly cleaned with

Alconox and warm water. When necessary a soft brush was used to remove adherent tissue and blood. The implants were then photographed to

provide a permanent record.

5.2. Tissue examination

During operation for the removal of five of the bone plates and

two of the hip devices, the tissue adjacent to the plate was removed

as a continuous strip and identified with respect to the anatomical

orientation of the plate for transverse sectioning at the screw holes.

These were embedded in parafin, sectioned to a thickness of 6 pm and

stained with either H&E, Gomoris Trichrome, Perls' Iron, or Bathophenanthroline Iron. Representative sections corresponding to each screw hole, stained with each stain, were then examined and the reaction to any corrosion products graded on the following scale:

0: thin fibrous membrane containing lipid cells

1: thin acellular fibrous membrane

2: mild chronic inflammatory response

3: moderate chronic inflammatory response without giant cells

4: heavy chronic inflammatory response with giant cells and a few

granulomas

5: severe inflammatory response with giant cells, granulomas and

necrosis

.

5.3. Metallurgical examination

Each of the implants was examined for evidence of any mechanical

damage, wear, burnishing marks, surface flaws and deformation of the

device. This information was recorded upon a standard report form as recommended in ASTM F561 - Recovery of Implant Engineering Examination.

In addition to the above, the extent of corrosion was graded using a scale of 0-5 in the following manner:

0: no surface degradation visible at 60X magnification

1: very mild surface degradation visible at 60X magnification

2: mild surface degradation easily visible at 60X magnification

3: moderate surface degradation visible without magnification

4: heavy degradation visible without magnification

5: very severe surface degradation.

The implants were further tested to determine their mechanical

properties. This involved both Rockwell hardness measurements and the

4: Alconox Inc., N.Y., N.Y. 10003

4 2 8
determination of their bend strengths. For the bone plates, four-point

bend tests were conducted as per ASTM F 382. In order to follow this

standard, however, only plates longer than 5 inches could be tested.

The bend strengths reported are defined as the bending moment required

to produce a permanent defleciton of 0.005 inches.

The bend strengths for the hip devices were measured using the

ASTM F 38 standard method. In this test, the load is applied axially

to the nail portion with the plate portion being held against a vertical support. The bend strength is agian defined as the bending moment

required to produce a permanent deflection of 0.005 inches with the

bending moment being calculated as the product of the perpendicular distance between the point of loading and the lateral edge of the device.

Following mechanical testing, transverse and longitudinal sections

were cut from both bone plates and screws to enable metallographic examination. This involed a measurement of both inclusion content and

grain size. A further section of the device was cut and used for the

determination of chemical composition by either emission or atomic absorption spectroscopy.

6. Results

6.1. Mechanical testing

The results from uhe four point bend tests conducted upon the bone

plates are presented in figure 1 as a function of their respective

hardness value. A good correlation is obtained and it is noticeable

that small changes in material hardness are accompanied by large differences in bend strengths. In figures 2 and 3, equivalent plots have

been made for the hip nail devices. Here the results have been separated

into two catagories, namely standard Jewetts and T-Beams, since the cross sections at the nail-plate junctions of these devices varied considerably.

The apparently poor correlation between bend strength and hardness will be

discussed later.

6.2. Corrosion examination

The corrosion examination revealed that, although none of the Co-Cr

or titanium devices exhibited any evidence of any corrosion, 100% of

both the stainless steel bone plates and hip nails were found to have

corroded. ' This corrosion was concentrated almost entirely at the screwplate interface, with the incidence of gross corrosion being negligible.

The severity of the corrosion for the stainless steel devices

was graded on a scale of 0-5. A mean corrosion index of 1.35 was measured

for both bone plates and hip nails. This compared to a mean corrosion

index of 1.22 for the corresponding screws, figures A and 5.

429
When the corrosion indices for the different plates, averaged over

all of the screw holes, were compared to the hardness of the individual

devices, it was apparent that no correlation could be obtained, figure

6, This would indicate that increased cold work of the alloy, manifested

in an increased hardness value, does not render the material more susceptible to interfacial corrosion,

The severity of corrosion was further compared to the length of implantation time for the various devices, and the results are displayed

in figure 7. It is clear that, from this data, the extent of corrosion

for fracture fixation devices is independent of the duration of implantation. This serves to illustrate well the peculiar nature of surgical

implant corrosion compared to those environments encountered by normal

corrosion-resistant materials. It was found, however, that those implants

attached to weight bearing limbs exhibited a significantly higher average

corrosion index (1,48) than those attached to the upper skeleton (0,98)

(P < 0,05)

6.3, Appearance of corrosion

In conjunction with the grading scheme mentioned above, the appearance of the corroded areas was examined using scanning electron microscopy, One of the problems with such an investigation, however, is that

the corrosion surfaces may be disturbed or damaged during the removal of

the screws. Such damage is difficult to distinguish from both that caused

by insertion of the screw and by possible movement during service. It was found, however, that by carefully following the scratches present

within the plate countersink, the cause of the scratch could generally be

determined. Representative photomicrographs of each corrosion grade are shown in figure 8, (a-f )

.

When the corrosion of a screw or plate hole was graded less than

three, the appearance of the corrosion surfaces was that of small areas

of pitting. Most noticeable, however, was the nature of the corrosion

graded greater than three. In these cases, a large amount of grain

boundary attack was apparent so that individual grains were released.

A clear example of this is shown in figure 9 where both the longitudinal and transverse removal of grains is visible for a plate hole

graded five. In other plates, the extent of preferential attack was

such that selected corrosion within the grains was apparent, figure 10.

This mechanism contrasted with that observed upon the screw chamfers

where the coalescence of individual pits into cracks was visible, figure

11. In both screws and plate countersinks, however, the location of the

corrosion corresponded to the area of surface damage caused by insertion

of the screws,

6.4. Metallurgical examination

The metallographic examination of the microstructures revealed that

almost all of the devices possessed grain sizes on the ASTM scale of

between 5 and 8. Occasionally, however, specimens having an extremely

large grain size were encountered. The inclusion content of all of the

specimens was D1.5 Thin or less.

4 30
6.5. Influence of composition

The influence of composition upon the severity of corrosion for

the fixation devices was analyzed for all of the elements as specified

by ASTM F 139 and, in addition, for copper and the chromium and nickel

equivalent elements. It was found that, apart from one element, the

severity of corrosion was clearly independent of composition. For

this one element, however, namely copper, a possible correlation could

be observed, figure 12,

Obviously, the final actual corrosion of a surgical implant is

dependent upon a number of factors, many independent of material characteristics. Consequently, an examination of the influence of corrosion is limited in its applicability for any given case. With sufficient numbers, however, the other factors should be averaged and a pattern emerge. Such is believed to be the case with the influence of

this element.

6.6. Results of tissue examination

Gross examination of tissue directly adjacent to bone plates re- vealed a smooth, glistening "pseudomembrane" of fibrous tissue. This

surface was interrupted by the screw holes which had tissue growing

into the crevices and screwheads. Small pieces of tissue in the

crevices were occasionally lost in dissection but usually almost all

of the tissue could be preserved. Tissue next to some but not all of

the screw holes had obvious discoloration.

Microscopic examination of each slide stained with H&G was performed to grade the tissue reaction. Examples of tissue sections

representative of each grade are shown in figure 13. It could be

seen that the tissue reaction was quite localized in most of the

sections. The morphology of the section indicated that the tissue

reaction was most severe at the screw-plate junctions. It was in these

areas that tissue reaction grading was performed. At other areas of

the plate, the tissue reaction was uniformly 0 or 1 grade.

3n areas of severe (grades 4,5) tissue reaction, macrophages and

multinucleate giant cells with intracellular blue-staining particulate

material were common. In addition, haemosiderin-like material was

also observed more frequently as the tissue reaction became more severe. Overall, the tissue reaction to the implants was mild. The mean

tissue grade was 2.0, corresponding to mild chronic inflammatory re- sponse on the average.

Sections stained with Perl's stain generally demonstrated an in- crease in the amount of positive material that paralleled the severity

of tissue reaction. Perl's stain is commonly used for staining iron

(Fe) but has the disadvantage of false positries because it contains

iron. Tissue detail with this stain was not as good but appeared to

show Perl's positive material both intracellularly and extracellular ly

Large deposits of the material around severe tissue reaction specimens

stained Perl's positive.

43 I
Bathophenanthrolene (BPA) staining is specific for ferrous iron.

Sections stained with BPA were most positive in areas where Perl ' s stain was most positive. BPA staining demonstrated small amounts of intracellular iron in macrophages in areas of severe tissue reaction. Addition of Thioglycolic acid to the BPA staining converted all ferric iron

to ferrous. This revealed particles which were BPA positive, particles

which stained green-blue, and opaque particles which did not stain.

This suggests that from kinetic limitations, not all ferric iron was converted to ferrous and possibly metallic particles were present because of failure to stain.

6.7. Comparison of tissue and corrosion examinations

The comparison of the tissue reaction around each screw hole with

the associated corrosion for that hole revealed a positive correlation,

whereby the greater the corrosion in each hole the more severe the extent

of the tissue reaction, figure 14. When a linear regression analysis was performed upon this data, a correlation coefficient of 0.41 was obtained,

indicating that the degree of scatter of the results was too high to

allow for any definitive conclusions. It must be remembered, however,

that both tissue and corrosion indices were based on subjective decisions and therefore liable to considerable error. Even so, in certain

individual cases, it was possible to obtain a correlation of the type

shown in figure 15,

7. Discussion

7.1. Mechanical properties

The ASTM recommended tests used in the present research are designed to measure the mechanical properties of either bone plates or hip nails in such a way that the loading conditions approximate those

occurring in vivo. Therefore, the results from these tests are indicative of the relative strengths which may be expected from the

different devices when implanted.

The present examination has revealed that a large variation in

mechanical properties may occur for both hip nails and bone plates,

with only small differences being apparent in Rockwell hardness values.

That this was so may be attributed to the interrelationship between

hardness value, extent of plastic deformation or cold work and the

true yield strength of the material. In particular, with austenitic

stainless steels, the increase in hardness that is the result of cold

work does not occur at the same rate as the increase in yield strength.

Consequently in the present investigation and within the range of

hardnesses measured, the small variations in hardness reflect large

differences in the degree of cold work of the sample and therefore also

of yield strength, which for a given geometry device is the property

measured with the test method.

A less satisfactory correlation was apparent between bend strength

and material hardness for the hip nail devices than for the bone plates.

One of the major reasons for this is the difficulty involved in measuring a hardness value for the hip device in a location representative

432
of the area of maximum stress. For the bone plates the extent of cold

work was uniform along the length of the plate, and therefore suitable

hardness measurements could be made. For the hip nail devices, the extent of cold work varied Lth location and so the hardness values did

not necessarily reflect the mechanical properties, measured with the

strength test.

This large variation in mechanical properties for apparently similar devices, is disturbing from a clinical standpoint. These fracture

fixation implants, and particularly the hip nail devices, are subjected

to large loads even in the non-weight bearing condition, and it lias been

shown here that a two-fold difference in bend strength may occur for

apparently similar devices. Therefore, devices may be utilized for es- sentially identical clinical situations, and yet perform very differently, i.e. undergo unwanted plastic deformation. Since a simple hardness test may be unreliable in determining the strength of any given

implant, data from mechanical tests should be available to the physician

to aid in making a choice of implant.

7.2. Corrosion examination

The results from the present investigation concur closely with

those from previous examination in that while no corrosion v;as observed

for the Co-Cr or Ti-alloy implants, interfacial corrosion was found

to have occurred in 100% of the stainless steel devices.

The similar severity of corrosion observed for both plate countersinks and screw chamfers is interesting in view of their different hardnesses. According to Cigada et al. (13), the crevice corrosion resistance of 316L stainless steel is decreased with increasing degree of

cold work. It would be expected, therefore, that the average corrosion

index for the screws would be greater than that for the countersinks.

That this was not so indicates that crevice corrosion above was not

the sole mechanism by which the materials degraded. A competing mechanism of crevice and fretting corrosion may be envisaged whereb> the

softer plates corroded more by fretting while the harder screws degraded more by crevice corrosion. This postulation is supported by

the fact that those devices implanted in weight bearing limbs exhibited

a higher corrosion index than those in non-weight bearing locations.

Furthermore, the average corrosion index of the plates was found to

be independent of hardness.

The S.E.M. photomicrographs of the areas of corrosion support the

theory of different mechanisms of corrosion operating upon the screw

and plate. Upon the screw chamfer, attack occurred initially by pitting and progressed by the coalescence of these pits into cracks.

Upon the plate countersinks, the mechanism resulted in intergranu lar

attack and the subsequent loss of grains of metal. This would have required the adjacent tissue to accept a significantly larger volume of

metallic debris than would be predicted on the basis of corrosion above.

It should be emphasized that this phenomenon of intergranular attack on

the countersink was observed in a number of plates, none of which ex- hibited any microscopic evidence of sensitization. Gi^da et al . ( 13)

4 33
have proposed that the anisotropy of corrosion observed within piate

countersinks may be related to the inicrostructure of the alloy and in

particular to the shape of the inclusions. In the present investigation, however, no evidence to support this contention was observed.

Rather the appearance of corrosion may be considered a function of the

propensity of the material towards intergranular corrosion. The factors governing this intergranular attack are currently being investigated .

The possible influence of copper concentration upon the corrosion

behavior of stainless steel is interesting, especially since this element is not governed by present ASTM specifications. Even though the

presence of a relationship between corrosion and copper concentration

is far from certain, it would be advisable for further research upon

this matter to be conducted.

Conclusions

1) Hardness measurements have been shown to be a poor indicator of the

strength characteristics of internal fixation devices. Therefore,

it is recommended that the strength be reported for a particular

device

.

2) While the number of devices examined which were manufactured from

materials other than stainless steel were small no evidence of

interfacial corrosion was observed, whereas 100% of the stainless

steel devices exhibited interfacial corrosion.

3) The corrosion between screws and plates has been found to be a conjoint crevice-fretting mechanism. Furthermore, the austenitic

stainless steel is subject to intergranular attack in the non- sensitized condition resulting in large amounts of particulate

material being released to the surrounding tissues.

Acknowledgements

This work was supported by grants from the Veterans Administration,

the National Institute for Arthritis and Metabolism and Digestive Diseases

and the National Institute for Dental Research. The cooperation of Zimmer

(USA), Inc., Warsaw, Indiana, for analysing the chemical composition is

also gratefully acknov;ledged

.

4 3 4
References

(1) Meachim, G. , Williams, D.F.,J, Biomed, Mat, Res,, 7_, 555, (1973),

(2) Brettle, J., Hughes, A.N. , "A metallurgical examination of surgical

implants which have failed in service", Injury, 2_, No. 2, p. 143,

(Oct. 1970).

(3) Hughes, A.N., Jordan, B.A., "Metallurgical observation of some metallic surgical implants which failed in -vivo " . J. Biomed. Mat.

Res. , 6, 33-48, (1972)

(4) Williams, D.F., Meachim, G. , "A combined metallurgical and histological

study of tissue-prosthesis interactions in orthopaedic patients", J. Biomed. Mat. Res. Symp., 8, No. 3, (1974).

(5) Galante, J., Rostoker, W. , Doyle, "Failed femoral stems in total hip

prostheses", J. Bone and Joint Surg., 57A , No. 2, 230-266, (March 1975).

(6) Cohen, J. , "Performance and failure of surgical implants in orthopaedic

surgery", J. Mat., 1_, 354, (1966),

(7) Taussig, L.M. , "Twenty years of surgical implant failure analysisa summary", Trans. 9th Int. Biomaterials Symposium, New Orleans,

(1977).

(8) Scales, J.T., Winter, G.D., "Corrosion of orthopaedic implants", J. Bone

and Joint Surgery, 4J_B, 810, (1959).

(9) Scales, J.T., Winter, G.D., Shirley, J.J., "Corrosion of orthopaedic

implants-Smith Peterson type hip nails", Brit. Med. Journal, 478-482,

(Aug. 1961).

(10) Weinstein, A.M., Amstutz, H. , Pavon, G. , Franceschinini , V.,

Orthopaedic implants-A clincial and metallurgical analysis",

J. Biomed. Mat. Res. Symp. No. 4, 297-325, (1973).

(11) Weinstein, A.M., Spries, W.P., Klawitter, J.J., Clemow, A.J.T., Edmunds,

J.O., "Orthopaedic implant retrieval and analysis study", in Corrosion

and degradation of implant materials, ASTM STP 684, 212-228, (1979).

(12) Colangelo, V.J., Green, N..D. , "Corrosion and fracture of type 316 SMO

orthopaedic implants", J. Biomed. Mater. Res., _3, 247-265, (1969).

(13) Cigada, A., Mazza, B., Mondara, G.A. , Pedeferri, P., Re, C.

Sinigaglia, D. , "Localised corrosion susceptibity of work-hardened

stainless steels in a physiological saline solution in corrosion and

degradation of implant material", ASTM STP 684, B.C. Syrett A. Archarya

Eds., 144-160, (1979).

4 35
(14) Winter, G.D., "Tissue reactions to metallic wear and corrosion

products in human patients", J. Biomed. Mat. Res. Symp., No.

5

(Part 1), 11-26, (1974).

(15) Willert, H.C., Semlitsch, M. , "Reactions of the Articular capsule to

artificial joint prostheses in biocompatibility of implant materials,

ed. D. Williams, Sector Publishing, London, (1976).

(16) Evans, E.M., Freeman, M.A.R., Miller, A.J., Vernon-Roberts, B.

,

"Metal sensitivity as a cause of bone necrosis and loosenign of the

prosthesis in total joint replacement", J. Bone and Joint Surgery,

56B , No. 4. (November 1974).

(17) Meachim, G. , Histological interpretation of tissue changes adjacent

to orthopaedic implants", in Biocompatability of Implant Materials,

ed. D. Williams, Secton Publishing, London, (1976).

4 3G
15

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zLU

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TYPE 1

Dimensions

Avg. Width 1.2 cm

Avg. Thickness 03cm

t

*

30

HARDNESS R,

40

Figure 1. Variation in bend strength with Rockwell hardness

for Cr-Ni-Mo stainless steel bone plates.

70n

Z 60-

X

<2 50"

UJ

o

40-

20

65

JEWETT

70

O

75 80

Figure 2. Variation in bend strength with Rockwell hardness

for Cr-Ni-Mo stainless steel Jewett hip nails.

437
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CO

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Figure 3. Variation in bend strength with Rockwell hardness

Cr-Ni-Mo stainless steel "T-beam" sliding hip nai]

30i

20

10

I.0 2.0 3.0

AVG. CORROSION INDEX

4.0

Figure 4. Histogram showing the range of average corrosion

indices for both bone plates and hip nails.

4 38
300i

CO*20CH z

zO 100-1 o

I 2 3 CORROSION INDEX ILQ

200-

100" 12 3 n4 CORROSION INDEX

Figure 5. Histograms showing the range of corrosion

indices measured for both the countersinks

and screw chamfers.

439
X

u

a:

90 loo

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. • • •

40

Figure 6. Average corrosion index of the fracture fixation

devices as a function of their Rockwell hardness.

X

IdQ

552

o

troco

o

o I <cr>

180mo.

50 I00 I50

IMPLANTATION TIME MONTHS

Figure 7. Average corrosion index of the fracture fixation

devices as a function of their time in-situ.

4 40

Figure 9. S.E.M. photomicrograph of a plate countersink showing intergranular corrosion.

Figure 10. S.E.M. photomicrograph of a screw chamfer showing pitting.

4 4 2
Figure 11. S.E.M. photomicrograph of a plate countersink showing

selective corrosion within the grains.

3.0

• Corrosion Index -vs-%Cu

2.0

Q

Z

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Figure 12. Average corrosion index of the fracture fixation

devices as a function of their copper content.

443
4 4 4
5-

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<

LU

OH

CO

to

25

1-

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CORROSION INDEX

Figure 14. Tissue reaction at individual screw holes

as a function of the associated corrosion

index of that hole.

5i

1 2 3 4 5 6

HOLE #

Figure 15. Comparison of tissue reaction at individual screw

holes with the associated countersink and screw corrosion index along the length of a bone plate.

4 45
Discussion

Question (D. F. Williams, University of Liverpool, U.K.); A few

examples of intergranular corrosion were shown. Could you say whether

this was a frequent finding and if so, could you comment on how this

correlates with the observation that none of the stainless steel

specimens were outside chemical specification?

Answer : Our S.E.M. study revealed that intergranular corrosion was common whenever the corrosion index was within the range 3-5 according

to our corrosion scheme mentioned in the text. In this respect it

would appear to be an extension of the general crevice corrosion

observed in all of the plates and therefore, it is not altogether

surprising that it occurred for plates within the chemical specifications.

Question (D. C. Richardson, Food and Drug Administration): In the

retrievals acquired after you began the prospective phase of your

program: 1) were any of the patients tested at removal for metal

sensitization, and, if so, 2) was there any semiquantitative correlation between the "index of tissue reaction" and the demonstration of

immune sensi ti vity/sensitization?

Answer : Unfortunately, our patients were not tested for metal sensitization.

Question (unidentified): Did you find evidence for fretting damage

and/or debris particles associated with the surfaces and tissue

specimens studied? If so, did any correlation exist with alloy

chemistry or type?

Answer : Conclusive evidence to demonstrate fretting damage could

only be obtained by examination under the S.E.M. Even then it was frequently difficult to differentiate between areas of fretting and

the damage caused by removal of the screw. We did see areas of

fretting particularly upon the plates as opposed to the screws, but

could not identify debris from this within the tissue samples. To

date, we have not examined sufficient numbers of plates to show any

correlation between fretting damage and alloy chemistry or type of

device.

Question (Anthony K. Kidlet, University of California at Los Angeles):

Did you see more corrosion with D.C.P. plates than with standard

plates, and if so do you think this has important clinical application

in terms of plate strength, and the degree of local tissue response

to the implant?

Answer : Corrosion occurred almost exclusively at screw-plate junctions.

Tissue response correlated with corrosion in that it was more marked

at screw holes. There was a significant difference in corrosion
between lower extremity plates and uppper extremity plates, suggesting

that motion from weight bearing might be important. Because of the manner in which D.C.P. plates are applied (i.e., compression with

only one or two screws), we would expect no difference between D.C.P.

and standard plates. We feel the degree of corrosion is unlikely to

contribute to catastrophic failure before fracture union except in

poorly-executed lower extremity fracture fixation.

Question (S. Leray, INSERM): Is it possible to relate the high

release of metallic material and subsequent tissue reaction due to

friction between screw and plate to the skin redness observed by

Brown and Merritt at corresponding sites, (paper given on May 1 on metal allergy)? i.e., distinguish cell mediated reaction from local

tissue damage and inflammation early.

Answer : Our seven prospective plate removals demonstrated no significant

skin change. Only three of these plates were removed because of

clinical symptoms.

) 4 4 7

THE EVALUATION OF EXPLANTED UMBILICAL VEIN GRAFTS

Steven Weinberg

Meadox Medicals, Inc.

103 Bauer Drive

Oakland, New Jersey 07436

The evaluation of retrieved vascular graft samples is critical if the clinical function of a vascular prosthesis is to be adequately

understood. During the past five years, 36 explanted human umbilical

vein grafts* have been evaluated after implant periods ranging from

1 minute to 42 months. The testing program included CST, ATR, SEM,

EDAX, histopathology, TEM, and compliance studies. Critical surface

tensions were stable and remained at the pre -implant value of about

25 dynes/cm for periods up to 42 months. Some lipid was identified

within the graft using IR analysis, however, results indicate that

this phenomena is primarily patient-related rather than graft-related.

No calcification of any graft samples has been noted to date. The

blood-contact surface of patent grafts is covered with protein, moreover, no neo-intimal proliferation has been seen within the graft

material. Histological and TEM evaluations have demonstrated that

the primary changes seen in a patent graft are: 1) a compaction of the

graft, and 2) a decrease in cellularity with implant time. In general

the graft has many characteristics similar to the ASV and excellent

clinical results have been seen thus far.

I . Introduction

The evaluation of explanted graft materials has received relatively little attention in the past considering the large number of

grafts that have been implanted since the early 1950' s. Reports which

exist in the literature include evaluation of explanted autogenous veins

[1,2 ? 31, DacronR grafts [4,5], and bovine carotid artery grafts [63;

J but information is limited on recent vintage vascular grafts such as

| PTFE and the umbilical vein prosthesis. With the exception of the

autogenous saphenous vein (ASV), the history of the biological -based

vascular graft has not been impressive. The ASV is the "gold standard"

i in small vessel replacement; however, as can be seen from the work of

I Szilagyi []_] and DeWeese [3] , this "gold standard" is not without its

morbidity and failure.

*Biograft® Meadox Medicals, Inc., Oakland, New Jersey

4 49
Before an evaluation of explanted graft materials can be undertaken, careful consideration must be given to the objectives of the

explant study. In many cases, grafts are explanted in the surgical

environment with little thought as to the information sought and what

preparation procedures must be utilized to best preserve the sample

for future evaluation. For example, if a graft is to be evaluated

for scanning electron microscopy, care must be taken to use the proper fixative to insure the highest quality scans; but, when a fixative

is utilized, limited mechanical studies can be conducted because of

resultant tissue fixation. In any study great care must be taken to

define the testing program prior to explantation if a maximum amount

of information is to be obtained from a small segment of graft material.

A complicating factor which can limit the information gained from

an explanted sample is the mode of "graft failure". Some of these

failures may, in fact, not be related to the graft; however, documentation of this point is not common. Typically, modes of "graft failure"

reported in the literature include infection [7,8], aneurysmal dilatation [9,10], and thrombosis [11,12], but little data has been published

on patent explanted human grafts or graft segments because of the com- plications associated with their retrieval. Further, if these explanted

grafts are retrieved surgically, they rarely make their way to the

manufacturer for evaluation because of several reasons, key among them

are: 1) medical, legal implications, 2) complexities associated with

proper graft retrieval, and 3) lack of interest in the subject.

In this paper I will focus on an explant program specifically

developed for clinical evaluation of the human umbilical vein graft

manufactured by Meadox Medicals, Inc., which goes under the tradename,

Biograft©. This graft is constructed from human umbilical cords which

are preserved in glutaraldehyde, stripped of the umbilical arteries

and most adventitia, sterilized, and then stored in a pure 50% ethanol

solution. A detailed description of this human umbilical cord graft

is not presented in this paper as other references exist on the subject [13,14].

2 . Methods

Our experience in the vascular graft field has shown that the

first hurdle which must be overcome in any graft retrieval program is

the acquisition of the samples. In our study the majority of the

umbilical vein grafts were obtained from Drs. Herbert Dardik, Irving

Dardik, and I. Ibrahim of Englewood Hospital. In addition, some graft

samples were obtained from Dr. William Abbott at Massachusetts General

Hospital. Attempts were made to obtain samples from other clinical

centers, but, these attempts were universally unsuccessful.

Figure 1 illustrates the testing program which was used on preimplant and explanted Biografts®. This program consisted of surface

4 50
analyses, biochemical assays, physical tests, and morphological studies.

The surface studies, conducted by Dr. Robert Baier at Calspan Corporation, included attenuated total reflection and critical surface tension.

These tests have been described in detail elsewhere [15] and will not

be repeated in this paper.

BIOGRAFT*

IN SITU EVALUATIONS

SURFACE

CST*

ATR*

CHARGE

SEM/EDAX*

* Explant Evaluation

MECHANICAL

POROSITY

BURST

UTS

COMPLIANCE*

BIOCHEMISTRY

XLD

Ts ENZYME

DIGESTION

COLLAGEN

EXTRACTION

MORPHOLOGY

GROSS*

LIGHT*

TEM*

Figure 1. Description of the testing program.

Mechanical testing focused on graft characteristics which are believed to affect in vivo graft function. These tests included compliance testing, porosity, burst strength, and ultimate tensile strength.

These tests coupled with biochemical assays such as cross-link density,

shrink temperature, enzyme digestibility, and soluble collagen extraction studies yielded an excellent understanding of graft strength and

tanning efficiency, respectively.

Histological and transmission electron examination of these samples were done by Drs. Michael Meenaghan and Joseph Natiella at the

State University at Buffalo, New York; whereas, the SEM work was completed at Calspan by Dr. Robert Baier.

45 I
3. Results

Thus far, a total of 36 human explant samples have been received

and evaluated with implant times ranging from 1 minute to 42 months.

It is impossible to review all the information in this paper, so key

points will be presented to illustrate the changes observed in the

umbilical vein graft with time. Comparison will be made when applicable to pre -implant data.

3.1 SEM

Figure 2A is a typical pre- implant scanning electron picture

(150X) showing the general architecture of the human umbilical cord

vein graft. For the most part the surface is relatively smooth, but,

as can be seen in this figure, some minor imperfections might occur

as a result of processing. The corrugated appearance of the lumen,

visible at 2000X, is a result of the internal elastic lamina which

remains intact and is located below the subendothelial layer. With

time the surface of the graft becomes smooth as a result of a uniform

coating of protein. Figure 2B is the same graft 3^ years later, demonstrating a typical surface appearance. This surface is primarily

protein with an occasional blood cell noted on the lumen. In the case of a thrombosed prosthesis, the surface is covered by a fiber network

with entrapped cells. The early blood contact events were documented

with human samples taken 1-10 minutes after blood contact. Figure 3A

is a sample taken 4 minutes after blood contact. Figure 3B represents

the same graft 6 months after implantation. In this case the coverage

of protein is not yet complete and the folds associated with the internal elastic lamina can be clearly identified. In this sample some fibrin- like strands are also present after 6 months.

3.2 CST

In order to evaluate the relative biocompatibility of the graft

surface, CST was chosen as the routine testing parameter. In contrast

to some biocompatibility tests, this analysis can be conducted on explanted grafts as well as pre-implanted controls. Figure 4 represents

a typical surface tension plot taken from a 3^ year old explanted

specimen. The CST value falls into the reported biocompatibility range

of 20-30 dynes/cm even after an extended implant period. The effect of

implant period on CST is shown in figure 5. On patent graft samples

the CST remains about 25 dynes/cm up to 42 months post -operatively.

CST's typically could not be obtained on thrombosed grafts because total

removal of the thrombus was impossible and measurements could not be

made on the surface without interference from the remaining clot.

452
150X (20kv)

Figure 2A. (Pre -implant).

iooM |_|

2B. (3h years explant).

453
10P GRAFT FLOW SURFACE AFTER 4 MINUTES

Figure 3A.

3B. (6-month explant)

.

4 54
Figure 4. Contact angle data plot revealing the critical surface

tension of an implanted, stabilized human umbilical

cord vein's blood flow surface to have remained in the

"biocompatible" range for more than 3 years.

4 5'
50 r

6 DACRON

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£

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20

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PTFE

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1

EH . TF

1 ±

4 6 8 42

IMPLANT TIME (Months)

ZONE OF

BIOCOMPATIBILITY

Figure 5. CST value after various periods of implantation.

4 5G
3.3 ATR

The control infrared spectrum is shown in figure 6A demonstrating

strong protein bands and weak or absent hydrocarbon peaks. In contrast, some explanted grafts have lipid peaks as demonstrated in the

3h year sample shown in figure 6B. The presence of this lipoidal

material appears not to affect the CST which in this graft was 25

dynes/cm. It should be stressed that even with some lipoidal material

within the graft, calcification has not been identified in any ex- planted samples. The lipid level within the graft appears to be more

patient- and hemodynamic -related than graft- or implant time-related.

This point is demonstrated in figures 7A and 7B which represent the

infrared spectra for two explanted grafts, 8 months and 34 months,

respectively. The quantity of lipid in the 8-month sample is significantly higher than that seen in the 34 -month sample, even though the

explant period differs by a factor of 4.

The work of Abbott [16], has demonstrated that a relationship

exists between early thrombosis and graft compliance. In fact,

Edwards [17] suggests that late graft failures of the autogenous

saphenous vein may be compliance -related. Figure 8 is a plot of

compliance versus pressure for the control human umbilical cord vein

and several explanted samples of the graft ranging in implant period

from 1 week to 36 months. A reduction in compliance is seen with this

graft, which we believe is primarily due to fibrous encapsulation of

the Dacron mesh material. For comparison, compliance values for FTFE,

ASV, and Dacron at a pressure of 105mm are also shown on this plot.

3.4 Compliance

457

Mi
INSTRUMENTAL ARTIFACTS

4000 3600 3200 2800 2400 2000 1800 !600 FREQUENCY (CM') 1400 1200 1000

Figure 6A. Typical internal reflection infrared spectra characterizing the pre- implant blood flow surfaces of stabilized

human umbilical cord veins as prepared for arterial grafting.

Figure 6B. Internal reflection infrared spectrum characterizing the

blood flow surface of an implanted, stabilized human

umbilical cord vein as harvested patent following 3h years

service as a human arterial graft.

4 5 8
I FREQUENCY (CM ) 4000 36C0 3200 2800 2400 2000 1800 1600 1400 1200 1000

0 \ 25 3 0 3 b 40 5 iMlCftONS' 6 7 8 ? 10

Figure 7A. Internal reflection infrared spectrum of the blood flow

surface of a stabilized human umbilical cord vein harvested patent after 8 -months implantation as a human

arterial prosthesis.

MICROMETERS ((.m) 2-5 3.0 3S 4C 5 6 7 6 9 10 II LIPID AND

PROTEIN ABSORPTION BANDS

2C 20-,-

1 . ; Q 0 4000 3600 3200 2800 2400 2000 1800 1A00 1400 1200 1000 FREQUENCY (CM'}

Figure 7B. Internal reflection infrared spectrum characterizing the

blood flow surface of a stabilized human umbilical cord

vein harvested after 34-months service as a prosthetic

arterial graft.

439
• FEMORAL ARTERY

Figure 8. Compliance versus pressure for a series of explant um- bilical vein grafts along with other graft materials.

a so
3.5 Morphology

Morphological studies of explanted Biografts® included procedures

ranging from gross evaluation to transmission and scanning electron

microscopy. Typical histological changes seen in a patent graft are demonstrated by a comparison of figures 9 and 10 which represent a preimplant and 8 -month explant samples, respectively. Shortly after

implantation the graft becomes compacted due to the hydrodynamic forces

imposed upon the graft material.

Figure 9. Histological section of pre-implant sample demonstrating the

intact media and adventitia.

4 G I
Figure 10. 8-month explanted sample demonstrating graft compaction

and mild reaction around the mesh.

As time progresses, the cellularity of the graft decreases leaving

the 42-month sample almost acellular (figure 11). Initially, the reac- tion to the Dacron mesh is relatively mild and, as can be seen in the

42-month sample, this reaction decreases with time (D) . The compressed

media is represented by the arrows and still can be distinguished from

the connective tissue zone.

4 62
At the EM level the internal elastic lamina remains intact as does

the external elastic lamina surrounding the smooth muscle cells.

Figure 11. "hh year explanted sample showing mesh material (D) and

the compressed media (arrows)

4. Discussion

Acquisition and evaluation of explanted devices has been, and still

remains, one of the most difficult problems in the device industry.

Most devices are explanted with minimal regard to future evaluation; and,

in general, relatively little information is reported in the literature

considering the large number of devices being implanted throughout the

world. Biocompatibility of graft materials has been evaluated using

various techniques ranging from protein absorption studies through animal implantation. In our case the CST was used as an indicator of biocompatibility even though the importance of this parameter has been at

issue for many years within the biomaterials field. Dr. Baier has long

I been a proponent of this concept and its general use has recently become

'more widespread. Natural blood vessels have a CST ranging from 20-30

dynes/cm which is similar to that of the unprocessed and processed umIbilical vein graft. The maintenance of this parameter even in the

absence of the endothelial cells has yielded excellent results in the

clinic and is currently being used as a routine QA parameter. Patent

4G3
grafts which have been explanted as a result of non-graft-related patient

death or as a result of graft revision for progressive disease, have

yielded CST values around 25 dynes/an. This has been the case even when

lipid has been identified within the graft wall. Explanted graft sam- ples, up to 42 months post-operative, have CST within the biological

(biocompatible) range. However, it should be noted that we have no

definitive evidence at this time indicating that a CST value outside

this range would be an indicator of an unacceptable implant.

Using infrared analysis, explanted grafts typically have strong

peaks at 1650cm~l and 1550cm"l showing proteinaceous deposition on the

surface. With some patients IR peaks may also be found at 1750cm~l and

2950cm" 1 indicating the presence of lipoidal material within the graft.

The age of the sample does not appear to relate to the presence or quantity of the lipid within the graft. Our data suggests that the

patient and his blood chemistry are more important in the lipid intake

phenomena than the biochemical nature of the human umbilical vein graft.

No calcification has been seen in any graft sample to date as evaluated

by IR or EDAX. Up to 3h years post -operative morphological changes

which have been identified within the graft are minimal. At gross

dissection the lumenal surface of most patent grafts retains its glistening appearance with minimal alteration of the blood interface as can

be seen in the 33-month specimen in figure 10A. In a few cases some changes have been seen at gross evaluation. Figure 10B shows a gross

specimen obtained at 12 months post-operative where circumferential

rings appear to be present on the surface. This sample was functional

at the time of explant and the significance of the change is yet undefined. At this time we have no explanation for this change, but it may

be a result of lengthening of the graft in situ or excessive graft length

at implantation.

4 G4
4 G 5
At the light microscopy level the patent graft retains its basic

structure with implant periods up to 3% years. The major changes seen

at the light level appear to be a compaction or reduction in wall thick- ness shortly after implantation due to hydrodynamic stresses, a mild

foreign body reaction around the Dacron supportive mesh material, and

a reduction in cellularity with time. No neo-intimal hyperplasia has

been seen on any graft sample so the internal caliber of the graft maintains its initial pre-implant value. In some sections the internal

elastic lamina becomes more visable at the light microscopy level as a result of lipid uptake within this structure. The internal elastic

lamina appears to act as a barrier to lipid infiltration into the body

of the graft; but, in a few TEM sections some lipid droplets have been

seen within the body of the graft.

As the graft ages in situ , some cellular debris and cellular degeneration of the smooth muscle cell is seen at the EM level, however,

the external basal lamina around the smooth muscle cells remains intact.

The internal elastic lamina which separates the subendothelial zone from

the media remains intact, at least up to 42 months, and the general mor- phological structure of the tanned umbilical vein graft remains intact.

The surface of the Biograft® after processing is similar in many

respects to the de -endothelial! zed surface of the ASV. After delivery

the endothelial cells coating the lumen of the vein graft slough from

the surface and only a few endothelial cells remain on the graft after

processing. The subendothelial layer between the lumen and the internal

elastic lamina remains intact and becomes the "biocompatible" bloodcontact surface.

A growing amount of data is being published with respect to the

relationship between graft compliance and patency. As was shown in fig- ure 8, the pre-implant compliance of the Biograft is similar to that of

the ASV and significantly higher than either the Dacron or PTFE graft.

With time the compliance of the graft decreases, and this reduction

appears to be independent of implant time. We believe that compliance

changes are, in part, due to encapsulation of the Dacron mesh surrounding the graft. It is not known, at this time, whether the ultimate

patency rate is or is not dependent upon changes in compliance, however,

future data may elucidate this point.

5 . Conclusions

In general, the human umbilical vein graft has many characteristics

similar to the ASV including CST, infrared spectrum, electronegativity,

compliance, and morphology. These factors may not in themselves be

controlling, but together they characterize a graft material which has

yielded impressive clinical results in difficult salvage and pheripheral

vascular cases. Data reported in this study were obtained at graft

revision, bypass extension, and graft failure; and as a result of this

explant evaluation, some general conclusions can be drawn concerning

this graft.

4 G6
1. The subendothelial surface of the Biograf becomes covered with a smooth proteinaceous layer which does not thicken or reduce the

graft's internal diameter with time.

2. The critical surface tension for patent grafts remain constant up

to 42 months post -operative at a value of approximately 25 dynes/ cm even with the presence of some lipid material within the graft.

3. Lipid accumulation in the graft wall appears to be patient- not

graft-related.

4. No calcification of the Biograf1® has been seen using any analytical

test to date.

5. Compliance of the pre -implant Biograf# is near the ASV, however,

reduction of compliance has been demonstrated after implantation.

6. Histologically, a graft becomes more compact as a result of hydrodynamic pressures and loses cellularity with time. The foreign

body reaction associated with the Dacron mesh material becomes less

pronounced as the implantation period increases.

Questions still remain with respect to the ten-year prognosis for

this prosthetic graft, and these, unfortunately, can only be answered

after extended implant periods. Thus far, results are impressive, and

clinical acceptance of this prosthesis is increasing all over the world.

6 . Acknowledgments

The author would like to thank and acknowledge the efforts of all

members of the Biograft® retrieval and evaluation team. In particular,

special thanks to Drs. Herbert Dardik, Irving Dardik, and I. Ibrahim

of Englewood Hospital, Englewood, New Jersey, whose close clinical

collaboration and graft retrieval efforts made successful completion

of this program possible. Thanks also to Drs. Michael Meenaghan and

Joseph Natiella for their detailed TEM and histological evaluations.

Special thanks also to Dr. Robert Baier, Ms. Ann Meyer, Charles Ackers,

Vito DePalma, and Dennis Goupil for their efforts on surface characterization of the umbilical vein graft, and to Drs. William Abbott, Joseph

Megerman, and Gil L'ltalien for compliance evaluation of pre-implant and

post- implant Biograft® samples. Personal thanks to Debra Creighton for

her efforts in typing this manuscript.

4 G7
References

[1] Szilagyi, D.E., Hageman, J.H., Smith, R.F., Elliott, J. P., Brown,

F., and Dietz, P., Autogenous vein grafting in femoropopliteal

atherosclerosis: The limits of its effectiveness, Surg. 86_, [6],

836-851 (Dec. 1979).

[2] Barboriak, J.J., Pintar, K., Van Horn, D.L., Batayias, G.E., and

Korns, M.E., Pathologic findings in the aortocoronary vein grafts:

A scanning electron microscope study, Atherosclerosis 29_, 69-80

(1978).

[3] DeWeese, J.A., and Rob, C.G., Autogenous venous grafts ten years

later, Surg. 82, [61, 775-784 (Dec. 1977).

[4] Sauvage, L.R., Berger, K., Barros D'Sa, A.A.B., Yates, S.G., Walker,

M.W., Robel, S.B., Lischko, M.M. , Wood, S.J., Davis, C.C., and

Rittenhouse, E.A., Dacron arterial prostheses, Graft Materials in

Vascular Surgery , Dardik, H. , ed. , pp. 153-168 (Symposia Specialists,

Inc., Miami, FL, 1978)

.

[5] Cooley, D.A., Wukasch, D.C., Bennett, J.G., and Trono, R. , Double

velour knitted dacron grafts for aorto-iliac vascular replacements,

Vascular Grafts , Sawyer, P.N., Kaplitt, M.J., eds., pp. 197-207

(Appleton-Century-Crofts , New York, N.Y., 1978).

[6] VanderWerf, B.A., Kumar, S.S., Rattazzi, L.C., Katzman, H.E., and

Schild, A.F., Experience with bovine heterografts in arteriovenous

fistulas for dialysis access, Vascular Grafts , Sawyer, P.N., Kaplitt,

M.J., eds., pp. 305-308 (Appleton-Century-Crofts, New York, N.Y.,

1978).

[7] Agrifoglio, G. , Constantini, S. , Zanetta, M. , and Castelli, P.,

Infections and analtomotic false aneurysms in reconstructive vas- cular surgery, J. Cardiovasc. Surg. 20_, 25 (1979).

[8] Baker, M.S., and Baker, B.H., Infected aortic bifurcation grafts,

Surg. 81, 731 (1976).

[9] May, J., and Stephen, M. , Multiple aneurysms in dacron velour graft,

Arch. Surg. 113, 320 (1978).

[10] Ottinger, L.W., Darling, R.C., Wirthlin, L.S., and Linton, R.R.

,

Failure of ultralightweight knitted dacron grafts in arterial recon- struction, Arch. Surg. Ill , 146-149 (Feb. 1976).

[11] Bartos, J., Vancura, J., and Tersip, K. , Early and late thrombosis

of prostheses implanted in the aorto-iliac region. Treatment and

prevention, J. Cardiovasc. Surg. (Torino) 1_2_, 19 (1971).

4GB
2] Stanton, P.E., Lamis, P. A., Gross, W.S., and McCluskey, D.

Correction of late aortic-bifemoral graft failures, Am. Surg.

497 (1977).

3] Baier, R.E., Akers, C.K., Perlmutter, S., Dardik, H. , Dardik, I.,

and Wodka, M. , Processed human umbilical cord veins for vascular

reconstructive surgery, Trans. Amer. Soc. Artif. Int. Organs

XXII (1976).

4] Dardik, H. , Ibrahim, I.M., Dardik, I.I., Glutaraldehyde stabilized

human umbilical cord vein as a vascular prosthesis, Graft Materials

in Vascular Surgery , Dardik, H. , ed. , pp. 279-295 (Symposia Specialists, Inc., Miami, FL, 1978).

5] Baier, R.E., Physical chemistry of the vascular interface: Composition, texture, and adhesive quality, Vascular Grafts , Sawyer,

P.N., Kaplitt, M.J., eds., pp. 76-107 (Appleton-Century- Crofts,

New York, N.Y., 1978).

5] Kidson, I.G., Abbott, W.A., Low Compliance and arterial graft

occlusion, Circulation Supp. I, 58_, [3], 1-4 (Sept. 1978).

7] Edwards, W.S., Arterial grafts: past, present, and future, Arch.

Surg. 113, 1225-1233 (Nov. 1978).

4 S3

Jki

WEAR OF POLYMERIC PROSTHESIS - CLINICAL REALITY, RETRIEVED IMPLANTS AND LABORATORY PREDICTIONS

Ian C Clarke, Ph.D.

Orthopaedic Biomechanics Laboratory

Orthopaedic Hospital (1)

Department of Orthopaedics and Mechanical Engineering

University of Southern California

Up to 17 years clinical experience with

polymeric components of hip prostheses has shown

that (a) polyethylene femoral balls have poor wear resistance, and (b) with one exception the

major series have generally had no reoperations

due to wear or fracture problems in polyethylene

acetabulae. Average wear rates expected in up

to 10 years use may vary from a low of 40

um/year to a high of 200 um/year, (c) there are

at least 5 published reports, each describing

between 2 and 6 cases of documented gross wear

or fracture of retrieved polyethylene acetabulae, (d) the effect of acrylic cement on polyethylene wear rates is unclear and (e) Delrin has

also been used apparently successfully for 10

years in the Christiansen total hip.

Up to 9 years followup with tibio-femoral

joints has not yet shown any wear revision problems. Retrieved polyethylene components feature

more extensive disruption and deformation than

in hips. Knee simulator studies indicated that

contact stresses, volumetric and linear wear

rates in various designs could vary by x270, x20

and xllO, respectively. Patello-femoral results

on implant performance are not yet available.

Simulator studies of various patellar designs

showed that volumetric and linear wear rates

could vary x20 and x210 times, respectively.

The clinical implications of these data may be

worthy of concern. Concern was expressed that

(a) the relatively large numbers of annual rates

of implant exchanges seen nationwide in this

country did not appear reflected in the collections of the current implant retrieval programs

and (b) the public dissemination of the retrieved implant data seldom seemed effective.

(1) 2400 South Flower Street^Los Angeles, CA 90007

47 I
1. Introduction

One of our interests in current implant retrieval programs involves the study of wear and plastic deformation observed in polymeric components of various joint-replacements

[17,35] (2). This provides a basis for realistic interpretation of problems encountered in-vivo with regard to material selection, implant design and patient usage, i.e.

clinical reality. It also provides the essential feedback

into experimental design and test protocols for laboratory

wear tests and prosthesis-design programs.

The stainless steel and polyethylene materials combination first used in the total hip joint [8] has now been accepted as a very adequate wear combination with up to 14

years followup in some cases [10,21,29], However, there is now an active search for better alternatives to polyethylene

for three reasons. One is that the increasing incidence of

such procedures in younger patients has placed considerable

demands on the implants due to higher patient activity levels and and longer life expectancies [2,6,18]» Second, the

conditions experienced by joint replacements other than the

hip are generally much more severe. In particular, the tibial and patellar components of knee-joint replacements are

at a considerable disadvantage compared to the acetabulum of

the hip joint. Thirdly, certain designs of prostheses, such

as surface replacements of the hip, are limited to very thin

component wall thicknesses due to space constraints [15]

The objectives of this paper are therefore to review:

1. published clinical observations of wear assessments

in various retrieved implants but mainly the hip and knee

joints

.

2. the role of laboratory wear studies in selection of

suitable biomaterials.

3. the wear data gathered from the implant retrieval

programs of the University of California at Los Angeles

(UCLA) and University of Southern California (USC).

Current state of the art is focused on metal/plastic

combinations of total joint replacements. Therefore the

specific focus of this paper is on the deformation, creep

and wear behavior of the polymeric components.

(2) Numbers in brackets indicate the literature

references at the end of this paper.

472
2. Polyethylene Hip Prostheses

2.1. Clinical reality

The majority of data on wear and creep phenomena from

implants comes from the hip joint and then, in rapidly descending order, the knee and ankle joints.

The adverse effects of any polymer, even polyethylene,

bearing against cartilage or bone in a hemiarthroplasty situation have been well documented over the last two decades

[20,24,26,40,67]. The rapid erosion of the polymer and the severe granulomatous tissue reaction (Fig. 1) to the debris

with concomittant loosening of the implant results in disaster.

POLYETHYLENE DEBRIS (20imi 3

)

FOREIGN BODY GRANULOMAS

HYPERTROPHIC

SYNOVIAL VILLI CAPSULAR

MICROABSCESS

BONE LYSIS 1 r

r CELL DEBRIS

P.E. PARTICLES

GIANT CELLS MACROPHAGES

NECROTIC TISSUE

OSTEOCLASTS

EROSION

1

PROSTHESES LOOSENING

Figure 1: Foreign body granulomas formed as a reaction to

the joint debris can effect synovium, capsule and bone.

Note that "of the three materials used in artificial joints,

high density polyethylene produced the most reaction" [61]

Wear occurs to a much lesser extent in total joint re- placements. However, it is not clear which factors control

the efficacy of debris removal from the joint. As Dr.

Willert has emphasized in this conference, it is the volume

of polymer which is retained in the joint that affects the

severity of local tissue reactions. Therefore the volume of wear particles produced and their size distribution (for

each material and implant design) may together determine the

473
debris retention rates and severity of the tissue reaction.

Wear of polyethylene acetabulae in total hip joint

prostheses does not appear to be a significant clinical

problem to date. Muller [41] reported that the wear plus

creep seen after 8 to 10 years usage in his revision procedures was less than 1 mm. In his hands, wear did not therefore "seem to be a major problem for 15 to 20 years." Likewise, Leinbach in his series of 2000 hip implantations and

experience in replacing 150 other prostheses has never seen

more than 1 mm of creep plus wear [34] . In the Mayo Clinic

series with up to 11 years followup and more than 10,000 patients, there have been no reoperations due to wear problems

[19].

Griffith et al. [29] studied x-ray evidence of 491

Charnley hips with 7 to 9 years followup (average 8.3

years). Of these, 64% appeared to have worn less than 60 um per year. This apparent "wear" included plastic deformation

of the socket as well as wear. Experimental studies by

Buchholz and Strickle [5] showed that the plastic deformation in 20 mm diameter hip joints could vary from 280 to 380

um depending on the contact stress (8 to 15 N/mm2). In the

clinical setting, this would imply an actual wear rate as low as 40 um/year. Thus, when the creep component was cor- rected for, 10 years of cup use would represent only 0.4 mm

or less wear.

474
Figure 3: Disrupted areas of polyethylene surface in acetabulum (SEM magnification x330)

This finding of insignificant cup wear was confirmed by

Beckenbaugh et al. [3] in their radiographic study of 333

Charnley procedures with 4 to 8 years followup. However, in

this and the study by Clarke et al. [16], concern was ex- pressed about the errors possible in radiographic measurements of such small quantities.

The highest range of radiographic migration reported in

4% of the cases by Griffith et al. [29] averaged 240

urn/ year, representing perhaps 210 urn actual wear/year.

Thus, in 10 years or more, wear of 2 mm would have taken

place in these cups.

2.2. Retrieval experience

In our combined USC/UCLA retrieval experience, we have

a group of approximately 30 retrieved polyethylene sockets

with 6 months to 8 years followup. There were no examples

of gross wear. The majority of the sockets varied from

highly polished minimal wear appearance (Fig. 2) to moderate surface disruption (Fig. 3) due to impregnation with

acrylic particles [17].
LEFT HIP Dowling et al (J.B.J.S., 1978)

s s

o o

A

Machining marks

still visible

A

Figure 4: Details of worn areas in Charnley sockets [21].

The cup appearances (Fig. 4) were essentially similar

to those reported elsewhere [21 ,47,48], Therefore at this

time we have made no effort to quantify the actual wear plus

creep phenomena present. At this time we have no information as to whether wear debris per se resulted or was involved in these cases of implant loosening.

Semlitsch [55] has described a Muller hip socket with 5 mm wear present after 7 years use. However, the femoral

ball had a large scratch on the surface which probably ac- counted for this severe wear. Amstutz ([1]) removed an acetabular component which had worn through from the reverse

direction. The cup was loose in the acrylic mantle and had

become severely abraded by the bone and remaining acrylic

sheath such that at revision surgery, a large hole was visible all the way through the polyethylene.

Studies reporting major problems with wear or fracture

of the polyethylene acetabulae have fortunately appeared

only rarely to date (Table 1). Rose et al. [47] reported

that "the wear rate can vary dramatically for essentially

identical prostheses but from different manufacturers."

However, this paper did not identify which of the prostheses

were at fault or quantify the wear described.

Bonvallet and Dautry [4] reported severe wear and bone

erosion in 6 out of a series of 34 Charnley hips with less

than 6 years followup. One had fractured into 5 fragments.

Rutt [50] reported 3 fractured polyethyelene sockets (2

traumatic) of the Charnley-Muller type at 4 to 6 years followup. Salvati et al. [51] reported two referred cases

476
where 2 Muller-type sockets had fractured into several

pieces through the remaining 1 mm wall thickness at the location of the superior deep groove. Followup times were 4

1/2 and 6 1/2 years (fig. 5).

NO. OF CASES F.U. YEARS ACETABULAR PROBLEM TOTAL NO. IN SERIES

WEAR FRACTURE

(+ WEAR)

Bonvallet t 4- 1 < 6 5 1 6 34

Rutt LSOl < 6 3 3 1095

Salvati tS( 1 < 7 2 2 R*

Greenwald 128 J 2 2 2 R*

Lazansky [33] < 7 2 1 3 1000

16

* Referred Cases

Table 1: Summary of studies reporting gross wear or wear

plus fracture of polyethylene hip sockets.

Figure 5: Worn and fractured polyethylene acetabulum described by Salvati etal. [51].

Greenwald [28] has two fractured Muller-type sockets,

one of which was in three fragments after only 2 years of

use. Lazansky [33] has revised 3 sockets where there was

excessive wear present (Table 2). Revell et al. [44] described a salvaged Charnley prosthesis which had excessive

wear present after only 2 years use. There was also considerable bone loss attributed to the effects of the debris.

477
1000 Cases in Series, (Charnley-THR)

200 Cases > 5 Years

32 Cases: Wear lmm^ at > 5 Years

3 WEAR REVISIONS

AGE CAUSE OF REOP. F U. YEARS NOTES

44F X-ray Wear 7 (Bilateral) Almost Worn Out

66M X-ray Wear > 5 Almost Worn Out

52M Stem Fx/Acetabular Wear > 5 Severe Wear

Figure 6: Polyethylene and other materials (a, concave)

have been used for either the acetabulum (a, concave component) or the femoral ball (b, convex component).

Experimental and clinical studies [44] indicate that convex polyethylene surfaces exhibit severe wear.

4 7 8
2.3. Reversed polyethylene geometries

The geometry of the polyethylene plastic component also

appears to have a significant effect on its wear resistance

(Fig. 6). Laboratory tests have shown that there is "significantly more polyethylene wear from a polyethylene

ball/metal socket than from a polyethylene socket/metal ball

configuration" [44] . The authors' clinical results with 16

polyethylene femoral components in a surface replacement hip

design confirmed that large quantities of polyethylene

debris were released with this configuration. The average

increase in wear rates was a factor of 6 as derived in simulator tests using the reversed polyethylene configuration in

ankle prostheses [41]. This brings up the question of the convex polyethylene patellar designs which will be discussed

in section 5.

3. Other Polymeric Hip Prostheses

3.1. Polyester (Polyethylene Terephthalate) hip components

Polyester has been used in acetabular cups as well as

the femoral balls of trunnion type of prostheses (Table 3).

Scheier and Sandel [52] compared 56 polyethylene and 43 polyester acetabulae in a clinical radiographic wear study.

They concluded that the average polyethylene wear (migration) was "somewhat slighter" than the polyester. They did

not comment on any clinical, radiographic, reoperation or histological findings.

MATERIAL FEMORAL ACETABULAR RESULT

Polyester • Similar PE (1976)?

Polyester (AP4) O Abandoned (1976)

PTFE

PTFE + MICA

Polyacetal (CO-P) •

•

•

Abandoned (1963) Abandoned (1972) Abandoned (1974)

Polyacetal (HoP-Del rin) • • In Use (72-80)*

Polyethylene •

Abandoned (1974)

Polyethylene • In use (63-80)*

Table 3: Historical summary of polymeric material and design choices in the hip joint (PE: polyethylene).

Polyester (AP4) was used with a special radiochemical

surface treatment [53] in the ball on a trunnion type of hip

prosthesis [64] . However, the accumulating polyester debris

seen after 3-4 years use had a deleterious effect on the

473
joint tissues and resulted in a foreign body reaction, bone

resorption and loosening [65] . This difference between polyester wear rates in the femoral ball or acetabular cup may

reflect a sensitivity to geometrical factors as described by

Revell et al. [44]

.

3.2. Polytetraf luoroethylene (Fluon, P.T.F.E.) components

The initial Charnley design incorporated P.T.F.E.

acetabulae. 300 of these had to be removed due to the granulomatous tissue reaction to the extensive erosion products

of P.T.F.E. [7,9]. A P.T.F.E. socket reinforced with mica

particles (Fluorosint) was also used clinically for 3 years

and then abandoned due to similar aggressive foreign body

reactions [54]

.

3.3. Polyoxymethylene Polyacetal hip components

The plastic copolymer "Ertacetal" reported by Semlitsch

[54] was initially tried for the ball of the Weber-Huggler

trunnion type of hip prosthesis. However, this material un- derwent biodegradation and "shrinkage" within 6 to 24 months

of implantation and was abandoned [50,54].

The homopolymer polyacetal "Delrin" has been used as

the trunnion collar and acetabulum in the Christiansen hip

system [13]. Clinical experience over 10 years with approximately 7,000 cases has provided satisfactory results [14].

As yet, there have been no detailed publications on clinical

or radiographic results of this procedure.

3.4. Laboratory wear studies

There is no universal agreement as to the clinical significance of the various wear screening programs using simplified specimen geometries [23,49]. Charnley has argued

over the years that there is absolutely no correlation

between clinical and experimental wear rates, citing his ex- periences with polyethylene and poly tetraf luoroethylene as examples [10]. Despite these reservations, the UCLA wear screening program [36,38] has ranked a variety of polymers,

many of them with known clinical behavior (Table 4). These

data verified that polyethylene was the polymeric material

of optimal wear resistance. The polymers known to perform

poorly in joint replacements such as nylon, polyester and

polytetraf luoroethylene ranked x530, x860 and xl600, respectively, above polyethylene. Delrin ranked at x47 and above.

However this material has apparently been very successful in

the Christiansen hip designs [14,23].

Joint-simulator studies have little better to offer in

4 80
the way of consistent data. So much so that Dumbleton [22]

remarked "It is my view that simulators are useful but that

they have been improperly used" and Swanson [57] concluded

in his review that "no significant feature of current practice has been based on results obtained in simulators."

It is generally believed that the volumetric wear rate

of hip prostheses does not vary with joint diameter whereas

the linear wear rate does [66] . However,

MATERIAL COEFFICIENTOF FRICTION WEAR RATE RATIO POLYMER/UHMWPE

1 Extruded UHMWPE .04-. 08 1.0

Moulded UHMWPE .05-. 10 0.9

Carbon Fiber- Reinforced UHMWPE

.05-. 13 1.6

Celcon .13-. 22 40

Delrln 150 Polyacetal s .15- .23 60

Delrln 500 .17-. 22 47

Polybdtylene .10-. 50 107

Polypropylene .18-. 25 132

Ekonol-TFE Copolymer .13-. 22 500

Nylon 6/6 .11-. 16 530

Ryton R4 (PPSt glass fiber) .25-. 28 700

Ryton BR07 (PPSt graphite fiber) .30-. 33 830

Polyester AP-4 .25-. 40 850

PTFE (Teflon) .08-. 12 1600

Hytrel .25-. 50 28,000

Urethane (Conap RN 2000) .06-. 08 Disintegrated

fable 4: Relative ranking of polymers in the UCLA wear

screening program.

4 8 I
AUTHOR THEORETICAL LABORATORY ideal ball diameter

(mm)

CHARNLEY 1959 J (ftfe) <25

GALANTE 1973 / <25

WEIGHTMAN 1973 / 22= 32

GOLD 1974 / > 28

BUCHOLZ 1975 / > 38

Table 5: Published theoretical and experimental predictions

on ball diameter versus wear.

when the relevant studies discussing volumetric wear are compared (Table 5), there are two theoretical studies indicating that the small-ball diameters are optimal, one experimental study which says it makes no difference and two

which suggest that it is the larger diameter balls which are optimal.

4. Polyethylene Tibial Components

4.1. Clinical results

Polyethylene and carbon-fiber reinforced polyethylene

appear to be the only two polymers currently used in knee

joint replacements. Publications to date deal only with the

polyethylene type and generally relate to complications of

tibial component loosening. In the Mayo Clinic's series

with a 9 years experience of approximately 3000 polycentric

and geometricknees , no components have had to be removed because of wear problems [19]. With 1 to 5 years followup of

461 total condylars, the Hospital for Special Surgery also

reported "no evidence of polyethylene wear or distortion"

[31].

4.2. Retrieved tibial components

A number of reports have described deformation and surface damage on removed polyethylene tibial components.

However, a prosthesis which has failed and requires revision

may reflect a multitude of problems including malpositioning

and impingement against either bone projections, osteophytes

or acrylophytes . Subluxation/dislocation, loosening, acrylic fragmentation and impaction may have occurred as well as actual wear. The question then becomes what represented ac4 82
tual "normal" wear and what was surface disruption of the

polyethylene created by the environment of the failing knee?

For example, Shoji et al. [56] described polyethylene damage on four polycentric total knees. Three apparently failed due to malpositioning and one due to impingement of the

bony tibial spine on the femoral component. In the latter

case, there was no loosening and "no abnormal wear." The

three other cases had "wear" areas with less than 1 to as much as 5.3 mm penetration.

Reckling et al. [43] reported an ex-vivo study of one geometric knee which was particularly interesting because it

had not failed at the time of the patient's death. With 8

months use, the polyethylene components had considerable

damage due to impingement against both femoral bone and

acrylic cement.

Walker and Hsieh [62] examined 15 knee prostheses re- moved after 7 to 42 months. The surfaces of the

non-conforming condylar prostheses (e.g. Marmor, DuoCondylar) appeared relatively smooth but did contain many small

pits (less that 0.5 mm wide) as well as cracks perpendicular

to the sliding direction. The authors indicated that these

surface defects were probably the result of fatigue pitting

[60,62] In contrast, the conforming tibial components contained

Figure 7: Pitting on ICLH tibial component after 7 months

use (both components were found to be loose [60]

483
Figure 8: UCI knee component removed after 3 years use.

numerous scores and wide pits up to 4 mm wide and 0.5 mm

deep (Fig. 7). The authors demonstrated that three-body

abrasion from entrapped cement particles was the likely

cause of these larger defects.

Figure 9: Fracture of a small ICLH polyethylene tibial component, history unknown [66].

4 84
Our USC/UCLA retrieval experience with approximately 40

condylar units was similar to that reported previously

[17,47,62]. The tibial components of knees generally featured much more evidence of deformation, impaction and abrasion by acrylic (and bone) and other surface defects than

did the hips (Fig. 8). So far, none of the studies of re- trieved knee joints have been able to provide any quantitative assessment of the relative wear magnitudes seen either

with respect to prosthesis design or whether acrylic cement

ingress had occurred.

As in the polyethylene acetabulae, cracking and fracture of polyethylene tibial components have also occurred.

Weightman et al. [66] reported one case of gross brittle

fracture of an ICLH tibial component and another with two

large cracks appearing in the same region (Fig. 9). The

authors concluded that "polyethylene is susceptible to degradative fatigue in the human body and that when subjected

to cyclic bending ... gross fracture can occur."

4.3. Laboratory wear studies

At present the only laboratory wear study of

tibial-femoral prostheses appears to be that by Treharne et

al. [45,58] and Young et al, [70] . Their simulator data on

tests of 5 condylar knees were extremely provoking (Table

6). These data indicated that the volumetric wear rates

(indicative of extent of debris formation) for the 5 prostheses varied by a factor of x20, depending on geometrical design and magnitude of the contact area. The linear

wear rates (indicative of wear-out problems) varied

TYPE

DYNAMIC

CONTACT

AREA

Amm2

DYNAMIC

AREA RATIO

TOTAL

AREA

mm2

Jt of TOTAL

AREA

T

WEAR RATE

min3/io6 cycles

VOLUMETRIC

WEAR RATIO

LINEAR

WEAR RATE

um/10^ cycles

RMC 1385 8.8 3220 *3 1.58 1.0 1.1

T-Condylar 283 1.8 283^ 10 3.69 2.3 13

UCI 278 1.8 3^81 8 32. M 20.5 117 Townley 263 1.7 2926 9 13.7^ 8.7 52

Anameric 158 1.0 2633 6 13.83 8.8 88

• area swept by condyles in 60° flexion arc

t assumed polyethylene density 3 0.935mg/mm' £ volumetric wear rate divided by area A

Table 6: Summary of experimental wear tests on total knee

replacements illustrating contact area and other geometrical

effects [45,68].

4 85
TYPE NOMINAL

CONTACT STRESS

N/mm2 (P.S.I)

RATIO

Charnley Hip 5-2 (750) 1 ICLH 0.01 (14.5) 0.02

Geometric 0.9 (130) 0.17

Duocondylar 11.6 (1700) 2.3

Marmor 26.9 (3900) 5.2 PE yield stress 14-21 (2-3000) 3.4

Table 7: Comparison of predicted Hertzian contact stresses

for 4 designs of total knee replacements [60]

.

by a factor of xllO for the same reasons. These were calculated assuming that the wear occurred uniformly across the

dynamic contact area. Further confirmation of the tremendous variation in knee design contact stresses comes from

the study by Trent and Walker [60] . They calculated that

the peak contact stresses for 4 types of condylar knees

(Table 7) varied by as much as x269.

5. Polyethylene Patellar Components

The results on patellar resurfacing implants do not appear

to be in yet, apart from the results of hemiarthroplasty

procedures performed with polyethylene patellae [24].

TYPE

*DYNAMIC CONTACT

AREA A(mm2)

AREA RATIO

VOLUMETRIC

WEAR RATE

mn>3/lo6 cycles

VOLUME WEAR RATIO

LI NEAR

WEAR um/10^ cycles

LINEAR

WEAR RATIO

RMC 840 8.6 6.1 1.0 7.3 1.0 Townley 172 1.8 82 13 476 65 T-Condylar 113 1.2 131 21 1160 159 Universal 104 1.1 160 26 1538 211 RMC - F.T. 98 1.0 136 22 1388 190

* area swept by condyles in 80° flexion arc volumetric wear rate divided by area A

Table 8: Summary of experimental wear tests on patellar

components of total knee replacements [46]

.

Treharne [46] has performed laboratory simulator stu4 86
dies on 5 designs of patello-femoral prostheses (Table 8).

Their data showed that the volumetric and linear wear rates

of the various designs varied by factors of x22 and x211,

respectively.

6. Polymeric Ankle Components

6.1. Retrieved implants

Groth et al. [30] reported on bilateral ankle autopsy

specimens, one with polyethylene (15 months implantation)

and one with carbon-fiber reinforced polyethylene (CPE, 12

months implantation). The polyethylene unit was extensively

worn (Fig. 9) and featured wrinkles perpendicular to the wear direction as well as "tiny cracks and pits." There was much less wear of the contralateral CPE ankle prosthesis

(Fig. 10). Removed tissues featured minimal amounts of

carbon fibers (20 to 100 um) and carbon debris (5 to 8 um)

Tissue reaction appeared minimal.

Figure 10: Polyethylene tibial component of Oregon

ankle removed after 15 months. Extensive scoring was noted

[30] due to wear as well as surface defects inflicted on the

talar unit during insertion.

487
6.2. Simulator wear studies

The simulated wear study of the ICLH ankle design by

Kempson et al. [32] predicted that less than 0.3 mm linear

wear would occur after 10 years use. The tibial and talar

components were polyethylene and stainless steel, respectively. Reversing this configuration increased the wear

rates by a factor of 6 on average [44]

.

Figure 11: Carbon-fiber reinforced tibial component of Oregon ankle removed after 12 months [30] in the same patient

as the component shown in Figure 10.

7. Discussion and Conclusions

Overall clinical results with 7 to 14 years experience

of hip prostheses illustrates that wear of the polyethylene

acetabulae has not been a problem. Radiographic estimation

of average wear rates vary from less than 0.04 mm/year to

perhaps a high of 0.2 mm/year. However, despite this, there

are at least 5 disquieting reports of gross wear and even

fracture of the polyethylene sockets. The explanation of

these phenomena or understanding of their future clinical

significance is today uncertain.

4 88
It has been suggested that the acrylic particles may

contribute the severest form of damage to the polyethylene

joint surfaces [17,48,62]. Certainly the visual effects are very dramatic. However, the few attempts at quantitative

verification of such proposed "accelerated" wear rates by

acrylic contamination are conflicting. Ankle simulation

studies by Revell et al. [44] indicated that "the damaged

polyethylene wore at its usual rate." In contrast, McKellop

et al. [38] measured a 36 fold increase in wear due to

acrylic particles trapped between the surfaces of their

friction and wear specimens. However, this could in part

reflect the differences between the stainless steel [32] and

titanium-6Al-4V [38] alloys tested. Therefore it is uncertain whether the ingress of acrylic particles could account

for the gross problems described above. Bonvallet and Dautry [4] and Rose et al. [47] implicated manufacturing variability on the abnormal and inconsistant wear results of the

polyethylene.

In the tibio-femoral prostheses, up to 9 years experience apparently has not resulted in any significant wear

problems requiring revision. What is not clear is whether

any tissue reaction to wear debris accelerated or was indeed

even totally responsible for these clinically loose

prostheses. There have been many tibial components removed

due to gross loosening and these generally featured much

more extensive deformation and abrasion than was seen in the

hip [44]. It is likely that, with time and improved fixation concepts, the knees will provide considerable additional problems with polyethylene deformation, wear and fracture. The contact stresses calculated for various designs

has been shown to vary by as much as x270 [60] . In addition, simulated knee studies of various prostheses have

predicted linear wear rates varying by as much as xl20

[45,69]. Therefore, in the much more severe environment of

the knee joint, it is anticipated that polyethylene deformation and wear will be considerably worse than that encountered in the hip to date. Revell et al. [44] suggested

that the annual production of 57 cu. mm. of polyethylene

debris, as seen in the hip, was a tolerable level. Some of

the patellar resurfacing components clearly exceed that

level (Table 8).

Polyethylene patellar replacements are at a peculiar

disadvantage because of the high loads imposed, their limited contact areas and convex geometries. The clinical results are not in yet for the patello-femoral prostheses.

However, one laboratory simulator study predicted very high

wear rates indeed for four types of patellar resurfacings

[46] . It is therefore likely that patellar wear will compound the problems of the knee joint replacements.

The issue of wear of convex or concave polyethylene

4 39
Figure 12: USCATS (Universal Scientific Computerized

Anatomical Test System) test equipment installed in Orthopedic

Hospital

.

a) close-up view of 10-channels of hip joint wear simulator with dynamic loading capabilities controlled by USCATS

computers.

b) one of 5 USCATS/MMED universal load frames programmed to test STH total hip prosthesis.

c) load frames can be adapted to many test configurations,

in this case a condylar knee prosthesis.

490
components has not been satisfactorily resolved. One study

suggested that the wear can increase 6 times for convex polyethylene ankle prostheses and has clinical evidence of wear problems from convex polyethylene femoral prostheses

[44] . However, the Christiansen hip prostheses has been

using this geometry with Delrin in thousands of cases with

satisfactory results [14,23]. Other joint replacements such

as the shoulder, elbow and ankle are also being designed

with convex polyethylene components. Is there a conflict

between design and material selections?

One of the problems of wear and deformation analyses of

retrieved implants is that it is a case of a too few, too

late. The numbers of procedures performed per year may

number 100,000 for hips and 80,000 for knees [42]. Yet only

a relative handful of the 8 to 20% revision rates find their

way for analysis. In addition, the implants may have failed

for a variety of biological and/or mechanical reasons which

too many times can only be guessed at. Even then it is difficult to both retrieve sufficient clinical and radiographic

data and quantify any changes detected. Lacking these data

and with the need to provide a predictive service to orthopaedics rather than a retrospective or historical outlook,

the Orthopaedic Biomechanics Laboratory of Orthopaedic Hospital is planning a series of experimental tests of actual

hip and knee prostheses. The experimental USCATS facility

incorporates computerized test-frames similar to that described by Young et al. (6/8, #9]. The USCATS nomogram depicts the concept of a Universal Scientific Computerised Anatomical Test System. This system includes a ten channel hip

simulator (Fig. 12) and 5 individual units (Fig. 13) which

can be programmed to simulate the load and motion behavior

of any selected joint. Thus 15 channels of wear simulation

capabilities are available for testing of "off-the -shelf"

prostheses as received from the manufacturer. With this ca- pability it is hoped to resolve some of the questions con- cerning design and material selection for various types of

implants

4 9 I
Acknowledgments

This work was supported in part by the Orthopaedic

Foundation of Los Angeles and National Institutes of Health

Award AM 16120 (1976-1979). Thanks are due to B. Fujikawa

and P. McGuire for preparation of photographs and drawings.

References

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Clarke, I.C., THARIES surface replacement: A review of the

first 100 cases, Clin. Orthop. 134, 87-101 (1978).

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and Radin E.L., Giant cell synovitis associated with failed

polyethylene patellar replacements, Clin. Orthop. 115 , 213-219 (1976).

[25] Galante, J.O. and Rostoker, W., Wear in total hip

4 3 3
prostheses. An experimental evaluation of candidate

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the friction and wear of metal on plastic total hip joints,

Clin. Orthop. UK), 270-278 (1974).

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[29] Griffith, M.J., Seidenstein, M.K., Williams, D.

and Charnley, J., Eight- year results of Charnley

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behavior of cement, Clin. Orthop. 137 , 24-36 (1978).

[30] Groth, H.E., Shen, G., Gilbertson, L., Farling, G.

and Shilling, J.M., Postmortem analysis of carbon-fiber

reinforced UHMWPE and UHMWPE prostheses retrieved from a single subject after a service life of 12 to 15 months, In

Trans. Orthop. Res. Soc, 2» 186 (Dallas, 1978)

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condylar knee prosthesis: The first 5 years, Clin. Orthop.

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[32] Kempson, G.E., Freeman, M.A.R. and Tuke, M.A.,

Engineering considerations in the design of an ankle joint,

Biomed. Eng. K), 166-180 (1975).

[33] Lazansky, M., 10 year results of total hip

arthroplasty (In preparation, 1980).

[34] Leinbach, I., Personal Communication (1980).

[35] McKellop, H., Clarke, I.C. and Markolf, K.,

Friction and wear evaluation of prostheses materials using a 12-channel screening device, in Proceedings of 21st National

SAMPE Symposium - Bicentennial of Materials Progress, pp

508-521, April 6-8 (Los Angeles, 1976).

[36] McKellop, H, Clarke, I.C, Markolf, K.L. and

Amstutz, H.C, High wear rates with Delrin 150 - a clinical

hazard? in Trans. Orthop. Res. Soc. J3, 7 (Dallas 1978).

[37] McKellop, H., Clarke, I.C, Markolf, K. and

Amstutz, H., Polyethylene wear in non-conforming contact, in

Trans. Orthop. Res. Soc. 4^ 34 (San Francisco 1979).

[38] McKellop, H., Clarke, I.C, Markolf, K. and

Amstutz, H.C, Wear properties of new high strength alloys

4 94
for prosthetic joints, in Trans. Orthop. Res. Soc. 4^ 71

(San Francisco, 1979).

[39] McKellop, H. , Griffin, G., Clarke, I. and

Markolf, K. , Increased wear of UMHW polyethylene after gamma

radiation sterilization, In Trans. Orthop. Res. Soc, J5,

99 (Atlanta, 1980)

[40] Mendes, D.G., Figarola, F. , Bullough, P.G. and

Loudis, P., High density polyethylene prosthetic femoral

head replacement in the dog, Clin. Orthop. Ill , 274-283

(1975).

[41] Muller, M. , Late complications of total hip

replacement, The Hip , Proceedings of the second open

scientific meeting of The Hip Society 319-327 (Saint Louis,

1974).

[42] Murray, W.R., Revision of conventional total hip

replacements, paper presented at A.A.O.S. Summer Institute

(Los Angeles, 1979).

[43] Reckling, F.W., Asher, M.A. and Dillon, W.L., A

longitudinal study of the radiolucent line at the

bone-cement interface following total joint replacement

procedures, J. Bone Jt. Surg., _59A, 355-358 (1977).

[44] Revell, P. A., Weightman, B., Freeman, M.A.R. and

Roberts, B.V., The production and biology of polyethylene

wear debris, Arch. Orth. Traum. Surg. jU, 167-181

(1978).

[45] Treharne, R.W. Richards Manufacturing Company.

In vitro testing of the RMC total knee,' Technical bulletin

No. 3468 (Tennessee, 1978).

[46] Treharne, R.W. Richards Manufacturing Company.

'Resurfacing of the patello-femoral joint,' Technical

bulletin No. 3910 (Tennessee, 1980).

[47] Rose, R.M., Crugnola, A., Ries, M. , Cimino, W.R.,

Paul, I., Radin, E.L., On the origins of high in-vivo wear

rates in polyethylene components of total joint prostheses,

Clin. Orthop. 145 , 277-286 (1979).

[48] Rostoker, W. , Chao, E.Y.S. and Galante, J.O., The

appearances of wear on polyethylene - a comparison of

in-vivo and in-vitro wear surfaces, J. Biomed. Mat. Res.

12, 317-335 (1978).

[49] Rostoker, W. and Galante, J.O., Contact pressure

dependence of wear rates of ultra high molecular weight

polyethylene, J. Biomed. Mat. Res. 1_3, 957-964 (1979).

4 35
[50] Rutt, A., Zur Atiopathogenese der aseptischen

Auslockerung von Huf tgelenktotalendoprothesen,

Etiopathogenesis of loosening after total hip replacement,

Arch, orthop. Unfall-Chir. 88, 139-152 (1977).

[51] Salvati, E.A., Wright, T.M., Burstein, A.H.,

Jacobs, B., Fracture of polyethylene acetabular cups, J.

Bone Jt. Surg. 61-A , No. 8, 1239-1242 (1979).

[52] Scheier, H. and Sandel, J., Wear affecting the

plastic cup in metal- plastic endoprosthesis, In Total Hip

Prothesis , N. Gschwend and H. Debrunner, eds., (Williams

and Wilkins Co., Zurich, 1976)

[53] Semlitsch, M., Artificial joint materials

development, Eng. in Med. 2, 89-97 (1973).

[54] Semlitsch, M., Technical progress in artificial

hip joints, Sulzer Techn. Rev. _4, 1-11 (1974).

[55] Semlitsch, M., Personal communication (1980).

[56] Shoji, H., D'Ambrosia, R.D. and Lipscomb, P.R.,

Failed polycentric total knee prostheses, J. Bone Jt.

Surg. 58-A , No. 6, 773-777 (1976).

[57] Swanson, S.A.V., Limitations of joint simulators,

in "Evaluation of Artificial Joints", pp 37-46, Pub: Biol.

Eng. Soc. (London, 1977).

[58] Treharne, R.W., Young, R.W. and Young, S.R.,

In-vitro wear testing of total knee implant devices, in

"Transactions of the Orthop. Res. Soc", 4_, 295 (San

Francisco, 1979).

[59] Treharne, R.W., Carignan, R.G., Young, R.W. and

Young, S.R., In-vitro testing of total knee implants, in

"Transactions of the Biomaterials Symposium", 3^, 79

(Clemson, 1979).

[60] Trent, P. and Walker, P., Wear and conformity in

total knee replacement, Wear J36, 175-187 (1976).

[61] Villacin, A.B. and Bullough, P.G., The response

of the tissue to implanted joint endoprosthesis, in Human

Joints and their Artificial Replacements , P.S. Walker, ed.

pp 409-422 (C.C. Thomas Pub., Springfield, 1977)

[62] Walker, P.S., Human joints and their artificial

replacement, p. 404, C.C. Thomas Pub. (Springfield,

1977).

[63] Weber, B.G. and Semlitsch, M. , Total hip

4 96
replacement with rotation- endoprosthesis: Problem of wear,

5th International Symposium (Netherlands, 1972).

[64] Weber, B.G. and Stuhmer, G., Trunnion bearing in

total hip prosthesis, Eng. in Med. 2, 203-210 (1976).

[65] Weightman, B.O., Paul, I.L., Rose, R.M., Simon,

S.R. and Radin, E.L., A comparative study of total hip

replacement prostheses, J. Biomech. 6^, 299-311 (1973).

[66] Weightman, B.O., Isherwood, D.P. and Swanson,

S.A.V., The fracture of ultra high molecular weight

polyethylene in the human body, J. Biomed. Mat. Res. 13 , 669-672 (1979).

[67] Wroblewski, B.M., Wear of high-density

polyethylene on bone and cartilage, J. Bone Jt. Surg.

62-B , 122 (1980).

[68] Young, R., Materials Testing Corporation (Los

Angeles, 1980).

[69] Young, S.R., Young, R.W. and Treharne , R.W.,

Dynamic contact area studies of several total knee plateaus,

in "Trans, of the Biomaterials Symposium ^, 186 (Clemson,

1979).

[70] Young, R.W., Young, S.R. and Treharne, R.W.,

Simulation of the hip joint using a computer controlled

system, in "Trans. Biomaterials Symposium" _3, 185 (1979).

4 37
Di scussion

Question (B. W. Sauer, University of Mississippi): I would first like

to complement Dr. Clark for an excellent presentation. His presentation

has clearly demonstrated the problems associated with the analysis of

retrieved implants. Contradictory data can be easily generated when

all factors influencing the implant are not considered during its

analysis. Factors such as patient age, weight and activity level;

surgical technique, including complications and errors; adequate

identification of the materials used in the implant etc. must be

taken into account before meaningful comparisons can be made between

implant designs or materials.

Answer : Dr. Sauer 1 s comments highlight for me the difference between

a meaningful implant-retrieval program and wasted effort. It is all

too easy to gather a hardware collection of 19 of this, 5 of that and

1 of everything else. However, assessing the clinical relevance of

these removed and/or falied implants is a different story. The

reality is that the cl i nical data is the hardest to collect and is

frequently incomplete as well as being the most difficult to quantitatively assess. Dramatizing only a little for example, the life

expectancy for any unilateral prosthesis in an arthritic hip of a 40

year old male farmer in Iowa is completely different from that of a 40 year old lady from New York with two bad rheumatoid hips and other

joint involvement. In addition, the surgeon's technique may play

more of a role than the implant hardware he uses. Insertion of a large stem with poor cement packing may result in failure by loosening.

Insertion of a smaller stem with a thick integral layer of cement may

eventually result in some proximal loosening followed by stem fracture.

Once again the patient, surgeon and implant are inextricably related

and must be carefully reviewed as a system.

In conclusion, while we consider implant-retrieval program a potentially valuable source of data and are extending our (JSC retrieval

system, we are also exploring the use of detailed clinical and radiographic analyses of large clinical series as well as extending the

role of bench testing of the associated implants.

Question (H. Willert, University of Goettingen, W. Germany): Mr.

Clark said no knee implant had been removed because of wear. My

questions are: 1) were there implants removed because of loosening,

and 2) if this was true, have you encountered, that loosening also

can occur as a result of excessive wear?

Answer : Excluding infection, implant loosening is accepted as the

major cause of joint-replacement failure as described in many clinical

publications and various implant-retrieval programs. However, there

has generally been little or no hi stopathol ogi cal analysis work done

on the interface tissues to determine conclusively whether wear

4 9 8
liebris and the associated foreign body response was either wholly or martially responsible.

It is, therefore, impossible to answer Dr. Willert's major

!uestion directly. However, to answer it indirectly, the wear debris/

issue reaction phenomena would appear a very powerful mechanism in

ausing the implants to fail. Charnley's experience with 300 hip

mplants failing due to Teflonomas, the severe granulatomous reaction

l|o excess PTFE debris [7], is a powerful remainder. Similar problems

ave also been encountered more recently with other polymers (Table

). Even polyethylene debris can produce exactly the same result

20,24,26,40].

Revel 1 et al . [44] correlated the design features of ankle,

nee, and hip prostheses with regard to polyethylene debris in the

issues and their clinical rates of loosening. They found that "bone

esorption and bone death were most commonly associated with the

resence of abundant polyethylene particles in macrophases and giant

alls. Such a cellular reaction, often seen with accompanying fibrosis,

pre seen in the articular soft tissues and also invading the bone of

le implant bed". Their conclusion was that such polyethylene debris

ormation can result in implant loosening. They also noted that the

amount of polyethylene debris and severity of cellular reaction were

^eater in relation to the tibial component of knee protheses".

iced with this evidence, I believe that Dr. Willert's concern about

?ar debris and tissue reactions is well justified.

439

INFORMATION UTILIZATION

5 0 I

Considerations Concerning International

Standards for Accumulating and Reporting

of Implant Experience with Cardiac Pacemakers

Robert C. Flink 1

Medtronic, Inc.

3055 Old Highway Eight

Post Office Box 1453

Minneapolis, Minnesota 55440

William Malette, M.D. 2 University of Nebraska

Creighton University

Omaha, Nebraska

In troduc ti on

Implantable cardiac pacemakers have been in use for

nearly two decades. Initially implanted to treat StokesAdams attacks, pacemakers are now indicated for a wide

variety of defects of the conduction system of the heart.

Recently control of tachyarrhythmias has become an area

of investigation. With expanding indications, the number

of implanted pacemakers has grown to several hundred thousand worldwide.

Technology has changed considerably over these decades.

Discrete circuits in epoxy have given way to hybrid circuits hermetically sealed in metal cans. Mercury-zinc

cells have been superceded by those based on lithium

resulting in longer-lived pacemakers. The early pacemakers

simply supplied an electrical stimulus to the heart. Sensing of cardiac activity became the next step. Now pacemaker parameters can be adjusted non-invasively for diagnostic purposes and to address the changing needs of the

patient

The large number of pacemakers in widespread use and

a rapidly changing technology are at once the causitive

and limiting factors in pacemaker standards work. Pacemaker standards work began in the Association for the

Advancement of Medical Instrumentation (AAMI). After

Secretary, Joint Working Group ISO TC150/SC2/WG2 , IEC

SC 62D WG6

2 Chairman, Joint Working Group ISO TC150/SC2/WG2 , IEC

SC 62D WG6

503
developing a draft standard under contract to the FDA, |_l] 3 international standards work was started with participation from both the International Organization for Standardization (ISO) and the International Electrotechnical Commission (IEC) in a joint working group.

The working group is made up of clinicians, clinical

engineers, manufacturers and government officials from

several countries. From its inception the working group

has emphasized writing standards which have clinical relevance and benefits. Accordingly, meetings are arranged

to afford opportunities for clinician involvement. Care

is also taken so that innovation may proceed unhampered.

A draft on pacemaker labeling and test methods is

presently in preparation for final ballot. [Zj The current

working group project is a standard for manufacturers'

reports of implant performance of pulse generators. [3] A

pacemaker is defined as a combination of a pulse generator

and a lead. [2I As the pulse generator is the element which

most frequently needs replacement, this is the focus of

current work.

The following discussion attempts to summarize basic

considerations and current status of work on implant experience reporting.

1. Working group objectives

By implant performance we mean the experience with

pacemakers implanted in patients. Because pacemaker

patients are, for the most part, living lives typical of

their age groups, they are active and mobile. Characterizing implant experience with pacemakers has the same uncertainty as characterizing any aspect of health of a large

popul ation

.

Characterizing implant experience with pacemakers can

be historical and of little value if pursued for its own

sake. It was necessary to define the clinical value and

the practical reasons for such reporting. The working

group determined that the principal reason for reporting

implant performance is to aid in managing pacemaker patients. A secondary objective is to provide information

of use to the clinician in selecting a model for implant.

J Figures in brackets indicate the literature references

at the end of this paper.

5 04
These decisions have important implications for what

aspects of implant experience are of interest and how experience is presented in reports.

2. Reports of value in patient management

For a report to be of value in the management of an individual patient it must say something relevant about

his pulse generator. This requires a discriminating view

of experience with pacemakers of the same model. Recent

experience with pulse generators of the same manufacturing

group or period is most relevant.

A clinician often has patients under his care with

pulse generators from a number of manufacturing groups as well as manufacturers. With current reports which discriminate by manufacturing groups, he can take an equally

discriminating view of patient management. Based on experience with the related manufacturing group, one patient

may require close follow-up, possibly replacement of his

pulse generator. Another patient with a pulse generator

from a different manufacturing group may require less

attention based on reports of implant experience with that

group

Clinical decisions to replace an implanted pulse gene

rator or to leave it implanted both entail risk. Hence,

the value of pertinent implant experience information.

Implant performance reporting in the past has effectively averaged experience over a given model and over

time. This is roughly analogous to the weatherman giving

you the average daily temperature, humidity and precipitation over the last three years in your region of the

country. What you need is a report on local conditions

today. In an emergency your welfare may depend on such

a discriminating report. The same is true of the pacemaker patient.

3. Reports of cumulative

implant performance

Among other pulse generator performance characteristics the working group has determined that the overview of

a model is of value at the time of selecting a pulse generator for implant. Cumulative performance is viewed as showing an overall track record of a given model. However

the draft standard asks that care be taken to warn the

clinician that such reports tend to obscure differences in

recent experience of each manufacturing group of the model
4. Issues currently under discussion

Incomplete information

Several factors including patient mobility cause a significant number of pulse generators to have little or

no follow-up reported to the manufacturer after implant.

Thus, at any point in time the manufacturer's implant experience information is incomplete. Even with periodic

follow-up, pulse generator function cannot be concretely

verified beyond the last follow-up event. Clinical centers, even those with large studies, only cover a small

percentage of the pacemakers in use. These reports have

value as indicators of overall model experience. However,

insufficient numbers exist in these studies to show variation by manufacturing period.

The concepts of active and passive systems have been

advanced to help in considering the problem of incomplete

information. The passive system (i.e. available data)

relies on assumptions about the data which is missing. An

active system (i.e. close follow-up) based on a random

sample of devices may provide information upon which to

characterize some aspects of the population of implanted

pulse generators.

Unreported mortality is one example. Recent pacemaker

patient mortality rates have been reported in several

published studies. [4-61 These studies show that an active

follow-up system on a sample basis could give an accurate

model for use with the passive system. Unreported explants

is another area where the active system may provide a model of the population of implants. These approaches are

undergoing careful analysis in the working group.

To further reduce the problem of incomplete data,

better communication of experience is necessary from

clinician to manufacturer so that he, in turn, can report

on a thorough and timely basis. Clinician guidelines in

this area will be included in future projects for the

working group.

The present draft divides explants down into categories without using the term "failure". There are

several reasons for this:

1. For a given patient, an out-of-specification device

may not be a clinical problem and the clinician may

elect to let it remain implanted. The same performance

in another patient may require explant.

Failure

50G
2. A patient may have unusual intracardiac signals which

cannot be sensed properly by a pulse generator. Some

consider this design failure.

3. A pulse generator which ceases to function due to

normal battery exhaustion after providing the expected

duration of a service can no more be considered a failure than a car which runs out of gas.

Characterization of explanted pulse generators is fundamental to any system of experience reporting and appropriately a subject of thorough discussion in the working

group

In summary, international standards for implant experience reporting for implantable pacemakers are on their

way. The working group has the mul tidisciplinary experts

necessary to write a challenging, yet practical standard.

Several issues have been resolved but major ones remain.

507
Re f erences

Pacemaker Standard: Labeling Requirements,

Performance Requirements and Terminology for Implantable Artificial Cardiac Pacemakers. FDA Contract

No. 223-74-5083. The Association for the Advancement

of Medical Instrumentation. August 1975.

Draft Proposal ISO/DP 5841-1, Implants for Surgery,

Cardiac Pacemakers, Part I: Implantable Ventricular

Pacemakers, January 1980.

Draft Proposal ISO/DP 5841-1, Implants for Surgery,

Cardiac Pacemakers, Part II: Manufacturers' Reports

of Implant Performance of Pulse Generators.

Forsberg, Sven A., Quantitation of the Gain in

Mortality and Life-Time after Pacemaker Treatment,

Acta Med. Scand. 204 , 11-15, 1978.

Fuse, K. , Mitsui, T., Ohkawa, S. and Sugiura, M.

,

Clinical and Pathological Factors Influencing the

Prognosis of the Long-term Paced Patients (Symposium

on Surgical Treatment of Arrhythmias, Tokyo 1977),

Japanese Circulation Journal 42 , 269-278 (May 1978) . Stoney, W. S., Finger, F. E. Ill, Alford, W. C. Jr.,

Burrus, G. R. , Frist, R. A. and Thomas, C. S. Jr.,

The Natural History of Long-Term Cardiac Pacing,

The Annals of Thoracic Surgery 2_3, 6 , 550-554,

June 1977o

508
AN ANALYSIS OF 130 REMOVED TOTAL

HIPS AND KNEES

R.Y. Hon', J.L. Lewis, R.L. Wixson and G.M. Kramer

Rehabilitation Engineering Program

Northwestern University

345 E. Superior Street

Chicago, Illinois 60611

Retrieval analysis is an efficient means of monitoring and evaluating the problems associated with total

joint replacements. In 5 years, 130 prostheses have been

collected from 8 hospitals in the Chicago area, including

75 hips and 52 knees. All study data are summarized and

coded for computer analysis.

Total hip replacements are being removed at a relatively constant rate with no evidence of an increase

in removal with time. In contrast, the majority of total

knee replacements collected were removed within 3 years

of the original surgery. Fractured and cracked components

appear to be almost always associated with loosening.

Unlike most other TJR components which usually debond at

the bone-cement interface, femoral stems, when loosened,

generally debond at the cement-component interface. Such

debonding may ultimately lead to gross component loosening.

1 . Introduction

Total joint replacement has proven to be a highly successful procedure for the rehabilitation and restoration of persons crippled by severe arthritis. The results following total hip replacement are

particularly dramatic with recent clinical series reporting good to

excellent long-term ten year results of 91% for the patients followed. [1]

Total joint replacement (TJR) however, is not yet a perfected

procedure, particularly for joints other than the hip. Prosthesis design and surgical procedures used to implant TJR's continue to evolve

to meet perceived current or potential problems. Monitoring and

! evaluating the usefulness of these changes is difficult because of

the lack of data on both frequency and types of TJR failure.

The most definitive means of obtaining such failure data is

through large clinical series where all the patients of a physician or group of physicians are followed. Such series provide information on

the actual performance of a prosthetic device and problems unique to a particular procedure become manifest. Although many clinical problems

and their incidence can be determined through such a series, many

patients and years are required to accumulate statistically significant

5 09
data, especially on the failed cases.

An alternative approach is to monitor and evaluate TJR performance

by the retrieval and examination of removed TJR implants. The study of

such retrievals, when coupled with surgical observations at the time of

arthroplasty revision and the clinical history of the patients, can yield detailed information on the in vivo function of the implant and

the conditions which led to its ultimate removal.

Retrieval studies cannot give absolute failure rates, since the

patient population from which the sample is drawn is unknown, but TJR

failure modes and their relative rate can be determined. Also, not all

implants which may be classified as clinical failures come to removal

so that retrieval studies do not monitor all failure modalities.

Nevertheless, retrieval analysis provides an efficient means of

obtaining detailed information on the in vivo behavior of implants,

particularly the failed implants which are of greatest interest, and

is a good means of monitoring and evaluating the failure modes of TJR's

in use.

This paper describes the TJR collection and analysis methods used

at the Rehabilitation Engineering Program of Northwestern University;

selected data on retrieved hips and knees is presented.

2. Materials

Over a period of six years, 130 prostheses were retrieved, including 75 hips and 52 knees; all were removed for clinical failure. The

original participants of the study were six surgeons associated with

the Northwestern University Medical School Hospitals. The study was

then gradually expanded to encompass eight hospitals in the Metropolitan

Chicago area with twenty-one contributing surgeons; no new contributors

have been added since 1978. The surgeons agreed to contribute all re- moved components so, to our knowledge, all the TJR's removed by these

physicians during their participation are included, although we have

no way to verify compliance.

Of the 130 prostheses, 61 hips were of the metal femoral component

and ultra-high molecular weight (UHMW) polyethylene acetabular component

type. In addition, 44 knees were of the type where 1 or 2 metal femoral

components articulate on 1 or 2 UHMW polyethylene tibial components.

Results from a close examination of the data on these particular 61 hips

and 44 knees are presented. The specific prosthesis types are given in

table 1.

Of the 61 hips, 44 (72%) were originally implanted by the participating surgeon, 16 (26%) were referrals, mostly from the Chicago area,

and one case was of uncertain origin. Of the 44 knees, 26 (59%) were originally implanted by the participating surgeon and 18 (41%) were

referrals.

5 i o
3. Methods

The study included (i) examination of patient medical records,

(ii) analytical review of patient roentgenograms, (iii) observations

at the time of revision surgery and (iv) postoperative examination

of the removed components.

The data form used to code all of the acquired data is given in

Appendix I. The form has been reviewed and updated on several occasions

and currently conforms to American Society for Testing and Materials

(ASTM) standard F-561-78 [2].

The medical history section of the data form is filled in by

checking the patient's records and x-rays. The patient is interviewed

to confirm and complete the medical history. When practical, a member

of the engineering staff attends revision surgery to record all surgical

findings; otherwise, the attending surgeon is interviewed.

The prosthetic components and all removed polymethylmethacrylate

(PMMA) cement are gas sterilized as a precaution and then examined

postoperatively in the laboratory. The postoperative study is normally

limited to gross visual examination using a 70X dissecting microscope.

The type and amount of prosthesis wear, the condition of the cement

mantle about the prosthesis, and prosthesis damage through abnormal

component- to-component contact or component-to-bone contact are among

the factors which are of interest.

Although the microscopic, microstructural and metallurgical analyses

called for by ASTM F-561-78 are not performed routinely, some or all of

these detailed tests may be undertaken when compelling circumstances are

present. For instance, if the patient history or the removed device

suggests a manufacturing or design flaw may have contributed to device

removal, then appropriate tests are performed to confirm or allay our

suspicions. In other instances some of the retrieval specimens may be

examined in detail as part of other laboratory projects.

Complete data collections was not always possible. Of the 130

study cases, 14(11%) have some missing items on the coding form. The

items most frequently missing were the patient's exact height and weight,

usually caused by a failure to complete the patient interview.

Photographic records taken of select X-rays, during revision

surgery and of the removed prosthesis are filed. The components are labelled and stored after testing. Confidentiality of patients' and

surgeons' names is strictly maintained.

Data from all medical records and analyses, summarized on the

coding forms, are transferred to magnetic tape for storage and later

computer analysis [3] using the university computer 1

. Through the use

of RIQS this system is capable of storing and sorting all the

data for further study using SPSS [5], a package of computer programs

1 Ctx:-6600> Control Data Corporation, Palo Alto, CA

5 if
specifically designed for statistical analysis. SPSS was developed so that various statistical tests, ranging from a simple correlation between two variables to an extensive non-linear multiple regression

involving many variables, could be employed quickly with relatively

little effort. A computer display terminal 2 in the laboratory permits

on-line, interactive study of the stored data.

4. Results and Discussion

Several terms are used in discussing the results. The following

is our definition of these terms:

Prosthesis Loosening : Although loosening has often been defined

radiological ly, for the purposes of this study, prosthesis loosening

is a gross, clinical observation made at the time of revision surgery.

A TJR prosthesis component was taken to be loose when, upon opening a joint, the attending surgeon could physically move the component with

mild to moderate hand pressure. Such looseness could usually be both

felt and seen with blood being expressed from between the prosthesiscement of cement-bone interfaces.

Cause of Failure : After a careful review of the patient history

and postoperative examination of the removed components, a final cause or factor leading to failure of the TJR is determined. As the observations and data used are somewhat imprecise, decisions on the cause of

removal were made conservatively and very strong, persuasive evidence

was required. Even under such strict conditions, a cause of TJR removal

could be identified with confidence in about 70% of the cases, Table 3.

Iatrogenic : Severe mal orientation of one or more of the prosthetic

components or inadequate patient care leading to immediate, postoperative

sepsis were among the factors included under the iatrogenically induced

removals category for the cause of failure.

Trauma : Cases were listed in the trauma category of the cause of

removals table when a specific major incident such as a fall could be

identified as initiating the onset of symptoms which then continued

until the time of arthroplasty revision.

Sepsis : Early sepsis was defined, for the purposes of this study,

as infections occurring within the immediate 6 month postoperative time

period following arthroplasty. All other infections were classed as late infections.

Idiopathic Loosening : There were a number of cases for which a clearly identifiable initiating factor leading to TJR removal was not

apparent. These were listed as having been removed for pain only or

as a result of idiopathic loosening, where pain is also implied. The

category of idiopathic loosening was only used when one or more of the

2 Tektronix - 4010 Computer Display Terminal, Beaverton, OR

5 I 2
prosthetic components was observed to be loose at the time of surgery.

There is a presumption in this definition. If it were shown that most

TJR's which function preperly were, in fact, loose as defined here,

then idiopathic loosening could no longer serve as a satisfactory

classification since this condition would not necessarily be related

to failure. These cases would then be more properly classed as having

been removed for pain only.

Pain Only : If neither of the prosthesis components were grossly

loose, the case was placed in the pain only category as the reason for

removal. Some of the components in the pain only category were removed

with very little effort so that suspicions of loosening lingered.

Other cases presented with very firmly fixed components; indeed,

considerable effort was required to dislodge some.

The results presented are of two types. The first are those

observations thought to be relevant to the clinician and relate to

the expected performance of the implants. The second group is related

more to information on basic processes and component design. The

latter group of results are necessarily more speculative, and need to

be continually checked and guided by the data. This speculation is

justified on the basis of the potential importance of the results and

on the lack of other means of obtaining such data.

The most frequent cause of total hip joint revision was idiopathic

loosening of one or more of the prosthetic components, table 3. One

. third of all the removed hips were so classified. The other major

causes of total hip removal were trauma (21%) and sepsis (15%). Iatrogenic factors were responsible for only 11% of the revisions.

By contrast, one third of the total knee revisions were performed

for iatrogenically induced reasons. The other major reasons for total

knee removal were idiopathic loosening (30%) and trauma (11%) .

The knee joint is an anatomically intricate joint, consisting of

three separate articulations, multiple constaining ligaments and

complex geometries. The relationships between multiple knee motions,

t rotation, antero-posterior sliding and flexion-extension, and knee

joint structures are not yet fully understood. Accordingly, knee

joint prosthesis design is a somewhat imprecise art with new designs

and surgical procedures continually evolving. All these factors are

| reflected in the high incidence of technical problems leading to total

knee revision.

The total time period, groups by years, for which the prostheses

were implanted before removal is plotted in figure 1 for hips and knees.

Both histograms seem to indicate a greater portion of the removals

4.1. Results Related to Prosthesis Performance

4.1 .1 . Cause of removal

4.1.2. Time between surgery and revision

5 I 3
occurred within 3 years after the original arthroplasty. However,

some of the removals were prejudiced toward early failure from the

very onset of the arthroplasty, namely those cases involving early

sepsis or technical problems. If such cases are eliminated, the rate

of total hip removal appears to be approximately constant or even slightly decreasing for at least 8 years. In particular, the data

does not support the often expressed fear that the loosening rate

may increase with time [9].

On the other hand, the incidence of total knee removal remains

elevated for the initial 2 or 3 year postoperative time period even after the iatrogenic and early sepsis cases are removed. Thus, total

knee patients may be at increased risk of joint failure during the

short-to- intermediate postoperative time period. There were insufficient

total knee cases retrieved after long-term use to be able to make any

predictions on the long-term survival rates of knees, although no evidence of any upsurge of late (i.e. greater than 3 years) loosening

was observed.

Total hip replacement has remained relatively unchanged with re- gard to overall design concept for the past decade and substantial

numbers of patients have been reciving total hip arthroplasties at

least since 1972 [6]. Thus, the rate of hip removal is probably not

influenced by recent rapid changes in the total hip population. However, the number of patients receiving total knee replacement has been

rising in recent years [6]. The lack of long-term total knee data is,

in part, a reflection of the relatively few patients with total knee

arthroplasties of long duration.

A second measure of TJR longevity is the time period that the

arthroplasty functioned before the development of major symptoms, i.e.,

pain or joint dysfunction, after surgery. This time period, obtained

during the patient interview, is, in some respects, a better measure

of the successful operative time of the failed TJR's, figure 2. It is

the time period that the patient would probably view as the time of

successful rehabilitation.

The histograms again show that a very large number of the total

knees that ultimately went on to revision had a relatively short

symptom-free period even when the early sepsis and iatrogenic cases

are eliminated. Indeed, twenty (46%) of the knee patients developed

sysmtoms with 3 months and twenty-eight (64%) had symptoms within 1 year after the original arthroplasty. Twenty-six (93%) of these

twenty-eight early symptom patients came to revision within 3 years.

The hip curve also shows a number of cases develop symptoms early

within 2 years, though certainly not as rapidly as the knee patients.

The data also seems to indicate a second group of patients may be

developing symptoms 4-5 years postoperatively. Although the evidence

is not strong and requires collaboration by further research, the

implication of this finding is that perhaps evaluation of new prosthesis

designs or procedures ought to be extended to 5 years.

5 1 A
4.1.3. Iatrogenic Cases

Although many of the removed prostheses demonstrated some evidence

of technical implantation problems, a certain number had problems that

obviously compromised the longevity or efficacy of the arthroplasty.

Those cases where such factors significantly contributed to the

eventual revision of the arthroplasty were classified in the iatrogenic

j category.

Fourteen knees and seven hips were revised as a result of problems which occurred at the time of surgery. Most of these problems

(95%). were related to improper component implantation, either through

inadequate bone preparation (e.g. skewed bone cuts), component

malalignment or poor cementing techniques, table 4. None of these

cases did well postoperatively.

Thirteen (93%) of the fourteen knees and five (71%) of the seven

hips developed symptoms of joint pain or joint dysfunction (such as varus or valgus deformity, joint subluxation or dislocation or limited

and restricted range of motion) within 1 year, table 5. In fact, eleven

(79%) of these knees and two (29%) of the hips developed symptoms within

3 months following the original TJR arthroplasty and all came to revision

within 3 years.

4.1.4. Trauma

In thirteen hip cases and five knee cases, the patient could

identify a specific, major incident which precipitated the onset of

major symptoms. As a group, these patients did very well postoperatively before the traumatic incident. Twelve (92%) of the hip patients

and four (80%) of the knee patients were employed or fully active with

minimal use of supports, table 6.

Four (.80%) of the knee patients and eleven (85%) of the hip

patients reported falling onto the joint which became symptomatic.

I Interestingly, two of the hip patients and four of the knee patients

had other joint replacements which were not affected by the fall and

remained asymptomatic. The two remaining trauma hip patients were

pedestrians hit by automobiles. The last patient of the group reported

j straining her knee while lifting her mother out of a bathtub.

4.1.5. Previously revised cases

Six of the knees and twelve of the hip cases presented with a history of multiple surgical procedures, table 7. The arthroplasty

had already been revised one or more times (9/12 hips and 6/6 knees),

| the rest had had other types of major joint surgery such as hemi prosthesis

implantation. Of all these cases, four (67%) of the knees and seven

(58%) of the hip patients developed new symptoms within 1 year postoperatively. Five (83%) of the knees and nine (75%) of the hips came

to a second revision within 3 years.

Although a small number of these multiply-operated cases which

eventually failed gave satisfactory long-term results (4-8 years), the

majority failed in a relatively short period of time. Patients who

5 I 5
undergo multiple procedures on their joints appear to be at increased

risk of early failure.

4.1.6. Fractured Components

Seven fractured femoral stems were recovered in this study,

table 8. In six (86%) cases, the patients had a body weight greater

then 75 kg (average wt = 86 kg). All seven patients were employed

and very active. The average postoperative time period prior to

fracture was 4 years (53 months) with a range of 2 to 8 years. The

fractured components included 6 of 36 Charnley-Mul lers and 1 of 4

Charnleys. None of the 19 Aufranc-Turner stems examined were

fractured. As expected, all of the femoral stems were easily removed; none of the actabular cups were loosened.

In three other cases, the UHMW polyethylene acetabular cup was

found to be cracked in the region of the weight-bearing dome of the

cup, table 9. None of these cups actually fractured, i.e, split in

half. All of these cracked cups were of the 32 mm inside diameter design and occurred in women weighing less than 75 kg. These patients were active and did not use any external supports. The average postoperative time period prior to fracture was 69 months with a range of

55 - 82 months.

Examination of the patient X-rays showed that the cement had

cracked around each of the components and in one case, the pelvic

wall of the acetabulum yielded so that part of the cup and cement protruded into the pelvic cavity. At revision surgery, the components

were found to be freely loose from the cement; the acetabular cement

was also broken and loosened from bone with a thick fibrous tissue

interposed between bone and cement. Thus three of ten loose cups were

cracked whereas, none of the 51 non-loose cups were cracked.

Four (.]4%l«l)HMW polyethylene tibial components out of twentyeight Geomedic^ type total knee replacements were found to be cracked

or fractured through the anterior cross bar, table 10. In contrast to

the total hip patients with cracked or fractured components, these

patients were very elderly women (average age = 75 years) and were generally inactive; one patient was active with use of a single

support. Also, three of the four patients weighed* less than 75 kg.

Two of the fractures occurred early, at 10 and 15 months, the other

two occurred late, at 46 and 68 months postoperatively.

Examination of the X-rays in two cases showed the PMMA cement

had cracked and loosened under only one of the tibial plateaux whereas

a third case showed general cement disintegration under the entire

tibial component. Roentgenograms of a fourth case were not available.

At revision surgery, three of the four tibial components were grossly loose with a fibrous tissue layer interposed between bone and

cement. The fourth component was apparently firm but easily removed;

a thick, fibrous tissue layer was reported interposed between bone

and cement and X-rays showed a lucent line between bone and cement.

5 i e
Thus three of seventeen loose components were fractured and one

of twelve non-loose components was fractured, although there was a large amount of fibrous tissue around this component.

4.1.7. Sepsis

Seventeen (16%) of the 105 cases under consideration in this report

were found, through positive culture, to be infected at the time of

revision surgery although only twelve of these seventeen were suspected

of being infected prior to revision, table 11.

Four (33%) hips and four (80%) knees were revised for early

sepsis.

In most of the cases, the components were not found to be grossly

loose at revision surgery; two acetabular cups, six femoral stems,

one femoral knee component and three tibial knee components were loose.

Late infections occurred at variable postoperative time periods

and had various etiologies. However, two knees and five hips previously had multiple surgical procedures and four other hips had a prior history of sepsis, so that, a majority (65%) of all the infected

cases had a predisposition toward the development of sepsis. Only

three cases presented with a history which indicated no increased risk

toward joint sepsis.

4.1.8 Radiolucent lines

A commonly reported intermediate to long-term X-ray finding

following TJR arthroplasty is the appearance of a radiolucent line

demarcating and separating the radio-opaque bone and PMMA cement. This

phenomenon was also observed in the current removal cases, but such a line was not always observed and no correlations could be obtained

between the existence of this line and other study observations, table 12.

All of the crosstabulations failed the chi-square test at the .05 level

of significance.

In particular, not all the infected hips or knees were observed

to have such lines. Not all the components found to be clinically

loose displayed a radiolucent line on X-ray and conversely, not all the

components with lines were grossly loose.

4.2. Results Related to TJR Science

4.2.1. Loosened interface and loosening etiology

The loosened interface varied with component. Since this observation may be important in understanding the etiology of the failure

process, the nature of the failed interfaces were recorded. This was

necessarily only approximate, since the condition in vivo could not

be accurately assessed, even at revision surgery. Interface failure

was classed as one of three: (i) bone- cement interface only, (ii)

cement-component interface only, and (iii) at both interfaces.

5 ! 7
A category was chosen if failure was predominantly of that type.

Cement- component only failure was assumed if the component, primarily

hip stems, came out freely, but all cement had to be forcibly removed.

The results are shown in table 13.

A significant observation from this data is that all (31/31)

loose total hip femoral components were loose at the cement-component

interface. This finding is at odds to the data for the other three

components which were loose more frequently at the bone-cement interface and less often at the cement-component interface. The most

frequently observed failed interface might be expected to be the one which failed first. If failure occurred first at the bone-cement

interface, which in turn led to cement-component interface failure,

a significant number of bone-cement only interface cases should be

seen.

The implication of this observation is that the hip stems are failing first at the cement-component interface and that this is the

weak element in the system. This implication does not have direct

data to support it; other processes are possible. However, it agrees

with other studies [8] which show failure of this interface leads to

high PMMA cement stresses, implying subsequent PMMA cement fracture

and bone-cement interface failure. This observation also supports

the need for more research on this interface regarding failure

processes and prosthesis design.

Another observation from this data is that the metal femoral

components of the knee rarely loosen and when they do or when a firmly

fixed component is removed, the PMMA cement is firmly fixed to the

component and there is not PMMA fracture. This implies that if the

PMMA cement remains fixed to the metal, there will be no cement

fracture.

The converse is observed with the UHMW polyethylene components,

i.e., the acetabular cups and the knee tibial components. Although

there were several cases where the cement-component interface only

failed, the more frequent observation in these cases was failure at

the bone-cement interface or both. In the cases where both interfaces

loosened, sections or pieces of cement were sometimes found well

adhered to the component or to bone. This implies cement fracture without total failure of the cement-component interface is possible. Thus,

failure of the bone- cement interface or cement fracture is the more

likely initial factor in the loosening process in these cases.

There were no components seen in which wear was a primary factor

in failure, although wear was observed in many UHMW polyethylene

components. Cups and knee tibial components will be discussed

separately.

On gross examination, many of the acetabular cups showed evidence

of smooth, 2-body wear between metal and plastic, but the amount or depth of wear was very difficult to measure. There were, in effect,

4.2.2. Wear

5 I 8
no significant dimensional changes and very little loss of material.

The specimen with the greatest measurable amount of wear was the single

Delrin cup collected where a reduction in wall thickness of approximately 2 mm was observed after 7^ years of active use.

There were, in addition, several acetabular cups with gross 3-body wear by cement particles. This demonstrates that inversion of the con- cave surface, by itself, will not prevent particle entrapment and

3-body wear. Another observation, possibly wear related, concerned

the cracked cups. Of the three cracked cups, one was Delrin, so only

two of the 60 UHMW polyethylene cups showed noticeable cracks. Also,

all three cups were loose, suggesting prior loosening as the factor

leading to the cracking; none of the 51 non-loose cups were cracked.

However, the additional significant factor was that of the ten loose

cups, three had been in place for greater than % years. These were

the three cracked cups. Thus, the cracked acetabular cups were

those that were both loose and had been implanted a long time. No

cracks were seen in the remaining seven loose cups which were implanted

less than 3 years.

The implication of this data is that some time-dependant process

is degrading the strength of the UHMW polyethylene, either wear or

material property degradation. Even if occurring, it would pose a negligible problem for up to a 10 year period of use, but it may be

of significance in the longer than 10 year period. The numbers to

support this hypothesis are small, but it points out a potential

problem which should be investigated.

With the knee tibial components, some visible smooth, 2-body

wear has occurred with Marmor type components (less than 1 mm in depth)

but no cracks have been apparent by gross examination. There is, very

frequently, gross 3-body wear by entrapped PMMA cement particles, but

this was usually associated with component loosening.

4.2.3. Stress Related Failure

A need for component design and comparison is a criterion of

failure. Stress level is one obvious possibility, but material type

and biological factors such as disease, etc., are also possibilities.

What factors influence component failure?

Since loosening of femoral stems and knee tibial components

appears to be the major problem with hip and knee prostheses, a criterion for loosening is the highest priority. Since loosening

implies failure of the interfaces or components, a stress criterion

is most appealing.

Does the removal data support a stress criterion for loosening?

To determine this, correlations between loosening and high force

variables will be sought. These variables are body weight, patient

activity level, trauma and component impingement with edge loading.

5 I 9
For all components, there was no significant correlation between

loosening and body weight or between loosening and activity level.

All the crosstabulations in tables 14 and 15 failed the chi -square

test at the .05 level of significance. However, there was a positive

correlation between loosening and trauma and between loosening and

component impingement.

With regard to trauma, four of five knees and twelve of thirteen

hips that filed due to trauma had loosened components at revision

surgery. /^Impingement of the femur with the anterior tibial lip of

Geomedi c ^

type tibial components was frequently observed. Such edge

loading generates high bone-cement interface tilting stresses posteriorly, and could possible lead to component loosening.

(ft) There were twenty-eight Geomedic wtype components. Fifteen of

eighteen loose tibial components had evidence of anterior tibial lip

impingement; two of the ten non-loose components had this impingement,

table 16. The crosstabulations of table 16, passed the chi-square

test at the .01 level of significance. These observations support

the hypothesis that extraordinary, high stresses can cause loosening,

but normal functional loads, even for the heavy or active patient, will

not cause loosening. This data does not constitute conclusive support,

but the hypothesis is supported by the data available.

Another observation that relates stress to failure is that fractured

or cracked components are nearly always associated with loosening. Since

broken components would imply relatively high stresses, this implies that

loosening generates high stresses. This is expected intuitively and has

been predicted from finite-element studies [ 7, 8 ].

5. Evaluation of the Northwestern University Joint

Implant Retrieval Program

Our implant retrieval program has the inherent problems of a retrospective study and data collection from multiple institutions. Results

of high statistical significance are difficult to obtain.

We initiated and have maintained our retrieval program on the basis

that it appeared to provide useful information on implant failure. This was a presumption which eventually must be verified; sufficient data

has now been collected and analyzed to decide on the actual value of

such a program. The questions that must be asked are:

(i) What useful new information has come out of our

retrieval program that wasn't already well known or available by some other means?

(ii) Of what use is the information; how will it alter

practices or designs?

(iii) Is the cost worth the effort?

520
With regard to the first question, we feel the most significant

results we have seen from our studies are as follows:

1) There is no evidence to support the hypothesis that the total

hip loosening and removal rate will increase with implantation

time up to 8 years, although there is a rise in the rate of

total hip symptom development around 5 years. This suggests

that 5 or 6 years might be a more appropriate time period for

evaluation new hip designs or procedures. Later, very longterm failure rates are not yet known.

2)_ Falls and other trauma can cause prosthesis component

loosening.

3). Fractured and cracked components are almost always

associated with loosening.

4). A previously revised joint is more likely to be revised

than an unrevised joint.

5) Radiolucent lines do not correlate well with loosening.

Components with no lucent lines can be loose; components

with thick lines may not be loose.

6} All loose femoral stems loosen at the cement-component

interface. Many UHMW polyethylene components loosen at

the bone-cement interface and are also often associated

with fracturing of the PMMA cement. The removed polythylene components usually have cement still fixed to

the component. In addition, metal femoral components of

knee prostheses seldom loosen and almost always have no fractured cement. These observations support the hypothesis

that stem loosening is frequently initiated by debonding at

the cement-metal component interface and that tibial knee

component loosening involves PMMA cement fracture and bonecement interface failure.

7) High stress due to trauma and impingement is related to tibial

component loosening.

8) There were no fractured Aufranc-Turner stems even though they

comprised nineteen of the 61 hip cases. Six of 36 CharnleyMuller stems fractured.

This listing leads to the second question of how this information

is now being used or will be used. Other investigators may find the

information useful, but its use can best be illustrated by examples

of how it has influenced our own practices.

First, the ongoing program has influenced our choice of research

projects. Loosening of tibial components of knee prostheses is the

major problem with knees; our study suggests many aspects of this

problem are stress-related. We have institued a comparative study of

the stress distributions about several knee prosthesis designs.

52 I
Second, we have avoided being overly concerned with broken components

and have concentrated more on prevention of loosening. Third, although

not listed here, an observation on many of the loose femoral stems was frequent poor PMMA cement distribution around the stem and poor cement

interdigitation with bone. We instituted a study of cementing

techniques for delivering PMMA cement to the femoral canal. Clinical

trials of the most appealing systems currently available are in

progress. Fourth, we stopped work on a wear project because of its

minor relative importance over the less than 10 year period. Finally, we have used detailed observations of the bone-cement interface to aid

in a project on the biomechanics of this interface.

In addition to these specific instances of direct use of re- trieval program results in specific projects and project selection,

there have been some positive indirect benefits. The procedures of

information collection and dissemination have established and maintained communication between surgeons in our area and our bioengineering team and has allowed the bioengineers direct access to implant

patients. Such patient contact is frequently difficult to maintain

for a basically engineering group. These contacts have given us a better understanding of the nature of patient and surgical problems

The work of analyzing the retrieval data has created an awareness

on our part of the detailed questions and problems of joint implants,

a sensitivity that probably would not exist to such a degree without

our retrieval program.

We have concluded that these benefits are worth the time and

funds required to maintain the program and we plan to continue it in

the future. Whether this would be so for other centers must be decided

on an individual basis, taking into account the needs and resources

available.

This program was supported by the National Institute for Handicapped Research, grant NIHR 23P-5589.8.
Table 1: Retreived Prostheses

NUMBER OF CASES: hips - 75

knees - 52

other - 3

130

PROSTHESIS TYPE:

HIPS KNEES

Aufranc-Turner 19 Duo-Patel lar 5 Charnley 4 Geomedic 28

Charnley-Mul ler 36 Marmor 5 T-28 1 Polycentric 2 CAD 1 St. Georq Sled 2

61 Total Condylar 1 UCI 1 McKee-Farrar 7 44

Others 7 75 Others 8

52

523
Table 2 ; General Patient Data

105 cases

AGE: Hips Knees

Number Percent Number Percent

less than 40 9 15% 0

40 - 49 3 5% 2 5%

50 - 59 11 18% 5 11%

60 - 69 25 41% 24 55%

70 - 79 8 13% 11 25%

greater than 80 5 8% 2 5%

61 44

SEX: hips knees

males 26 11 females 35 33

WEIGHT: Hips Knees

Number Percent Number Percent

normal 27 44% 16 36%

overweight 33 54% 25 57%

unknown 1 2% 3 7%

61 44

less than 75 kg 36 59% 25 57%

greater than 75 kg 25 41% 19 43%

61 44

DISEASE: Hips Knees

Number Percent Number Percent

osteoarthritis 27 44% 29 66%

rheumatoid arthritis 7 11% 11 25%

traumatic arthritis 8 13% 4 9%

CDH 3 5% 0

other 16 26% 0

61 44

PRIOR REVISION: Hips Knees

Number Percent Number Percent

yes 15 25% 8 18%

no 46 75% 36 82%

61 44

SYMPTOM DURATION: Hips Knees

Number Percent Number Percent

less than 1 yr 48 79% 27 61%

1 - 2 yrs 11 18% 1 2 27%

greater than 2 yrs 2 3% 5 11%

61 44

524
Table 3: Patient Clinical Data

PRIMARY PREOPERATIVE INDICATION FOR REMOVAL OF TJR:

Hips Knees

Number Percent Number Percent

loosening with pain 35 57% 20 45%

pain only 1 2% 12 27%

sepsis 8 13% 4 9%

dislocation/subl uxation 9 15% 5 11%

bone fracture 1 2% 1 2%

prosthesis fracture 7 12% 1 2%

other 0 1 2%

61 44

REVISION PROCEDURE:

Hips Knees

Number Percent Number Percent

replace component 34 56% 14 32% new prosthesis 17 28% 21 48%

suction- irrigation 6 10% 3 7%

pseudo-arthrosis 3 5% 0

arthrodesis 0 5 11%

other 1 61

21 1 44

2%

SUMMARY REASON FOR TJR REMOVAL:

Hips Knees

Number Percent Number Percent

iatrogenic 7 11% 14*

32%

sepsis-early 4 7% 2* 5%

sepsis-late 5 8% 1 2%

trauma 13 21% 5 11%

idiopathic loosening 33% 30%

prosthesis fracture 6 10% 2%

pain only 2 3% 3 7%

other 3

61 5% 5 44

11%

* 2 early sepsis listed as iatrogenic

** 1 prosthesis fracture listed under trauma

** 3 prosthesis fractures listed under idiopathic

loosening

5 2

r

,
Table 4: List of Iatrogenic Problems

Case Joint Technical Problem

1 knee Malalignment of femoral component (flexed 30°)

Tibial component also malaligned.

2 knee Malalignment - both components.

3 hip Malalignment of femoral component

(introverted)

.

4 hip Malalignment of acetabular component.

5 hip Malalignment of femoral component, stem perforated posterior-medial femoral cortex.

6 knee Malalignment of tibial component.

7 knee Too much cement suopriorlv nnnr honp

preparation inferiorly.

8 knee Femoral component flexed, patellar impingement .

9 knee Tibial comDonent misDlaced. set deeD and

tibial eminance is hitting in intra-condylar

notch.

10 knee Femoral component placed too far anteriorly.

11 hip Acetabular malalignment.

12 knee Femoral component malal igned.

13 knee Bone Fx, tibial side-improper bone cuts.

14 knee Bone in intra-condylar notch hitting

femoral component.

15 hip Malalignment of femoral component.

16 hip ImoroDPr ioint closurp. allows subluxation.

17 knee Femoral -excessive bone removed and

excessive cement; Tibial-malalignment and

excessive cement.

18 hip Malalignment of both components.

19 knee Excessive cement superiorly, impingement on tibial component and soft tissue.

20 knee Malalignment of femoral component.

21 knee Tibial component malalignment.

1 526
Table 5: Symptom - Free Period of TJR

Iatrogenic Cases

Hips Knees

SvmDtom - Frpe Period

Number Percent Number Percent

less than 3 mo. 2 29% 11 79%

greater than 3 mo. 3 43% 2 14%

but less than 1 yr.

greater than 1 yr. 2 29% 1 7%

7 14

527
Table 6 - Patient Activity, Trauma Cases

HIPS* working/

active

active with

support inactive

before

symptoms

10 2 0

a ftor

symptoms

2 6 5

KNEES working/

active

active with

support

inactive

before

symptoms

4 0 1

after

symptoms

2 0 3

* 1 case missing

528
Table 7: Time Period of TJR USE

Multiply-Operated Cases

Symptom - Free Period

Number

Hips

Percent

Knees

Number Percent

less than 3 mo. 5 42% 3 50%

greater than 3 mo. but less than 1 yr.

2 17% 1 17%

greater than 1 yr. 5

12

42% 2

6

33%

Total TJR Implantation

T •? ma i \ ine Number

Hips

Percent

Knees

Number Percent

less than 1 yr. 4 33% 3 50%

1 - 2 yrs 4 33% 0

2 - 3 yrs 1 8% 2 33%

3-4 yrs 1 8% 0

4-5 yrs 1 8% 1 17%

5-6 yrs 0

- 0

6-7 yrs 0 0

7-8 yrs 1

12

8% 0

6

529
Table 8: Summary of Data on Fractured Stems

SEX:

WEIGHT:

male

7 cases

5, female

less than 75 kg - 2 greater than 75 kg - 5

PROSTHESIS TYPE Charnley-Muller 6 of 36

Charnley 1 of 4

Aufranc-Turner 0 of 19

OTHER JOINTS WITH

PROSTHESES none 5 contralateral joint 2 contralateral joint and others 0

others 0

PATIENT ACTIVITY

working/

active

active with

support inactive

before

symptoms 7 0 0

after

symptoms 0 5 2

SYMPTOM- FREE TIME PERIOD OF TJR USE:

<uto

to

3 4

Years
Table 9: Summary of Data on Cracked Cups

3 cases

SEX: male - 0, females - 3

WEIGHT: less than 75 kg - 3

greater than 75 kg - 0

PROSTHESIS TYPE: Charnl ey-Mul ler 2 of 36

Aufranc-Turner 1 of 19

Charnley 0 of 4

OTHER JOINTS WITH

PROSTHESES: none 2 contralateral joint 1 contralateral joint and others 0

others 0

PATIENT ACTIVITY:

working/

active

active with

support inactive

before

symptoms 3 0 0

after

symptoms 3 0 0

SYMPTOM- FREE TIME PERIOD OF TJR USE

CDto

1 1 1

1 , 1, 1

2 3 4 5 6

Years

53 I
Table 10: Summary of Data on Broken Tibial Components

4 cases

SEX: male - 0, female - 4

WEIGHT:

PROSTHESIS TYPE

less than 75 kg - 3

greater than 75 kg - 1

Geomedic

Others

4 of 28

0 of 16

OTHER JOINTS WITH

PROSTHESES: none contralateral joint

contralateral joint and others

others

PATIENT ACTIVITY:

working/

active

active with

support inactive

before

symptoms

0 1 3

after

symptoms

0 1 3

SYMPTOM-FREE TIME PERIOD OF TJR USE:

5 —

QJ O

Years

532
Table 11: Sepsis Cases, Summary Data

17 cases PREOPERATIVE INDICATION

FOR TJR REMOVAL: Hips Knees

loosening with pain 4 1 infection _8 4

12 5

SYMPTOM-FREE TIME PERIOD

OF TJR USE: Hips Knees

less than 3 mts 2 4

4 - 6 mts 2 0

7 - 12 mts 0 0

1 - 2 yrs 3 1 2 - 3 yrs 0 0

greater than 3 yrs 5 0

5

LOOSENING: Hips - acetabular component 2/12

- femoral stem 6/12

Knees - femoral component 1/5

- tibial component 3/5

533
Table 12 : Radiolucent Lines and Loosening

Aseptic Hips:

Femoral Stem Acetabular Cup

not not

loose loose loose loose

1 ine

present

14 8

1 ine

\J i t: be r 1 L 6 28

no

1 ine

17 10 no

1 ine

4 11

X

2 - = .062 X

2 .114

Aseptic Knees:

Femoral Component Tibial Component

not not

loose loose loose loose

1 ine

present

4 14

1 ine

present

20 10

no

1 ine

1 20 no

1 ine

3 6

x

2 = 1.312 x

2 = 1.951

X

2 = 3.84

.95

S3 A
Table 13: Aseptic Loosened Interfaces

LOOSENED INTERFACES

COMPONENT BONE-PMMA

PMMACOMPONENT BOTH mot i nncc INU 1 LUUot

HIP - FEMORAL

0 20 11 18

HIP - ACETABULAR

4 3 4 38

KNEE - FEMORAL

7 1 1 30

KNEE - TIBIAL

12 4 13 10

49 ASEPTIC HIPS

39 ASEPTIC KNEES
Table 14 : Prosthesis Loosening and Patient Weight

Aseptic Hips:

2 cases missing

Femoral Stem Acetabular Cup

loose

not

loose loose

not

loose

less than

75 kg.

12 13

less than

75 kg.

8 17

more than

75 kg.

17 5 more than

75 kg.

2 20

x. 2 Aseptic Knees:

= 3.095 X

2 = 2.427

1 case missing

Femoral Component Tibial Component

loose

not

loose loose

not

loose

less than

75 kg.

3 18 less than

75 kg.

11 10

more than

75 kg.

2 13 more than

75 kg.

9 6

x

2 = .147 x

2 = .025

X

2 = 3.84

;95

53 G
Table 15 : Prosthesis Loosening and Patient Activity

Aseptic Hips:

Femoral Stem Acetabular Cup

loose

not

loose loose

not

loose

active 28 16 active 8 36

not

active

3 2 not

active 2 3

x

2 = Aseptic Knees:

.109 x

2 = .315

Femoral Component Tibial Component

loose

not

loose loose

not

loose

active 3 20 active 15 8

not

active

2 14 not

active

8 8

x

2 = .191 x2 = .384

X

2 = 3.84

.95

i

I

537
Table 16 : Geomedic Tibial Component Loosening

Through Anterior Lip Impingement

loose

not

loose

impingement on anterior tibial lip 15 2

no impingement on anterior tibial lip 3 8

X

2 = 8.318

.99

5 3 8
FIGURE 1

TOTAL TJR IMPLANTATION TIME PERIOD

to o

s30 -

25 -

20 -

15

10 -

5 -

0

tod>

to

03

<_> M-O

S-<D XIE

13

30 -

25 -

20 -

15 -

10 -

5 -

0

0

O all cases A early sepsis and iatrogenic cases deleted

HIPS

O

f 0 1 4

I

5 6

Years in Use

1 T

10

O all cases A early sepsis and iatrogenic cases deleted

KNEES

I T

5 6 7 Years in Use10

539
FIGURE 2

SYMPTOM - FREE TIME PERIOD OF TJR

O all cases A early sepsis & iatrogenic cases deleted

HIPS

9

2

<? 0

t~ ~~r~ ~r~

1

~r~ ~i T

3 4 5 6 7 8

Years in Use

10

O all cases A early sepsis & iatrogenic cases deleted

KNEES

I 2. i i i 1 4 5 6 7

Years in Use

10

540
References

[ i ] Charnley, J. and Cupric, Z., The nine and ten year results of

the low-friction arthroplasty of the hip, Clin. Orthop. 95_: 9-25 , 0 973);

[ 2 ] Annual Book of ASTM Standards, Part 46 , pp. 958-962 (American

Society for Testing and Materials, Philadelphia, PA, 1979).

[ 3 ] Kramer, 6.M. and Hon , R.Y., Total joint replacement data

collection and analysis system - TJDCAS, report of the

Rehabilitation Engineering Program, Northwestern University,

Chicago, IL 60611 (May, 1980).

[ k ] Borman, L. , Chalice, R. , Dillaman, D., Dominick, W. , and

Kron, P., Remote Informaiton Query System, Information

Services Technical Report 74-003, Document Number 193,

Vogelback Computing Center, Northwestern University, Evanston,

IL (1975).

[ 5 ] Nie, N.H., Hull, CD., Jenkins, J.G., Steinbrenner, K. , and

Bent, D.H., Statistical Package for the Social Sciences , Second Ed. , (McGraw-Hill Book Co., New York, N.Y., 1975).

[ 6 ] Hori, R.Y., Lewis, J.L., Zimmerman, J.R., and Compere, C.L.,

The number oftotal joint replacements in the United States,

Clin. Orthop. 132, 46-52 (1978).

[ 7 ] Bartel , D.L. and Samehyeh, E., The effect of cement modulus

and thickness on stresses in bone-prosthesis systems, Proc.

of 22nd Annual Meeting of the ORS, New Orleans, LA (1976).

[ 8 J Huiskes, R. , Some fundemental aspects of human joint replacement,

report of Laboratory for Experimental Orthopaedics, University

of Nijmegen, The Netherlands (1979).

[ 9 ] Beckenbaugh, R.D. and Ilstrup, D.M., Total hip arthroplasty. A

review of three hundred and thirty-three cases with long-term

followup. J. Bone Jt. Surg. 60-A : 306-313, 1978.
APPENDIX I

5 «1 2
June 5, 1979

Rev. 6

NORTHWESTERN UNIVERSITY REHABILITATION ENGINEERING PROGRAM

REMOVED PROSTHESIS ANALYSIS

CLINICAL DATA

Recorder

COLUMN ITEM

GENERAL INFORMATION

1-19 Patient Name

20-28 Social Security No.

29-31 Data Collection Center _

32-34 Surgeon

35 Patient Source

36-37 Age

38 Sex

39-41 Shift Check _6 _7 J3

42-44 Height (in cm)

45-47 Weight (in kg)

48 Overweight Condition

PRE-OPERATIVE ANALYSIS

49 Joint Involved _

50 Side Involved

51-56 Date of Original TJR*

57 Original Diagnosis

leading to TJR

Recording Date

Series No.

(use 3 letter abrev. of institution)

1) physian's own case 2) referral case

1) male 2) female

(in ft. -in.)

(in lbs)

1) none 2) moderate 3) marked

1) hip 2) knee 3) ankle 4) other

1) right 2) left

TdayT TyrTT

1) osteoarthritis

2) rheumatoid arthritis

3) traumatic arthritis

4) sepsis

5) CDH

6) other (specify)

Manufacturer and Model of Prosthesis

* If day is not given, the first of the month will be assumed; if month is not

given, January is assumed; if date is not known, set year to "99".

This code conforms to ASTM F-561-78.

5 43
Series No.

COLUMN ITEM

58-63

64

65

66

67

68

75

76-78

79-80

1-9

10

FOR OFFICE USE ONLY

Original Prosthesis Type

Antibiotics at Previous TJR

If YES, Reason

History of Foreign Body

Reaction

Arthroplasty previously revised

Other Joints with Prosthesis

1) yes 2) no 3)unknown

1) prophylactic

2) positive culture at surgery

3) history of sepsis

4) other

5) no antibiotics 6) unknown

1) yes 2) no 3)unknown

1) yes (specify) 2) no

1 ) none

2) contralateral joint only

3) contralateral joint and others

4) others

69-71 Length of Time Symptoms Have Persisted _ _ (months)

FOR OFFICE USE ONLY

72-74 Length of Time TJR in Use Before Onset

of Symptoms _ (months)

Blank

Shift Check _6 _7 _8

Card No. 7 A

Social Security No.

Initial Factor Leading to Removal Symptoms

1) iatrogenic**

2) infection

3) trauma or fall

4) idiopathic

5) autopsy

6) other

** Iatrogenic problems include: poor component orientation, poor bony

preparation, bone fracture, etc.

-2-

544
Series No.

COLUMN ITEM

11-12 Primary Pre-op Indication of Removal of TJ

01) loosening with pain 07)

02) loosening with minimal pain 08)

(prophylactic removal) 09)

03) pain only 10)

04) infection 11)

05) dislocation/subluxation 12)

06) bone fracture 13)

autopsy

prosthesis fracture

restricted ROM prominence of bursae

unsatisfactory position of implant

hyper-sensitivity reaction

other

13-14 Secondary Pre-op Indication for Removal of TJ

01) loosening with pain

02) loosening with minimal pain

(prophylactic removal)

03) pain only

04) infection

05) dislocation/subluxation

06) bone fracture

15-16 Contributory Conditions

01) none

02) alcoholism

03) drug addiction

04) senility

05) neuromuscular disorder such

as hx of polio, CVA, etc.

Patient Activity

17 Prior to onset of symptoms

18 After onset of symptoms

Joint Range of Motion

19 Prior to onset of symptoms

20 After onset of symptoms

Ability to Walk Up Stairs

21 Prior to onset of symptoms

22 After onset of symptoms

07) autopsy

08) prosthesis fracture

09) restricted ROM

10) prominence of bursae

11) unsatisfactory position of implant

12) hyper-sensitivity reaction

13) other

14) none

06) multiple previous procedures

07) other

1) active and working

2) active, uses no supports or one support intermittently

3) active, uses 1 support

4) active, uses 2 supports

5) inactive, uses 1 or 2 supports

6) inactive, wheelchair

7) inactive, confined to bed

8) other

1) full ROM

2) functional ROM

3) restricted and limited ROM

4) joint contracture, .imited ROM

1) normally

2) slowly, alternating

3) one stair at a time

4) unable

5 4 5
Series No.

COLUMN ITEM

23

24

25

26

27

28

29-34

35-40

41-43

44

45

45-51

52-54

Ability to Stand from Sitting Position

Prior to onset of symptoms

After onset of symptoms

Ability to Put On Shoes and Socks

Prior to onset of symptoms

After onset of symptoms

1 ) no arms required

2) arms required

3) other help required

1) easily

2) with difficulty

3) socks only, cannot tie shoes

4) unable

Pain at Rest

Pain with Weight-bearing

X-RAY FINDIN.6S

TJR on Current Pre-Op X-Ray

1) yes 2) no

1) none 2) mild 3) moderate 4) severe

1'

Proximal Component(s)

Distal Component(s)

01) loose

02) dislocated

03) component fracture or deformation

04) bone fracture

05) radiolucent line present

06) migration or settlement

07) malalignment

Shift Check _6 _7 _8

Heterotrophic Bone Formation

PMMA on X-Ray _

08) increased density(sclerosis,

compaction]

09) penetration of implant

through bone

10) other

1 1

) normal

12) x-ray not available

00) no other factors

1) yes 2) no 3) x-ray not available

1 ) cement cracked

2) excessive cement seen in joint

3) normal

4) no cement

5) x-ray not available

PRESENT REVISION SURGERY

Date of Surgery*

TmoTT TdayT TyrTT

Length of Time TJR in Use _ _ (months)

5 4G
Series No.

COLUMN ITEM

55 Revision Procedure _ 1) replace component (s)

2) arthrodesis

3) new prosthesis (specify)

4) suction-irrigation

5) Girdlestone (pseudarthrosis)

6) other (specify)

GENERAL APPEARANCE AT SURGERY

55 Fibrous Membrane Between Bone & PMMA _ 1) a little 2) a lot 3) no

57 Excessive PMMA Around Components 1) a little 2) a lot 3) no

58 PMMA Fragment(s) in Joint & Synovium _ 1) a little 2) a lot 3) no

59 Proximal Component(s) Poorly Oriented 1) a little 2) a lot 3) no

60 Distal Component(s) Poorly Oriented 1) a little 2) a lot 3) no

61 Component(s) Dislocated 1) yes 3) no

62 Proximal Component(s) Fractured 1) yes 3) no

63 Distal Component(s) Fractured 1) yes 3) no

64 Soft Tissue Rubbing or Impingment by Prosthesis 1) yes 3) no

65 Dony Contact by Component(s) D yes 3) no

66 Sepsis 1) yes 3) no

67 Synovium Stained by Metallic Debris 1) yes 3) no

68 Joint Ligaments Intact _ 1) yes 3) no

69 Musculature Surrounding Joint Intact 1) yes 3) no

70 Foreign Body Reaction 1) yes 3) no

71 Abundance of Scar Tissue 1) yes 3) no

72 Abundance of Granulation Tissue 1) yes 3) no

73 Bursal Fluid 1) yes 3) no

74 Caseation 1) yes 3) no

75 Boney Reaction 1) yes 3) no

76-78 Shift Check _6 J_ _8

79-80 Card No. 7 B

-5-

54 7
Series No.

COLUMN ITEM

1-9 Social Security No.

Degree of Loosening

10-11

12-13

14-15

16-17

18-19

20-21

Proximal Component

Distal Component

Loosened Interface

Proximal Component

Distal Component

Cement Fractures

Proximal Component

Distal Component

Component

#1 #2

1) freely loose, component easily removed

2) loose, component removed with little

effort

3) loose, component removed with

difficulty

4) firm, component removed without great

effort

5) firm, component removed only with

great effort

6) component not removed

1 ) bone/cement

2) cement/prosthesis

3) both of above

4) bone/prosthesis

5) not loosened but removed

6) component not removed

1 ) fresh from removal

2) old

3) both of above

4) no cement

5) none

6) component not removed

TISSUE EXAMINATION

5<1 8
July 28, 1979

rev. 6

NORTHWESTERN UNIVERSITY REHABILITATION ENGINEERING PROGRAM

REMOVED PROSTHESIS STUDY POST-REMOVAL ANALYSIS

Series No. COLUMN ITEM

22-23

24-25

26-27

28-29

30-31

32-33

34-35

36-37

38-39

40-41

Component

#1 #2

PMMA, Amount Used

Superior Component

Inferior Component

Bony Interdigitation of PMMA

Superior Component

Inferior Component

PMMA Distribution

Superior Component

Inferior Component

1) excessive

2) insufficient

3) normal

4) no cement

5) component not removed

6) unknown

1 ) good

2) moderate

3) poor

4) no cement

5) component not removed

6) unknown

1) good even coverage

2) small part of prosthesis uncovered

3) large part of prosthesis uncovered

4) no cement

5) component not removed

6) unknown

Prosthesis Articulating Surface Wea

Superior Component

Inferior Component

Amount of Surface Wear

Superior Component

Inferior Component

1 ) si ight or none

2) shiny, smooth 2 -body wear

3) dull, slightly rough 3-body wear

4) rough, abrasive 3-body wear

5) gross, pitting, gouging 3-body wear

6) component not removed

7) unknown

1) none

2) slight

3) moderate

4) severe

5) component not removed

6) unknown

42-44 Shift Check 6 7 8

549
Series No.

COLUMN ITEM

45

46

47

48

49

50

51

Component Damage

Abrasive Wear or Deformation of Either

Component Due to Bony Contact or Impingement _

Abrasive Wear or Deformation of Either

Component Due to PMMA Cementophyte Contact

Abrasive Wear or Deformation of Either

Component Due to Abnormal Opposing

Component Contact

1 ) yes 2) no

1) yes 2) no

1 ) yes 2) no

Iatrogenic Problems

Superior Component

Inferior Component

Swab from Implant Site, Sterile

If NO, Pathogen _

FINAL CONCLUSIONS

52-53 Cause of TJR Failure

01) iatrogenic

02) sepsis - early

03) sepsis - late

04) trauma or fall 05) idiopathic loosening

1) excess bone removed or inadequate

bone preparation

2) bone fracture

3) component malalignment

4) other (specify)

5) none

6) component not removed

1 ) yes 2) no 3) unknown

1) Staph. Aureus

2) Staph. Albus

3) Staph. Epidermidis

4) Pseudomonas Aeruginosa

5) Clostridium Perfringens

6) E. Coli

7) other

8) no sepsis

06) autopsy

07) prosthesis fracture

08) pain only

09) other (specify)

10) unknown

MATERIAL PROPERTIES ANALYSIS

METALLIC COMPONENTS #1 , #2

54-60 Dimensions of Implant (mm) #1

61-67 §2

_ x _ x length width thickness

_ x _ x length width thickness

-8-

550
Series No.

COLUMN ITEM

Macroscopic Examination

68-69 Wear or Burnishing

70-71 Galling

72-73 Scratching

74-75 Change of Shape

76-78 Shift Check J5 _7 _8

79-80 Card No. 7 C

#1 #2

1) a little 2) a lot 3) no

1) a little 2) a lot 3) no

1) a little 2) a lot 3) no

1) a little 2) a lot 3) no

1-9 Social Security No.

10-11 Mechanical Damage

12-13 Macroporosity

Microscopic Examination

14-15 Inclusion Content (ASTM E-45)

16-17 Grain Size (ASTM E-112)

18-19 Grain Boundary Constituents

20-21 Microporosity

#1 #2

22-23 Corrosion

24-25 Mechanical Failure

1 ) none

2) fatigue

3) torsion

4) impact

5) stress-corrosion

1) a little 2) a lot 3) no

1) a little 2) a lot 3) no

meets standard specifications

1) yes 2) no

1) yes 2) no

1) yes 2) no

1 ) yes 2) no

1 ) none

2) general corrosion

3) pitting corrosion

4) crevice corrosion

5) galvanic corrosion

6) static overstress causing plastic

deformation *

7) corrosion fatigue

8) combination of above

(identify )

26-27 Device Flaws

28-33 Type of Material as Determined

by Chemical Composition

9) other (specify

1) yes (type and origin

2) no

1

-9-

55 I
Series No.

COLUMN ITEM

Mechanical Properties (samples should be taken from areas representative of

the original material)

34-39 Sample Size (mm) x x length wTdth thickness

40-42 Shift Check _6 _7 _8

43 Sample Orientat-ion _ 1) parallel to principal load direction

2) perpendicular to principal load direction

3) diagonal to principal load direction

44 Hardness Test Method 1) Brinell 5) Knoop

2) Rockwell B 6) Scratch

3) Rockwell C 7) Other

4) Vickers

45-48 Hardness Number _ 49-54 0.2% Offset Yield Stress (MPa) .

55-60 Ultimate Tensile Strenght (MPa) .

61-63 Per Cent Elongation _ .

64-66 Per Cent Reduction in Area _ _ . _

POLYMERIC COMPONENTS #1, #2

67-71 Blank

72-75 Series No. L_ -

76-78 Shift Check _6 _7 _8

79-80 Card No. 7 D

-10-

552
Discussion

Question (I. Clarke, University of Southern California): 1) With

reference to the DELRIN socket, Delrin has not been reported as used

in the U.S.A. total joints. How did you ascertain that it was indeed

'Delrin' i.e., homopolymer polyacetal and not co-polymer, 'ERTACETAL'?

Where did it originate? Was there any histological correlation with

respect to wear debris?

2) With regard to the zero fracture incidence of Aufranc hips

you received, could this be due to the fact that their mode of failures

was from loosening as opposed to fracture?

Answer : Thank you for your interesting questions. I shall answer

them in the order in which you asked them.

1) "Delrin" is the trade name used by DuPont for their form of

polyformaldehyde resin. Polymerized formaldehyde is sometimes referred

to as a polyacetal because of the repeating oxymethylene units (-0CH2 _

) in the polymer structure.

Polyformaldehyde is an inherently unstable polymer and on heating,

decomposes to the monomer. Polyacetal s are stabilized by capping the

hydroxyl end groups of the polymer chains or by introducing co-polymers

which act as blocks for they polymer chains.

Even stabilized polyacetal s will give off some formaldehyde when

heated. This test was used to confirm that the actabular component

collected was indeed a polyacetal. We took the component to be

"Delrin" because there had been reports in the literature that this

particular polymer had been used in Europe to manufacture acetabular

components.

Unfortunately, our laboratory does not have the ability to

perform infrared spectrum analysis on polymers so we have no way of

determining whether the component is simply a polyformaldehyde resin

or whether the polyacetal had been compounded with a co-polymer.

The word "Protosul" was etched onto the stem of the femoral

component. The prosthesis was probably manufactured by Protek of

Berne, Switzerland.

There was no histologic section made of tissue adjacent to the

total hip implantation site and accordingly no attempts were made to

look for wear debris embedded in the periarticular soft tissue.

The acetabular component had been in place and functioning for

almost seven years. The articulating surface was smooth and shiny

with no evidence of cement wear particles. There was no surface

pitting, at least to visual inspection with a stereomicroscope.
The femoral component had worn into the polymer cup a distance

of about 2 mm. It was difficult to tell if the loss of material was

due to cold flow or wear but we took wear to be the primary surface

phenomenon as the cup showed little evidence of having deformed in

any way.

2) From our analysis, to date, there did not appear to be any

difference in the failure mechanics between Auf ranc-Turner hips and

other hip stems. Essentially, all the stems seemed to debond at the

cement-metal interface first and then go on to subside or drift into varus or severely loosen or fracture.

The Auf ranc-Turner hips did not fracture. We have not determined

the unique design feature of Auf ranc-Turner hips that resists stem

fracture.

Question (Vimal Desai , Johns Hopkins University): Did you look at

the amount of bone resorption and could you form a correlation between

the incidence of loosening and the incidence of bone resorption from

your study?

Answer : First, let me restate our definition of loosening. For the

purpose of this study, a prosthesis component was taken to be loose

if it could be physically moved with mild to moderate hand pressure

at the time of revision surgery. Often, such looseness could be both

felt and seen with blood being expressed from between the bone-cement

or cement-prosthesis interfaces.

Secondly, I am going to take your reference to bone resorption

to mean radiographic evidence, specifically the development of a radiolucent line demarcating bone and radio-opaque PMMA cement.

Finally, for the purposes of illustration, I shall confine my

remarks to the femoral hip stem only.

Using the radiographs taken just prior to TJR revision, we measured the maximum thickness of the lucent line around the prosthesis

components. After correcting for any magnification of the radiograph

figures, the results were recorded as "no line", "thin line" (less

than 3 mm) or "thick line" (greater than 3 mm).

A cross tabulation between clinical loosening and the presence

of a radiographic lucent line is attached in figure A. There is no apparent correlation between loosening and a lucent line.

In a recent article (J.B.J. S. 60-A: 306-313, 1978) Beckenbaugh

and Ilstrup reviewed a number of their cases at the Mayo Clinic and

attempted to characterize radiographic loosening of the femoral

component using such variables as subsidence or varus drift (after

Charnley). Attached is a cross-tabulation table, figure B, between

554
clinical loosening (our definition) and radiographic loosening (Mayo

definition).

In this case, a very good correlation is obtained between clinical

and radiographic loosening. What is surprising is that in some

cases, femoral stems which had obviously shifted in position radiographically, were firmly fixed and difficult to remove at revision

surgery.
Figure A

Crosstabulation Between Clinical Loosening and

Radiological Lucent Line for Total Hip Femoral

Stems

RADIOLUCENT LINE

03

E= OJ i—

<

co Z o

UJ o

gooo

_j

gj

4-> CO

C_3 O o

•—

i

c o

2=

t—

t

_i

<_>

no thin thick

1 ine line 1 ine

10 14 10 34

3 7 9 19

13 21 19 53

* 2

, = 2.08

P

= 0.37

556
Figure B

Crosstabulation between Clinical Loosening and

Radiographical Loosening of Total Hip Femoral

Stems

CLINICAL LOOSENING

Idose

not

loose

loose 28 6 34

not loose 4 13 17

32 19 51

X

2

= 16.78

p is very small

557
t
THE METHOD OF IMPLANT RETRIEVAL ANALYSIS

AT THE HOSPITAL FOR SPECIAL SURGERY

Timothy M. Wright, Ph.D.

Albert H. Burstein, Ph.D.

Department of Biomechanics

The Hospital for Special Surgery

535 East 70 Street

New York, NY 10021

An implant retrieval analysis program was established

at The Hospital for Special Surgery in December, 1977, and

since then over 1300 implants have been gathered and examined. The primary objective of the program is to identify

problem areas in design and materials of implants with em- phasis on total joint prostheses. All implants removed in

the operating rooms at the Hospital and, in a few instances,

at other institutions in the U.S.A. are included in the program. In addition, protocols have been established to re- trieve whole joints (containing total joint implants) which

have been removed en-bloc at autopsy or amputation. Examination of retrieved implants includes visual and light

microscopy inspection, a review of the patient's radiographs

and medical records, scanning electron microscopy of fracture

and articulating surfaces, and metallurgical analysis where

appropriate. Additional procedures, including examination

of properties of bone and structure, are performed on the

joints removed en-bloc. The biomechanical data obtained

from the implant retrieval analyses are included in a data

file of radiographic and medical history information for use

in statistical analysis.

1. Introduction

Many orthopaedic surgical procedures include implantation of

prosthetic devices. Often times these implants are removed routinely,

such as in the case of many fracture fixation devices. Other prostheses, such as total joint replacements, are regarded as permanent

and are removed only when a complication arises, such as infection

and loosening or fracture of the prosthetic components. Regardless

of the reason for removal, examination of these removed devices can provide information concerning their performance on both the material

and structural levels.

An implant retrieval system has been operational in the Department of Biomechanics at the Hospital for Special Surgery since December, 1977. Over 1300 implants have been gathered. A significant

559
portion (more than 250) are total joint replacements obtained from

revision or removal surgery. The emphasis of the retrieval program

has been to analyze the components from these joint replacements,

though all other fractured or severely damaged implants have also

been examined. The objective of the analysis is to identify damage

mechanisms and correlate them with design features and material

properties.

2. Materials

All implants removed in the operating rooms at the Hospital for

Special Surgery and, in a few instances, implants removed at other

institutions in the U.S.A. are collected. Implants are currently

collected at the rate of approximately 400 per year with about 100 of

the 400 implants being total joint prostheses (table 1) . At present,

Table 1. Revision and removal procedures at the

Hospital for Special Surgery

Total Hip Replacements

1977

1978

1979

Revisions

26

25

41

Component

Removals

6

11

15

Total

32

36

56

Total Knee Replacements

1977 28

1978 29

1979 41

30

31

43

approximately 110 total knee joint prostheses and 120 total hip

joint prostheses have been collected. There are also approximately

25 other total joints including total shoulder, wrist, finger, elbow

and ankle implants.

In addition to the implants that are removed at surgery, there

is also a growing collection of whole joints (containing total joint

implants) which have been removed en-bloc at autopsy or at amputation,

This represents a new program at the Hospital for Special Surgery

having commenced in June, 1978. Four such specimens have been re- trieved to the present time: a hip and two knee joints obtained from

autopsies; and a knee joint obtained from an above-knee amputation

necessitated by vascular disease in the foot.

3.1

3. Methods and Procedures

Procedures for obtaining removed implants

Implants that are removed at surgery are first forwarded to the

Pathology Department where they are logged in the Pathology records.

They are then sent directly to the Biomechanics Department where they are catalogued (including patient name and record number) and placed

5G0
individually in boxes to await inspection and/or storage. The removal,

transportation and cataloging procedures are performed according to

instructions from Biomechanics personnel to minimize any mishandling

of the implants. Such mishandling could obliterate evidence of in

vivo damage on the components or create artifactual damage which

might be falsely interpreted as having occurred in vivo .

The procedure for acquiring joints removed en-bloc is somewhat

different. Because of the large population of patients with rheumatic

diseases at the Hospital for Special Surgery and because of the

affiliation between the Hospital for Special Surgery and the New

York Hospital, critically ill patients who have total joint replacements are identified by the medical staff of the Hospital for Special

Surgery and autopsy permission is obtained. For amputation of limbs

with total joint replacements, patient consent is obtained by the

patient's surgeon at the Hospital for Special Surgery. Joints removed

at autopsy or amputation are again catalogued in the Pathology Department records and a tissue specimen is obtained from the synovium of

the joint at that time. This is done with a small, longitudinal straight

line incision in a region chosen so as not to measurably alter the

joint kinematics. The remainder of the examination of the joint is

performed in the Biomechanics Department, as described below.

3.2 Patient records and radiographs

For all removed implants, a complete set of patient medical

records and radiographs are available. In most instances, a complete

history of the joint implant can be obtained from the medical records.

Missing information is obtained directly from the patient and/or the

physician. Included in the records for each removed total joint is a summary review of the patient's status by the physician containing

information pertinent to the condition of the patient before and

after surgery and the surgeon's impression of the condition of the

joint at surgery. Serial radiographs of the patient's joint are reviewed with the surgeon and a more detailed diagnosis for removing

the implant is obtained. Whenever possible, a member of the Biomechanics Department is present in the operating room at the time of

implant removal. Direct observations of the implant's condition are noted at this time, especially in cases where the implant has obviously

undergone mechanical failure. These observations are then added to

the patient's record file, a schematic of which is shown in figure 1.

3.3 Methods for examining retrieved implants

All removed implants are visually examined for evidence of

mechanical damage and gross deformation and, in the case of the

polyethylene components, discoloration due to absorption of body

fluids. A detailed examination of the entire surface of each component is then performed using a stereo-optical light microscope at a magnification of ten times. Both the visual and light microscopy

inspections are performed by two individuals (the light microscope

has dual binocular tubes for viewing by two people simultaneously)

5G I
DEMOGRAPHICS

e.g., Patient Name, Birthdate

P RE-OPERATIVE DATA

e.g., Primary Diagnosis

I

?AT

iar

1

[IV

sis

i

> OPERATIVE DATA

e.g., Prosthesis Type, Surgeon

COMPLICATIONS

e.g., Fracture, Infection

FOLLOW-UP DATA

e.g., Joint Evaluation Score

A

REVISION SURGERY

e.g., Diagnosis, Revision

Prosthesis Type

GAIT ANALYSIS DATA

e.g., Stance Times

RADIOGRAPHIC DATA

e.g., Alignment, Lucent Lines - RETRIEVAL DATA

e.g., Grading Score

Figure 1. Schematic diagram of a patient's

medical record file.

During light microscopy examination, each component is subjectively

graded on the amount of mechanical damage present. Polyethylene

components (e.g., acetabular cups from total hip replacements and

tibial and patellar components from total knee replacements) are graded for embedded polymethylmethacrylate (PMMA) cement debris,

pitting, wear tracks, burnishing, surface cracks and surface deformation. Metal components (e.g., femoral stems from total hip replacements and femoral components from total knee replacements) are graded

for wear scratches, corrosion and fracture. Grading is done on both

the severity of the damage and its distribution over the surface of

the component.

Scanning electron microscopy is used to perform fractography on those components which have broken and to identify the characteristic

features of the various wear processes. With fractography, an attempt

is made to determine the fracture mechanism (e.g., fatigue), the

crack initiation point and any pertinent features (e.g., porosity in

cast metallic components) which contributed to the fracture.

562
3.4 Methods for examining joints removed en-bloc

The protocol for examining whjle joints was developed using a hip joint recovered at autopsy [l] . The protocol includes range of

motion measurements, mechanical testing of the bone tissue, and

whole joint structures , estimation of debris in the surrounding

synovium and standard retrieval analysis of the prosthetic components.

Care is taken to obtain whole joints directly from the operating

room for amputation specimens and at autopsy for cadaver joints.

Within one to two hours, the fresh joint is taken through a series of

range of motion movements. Radiographs are taken of the joint in a neutral position and at the extremes of motion. The joint is then

taken to the Pathology Department for cataloging and for the removal

of a small synovial tissue specimen as previously described. Then

the joint is returned to the Biomechanics Department where it is

frozen and stored for the testing program.

The program begins with a dissection of the joint capsule. The

dissection is recorded photographically and general features (such

as the appearance of the soft tissues around the capsule) are noted.

Samples of the synovium are examined histologically for a qualitative

analysis of the type of debris present. This analysis is based on

the size, shape and refractile quality (under polarized light) of the

debris particles [2]

After dissection of the joint capsule, several other procedures

are performed. The cortical bone from the metaphyseal region of the

bones obtained with the joint is machined into standardized specimens

and tested in uniaxial tension (or compression) following established

methods [3,4]. These results can be compared to existing mechanical

data for human bone of the same age taken from individuals without

joint replacements [5]

The components themselves are mechanically tested while still

in-situ. These tests provide knowledge of the in-vivo fixation

strength of normal (i.e., not loosened or infected) total joint re- placements. Such tests are generally carried out only until the

initial failure of the bone-cement-prosthesis system is observed,

so as not to disturb the underlying trabecular bone morphology.

Initial failure is determined using acoustic emission, a non- destructive testing technique which records stress waves released

from damage mechanisms within a material undergoing deformation.

Acoustic emission has been shown to be a much more sensitive technique than, for example, attempting to measure changes in the load

versus deformation behavior, when recording the intitiation of damage in a loaded structure. Experiments using acoustic emission on biological tissues have shown it to be a useful technique for

Figures in brackets indicate the literature references at the end

of this paper.

5G3
investigating damage mechanisms in these materials [6,7]. One

example of in-situ component testing is eccentric compressive loading of the medial plateau of total condylar tibial total knee

components. Several patients with failures of total condylar knee

replacements associated with cold flow of the tibial component have

had revision surgery at the Hospital for Special Surgery. The wear

patterns on the removed components revealed the eccentric loading.

By in-situ mechanical testing of total condylar components which

did not undergo mechanical failure (such as the one knee replacement

recently obtained at autopsy) and correlation with finite element

predictions [8] , an understanding of the cause of the problem and

possible design alterations to eliminate this type of failure can be found.

After testing, the components are removed and examined following

the same procedures outlined above including visual and light microscopy inspection, subjective grading of articulating surfaces and

scanning electron microscopy of wear surfaces. In some specimens the

components are left in-situ and the entire specimen embedded in an epoxy resin and cross-sectioned. This procedure allows examination

of the bone-cement and cement-prosthesis interfaces and stereological

examination of the trabecular bone surrounding the implants for com- parison with trabecular morphology in normal joints without prostheses.

4. Typical Results

Implant retrieval programs, such as the one described here, generate large amounts of information. Results are always changing as more devices are collected and added to ongoing studies. In this

section, some typical findings from the retrieval program at the

Hospital for Special Surgery are presented.

4.1 Fractured femoral components

Fracture of the femoral component in total hip replacement is one of the most noted forms of device failure [9-13] . At the

present time, twenty-six fractured stems have been collected, twenty

from the Hospital for Special Surgery and six from other cooperating

institutions. The majority of the stems are of the Charnley design

(10 out of 26) with the remainder being either Mueller (6 out of 26)

,

T28 (5 out of 26) , or Bechtol (5 out of 26) designs. Fourteen of the

fractured stems (8 of the Charnley type and all of the Mueller type) are cobalt alloy and the remaining twelve are stainless steel.

The mechanism of fracture was fatigue in twenty- five of the

stems. One stem, a cobalt alloy Charnley design, fractured catastrophically when the patient sustained a fall from a ladder.

Examination of the fracture surface revealed no apparent previous

fatigue damage.

In several cases, material defects and stress concentrations

were found as the cause of fatigue crack initiation. The most prevalent

5G4
material defect was interdendritic porosity in stems cast from cobalt

alloy. At least four of the fourteen cast cobalt alloy stems showed

significant porosity in the region of crack initiation (fig. 2)

Figure 2. Scanning

electron photomicrograph

of the fracture surface

of a Charnley stem cast

from cobalt alloy showing

dendritic structure at the

crack initiation site. A

100 micron reference bar

is included at the bottom.

Time implanted was 74 months.

Two forms of stress concentration also lead to crack initiation.

A stainless steel Charnley fractured in fatigue which initiated at a nick on the anterolateral corner of the stem cross-section. It was

not possible to determine if the nick had been caused by a drill bit

during reattachment of the greater trochanter or by subsequent migration and rubbing of the reattachment wire against the stem, though

clearly one or both were responsible. Another form of stress concentration occurred in four of the five fractured T28 stems. All four

stems fractured in fatigue and all had multiple cracks (always more

than three) in addition to the crack causing failure (fig. 3) . hese cracks often initiated on the medial side of the stem. Their

resence can be attributed to the trapezoidal cross-sectional shape,

Vhich causes higher stresses on the medial side than on the lateral

side. When the stem is overstressed, the medial side yields first in

compression, causing areas of residual strain which with continued

cyclic loading can become tensile and act as a stress concentration.

Ml four of the femoral components were the small stem size and all

four were implanted in relatively active male patients weighing over

31.0 kilograms, so the potential for high stresses was present.

5G5
Figure 3. Multiple cracks emanating from the medial side of a fractured small stem T28 prosthesis made from stainless steel.

Time implanted was 52 months.

4.2 Permanent deformation and fracture

of polyethylene components

Reports of removed ultra-high molecular weight polyethylene com- ponents from total joint replacements have concentrated on the mechanisms of wear occurring on the articulating surface [14-16]

.

Another equally disturbing problem with many of these components is

structural failure caused by gross or excessive permanent deformation

and fracture. In the retrieval program at the Hospital for Special

Surgery these failures have been noted in acetabular cups from total

hip replacements, in tibial and patellar components from total knee

replacements, and in the polyethylene inserts used in triaxial-type

joint replacements in the upper limb.

As with the metallic femoral stems the fracture mechanism in the

polyethylene components was primarily fatigue. Once again the initiation of the fatigue process often occurred at a stress concentration.

For example, fracture in acetabular cups originated at the base of

the circumferential grooves machined in the components to provide

good fixation to cement [17] . The lack of adequate structural support

from surrounding cement and cancellous bone was often associated with

the fracture. For example, poor cancellous bone under the medial

side of a Freeman-Swanson tibial component combined with the fact

that the extreme medial and lateral edges of the component were supported on the cortical shell of the tibia lead to the fracture

shown below in figure 4.

5E6
Figure 4. Freeman-Swanson type polyethylene tibial component showing

partial fracture (arrow) . Time implanted was 60 months.

Excessive permanent deformation leading to structural failure

was also associated with poor cement and cancellous bone support in

many instances. A stress fracture in the trabecular bone under the

medial tibial plateau, for example, allowed gross deformation of a total condylar II tibial component (fig. 5) even though the peg

remained well-fixed.

Figure 5. Total condylar II polyethylene tibial component

with excessive deformation of the plateau relative to the peg.

Time implanted was 25 months.

5G7
5. Discussion

An objective of most implant retrieval programs is to identify

problem areas in prostheses and, therefore, indirectly suggest solutions. One area where this objective has been clearly met is in the

mechanical performance of femoral components in total hip replacement.

Material defects in fractured stems have been found by a number of

investigators [10,11,18,19]. In an attempt to diminish the incidence

of these defects, manufacturers have responded by introducing improved

manufacturing techniques such as forging [20] and hot isostatic

pressing [21] . These processes decrease the number of defects like

interdendritic porosity and significantly improve the mechanical load

carrying capability of the stems [22] . In the particular case of the

retrieval program at the Hospital for Special Surgery, the high incidence of porosity in cast stems, along with results of static testing

of cast stems [23] , lead to a change in the total hip replacement

systems used at the hospital.

The poor mechanical performance of polyethylene is a more recent

discovery and has yet to be examined in any detail. Few reports of

fractured polyethylene components have appeared in the literature

[17,24] and permanent deformation is usually discussed as a combined

mechanism with wear. Some solutions are available in the form of

metal backing (such as the trays under plastic tibial components) and

composite reinforcement with carbon fibers. Much less is known,

however, about the stress fields in and around polyethylene joint

replacement components when compared to the femoral stem, which has

received considerable attention. As more stress analysis information

becomes available to aid in interpreting the damage found on retrieved

polyethylene components, more improvements, including changes in

design and material, will hopefully result. This process has already

begun for patellar [25] and tibial [8] components.

6. Conclusions

The retrieval program at the Hospital for Special Surgery has

met its primary objective in that problem areas in design and materials

for total joint prostheses have been identified. Two areas discussed

here, namely, material defects in cast femoral stems and gross deformation in polyethylene components, were important considerations in the

decision to change the commercial joint replacement systems stocked

in the operating room and in the alteration of design criteria for

custom and newly developed prostheses.

1

1 ' -

" '

1 This research was supported by the Clark Foundation.

568
References

[1] Wright, T.M. , Hughes, P.W., Torzilli, P. A., and Wilson, P.D., Jr.,

A method for the postmortem evaluation of an in-situ total hip

replacement, J. Bone Joint Surg. 61A , 661-668 (1979)

[2] Charosky, C.B., Bullough, P.G., and Wilson, P.D., Jr., Total hip

replacement failures. A histological evaluation, J. Bone Joint

Surg. 55A , 49-58 (1973)

[3] Reilly, D.T., Burstein, A.H., and Frankel , V., The elastic modulus

for bone, J. Biomech. 7_, 271-275 (1974) .

[4] Reilly, D.T. and Burstein, A.H., The elastic and ultimate properties

of compact bone tissue, J. Biomech. 8_, 393-405 (1975) .

[5] Burstein, A.H., Reilly, D.T., and Martens, M. , Aging of bone tissue:

mechanical properties, J. Bone Joint Surg. 58A , 82-86 (1976)

[6] Wright, T.M., Arnoczky, S.P., and Burstein, A.H., In-situ monitoring

of ligament damage in the canine knee by acoustic emission, Matls.

Evaluation 37, [13], 47-50 (1979).

[7] Wright, T.M. , Vosburgh, F., and Burstein, A.H. , Permanent deformation of compact bone monitored by acoustic emission, Trans. 26th

Ortho. Res. Soc. 5_, 57 (1980).

[8] Bartel, D.L., Santavicca, E.A., and Burstein, A.H., The effects of

pegs and trays on stresses associated with loosening of knee

prostheses, Trans. 26th Ortho. Res. Soc. 5_, 165 (1980) .

[9] Bechtol, CO., Failure of femoral implant components in total hip

replacement operations, Ortho. Rev. 4_, 23-29 (1975) .

[10] Charnley, J. , Fracture of femoral prostheses in total hip replacement - a clinical study, Clin. Ortho. Ill , 105-120 (1975)

[11] Collis, D.K., Femoral stem failure in total hip replacement, J. Bone Joint Surg. 59A, 1033-1041 (1977).

[12] Ducheyne, P., de Meester, P., Aernoudt, E., Martens, M. , and Mulier,

J.C. , Fatigue fractures of the femoral component of Charnley and

Charnley-Mueller type total hip prostheses, J. Biomed. Matls. Res.

Sym. 6, 199-219 (1975)

[13] Galante, J.O. , Rostoker, W. , and Doyle, J.M., Failed femoral stems

in total hip prostheses, J. Bone Joint Surg. 57A , 230-236 (1975).

[14] Dowling, J.M. , Atkinson, J.R. , Dowson, D. , and Charnley, J., The

characteristics of acetabular cups worn in the human body, J. Bone

Joint Surg. 60B , 375-382 (1978).

5G9
[15] Rostoker, W., Chao, E.Y.S., and Galante, J.O. , The appearances of wear on polyethylene - a comparison of in-vivo and in-vitro wear

surfaces, J. Biomed. Matls. Res. 12_, 317-335 (1978) .

[16] Rose, R.M., Crugnola, A., Ries, M. , Cimino, W.R., Paul, I., and

Radin, E.L., On the origins of high in-vivo wear rates in polyethylene components of total joint prostheses, Clin. Ortho. 145 , 277-286 (1979)

.

[17] Salvati, E.A., Wright, T.M., Burstein, A.H., and Jacobs, B.,

Fracture of polyethylene acetabular cups. Report of two cases,

J. Bone Joint Surg. 61A , 1239-1242 (1979)

.

[18] Martens, M. , Aernoudt, E., de Meester, P., Ducheyne, P., Mulier,

J.C., de Langh, R. and Kestelijn, P., Factors in the mechanical

failure of the femoral component in total hip porsthesis, Acta

Ortho. Scand. 45_, 693-710 (1974) .

[19] Rostoker, W., Chao, E.Y.S., and Galante, J.O., Defects in failed

stems of hip prostheses, J. Biomed. Matls. Res. 12_, 635-651 (1978).

[20] Kesh, A.F. and Kummer, F.J., New manufacturing and processing techniques for the fabrication of cobalt-chromium surgical implants,

Trans. 24th Ortho. Res. Soc. 3_, 311 (1978).

[21] Luckey, H.A. and Barnard, L.J., Improved properties of Co-Cr-Mo

alloy by hot isostatic pressing of powder, Trans. 24th Ortho. Res.

Soc. 3_, 296 (1978) .

[22] Burstein, A.H. and Wright, T.M., Mechanical performance of three new materials in total hip stems, Trans. 25th Ortho. Res. Soc. 4_, 41 (1979)

.

[23] Reuben, J.D., Eismont, F.J., Burstein, A.H., and Wright, T.M.

,

Comparative mechanical properties of forty-five total hip stems,

Clin. Ortho. 141, 55-65 (1979).

[24] Weightman, B., Isherwood, D.P., and Swanson, S.A.V., The fracture

of ultrahigh molecular weight polyethylene in the human body, J. Biomed. Matls. Res. 13_, 669-672 (1979) .

[25] Hayes, W.C. and Levine, B.M., Finite element anlaysis of patellar

resurfacing procedures, Trans. 26th Ortho. Res. Soc. 5_, 163 (1980).

570
Discussion

Question (Anthony K. Hedley, U.C.L.A.): The authors suggest that the

disappearance or resorption of bone from under tibial components with

central pegs is due to overloading of the cancellous bone leading to

"bone failure". I would like to know what histological evidence he

has for this supposition. Were healing microfractures seen in the

supporting bone? Was the population present predominantly osteoblastic

or osteoclastic?

The phenomenon of "stress relief" has been demonstrated in many

situations where stress concentrating devices have been employed,

such as fixation pegs, and I would like to ask why he does not accept

that the changes he has seen are not due to resorption due to stress

relief of the bone under the plateaus rather than overloading which

in the i_n vivo situation is characterized by progressive hypertrophy,

sclerosis and the presence of microfractures.

Answer : Dr. Hedley has raised a good point. At this time, we have

no histological evidence of microfractures in the region of the

tibial plateaus in those cases demonstrating gross deformation of the

polyethylene plateau while the central peg remained well-fixed. We

based our understanding of the problem on the following facts: 1) in

general, these cases involved very heavy and relatively active (i.e.,

ambulating freely) patients; 2) often, the plateau which eventually

crushed was loaded to a much greater degree as shown by radiographs

which demonstrated the eccentric loading; and 3) while histological

evidence of microfractures was not sought, radiographic evidence of a stress fracture in the plateau prior to failure was present in one of

the cases.

Question (D. F. Williams, University of Liverpool, U.K.): Could you

comment on whether chemical degradation has any role on the wear of

the high density, ultra-high molecular weight polyethylene?

Answer : There is little doubt that the gross appearance (color and

texture) of UHMW polyethylene changes during implantation for long

periods of time as seen in our, as well as other researchers, collection

of retrieved implants. This would lead one to suspect some form of

chemical change, though we have not investigated what effect such

changes would have on damage mechanisms in the polyethylene.

Question (Roy Hori , Northwestern University): Regarding your comments

on polyethylene wear, how do you account for the many hip cups and

knee components which were in use by active patients for a long time

with very little wear. We have many such cases in our study and I suppose you might also, cases where the cause of removal did not

involve loosening, e.g., sepsis.

Also in this regard, your study shows many ICLH prostheses with

severe surface pitting. I believe the ICLH has one of the largest

57 I
contact areas of the currently available TKA's. If the ICLH has such

high contact stress, do any of the other prostheses have any hope.

By the way, we have several Marmors with little wear after several

years of use.

Answer : We also have polyethylene components that show little wear

or mechanical degradation, though we have not found these to be

associated with one removal diagnosis versus another (e.g., sepsis versus loosening). Rather we have found the amount of wear to be

related to patient weight and implantation time. For example, we

have graded thirty-eight tibial components from retrieved total

condylar knee replacements using the subjective grading system

explained in our paper. We correlated the total damage grade with

patient weight and the length of time the prosthesis was implanted

and found significant (P<.01) positive correlations for both variables.

The heavier the patient or the longer the patient used the prosthesis,

the more damaged we found it to be upon removal. Of course, there

are exceptions, in which little damage occurs even for heavy individuals

and/or long implantation times. We have found, however, that in most

of these cases, the patients were relatively inactive. Activity

level, being a difficult parameter to obtain and quantify, was not

included in our analysis.

The ICHL prostheses referred to in our paper and presentation

were all implanted for long periods of time (at least five years),

and this is one of the reasons they demonstrated such considerable

damage. It is correct to consider the ICLH as having a large contact

area at least in full extension. We have measured the contact areas

and contact pressures of a number of contemporary knee designs and

found the contact area of the ICLH to be one of the largest, though

the area decreases sharply as the joint goes into flexion. The

contact stresses, even for the ICLH, exceeded the compressive yield

stress of UHMW polyethylene when the prosthesis was loaded to physiological loads at 0, 30, 60, and 90° of flexion. This does, in

fact, present a bleak picture for polyethylene in long term implantation as an articulating surface.

572
An Interactive Computer System for

Implant Data Retrieval/Analysis

S.D. Cook and A.M. Weinstein

Biomaterials Laboratory

Tulane University

New Orleans, LA 70118

An interactive computer system for the storage,

retrieval and analysis of clinical and material characterization data associated with orthopaedic implants

is described. The system consists basically of four

independent modules. The essence of the system centers on the cross-referencing capabilities which are unlimited. The system has been designed for use by

non-computer trained personnel.

1. Introduction

The evaluation of retrieved orthopaedic implant devices can

provide information about implant performance and potential health

care benefits not available by any other method (1,2) . The evaluation of clinical procedures and material characteristics can also provide criteria for establishing minimum performance levels for an implant device. To date, implant retrieval studies have been performed

by many investigators using widely different experimental protocols

(1-5). Attempts to compare the results of these investigations are frequently difficult if not impossible.

A protocol for the retrieval and analysis of metallic orthopaedic

implants used in humans has been developed by the American Society for

Testing and Materials (ASTM) (5) . The clinical data to be recorded

and the material characterizations to be performed when an implant is

retrieved are given in this protocol. The ASTM F 561 standard recommended forms for the recording of data with regard to. the clinical ex- perience and material examinations. The clinical data required includes

a case history, roentgenogram review, tissue culture, and a histological

evaluation of tissue adjacent to the implant. The material characteristics to be determined, utilizing standard ASTM testing practices,

where applicable, includes chemical composition, macroscopic and microscopic examination and mechanical property determinations.

^Figures in parentheses indicate the literature references at the end

of this paper.

573
Once standard methods for examining and recording data on retrieved

implants are followed, the results of independent investigators can be

easily correlated in order to relate clinical performance with material

characteristics. This information should lead to better implant performance through its use in updating material and device standards. The

problem with such a system is the voluminous data bank involved and the

need for easy access, sorting and cross-referencing of the data to provide meaningful results. Thus, this system is ideally suited for implementation on an interactive digital computer system. Once the data is

adapted for computer manipulation, for example, actuarial statistical

analysis can be performed to predict survival rates. Thus, the use of

such a system as an early warning vehicle to improve health care should

not be overlooked.

2. System description

The implant retrieval and analysis computer system described in

this paper contains four independent program modules which were written

in either the FORTRAN or COBOL computer languages. The system is cur- rently being used in an interactive mode on a Digital Electronics

Company (DEC) system 2060 digital computer. In this configuration all

data is entered to the implant retrieval and analysis system from a keyboard and all input and output is displayed on a cathode ray tube (CRT) screen. A hard copy output on a line printer is also possible. All

programs in the system are completely documented for an experience programmer or nonprogrammer user. Although the system is currently used

in an interactive mode, it was also designed for use in a batch environment where all data input and cross referencing information is entered

from data cards. The format for these cards and the use of the system

in the batch environment is contained in the user documentation.

The implant retrieval and analysis system was written in standard

computer languages and contains no computer installation dependent

subsystems. It is, therefore, completely portable to other computer

installations regardless of manufacturer or type of computer system used,

as long as a FORTRAN and COBOL compiler are available. Since large

quantities of retrieval data (greater than 1000 cases) may eventually

be stored, all input data is placed onto magnetic tape for storage. It

should be noted that most computer installations charge for permanently

occupied disk storage space. However, if only smaller quantities of

data are anticipated or in the period when massive amounts have not yet

been accumulated, the user has the option to store data records on disk.

Disk storage has the advantage of easier accessibility and faster re- sponse but is not economically practical for large quantities of data.

As noted above, the implant retrieval and analysis system contains

four separate independent modules; one for initial clinical and material data entry, a cross referencing module to allow manipulation and

statistical treatment of all data, a printing module to provide hard

copy of any or all data, and an editing and updating module to allow

entry of follow-up or missing data to a case that was previously entered.

The use of these modules and their specific features will be described

in the following sections.

57<l
3. Data input module

"ADDREC" is the implant retrieval and analysis module for the input of clinical history and material characterization data associated

with each implant device. The input data required corresponds closely

to that contained on ASTM F 561 standard forms (figures 1 and 2) for

the retrieval and analysis of metallic orthopaedic implants. These

forms are, however, to a certain degree applicable for both metallic

and nonmetallic devices. Based upon these forms, a new set of forms were developed by the authors incorporating the recommended information, however, extending beyond this and revised to be more suitable

for computer entry and analysis. The form was also made less ambiguous,

providing for easier multicenter interaction. These forms are shown

in figures 3 and 4. It should be noted that very specific data re- sponses are requested in a manner which can be easily entered and stored

in coded form on the computer.

The input module "ADDREC" was written entirely in the FORTRAN

computer language and was designed for use by individuals with little

or no computer experience. Continuous data checks are provided in

the program to prevent erroneous data input and help files containing

directional information are accessible during execution, if needed, to explain in detail the type of response expected. These features are illustrated in example 1. In the example, the program prompt asks

the user to enter the diagnosis at insertion. Unsure of how to respond, the user enters a "?" and the program responds with additional

descriptive information, as shown in example 1. The user then enters

the letter "U" mistakenly. This is an incorrect entry since the possible range of responses is only the letters A through S. The program responds with the message "Invalid Data Entry" and repeats the

question. The user then enters the letter "0", which is a valid entry and the program advances to the next question. Since an implant

device may contain multiple components and a material characterization

study may be conducted for each component, the "ADDREC" module is

capable of accepting multiple material characterization forms for each

clinical history form. An example of the use of "ADDREC" module for

the entry of data for a two component total hip replacement is shown

in example 2.

It should be observed in example 2 that question number 15 was

not asked. Question 15, the bone the device was inserted or attached

to, is only asked if the device is not a joint replacement. If the

device is a joint replacement, this information plus the implant type,

question 9, is sufficient for the computer system to know where the

implant was placed.

It should also be observed in example 2 that each computer prompt

was answered with a "?" to obtain further explanation of the expected

response. Obviously, this would usually be unnessary since the retrieval data forms were designed based upon the computer system^ however, the option is available if needed, for example if data for a case

is being entered prospectively directly from a dictated operative report. Thus, data entry to the system is a simplified task easily

575
undertaken by a secretary or technician once the retrieval data forms

have been completed.

Among the other useful features in the "ADDREC" module is the

ability to review a clinical or material examination form before proceeding to the next form or case as demonstrated in example 3. Upon

completion of each clinical or material form the computer prompt asks

if you would like to review the data entered. A "yes" response presents a shorthand version of the data entered. A user may then choose

to return to a particular question if a wrong entry has been made as illustrated in example 3. In the example, upon completion of a clinical form, the user requests a review of the data entered and notices

an incorrect entry for functional level attained following surgery.

The user returns to that question and enters the correct response. The user then requests another review of the data entered and being satisfied with the entry proceeds to the materials form. It should be observed that the use of the "?" response yielded additional user information.

If no data is available for a particular question at the time of

data entry, the user may respond with simply a carriage return. The

program then warns the user that no data was entered for the question

and proceeds to the next question. The user can correct the entry if

the carriage return was mistakenly used as described in the preceeding

paragraph or can at a later date return to the case and enter the missing information with the "UPDATE" module described in a subsequent

section.

4. Cross referencing module

"SELECT" is the implant retrieval and analysis module used for cross referencing the data entered into the module "ADDREC." "SELECT"

was also written entirely in FORTRAN and is completely documented for

the user. The "SELECT" module was designed for use by individuals with

no computer experience and contains many computer prompts with additional help information available both before and during execution.

Consistent with the "ADDREC" module a "?" response to any computer

prompt will yield additional information concerning the range of user

responses. A user may cross reference as few or as many variables at one time as he chooses. There are a total of 54 possible variables to cross reference. These span from single criteria, such as a hospital

or particular device, to ranges in values of variables such as ranges

of weights of patients or ranges of dates in-situ. To retrieve a particular patient's file, the user may use the patient's case number,

name, or identification number. The case number is an installation

supplied number and may be the only method of retrieving a specific

file if the patient's name is not entered on the computer files and no identification number (Social Security Number or hospital number) was known for the case.

The use of the "SELECT" module is illustrated in example 4, which

is a cross reference in which it was desired to obtain all cases on

file for which the patients were 20-50 years old, weighing 150 to 200

576
lbs, who had hip replacements utilizing stainless steel for the stem com

ponent which had failed due to fatigue. In this session, the user first

obtains a se: of instructions and obtains a list of possible cross referencing variables by responding with a "?" to the computer prompt

asking for which variables he would like to cross reference. The user

enters the number associated with each variable that is to be cross

referenced. The computer then prompts for the specific information for

each of the variables that were chosen. Upon completion of the cross referencing information, the program searches its data banks for cases which satisfy the criteria chosen and responds with the number of cases searched (which are the total number of cases in the data bank) and the

number of cases found satisfying the cross referencing criteria. The

cases satisfying the cross referencing criteria are automatically written onto a new data file which can then be displayed on the CRT screen,

printed on a line printer, or used for further statistical manipulation.

These portions of the implant retrieval and analysis system are handled

in the module "PRINT"

As noted above, the "SELECT" module can be used to retrieve a particular patient file by entry of patient case number, name or identification number. This feature is particularly useful for the surgeon for

instant and efficient review of patients' files on followup since the

system can be used for prospective studies with data initially entered

at the time of surgery.

5. Print module

"PRINT" is the retrieval and analysis system module used to decode

all data from its computer stored format and to prepare a printout of

the case on a CRT terminal and/or a line printer. The "PRINT" mode was written entirely in the COBOL computer language, is well documented

and exceedingly easy to use. A printout of the sample case entered

with the "ADDREC" program is shown in example 5. Thus, the user has

at his instant disposal any particular case in his data banks and the

ability to generate printouts of all cases satisfying the cross referencing criteria as described in the "SELECT" module description above.

6. Editing and update module

The "UPDATE" module of the implant retrieval and analysis system

was written to provide an efficient mechanism for updating or changing

input data associated with a previously entered case. Since the re- trieval and analysis system can be used for prospective as well as retro

spective studies, clinical data and some data with regard to the implant (example: type, manufacturer) may often be entered before the

device is actually retrieved. Upon retrieval of the implant device,

material characterization forms are completed and this data along with

any additions to the clinical data may be easily entered using the

"UPDATE" module. The "UPDATE" module can also be used to add or change

any information in a previously entered case which may have been incorrect or missing at the time of initial input. The use of the "UPDATE"

module for this type entry is very similar to the method illustrated

in example 3. The first entry to the "UPDATE" module is the patient

577
case number, name or identification number. The "UPDATE module then

retrieves that case and displays the record to the user. Changes are then made in the record by transferring to the item number which needs

data to be added or corrected. The user also has the option of entering a complete materials form for as many components as required. This

latter type of usage is needed if the clinical data was entered prospectively and the device is subsequently retrieved and materials characterization forms completed. "UPDATE" supplies user prompts throughout the process and has additional help files which can be accessed by

a "?" response to any prompt.

7 . Summary

The implant retrieval and analysis computer system described in

this paper provides a powerful tool for the analysis of orthopaedic

implant performance. The system was designed to be extremely portable

to other computer installations and extremely flexible in modular concept. No previous computer experience is required for the operation

of the system and it was designed to simplify the interaction of

multiple investigators interested in implant retrieval. In addition,

memory space has been minimized through the storage of data in coded

form on the computer; however, provisions have been made in the data

storage for the addition of alternate input items at a later date as they are found to be necessary. These additional input items can be

added without any disruption of existing data files and minimal programming changes.

The implant retrieval and analysis study by the Biomaterials

Laboratory at Tulane University is ongoing and we expect to have over

500 cases entered to the system by the end of the year, and well over

1000 cases by the end of 1981. The system is being continuously

updated and refined to provide more powerful features including statistical options and computer graphics as well as possible additions

and modifications to the data entered.

Information regarding the acquisition of the implant retrieval

and analysis system may be obtained from the authors.

8. Acknowledgements

The authors would like to acknowledge the support of the

National Institute of Arthritis, Metabolism, and Digestive Diseases,

National Institutes of Health and the Tulane University Computer

Center.

578
Figure 1. ASTM F561 Case History Review Form

Patient name

Recovery of Implant

Case History Review Case Case

1.3.

5.7.

8.

9. 10a.

10b.

10c. n.

I .19

13.

Date Inserted

Implant Type

Patient Date of Birth

Implant ' ocation

Date Removed

Patient Sex _ Patient Weight

Patient Activity or Occupation

History of foreign body sensitivity

Diagnosis at Insertion Trauma—simple or comminuted; open or closed

Contributory conditions (eg., alcoholism, seni 1 i ty)

Operation at Insertion

Antibiotics at insertion, if YES, answer the following:

a) Reasons for antibiotics

i) «) ~

iii)

'

b) Type

c)

d) Dosage

Duration

Functional level cf the patient attained between insertion and removal

ambulatory, ambulatory with aids, non ambulatory Comment on relevant physical activity or event for this treatment

14. Roetgencgram review (Indicate YES , NO, D0U3T , or NOT APPLICABLE)

15.

bony change in relation to implant

absorption or rarefaction

increased density (sclerosis - compaction)

non-union

bone fragments held apart

migration of implant

malalignment

fracture of bone

penetration of implant across joint space penetration of implant through bone

other

other

Reason(s) for removal (Indicate YES or NO - mark primary reason with

an asterisk)

~b)

~c)

~d)e)

"f) "g)h) 1)

1)

">-) 1)

_a) Routine

_c) Late infection

(> 6 months)

e) pain in the vicinity of implant

_g) prominence of bursae

j) unsatisfactory

position of implant

_k) allergic or hypersensitive reaction

m) ether (specify)

_b) early infection

(< 6 months)

_d) breakage or deformation

of implant

f) stiffness of joint in vicinity of implant

_h) instability

_j) non-union

1) reasons not known

Findings at surgery (Indicate YES, NO, D0U3T , or NQT_ APPLICABLE)

. ... .2) PUS

c) granulation

tissue

e) bursal fluid

g) fractured grouting

.. Ob-nc -

. i) boney reaction

17, Swab from implant site (YES or NO)

_a) sterile, if NO, indicate type

18. Examination of tissue

579

b) scar tissue

_d) foreign body (debris

or stained tissue)

f) implant easily removed

h) caseation
Figure 2. ASTM F561 Metallurgical Review Form

Recovery of Implant

Metallurgical Examination Case #

(This report for component § of total components)

1. Implant Type

2. Number of comoonants

3. Macroscopic examination (YES, NO, DOUBT, or NOT APPLICABLE)

a) wear or burnishing

~b) galling

_c) scratching

_d) change of shape

_e) mechanical damage

f) macro porosity

Location Estimate Degree

4. Microscopic examination (Indicate location and orientation of sample)

a) Inclusion content (ASTM E45)

b) Grain size (ASTM E112)

'

c) Grain boundary constituents

d) Mi croporosi ty

e) Other distinguishing features (ex. cast stainless steel-delta ferrite)

i ii iii

5. Type of material (indicate method of determination)

a) chemical composition

6. Corrosion (if YES, identify)

a) general corrosion

b) pitting corrosion

c) crevice corrosion

d) galvanic corrosion

7. Mechanical failure (if YES, identify mode)

a) fatigue

b) torsion

c) impact

d) stress-corrosion

e) static-overstress beyond yield strength

f) corrosion-fatigue

g) combination of above (identify)

h) other (specify)

8. Device flaws (if YES, identify type and origin)

i iiMechanical properties (indicate N/A if not available).

Samples should be taken from areas representative of the original naterial

.

a) sample size and orientation

b) iiardness (indicate type)

c) .2% offset yield stress

d) ultimate tensile strength

e) % elongation in in.

f) reduction in area

g) other ASTM recommended tests as applicable (ex. transverse bend tests).

1C. Dimensions of implant

11. Conclusion __

580
Figure 3. Clinical Case History Form

Implant Retrieval and Analysis

Biomaterials Laboratory

Clinical Case History

1. Case Number:

2. Patient's Name:

3. Patient's Social Security or Hospital I.D. No.:

4. Patient's Sex:

5. Patient's Normal Occupational Activity Level:

A: Extremely active

B: Moderately active (normal)

C: Slightly active

D: Sedentary

E: Other

6. Patient's Weight (lbs):

7. Patient's Birthdate (month, year):

8. Hospital:

A: Veterans Administration - New Orleans

B: Veterans Administration - San Francisco

C: Charity Hospital - New Orleans

D: Moore Clinic - South Carolina

E: Tulane Medical Center - New Orleans

F: Veterans Administration - Alexandria, La.

G: Veterans Administration - Jackson, Ms. H-K: Others

9. Generic Implant Type:

A: Ankle H: Plate

B: Hip I: Hip nail plate

C: Rod J: Staple

D: Knee K: Shoulder

E: Elbow L: Wris t

F: Pin M: Finger

G: Screw N: Others

58 1
Figure 3 continued

Date of Implantation (month, year):

Date of Removal (month, year)

:

Diagnosis(es) at Insertion;

A: Unknown K: Malunion of fracture

B: Primary osteoarthritis L: Tumor

C: Secondary osteoarthritis M: Loosening of prosthesis

D: Rheumatoid arthritis N: Malposition of prosthesis

E: Dislocation of joint 0: Trauma - simple - closed

F: Asceptic necrosis P: Trauma - simple - open

G: Pain Q: Trauma - comminuted - closed

H: Pagets disease R: Trauma - comminuted - open

I: Congenital deformity S: Other

J: Pseudoarthrosis or non-union

Was the implant inserted left, right or middle?

Was the implant a joint replacement?

If no, answer 15.

To which bone was the implant attached or inserted?

A: Femur E: Radius

B: Tibia F: Ulna

C: Fibula G: Spine

D: Humerous H-J Others

Functional level attained after insertion:

(A-C, lower extremities; D-F, upper extremities)

A: Ambulatory D: Functional

B: Ambulatory with aids E: Functional with brace

C: Not ambulatory F: Not functional

Reasons for removal:

A: Routine H: Instability or loosening

B: Early infection < 6 months I

:

Unsatisfactory implant position

C: Late infection > 6 months J: Non-Union

D: Breakage of implant K : Allergic or Hypersensitive reaction

E: Pain related to implant L: Reason unknown

F: Stiffness related to implant M: Other

G: Prominence of bursae

582
Figure 3 continued

Finding(s) at surgery:

A: Pus

B: Granulation

C: Foreign body (debris or stained tissue)

D: Bursal fluid

E: Implant easily removed

F: Fractured grouting agent

G: Boney reaction

H: Loose prosthesis

I-K: Others

19. Was a radiographic review performed?

If yes, finding(s) :

A: Bony change in relation to implant

B: Reabsorption or osteoporosis

C: Increased density (sclerosis - compaction)

D: Hip nail used alone has backed out

E: Bone fragments held apart

F: Migration of implant

G: Malalignment

H: Fracture of bone

I: Penetration of implant across joint space

J: Penetration of implant through bone

K: Loosening

L: Others

20. Was a swab performed?

If yes, was the swab sterile?

21. Was an examination of the tissue performed?

22. Were antibiotics administered before or after insertion of the device?

583
Figure 4 Materials Examination Form

Implant Retrieval and Analysis

3iomaterials Laboratory

Materials Examination

Case Number:

Patient's Name:

Patient' s I.D. No.

:

Component of

What is the specific implant component?

A: Ankle distal P: Plate bone

B

:

Ankle proximal Q: Plate Jewet

C: Elbow humeral R: Plate Richards screw

D: Elbow ulnar S: Plate sliding nail

E: Hip acetabular T: Rod IM

F: Hip femoral stem U: Rod spinal

G: Hip femoral surface V: Screw cancellous

H. Joint MCP W: Screw cortical

I: Joint PIP X: Screw plate

J: Knee femoral Y: Shoulder humeral

K: Knee patellar Z: Shoulder other

L: Knee tibial + : Staple

M: Nail Richards screw *

:

Wrist

M: Nail sliding nail t • Other 1

0: Pin $: Other 2

Manufacturer of the implant:

A: A-0 J: 3-M

B

:

Biomet K: OEC

C: Cintor L : Os teonics

D: Cutter M: Richards

E: DePuy N: U.S. Surgical

F: Downs 0: Wright-Dow Corning

G: Howraedica P: Zimmer USA

H: Hexcel Q-T: Other

I. Medtec

584
Figure 4 continued

Implant material?

A: Stainless steel E

B : Co-Cr-Mo F

C: Titanium (Ti-6A1-4V) G

D: Polyethylene (UHMWPE) H-J: Others

MP35N

Silastic

Aluminum Oxide

Was a macroscopic exam performed?

If yes, then scale for following is 0.0 - 4.0

0 = none 1 - mild 2 = moderate 3 = severe

A:

B:

C:

Wear

Galling

Burnishing

4 = N.A.

D: Change in implant shape

E: Mechanical damage

F: Macro porosity

Was a microscopic examination performed? Y or N

A: Inclusion content ASTM #45, i.e. DO.OT

B: Grain size ASTM E112, i.e. 4.5

Was a corrosion examination performed?

If yes, scale is 0.0 - 5.0

If Y, then:

A:

B:

C:

D:

Gross corrosion

Crevice corrosion

Galvanic corrosion

Fretting corrosion

Was there mechanical failure?

If yes, failure modes:

Fatigue

Torsion

Impact

Stress- corrosion

Overs tress

Corrosion-Fatigue

Other

Was there a fabrication flaw?

Was there a mechanical property exam performed?

If yes

Hardness, i.e. B31

Offset yield strength (Psi)

Ultimate tensile strength (Psi)

% Elongation

Gauge length (in.)

Reduction in area

Bend strength (Psi)

58"
References

(1) Weinstein, A.M., Spires, W.P., Klawitter, J.J., Clemow, A.J.T.,

Edmunds, J.O., Orthopaedic implant retrieval and analysis study,

Corrosion and degradation of implant materials, ASTM STP 684,

212-228, 1979.

(2) Weinstein, A.M., Clemow, A.J.T., Starkebaum, W. , Milicic, M.

,

and Klawitter, J.J., An analysis of retrieved intermedullary

rods, submitted to the J. of Bone and Joint Surgery , July 19 79.

(3) Brettle, J., Hughes, A.N. , A metallurgical examination of surgical implants which have failed in service, Injury , 2_, (2),

143, October 1970.

(4) Scales, J.J., Winter, G.D., Shirley, H.J., Corrosion of orthopaedic implants - Smith-Peterson type hip nails, Brit. Med.

Journal , 478-482, August 1961.

(5) Weinstein, A.M., Amstutz, H. , Pavon, G. , Franceschinini , V.,

Orthopaedic implants - a clinical and metallurgical analysis,

J. Biomed. Mat. Res . Symp

.

, No. 4, 297-325, 1973.

(6) 1978 Annual Book of ASTM Standards, Part 46, American Society

for Testing and Materials, Philadelphia, PA., 1978.

5 06
Example 1. Use of Help ("?") and Data Check Features

12.) ENTER DIAGNOSIS(S) AT INSERTION. SEPARATE WITH COMMAS.

THE FOLLOWING IS A LIST OF POSSIBLE DIAGNOSES AT

INSERTION:

A: UNKNOWN

B: PRIMARY OSTEOARTHRITIS

C: SECONDARY OSTEOARTHRITIS

D: RHEUMATOID ARHTRITIS

E: DISLOCATION OF JOINT

F: ASCEPTIC NECROSIS

G: PAIN

H: PAGETS DISEASE

I: CONGENITAL DEFORMITY

J: PSEUDOARTHROSIS OR NON-UNION

K: MALUNION OF FRACTURE

L : TUMOR

M: LOOSENING OF PROTHESIS

N: MALPOSITION OF PROTHESIS

0: TRAUMA-SIMPLE-CLOSED

P: TRAUMA-SIMPLE-OPEN

Q: TRAUMA-COMMINUTED-CLOSED

R: TRAUMA-COMMINUTED-OPEN

S: OTHER

12.) ENTER DIAGNOSIS(S) AT INSERTION. SEPARATE WITH COMMAS.

U

** INVALID INPUT **

12.) ENTER DIAGNOSIS(S) AT INSERTION. SEPARATE WITH COMMAS.

0

1?.) WAS THE IMPLANT INSERTED LEFT, RIGHT OR MIDDLE.

TYPE L OR R OR M RESPECTIVELY .

L

587
Example 2. Use of Input Module

§RUN ADDREC

WOULD YOU LIKE INSTRUCTIONS? Y OR N

'ADDREC . FOR ' IS A PROGRAM DESIGNED TO ACCEPT CLINICAL AND

MATERIALS CHARACTERIZATION DATA REGARDING ORTHOPAEDIC IMPLANT

RETRIEVAL FROM STANDARD FORMS DEVELOPED BY THE BIOMATERIALS

LABORATORY, TULANE UNIVERSITY. THE CLINICAL DATA, I.E. AGE,

DATE OF REMOVAL, TYPE OF IMPLANT, ETC. IS STORED IN A DATA

FILE CALLED ' PERSON. MST ' . THE MATERIAL EXAMINATION DATA, I.E.

CORROSION, FAILURE, ETC., IS STORED IN A DATA FILE CALLED

'MATEXM.MST 1 . IT SHOULD BE NOTED THAT ALL DATA IS STORED IN

CODED FORM FOR EFFICIENT COMPUTER USAGE AND MAY BE PRINTED OUT

IN DECODED FORM WITH THE PROGRAM 1 PRINT. CBL" .

ONCE THE USER HAS THE STANDARD FORMS, HE MAY BEGIN

INPUTTING THE DATA. SOME DATA HAS BEEN SIMPLIFIED SO THAT IT

CAN BE ENTERED IN CODED FORM. FOR EXAMPLE, THE TYPE OF

IMPLANTS HAVE BEEN CODED SO THAT AN 'A' REPRESENTS A HIP

PROTHESIS OR A 'C REPRESENTS A KNEE PROTHESIS. THIS IS DONE

TO REDUCE COMPUTER STORAGE SPACE AND INPUT TIME.

IF THE USER DOES NOT KNOW THE CODES FOR A SPECIFIC INPUT,

HE CAN TYPE A »?' AND THE PROGRAM WILL DISPLAY EACH CODE AND

IT'S REPRESENTATION.

THERE ARE ALSO SOME OTHER SPECIAL DATA FEATURES. DATES

ARE TO BE ENTERED AS THE MONTH AND YEAR. FOR EXAMPLE,

DECEMBER 1939 SHOULD BE ENTERED AS 1239 . NOTE THAT THERE IS

NO DECIMAL POINT AND LEAD ZEROS MUST BE INCLUDED. MULTIPLE

ANSWER QUESTIONS DO NOT HAVE TO BE ENTERED IN ALPHABETICAL

ORDER, BUT EACH RESPONSE MUST BE SEPARATED BY A COMMA WITHOUT

ANY ELANK SPACES.

AT ANY POINT AFTER A QUESTION HAS BEEN ASKED BY THE

PROGRAM THE USER MAY TYPE 'BACK' OR 'HELP'. 'BACK' WILL ALLOW

THE USER TO GO BACK OR AHEAD TO A PREVIOUS OR LATER QUESTION.

THE DATA OF THE QUESTION IN WHICH THE USER TYPES BACK OR HELP

IS ONLY AFFECTED WHEN THE USER CHANGES IT'S INFORMATION. IF THE USER DOES NOT KNOW THE NUMBER OF THE QUESTION HE WISHES TO

RETURN TO, HE MAY TYPE A '?' AND THE PROGRAM WILL LIST THE

QUESTIONS. TYPING 'HELP' WILL DISPLAY THIS MESSAGE.

AT THE END OF EACH FORM, THE USER HAS THE OPTION OF

REVIEWING THE DATA INPUT FROM THAT FORM. HE MAY THEN CHANGE

ANY DATA BY TRANSFERRING TO THAT SPECIFIC QUESTION. THE

PROGRAM WILL PROVIDE THE APPLICABLE PROMPTS.

AT THE END OF THE CLINICAL DATA FORM THE USER WILL BE

ASKED HOW MANY COMPONENTS THERE ARE IN THE RETRIEVED IMPLANT

DEVICE. THIS REFERS TO THE NUMBER OF IMPLANT COMPONENTS THAT

HAVE A MATERIAL EXAM- INATION FORM. THE PROGRAM WILL ACCEPT

MATERIAL EXAMINATION DATA FOR EACH COMPONENT. THE PROGRAM

WILL ALSO DISPLAY WHICH COMPONENT DATA YOU ARE ENTERING.

588
(Example 2 cont.)

UNDER NO CIRCUMSTANCES SHOULD ANY DATA BE ENTERED WITH

QUOTES. YOU MAY END THIS PROGRAM ONLY AT THE COMPLETION OF

THE LAST COMPONENT, OTHERWISE DATA MAY BE LOST.   END OF ADDREC . FOR HELP FILE ** **

1.) ENTER CASE NUMBER. (4-DIGIT INTEGER)

?

THE CASE NUMBER IS A FOUR DIGIT INTEGER CODE AT THE TOP OF THE

FORM. PLEASE DO NOT PUT IN A DECIMAL POINT.

1. ) ENTER CASE NUMBER. (4-DIGIT INTEGER)

1051

2. ) ENTER PATIENTS NAME.

LAST NAME FOLLOWED BY ONE BLANK AND THE FIRST INITIAL.

?

PATIENTS NAME. UP TO 12 LETTERS FOR LAST NAME FOLLOWED BY ONE

SPACE THEN THE INITIAL OF FIRST NAME I.E. FOR ROBERT JONES

TYPE IN JONES R

2. ) ENTER PATIENTS NAME.

LAST NAME FOLLOWED BY ONE BLANK AND THE FIRST INITIAL.

SMITHERS J

3. ) ENTER PATIENT ID- .

?

PATIENT ID NUMBER IS UP TO A NINE DIGIT LETTER AND /OR NUMBER

RESPONSE THAT CORRESPONDS TO THE PATIENTS IDENTIFICATION

NUMBER

3. ) ENTER PATIENT ID- .

439806574

4. ) ENTER PATIENTS SEX. M OR F .

?

M STANDS FOR MALE, F STANDS FOR FEMALE.

589
(Example 2 cont.)

4. ) ENTER PATIENTS SEX. M OR F .

M

5. ) ENTER PATIENTS NORMAL OCCUPATIONAL ACTIVITY LEVEL

.

?

THE FOLLOWING IS A LIST OF POSSIBLE ACTIVITY LEVELS

EXTREMELY ACTIVE

MODERATELY ACTIVE (NORMAL)

SLIGHTLY ACTIVE

SEDENTARY

OTHER

5. ) ENTER PATIENTS NORMAL OCCUPATIONAL ACTIVITY LEVEL.

B

6. ) ENTER PATIENTS WEIGHT IN LBS (3-DIGIT INTEGER)

9

ENTER WEIGHT IN LBS. ? DIGIT INTEGER

INCLUDE ZEROES BEFORE WEIGHT IF LESS THAN 100 LBS

6. ) ENTER PATIENTS WEIGHT IN LBS (3-DIGIT INTEGER)

171

7. ) ENTER PATIENTS BIRTH DATE. MONTH AND YEAR. 1259

ENTER BIRTH DATE IN THE FOLLOWING FORMAT. FOR DECEMBER 1945

TYPE IN 1245 . NO DECIMAL PLEASE. INCLUDE LEAD ZEROS.

7. ) ENTER PATIENTS BIRTH DATE. MONTH AND YEAR. 1259

0748

8. ) ENTER THE HOSPITAL CODE.

5 90
(Example 2 cont.)

THE FOLLOWING IS A LIST OF CODES FOR HOSPITALS

VETERANS ADMINISTRATION - NEW ORLEANS

VETERANS ADMINISTRATION - SAN FRANCISCO

CHARITY HOSPITAL - NEW ORLEANS

MOORE CLINIC - SOUTH CAROLINA

TULANE MEDICAL CENTER - NEW ORLEANS

VETERANS ADMINISTRATION - ALEXANDRIA, LA. VETERANS ADMINISTRATION - JACKSON, MISS.

H-K: OTHERS

8. ) ENTER THE HOSPITAL CODE.

E

9. ) ENTER GENERIC IMPLANT TYPE,

9

THE FOLLOWING IS A LIST OF GENERIC IMPLANT CODES:

A ANKLE

E HIP

C ROD

D KNEE

E ELBOW

F : PIN

G SCREW

H PLATE

I HIP NAIL PLATE

J STAPLE

K : SHOULDER

L : WRIST

M FINGER

N : OTHER

9. ) ENTER GENERIC IMPLANT TYPE.

B

10. ) ENTER IMPLANTATION DATE. MONTH AND YEAR. I.E. 0679

ENTER IMPLANTION DATE IN THE FOLLOWING FORM. FOR DECEMBER

1959, TYPE IN 1259 . NO DECIMAL PLEASE. INCLUDE LEAD ZEROS.

59 I
(Example 2 cont.)

10. ) ENTER IMPLANTATION DATE. MONTH AND YEAR. I.E. 0679

0179

11. ) ENTER DATE OF REMOVAL. MONTH, YEAR. IE. 0667

ENTER DATE OF REMOVAL IN THE FOLLOWING FORMAT. FOR DECEMBER

1959, ENTER 1259 . NO DECIMAL PLEASE. INCLUDE LEAD ZEROS.

11. ) ENTER DATE OF REMOVAL. MONTH, YEAR. IE. 0667

0280

12. ) ENTER DIAGNOSIS (S) AT INSERTION. SEPARATE WITH COMMAS.

9

THE FOLLOWING IS A LIST OF POSSIBLE DIAGNOSES AT

INSERTION:

A: UNKNOWN

B: PRIMARY OSTEOARTHRITIS

C: SECONDARY OSTEOARTHRITIS

D: RHEUMATOID ARHTRITIS

E: DISLOCATION OF JOINT

F: ASCEPTIC NECROSIS

G: PAIN

H: PAGETS DISEASE

I: CONGENITAL DEFORMITY

J: PSEUDOARTHROSIS OR NON-UNION

K: MALUNION OF FRACTURE

L: TUMOR

M: LOOSENING OF PROTHESIS

N: MALPOSITION OF PROTHESIS

0: TRAUMA-SIMPLE-CLOSED

P: TRAUMA-SIMPLE-OPEN

Q: TRAUMA-COMMINUTED-CLOSED

R: TRAUMA-COMMINUTED-OPEN

S: OTHER

12. ) ENTER DIAGNOSIS(S) AT INSERTION. SEPARATE WITH COMMAS.

F.G

13. ) WAS THE IMPLANT INSERTED LEFT, RIGHT OR MIDDLE.

TYPE L OR R OR M RESPECTIVELY .

9

ENTER REATIVE POSITION OF PROSTHESIS.

LEFT SIDE = L, RIGHT SIDE = R, MIDDLE = M

592
(Example 2 cont.)

1?.) WAS THE IMPLANT INSERTED LEFT, RIGHT OR MIDDLE.

TYPE L OR R OR M RESPECTIVELY .

L

14.) WAS THE IMPLANT A JOINT REPLACEMENT? Y OR N.

?

ENTER Y OR N ACCORDING TO WHETHER THE

PROSTHESIS WAS A JOINT REPLACEMENT.

14.) WAS THE IMPLANT A JOINT REPLACEMENT? Y OR N.

Y

16.) ENTER THE MAXIMUM FUNCTIONAL LEVEL ATTAINED

FOLLOWING IMPLANT INSERTION.

THE FOLLOWING ARE POSSIBLE FUNCTIONAL LEVELS:

(A-C:LOWER EXTREMITIES, D-F:UPPER EXTREMITIES)

AMBULATORY

AMBULATORY WITH AIDS

NOT AMBULATORY

FUNCTIONAL

FUNCTIONAL WITH BRACE

NOT FUNCTIONAL

16.) ENTER THE MAXIMUM FUNCTIONAL LEVEL ATTAINED

FOLLOWING IMPLANT INSERTION.

17.) ENTER REASON(S) FOR REMOVAL. SEPARATE BY COMMAS

9

THE FOLLOWING IS A LIST FOR REASONS OF REMOVAL

A: ROUTINE

B: EARLY INFECTION < 6 MONTHS

C: LATE INFECTION > 6 MONTHS

D: BREAKAGE OF IMPLANT

E: PAIN RELATED TO IMPLANT

F: STIFFNESS RELATED TO IMPLANT

G: PROMINENCE OR BURSAE

H: INSTABILITY OR LOOSENING

I: UNSATISFACTORY IMPLANT POSITION

J: NON-UNION

593
(Example 2 cont.)

K

LM

ALLERGIC OR HYPERSENSITIVE REACTION

REASON UNKNOWN

OTHER

17.) ENTER REASON(S) FOR REMOVAL . SEPARATE BY COMMAS

18.) ENTER FINDINGS AT SURGERY. SEPARATE BY COMMAS.

THE FOLLOWING IS A LIST OF FINDINGS AT SURGERY:

A: PUS

B: GRANULATION

C: FOREIGN BODY (DEBRIS OR STAINED TISSUE)

D: BURSAL FLUID

E: IMPLANT EASILY REMOVED

F: FRACTURED GROUTING AGENT

G: BONEY REACTION

H: LOOSE PROSTHESIS

I-K: OTHERS

18.) ENTER FINDINGS AT SURGERY. SEPARATE BY COMMAS.

19.) WAS A RADIOGRAPHIC REVIEW PERFORMED? Y OR N.

ENTER Y OR N AS TO WHETHER A RADIOGRAPHIC REVIEW WAS

PERFORMED.

THE FOLLOWING IS A LIST OF RADIOGRAPHIC OBSERVATIONS:

A: BONY CHANGE IN RELATION TO IMPLANT

B: RESORPTION OR OSTEOPOROSIS

C: INCREASED DENSITY (SCLEROSIS - COMPACTION)

D: HIP NAIL USED ALONE HAS BACKED OUT

E: BONE FRAGMENTS HELD APART

F: MIGRATION OF IMPLANT

G: MALALIGNMENT

H: FRACTURE OF BONE

I: PENETRATION OF IMPLANT ACROSS JOINT SPACE

J: PENETRATION OF IMPLANT THROUGH BONE

K: LOOSENING

L-O: OTHERS

19.) WAS A RADIOGRAPHIC REVIEW PERFORMED? Y OR N.

ENTER REVIEW FINDING(S). SEPARATE WITH COMMA.

D,E

F

Y

5 34
(Example 2 cont.)

G

20.) WAS A SWAB PERFORMED? Y OR N.

7

ENTER Y OR N AS TO WHETHER A SWAB WAS PERFORMED IF Y THEN

ANSWER THE NEXT QUESTION EITHER Y OR N AS TO WHETHER THE SWAB

WAS STERILE

20. ) WAS A SWAB PERFORMED? Y OR N.

Y

WAS THE SWAB STERILE? Y OR N

Y

21. ) WAS AN EXAMINATION OF THE TISSUE PERFORMED. Y OR N

7

ENTER Y OR N AS TO WHETHER AN EXAMINATION OF THE TISSUE

WAS PERFORMED.

21.) WAS AN EXAMINATION OF THE TISSUE PERFORMED. Y OR N

N

22.) WERE ANTIBIOTICS ADMINISTERED BEFORE OR AFTER INSERTION OF DEVICE?

Y OR N

ENTER Y OR N AS TO WHETHER ANTIBIOTICS WERE

ADMINISTERED TO PATIENT BEFORE OR AFTER THE PROSTHESIS WAS

INSERTED.

22.) WERE ANTIBIOTICS ADMINISTERED BEFORE OR AFTER INSERTION

OF DEVICE? Y OR N

Y

WOULD YOU CARE TO REVIEW THE RECORD? Y OR N.

CASE NO. 1051, NAME SMITHERS J ID-NUMBER 439805574, SEX M

WEIGHT 171, ACTIVITY LEVEL B BIRTH DATE 0743, HOSPITAL E, IMPLANT B IMPLANT DATE 0179, REMOVAL DATE 0280

DIAGNOSIS FG , POSITION L, JOINT? Y BONE TYPE , FUNCTIONAL LEVEL A
(Example 2 cont.)

REASONS FOR REMOVAL DE , FINDINGS AT SURGERY F

RADIOGRAPHIC REVIEW? Y , RADIOGRAPHIC FINDINGS G

SWAB? Y, STERILE SWAB? Y, TISSUE EXAM? N ANTIBIOTICS? Y IS THERE SOME DATA YOU WISH TO CHANGE? Y OR N

N

ENTER NUMBER OF COMPONENTS.

2

ENTER THE DATA FOR COMPONENT 1

1.) ENTER THE SPECIFIC IMPLANT COMPONENT TYPE

.

?

THE FOLLOWING IS A LIST OF SPECIFIC IMPLANT CODES

A: ANKLE-DISTAL

B: ANKLE-PROXIMAL

C: ELBOW-HUMERAL

D: ELBOW-ULNAR

E: HIP-ACETAEULAR

F: HIP-FEMORAL STEM

G: HIP-FEMORAL SURFACE

H: JOINT-MCP

I: JOINT-PIP

J: KNEE-FEMORAL

K: KNEE-PATELLAR

L: KNEE-TIB IAL

M: NAIL-RICHARDS SCREW

N: NAIL-SLIDING NAIL

0: PIN

P: PLATE-BONE

Q: PLATE-JEWET

R: PLATE-RICHARDS SCREW

S: PLATE-SLIDING NAIL

T : ROD-IM

U: ROD-SPINAL

V: SCREW-CANCELLOUS

W: SCREW-CORTICAL

X: SCREW-PLATE

Y: SHOULDER-HUMERAL

Z: SHOULDER-PROXIMAL

+: STAPLE

*: WRIST

! : OTHER 1 $: OTHER 2

596
(Example 2 cont.)

1.) ENTER THE SPECIFIC IMPLANT COMPONENT TYPE,

2.) ENTER THE IMPLANTS MANUFACTURER

THE FOLLOWING IS A LIST OF MANUFACTURERS:

A-0

BIOMET

CINTOR

CUTTER

DEPUY

DOWNS

HOWMEDICA

HEXCEL

MEDITEC

3-M

CEC

OSTEONICS

RICHARDS

U.S. SURGICAL

WRIGHT-DOW CORNING

ZIMMER USA

OTHERS

2.) ENTER THE IMPLANTS MANUFACTURER,

3.) ENTER IMPLANT MATERIAL CODE,

THE FOLLOWING IS A LIST OF MATERIAL TYPES

STAINLESS STEEL

CO-CR-MO

TITANIUM TI-6AL-4V

POLYETHYLENE UHMWPE

MP35N

SILASTIC

ALUMINUM OXIDE

H-J: OTHERS

3. ) ENTER IMPLANT MATERIAL CODE.

A

4. ) WAS A MACROSCPIC EXAMINATION PERFORMED? Y OR N.

597
(Example 2 cont.)

ENTER Y OR N AS TO WHETHER A MACROSCOPIC EXAMINATION WAS

PERFORMED. IF YES , THEN THE SCALE FOR THE FOLLOWING QUESTIONS

IS FROM 0.0 TO 4.0

4. ) WAS A MACROSCPIC EXAMINATION PERFORMED? Y OR N.

Y

RATE THE WEAR.

0-NONE , 1-MILD, 2-MODERATE , 3-SEVERE, 4-N. A. I.E. 2.8

1.0

RATE THE GALLING.

0-NONE, 1-MILD, 2-MODERATE, 3-SEVERE, 4-N. A. I.E. 2.8

0.0

RATE THE BURNISHING.

0-NONE, 1-MILD, 2-MODERATE, 3-SEVERE, 4-N. A. I.E. 2.8

0.0

RATE THE CHANGE IN IMPLANT SHAPE.

0-NONE, 1-MILD, 2-MODERATE, 3-SEVERE, 4-N. A. I.E. 2.8

0.0

RATE THE MECHANICAL DAMAGE.

0-NONE, 1-MILD, 2-MODERATE, 3-SEVERE, 4-N. A. I.E. 2.8

1.0

RATE THE MACRO POROSITY.

0-NONE, 1-MILD, 2-MODERATE, 3-SEVERE, ii-N. A. I.E. 2.8

0.0

5. ) WAS A MICROSCOPIC EXAMINATION PERFORMED? Y OR N.

ENTER Y OR N AS TO WHETHER A MICROSCOPIC EXAMINATION WAS

PERFORMED. IF YES, THEN THE SCALES FOR THE FOLLOWING

QUESTIONS ARE ON THE FORM.

59 8
(Example 2 cont.)

5. ) WAS A MICROSCOPIC EXAMINATION PERFORMED? Y OR N.

Y

ENTER INCLUSION CONTENT ASTM E45. IE. D1.0T

D2.5T

ENTER GRAIN SIZE ASTM El 12- IE. 4.5

6.5

6. ) WAS THERE A CORROSION EXAMINATION PERFORMED. Y OR M

?

ENTER Y OR N AS TO WHETHER A CORROSION EXAMINATION WAS

PERFORMED. INDEX SCALE: 0.0 TO 5.0

6. ) WAS THERE A CORROSION EXAMINATION PERFORMED. Y OR N

Y

ENTER GROSS CORROSION INDEX. SCALE: 0.0-5.0

0.0

ENTER CREVICE CORROSION INDEX. SCALE: 0.0-5.0

1.5

ENTER GALVANIC CORROSION INDEX. SCALE: 0.0-5.0

0.0

ENTER FRETTING CORROSION INDEX. SCALE: 0.0-5.0

0.0

7. ) WAS THERE MECHANICAL FAILURE? Y OR N.

?

ENTER Y OR N AS TO WHETHER THERE WAS MECHANICAL FAILURE.

THE FOLLOWING IS A LIST OF FAILURE MODES:

A : FATIGUE

B: TORSION

C: IMPACT

D: STRESS-CORROSION

E: OVERSTRESS

F: CORROSION-FATIGUE

G: OTHER

539
(Example 2 cont.)

7. ) WAS THERE MECHANICAL FAILURE? Y OR N.

Y

ENTER FAILURE MODE(S). SEPARATE WITH COMMAS.

A

8. ) WAS THERE A FABRICATION FLAW? Y OR N

?

ENTER Y OR N AS TO WHETHER THERE WAS A FABRICATION FLAW

8. ) WAS THERE A FABRICATION FLAW? Y OR N

N

9. ) WAS A MECHANICAL PROPERTY EXAMINATION PERFORMED? Y OR N

?

ENTER Y OR N AS TO WHETHER A MECHANICAL PROPERTY EXAMINATION

WAS PERFORMED. SCALE (S) FOR DATA ON FORM

9.) WAS A MECHANICAL PROPERTY EXAMINATION PERFORMED? Y OR N

Y

ENTER HARDNESS.

3-CHARACTERS I.E. B31

B90

ENTER OFFSET YIELD STRENGTH (UNITS PSI

)

7-CHARACTERS I.E. 70000.0

75000.0

ENTER ULTIMATE TENSILE STRENGTH (UNITS PSI)

7-CHARACTERS I.E. 180000.

100000.

ENTER % ELONGATION.

5-CHARACTERS I.E. 25.00

8.000

ENTER GAUGE LENGTH (UNITS INCHES).

3-CHARACTERS I.E. 1.3

1.0

GOO
(Example 2 cont.)

ENTER REDUCTION IN AREA.

5-CHARACTERS I.E. 12.45

20.00

ENTER BEND STRENGTH (UNITS PSI )

7-CHARACTERS I.E. 70000.0

** NOTICE: NO DATA WAS ENTERED !!! »

WOULD YOU CARE TO REVIEW THE RECORD? Y OR N.

Y

CASE NUMBER 1051, COMPONENT NUMBER 1 SPECIFIC IMPLANT TYPE F , MANUFACTURED 0

MATERIAL A, MACRO EXAM ? Y, WEAR 1.0, GALLING 0.0

BURNISHING 0.0, SHAPE CHANGE 0.0, MECH DAMAGE 1.0, POROSITY

0.0

MICRO EXAM ? Y, INCLUSION CONTENT D2.5T

GRAIN SIZE 6.5, CORROSION EXAM ? Y, GROSS INDEX 0.0

CREVICE INDEX 1.5, GALVANIC INDEX 0.0, FRET INDEX 0.0

MECH FAILURE ? Y, FAILURE MODES A FABRICATION FLAW ? N, FLAWS , MECH PROPERTY EXAM ? Y HARDNESS B90, OFFSET YIELD STRENGTH 75000.0, TENSILE STRENGTH

100000.

% ELOGATION 8.000, GUAGE LENGTH 1.0, AREA REDUCTION 20.00

BEND STRENGTH

IS THERE SOME DATA YOU WISH TO CHANGE? Y OR N

N

ENTER THE DATA FOR COMPONENT 2

1. ) ENTER THE SPECIFIC IMPLANT COMPONENT TYPE.

E

2. ) ENTER THE IMPLANTS MANUFACTURER.

Q

3. ) ENTER IMPLANT MATERIAL CODE.

D

4. ) WAS A MACROSCPIC EXAMINATION PERFORMED? Y OR N.

N

5. ) WAS A MICROSCOPIC EXAMINATION PERFORMED? Y OR N.

N GO I
(Example 2 cont.)

6. ) WAS THERE A CORROSION EXAMINATION PERFORMED. Y OR N

N

7. ) WAS THERE MECHANICAL FAILURE? Y OR M.

N

8. ) WAS THERE A FABRICATION FLAW? Y OR N

N

9. ) WAS A MECHANICAL PROPERTY EXAMINATION PERFORMED? Y OR N

N

WOULD YOU CARE TO REVIEW THE RECORD? Y OR N.

Y

CASE NUMBER 1051, COMPONENT NUMBER 2 SPECIFIC IMPLANT TYPE E, MANUFACTURED Q

MATERIAL D, MACRO EXAM ? N , WEAR , GALLING

BURNISHING , SHAPE CHANGE , MECH DAMAGE , POROSITY

MICRO EXAM ? N, INCLUSION CONTENT

GRAIN SIZE , CORROSION EXAM ? N , GROSS INDEX

CREVICE INDEX , GALVANIC INDEX , FRET INDEX

MECH FAILURE ? N , FAILURE MODES

FABRICATION FLAW ? N , FLAWS , MECH PROPERTY EXAM ? N HARDNESS , OFFSET YIELD STRENGTH , TENSILE STRENGTH

% ELOGATION , GUAGE LENGTH , AREA REDUCTION

BEND STRENGTH

IS THERE SOME DATA YOU WISH TO CHANGE? Y OR N

N

DO YOU HAVE MORE CASES TO ENTER? Y OR N

N

STOP

END OF EXECUTION

$

G02
Example 3. Use of Case Review and Correction Feature

22.) WERE ANTIBIOTICS ADMINISTERED BEFORE OR AFTER INSERTION OF

DEVICE? Y OR N

Y

WOULD YOU CARE TO REVIEW THE RECORD? Y OR N.

Y

CASE NO. 1055, NAME JONES J ID-NUMBER 145667812, SEX F WEIGHT 112, ACTIVITY LEVEL B BIRTH DATE 0148, HOSPITAL A, IMPLANT G

IMPLANT DATE 0178, REMOVAL DATE 0678

DIAGNOSIS A , POSITION L, JOINT? N BONE TYPE A, FUNCTIONAL LEVEL A REASONS FOR REMOVAL A , FINDINGS AT SURGERY

RADIOGRAPHIC REVIEW? N, RADIOGRAPHIC FINDINGS

SWAB? Y, STERILE SWAB? Y, TISSUE EXAM? N ANTIBIOTICS? Y

IS THERE SOME DATA YOU WISH TO CHANGE? Y OR N

Y

WHICH QUESTION DO YOU WISH TO RETURN TO? INTEGER NO.

THE FOLLOWING IS A LIST OF QUESTION NUMEERS.

NOTE, YOU MAY RETURN ONLY TO A QUESTION ON THE FORM

YOU ARE CURRENTLY WORKING ON.

CLINICAL EXAMINATION FORM:

1 : CASE NUMBER

2 : NAME

3: ID-NUMBER

4: SEX

5: ACTIVITY LEVEL

6: WEIGHT

7: BIRTH DATE

8: HOSPITAL CODE

9: GENERIC IMPLANT CODE

10: IMPLANTTION DATE

1 1 : REMOVAL DATE

12: DIAGNOSIS AT INSERTION

13: LEFT, RIGHT, MIDDLE POSITION

14: JOINT?

15: BONE IN WHICH INSERTED

16: FUNCTIONAL LEVEL ATTAINED

17: REASON (S) FOR REMOVAL

18: FINDINGS AT SURGERY

19: RADIOGRAPHIC REVIEW PERFORMED?

£ 03
(Example 3 cont.)

20: SWAB PERFORMED?

21: TISSUE EXAM PERFORMED?

22: ANTIBIOTICS?

MATERIAL EXAMINATION FORM

1: SPECIFIC IMPLANT TYPE

2: MANUFACTURER

3: IMPLANT MATERIAL

4: MACROSCOPIC EXAM

5: MICROSCOPIC EXAM

6: CORROSION EXAM

7: MECHANICAL FAILURE

8: FABRICATION FLAW

9: MECHANICAL PROPERTY EXAM

WHICH QUESTION DO YOU WISH TO RETURN TO? INTEGER NO,

16

16.) ENTER THE MAXIMUM FUNCTIONAL LEVEL ATTAINED

FOLLOWING IMPLANT INSERTION.

THE FOLLOWING ARE POSSIBLE FUNCTIONAL LEVELS:

(A-C:LOWER EXTREMITIES, D-F : UPPER EXTREMITIES)

AMBULATORY

AMBULATORY WITH AIDS

NOT AMBULATORY

FUNCTIONAL

FUNCTIONAL WITH BRACE

NOT FUNCTIONAL

16.) ENTER THE MAXIMUM FUNCTIONAL LEVEL ATTAINED

FOLLOWING IMPLANT INSERTION.

B

WOULD YOU CARE TO REVIEW THE RECORD? Y OR N.

Y

CASE NO. 1055, NAME JONES J ID-NUMBER 145667812, SEX F WEIGHT 112, ACTIVITY LEVEL B BIRTH DATE 0148, HOSPITAL A, IMPLANT G

IMPLANT DATE 0178, REMOVAL DATE 0678

DIAGNOSIS A , POSITION L, JOINT? N BONE TYPE A, FUNCTIONAL LEVEL B REASONS FOR REMOVAL A , FINDINGS AT SURGERY

G 04
(Example 3 cont.)

RADIOGRAPHIC REVIEW? N , RADIOGRAPHIC FINDINGS

SWAB? Y, STERILE SWAB? Y , TISSUE EXAM? N ANTIBIOTICS? Y

IS THERE SOME DATA YOU WISH TO CHANGE? Y OR N

N

ENTER NUMBER OF COMPONENTS.

1

ENTER THE DATA FOR COMPONENT 1

$

605
Example 4. Use of Cross Referencing Feature

§RUN SELECT

WOULD YOU LIKE INSTRUCTIONS? Y OR N

'SELECT. FOR* IS A PROGRAM DESIGNED TO CROSS REFERENCE DATA

WHICH IS ASSOCIATED WITH EACH CLINICAL AND MATERIAL

EXAMINATION RECORD.

INPUT TO THE 'SELECT. FOR' PROGRAM STARTS WITH THE USER

TYPING THE ITEMS TO BE CROSS REFERENCED. TYPING A '?' AT THIS

POINT WILL GIVE THE USER THE LIST OF POSSIBLE ITEMS THAT MAY

BE SELECTED AND THE CORROSPONDING ITEM NUMBER. THE USER THEN

ENTERS FROM THE KEYBOARD EACH ITEM NUMBER TO BE CROSS

REFERENCED SEPARATED BY COMMAS.

THE PROGRAM THEN AUTOMATICALLY ASKS THE USER FOR SPECIFIC

INFORMATION ON THE ITEMS HE HAS CHOSEN TO CROSS REFERENCE.

BRIEF INSTRUCTIONS MAY BE OBTAINED FOR EACH PARTICULAR ITEM

SELECTED BY TYPING A '?' WHEN ASKED FOR SPECIFIC INFORMATION.

IF THE USER MAKES A MISTAKE WHILE INPUTING DATA ON AN

ITEM FOR CROSS REFERENCE, THE RUBOUT KEY CAN BE USED FOR

CORRECTIONS. HOWEVER, SHOULD THE USER MAKE A MISTAKE ON AN

ITEM AND PRESS THE CARRIAGE RETURN KEY THE ERROR CANNOT BE

CORRECTED USING THE RUBOUT KEY. THE USER MUST EXIT THE

PROGRAM BY TYPING A 'CNTRL C AND START THE CROSS REFERENCE

PROCESS OVER.

INPUT FILES FOR THE SELECT PROGRAM ARE PERSON. MST AND

MATEXM.MST. PERSON. MST IS THE MASTER FILE OF CLINICAL DATA

AND MATEXM.MST IS THE MASTER FILE FOR THE MATERIAL EXAMINATION

DATA.

OUTPUT FROM SELECT. FOR CONSISTS OF THE FILE SELDAT.MST

AND CONTAINS THE CLINICAL DATA OF EACH 'SELECTED' CASE

FOLLOWED BY THAT CASE'S MATERIAL EXAMINATION DATA, THEN THE

NEXT CLINICAL DATA ETC. THIS FILE CM THEN BE USED AS INPUT

FOR THE PROGRAM ' PRINT. CEL'.

WHAT ITEM(S) DO YOU WISH TO CROSS REFERENCE?

IF MORE THAN ONE, SEPARATE WITH COMMAS.

1 : CASE NUMBER (RANGE)

2 : NAME

3: PATIENT ID

4: SEX

5: WEIGHT (RANGE)

6: ACTIVITY LEVEL

7: EIRTH DATE (RANGE)

3: HOSPITAL

6 0S
(Example 4 cont.)

9: GENERIC IMPLANT CODE

10: IMPLANT ION DATE (RANGE)

1 1 : REMOVAL DATE (RANGE)

12: LENGTH OF TIME IN PLACE (RANGE)

13: DIAGNOSIS AT INSERTION

14: LEFT, RIGHT, MIDDLE POSITION

15: JOINT REPLACEMENT (Y,N)

16: BONE IN WHICH INSERTED (ONLY IF QUESTION 15 IS NO)

17: FUNCTIONAL LEVEL ATTAINED AFTER DEVICE INSERTION

18: REASON (S) FOR REMOVAL

19: FINDING(S) AT SURGERY

20: RADIOGRAPHIC REVIEW PERFORMED (Y , N

21: RADIOGRAPHIC REVIEW FINDINGS

22: SWAB PERFORMED (Y ,N)

2?: SWAB STERILE(Y,N)

24: TISSUE EXAMINATION (Y,N)

25: ANIBIOTICS (Y,N)

26: SPECIFIC IMPLANT COMPONENT TYPE

27: MANUFACTURER OF IMPLANT

28: IMPLANT MATERIAL

29: MACROSCOPIC EXAMINATION PERFORMED (Y,N)

30: RANGE OF WEAR

31 : RANGE OF GALLING

32: RANGE OF BURNISHING

33: RANGE OF CHANGE IN IMPLANT

34: RANGE OF MECHANICAL DAMAGE

35: RANGE OF MACRO POROSITY

36: MICROSCOPIC EXAMINATION PERFORMED(Y , N)

37: INCLUSION CONTENT

38: GRAIN SIZE (RANGE)

39: CORROSION EXAMINATION PERFORMED (Y , M)

40: RANGE OF GROSS CORRSION

41: RANGE OF CREVICE CORROSION

42: RANGE OF GALVANIC CORROSION

43: RANGE OF FRETTING CORROSION

44: MECHANICAL FAILURE(Y,N)

45: FAILURE MODES

46: FABRICATION FLAW(Y,N)

47: MECHANICAL PROPERTY EXAMINATION PERFORMED(Y ,N)

48: HARDNESS (RANGE)

49: RANGE OF OFFSET YIELD STRENGTH

50: RANGE OF ULTIMATE TENSILE STRENGTH

51: RANGE OF PERCENT ELONGATION

52: RANGE OF GAUGE LENGTH

53: RANGE OF REDUCTION IN AREA

54: RANGE OF BEND STRENGTH

WHAT ITEM(S) DO YOU WISH TO CROSS REFERENCE?

IF MORE THAN ONE, SEPARATE WITH COMMAS.

5,7,9,28,45

ENTER RANGE OF PATIENT WEIGHTS TO CROSS REFERENCE,

I.E. 100,190
150,200

(Example 4 cont.)

ENTER THE RANGE OF DATES FOR PATIENT 3JRTH DATES.

IE. BETWEEN DECEMBER 1932 AND MARCH 1980 YOU WOULD ENTER

0130,0160

ENTER GENERIC IMPLANT CODE YOU WISH TO CROSS REFERENCE.

THE FOLLOWING IS A

A ANKLE

B HIP

C ROD

D KNEE

E ELBOW

F PIN

G SCREW

H PLATE

I HIP NAIL PLATE

J STAPLE

K SHOULDER

L : WRIST

M FINGER

N OTHER

ENTER GENERIC IMPLANT CODE YOU WISH TO CROSS REFERENCE.

B

ENTER MATERIAL YOU WISH TO CROSS REFERENCE.

?

THE FOLLOWING IS A LIST OF MATERIAL TYPES:

STAINLESS STEEL

CO-CR-MO

TITANIUM TI-6AL-4V

POLYETHYLENE UHMWPE

MP35N

SILASTIC

ALUMINUM OXIDE

H-J: OTHERS

ENTER MATERIAL YOU WISH TO CROSS REFERENCE.

A

ENTER FAILURE MODE(S). SEPARATE WITH COMMAS.

G 08
(Example 4 cont.)

THE FOLLOWING IS A LIST OF FAILURE MODES

A: FATIGUE

B: TORSION

C: IMPACT

D: STRESS-CORROSION

E: OVERSTRESS

F: CORROSION-FATIGUE

G: OTHER

ENTER FAILURE MODE(S). SEPARATE WITH COMMAS.

NUMBER OF CASES READ: 111.

NUMBER OF CASES SATISFYING

CROSS REFERENCING CRITERIA : 1.

END OF EXECUTION

$
Example 5. Use of Print Module

RUN PRINT

WOULD YOU LIKE TO SEE OUTPUT ON THIS SCREEN, THE LINE

PRINTER, BOTH, OR EXIT PROGRAM ?

ENTER SCREEN , PRINTER , BOTH , EXIT

SCREEN

*##**#«**«********#**#**#*********«*****#» ##** «•***»#***#»###

CASE NUMBER 1051

#*#*##***#*#****«*»»#***#**#**#*##*******#***#** ##**********«***

CLINICAL HISTORY

PATIENT I.D. NUMBER : 439-80-6574

PATIENTS NAME : SMITHERS J

SEX: MALE DATE OF EIRTH: 07-48

PATIENT WEIGHT : 171 LBS.

ACTIVITY LEVEL : MODERATELY ACTIVE (NORMAL)

HOSPITAL : TULANE MEDICAL CENTER - NEW ORLEANS

IMPLANT TYPE : HIP

IMPLATATION DATE : 01-79 REMOVAL DATE : 02-30

DIAGNOSIS AT INSERTION : ASEPTIC NECROSIS

G I 0
(Example 5 cont.)

PAIN

IMPLANT POSITION : LEFT

THE IMPLANT WAS A JOINT REPLACEMENT.

FUNCTIONAL LEVEL ATTAINED : AMBULATORY

REASON (S) FOR REMOVAL :

BREAKAGE OF IMPLANT

PAIN RELATED TO IMPLANT

FINDINGS AT SURGERY :

FRACTURED GROUTING AGENT

A RADIOGRAPHIC REVIEW WAS PERFORMED.

RADIOGRAPHIC REVIEW FINDINGS :

MALALIGNMENT

A SWAB WAS PERFORMED.

THE SWAB WAS STERILE.

A TISSUE EXAMINATION WAS NOT PERFORMED.

ANTIBIOTICS WERE ADMINISTERED.

************************** **##*##*#**#**#*#*«*»* *#*##»***#**#*##

MATERIAL EXAMINATION DATA

CASE NUMBER : 1051 COMPONENT NUMBER : 1

IMPLANT TYPE : HIP-FEMORAL STEM

MANUFACTURER OF IMPLANT : OTHERS

IMPLANT MATERIAL : STAINLESS STEEL

A MACROSCOPIC EXAMINATION WAS PERFORMED.

SCALE : 0-NONE, 1-MILD, 2-MODERATE, ^-SEVERE, 4-N.A.

e i i
(Example 5 cont.)

WEAR : 1.0

GALLING : 0.0

BURNISHING : 0.0

CHANGE IN SHAPE : 0.0

MECHANICAL DAMAGE : 1.0

MACRO POROSITY : 0.0

A MICROSCOPIC EXAMINATION WAS PERFORMED.

INCLUSION CONTENT ASTM E45 : D2.5T

GRAIN SIZE ASTM E112 : 6.5

A CORROSION EXAMINATION WAS PERFORMED.

GROSS CORROSION INDEX : 0.0

CREVICE CORROSION INDEX : 1.5

GALVANIC CORROSION INDEX : 0.0

FRETTING CORROSION INDEX : 0.0

THERE WAS MECHANICAL FAILURE. FAILURE MODES :

FATIGUE

THERE WAS NOT A FABRICATION FLAW.

A MECHANICAL PROPERTY EXAMINATION WAS PERFORMED.

HARDNESS : B90

OFFSET YIELD STRENGTH : 75000.0 PSI

ULTIMATE TENSILE STRENGTH : 100000. PSI

PERCENT ELONGATION : 3.000

GAUGE LENGTH : 1.0 INCHES

REDUCTION IN AREA : 20.00

BEND STRENGTH : PSI

6 I 2
(Example 5 cont.)

MATERIAL EXAMINATION DATA

CASE NUMBER : 1051 COMPONENT NUMBER : 2

IMPLANT TYPE : HIP-ACETABULAR

MANUFACTURER OF IMPLANT : OTHERS

IMPLANT MATERIAL : POLYETHYLENE UHMWPE

A MACROSCOPIC EXAMINATION WAS NOT PERFORMED.

A MICROSCOPIC EXAMINATION WAS NOT PERFORMED.

A CORROSION EXAMINATION WAS NOT PERFORMED.

THERE WAS NO MECHANICAL FAILURE

THERE WAS NOT A FABRICATION FLAW.

A MECHANICAL PROPERTY EXAMINATION WAS NOT PERFORMED.

WOULD YOU LIKE TO SEE OUTPUT ON THIS SCREEN, THE LINE

PRINTER, BOTH, OR EXIT PROGRAM ?

ENTER SCREEN , PRINTER , BOTH , EXIT

EXIT

XI

6 I 3

A DATA RETRIEVAL SYSTEM FOR IMPLANT FAILURES

IN TOTAL JOINT REPLACEMENT SURGERY

David J. Schurman, M.D.*

David S. Burton, M.D.*

Donald A. Nagel, M.D.*

Dennis McShane, M.D. **

Stanford University

School of Medicine

Department of Surgery

*Division of Orthopedic Surgery

and

**Department of Medicine

A prospective information system to measure arthritis

surgery outcomes was developed cooperatively and over a period of years with the American Rheumatism Association

Medical Information System and a national group of arthritis

surgeons. The system called ASP (Arthritis Surgery Proforma) defines the essential minimum data for assessing

surgical outcomes and is designed for use by multiple institutions in cooperative or independent studies.

To best implement the use of ASP, a Time-Oriented

Record (TOR) is suggested. TOR allows for uniformity in

data collection over time and uniformly among different

investigators. The chart system itself can be modularized

by sections such as history, physical exam, complications

and x-ray findings. Data includes stratifying, intervention

and outcome variables. A new diagnostic system was developed that is indexed by ICD code where it exists.

An advanced computer system in operation checks, stores,

retrieves and analyzes data. This computer system known as TOD (Time-Oriented database) is nationally accessible through

local phone lines via TELENET.

Stanford's experience with 584 total hip or knee re- placements is briefly defined for the 21 patients requiring

revision surgery fc*non septic loose or broken prostheses.

This group of revision patients specifically includes only

those patients whose failed prosthesis were initially put in

at Stanford. Failed prostheses tended to occur in: 1) non

rheumatoids; 2) men more than women; 3) heavier patients

especially women; 4) accelerate with time since implantation and; 5) in younger patients. Complications were

described by specific product or manufacturer and identified

to specific surgeon.

G I 5
1 . Introduction

"Man's search is not so much for pleasure as it is a search for

the relief of pain." Arthritis is both a painful and common condition.

Surgical replacement of arthritic joints relieves this pain and re- stores function and as a result, it is no surprise to find that tens of

thousands of these operations are performed annually. Although implant

surgery is a recent explosive phenomenon of great success, there is a

need for serious critical assessment in order to optimize this technology and prevent unnecessary failure. ShortcxmLngs and delays in

collection and analysis unnecessarily increase human suffering and

expense. Of the several hundred available prosthetic designs for total

hip or knee replacement which are equivalent, superior or deficient?

Which materials and designs are least associated with loosening or

breakage? What are the exact risks and reoperation rates for different

catagories of patients?

The best way to understand risk in patients undergoing prosthetic

replacement is to do so within the context of a population over time.

It is not sufficient to examine patients or prostheses that have had

problems without knowing something about the population from which they were sampled. What we need is an honest denominator . It is of great

interest to know why a particular prosthesis failed. To make this

information more relevant, we must know how similar prostheses fared in

other patients. Aside from knowing the failure rate, one would like to

know how the failure rate is influenced by patient factors such as age,

physical activity, weight, disease, etc. Is the failure rate different

among surgeons dealing with similar patients? What is the failure rate

of the same design made by different manufacturers? Perhaps some prosthetic components will work well in certain circumstances but poorly in

others.

Information about the results of total joint replacement may be

derived from several approaches. These include anecdotal experience,

randomized clinical trials at single or multiple cooperative institutional centers, retrospective analyses of patient courses, or a prospective recording of data in clinical care settings with pre-determined hypotheses. In the present discussion we have chosen to con- centrate on the aspects of the last approach.

In ascertaining the effects of joint replacement in the arthritic a time-oriented approach has been selected to be applied ultimately in a multi-institutional cooperative venture. To understand this approach one needs to comprehend information acquisition in the clinical care

setting.

The time-honored way of denoting aspects of a patient's disease

process is the narrative progress note - a prose recording of items

felt to possibly have import and justification for courses of action

taken by the clinician in the patient's behalf. Retrieval of uniform or consistent observations from patient to patient by even one physician over time becomes difficult with conventional records. Anyone

who has ever been involved in chart reviews for retrospective studies

understands the limitations of the traditional chart. Similar limiG ! g
tations axe found when traditional charting techniques are used for

prospective studies (1)

Structure has been imbued into the prose chart through the Problem-Oriented approach of Weed and others (2) . While data about the

patient's course are organized according to problems and indexed ac- cording to subjective complaints, objective physical and laboratory

findings, clinical impressions, and management programs this approach

is still based on the unstructured narrative format with all its limitations .

2. Time-Oriented Record (TOR)

The Time-Oriented Record (TOR) evolved from two considerations.

First, a core set of observations could be used by different investigators; and second, these observations can be repeated uniformly

through time. The chosen descriptors (i.e., elements, evaluations or

facts) are, in fact, what has been termed the Arthritis Surgery Proforma (ASP) . When this set of information is utilized over time, a

patient's chart becomes a two dimensional array (Figure 1) . A TimeOriented Record can visually demonstrate changes in any one variable

over time and also, readily allows one to look for associations between

variables (Figure 2). The TOR concept serves: 1) the clinician as an outstanding method of charting for everyday patient care and; 2) the

researcher by ensuring more reliable data collection and ease in com- puter tabulation.

Within the TOR database three types of descriptors have come to be

recognized as necessary to bracket aspects of the disease process.

These three non-exclusive variables are: 1) stratifying; 2) intervention and; 3) outcome. Stratifying variables are features which are

known or suspected to be related to outcome. They include age, race,

sex, weight and variables representing disease severity. Stratifying

variables also include symptoms, physical exam measurements, e.g.,

range of motion, or laboratory tests. Intervention variables include

those treatments which are applied to the patient during individual

encounters. In particular, we are concerned with the type of prosthesis inserted and to some extent the type of medication given.

Outcome can be defined by variables relating to discomfort, disability,

drug toxicity, death, cost of treatment, or psychosocial perturbations

(3) . We are especially interested in the outcomes of prosthetic failure such as infection, loosening, breakage and the function and pain of

a specific joint.

Items of the database should be defined and coded in an easily

implementable fashion. In other words, the actual chart used by the

physician or the patient should be tailored to the individual collecting the data. Many other important considerations have been identified for the successful implementation of the Time-Oriented Record.

Research aspects and patient care aspects in chart design should be

merged as much as possible. At least one person, preferably the organizer of any arthritis surgery program, should be dedicated to the

6 I 7
use of the format and be constantly surveying its application. Patient

self-administered records for assessing historical and functional

information can be more reliable than physician acquired information

(5) and increase the efficiency of patient - physician contact. To

improve the quality and accuracy of the data collected, multiple levels

of informational cross-checking are useful. Patient self-administered

records can be implemented by technical or lay help familiar with the

intention and meaning of the forms. Physical therapists or nurses can perform and note many parts of the physical examination. In the university clinic, a resident can rapidly double-check the patient's and

therapist's findings for accuracy. In turn, the house officer can be

rechecked by an attending surgeon thereby resulting in a system of

information collection in which two or three "experts" screen each

piece of information. A pre-printed, color-coded, standardized form

makes this system of re-checking convenient and easy. The few patients

who do not enjoy filling out such questionnaires preoperatively quickly

and aggressively gain interest in them postoperatively. A single

charting system for any one program should be utilized. We have found

a color-coded modular chart to be of great help. For example, one module may relate to history, another to physical exam, a third to the

operation, and so forth.

3. Arthritis Surgery Proforma (ASP)

The historical development of the Arthritis Surgery Proforma (ASP) as well as its implementation and continuing evolution is of some interest. ASP is the outgrowth of many years of prospective planning and

organization. In 1973, a national group of rheumatologists all of whom

were experienced in data collection met and formed the American Rheumatism Association Medical Information System (APAMIS) . Their purpose was to create a national communication network for following patients

with arthritis. In that same year, one of the authors (DJS) joined

ARAMIS as an orthopedic surgeon with similar interests and the intent

of developing an information system for patients undergoing arthritis

surgery. ARAMIS itself has grown over the years to become a computer

network of about ten nationally based institutions and one in Canada.

The communications format utilized is under continuous development by a

committee formed from approximately 30 institutions under the auspices

of the American Rheumatism Association known as the Uniform Database in

Rheumatic Disease Committee. The origins of ASP grew within this committee. ASP was presented and discussed at the semi-annual national

meetings of the Committee. At the last national meeting in 1978, a subcommittee of rheumatologists joined with the author (DJS) to insure

that ASP would contain the minimal information relevant to and required

by rheumatologists. The suggestions were ratified by the general Committee and remain within ASP. In 1979, under the auspices of the Stanford Arthritis Center, a three day meeting was held with four nationally representative orthopedic groups. Those attending this meeting

included Harlan C. Amstutz, M.D. from UCLA, Robert Fitzgerald, Jr.,

M.D. from the Mayo Clinic, Clement Sledge, M.D. from Robert Brigham

Hospital, David J. Schurman, M.D. from Stanford and a data analyst from

each of those institutions.

E < 8
The year 1979 was an ideal time in the history of joint replacement surgery to achieve agreement on a prospective information system.

It was the end of the first decade of joint replacement surgery in this

country. The failures of other similar groups to reach agreement were

instructive. Participants had a great deal of hands-on experience with

exactly what was needed. And the group was able to benefit from the

experience of our ARAMIS colleagues and leap-frog some of their difficulties.

With complete agreement from the four institutions, the Arthritis

Surgery Proforma was born (Tables 1 & 2) . The concept of ASP was that

of a minimum core of questions that would be asked by all investigators

participating in any prospective cooperative study. Unlike our rheumatologic colleagues who sought to completely define a total information

system concerning every aspect of rheumatologic care, the Arthritis

Surgery Proforma sought to define an essential minimum in assessing the

outcomes of arthritis surgery and to include parameters of proven value

only. It was a time ripe for such a meeting. From many previous years

of experience, it became easier not harder for members to compromise on

coding system. There were many pieces of information that all institutions had regularly collected. Some of these elements were maintained as part of the ongoing system. It was a surprise and delight to

find many common elements dropped by unanimous consent because of their

lack of proven value despite their previous ubiquity. Shortly after

this meeting, arthritis surgeons from the following institutions either

ratified or expressed serious interest in fully cooperating with this

program: George Washington University, the University of Chicago, the

University of California in San Francisco and the USC program.

While ASP is an essential set of questions for defining the progress and outcome of patients undergoing total joint replacement surgery, there is both the need and the latitude for incorporating additional questions and descriptors. ASP is a viable system and it is

meant to improve with age. Collaborating scientists can use additional

descriptors and are encouraged to do so. Some investigators may want

to record large numbers of additional details about one or another

specific areas of interest. ASP in no way discourages such additional

data collection and analysis. On the contrary, the very concept of ASP

seeks to make such special collections of information more significant

by relating these findings to a critical standard reference of outcome

variables (i.e., ASP). The use of a core data set does not prevent

individualization within cooperating centers beyond the standard framework. By agreeing to collect the same items in the same manner, co- operating centers can emerge in multi-institution clinical trials without sacrificing independently pursued studies based on self-determined

hypotheses. This fact underlies the concept of ASP, TOR and the computer system known as TOD (to be described below)

4. Computers and Databanks

There are three major prongs to ASP. The first is the data itself. The second is the use of a time-oriented record which allows for

6 I 3
easy collection of the data. Ihe third is the computerization of this

information. The use of the computer is optional to the value of ASP

but the ability to analyse recorded data quickly and efficiently is a primary concern to any researcher. While no one computer software

system is essential to ASP, we will describe the system which we have

been using and which evolved with ASP over the past eight years. This

computer system is available for use by any orthopedic institution or

investigator in the country at cost. The system is accessible through

telephones at local telephone rates via TELENET.

A databank is simply a group of Time-Oriented Records, i.e. , a group of patients each with TOR records. The databank is, therefore, a three dimensional array of: 1) a set of patients; 2) each with their own file of information (elements) , displayed over time (visits) as depicted graphically in Figure 3.

5. Time-Oriented Data (TOD)

A software computer system termed TOD (Time-Oriented Database) has

been developed for the entry, storage and retrieval of information

contained in the three-dimensional databank at the Stanford Center of

Information Technology. TOD is a schema driven, positional databank

system developed to insure accuracy of data entry and to maximize

retrieval speed while minimizing retrieval cost. The schema is the map

and compass which the investigator uses to drive the various TOD programs. The schema is a master flow chart or organization plan which

directs entry, storage and retrieval programs to handle each piece of

information according to the different needs of each type of databank.

The schema defines, for each position in the databank, the name of each

element (of the database) , its units, data type, qualifiers and all

characteristics needed for processing that element. This schema approach results, therefore, in only the actual element value being

stored in the databank file. The position of the value within the

databank cube determines its meaning.

6. TOD File Structures

TOD file structures consist of simple arrays which, given the

nature of the software envircment, permits the most cost efficient

retrieval of data for statistical purposes.

There are two types of TOD schema elements: Headers and Parameters. Header elements are those defined once for each patient, such

as name, date of birth, etc. Parameter elements are those items re- corded at each encounter such that multiple values of the element exist

for each patient. TOD is designed to study the changes in variables over time.

There are six principal files comprising a TOD databank. These

files are: the Descriptor, Header Entry, Parameter Entry, Header Retrieval, Parameter Retrieval and Subset Library. Their interrelationships are diagrammed in Figure 4.

£20
The Descriptor File is the machine-readable form of the schema.

It is referenced by every TOD program and completely defines the specifics of each databank. Each element of the database is defined

according to schema number, long and short names and computer-compatible coding termed element type. As indicated in Figure 5, additional aspects of element definition including units, compression

factors (cell and scale factors) , limit ranges and qualifiers are

aspects of the Descriptor File definition of the database. The last

attribute in Figure 5 - TRANSPOSED determines whether information for

the specified element will also be stored in the appropriate retrieval

files.

The Header Entry File contains one Header Record for each patient.

Each Header Record is a character string consisting of a TOR number

(computer assigned thereby keeping each patient unique) , a counter of

the total number of visits for the patient in the Parameter File, and

pointers to the first and last visits in the Parameter File for the

patient. The remainder of the Header Record consists of "n" spaces

(where "n" is the number of Header elements specified in the schema)

represented by "super dots". Information is pigeon-holed between dots

as determined by the schema. The "super dots" are sinply markers that

the computer uses to locate information. The dots are adjacent when no

information is stored and slide apart as information is added thus providing economy of storage space. The Header Entry File consists of an

array of N such Header Records. The Header Record is graphically re- presented in Figure 6.

The Parameter Entry File contains one record for each patient

visit. Each visit record is in the form of a floating point array

consisting of "n" spaces where "n" is the number of parameter elements

defined by the schema. The visit record also contains keys that contain the TOR number, visit number and pointers that allow chaining to

the previous and subsequent visit records of the patient. The Parameter Entry File consists of an array of such visit records. The

Visit Record is depicted in Figure 7.

Data are entered into the above two files from the patient care

documents and subsequently used for checking, validating and listing

individual patient courses.

The data contained in the Header and Parameter Entry Files are duplicated in two additional files termed Header and Parameter Retrieval Files. Data are organized by element within these two files

thereby achieving quick and cost-efficient retrieval of information for

statistical analysis. It is these two files coupled with the Subset

Library File that make TOD a unique software system for medical research. All statistical retrieval programs reference these Retrieval

Files. Parameter Retrieval File data are stored as integers in order

to accelerate most of the I/O and statistical processing. The scale

and cell factors of the Descriptor File contain specifications for

placement of the decimal point, which is not inserted until the results

of analysis are ready to be displayed to the user. A diagramatic

62 I
representation of a Retrieval File Record is given in Figure 8.

The Subset Library File contains records created by the Subsetting

Programs. These programs allow the user to specify stratifying characteristics for grouping patients. Each member of the Subset Library

consists of two records: one indicates (in machine-readable form) how

the subset was defined; the other is a bit string equal to the number

of patients in the databank, indicating which patients belong to the

subset. The Subset Library is referenced by all retrieval programs to

determine which patients to process.

All analytic programs as noted in Table 3 access the Retrieval

Files in concert with a defined subset of the patient population as specified in the Subset Library File. Each program has code embedded

within it for extracting the requisite data, employing the appropriate

statistical tests and formatting the output to the specifics of the

program utilized. The retrieval process is a one step on-line procedure with "turn-around" measured in seconds of specification.

Salient TOD characteristics are: 1) that each ingredient of the

system is simple in itself; 2) that each program is independent of

others and; 3) that file structures are rudimentary. The interaction

of these elements produces a system which is complex yet flexible; fast

but simple and inexpensive to use.

Because the TOD/Descriptor File determines the meaning of the

positional data bank information, multi-center databanks can be stored

as separate Header and Parameter Files with commonality defined by

choosing to store similar data at identical positions in respective

databanks. This creates the ability to combine data from individual

databanks to increase the denominators for testing hypotheses or to

compare the population within one data bank to that of another or to

compare one sub-population to another within the same data bank. This

is made possible by inter-institution agreement upon the elements of a structured database they will collect as a common core.

The collaboration and utilization of TOD on a national network

scope currently exists in Rheumatology (ARAMIS) , stroke and traumatic

coma (NINCDS pilot) and in Arthritis Surgery Proforma. Aspects of the

latter' s implementation will serve as illustration of the national data

bank network approach.

7. Stanford ASP Databank

At the time of this writing, the ASP databank at the Stanford

Orthopedic program has TOR records on the TOD computer system for 380

patients who have undergone 584 total hip replacements (THR) or total

knee replacements (TKR) . This number includes 374 THR1 s in 252 patients and 210 TKR' s in 139 patients. Twenty four percent of patients

with THR had bilateral operations and 34% of TKR's were bilateral.

Seventeen patients or 4.5% had at least one THR and one TKR of which

only three patients had both bilateral THR and TKR. The types of THR's

62 2
are as follows: 120 Charnley-Mullers , 135 Aufranc-Turners , 63 Trapazoidal Twenty Eights, 24 long stem prostheses, 2 Harris and 14 others.

Trochanteric osteotomy was performed in only nine operations. The

types of TKR's included: 41 Geometries, 71 Total Condylars, 27 Guepar

hinges, 57 Zimmer offset hinges, 6 Condylar hinges, 5 Duopatellars and

3 others. The patella was resurfaced with a plastic button in 81

operations. The average followup for patients with THR's is 2.8 (+0.1

s.e.) years and 2.2 (+ 0.2 s.e.) years for TKR's.

The age at the time of the first THR was 60.2 (+1.0 s.e.) years

ranging from 15 to 90 years. TKR patients' age was 63.2 (+ 1.1 s.e.)

years ranging from 22 to 85 years. The difference in average age between THR and TKR patients was significant at the .05 level (T-test)

Females comprised 56% of THR patients and 67% of TKR patients (p <^.05)

The mean weight of patients with THR's did not differ from those with

TKR's and was 155 pounds. Men undergoing joint replacement averaged

172 pounds without significant difference between THR and TKR groups.

The female weights averaged 143 pounds with THR females weighing 137.5

(+ 2.2) pounds and TKR females weighing 152.5 (+ 3.5) pounds (p \ .001)

Primary diagnoses for THR patients were as follows (in percentages) : osteoarthritis 50; osteonecrosis 17.2; polyinflammatory 12.5;

dysplasia or protrusio 10.3; traumatic 7.3; post infectious 0.4; neuropathic 0.4; other 1.9. Secondary diagnoses included the following

numbers of patients having revisions: 21 total joint replacement

failures; 13 hemiarthroplasty failures and 2 failed arthrodeses.

Primary diagnoses of TKR patients included the following by percentage: osteoarthritis 50; polyarthritis 33.8; post traumatic 10.3;

neuropathic 2.2; others 3.7. Secondary diagnosis included nine patients with failed TKR and one failed arthrodesis.

8. Loose or Broken Prostheses - Non Septic

Twenty one patients in the Stanford ASP data bank developed loose

or broken prostheses after a Stanford total joint replacement. Two

patients had loose prostheses immediately following an initial THR

implant. One of these patients had had 12 previous failed hip operations including pinning and arthrodesis after sustaining a fracture.

Her femoral stem was inadvertantly malpositioned in the femoral canal

protruding through the foramen left by a previous hip nail. This was

replaced with a long-stemmed femoral prosthesis after which she improved but continued pain being incapacitated by a stroke four years

later. The other patient had rheumatoid arthritis with protrusio

acetubulum. Postoperatively her acetabular cup was loose. The cup was

replaced and she has been followed for six months with no pain and

improved function.

Nineteen patients developed loose or broken prostheses after the

initial post operative period. Let us look directly at total knee

problems. Two Zimmer offset hinges of 52 broke at 2.6 and 3.2 years

after insertion. One of 23 Guepar hinge knees broke at 2.4 years.

6Z3
The followup of the non-broken hinge knees averages 2.9 years (s.d.

1.6). The two differently manufactured prostheses were almost alike.

All breaks occurred at the ends of notches in the stems. Two of the 75

hinges loosened after 1.1 and 5.4 years. Both loosened after falls

although the latter patient showed evidence of progressive signs of

loosening before the fall.

Two of 28 patients with 34 Geomedic knees loosened after 2.5 and

4.5 years. The average followup of the non- loosened knees was 3.6

(s.d. 1.7) years. The first patient was a 200 pound woman with degenerative arthritis and the other was a 128 pound male with rheumatoid

arthritis. Both underwent successful surgical revision.

The 11 remaining patients had loosened total hip replacements

which required revision. One of these 11 patients also had a broken

Charnley-Muller Howmedica femoral stem. The femoral component showed

radiographic signs of loosening for 16 months prior to breakage with

only occasional minimal symptoms. This 65 year old white male 174

pound osteoarthritic working physician fractured his prosthesis non- traumatically 4.2 years after insertion. The component was replaced

with only a three month followup.

The 12 patients with loosened total hip replacement components had

13 involved joint failures. The one patient with bilateral loosened

components had surgery for congenitally dislocated hip in 1973. The

acetabulae were erroneously placed in the pseudo-acetabulae . Both cups

subsequently loosened and were replaced at six months and 1.6 years.

These replacements were also placed high in the pelvis and in turn

relcosened. The patient appropriately sought treatment elsewhere.

Each of the 11 remaining patients had a problem with a single

loosened femoral component (Tables 4 & 5) . Three of these patients

had their initial operation at our hospital for a loose total hip

femoral prosthesis performed elsewhere. The first of these patients

had an immediate postoperative failure after replacement. After four

months he underwent his second Stanford replacement which also loosened. The patient went elsewhere thereafter for his fourth attempt and was lost to followup. The second patient successfully underwent re- placement with a long stem prosthesis and was last seen two years postreplacement doing well. The third patient had a long stem femoral

replacement and did well for two years. After seven months of progressive difficulty he underwent another revision for loosening and is

now two months postoperative, and except for seme phlebitis is doing

well.

The remaining eight patients which eventually underwent replacement for loosening between 2.5 and 6.3 years after insertion with an average time of 4.6 years. The average total hip that did not loosen

has been followed for only 2.9 (+ 0.1 s.e.) years with only 22.9%

followed for 4.6 years or longer. Seven of these patients were re- placed with Aufranc-Turner prostheses and one with a Charnley-Muller.

None of the 62 T-28 prostheses loosened but these were only followed

62<1
for an average of 1.9 (+0.2) years and all were performed by one

surgeon who had no loosenings. This surgeon performed 19% of the hip

operations. A second surgeon operated on 12 of the 13 joints which

became loose on a delayed basis and one of the two which was initially

loose. This surgeon's hip patients have been followed 3.1 (+ 0.1 s.e.)

years. He had performed 76.9% of the THR operations. A third surgeon

performed only six hip replacements altogether of which one became

initally loose and another had delayed loosening at 6.3 years.

The 11 patients with replaced loosened femoral components were

studied for differences in a variety of factors as compared to 240

patients that had no loose or broken prostheses and underwent total

hip replacement (Table 5) . There were more men than women with loose

components although for those without loosening it was the reverse.

Vfeight was 15 pounds heavier for those that loosened although all of

this discrepancy was in heavier women. No patient with a loose hip

component weighed more than 200 pounds! Those with loosening were

younger by about four years. Ability at walking prior to the first

Stanford total hip was a bit better for the group which loosened as was

upper extremity function. This is in part explained by the fact that

all patients with loosened femoral components had a primary diagnosis

of trauma, osteoarthritis or osteonecrosis and none had rheumatoid arthritis. In the non-loosened patients 11.5% had inflammatory polyarthritis.

There were 13 patients (with the same number of prostheses) who

had a loose THR that had been performed elsewhere which we revised and

which have not yet loosened. Their followup averaged only 2.6 (+0.7

s.e.) years. Fewer of these patients which have not reloosened were

male, 38%, as compared to our THR's that loosened, 73%. These 13

patients had an average age of 60.4 years and weighed 152.9 pounds and

had an average operative time of 190 (+15 s.e.) minutes. Thus those

with successful resivions were older and lighter and more operative

time was spent on their revision surgery.

This work was supported in part by NIH grant No. AM 21393 and NIH

Grant No. AM 20610.
References

(1) Fries, J.F., Alternatives in medical record formats. Med. Care

12, 871-881 (1974)

.

(2) Vfeed, L.L. , Medical records, medical education and patient care. Cleveland, Press of Case Western Reserve University (1969)

.

(3) McShane, D. J. , Harlow, A., Kraines, R.G. and Fries, J.F., TOD: A

software system for the ARAMIS data bank. Computer 12, 34-41

(1979)

.

(4) Fainstat, M. , McShane, D.J. and Lages, W.L. , A new time-oriented

database chart system for computer entry into ARAMIS. Abstract

for American Rheumatism Association Annual Meeting (May, 1980)

.

(5) Liang, M.H. , Schurman, D.J. and Fries, J.F., A patient administered questionnaire for arthritis assessment. Clin. Ortho. and

Pelated Res. 13, 12-129 (March/April, 1978).

G2G
ARTHRITIS SURGERY PROFORMA

Table I

General Information

Patient Name

Medical Record Number

Date of Birth

Home Address

Handedness

Marital Status

Ethnic Origin

Date Disease or Difficulty Began

Concurrent Disease (includes date

onset)

Diabetes Millitus

Phlebitis

Pulmonary Embolism

Myocardial Infarction

Other Heart Disease: Specify

Alcohol: Amount & duration

Bone Infection: Specify

Joint Infection: Specify

Previous Joint Operations: Specify

Ambulation

Walking aids: Code 0 - None; 1 - One support parttime; 2 - One

support fulltime; 3 - Two supports; 4 - Walker; 5 - Wheelchair; 6 - Bedridden.

Maximum distance able to walk at

one time: Code 0 - One mile or

more; 1 - 1/2 mile; 2 - 1/4 mile;

3 - Indoors around house; 4 - Unable.

Ability to climb stairs: Code 0 - No difficulty; 1 - Mild difficulty; 2 - Need handrail; 3 - Extreme difficulty; 4 - Unable.

Limp: Code 0 - None; 1 - Minimal;

2 - Mild; 3 - Moderate; 4 -

Severe.

Medications : Current & Historical

Intra-articular steriods: Yes or No

Specify joint (s) infected

Number of injections

Non Narcotic Analgesics: Specify

type & dose for each category (includes ASA & NSAI)

Narcotics

Corticosteriods

Penicillamine

Chrysotherapy

Chemotherapy

Joint Involvement

Specify with each joint or anatomic

area; yes, if definite involvement,

very painful or disabling. Right & left specification for each peripheral joint. Code: 0, not involved

& 1, involved.

Foot Elbow

Knee Shoulder

Hip Neck

Hand Back

Activities

All activities coded as follows:

0 - No problem; 1 - Mild difficulty;

2 - Moderate difficulty; 3 - Severe

difficulty; 4 - Unable.

Put on socks (L & R)

Arise from chair without using

arms Use knife & fork

Bathing & personal hygiene

Drive car

Sports: Code in each category.

Specify yes or no if any one within

category is performed.

Light sports: Golf, swim, bowl,

garden

Heavy sports: Jog, tennis, ski,

skate

627
ARTHRITIS SURGERY PROFORMA

Table I (continued)

Joint Pain (for each operative

joint)

Pain at rest

Pain with activity

Total pain sum: Sum of rest & activity pain. Code 0 - None;

1 - Minimal, i.e., occasional & slight; 2 - Mild, i.e. , regular 6 slight, takes occasional analgesics; 3 - Moderate, i.e. , frequent use of analgesics; 4 - Severe, i.e., regular use of an- algesics.

Did operation help you? Code 0 - Much better; 1 - Little better;

2 - No change; 3 - Little worse;

4 - Much worse.

If operation did not help was it

because: Code 0 - Problem not involving the joint operated on; 1 - Problem in other joint (s)

;

2 - Problem in the joint that was operated on.

Physical Exam - Knee

Recorded separately for each knee.

All limits or motions recorded in

degrees.

Flexion

Flexion arc Varus - valgus

ML instability in extension;

AP instability in 90 flexion;

Code 0 - None; 1 - Minimal;

2 - Mild; 3 - Moderate; 4 - Severe

Effusion: Code 0 - None; 1 -

Some; 2 - Severe

Patello femoral tenderness:

Code 0 - None; 1 - Some; 2 - Severe

Patella tracking: Code 0 - Normal; 1 - Subluxed; 2 - Dis

located

Patella status: Code 0 - Present;

1 - Patellectomy

Physical Exam

Height: Inches

Weight: Pounds

Apparent lower extremity difference.

Code 0 - Equal; 1 - Right longer;

2 - Left longer.

Amount of apparent difference (in

cm) . True lower extremity length (for

R & L in cm)

.

Problems in non-operated joints:

Code 0 - Normal; 1 - Involved & not impairing; 2 - Involved & impairing.

Physical Exam - Hip

Recorded separately for each hip.

All limits or motions measured in

degrees.

Flexion

Flexion arc Adduction (in extension)

Abduction (in extension)

Abduction muscle power: Code 0

• Normal; 1 - Weak; 2 - Absent

Trendelenburg: Code 0 - Normal;

1 - Equivocal; 2 - Positive.

628
ARTHRITIS SURGERY PROFORMA

Table I (continued)

Diagnosis

Diagnosis #1: Disease

Diagnosis #2: Previous surgery

Diagnosis #3: Additional

Complications

Pneumonia

Myocardial Infarction

Pulmonary Embolism

Cerebrovascular Accident

Nerve Palsey

Abnormal Wound Healing

Deep Infection

Micro-organism

Clinically Loose Prosthesis

Prosthesis Breakage: Indicate

proximal or distal component

Intra-operative Bone Fracture

Post-operative Bone Fracture

Trochanteric Non-Union: Code 1 -

1 cm; 2 - 1-2 cm; 3 - 2 cm

Dislocation

Subluxation

Hematoma: Code 1 - Not drained;

2 - Surgically drained; 3 - Spontaneous drainage; 4 - Other

Lost to Followup

Death

Operation

Name of Operation

Size of Prosthesis

Manufacturer of Prosthesis

Surgical approach

Radiographic Measurement of CementBone Interface

For proximal & distal prosthesis

each.

Lucencies: Code 0 - None; 1 - incomplete; 2 - complete

Lucency width: Code 0 - None;

1 - 1 mm; 2 - 1-2 mm;

3 - 2 mm

Subsidence (in mm)

Cement Fracture

Calcar Resorbtion

Osteolysis

Cortical Hypertrophy
DIAGNOSIS

Table 2

ASP ICD

CODE CODE

901 POLYARTHRITIS OF UNKNOWN ETIOLOGY 714.9

901.1 Rheumatoid Arthritis 714.0

901.2 Juvenile Rheumatoid Arthritis 714.3

901.3 Ankylosing Spondylitis 720

901.4 Psoriatic Arthritis 696

901.5 Reiter's Syndrome 099.3

902 CONNECTIVE TISSUE DISORDERS

902.1 Systemic Lupus Erthremotasis 710

902 . 2 Scleroderma 710 .

1

902.3 Polymyositis - Dermatomyositis 710.3

902.4 Mixed Connective Tissue Disease 734.91

903 OSTEOARTHRITIS 715

904 POST TRAUMATIC

904.1 Closed Reduction only

904.2 Open Reduction only

904.3 Surgery Proximal

904.31 Surgery Proximal & Reduction

904.4 Surgery Distal

904.41 Surgery Distal & Reduction

904.5 Surgery Proximal & Distal

904.51 Surgery Proximal; Distal & Reduction

904.6 Unreduced Dislocation

904.61 Unreduced Dislocation & Failed Surgery

905 SEPTIC 711.9

905.1 Active Infection

905.2 Previous Infection

906 METABOLIC OR ENDOCRINE

906.1 Gout 274

906.2 Gaucher' s Disease 272.7

906.3 Paget' s Disease 731

906.4 Hemaphilia 286

906 . 5 Chondrocalcinosis 275 .

4

Primary Bone Tumor - benign 213.9

Primary Bone Tumor - malignant 170.9

Metastic Tumor 198.5

907 TUMOR

907.1

907.2

907.3

908 PRIMARY HIP DISEASE

908.1 Congenital Dislocation

908.2 Subluxation

908.3 Primary Protusio

754.30

G30
DIAGNOSIS

Table 2 (continued)

ASP

CODE

909 OSTEONECROSIS

909.1 Alcoholic

909.2 Corticosteriod Induced

909.3 Hemoglobinopathy

909.4 Legg Perthes

909.5 Post Traumatic

909.6 Caissons

ICD

CODE

733.4

303.9

962.0

282.7

732.1

993.3

910 FAILED PRIOR SURGERY - Secondary Diagnosis

910.1 Osteotomy - hip 77.3

910.2 Osteotomy - knee 77.3

910.3 Arthrodesis 81.20

910.4 Open Reduction

910.5 Cup Arthroplasty

910 . 6 Hemiarthroplasty

910.7 Total Joint Replacement

911 FRESH TRAUMA

911.1 Proximal Fracture

911.11 Proximal Fracture & Dislocation

911.2 Distal Fracture

911.21 Distal Fracture & Dislocation

911.3 Proximal & Distal Fracture

911.31 Proximal & Distal Fracture; Dislocation

912 NEUROPATHIC (Charcot)

6 3 I
Table 3

Analytic Programs for Accessing the Retrieval Files

PROFILE - Histographic Distribution

CRITTER - Diagnostic Criteria Counts

SCATTER - X-Y Graph of Variables

MULTREVU - Mean and Standard Error of Variable in Subsets

OUTCOME - Life Table Analysis of Variables

AUTOSET - Computer Assisted Consultation

LIST - List of Variables in Subset

TIMESCAT - X-Y Graph of Variable Over Time

SUBSET - Group Meeting Specified Criteria

MW - Ranking Variables by Logistic Regression

STATPAC - Extraction Program to Pass Data to SPSS/SAS/BMDP

CONTING - Contingency Tables

632
TABLE 4

Revision of THR's for Loose Femoral Stems

Diagnosis

Loose THR

ON/

Renal

TX

Loose THR

Loose THR

ON/Trauma

ON

DJD

DJD

' Arth

'Arth

DJD

Revision*

Time

0.4

2.3

2.7

2.8

3.7

4.1

4.2

5.1

5.3

5.9

6.3

Result

Loose

Good

Good

Good

Good

Poor

Fair

Fair

Good

Good

Fair

* Years

** Sought treatment elsewhere and lost to followup.

Followup*

1.3**

0.2

Died I.M.

0.1

2

3

0.6**

0.3

0.3

2.1

1.0

0.3

633
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63 4
REPRESENTATION OF PATIENT COURSE

TIME

T "i

1—

CO

DC

<

<

Q.

Figure 1

G35
(P26I

1.P27)

IP28)

IP79I

IP30)

IP35I

(P36) ^ (P37)

(P38)

1P391

IP42I

(P«)

STANFORD UNIVERSITY HOSPITAL (71 STANFORD MEDICAL CENTER

STANFORD, CALIFORNIA M30E

DIVISION of ORTHOPEDIC SURGERY

PAIN fconlmg*fil

How many joints have become painful or swollen since you

Fo' how many hours are your joinis stiff in the n

> the way your body funi

AMBULATION How well arc you able to walk?

II you do not require support, do you limp?

How well can you climb stairs?

bo you wear

0 ~ no 1 •

* brace or joint immobilize!

WORK

What is your

0 = roll time

current work status?

- pan t.m« 2 - retirM njiurally

1 f you are no

problems7 working full lime, is it because ' 0 - no 1 yet

in today's date

Figure 2

Example of Time-Oriented Record

In this format, the date is entered in the column opposite PI and data

for that visit entered on each page above it.

636
VISITS

Graphic Representation of a Database

Figure 3

637
HEADER

FILE

TRANSPOSED

HEADER

FILE

1

DESCRIPTOR

FILE

T

ENTRY

TRANSPOSE

IBSE"

T

SUBSET

LIBRARY

T

ALL

RETRIEVAL

PROGRAMS

T

OUTPUT

PARAMETER

FILE

TRANSPOSED

PARAMETER

FILE

r

Figure 4

Schematic Relationship of the Principal Files

638
DATABASE ELEMENT NUMBER

LONG NAME

SHORT NAME

ELEMENT TYPE

UNITS

CELL SIZE

SCALE FACTOR

LOW LIMIT

HIGH LIMIT

LOW NORMAL VALUE

HIGH NORMAL VALUE

ABNORMAL DIRECTION

INITIAL VALUE

WIDTH

EQUIVOCAL

SAME

COMPUTED

PROTECTED

TRANSPOSED

Graphic Representation of the Descriptor file

Figure 5

639
Fl RST VISIT POINTER

LAST VISIT POINTER

TOTAL NUMBER VISITS DATA

TOR NUMBER

Graphic Representation of a Header Record

Figure 6

640
PREVIOUS VISIT POINTER

SUBSEQUENT VISIT POINTER

I

• • •

1 1

V SIT NUMBER

1 DATA

TOR NUMBER

Graphic Representation of a Single Visit Number

Figure 7

64 1
ELEMENT "X

\

DATA 1 DATA 2 DATA N

TOR NUMBER 1 TOR NUMBER 2 TOR NUMBER N

Graphic Representation of a Retrieval File

Figure 0

$42
PREDICTION OF FEMORAL COMPONENT PERFORMANCE THROUGH

IMPLANT RETRIEVAL INFORMATION

H.S. Dobbs

Department of Biomedical Engineering

The Institute of Orthopaedics

Royal National Orthopaedic Hospital

Brockley Hill, Stanmore

Middlesex, HA7 4LP, England

The use of standard actuarial methods for the analysis

of total hip replacement performance is demonstrated by means

of a study of the survival of total hip replacements in patients operated on at the Royal National Orthopaedic Hospital. Two types of Stanmore cobalt chrome molybdenum

prostheses were considered : (1) metal-on-metal prostheses

of various developmental designs inserted between 1963-72

(173) (2) metal-on-plastic prostheses of one design inserted between 1969-72 (248). The survival criterion was

taken to be non-removal of the prosthesis and all cases not removed were regarded as survivors. The results indicate that for metal-on-metal prostheses the overall probability of survival was only 53% after 11 years and the

average annual probability of removal irrespective of cause was 5.5%. As expected, for metal-on-plastic prostheses the

results were considerably better, the figures being 88%

after eight years and 1.5% respectively. For both prosthesis types the predominant failure mode was loosening

and for this failure mode the annual rate of removal

increased as the follow-up time increased, suggesting

that loosening is a wearing-out process. Femoral component

fracture occurred less frequently, but also appeared to

be a wearing-out process. Finally, the advantages of the

survival method as compared with conventional methods are discussed, and it is demonstrated how the analysis can be

used to predict the probability of survival at sometime

in the future.

Follow-up studies of patients having total hip replacements appear

regularly in the literature. Typically these studies are concerned with

the causes of failure, the types of complications and the effects of

various factors on the outcome. These factors may be surgical, clinical

or pathological, or they may relate to the design or manufacture of the

prosthesis. The outcome may be assessed in terms of function, movement

and relief of pain. Usually these studies include statistics, but sometimes these statistics are not as meaningful as they might be, and can

not readily be compared with statistics presented in other studies.

1. Introduction

64 3
Thus for example, in determining the incidence of some failure mode or other only the overall incidence may be given i.e. the number of failures within a certain time period divided by the number in the study.

But how is a two year follow-up to be compared with a four year followup? Moreover sometimes the study is concerned with a group of patients

with varying follow-up periods, in which case the significance of the

overall incidence becomes even less clear.

Fortunately actuarial methods exist for constructing life tables

which enable both the annual and overall failure (or survival) rates to

be determined as a function of time for a group of patients with varying

follow-up periods. These methods are used in other branches of medical

research, for example in studies concerning the survival of patients

suffering from a particular disease. In these studies survival may be

measured from a particular stage in the disease, or from the time when

a particular operation took place. The end-point may be the death of

the patient, or the reappearance of symptoms. Similar methods are used

in engineering applications to study the reliability of components.

Figure 1 shows the time dependence of the conditional failure rate for a typical engineering component. This curve, called the "bathtub" curve because of its shape, is composed of three distinct regions. It can be seen that a failure rate decreasing with time is characteristic of a running-in process, whereas one increasing with time is characteristic

of a wearing-out process (1)1.

annual probability of failure versus time

LU

h-<

Figure 1. Bathtub curve J£<

Li.

TIME

infant mortality ageing

When considering total hip replacements it is the survival of the

prosthesis in situ which matters and for the purposes of the present

study the survival criterion was taken to be non-removal. Survival was measured from the date of insertion to the date of removal and a removal

was considered to have occurred when all or part of the component was removed regardless of whether the component was subsequently reinserted.

The chosen endpoint, namely removal, was perhaps not sufficiently severe,

but it was relatively unambiguous and provided a conservative estimate

of the chances of obtaining an unsatisfactory result. In principle any

Figures in brackets indicate literature references at the end of this

paper.

64 4
endpoint is possible and a more severe but subjective one such as the

onset of pain could have been chosen instead.

Using these methods the survival of more than 400 total hip replacements inserted at the Royal National Orthopaedic Hospital over the

period 1963-1972 was studied. The annual removal rate as well as the

overall survival rate were determined as a function of time. Similarly

the annual removal rate was determined for different failure modes, and

the time dependence of removals due to loosening and fracture was determined. The behaviour of the earlier metal-on-metal (m/m) prostheses was

compared with that of the more recent metal-on-plastic (m/p) ones. Finally the information obtained is used to assess the likelihood of any

given total hip replacement being satisfactory at some time in the future.

2. Clinical and component details

Between April 1963 and August 1972, 173 total hip replacements using

Stanmore metal-on-metal components were done. Sixty-one per cent of the

operations were done by one surgeon, 29% by two others and the remaining

10% by a further ten. A pre-and postoperative antibiotic cover was

given to all the patients and a local antibiotic powder, or irrigation

was used at operation. In most cases the trochanter was detached in the

method recommended by Charnley (2) although in a few cases the posterior approach was used, in which case the trochanter was not detached.

All but one of the femoral components and all but 15 of the cups were

inserted using acrylic bone cement.

Between June 1969 and April 1972, 248 total hip replacements using

Stanmore metal-on-plastic components were done. Eighty-five per cent of

the operations were done by four surgeons and the remaining 15% were

done by a further five. The surgical and clinical details were similar

to those for the former group, although in this group a larger percentage of the operations were done using the posterior approach. Table 1 summarises the insertion details for the two groups.

Table 1 : Insertion details

metal-on-metal metal-on-plastic

No. of insertions 173 248

Type of component Mks 1-5 Mk 6 Insertion date 1963-1972 1969-1972

The metal-on-metal components were Marks 1-5 and articulated on metal cups of various designs. The metal-on-plastic components were

all Mark 6's and articulated on a plastic cup of one design. All the

components were manufactured by one manufacturer using air melt air

cast cobalt chrome molybdenum alloy. Table 2 gives the number of

insertions on a biennial basis. A previous publication gives additional

information including the sex, age and weight of the patients, the

design of the components, and the number of each mark (3).
Table 2 : Number of insertions on a biennial basis

Interval

(Jan-Dec)

Number of m/m Number of m/p

All marks

1963-1964 3 1965-1966 17

1967-1968 103

1969-1970 35 73

1971-1972 15 175

3„ Method

First, the length of the follow-up was determined for each patient.

Since most of the patients in this study were being followed-up routinely

at yearly intervals, their notes were reviewed. If for some reason the

patient had not been seen recently, then a questionnaire was sent. Thus

for each patient the length of the follow-up was determined either from

the notes or from the questionnaire. In this study the final review was

made in March 1979.

Next, the condition of the patient at the time of the last followup was determined. For each patient there were only two possible outcomes, namely removal or "withdrawal". "Withdrawals" consisted either

of patients whose components had not been removed (i.e. they survived) or of patients who had died or who had been lost to the follow-up. Based

on this assessment the required information was obtained from the notes

or from the questionnaire.

Survivorship tab les (modified life tables) were constructed using

the method described in Armitage (4). The following is a brief account

of the method:

(1) The time interval was chosen. In this case a one year interval was chosen since it gave a suitable number of intervals.

(2) The patients were classified according to the time interval during

which their condition was last recorded. Thus a component removed

after fifty months was classified as a removal within the interval

four to five years. On the other hand a component which at the

last follow-up was found to have survived after fifty months, or which was in a patient who died or was lost to the follow-up after

fifty months was classified as a withdrawal within the same interval.

(3) The number of components surviving at the start of each interval was obtained by subtracting the number of removals plus the number

of withdrawals from the number of survivors at the start of the

previous interval.

(4) For any given interval the number of components at risk was obtained by subtracting half the number of withdrawals from the

number at the start : it was assumed for convenience that the withdrawals survive half the interval.

(5) The probability of removal within any interval was obtained by

dividing the number of removals by the number at risk.

GOG
(6)

(7)

(8)

The probability of survival was obtained by subtracting the probability of removal from one. The percentage of survivors after any time period was obtained by

successive multiplications of the probability of survival.

The standard error due to sampling variation in the probability of

removal was obtained using the usual formula.

4.1.

4. Results

Removals irrespective of cause

Tables 3 and 4 give the removal and withdrawal data on an annual

basis for the two groups. From these data the survival tables were obtained using the above method. These tables are not given here, but are included in the articles cited previously (3).

Table 3 : Removals and withdrawals : metal-on-metal

Interval Removals OK's Deaths Losses

(years)

0-1 3 9Z

oo 1-2 5

11 2-3 12 11

"5 J 3-4 9 3

oJ

9z 4-5 8 5

cD z9 5-6 3 6 J

oz 6-7 3 10 1 1 7-8 5 17 3 1 8-9 2 11

9-10 1 12 1 10 - 11 1 3 1 11 2 7 1

Total 54 74 22 23

4 : Removals and withdrawals : metal--on-plastic

Interval Removals OK's Deaths Losses

(years)

0-1 4 4 19

1-2 3 2 2-3 1 4 3-4 2 1 1 4

4-5 4 18 2 5 5-6 2 42 2 6-7 1 82 2 7-8 1 39 2 8-9 1

Total 15 183 16 34

647
a) Overall probability of survival as percentage versus

time since operation in years

Figure 2. Survival of

metal-on-metal total

hip replacements

Figure 3. Survival of

metal-on-plastic total

hip replacements

YEARS

b) Annual probability of removal as percentage versus

time since operation in years

YEARS'

a) Overall probability of survival as percentage versus

time since operation in years

50

15 YEARS

b) Annual probability of removal as percentage versus

time since operation in years

YEARS

648
From the tables, figures 2 and 3 were obtained which show the overall probability of survival and the annual probability of removal for

the two prosthesis types. It can be seen that for metal-on-metal prostheses the overall probability of survival was 53% after eleven years,

i.e. almost one in every two prostheses was removed within this period.

The average annual probability of removal was 5.5%. For metal-on-plastic

prostheses the figures were 88% after eight years and 1.5% respectively.

It can be seen from figures 2 and 3 that for both metal-on-metal and

metal-on-plastic prostheses the annual failure rate was approximately

constant (independent of time) and this observation was confirmed by more detailed statistical analysis. For the metal-on-metal case however the

evidence for a constant failure rate was stronger if the first two postoperative years were omitted. Thus there was a suggestion that the

failure rate increased over the first two years and then reached a constant values of 6% thereafter. There was also a suggestion that for

both cases the failure rate increased after very long follow-up times as the consequence of a wearing-out process, but the evidence was insufficient to be sure about this.

4.2. Removal according to cause

Table 5 shows the cause of removals for both metal-on-metal and

metal-on-plastic removals. It can be seen from the table that the

majority of components were removed for looseness (78% for metal-on-metal

and 60% for metal-on-plastic)

Table 5 : Cause of removals

Cause Metal-on-metal Metal-on-plastic

number number

Loose 42 9

Dislocated 2 3

Infected 4 -

Broken 3 2 Other 3 1

Total 54 15

Because looseness was the predominant failure mode it was investigated

in further detail (3). It was noted that for the metal-on-metal failures

it was the cup which was loose in the majority of cases, presumably due

both to the method of fixation and to high frictional torque, whereas

for the metal-on-plastic failures it was the stem. The time-dependence

of loosening was studied by constructing life tables as before. Figure

4 shows the behaviour of the annual failure rate, in this case using a two year time interval. There was a suggestion for both metal-on-metal

and metal-on-plastic prostheses that the rate increased with time. This

result is consistent with the view that loosening is related to the

mechanical breakdown of interdigitations between acrylic cement and bone

(5,6).
Annual probability of removal for loosening as percentage

versus time since operation in years

metal-on-metal

Figure 4.

<

UJo

Annual probability of femoral component fracture as a percentage versus time since operation

in years.

metal-on-metal and metal-on-plastic combined.

10 -

Figure 5.

g 05 <

LUO

crLUa

5YEARS

10

As regards other failure modes little can be said on account of the

relatively small numbers involved. It was evident, however, that removals

due to dislocations and due to infections tended to occur early on. The

time dependence of the fracture rate was determined as shown in figure 5 by combining the data for the two groups giving a total of five fractures.

Although the data is too scanty to permit any firm conclusion to be drawn

G50
the trend suggests a wearing-out process consistent with the view that

the components fail by metal fatigue (7,8,9).

5. Discussion

To determine the validity of the chosen survival criterion, the

patients were asked either at follow-up or by means of the questionnaire

to give an assessment of their total hip replacement. For patients whose

components had not been removed most were satisfied with their result,

had little or no pain and were sufficiently active to cope with their

daily needs. At least 90% of patients with metal-on-plastic joints fell

into this category, and many were more active. On the other hand, for

both types of joint there were a very few cases in which the component

had not been removed even though there was considerable pain. These

results, therefore, suggest that the survival criterion gave a reasonable but conservative estimate of the chances of having an unsatisfactory

result.

As Armitage points out, two important assumptions underlie these

life table calculations. First, it is assumed that the withdrawals are subject to the same probabilities of removal as the non-withdrawals.

This is a reasonable assumption for withdrawals who are still in the

study, but it may be a dangerous assumption for those who were lost to

the follow-up, since failure to be followed-up for any reason may be

related to the condition of the prosthesis. Secondly, the various values

of the annual probability of removal are obtained from patients who

entered the study at different points in time and it must be assumed

that these probabilities remain reasonably constant over time.

In order to assess the magnitude of the error introduced by the

first assumption the number of patients lost to the follow-up was determined. As shown in tables 3 and 4 there were 23 (13.3%) in the metalon-metal study and 34 (13.7%) in the other. Because these percentages

are small one can be reasonably sure that the resulting error is small.

To verify this, one may calculate the worst possible probability of sur- vival by assuming that all these losses resulted in removal, in which

case the following values would be obtained : for metal-on-metal 45%

instead of 53% and for metal-on-plastic 76% instead of 88%. These

values demonstrate that the error is small and emphasise the need for as complete a follow-up as possible. To assess the error introduced by the

second assumption it was noted that for both studies the majority of

insertions fell within a four year period (see table 2) . Since this is a relatively short time, and since the majority of the operations were

done by only a few surgeons one can be reasonably sure that the resulting error is small. In addition, because the two types of prostheses

were being inserted concurrently by the same surgeons one would expect

that errors due to the second assumption would not invalidate a com- parison.

It is interesting to compare the value of the overall probability

of removal (one minus the overall probability of survival) obtained

using survival methods with that which would have been obtained by con- ventional statistics. Using survival methods the values obtained were

47% for metal-on-metal after 11 years and 12% for metal-on-plastic after

65 I
eight years, whereas had the results been obtained simply by dividing

the number of removals by the number of insertions the values would have

been 31% and 6% respectively and had losses and deaths been deducted,

42% and 8%. Thus, it can be seen that conventional methods provide a more conservative and less accurate estimate than obtained by survival.

This is true in all cases where there are losses and where the insertion dates vary.

To predict the survival probability at some future time, say after

a twenty year period, the curves in figures 2 and 3 can be extrapolated.

In this manner the median survival time can be obtained from the intercept at the 50% level:

metal-on-metal, median = 11.8 years

metal-on-plastic, median = 34.5 years

Alternatively, since the observed annual failure rate is approximately

constant, and since a constant failure rate implies an exponential distribution of failure times, an exponential model can be used instead,

i.e.

P = 1 - e

where P is the overall probability of failure, t is the time after which

the failure probability is to be predicted and X is the value of the

constant failure rate, determined from the data. For this model it is

easy to show that the mean lifetime is l/\ , and the probability of

survival after any time period can be obtained using the above formula.

Thus, using the values of X obtained previously, namely 5.5% and 1.5%,

the following values were obtained for the probability of survival after

twenty years:

metal-on-metal, probability = 33%

metal-on-plastic, probability = 74%

Both these methods of predicting future trends have the same disadvantage, namely they presuppose that past behaviour will be manifest in the

future. Thus, neither method allows sufficiently for ageing or wearingout processes and both fail to take into account the possibility that

failures due to loosening and fracture may occur with even greater frequency after longer follow-up times. Consequently, although both methods

demonstrate the type of predictions that can be made, these particular

predictions must be treated with caution.

I am grateful to the following for their assistance: James Roger,

Department of Applied Statistics, Reading University; Professor J.T.

Scales and the members of the Department of Biomedical Engineering,

Institute of Orthopaedics; Mr. J.N. Wilson and those surgeons at the

Royal National Orthopaedic Hospital whose cases I reviewed; the staff of

the Medical Records Departments; and the patients who returned questionS52
naires. The work was supported by funds made available by the Department

of Health and Social Security, contract number R/E1049/39 STS B5.

References

(1) Cox, D.R., Renewal Theory , Monograph on applied probability

(Methnen, London, 1962).

(2) Charnley, J. and Ferreira, A., Transplantation of the greater

trochanter, Journal of Bone and Joint Surgery, 46B , (2), 191-197

(1964).

(3) Dobbs, H.S., Survivorship of total hip replacements, Journal of

Bone and Joint Surgery, 62B , (2), 168-173 (1980).

(4) Armitage, P., Statistical Methods in Medical Research , 408-414

(Blackwell, Oxford, 1971).

(5) Homsy, C.A., Some mechanical aspects of methylmethacrylate prosthesis seating compound, The Hip, Proceedings of The First Open

Scientific Meeting of the Hip Society , 156-163 (C.V. Mosby, St.

Louis, 1973).

(6) Evans, E.M. et al, Metal sensitivity as a cause of bone necrosis

and loosening of the prosthesis, Journal of Bone and Joint Surgery,

56B , (4), 626-642 (1974).

(7) Dobbs, H.S., A model to predict the incidence of fracture in

femoral components, Journal of Bioengineering, 1_, (3), 189-196

(1977).

(8) Dobbs, H.S., The incidence of fracture in total hip replacement

femoral components, Engineering in Medicine, _7, (2), 107-110 (1978).

(9) Dobbs, H.S., The fracture of femoral components - an act of God?,

Engineering in Medicine, 8, (4), 237-240 (1979).

653

LEGAL AND REGULATORY IMPLICATIONS OF IMPLANT

RETRIEVAL AND ANALYSIS

Henry R. Piehler^

Duke University

Department of Mechanical Engineering

and Materials Science

Durham, NC 27706

Lewis E. Sloter II Vought Corporation

Advanced Technology Center

Dallas, TX 75266

Implant retrieval and analysis can provide valuable

input into the decisions made by our courts and regulatory agencies. The procedures used by these bodies in

reaching their decisions, however, often place restraints

on the ways in which the retrieval and analysis are performed in the first place. Implant retrieval and

analysis is but one method by which risk reduction can

be accomplished, i.e., the development and utilization

of a clinical and/or device-related data base. The

polling of experts and fault/failure analyses are viable,

even preferable, alternatives to achieve expeditious

risk reduction in certain situations. A threshold question which must be answered by any court or regulatory

agency prior to a compensatory or regulatory decision is

whether a device flaw (production or design) did indeed cause the failure or malfunction. Procedural modifications to liability trials and regulatory enforcement which

respond to this threshold question are described, as are performance evaluation procedures which follow from the answer to this question. Laboratory fatigue data and

results from litigated cases are introduced to indicate

that risk reduction can expeditiously be accomplished

through performance testing, and conformance to the performance standards can reduce or eliminate liability

exposure.

1. Introduction

Implant retrieval and analysis has been and continues to be a valuable tool for reducing risks to patients, by pointing to modifications

either in clinical practice or device design or manufacture. Surgeons,

Present mailing address: Department of Metallurgy and Materials Scien

Carnegie-Mellon University, Pittsburgh, PA 15213.
manufacturers, and the academic community have all been involved in

both retrospective and prospective implant retrieval and analysis,

which constitutes the principal voluntary private sector effort at

reducing risks to patients. Our country has two additional pluralistic checks to ensure that patients are not subjected to unreasonable

risks stemming from the use of implants: the courts and the Bureau

of Medical Devices (BMD) of the Food and Drug Administration. The

courts function primarily to compensate patients who have suffered

damages resulting from past deficiencies in an implant or its utilization. The BMD, on the other hand, attempts to prevent future

damages to patients by imposing various forms of regulation to reduce

or el iminate ri sks.

A thorough failure analysis of a retrieved implant is the key to

responsive medical device and/or malpractice litigation. In order to

reach its conclusion, a court must not only explore the mechanism of

failure but, more importantly the cause or source of failure. If

the alleged device flaw is its inherent design, then statistical information concerning the performance of this device compared to

alternate devices would be highly significant in showing that the

present design is defective. If, on the other hand, the device is

flawed in manufacture, i.e., it deviated from the manufacturer's

specifications, then statistical information concerning the performance of an unflawed device is still useful in showing that an unflawed

device would not have failed under the same service conditions. However, in either a design or a production defect case, it must be shown

that the flaw caused the failure or malfunction. It is important to

note that, unlike for most adverse reactions involving drugs, for

example, detailed causal inferences can often be drawn from a careful

examination of only one failed device and its related clinical information.

The same requirements for establishing causal links between device flaws and failures are essential for responsible regulation by

the BMD. Unlike the courts, the effort of the BMD is seldom heavily

focussed on the failure of a single implant. Its principal goal is

to reduce unreasonable risks to implant recipients as a class. Hence

the BMD is at the first level principally concerned with the incidence of failure(s). However, incidence-of-fail ure data must be

supplemented with sufficient determinations of the sources or causes

of failure before an appropriate regulatory intervention procedure

can be developed and implemented.

The use of implant retrieval and analysis to develop and use a clinical and/or device-related data base for patient treatment is but one means by which risk reduction can be accomplished. These same data may be useful in developing a performance test to rank existing

or new materials and/or devices. Various fault/failure analysis procedures are also often valuable to reduce risks, particularly at the

design and development stages. Finally, polling of experts may also

be used in certain situations to reduce risks especially where data

are scarce and decisions must be made immediately.

65 6
After amplifying the material described above, specific recom- mendations for the use of implant retrieval and analysis in responsive litigation and regulation will be presented.

2. Risk Reduction Procedures

As mentioned in the Introduction, there are three principal types

of procedures for risk reduction. These are based upon

p 1. Clinical and/or Device-Related Data Bases [1]

2. Fault/Failure Analysis Procedures [2]

3. Polling of Expert Opinion [3]

Polling of expert opinion is often the only resort if data are

not currently available, and cannot be acquired in time to avoid a potentially hazardous situation which must be dealt with almost immediately. In a sense, juries are asked to evaluate or poll expert

testimony in medical device and/or malpractice cases. Very often

causation questions involved with device failure can be addressed only

by seeking expert opinion, possibly assisted by modelling, analysis,

and some simulative testing. Unambiguous usage data are typically

not available to answer with certainty questions such as whether an unflawed device would not have failed under conditions similar to

that causing failure in a flawed device. Since expert opinion is

based so highly upon an individual's training and experience, it is

the most difficult risk reduction procedure to ventilate for public

scrutiny. In order to help evaluate expert testimony, ASTM Committee

E-40 on Technical Aspects of Products Liability Litigation has developed E-620-77, "Standard Practice for Reporting Opinions of Technical

Experts". Similar standard recommended practices for evaluation of

technical data and examination and tests of items that are or may be- come involved in products liability litigation are expected to be

issued shortly.

Fault/failure analysis procedures were developed and refined by

the aerospace industry. These procedures are especially useful for

evaluating the reliability of complex systems. These procedures are generally divided into two categories:

1. the functional fault/failure analysis (often referred to

as the "top down" or "system" approach)

2. The hardware faul t/ failure analysis (often referred to as the "bottom up" or "hardware" approach)

The first approach is particularly useful during the design stages,

where individual hardware items have not been specified. The second

is especially useful in isolating and examining the consequences of

the failure of individual hardware items. Both of these approaches

Figures in brackets indicate the literature references at the end of

this paper.

G57
are strengthened by the subsequent use of a criticality analysis,

which focuses on the expected frequency of occurrence of particular

failure modes as well as their effect on system performance.

Clinical and/or device-related data bases are most useful in

evaluating the effectiveness of alternate treatment procedures for

chronic or long term conditions. In fact, a period of years is

typically required to generate a data base which is adequate for use

in evaluating alternate treatment procedures, since data from a sufficiently defined subset of patients similar to the patient at

hand must be available. Causal connections are most often inferred

when using statistical data bases, and, as will be shown subsequently,

such inferences may lead to inappropriate remedial measures. It should also be pointed out that the development and use of performance

tests based on clinical and/or device-related data bases is an alternate means for risk reduction. These two alternate means to risk

reduction are illustrated in figure 1.

Clinical and/or

Device-Related

Data Base

Infer Causal Patterns

Develop Performance Tests

Reduce Risks

Figure 1. Paths by which data bases can be used to reduce

risks to patients.

3. Current Status of Product Liability Litigation System

The apparent upsurge in the number of product liability cases filed annually during the last 15 years has been attributed both to an increase in consumer awareness and some fundamental changes in product

liability law itself. The basis for recovery is now primarily based

on the doctrine of strict liability, which examines the performance of

the product itself, rather than negligence, which focuses on the behavior of the manufacturer. Strict liability has been enunciated in

Section 402A of the Restatement (Second) of Torts (1965) as

(1) One who sells any product in a defective condition un- reasonably dangerous to the user or consumer or to his

property is subject to liability for physical harm thereby

caused to the ultimate user or consumer, or to his property

if

658
(a) the seller is engaged in the business of selling such

a product, and

(b) it is expected to and does reach the user or consumer without substantial change in the condition in which

it was sold.

(2) The rule stated in Subsection (1) applies although

(a) the seller has exercised all possible care in the

preparation and sale of his product, and

(b) the user or consumer has not bought the produce from

or entered into any contractural relation with the

sel ler.

The application of Section 402A to production defect cases has

produced no substantial difficulties. Its use in design defect cases

has been much more troublesome, however, especially in those states

which have removed the "unreasonably dangerous" criterion for defectiveness. This continuing uncertainty in the basic tort law is one of the factors cited by the Interagency Task Force on Product Liability

[4] as contributing to the current "product liability crisis". The

other two factors are

• questionable insurance rate making practices

• defective products themselves.

The last several years have witnessed the introduction of scores

of state and federal product liability statutes directed at either in- surance or tort reform. The plaintiff's bar has argued vehemently that

what are reported as losses by insurance companies include not only

payments to claimants, but reserves for known claims, and even reserves

for claims incurred but not reported (IBNR). As has been pointed out

earlier [5], however, these reserves are necessary in insuring a product,

since, unlike automobile insurance which is paid annually, product

liability insurance is paid only once in the year the product is manufactured, yet must be sufficient to pay for claims during the entire

lifetime of the product. Representatives of the insurance industry have

been trying to explain this accounting procedure in their arguments,

yet lacked sufficient data to substantiate their position. These representatives point instead to the rapidly rising number of product liability cases (one source estimated one million annually) and the rapid

rise in the size of awards as the primary reason for the "product

liability crisis". This number, however, is at least an order of

magnitude too high [5J. As the title of reference 5 suggests, this

crisis is indeed a crisis of uncertainty, especially since no one can

say with any degree of certainty whether specific insurance reform

proposals will reduce rates or whether tort reform measures will weed

out what are perceived as nonmeri torious cases.

659
Several insurance and tort reform bills have been passed

various states. Since no two of these bills are identical, substantial

nonuniformity is being introduced in our country, creating enormous difficulties for those engaged in interstate commerce. The federal

government has attempted to alleviate this nonuniformity by developing

legislation of its own. The Risk Retention Act, H.R. 6152, was passed

by the House on March 10, 1980. A companion bill, S.1789 is still

pending in the Senate. 3cth these bills would allow, under the

cirec.i:'" : -~ - r,e Ie?=rtment of Commerce, "risk retention" groups to

be formed for the purpose of group purchase of product liability . The "Model Uniform Product Liability Act" [6] which was offered by

the Commerce Department for voluntary 'Jse by the states, has, however,

been introduced as H.R. 5976 in the House, where it is still pending.

The "model" law covers: basic standards of responsibility, un- avoidable defects, relevance of the state of the art and of compliance

with standards, requiring notice of possible claims, statutes of re- pose, alteration/modification :.. third parties, relevance Df user's

conduct, multiple defendants, the relationship of product liability and

workers' compensation, responsibilities of sellers, sanctions against

bringing frivolous claims and defenses, arbitration, expert •ntnesses,

non-economic losses, the collateral source rule, and punitive damages.

4. Regulation by the Bureau of Medical Devices

With the enactment of the Medical Device Amendments of 1976, the

FDA was empowered to regulate medical devices as well as drugs according to the level of risk which the device presents. The history of

device regulation prior to 1976 has been reviewed elsev/here [7]. This

regulation is accc~:" i s^ed by categorizing devices into one of three

classes

:

Class I. General Controls, which include regulations concerning

good manufacturing practice and fraudulent mislabeling.

Class II. Performance Standards, which must be met to reduce

device risks to an acceptable level.

Class III. Premarket Approval, for those devices for which performance standards cannot reduce device risks to an acceptable level .

The decision as to which class is appropriate is made by the Bureau

of Medical Devices on the basis of recommendations from a classification

panel, which reaches its decision on the basis of existing data and

polling of expert opinion. To date, the Orthopedic Classification Panel

has placed the vast majority of orthopedic implants into Class II,

Performance Standards.

Recognizing the enormity of the task involved in developing such

a large number of performance standards, the BMD published a proposed

6 SO
"Voluntary Standards Policy for Medical Devices; Request for Comments"

[8] on February 1, 1980. This procedure would have the FDA endorse

voluntary standards which meet its "Criteria for Endorsement of Voluntary Standards." If an industry complies with such an endorsed

standard, then the FDA might defer establishment of a mandatory

standard.

Comments from the Pharmaceutical Manufacturers Association (PMA)

£9] question whether this type of endorsement is indeed permissible

under existing statutes. Their principal argument against such an en- dorsement is that this procedure essentially bypasses the detailed

procedures for the promulgation of standards by the BMD, primarily

because this endorsement fails to provide an opportunity for comment

and does not provide for the creation of an administrative record.

PMA urges that the BMD proceed instead with the promulgation of performance standards under their current mandate, possibly using existing

voluntary standards as proposed performance standards.

The BMD has a continuing interest in clinical and/or devicerelated data bases in carrying out its regulatory mandates. As described in this volume, there are currently several such data bases being

created. There is, however, substantial nonuniformity among these data

bases. ASTM Committee F-4 on Medical and Surgical Materials and Devices has responded to this need for uniformity by promulgating F-561-

78, "Standard Practice for Retrieval and Analysis of Metallic Surgical

Implants." There was some suggestion that the ASTM might act to aggregate data based upon a compilation of these completed recommended

practices. To date, however, not a single such recommended practice

has been forwarded to the ASTM. Hence it is clear that these data bases

will not emerge spontaneously, but must be developed by people or groups

with a continuing self interest and need to use the data bases.

Since the development of these clinical and/or device-related

data bases is at least partially funded from federal sources, the question of accessibility to the data base via the Freedom of Information

Act (FOIA) naturally arises. The latest opinion on this point [10] is

that, if data are requested and received by an agency, then these data

become part of the agency's record and are discoverable under the FOIA.

If, on the other hand, an agency has not requested or received such

data, they are not compelled to ask the contractor for these data on the basis of an FOIA request. One wonders, however, whether requests

for data will not now become routine with agencies, or whether the

terms and cost of a contract will reflect who has access to these data

bases.

5. Technical Causation: The Core Concern

The authors have previously urged [11] that medical device or com- bined medical device and malpractice litigation should focus on the issue

of technical causation, i.e., establish the direct causal relationship

between a flaw and a failure or malfunction. The initial concern for

60 I
combining medical device and malpractice litigation was that the two

theories; one based on product performance, the other on a surgeon's

behavior; were fundamentally incompatible. This concern turned out to

be specious, however, in light of the fact that a surgeon and other

medical personnel constitute a vital link between the device manu- facturer and the patient. To ignore this link would not provide an adequate examination of the medical device in the environment of its

actual use. It was thus concluded that it is imperative to include

clinical descriptions and evaluations even in a case based solely on product liability, since the clinical performance might contribute to or solely cause the failure or malfunction of the medical device.

The entire seriated trial for a products liability case involving

a medical device is shown diagramatically in figure 2. Both clinical

and/or device-related technical causation answers are clearly admitted.

If the technical causation question is answered affirmatively, then the

injury causation question as to whether the malfunction caused the

injury would be asked. If this question is answered affirmatively,

the plaintiff would establish liability.

A causation-based record keeping system has also been proposed for

use either by the BMD [7] or by a voluntary private-sector organization [12] to provide for responsive standardization and/or regulation.

There appears to be some progress being made to aggregate the various

private-sector clinical data bases to respond to this need. It is

important, however, to recognize that causal patterns can often be determined more rapidly and accurately by focussing on failed devices in

addition to clinical histories.

6. Recommendations for the Use of Implant Retrieval and

Analysis in Responsive Litigation and Regulation

A structured causation-seeking approach such as is embodied in the

seriated trial would enhance the quality of any liability or regulatory

decision. Amassing frequency of failure data alone, even after drawing

statistical inferences, can lead to inappropriate remedial actions. For

example, it was shown in reference [13] that, while fretting corrosion

was observed in the proximal screw-hole countersinks, this fretting

corrosion often did not initiate the corrosion-fatigue failure. A causal

inference would undoubtedly be drawn on a statistical basis as a result

of the mere conjoint appearance of fretting and fatigue-crack initiation

at the proximal screw-hole countersink. The natural tendency would be

to try to alleviate fretting, but this would have no effect on those devices for which the fatigue fracture was not fretting initiated.

It is also apparent that laboratory performance tests, based on implant retrieval and analysis experience, are also useful tools for device

improvement and lessening of the burden of litigation and regulation of

the manufacturer as well. For example, the simulated corrosion-fatigue

device performance test described in reference 13 was used to test Jewett

nails of identical design fabricated from both 31 6L stainless steel and

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Ti 6A1 4V. The results of these tests are shown in figure 3 in the form

of cyclic load applied at the end of the nail versus number of cycles to

failure [14].

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steel and Ti 6A1 4V Jewett nails tested in Ringers solution.

The difference in performance of these devices is striking and certainly

suggests that Ti 6A1 4V should be given serious attention as an implant

material. Since loads applied to retrieved implants are virtually un- known, this superior performance of Ti 6A1 4V, if it translates into

improved in vivo performance, would have taken years to observe from

analyses of retrieved implants.

Whereas the authors recognize that this corrosion-fatigue performance

test does not simulate every aspect of i n vivo performance, it nevertheless appears to be a valuable initial step. Since the test is new and

not widely proven, its adoption by the BMD as a performance standard is

premature, if appropriate at all. However, its adoption as a regulatory

guideline seems to make sense to us. In fact, many of the standards

6G4
already in existence would appear to be prime candidates for recognition

as regulatory guidelines. It would appear to us that prudent manufacturers would adhere to these guidelines, and this procedure would circumvent the difficulties involved with the endorsement of standards or mandatory performance-standard development.

Even if such regulatory guidelines were universally utilized, the

question still remains as to their persuasiveness in product liability

litigation. One can get some insight into the relationship between

product standards and litigation experience by examining what happened

with children's flammable fabrics litigation after the 1953 Flammable

Fabrics Act was amended [15]. The incidence of litigation based primarily on children's sleepwear began rising with the advent of strict

liability, even though this sleepwear conformed to the then existing

mandatory federal standard. After these standards were made more

stringent in 1972 and 1975, the number of product liability claims

dropped virtually to zero, as has the incidence of serious burns from

conforming sleepwear. The lessons from this experience are quite simple:

Courts will continue to attack standards, even mandatory federal standards, if these are shown

to be societally unacceptable

Any standard which reduces risks to users reduces

the incidence of product liability litigation,

regardless of the degree of blessing conferred

upon the standard by the federal or any other

government.

It is recognized that the potential for such a drastic risk reduction stemming from the use of implants is unlikely, largely because it

is widely accepted that the vast majority of implant failures are clinical rather than device-caused. However, if a standard does nothing more

than clarify the magnitude and nature of the clinical contribution to a device failure, the recognition of and response to this clinical information can reduce risks to patients as well.

GG5
References

1. Rosati, R. A., McNeer, J . F. , Starmer, C. F., Mittler, B. S. s Morris, J. J., Jr., and Wallace, A. G., A new information system

for medical practice, Arch. Intern. Med. 1_35 1017-1024 (1975).

2. Fault/failure analysis procedure, ARP 926A, Society of Automotive

Engineers, Inc., Warrendale, PA.

3. Middendorf, W., A modified del phi method of solving business problems, IEEE Trans, on Eng. Management, EM -20 [4], 130-133 (Nov.

1973).

4. Final report of the federal interagency task force on product

liability, NTIS, Springfield, VA (Nov. 1977).

5. Product liability tort reform: crisis of uncertainty, Dept. of

Eng. and Public Policy, Carnegie-Mellon Univ., Pittsburgh, PA

(May, 1979).

6. Model uniform product liability act, 44 FR, 62714-62750 (Oct. 31,

1979) .

7. Piehler, H. R., et al . , Regulating orthopaedic surgical implants,

Orthopaedic Rev. VII, [1], 75-81 (Jan. 1978).

8. Voluntary standards policy for medical devices; request for com- ments 45 FR, [23], 7490-7493 (February 1, 1980).

9. Comments by Pharmaceutical Manufacturers Association, letter to

Hearing Clerk (HFA-305), April 29, 1980.

10. Peter H. Forsham, et al . , Petitioners, v. Patricia Roberts Harris,

Secretary of HEW, et al., No. 78-1118, 48 LW, 4232-4238 (March 3,

1980) .

11. Sloter, L. E., and Piehler, H. R., Combined medical device and malpractice litigation: conflict or imperative?, J. Prod. Liab. 2_, 165-185 (1978).

12. Piehler, H. R., Epilogue, Orthopaedic Rev. V_n [7], 108 & 110

(July, 1978).

13. Sloter, L. E., and Piehler, H. R., Corrosion-fatigue performance

of stainless steel hip nails - Jewett type, in Corrosion and Degradation of Implant Materials , ASTM STP 684, 173-195 (1979).

14. Personal communication, Marc Portnoff, Carnegie-Mellon University

(May, 1980).

15. Personal communication, Association of Trial Lawyers of America,

Washington, DC (July, 1979).

ess
WORKSHOP ON IMPLANT RETRIEVAL PROGRAMS

Prologue

On Saturday morning, following the Implant Retrieval Conference,

a small workshop was held to discuss implant retrieval. The attendees

were all invited participants actively involved in implant retrieval

and analysis programs. The objectives of the workshop were to air the

current problems and protocols to see if we could begin to move toward

a national system(s) for gathering, analyzing and pooling data. The

morning was organized with two hours for simultaneous meetings of an orthopaedic group and a cardiovascular group. These two groups reconvened for a one hour final session. It is the proceedings of the joint

session that are herein reported along with relevant appended material.

The orthopaedic section was chaired by Stanley Brown with the

assistance of Steven Gordon. The cardiovascular section was chaired

by Donald Gibbons with the assistance of Frances Pitlick. Without

their thoughts and efforts, these workshop sessions would never have

taken place so successfully.

Stanley A. Brown, Workshop Chairperson, May, 1980

6G7
Summary of Orthopaedic Group Proceedings

CHAIRPERSON BROWN: To begin and bring this session to order as a joint reporting session of the two groups, I would like to announce

that the proceedings from this hour will be published in the Conference

proceedings book. What I would like to do first is give you a brief

summary of what we think came out of the orthopaedic group workshop

and ask Don Gibbons to similarly report on the results of the cardiovascular group workshop. I would then like to discuss several subjects

which I think are common areas of interest which we did not discuss

in the orthopaedic workshop. They are problems of: 1) who is going

to fill out necessary forms, 2) patient confidentiality, and 3)

issues that pertain to the legal aspects of this particular problem.

Being common problems, we did not pursue this discussion in the

previous group session.

The orthopaedic group met, and started out by discussing the

kinds of information that we want to gather in implant retrieval and

analysis programs, the forms that can be used, and the methods of

storing and handling this information. It was felt that, first of

all, there have been several papers presented at the meeting that

provided us with some starting points in terms of methods, protocols

and forms. Secondly, the feeling was that we should look toward the

next meeting of the ASTM committee F-4 on Medical and Surgical Materials

and Devices for reconvening. The committee meets in Denver in the

middle of this month, and we intend to have a second working session

on this subject there.

The starting point for our discussion today was the problem of

clinical information retrieval; what sort of information do we need

to obtain concerning the patient, and concerning the clinical perfor- mance of the device. Secondly, we addressed materials issues, and

thirdly, biological issues. One of the things that came out early in

the discussion was that if we are to have effective forms for asking

these questions, then sections of these forms should be prepared by

the specialists of that particular area. The clinical forms should

be written in the clinician's language; the materials form should be

written in the language of the material scientist; the biologist or pathologist should be involved in the preparation of the questions

concerning the histologic evaluations of performance.

Four documents for implant retrieval and patient analysis were presented during the Conference. They were the total hip system from

Northwestern, the program from Tulane, the plate study from Dartmouth

and the AO/ASIF, and the clinical protocol from Stanford. Two additional protocols were presented to the orthopaedic workshop: one for

hip prostheses from Case Western, and one for knee prostheses from

the Hospital for Special Surgery. Starting with these, I agreed to

"cut-and-paste" all the sections that are in those forms now and com- bine them en masse according to the different ways of asking the same

6 G 8
question (e.g., the level of activity of the patient). Different

people are asking these questions different ways. There may be a way

of combining them so that we can all ask the question the same way,

all provide the same kind of answers, and hence can produce a common

data base that we can pass from institution to institution. Then,

when we read someone's publication, we can all understand what they

are saying.

This large core of data will hopefully be available for the

coming F-4 meeting and will be included in the published proceedings

of this workshop. Thus, as the first step, we will have all of these

ways of asking questions down on paper, on record, and then we can

begin to look at how we want to refine them so that we have a more

concise document.

The group's feeling in terms of this large compendium was that

there is a core set of data that we should all be gathering, which

will be a subset of the entire document. The rest of the document

will have types of data that are specific to the different types of

studies that are being done. Some people are looking at one aspect;

some people are looking at others. The implication is not that

the entire form be filled out, but that the entire form will provide

a standardized set of questions, a standardized way of gathering

data; then we will simply extract those pieces of the data that we

want for our own studies.

The reason for heading in this direction is to look toward the

compilation of a national data pool. At the recommendation of Dr. Horowitz, we have been advised to contact Dr. David Lide at the

National Bureau of Standards, concerning the National Standards Data

Reference System which is an ongoing and funded system for generating

national data pools in numerous other areas. It was the feeling of

the group that if we can approach NBS and present a statement of need

for compiling this data, then we might be able to get financial support and technical and organizational assistance. We also were told

I by a number of the industrial representatives that we should look to

j the industrial commercial sector for some financial assistance in

; these efforts as well. Concerning the technical details that we were

able to address in the two-hour meeting, there were three papers presented yesterday and the day before specifically concerning the

evaluation of corrosion at contact areas between bone plates and bone

screws. Starting with this because I felt it was something we could

actually come to terms with, the subsequent discussion generated the

feeling that the concept of a two-part scheme where we evaluate the

[size of the contact area and the degree of attack of the contact area

is one that we could work into a fairly common language. To address

this, a number of us will try to develop a standard set of photographs,

probably scanning electron micrographs, similar in concept to the

ASTM grain size (E-112) and inclusion charts (E-45) which we can then

all have and use to make comparisons during the microscope examinations

of a particular contact area. Thus, we can then begin to quantify and

GG9
standardize our evaluations. The next step of how deep the corrosion

attack is becomes more difficult. I think with the generation of the

photographs, which probably will be ultimately turned into drawings

so that they will reproduce better, will give us a starting point.

This, I think, is one area where we can begin to move forward directly.

The next area which we looked at, and in many respects may be

the more important one, concerned the evaluation of prostheses such

as total hips, hemiarthroplasties, total knees, in terms of what we

see as evidence of wear and degradation. There is a need to develop

the same kind of standardized reference charts or reference codes to

take these currently, very subjective, evaluations and try to make

them objective and quantitative so that we can generate data and put

them into a computer in common language.

I want to reemphasize that one of the most important aspects in

which I think we have succeeded at our meeting is that of communication. This must be on an institutional level, on a national level,

and ultimately on an international level. It must be between three

groups: the surgeons, the biomaterial scientists and bio-engineers,

and surgical pathologists. Fortunately, we had a surgical pathologist,

Jim Anderson, with us today who described what can happen in an institution where the surgical pathology department is interested and

involved. Jim has agreed to help further by way of communication and

advertising so that perhaps we can begin to get more of this three-way

effective communication.

Finally, there were twelve groups that expressed an interest in

active participation in the development of these forms and moving

further toward standardizing our evaluation of orthopaedic implants.

These were the groups from Northwestern, Taussig Associates, Johns

Hopkins, Hospital for Special Surgery, the University of Utah,

Howmedica, Tulane University, Stanford, Zimmer U.S.A., the FDA, Case

Western, NBS Materials Science Center, and my own group.

That concludes the summary from our group meeting. Are there

any discussions from the floor concerning my report? Anything that

the people who were in attendance feel I left out? The floor is open

for discussion.

MR. WEISMAN (Howmedica): There was a reference made in the

meeting to the fact that the information should also reflect the success rate in the use of the devices as well as some of the problems

relating to what we have been discussing for the past several days.

I think this is a very significant issue. In some way, the total user population has to be considered.

CHAIRPERSON BROWN: Agreed; we must not simply compare removed

implants, but must, in fact, try to find out why they are removed

and compare them with those that are currently performing well. We

thus may find out why those that are doing well are doing well and why

those that are explanted are being explanted. It is a good point.

670
Any further discussion? If not, then we will next hear from the

second group that met this morning.

Cardiovascular Group

CO-CHAIRPERSON GIBBONS (Case Western Reserve University): I, together with Dr. Frances Pitlick (NHLBI-DBT) chaired the session on cardiovascular implants. The report which follows represents a summary

of the deliberations of this session which consisted of a group of 22

biomedical scientists, surgeons and pathologists who were actively

engaged in cardiovascular device retrieval.

After a preliminary discussion, the group divided into two subgroups; one addressing the problems associated with heart valve implant retrieval, and the other vascular graft retrieval. The specific

objective of the discussion groups was to identify the types of data

required for evaluation of implant performance and possible modes of

failure; to discuss the availability of protocols for retrieval of

natural or man-made heart valves and grafts from man and from re- search animals; and to make recommendations for future actions.

First, the stages of implant history were defined:

i) surgical implantation

ii) clinical followup

iii) explantation (at surgery or autopsy)

iv) analysis of retrieved implant,

hi stopathol ogy , engi neeri ng/materi al

Stages (i) and (ii)

Both valve and graft subgroups unanimously emphasized that a registry of implanted grafts together with essential surgical and patient

data was one of the most important and, at the same time, most difficult

parameters to assemble. A data base regarding the number of implants

per year was essential to establish an appropriate denominator for any

effective study on performance. That these data are essential was amply

illustrated by the presentations at the conference just concluded. The

approach necessary to acquire such data is by no means obvious at this

time.

SNOMED (Standard Nomenclature of Medicine) was identified as a computerized registry/data base which may serve as a model for data

collection or which may facilitate this type of work. It was noted

that SNOMED does not currently have the required vocabulary in the

cardiovascular area, but it could be modified and expanded.

Stage (iii)

For implants retrieved at surgical revision, it was felt that an excellent rapport and working relationship is essential if usable data

is to be retrieved. Thus, any retrieval program would, of necessity,

have to be based on a number of small "regional" groups. The resultant

67 I
information could then be consolidated at a larger center, provided that

a common data format is utilized by all the "region" groups. It was also suggested that there is a need for the development of an information

sheet for surgeons listing the essential data required for the effective

analysis of retrieved grafts and valves. This could also help the surgeons

appreciate the requirements necessary for the analysis of material oriented

parameters.

It was brought to the attention of the group that the Academy of

Pathologists is attempting to create a data bank of all autopsies; this

bank could serve as a basis for establishing incidence of death due to

valve or graft failure.

It was agreed that retrieval of implants at all autopsies would

be an important feature of a retrieval program. However, it was noted

that, unless death is due to implant failure, the pathologist may have

difficulty in identification of implant recipients during autopsy, un- less the implant is in the chest or abdominal cavity. This naturally

leads one to the conclusion that some easily identifiable "flag" must

be placed on the outside jacket of the patients' records. It also

suggests that autopsy pathologists should receive some minimal "education" in implants and the importance of the information to be gained

by implant retrieval. Since the information to be gained may not

directly benefit the patient in question, the surgeon and pathologist

should understand the importance of cumulative data to further medical

practice. The pathologist as well as the surgeon may not appreciate

or recognize some of the constraints upon the engineer or biochemist

with regard to evaluation techniques in their particular areas; a coordinated protocol should be capable of addressing this issue.

A draft report by Harrison et aj_. , under contract to the FDA

regarding heart valve retrieval and identification could serve as an initial basis for the development of valve data collection. The evaluation form will be appended to these proceedings. It has received minor

revisions as a result of our discussions and could serve as a model way

to collect data.

The Laval University/University of Manitoba protocols represent a basis for graft retrieval and identification. These should be supplemented by those used for specific graft types which have been developed

in some of the manufacturers laboratories. Representatives of this

later group indicated their willingness to contribute their protocols.

Stage (iv)

In certain respects the analysis stage probably represents one in

which it will be easiest to develop a set of protocols. It was agreed

that some uniformity of procedures was desirable and their development

would appear to be feasible utilizing protocols already in use by several investigators. In a further discussion of protocols, it was noted

that preparation or use of samples for one form of testing often precludes use of the sample for other types of testing. Thus, there is a

672
need for a triad system for analysis of specimens. Such a system

would emphasize nondestructive testing by the pathologist, who is

first to receive the specimen, and then the engineer. Destructive

procedures would be undertaken by both types of investigators only

after nondestructive testing had been completed or accommodated. The

special needs of the biologically oriented investigator who wishes to

study enzyme activities or cellular responses were also discussed.

The mechanism(s) to achieve the protocols described in the

previous paragraphs were discussed at length. The graft retrieval

subgroup discussed the desirability of "regional" retrieval and

analysis centers. It was recognized that although many of the manufacturer's laboratories are experienced in this field it would not be

appropriate for them to be used as a focus for "regional" centers.

However, their contributions to a "noncommercial" center were acknowledged as being vital to the success of any program.

At least one multi-center ad hoc group of cardiovascular surgeons

was identified as a group interested in establishing and participating

in data registry of heart valve implants and the clinical progress of

the recipients. The potential of voluntary organizations was also

discussed. The potential of ASTM in serving as an agent in establishing

a registry was also discussed. While there are ASTM groups addressing

cardiovascular implants, the current emphasis of many of these groups

is on materials design rather than performance standards. AAMI has

been concerned primarily with performance standards. Many members of

the group felt most comfortable with the proposal that a voluntary

agency with broad interests (rather than specifically implant oriented),

serve as the coordinator of the implant registry effort.

It was agreed that the NHLBI might well be an appropriate agency

to sponsor a working group or a workshop for the development of graft

and valve retrieval and analysis protocols. Dr. Watson of NHLBI

pointed out that an interagency Technology Committee on Cardiovascular

Biomedical Engineering existed which may well be helpful since information from the analysis of retrieved grafts and valves was of interest

to both NHLBI and FDA-BMD.

It was emphasized by a number of participants that the financial

cost of appropriate analysis of a retrieved implant is not insignificant. It was estimated that the current cost is about $600 an implant

with the assumption that the specific equipment and personnel with

the appropriate knowledge were already available.

The meeting concluded with the recommendations that a registry

be established identifying the patients receiving implants and that

their clinical course, explantation procedures, pathological and

engineering analysis of the explanted valves and grafts be included

in this registry. Finally, protocols for the analysis of explanted

heart valves and grafts would be collected and collated with the

objective that they serve as the basis for the development of common

set of protocols to be used in the analysis of retrieved synthetic

and tissue valves and grafts.

673
I think, at this point, I would like to ask whether members of

either of the two subgroups would like to identify themselves and add

anything that they feel we have missed in this summary?

Hearing no comments, I would like to close by saying that one thought that was expressed a number of times was that we are dealing

with a specialized activity. It is not an activity to which any

pathologist, polymer scientist, or material scientist can immediately

contribute. It has to involve a commitment on their part to understand

the specialized problems associated with implants. In addition, I would like to add that there are protocols available in the area of

grafts which could be used to provide a basis for some more generalized

protocol. So we do have in the graft area, as well as for valves, some basic ideas from which to try to develop a suitable beginning.

That, then, represents the end of our group's report.

CHAIRPERSON BROWN: Did you discuss any plans toward having these

four graft protocols included in the proceedings of this workshop?

CO-CHAIRPERSON GIBBONS: No, not the details of the protocols. We

had agreed, however, that at least we would include in the workshop

the types of information each of these groups extracted. Probably

the details of the protocols would be too cumbersome. Certainly

there was an agreement, I think, of all of the graft group to have at

least the listing of what they did evaluate.

DR. PITLICK (NHLBI): We didn't look at that specifically. Unless

there is an objection, I don't think it would be a problem to include

what types of information are available in the protocols that we have.

CHAIRPERSON BROWN: I think from my own point of view that one of

the important things to try to accomplish from this workshop is to

have material assimilated into one compendium so that we could look

at different alternatives. Having seen the alternatives, we could

then begin to either select the ones that make the most sense or simply dovetail them together to make a master list from which we can extract that set of observations and questions that are pertinent to

the particular analysis under way. One reason that I am pushing this

and would encourage rapid response is that the goal of the Conference

committee is to have the proceedings available in four to six months.

This means that we have a four week deadline to review the manuscripts

from the previous two days; also that Don Gibbons and I are making a commitment to have the proceedings from this workshop edited by the same time.

I would strongly encourage and invite people to submit their documents to us as soon as they get home. If you are not going home for

two weeks, call somebody in the office and have them send them to us so that they can be incorporated. Then we can really have a starting

point upon which to build. Don, do you see any problem from your end

as to getting that done?

674
CO-CHAIRPERSON GIBBONS: Just sleepless nights.

CHAIRPERSON BROWN: We are getting used to them. A point that has

been brought up repeatedly is "what is good performance?". This is obviously the objective, as opposed to what are we seeing in our retrieval

and analysis of removed implants, many of which are failures, and some

of which are routine. It brings to mind a subject that we have tossed

about from time to time on which I have not seen any progress (although

I think Case Western University is making progress) and that is removal

at autopsy. A lot of successful implants are going to the morticians.

I wonder if anyone in the audience has had any experience or made any

progress toward getting successful implants at autopsy so that they can

be analyzed and we can learn from a good one?

DR. SCHOEN (University of Florida): I think the problem is a substantially different one in the orthopaedic and the cardiovascular areas

and is perhaps somewhat different in the graft and the valve areas. I think the valves are probably the best example of the area that is included in every normal autopsy. Within that area, we are developing an understanding of what is good, as well as what is bad. The grafts are

a little more difficult, but I don't think as difficult as the orthopaedic prostheses.

We have discussed one possibility. There needs to be some identification of a patient coming down to autopsy who has a prosthesis of

any sort that is not included in the standard autopsy, basically the

chest and the abdomen. I do not think we have made much progress in

this. I am not sure exactly what is necessary to develop some sort of

a flagging of a chart.

I think it is also necessary to understand the practical limitations of what is obtained in the way of clinical information when a patient comes down to autopsy. The autopsy generally has to be done

in a period of a couple of hours after the patient's arrival and much

of the clinical information is still on the floor or perhaps even in

another hospital.

Nevertheless, there has to be some mechanism, I don't know what

it is; perhaps it can't be done. But we ought to be thinking about

some mechanism of identification.

DR. QUIJANO (Hancock Laboratories): Isn't it obvious to the

pathologist at autopsy that there has been a median sternotomy in order

to implant a valve? Then he will'also get a sheet that says that there

is a valve in this patient.

CHAIRPERSON BROWN: The same is true with orthopaedics. You can not

put a plate on the tibia without leaving a scar.

675
DR. SCHOEN: But there are two aspects. One is that some of the

most interesting patients are going to be the ones that had a valve

implanted 15 years ago at another institution, and the reason that they

are in the hospital is to have their colon cancer removed or something

totally unrelated to the fact that the valve prosthesis is in there.

The surgeon or the physician taking care of the patient at that time

may simply not know.

Certainly a median sternotomy is obvious, and that incision is

almost repeated in the standard autopsy. One needs a special permission

to enter the extremities. And special procedures have to be developed.

I guess some have been developed already, and I think that is one critical

issue in developing the background of these patients that Sidney Weisman

emphasized before. We want to know which patients have done well and have

died in spite of their prosthesis rather than because of them.

DR. GIBBONS: May I amplify that thought from the point of view

that if the patient has always been in a single institution, we have

the idea of having a very visible flag on the front cover of the

patient's record. The pathologist is not going to leaf through it,

however, even if it is available in time. Of course, there will always be a subgroup of patients who received implants in another hospital and, therefore, it is a problem of educating the pathologists

in each hospital to be aware of and to look out for these patients.

I think it is the responsibility of the pathologists in each hospital.

I see Dr. Anderson wants to amplify.

DR. ANDERSON (Case Western Reserve): Pat Parks, who is here, and

I have done many autopsies, and we both can speak to the fact that, at

least at our institution, a complete review of the record is necessary

before one goes ahead with the autopsy. That, coupled with the scar,

certainly gives us a clue as to what is there.

In regard to special procedures, at least in the state of Ohio, a complete autopsy is a complete autopsy. And we do not need special permission to look at the extremities. The only problem that we have is

that if we somehow damage or disfigure portions of the body which are shown in the funeral home, we get into trouble with the funeral directors and morticians. But everything else, for the most part, is permissible at our institution.

DR. WESOLOW (Yale University): I have had an experimental program for 20 years on experimental grafts, and I have a specific interest

in recovering human prostheses, both successful ones and unsuccessful

ones. The unsuccessful ones are less of a problem. They come back to

the surgeon, and being a surgeon, I deal with not only my own, but other

unsuccessful ones.

The successful ones are more difficult. In past days, pathologists

and others were not really interested in recovering these things. It

676
was a personal interest to be able to correlate the experimental data

with the patient in terms of predictability and also with a view to improving prostheses.

Two mechanisms helped to make the system work. I had an experimental research lab and I cut my own sections. In order to enlist the

aid of a pathologist at the institution, my histologic unit was officially a part of the department of pathology, administratively, although

I ran the sections. This allowed me to be legally a pathologist and

to gather specimens —which is one wrinkle.

The second, and much more successful mechanism, was direct enlistment of the patient and the family. At the time of implantation, I made it well known that I was interested in the prosthesis and that I would like to recover it. I would get calls from as far away as 100

or 200 miles: "My husband just died. Would you like the graft?" And

I would get in an automobile, drive up and recover it. I have also gone

into funeral parlors and all sorts of places in order to do this. I also

got a reasonable collection of relatively normal vascular prostheses

this way.

CHAIRPERSON BROWN: I think you have hit on one of the keys here; that

the whole process of informed consent at the time of implantation should

express a statement of interest in analysis and retrieval of implants so that we can look at the good ones as well as the bad ones.

DR. BLAIS (National Health and Welfare, Canada): One aspect which

has been an undercurrent in much of the discussion and yet has been

omitted is the question of blowing our own horn. On the average, the

pathologists, the hospitals and the personnel peripheral to, and yet

essential to any type of recovery program, are not fundamentally

interested in what we are talking about. So it is the responsibility

of each and every one of us to visit those who have potential value in

the recovery process and to perhaps barter with them in other aspects,

with intangibles like publications and things of this sort. In other

words, there are two things to push for: (a) One is to make the average

pathologist or forensic chemist working for a police laboratory or hospital interested from his own point of view in the implant and the implant

pathology, and (b) to motivate him perhaps, not with money, but with other

aspects which are barterable within our field of interest.

CHAIRPERSON BROWN: I would like to reinforce that statement and suggest

we add an acknowledgment at the end of this workshop's proceedings, a very

sincere and warm acknowledgment to all those O.R. supervisors, circulating

and scrub nurses, and ward and clinical department secretaries who have

made possible a large part of the implant retrieval and analysis that we

have presented at this meeting. I hope that they will continue to remain

our allies.

VOICE: Amen!

677

•I
DR. WATSON (NHLBI): I wonder, Mr. Chairperson, is there any plan to

present a four- or five-page summary of this workshop prior to the

publication of proceedings? It might be useful in terms of the recom- mendations and general intent of the meeting. I know at NIH we would

be interested in providing this to advisory groups and study sections.

I think other groups might also be interested in a summary so that

they could take it to their own institutions.

CO-CHAIRPERSON GIBBONS: May I answer from the cardiovascular group.

It is my intention, with Dr. Pitlick, to attempt to do that and to circulate to those at the workshop beforehand early notes and drafts that we will then attempt to put together. It is our intention to try, and

indeed, do that before actual publication.

CHAIRPERSON BROWN: I would certainly be willing and in favor of my

doing the same for the orthopaedic workshop. But I am not sure if we

can commit the committee to try to generate a summary from the two

conference days that could be circulated ahead of time. I think our efforts are better directed toward getting the entire book out quickly.

DR. RUFF (National Bureau of Standards): We could certainly treat

the proceedings of todays workshop as a somewhat separate entity and

make it available to the Conference sponsors in advance of the book

publication. Perhaps this would respond to the suggestion here.

CHAIRPERSON BROWN: One other question that I would like to put to

the floor concerns the subject of patient confidentiality and patient

identification. This discussion should then lead into whether there

are any legal problems that will arise from storage of patient information.

MR. WEISMAN (Howmedica): I think that question was brought up at

the Conference four years ago and discussed. I think it was agreed

upon that there should be some sort of a hidden code for preserving

the hospital information in a confidential manner. It was suggested

that that information would remain within the institution, but there

would be a reference number.

CHAIRPERSON BROWN: I think that was what was decided four years ago

but my question now is what is the current legal situation? Henry, do

you have any comments?

DR. PIEHLER (Duke University): I think the way to start is to ask

if anyone has ever had any problems of this nature.

DR. SCHURMAN (Stanford University): We have not had problems with

it, but it is something that is of concern at our university since we

have a national data bank center and like all institutions, we are governed by laws that I understand imperfectly. Nevertheless, there

are regular steps and regulations for this. In order to collect information on patients beyond the ordinary charting, the patients are,

at least at our institution, deemed to be part of an experiment.

678
Therefore, the protocol has to go through a Human Subjects Committee

for approval, which our protocol has for many different studies. There

are laws, or at least rules, that govern this. One is the guarantee of

the protection of privacy of the patient. This is done when computers

are involved by using secret codes that can only be accessed by the

physician who is actually treating the patient. Whereas the data of

a large group of patients can be available to numerous investigators,

there are steps taken to guarantee that the identity of an individual

within that group is not identified. That means an exclusion of clear

identifying information. For example, you cannot pull out of our com- puter someones records on the basis of their age, sex, height, and

weight. We allow our investigators to use only prearranged subsets.

They can not define their own subsets.

I think there are Federal laws governing privacy. Someone in the room might know it.

CHAIRPERSON BROWN: In our institution, we are not allowed to put a patient's name in the computer. I think the way around this is simply

to maintain a record of the patient's code number that you put into the

computer and somewhere else, probably in the clinic. You keep the

record that has the name attached to that number. Then someone else

who uses the computer on a time-sharing system can not retrieve the

patient's name.

CO-CHAIRPERSON GIBBONS: Obviously the point that Dr. Schurman has

made is true for all of us. We have to go through a Human Involvement

Committee. In our particular case, technically it involves the use of

discarded tissue. In other words, it has to have gone officially

through pathology. We are then allowed to use "discarded" tissue. And

each of us has our own way of attempting to maintain confidentiality

within our interpretation of the legal world. All of us try to achieve

it by making sure that from the data that is published or generally made

available, that no one could go back and say that had to be Patient X. This is really what you have to make sure of: that data can not possibly

be then traced backwards.

MR. WEISMAN (Howmedica): There is another question that has to be

addressed, and that is about the ownership of the prosthesis. Actually,

the prosthesis belongs to the patient, and you have to be extremely careful not to do anything to that prosthesis unless you have permission

from the patient or his heirs to handle that. I believe we ought to address that from the legal point of view of what the implications may be

in gathering implements and how to handle them.

DR. PIEHLER (Duke University): There is some help in that from the

ASTM Committee E-40 [Technical Aspects of Products Liability Litigation]

which is, I believe, going to have a standard within this year on testing

sequences. This standard has been six years in development, and it is

very interesting as to the positions that different manufacturers take

toward this very important issue.

679
Automobile manufacturers, for example, don't want anybody touching anything because typically the plaintiff always has the evidence

first. Whereas, implant manufacturers want to "hack and hew" because

typically they get it back from the doctors before the plaintiff or anybody else has it. Basically, the way the ASTM draft standard reads

is that you should make every effort to inform all interested parties,

particularly if the litigation is reasonably foreseeable. But it also

says that under circumstances like the generation of information or like the situation where you might have a perishable item, that you may

proceed with unilateral destructive testing if you take adequate steps

to preserve the nature of the device and also leave enough for other

people to repeat your tests as well as any other reasonable test that

might be performed.

This document, I think, will be out very shortly. What weight it

will have is another question, since it is entirely voluntary. But I think it addresses this issue. And one of the things that it recognizes is that there is value in doing unilateral destructive testing,

but it also recognizes legitimate rights of other people to obtain

their information.

CHAIRPERSON BROWN: I think part of the issue on patient ownership

of the material goes back to the point that Dr. Wesolow was making earlier.

That is, telling the patient at the time of implantation that this is inter

esting material that we would like to analyze at the time of removal or at

the time of death.

One of the most beautiful studies I have ever heard was presented

at the University of Ottawa (Conference on Internal Fixation of Fractures,

May 10-12, 1979) by Mr. A. J. Partridge from Sussex, England who was working with the geriatric population. He has had hips and all kinds of

other devices that he has implanted willed to him. As a result, he is

generating a very nice series of analysis of the performance of his

particular devices. It is by starting with the patient at the time of

implantation that true performance data will be generated.

CO-CHAIRPERSON GIBBONS: May I say that we have a proposal for an extensive prosthesis retrieval and analysis program at Case Western

Reserve University. An integral part of that is the surgeons who are involved in informing the patients prior to the implantation that we request them to be part of this analysis. So it does meet the kind

of comments that Mr. Weisman just made as part of an overall protocol.

DR. SCHOEN (University of Florida): I think a point needs to be

amended to this which creates a little difficulty. The person interacting with the patient prior to implantation is generally the surgeon

or the physician. I think these people are concerned, perhaps rightfully so, that while they may indicate to a patient that a particular

procedure does not have a 100 percent chance of success, there is some reluctance to indicate to the patient that there is a certain interest

680
in what is being done because it is of an experimental nature. I think

this is a particularly touchy issue. It perhaps can be accomplished,

but I think it is very delicate.

CHAIRPERSON BROWN: That is why I am saying we should state we have

an interest, rather than saying we are performing an experiment, which,

in fact, we are.

DR. WILKINSON (Strathclyde, U.K.): Could I bring up one point from

a U.K. study in which the medical profession objected to retrieval data

which might identify sources of excellence or lack of excellence between

different hospitals or different surgeons. Perhaps this is something

else that we ought to consider here today.

CHAIRPERSON BROWN: On that point, I think this meeting has been very

refreshing compared to previous meetings at which we discussed the problems of doing implant retrieval and analysis. At this meeting we have

heard the presentation of a large number of cases, examination of a large number of implants, and virtually no discussion of the problems

of manufacturers being afraid that we are going to threaten one over

the other, nor of surgeons being afraid that we are going to reveal

that some may be better than others. This is obviously a critical

issue to all, but it appears as though we are making some very com- forting progress in this important area.

DR. HOROWITZ (Johns Hopkins University): On the cardiovascular

protocols that you mentioned, I heard that we were going to bring those

together for the publication, but I didn't hear you follow through and

say that we were going to bring those to the coming ASTM meeting in

Denver as we are with the orthopaedic protocols. Is it possible to have

the cut-and-pasted version of that brought before the ASTM committee so that it could be worked on at that time also?

CO-CHAIRPERSON GIBBONS: Dr. Kaye, who is part of this group, is

chairperson of the ASTM F-4 Cardiovascular Subcommittee and hopefully he will

be there or will get it into the ASTM proceedings. Is that a fair statement, Dr. Kaye?

DR. KAYE (Mayo Clinic): That is correct.

CHAIRPERSON BROWN: Any further comments or discussion from the floor?

DR. BLAIS (National Health and Welfare, Canada): Maybe as an appropriate epilogue it can be said that part of the success that we have

had up north is that for the first time ever a mixture of certain scientists applied and respected the constraints of the surgeons. There are many surgeons who participated within our program on the premise that we would protect them if the need arose. And we have held to our word up

to now and will honor it further.

68 I
CHAIRPERSON BROWN: I would like to conclude the Workshop by express

ing a note of thanks to you all. We were a little skeptical whether we would be able to accomplish anything in this session. Speaking from my

own vantage point, I think we have, in fact, made much progress and have

set a basis for getting things going in the near future. Ladies and

gentlemen, the meeting is now adjourned.

Epi logue

As was stated during this Workshop, and was indicated by the success

of the Conference as a whole, we all, physicians, material scientists,

and pathologists, owe a tremendous amount of gratitude to the operating

room teams for helping gather implants, and to the ward and department

secretaries for helping gather the clinical information. Without their

help, this meeting would have been very quiet; without their help we

can not expect to make progress in the future. Thank you all!

Appendix A (attached) is a Compendium Code for Evaluation of

Properties and Performance of Orthopaedic Patients and Implants. This

document is the cut-and-paste product as described earlier. It was re- viewed and revised by the Implant Retrieval Task Force of ASTM Committee

F-4, at the May 1980 Denver meeting. The document is now a subject for

the task forces' activities.

In the cardiovascular area, the following documents are appended

to the workshop proceedings:

Appendix B : In 1979, Harrison et aJL , prepared a monograph for

the FDA (Contract 01317) on "Identification and Evaluation of Explanted

Heart Valve Prosthesis". The evaluation form in this monograph was re- viewed by several members of the heart valve subgroup, including Drs.

F. Schoen and P. J. Parks. Mr. E. Mueller has incorporated a number of

their suggestions in a revised evaluation form check list.

Appendix C : The analysis protocols used by Gortex, Inc., USCI

Surgical Products and Meadox.

In addition, comments on retrieval and analysis from their own experience by the Laval University, Quebec, Canada, group (Prof. M. Guidoin) can be found in the last section of their paper in the

Conference proceedings.

Participants in the Orthopaedic Workshop

JAMES M. ANDERSON, Case Western Reserve University

STANLEY A. BROWN, University of California - Davis

I. CLARK, University of Southern California

ALASTAIR J. T. CLEMOW, Tulane University

STEPHEN D. COOK, Tulane University

A. U. DANIELS, University of Utah

682
Participants in the Orthopaedic Workshop (continued)

STEPHEN L. GORDON, NIAMDD

ROY Y. HORI, Northwestern University Medical School

EMANUEL HOROWITZ, Johns Hopkins University

WILLIAM RUFF, National Bureau of Standards

DAVID SCHURMAN, Stanford University

HARRY B. SKINNER, Tulane University

WARREN STARKEBAUM, Zimmer USA

SIDNEY WEISMAN, Howmedica, Inc.

ROSEMARY WILKINSON, University of Strathclyde, U.K.

TIMOTHY M. WRIGHT, The Hospital for Special Surgery

Participants in the Cardiovascular Workshop

D. F. GIBBONS, Case Western Reserve University

F. PITLICK, NIHLBI-DTB

S. BARENBERG, University of Michigan

P. BLAIS, National Health and Welfare, Canada

K. BOTZKO, USCI Surgical Products

B. BOYCE, W. L. Gore Associates, Inc.

C. GOSSELIN, Laval University, Canada

R. G. GUIDOIN, Laval University, Canada

R. D. JONES, Surgical Research, St. Lukes Hospital

M. KAYE, Mayo Clinic

M. W. KING, University of Manitoba, Canada

D. LEDERMAN, AVCO Medical Products

W. LETZING, FDA-BMD

R. J. LEVY, Childrens Hospital Medical Center

E. MUELLER, FDA-BMD

P. J. PARKS, Case Western Reserve University

R. C. QUIJANO, Hancock

F. SCHOEN, University of Florida

R. STROMBERG, FDA-BMD

P. SUNG, FDA-BMD

J. WATSON, NIHLBI-DTB

S. WEINBERG, Meadox

S. WESOLOW, Yale University

S. YOGANATHAN, Georgia Institute of Technology

683
Appendix A

COMPENDIUM CODE FOR EVALUATION OF PROPERTIES AND PERFORMANCE

OF ORTHOPAEDIC PATIENTS AND IMPLANTS

The attached document is a compilation of the questionnaires

developed for implant retrieval and analysis and patient evaluation at

the following centers: Stanford (Arthritis Surgery Proforma), Northwestern, Case Western Reserve, Hospital for Special Surgery, Tulane,

Dartmouth, and the AO/ASIF. While some of the material in the compilation is also presented in the other papers included in this proceedings,

it was felt that pooling of the ideas would make the subsequent development and adoption of a National Consensus document easier.

The objectives of the compendium development are to create an all

inclusive list of line item questions with specific letter or number

code answers in a form which is compatible with computer storage and

analysis of data. The compendium will of necessity be a far more extensive list of items than that which would be used for a particular implant or patient analysis. Thus, the compendium is to serve as a master

code list from which basic or core documents can be excerpted for the

purposes of a particular study. If we can all reach an agreement as to

the line item designation for each inquiry, then our respective computer

data banks can be superimposed when pooling data.

The Compendium as presented here represents the efforts of one individual; it does not represent a group consensus. As a first step,

this document has been divided into 16 sections, with each section subdivided into major and minor questions or items. For example, Section 1 is patient identification; the first items in section 1 are questions

asked by all the centers, e.g., patient name, patient weight. The items

with letter designations are more specific in nature, and do not neces- sarily apply to all centers, e.g., 1C patient home address, handedness,

marital status, ethnic origin, and date of difficulty or disease onset.

Thus, the numbered items represent a compendium core, while the lettered

items represent additional inquiries. In some sections, especially in

patient diagnosis and level of activity, there is significant redundancy

between the numbered and lettered items. This is because different cen- ters have slightly different ways of asking or answering some of the

questions. Ultimately, it is anticipated that these redundancies will

be resolved into unified questions and answer codes.

This document is being published herein to inform the reader about

the current status of this effort. The document is also being submitted

to a task force within the Implant Retrieval Section (F4.20.07) of the

American Society for Testing and Materials (ASTM) committee F-4 on Medical and Surgical Materials and Devices, 1916 Race Street, Philadelphia,

Pennsylvania 19103. The task force will modify the document and submit

it to the consensus process of the Society. The result will be a Compendium code from which core documents can be extracted. (F-561 will

probably remain as core document.) People interested in contributing to

the development of the compendium code should contact ASTM.

684
1. PATIENT IDENTIFICATION

1.1 Case # 1.2 Patient name

1.3 Patient S.S. or hospital I.D. #

1.4 Sex 1-male, 2-female

1.5 Weight

Overweight condition A-normal , B-moderate, C-marked

1.6 Height 1.7 Date of Birth (Mo/Yr)

1.8 Hospital of implantation (Use four-letter code.

1.9 Hospital of removal

1.10 Date of implantation (Mo/Yr)

1.11 Date of removal

1.12 Joint involved A-hip, B-knee, C-ankle, D-finger, E-elbow, F-shoulder

1.13 Bone involved A-femur, B-tibia, C-fibula, D-humerus, E-radius,

F-ulna, G-spine, H-J-others

1.14 Side involved A-right, B-left, C-middle

IA. Patient source A-physician ' s own case, B-referral case Surgeon: implantation; removal

IB. Patient's normal occupational activity level

A-extremely active B-moderately active (normal)

C-sl ightly active D-sedentary E-other

IC. Home address

Handedness L R Marital status Ethnic origin

Date disease or difficulty began

ID. Apparent lower extremity difference

0-equal , 1 right longer, 2 left longer

Amount of apparent difference cm

True lower extremity length R L cm

IE. Problems in non-operative joints

0-normal , 1-involved and not impaired, 2-involved and impaired,

3-bi lateral procedures

IF. Intra-articular steroids Yes, No; joints ; # inject

IG. Non-narcotic analgesics type, dose (include ASA

and NSAI)

Narcotics Chrysotherapy

Corticosteroids Chemotherapy

Penici 1 1 amine

685
2. PATIENT DIAGNOSIS

Primary diagnosis, reason for implantation

A-unknown

B-primary osteoarthritis

C-secondary osteoarthritis

D-rheumatoid arthritis

E-dislocation of joint

F-aseptic necrosis

G-pain

H-Paget's disease

I-congenital deformity

J-pseudoarthrosis or non-union

K-mal union of fracture

L-tumor

M-loosening of prosthesis

N-mal position of prosthesis

0-trauma - simple - closed

P-trauma - simple - open

Q-trauma - comminuted - closed

R-trauma - comminuted - open

S-traumatic arthritis

2.1A. POLYARTHRITIS OF UNKNOWN ETIOLOGY

Rheumatoid arthritis

Juvenile rheumatoid arthritis

Ankylosing spondylitis

Psoriatic arthritis

Reiter's syndrome

CONNECTIVE TISSUE DISORDERS

Systemic lupus erythematosus

Scleroderma

Polymyositis - dermatomyosi tis

Mixed connective tissue disease

OSTEOARTHRITIS

POST TRAUMATIC

Closed reduction only

Open reduction only

Surgery proximal

Surgery proximal and reduction

Surgery distal

Surgery distal and reduction

Surgery proximal and distal

Surgery proximal , distal and

reduction

Unreduced dislocation

Unreduced dislocation and failed

surgery

FRESH TRAUMA

Proximal fracture

Proximal fracture and dislocation

Distal fracture

Distal fracture and dislocation

Proximal and distal fracture

Proximal and distal fracture;

dislocation

NEUROPATHIC (Charcot)

SEPTIC

Active infection

Previous infection

METABOLIC OR ENDOCRINE

Gout

Goucher's disease

Paget 's disease

Hemophil ia

Chondrocal cinosis

TUMOR

Primary bone tumor - benign

Primary bone tumor - mal ignant

Metastatic tumor

PRIMARY HIP DISEASE

Congenital dislocation

Subl uxation

Primary protusio

OSTEONECROSIS

Alcohol ic

Corticosteroid induced

Hemoglobinopathy

Legg-Perthes

Post traumatic

Caissons

686
Other, concurrent diseases X--none A-sem 1 1 ty K--myocardial infarction

B-chronic obstructive pulmonary miM-bone infection

disease N-joint infection

C- hypertension 0-•renal disease

D-diabetes mellitus P"-thrombophl ebi tis

E-peptic ulcer disease Q-peripheral vascular disease

F-obesi ty K-•al cohol i sm G-hyperthyroidism s--neuromuscular disorder

H-coronary artery disease

I-congestive heart failure

J-cardiac arrhythmia

2.3 History of foreign body reaction

2.4 History of metal sensitivity A-none, B-nickel , C-chrome, D-cobalt

2.5 Previous surgery A-ORIF, B-TJR, C-hemi-arthroplasty , X-none

2.5A.

2.5B.

D-medial meniscectomy

E-lateral meniscectomy

F- joint debridement

G-removal of loose bodies

H-l igamentous reconstruction - med. collat.

1-1 igamentous

lat. collat.

J-lig. recon.

K-lig. recon. L-synovectomy

reconstruction -

- ant. cruciate

- post, cruciate

M-patellectomy

N-patellar shaving

0-drill ing/shaving of femur

P-drill ing/shaving of tibia

Q-osteotomy - high tibial

R-osteotomy - femoral

S-patellar realign. - proximal

T-patellar realign. - distal

U-Maquet procedure

V-Hauser procedure

W-arthroscopy

FAILED PRIOR SURGERY

Osteotomy - hip

Osteotomy - knee

Arthrodesis

Internal fixation

Cup arthroplasty

secondary diagnosis

Hemiarthroplasty

Hip

Knee

Total joint replacement

Hip

Knee

Unicompartmental

2A. Physical exam HIP

Flexion, flexion arc, adduction in extenstion,

abduction in extension

Abduction muscle power 0-normal , 1-weak, 2-absent

Trendelenburg 0-normal, 1-equivocal, 2-positive

G87
2B. Physical exam KNEE

a.

b.

2C.

Recorded separately for each knee.

All limits or motions recorded in degrees

Flexion

Flexion arc

Varus - valgus

ML instability in extension

0-none, 1-minimal, 2-mild,

3-moderate, 4-severe

AP instability in 90° flexion

0-none, 1-minimal, 2-mild,

3-moderate, 4-severe

Pain walking (0-15)

Pain at rest (0-15)

Walk (0-12)

Stairs (0-5)

Transfer (0-5)

ROM (0-18)

Strength (0-10)

Total Knee Score

Effusion 0-none, 1-some,

2-severe

Patello femoral tenderness

0- none, 1-some, 2-severe

Patella tracking 0-normal

,

1- subluxed, 2-dislocated

Patella status 0-present,

1 -patellectomy

Flexion deformity (0-10)

Instability (0-10)

Cane (0-1)

Crutches (0-3)

Extension lag (0-5)

Valgus deformity (0-9)

Varus deformity (0-9)

Joint range of motion

Prior to onset of symptoms

After onset of symptoms

1- full ROM

2- functional ROM

3- restricted and limited ROM

4- joint contracture, limited

ROM

2D.

2E

Total pain sum: Sum of rest and activity pain

0-none; 1-minimal, i.e., occasional and slight; 2-mild, i.e.,

regular and slight, takes occasional analgesics; 3-moderate, i.e

frequent use of analgesics; 4-severe, i.e., regular use of

anal gesics

Other joint involvement: yes or disabling. Right or Left

foot, knee, hip,

neck, back

if definite involvement, very painful

0-not involved, 1 -involved

hand, elbow, shoulder,

668
3. SURGICAL IMPLANTATION PROCEDURE

3.1 Hospital 3.2 Surgical team

3.3

3.4

3.5

3.6

3.7

Anesthesia A-general , B-spinal

Incision time , close time

Tourniquet used Yes time

Blood replacement

Surgical approach

No,

# units

A-intravenous , B-oral , C-intramuscular

3.8 Were antibiotics used? Yes No

3.9 Reason for antibiotics A-prophylactic, B-positive culture,

C-history of sepsis, D-other

3.10 Antibiotic route

3.11 Antibiotic used

A-keflin F-erythromyci n B-penicillin G-cloxacil 1 in

C-methi ci 1 1 i n H-di cl oxaci 1 1 i n D-gentamycin I -keflex

E-cleocin (clindamycin) J-ancef

K-carbenicill in

L-tetracycl i ne M-cephazol ithin

N-kefzol

3.12 Anticoagulation A-aspirin, B-heparin mini-dose IM, C-dextran,

D-heparin full dose IV, E-coumadin, X-none

3.13 Other concomitant procedures

A-quadricepsplasty

B-valgus release

C-perineal nerve dissection

D-patel lectomy

E-patellar realignment

F-l igamentous release

G-posterior capsular release

H-debri dement

.14 Generic implant type

A-ankle F-pin

B-hip G-screw

C-rod H-plate

D-knee I-hip nail

E-elbow J-staple

plate

K-shoul der

L-wrist

M- finger

N-others

G89
4. POST OPERATIVE COMPLICATIONS

4.1 Pneumonia Yes No

4.2 Myocardial infarction Yes No

4.3 Pulmonary embolism Yes No

4.4 Cerebrovascular accident

Yes No

4.5 Nerve palsy Yes No

4.6 Abnormal wound healing

Yes No

4.13 Infection A-none, B-superficial

,

4.14 Infectious organism

A-Staph aureus B-Staph epidermidis (albus)

C-Streptococcus

D-E. coli

E-Pseudomonas aeruginosa

F-Clostricium perfringens

4.7 Fracture Yes No

4.8 Arterial vascular problem

Yes No

4.9 Sterile wound drainage

Yes No

4.10 Trauma Yes No

4.11 Thrombophlebitis Yes No

4.12 Death Yes No

C-deep

G-Bacteroides

H-Enterobacter

I-Klebsiella

J-Diphtheroids

K-anaerobic

L-mixed

4A. Pain in fracture/implant area A-none, B-seldom, C-yes

Weather sensitivity A-none, B-seldom, C-yes

Swelling A-none, B-seldom, C-yes

Inflammation, redness A-none, B-yes, when

4B. Intra-operative bone fracture Yes No

Post operative bone fracture Yes No

Trochanteric nonunion 0-no, 1=1 cm, 2=l-2cm, 3=2 cm

4C. Hematoma 1-not drained, 2-surgically drained, 3-spontaneously

drained

4D. Dislocation Yes No Subluxation Yes No

4E. Clinically loose prosthesis Yes No

Prosthesis breakage Yes No

Lost to follow up Yes No

G90
5. FUNCTIONAL ACTIVITY

5.1 Functional level attained after insertion:

(A-C, lower extremities; D-F, upper extremities)

A-ambul a to ry

B-ambulatory with aids

C-not ambulatory

D- functional

E-functional with brace

F-not functional

Patient activity

Prior to onset of symptoms

After onset of symptoms

1 - active and working

2- active, uses no supports or

one support intermittently

3- active, uses one support

4- active, uses two supports

5- inactive, uses one or two

supports

6- inactive, wheelchair

7- inactive, confined to bed

8- other

5.2 Ambulation

A. Walking aids 0-none, 1-one support part-time, 2-one support

full-time, 3-two supports, 4-walker, 5-wheel chai r , 6-bedridden

B. Maximum distance able to walk at one time 0-one mile or more,

1-one-half mile, 2-one-fourth mile, 3-indoors around house,

4-unable

C. Limp 0-none, 1-minimal, 2-mild, 3-moderate, 4-severe

D. Gait data

Velocity meter/mi n. Gait cycle (sec.

Cadence steps/mi n. R-SLST (sec.)

L-SLST (sec.)

Initial double support

Terminal double support

5.3 Ability to walk up stairs

Prior to onset of symptoms 1 -normally

After onset of symptoms 2-slowly, alternating

Ability to climb stairs 0-no difficulty, 1 -mi 1 d difficulty, 2-need

handrail, 3-extreme difficulty, 4-unable

3- one stair at a time

4- unable

69 I
5.4 Activities

A. Put on socks (L&R) 0-no problem

1 -mi 1 d difficulty

2-moderate difficulty

3- severe difficulty

4- unable

Arise from chair without using

arms

Use knife and fork

Bathing and personal hygiene

Drive car

B. Ability to stand from sitting position

Prior to onset of symptoms 1- no arms required

2- arms required

3- other help required

After onset of symptoms

C. Ability to put

Prior to onset

After onset of

on shoes and socks

of symptoms

symptoms

1- easily

2 - with difficulty

3-socks only, cannot tie

shoes

4- unable

D. Light sports:

garden

Heavy sports:

skate

jog, tennis , ski

,

gol f swim, bowl

,

Sports: Code in each

category.

Specify yes or no if any one within category is

performed.

5.5 Joint pain (for each operative joint)

Pain at rest

Pain with activity

Total pain sum: sum of rest and activity pain

0-none; 1-minimal, i.e., occasional and slight; 2-mild, i.e.,

regular and slight, takes occasional analgesics; 3-moderate, i.e.,

frequent use of analgesics; 4-severe, i.e., regular use of

anal gesics

5.6 Did operation help you?

0-much better, 1 -little better, 2-no change, 3-little worse, 4-much worse

If operation did not help, was it because

0-problem not involving the joint operated on, 1-problem in other

joint(s), 2-problem in the joint that was operated on

692
6. ROENTGENOGRAPH! C REVIEW

6.1 Bony change around implant A-calcar resorbtion, B-cortical hypertrophy, C-sclerosis or compaction, D-heterotrophic bone formation,

E-osteolysis , F-cysts, G-osteoporosis , H-normal

6.2 Migration of implant, subsidence mm

6.3 Implant deformity A-bent, B-rotated, C-tilted

6.4 Implant loosening Yes No

6.5 Prosthesis fracture Yes No

6.6 Bone fracture A-tibial plateau, B-femoral condyle, C-femoral shaft,

D-tibial shaft, E-bone adjacent to implant

6A. PMMA A-normal , B-cracked, C-excessive cement seen in joint, D-no

cement seen Lucent lines A-none, B-incomplete , C-complete

Lucency width mm

Location A-proximal , B-medial , C-lateral, D-distal

Lucency progressive Yes No

6B. Subluxation A-posterior, B-anterior, C-medial, D-lateral

E- rotatory

Dislocation A-posterior, B-anterior, C-medial, D-lateral

6C. Fracture healing A-primary union, B-light callus, C-heavy callus,

D-delayed union, E-pseudoarthrosis

6D. Penetration of implant across joint space Yes No

Penetration of implant through bone Yes No

iE. Scintimetry A-hot distal femur, B-hot proximal tibia, C-hot

proximal femur, D-hot acetabulum, E-other hot spot

iF. Radiographic alignment

AP femur/tibia pre TKR (degrees)

(normal = 90°) AP prosthesis/tibia pre TKR (degrees)

(7° valgus normal = 83°) AP prosthesis/femur (degrees)

(no tilt normal = 90°) lat prosthesis/tibia (degrees)

(degrees of flexion) lat prosthesis/femur (degrees)

Overall alignment femur/ tibia post TKR (degrees)

693
7. REASONS FOR IMPLANT REMOVAL

7.1 Primary indication for implant removal

7.2 Secondary indication for implant removal

A-routine

B-early infection <6 months

C-late infection >6 months

D-breakage of implant

E-pain related to implant

F-stiffness related to implant

G-prominence of bursae

H-instabil ity or loosening

I-unsatisfactory implant position

J-non-union

K-allergic or hypersensitive

reaction

L-loosening with pain

M-dislocation/subluxation

N-restricted range of motion

0-patel lofemoral disease

P-autopsy

Q-reason unknown

R-other

7A. Contributory conditions

01- none 05-neuromuscul ar disorder such

02- alcohol ism as hx of polio, CVA, etc.

03- drug addiction 06-multiple previous procedures

04- senility 07-other

7B. Initial factor leading to removal symptoms

1- iatrogenic** 4-idiopathic

2- infection 5-autopsy

3- trauma or fall 6-other

**Iatrogenic problems include: poor component orientation, poor

bony preparation, bone fracture, etc.

7C. Results of allergy testing (LIF test)

No sensitivity

1

Ni

2 Co

3

Cr

4

No cell migration

5

A-pre-implantation

B-fol low-up

C-implant removal

D-follow-up

£34
8. FINDINGS AT SURGERY

8.1 General observations

A-pus

B-granulation tissue

C-foreign body reaction

D- tissue staining (debris)

E-bursal fluid

F-abundant scar tissue

G-implant easily removed

H-bony reaction

I-loose prosthesis

8.2 Components removed

A-prox fern B-acetabul ar C-dist fern D-tibial plateau

E-patellar button

8.3 Biopsy taken

A-from over plate as

in figure

B-pseudo joint capsule

C-fibrous tissue

D-synovial fluid

E-bone/cement interface

E-patellar button

F-other TJR

G-internal fixation device

H-some (not all) bone screws

( Chemical Analyses

suture

FORMALIN T" suture

( Histology

8A. Subsequent procedure A-fusion, B-new TJR, C-another int. fix.,

D-pl aster

8B. Findings relative to fracture fixation plates

Scar O-inconspicuous , 1 -distinct, 2-red, 3-eczematous

Tissue over plate 0-soft, 1 -thickened , 2-bony

Coloration 0-none, 1(+), 2(++); color: white, gray, brown, black

Tissue contacting plate O-intimate, 1 -cavity, 2-serum

Collar around screw head O-connective, 1-bony, 1/2-combination

Plate bed O-vascularized, 1-avascular, 1/2-combination

Biopsy of plate capsule proximal distal

8C. Findings relative to prostheses

Fibrous membrane between bone and PMMA 1-a little, 2-a lot, 3-no

Excessive PMMA around components 1-a little, 2-a lot, 3-no

PMMA fragment(s) in joint and synovium 1-a little, 2-a lot, 3-no

Proximal component(s) poorly oriented 1-a little, 2-a lot, 3-no

Distal component(s) poorly oriented 1-a little, 2-a lot, 3-no

Component(s) dislocated 1-yes, 3-no

Proximal component(s) fractured 1-yes, 3-no

Distal component(s) fractured 1-yes, 3-no

Soft tissue rubbing or impingement by prosthesis 1-yes, 3-no

Bony contact by component(s) 1-yes, 3-no

Joint ligaments intact 1-yes, 3-no

Musculature surrounding joint intact 1-yes, 3-no

695
8D. Degree of loosening

Component 1 -freely loose, component easily

#1 #2 removed

Proximal component 2-loose, component removed with

Distal component little effort

3- loose, component removed with

difficul ty

4- firm, component removed without great effort

5- firm, component removed only

with great effort

6- component not removed

8E. Loosened interface

1 - bone/cement

2- cement/pros thesis

3- both of above

4- bone/prosthesis

5- not loosened but removed

6-component not removed

8F. Cement fractures

Proximal component 1 -fresh from removal

Distal component 2-old

3- both of above

4- no cement

5- none

6- component not removed

Proximal component

Distal component

696
9. HIST0PATH0L06Y

9.1 Fibrous tissue X-none, A-plate biopsy, B-prosthesis area

9.2 Thickness mm

9.3 Inflammation Yes No

9.4 Cells PMN

9.5 Cells FBGC 9.4 - 9.8, score scale 0 to 5 9.6 Cells macrophage

9.7 Cells lymphocytes

9.8 Cells plasma cells

9.9 Morphology A-granul ation , B-capsular

9.10 Debris in cells X-none, A-PMMA, B-UHMWPE, C-metallic

9.11 Intercellular debris X-none, A-PMMA, B-UHMWPE, C-metallic

9.12 Pseudojoint capsule Yes No

9.13 Thickness mm

9.14 Inflammation Yes No

9.15 Cells PMN

9.16 Cells FBGC

9.17 Cells macrophage 9.15 - 9.19, score scale 0 to 5 9.18 Cells lymphocytes

9.19 Cells plasma cells

9.20 Morphology A-fibrous, B-granular, C-synovium

9.21 Debris in cells X-none, A-PMMA, B-UHMWPE, C-metallic

9.22 Intercellular debris X-none, A-PMMA, B-UHMWPE, C-metallic

9.23 Synovial fluid Yes No

9.24 Centrifuged G's

9.25 Color

9.26 Debris X-none, A-PMMA, B-UHMWPE, C-metallic

9.27 Size range to micron

9.28 Cells A-few, B-moderate, C-many

9.29 Cell type

9.30 Bone/cement interface X-none, A-pelvic, B-prox fern, C-dist fern,

D-tibia

9.31 Macro A-hemopoetic, B-white glistening

9.32 Bone Yes No

9.33 Location

9.34 Trabeculae A-organized, B-disorganized

9.35 Tissue A-osteoid, B-calcified

9.36 Marrow A-normal , B-abnormal

69 7
10. IMPLANT IDENTIFICATION

10.1 Implant classification A-prosthesis proximal, B-prosthesis distal,

C-fixation device

10.2 Ankle A-Howmedica, B-Newton, C-Scholz, D-Oregon

10.3 Knee

A-TCP I I-UCI P-Guepar

B-TCP II J-Duocondyl ar Q-Spherocentric

C-TCP III K-Shiers R-Maclntosh

D-I/B L-Duopatella S-Geomedic

E-I/B P.S. M-Gunston T-Stabilocondyl ar F-Unicondyl ar N-Freeman-Swanson U-McKeever

G-Polycentric 0- -Walldius V-Geopatel 1 a H-Marmor W-Custom design

Total hip

A-Charnley H-Bateman UPF N-Tharies

B-Charnley-Mul ler I-AuFranc-Turner 0- Moo re C-Muller J-Weber P-Thompson

D-CAD K-Bechtol Q-Bipolar

E-T-28 L-Christiansen R-Porous coat

F-Series II M-Gi liberty S-Rough stem

G-Anitomic

10.5 Total hip stem/neck length / A-std, B-short, C-long

10.6 THR head diameter mm

10.7 Total shoulder A-Neer, B-Zimmer

10.8 Elbow A-Mayo, B-Tri-axial , C-Schlein, D-Coonrad

10.9 Wrist A-AMC, B

10.10 Finger A-MCP, B-PIP, C-Schultz

10.11 Plate type A-compression , B-sel f-compressing, C-semi tubular,

D-"T", E-thin, F-uniform strength

Plate width A-std, B-wide

10.12 Plate number of holes / screw diameter (4.5, 3.5, 2.7,

2.0)

10.13 Screws number , type A-hex, B-philips, C-cruciate,

D-single slot, E-cancel lous , F-malleolar

10.14 Plate, nail plate

A-Smi th-Peterson & Thornton E-Jewet

B-Smi th-Peterson & McLaughlin F-sliding nail

C-compression screw G-Massie

D-angle blade plate

G9 8
10.15 Rods

A-Kuntscher

B-Rush

C-Hansen-Street

D-Schneider

E-Lottes

10.16 Staple

10.17 Wire

10.19

10.18 Implant manufacturer

A-Allo Pro

B-AO/ASIF

C-Cintor

D-Biomet

E-Cutter

F-DePuy

G- Downs

H-Howmedica

I-Hexcel

J-Medtec

K-3-M

L-0EC

M-Osteonics

N-Protec

Implant material

A-Stainless steel wrought

B-Stainless steel forged

C-Stainless steel cast

D-Co-Cr-Mo (Prot-2) cast

E-Co-Cr-Mo (Prot-2) forged

F-Co-Cr-Mo (Prot-2) HIP

G-Micrograin

H-Co-Cr-Ni-W

I-Ti CP

J-Ti 6A1, 4V

F-Steinmann

G-Ki rschner

H-Enders

I-Smi th-Peterson

J-Harrington

0-Richards

P-U.S. Surgical

Q-Wright-Dow Corning

R-Zimmer USA

S-Zimmer GB

T-Custom

K-Co-Ni-Cr-Mo (MP35N, Prot-10)

L-Co-Ni-Cr-Mo-W-Fe

M-Co-Ni-Cr-Mo/Co-Cr-Mo

N-Silastic

0-Al 2 0 3 P-Polyester

Q-Acetal

R-C-UHMWPE

S-C-PTFE

639
11. NON-DESTRUCTIVE EVALUATION, METALLIC COMPONENTS

11.1

11 .2

11.3

Was a macroscopic exam performed? Yes No

If yes, then scale for following is 0.0 - 4.0

0-none, 1-mild, 2-moderate, 3-severe, 4-NA

Wear

Calling

Burnishing

D. Change in implant shape

E. Mechanical damage

F. Macro porosity

Was a corrosion examination performed?

If yes , scale is 0.0 - 5.0.

A. Gross corrosion

B. Crevice corrosion

C. Galvanic corrosion"

D. Fretting corrosion

Yes No

Was there mechanical failure?

If yes, failure modes:

A-fatigue

B-torsion

C-impact

D-s tress-corrosion

Yes No

E-overstress

F-corrosi on-fati gue

G-other

Was there a fabrication flaw? Yes No

11A. Prosthesis articulating surface wear

A-slightly or none B-shiny, smooth 2-body wear

C-dull , slightly rough 3-body wear

D-rough, abrasive 3-body

E-gross pitting, gouging 3-body

F-unknown

11B. Component damage

Abrasive wear or deformation due to bony contact or impingement,

Yes No

Abrasive wear or deformation due to PMMA cementophyte contact.

Yes No

Abrasive wear or deformation due to abnormal opposing component

contact. Yes No

11C. Femoral stem burnishing (use chart A)

Burnishing

Burnishing

Burni shing

Burnishi ng

Burnishing

side of col lar

under collar

proximal stem

distal stem _

ti p of stem _

A-none

B-small superficial spots

C-large superficial or

small deep

D-many superficial

E-large significant areas

700
11D. Bone plate corrosion

and C or D)

average

total (use charts B,

Size: 1 -small

2 -medium

3- 1 arge

Depth: 1 -minimal

2- significant

3- severe

Corr = size + depth

Nature: 1 -plastic def

2- burni shed

3- rough

4- parallel lines

5- cracks

6- corrosion

7- needle pitting

8- gross pitting

9- rain bow

12. DESTRUCTIVE, METALLOGRAPHIC EXAMINATION

12.1 Metal lographic sample orientation (sketch location)

Relative to principal load Relative to principal cold

roll ing

A-parallel D-parallel

B-perpendicular E-perpendicul ar

C-di agonal F-di agonal

12.2 Void content (gas porosity) (E-45 used for counting)

12.3 Inclusion content (E-45) / A-meets spec, B-out of specs

12.4 Grain size (E-112) / A-in specs, B-larger, C-smaller

12.5 Etch technique

12.6 Grain boundaries A-clean, B-precipitates , C-sensitized

12.7 Inclusion location A-intergranular, B-interdendritic , C-dispersed

12.8 Inclusion characteristics

12.9 Carbide distribution A-random, B-preferential orientation

HARDNESS TESTING

12.20 Macrohardness sample orientation (code of 12.1)

12.21 Macrohardness / Rockwell scale: A, B, or C

12.30 Microhardness sample orientation (code of 12.1)

12.31 Microhardness / A-Brinell, B-Vickers, C-Knoop, D-scratch

12.40 Mechanical testing performed Yes No

12.41 0.2% offset, yield stress MPa

12.42 Ultimate tensile strength MPa

12.43 Percent elongation %

12.44 Gauge length cm

12.45 Reduction in area

12.46 Bend strength

70 1
13. PMMA EXAMINATION

13.1

13.2

13.3

13.4

13.5

PMMA sample A-acetabul um, B-prox fem, C-distal fern, D-prox tib,

E-other

PMMA manufacturer A-Simplex, B-Zimmer

Amount of PMMA used

1 - excessive

2- insufficient

3- normal

Bony interdigitation of PMMA

1- good

2- mo derate

3- poor

PMMA distribution

1- good even coverage

2- small part of prosthesis uncovered

3- large part of prosthesis uncovered

4- no cement

5- component not removed

6- unknown

4- no cement

5- component not removed

6- unknown

4-no cement

5- component not removed

6- unknown

13A. PMMA macroscopic A-smooth, B-wrinkled, .C-papillary (sketch)

13B. PMMA metal lographic % deformation (location ) Fracture(s) X-none, A-interparticle, B-intraparticle

location

Porosity % size range mm

Folds location comments

Bone/blood debris

13C. PMMA I.R. data

Other PMMA analysis

702
14. POLYMERIC ARTICULATING SURFACES

SUMMARY OF DAMAGE FROM USE (as derived from charts E or F)

14.1 Cement debris 1-none

14.2 Pitting 2-slight

14.3 Scratches 3-moderate

14.4 Burnishing 4-severe

14.5 Cracks

14.6 Wear

14.7 Creep

14.8 Discoloration

14.9 Iatrogenic from removal

14.10 Patellar eccentricity

14.11 Abrasive wear or deformity due to bony contact or impingement

Yes No

14.12 Abrasive wear or deformity due to PMMA cementophyte contact

Yes No

14.13 Abrasive wear or deformity due to abnormal opposing component

contact Yes No

14A. Prosthesis articulating surface wear

A-slight or none B-shiny, smooth 2-body wear

C-dull , slightly rough, 3-body

D-rough, abrasive 3-body

E-gross pitting, gouging 3-body

F-unknown

14B. Low M.W. 95°C xylene extraction location, %

14C. Optical transmission location, surface wear

Optical transmission depth of plastic deformation mm

Optical transmission defects , type , size mm

14D. Thermal analysis type , location , observation

14E. Spectroscopic analysis type , location

observation

7 03
15. FINGER PROSTHESIS

15.1 Location A-MP, B-IP

15.2 Material, hinge A-silicone rubber, B-polyoefin, C-metal , D-other

15.3 Material, tang A-silicone, B-steel , C-Ti 6,4, D-other

15.4 Macroscopic A-fractured, B-wear/abrasion, C-discoloration

15.5 Location of 15.4 A-hinge, B-tang, C-other

15.6 Microscopic, hinge

15.7 Microscopic, tang(s")

16. FAILURE ANALYSIS

16.1 Mode of failure (confirm by SEM)

A-fatigue

B-torsion

C-impact

E-overstress

F-corros ion- fatigue

G-other

D-s tress-corrosion

16.2 Fabrication flaw related

A- no B-gas porosity

C-weld-filled defect

D-surface scratches

E-other surface defects

16.3 Related to implantation

A-no

B-surface scratches

C-surface deformation

D-screw-plate corrosion

E-stress concentration

16.4 Fluorescent penetrant studies A-no cracks, B-cracks

16.5 Radiography A-no defects, B-porosity, C-defects

7 04
RETRIEVED IMPLANT ANALYSIS - SUGGESTED SUMMARY WORKSHEET

Patient Data

Male rj Female /_/ Age yrs.

Weight lbs., kg. Height ft., m.

Reason for implant

Reason for removal

Interval between insertion and removal yrs. mo.

Analysis of prosthesis completed /_/ not applicable / /

Histopathology analysis completed /~ not applicable /_/

Biomechanical analysis completed /_/ not applicable [_/

Summary diagnosis completed / /

Final Conclusions

Cause of TJR failure

01 - iatrogenic 06-autopsy

02- sepsis - early 07-prosthesis fracture

03- sepsis - late 08-pain only

04- trauma or fall 09-other (specify)

05- idiopathic loosening 10-unknown

7 O

r

j

CHART B

PROTOTYPE

STANDARD REFERENCE CHART FOR DETERMINATION

OF DAMAGED AREA SIZE ON SCREW HEADS

FROM PLATE-SCREW CONTACT AND CORROSION

Size numbers and areas to be determined later

707
CHART C

Hospital Series

Name Plate

Birth Date Screws

Date Impl. rem. Bone

Date Analysis SEM?

Holes Screw rxcrnoiKs

Area Code Area Code

^ ^ © up

r vi

(§) ip

><pkr j/i —V. CP nir ®' LJ/I

h[Y ®

®CP

®nip

®ip

<!)(/ ®IP

®ip

® fPi

® iakj

pin

708
CHART D

Hospital Series

Name Plate

Birth Date Screws

Date Impl. rem. Bone

Date Analysis SEM?

s

7 09
CHART E

ACETABULAR COMPONENT MACROSCOPIC EXAMINATION

Right Left

Mfg , style

Patient name Patient number

Iatrogenic damage at removal (mark locations on diagrams)

S S

Surface markings

right

S I A P a cement debris

b pitting

c scratches

d burnishing

e cracks

f wear

g creep

h discoloration

i iatrogenic

A-none

B-sl ight

C-moderate

D-severe

7 I 0
<ino

+->

CU

+-> fO

Cl. =*t=

CUE

CU

SCO

rO

4->

+J

CUu

o

tO —

>— s:

-•-> CU —i rD —

ra a.

S-cu

+->

fO D.

S-

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7 • I
Appendix B

IDENTIFICATION AND EVALUATION

OF EXPLANTED HEART VALVE PROSTHESES

A Monograph

Earl C. Harrison, M.D.

S. M. Hansen, M. Ed.

Ira Schulman, M.D.

William Parnassus, M.D.

Wesley Bloom, B.F.A.

Division of Cardiology and Department of Pathology

University of Southern California School of Medicine

and LAC/USC Medical Center

Los Angeles

and

Paul Massier, M.S. (M.E.)

Muzaffer Cizmecioglu, Ph.D.

Randall Beer, B.S. (C.E.)

Energy and Materials Research Section

Jet Propulsion Laboratory, California Institute of Technology

Pasadena

Revised June 18, 1980

Sponsored under Contract No. 955315

Jet Propulsion Laboratory

California Institute of Technology

7'2
ACKNOWLEDGMENTS

We would like to acknowledge the assistance of the following

individuals who have been kind enough to share their knowledge

and time with us in the development of this monograph: Dr. John

Roschke, Jet Propulsion Laboratory, and Dr. Dorothy Tatter,

Department of Pathology, LAC-USC Medical Center; Dr. Francis Buck,

Department of Pathology, LAC-USC Medical Center; Dr. Thomas Noguchi,

Los Angeles County Coroner; Mr. Andy Gero, Chief Photographer, LACUSC Medical Center; Mr. Sam Goodenough of Shiley Laboratories;

Mr. Daniel Schiekele of Cutter Laboratories; Mr. Douglas Steed of

Edwards Laboratories; and Dr. Manuel Tascone of Hancock Laboratories.

Los Angeles

May 1979

THIS WORK WAS JOINTLY PERFORMED BY JET PROPULSION LABORATORY,

CALIFORNIA INSTITUTE OF TECHNOLOGY, AND THE UNIVERSITY OF SOUTHERN

CALIFORNIA, FOR THE FOOD AND DRUG ADMINISTRATION BY AGREEMENT WITH

THE NATIONAL AERONAUTICS AND SPACE ADMINISTRATION.

7 I3
TABLE OF -CONTENTS

1. Introduction to and Use of Monograph •

2. Glossary of Heart Valve Related Terms

3. Generic Schema of Some Major Valve Types

Valve Identification Flow Diagrams (Tables I - IV)

5- Valve Information Charts

6. Addresses of Valve Manufacturers

7. Evaluation Form (Protocol to be completed by user)

I. Patient Information

II. Prosthesis Information

III. Specimen and Handling

IV. Prosthesis Examination

V. Gross Pathology

VI. Histopathology

VII. Summary Sheet

7 I 4
IDENTIFICATION AND EVALUATION

OF EXPLANTED HEART VALVE PROSTHESES

INTRODUCTION

THIS MONOGRAPH CONSISTS OF TWO MAJOR PARTS:

Part 1: Infornation Mater ia 1 s, Tab 1 es , Charts, etc. for the Identification

of heart valve prostheses

Part 2: Evaluation Form (a write-in protocol) for explanted heart valve

prostheses

BEFORE USING THIS MONOGRAPH, WE ASK THAT YOU PLEASE READ THE FOLLOWING:

1. Scan the monograph and identify the two portions indicated above.

2. Review both the identification flow diagrams and charts and the other

informational materials in order to familiarize yourself with their content

and use. This will facilitate reference to these portions at a later time.

3. The evaluation form itself (write-in protocol) is divided into six parts:

I. Patient Information; II. Prosthesis Information; III. Specimen and

Handling; IV. Prosthesis Examination; V. Gross Pathology; and VI. Summary

Sheet. Throughout the form, informational paragraphs have been indicated

by a black dot. Please read and understand these portions thoroughly.

4. While filling cut the eva 1 uat ion .form (boxed sheets) e i ther write in the

appropriate response in the squares provided, or place a check mark or number, as appropriate. Please fill in a 1

requested information as com- pletely as possible.

5. The headings for aortic (A), mitral (M) , and tricuspid (T) valves are provided in the event that the patient has more than one prosthesis. In these instances, please check the appropriate boxes as applicable to each

valve. In all other cases, where the patient has only one prosthesis,

place checkmarks in the boxes applicable to that valve only. (Example:

If the patient being autopsied has a prosthetic aortic valve, all your

checkmarks will be in the "A" column.)

6. Where you have been asked to draw or sketch findings in the evaluation

form portion of the monograph, please approximate, your drawing(s) as closely as possible to the objective data. Wherever necessary, use the

transparent template attached to the back cover of this monograph to approximate size of occlusion, tissue overgrowth, etc.

7. Should you wish, please do not hesitate to write notes or remarks in the blank areas provided, or in margins.

EVALUATION FORM COMPLETED BY: (Please print)

Name: -M - D -

Title:

Address:

Phone Number: (Area code )
p
PART i
I
GLOSSARY OF HEART VALVE-RELATED TERMS

BASE RING. The circular structure in the plane of the valve annulus

which supports the cage in the case of mechanical prostheses, and which supports the stent in the case of bioprostheses.

SIOPROSTHESES Non mechanical prosthetic tissue heart valves which Include

homografts (human cadaver), heterografts (animal cadaver),

and fascia lata valves (transplants from thigh tissue).

CAGE The portion of a mechanical prosthesis which, in conjunction with the base ring, restrains and limits the movement of the ball or disc. The cage is composed of struts

which are joined to the base ring.

Single cage struts emerge on only one side of the base ring plane

Double cage struts emerge on both sides of the base ring plane

Open cage converging struts do not connect at the apex

Closed cage struts join at apex in a cruciform manner

CAGED-BALL VALVE .... Hemodynami ca 1

1 y , a central occluder type prosthesis in which

a ball -shaped occluder (poppet), moves within the cage.

CAGED-DISC VALVE. ... Hemodynami ca 1 ly a central occluder (peripheral flow) type

prosthesis in which a disc-shaped occluder (or poppet), moves within the cage.

CUSPS ... Leaflets of a b i opros thes i s (or tissue valve) mounted on a stent

DACRON Trade name by DuPont for a polyester fiber, e.g., Polyethyleneterephatalate, used as a sewing ring cloth.

DELRIN Trade name by DuPont for pol yforma 1 dehyde , a thermoplastic

material based on acetal resin. Th f s is used in the

construction of prostheses occluders.

! HETEROGRAFT A non-mechanical tissue valve made of animal cadaver and

fascia lata valves (transplants from thigh tissue).

HOMOGRAFT A non-mechanical tissue valve made of human cadaver.

7 I 9
POLYPROPYLENE A thermoplastic material made from the polymerization of

propylene. It is used as sewing ring material.

PRIMARY FLOW Space available for blood flow through open valve at the

ORIFICE narrowest point of valve inlet.

PYROLITE CARBON A thick, structural carbon coating with un i que .comb i nat ion

of properties. It is biocompatible in the broadest sense; generally deposited on a graphite substrate such as a valve leaflet or occluder.

RIGID PROSTHESES ... .A classification of prosthetic heart valves which includes

caged-ba'l 1

, caged-disc and tilting-disc prostheses.

SECONDARY FLOW Minimum built-in area available for blood flow rather

ORIFICE. than those at the primary valve orifice.

SEWING RING A cuff-like cloth casing around the base ring that the

surgeon uses to attach to the valve annulus.

SILASTIC Silicone rubber used as an occluder in caged-ball prostheses .

STELLITE A metal alloy that includes molybdenum, chromium and tungsten. This is used in the construction of struts and base

r i ng of a va 1 ve

.

STENT The structure which is attached at a right angle to the

base ring of a b ioprosthes i s ; the stent supports the valve

1 eaf lets

.

STRUT The structure which projects vertically from the base ring

to form a cage. They are made of bare metal, coated with

cloth, plastic or pyrolytic carbon, or else are composite

in nature.

TEFLON Trade name by DuPont for polytetral f 1 uoroethylene fiber or cloth.

TILTING-DISC VALVE . Jlemodynam i ca 1 1 y , a central flow type prosthesis in which

the occluder (poppet) is a free-floating pivoting disc.

OCCLUDER Moving ball or disc within the cage of a valve prosthesis

OR POPPETT which permits or stops the blood flow by opening or closing

the valve orifice. In caged-ball and caged-disc valves, the

poppet sits at the base in the closed position, and rests in the cage away from the valve orifice in the open position,

thus allowing the blood to flow peripherally around the

poppet. In tilting-disc valves, the disc tilts to a variable

angle in the open position permitting blood to flow; in the

closed position, the disc fits into the circumference of

the inflow ring.

TITANIUM A metal used in the construction of valve, struts, cages and stents. 720
GENERIC SCHEMA OF

SOME MAJOR TYPES OF HEART VALVE PROSTHESES

DOUBLE

CAGED

BALL

SINGLE

CAGED

BALL

CAGED

DISC

TILTING

DISC

BIOPROSTHESIS

(TISSUE VALVE)

72 I

VALVE PARTS

1

OCCLUDER

2. STRUT

3- VALVE ORIFICE

A. SEWING RING (cloth)

5. BASE RING (inside

sewing ring)

6. HORIZONTAL BARS OR STRUTS

7- DISC STOPPER

8. STENT

9. TISSUE CUSP (or valve

leaflet)

DIMENSIONS

A. OUTER DIAMETER

B. ANNULUS DIAMETER

C. MOUNTING DIAMETER

D. ORIFICE DIAMETER

E. STRUT PROJECTION

F. STENT INSIDE DIAMETER

G. HEIGHT
TABLE I

CAGED-BALL (High Profile) VALVES

Observat ion Type of Prosthesis Site*

. Double cage

Cage

JDpen cage

Bare metal struts; mechanical

'fixation (sutureless)

Single

' cage

Cloth covered

struts

Bare meta I struts

Three

struts

C losed caae

Cloth covered

' struts

Four struts

Bare

"met a I struts

Cloth-

.covered

struts

aortic; M i t r a I ; T = t r i cuspid

Feet in va I ve _

ori f i ce

No feet in

' va I ve orifice

Cloth-covered

oase r inn

Metal inner ring extends onto inflow surface of - sewing ring

Smeloff-Cutter

McGovern-Cromi;

Braunwa Id-Cutter

Starr-Edwards 1000

Starr-Edwards 1200

A.M.T

Inner ring does not extend Scarr . Edwards 126o onto sewing rtng

Pyrolytic ball; serrated ring edge

Small metal apical

" opening, cloth covered

Metal struts welded at apex ~~~

Compos i te cloth and

metal studded

inner ring

Plain cloth

covered struts

Composite struts with

metal track on inner surface of each

OeBakey-Surg i too I

Starr-Edwards 2300

Surg i tool 200

Starr-Edwards

2310, 2320

Starr-Edwards

2^00

Plastic inner . ring, with serrated ring edge

Smooth metal base ring

Fl uted

base ring

Cloth-covered

inner ring, metal struts not welded

at apex

Harken Ba I I

Starr-Edwards

6000

Starr-Edwards

6120

Compos i te inner ring

Tiny meta I studs

in ori f ice

Compos i te struts

wi th metal track in inner aspect of each

Starr-Edwards 6300l

Starr-Edwards

6310, 6320

Starr-Edwards 6^00

,M,T

M , T

M,T

M.T

M ,T

722
TABLE I I CAGEO-OISC (Low Prof i le) VALVES

Observat ion Type of Prosthes i s S i t:

Doub I re "cage

Two open cages

each has k bare metal struts

Cooley-Cutter

One closed, one

open cage; each with k bare metal struts

. Kay-Suzuki

Open

'cage (3 struts) Cross- Jones

S i ng I e "cage

Closed

' cage

k bare metal struts intersect

at apex of cage

struts form

2 non- i ntersect ing bars

•Perforated base ring

Smooth base ring with

circularly marked disc Very narrow base ring ,

Bare metal struts £ bars; smooth base ring

'Covered struts S bars; serrated base ring

.No muscle _

guard

,Two muscle —

guards

Four muscle

' guards

2 incurving bars covered wi th "" Teflon tubing

Struts coated

•with pyrolytic

carbon

Starr-Edwards 650C

Starr-Edwards 6520

Harken Disc

. Kay-Shiley T.

.Kay-Shi ley KG

Kay-Shi ley TG

Seal 1 -Surg I tool ~ 103. 1CU

Beal 1-Surgitool ~ 105, 106

723
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730


EVALUATION FORM

I. PATIENT INFORMATION

NAME

ADDRESS

last f i rst ^ 0.

number street

c i ty s tate zip

HOSPITAL

name

numbe r street

m c

c i ty

BIRTH DATE

RACE

HEIGHT

MARITAL STATUS

montn day year

AGE

CAUCASIAN

ORIENTAL

BLACK

OTHER

s ta te

SEX

zip

h

HISPANIC

cm. LENGTH cm. WEIGHT kg

SINGLE

DIVORCED

MARRI ED WIDOW(ER)

SEPARATED

OTHER

PREVIOUS KNOWN CLINICAL EVENTS (Is patient known to have had...)

ACUTE* CHRONIC'** Rx*

CONGESTIVE HEART FAILURE

MYOCARDIAL INFARCT I ON

CEREBROVASCULAR ACCIDENT

ENDOCARDITIS

ATRIAL FIBRILLATION

PULMONARY EMBOLUS

PERIPHERAL EMBOLUS

HEMOLYTIC ANEMIA

CHOLELITHIASIS

ANTICOAGULATION THERAPY

OTHER (specify)

* 1 month or shorter

'* longer than one month

'** check if treated 733
ORIGINAL VALVE FUNCTIONAL DESCRIPTION

STENOSIS

REGURGITATION

NORMAL

INDICATION FOR ORIGINAL VALVE REPLACEM

RHEUMATIC-TYPE DEFORMITY

CALCIFIC AORTIC STENOSIS,3 CUPS

CALCIFIC AORTIC STENOSIS, 2 CUPS

AORTIC STENOSIS, OTHER

ENDOCARDITIS

ACTIVE

HEALED

CONGENITAL LESION

OTHER, EXPLAIN
^1 Y H A CLASSIFICATION (Just prior to surgical explantation or deatfi)

i Dn Dm Div

ARD'I OPULMONARY RESUSCIATION PERFORMED? UNKNOWN

THE RECIPIENT OF A CARDIAC VALVE PROSTHESIS MAY HAVE IN HIS POSESSION A CARDIAC

VALVE- IDENTIFICATION CARD WHICH LISTS:

VALVE TYPE

VALVE SIZE

VALVE SERIAL NUMBER

VALVE MANUFACTURER

IMPLANT SITE

IMPLANT DATE

IMPLANTING SURGEON

9 THE ABOVE INFORMATION MAY ALSO BE PRESENT IN THE PATIENT'S HOSPITAL PROGRESS

CHART OR IN THE OPERATIVE NOTES

9 IN THE EVENT THAT THE IDENTIFICATION CARD (OR THIS INFORMATION) CANNOT BE LOCATED, THE IDENTIFICATION KEY AND CHARTS PROVIDED IN THE FRONT PORTION OF

THIS FORM SHOULD BE USED TO DETERMINE THE VALVE MANUFACTURER, MODEL , NAME,

MODEL NUMBER , AND TYPE/CONFIGURATION

9 IN MANY VALVES, THE SERIAL NUMBER IS FOUND UNDERNEATH THE FABRIC OF THE OUTER

ASPECT OF THE BASE RING. - TO OBTAIN SERIAL NUMBER IN THIS MANNER SHOULD BE CONSIDERED A LAST RESORT. - BE SURE TO DOCUMENT ALL PERTINENT INFORMATION

PRIOR TO THE REMOVAL OF THE FABRIC

© THROUGHOUT THIS FORM, "M" DENOTES MITRAL, "A" DENOTES AORTIC, AND "T" DENOTES

TRICUSPID VALVES. 4S THE INCIDENCE OF PULMONARY VALVE REPLACEMENT IS EXTREMELY

RARE, NO PROVISIONS HAVE BEEN MADE TO ACCOMMODATE IT. IF, HOWEVER, YOU HAVE

OCCASION TO EVALUATE AN EXPLANTED PULMONARY VALVE, PLEASE CHANGE ONE OF THE

HEADINGS (e.g. M, A, or T) to "P" AND PROCEED AS FOR OTHER VALVES

ALVE IDENTIFICATION INFORMATION AVAILABLE NO

MPLANT SITE MITRAL AORTIC I 1 TRICUSPID PULMONARY

IANUFACTURER

M A

J

CUTTER LABORATORIES

EDWARDS LABORATORIES

HANCOCK LABORATORIES

KASTEC

OTHER (specify)

M

SAINT JUDE MEDICAL

SHI LEY LABORATORIES

SURGITOOL

73'
II. PROSTHESIS INFORMATION

TYPE/CONF MATI GURAT i ON OF VALVE

DOUBLE CAGED BALL

SINGLE CAGED BALL

CAGED DISC

TILTING/PIVOTING DISC

BIOPROSTHESIS (e.g. porcine valve)

B

I -LEAFLET , CENTRAL OPENING

OTHER (specify)

MITRAL VALVE PROSTHESIS - implant information

NAME CF PROSTHESIS

IMPLANT DATE

month day year

DURATION

month day

EXPLANT DATE

MODEL NUMBER

SERIAL NUMBER

mon t h day year

SIZE

IMPLANTING HOSPITAL

IMPLANTING SURGEON(s) 1 .

J LTJ

year

S ZE NUMBER

OR

name

i

1 number s treet

ci ty state zip

1

.

last name 1

:

i rst

2. last name f i rst

(indicate surgeon(s)' position by placing appropriate number in box)

attending staff thoracic resident other resident

other (specify) — r

L

number s t reet TD CI

state zip
AORTIC VALVE PROSTHESIS - implant information

NAME OF PROSTHESIS

IMPLANT DATE

EXPLANT DATE

MODEL NUMBER

SERIAL NUMBER

IMPLANTING HOSPITAL

month day year

DURATION

month day year

SIZE L

month day ye3r

mm

SIZE NUMBER

. .OR

IMPLANTING SURGEON (s

1

1 1 1 name

1

i numbe r street

i i city s tate zip

]

last name f i rst

2. i 1 ! i 1

i

last name first

(Indicate surgeon(s)' position by placing appropriate number in box)

attending staff 1 [ thoracic resident | j other resident

other (specify)

number street

c i ty

TRICUSPID VALVE PROSTHESIS - implant information

NAME OF PROSTHESIS

state zip

IMPLANT DATE

EXPLANT DATE

month

n m

day

m

year

CD

DURATION

month day year

mor.t'h day " yeai

73 7
MODEL NUMBER

SERIAL NUMBER

sue rm mm.

SIZE NUMBER

OR

IMPLANTING HOSPITAL mname

numbe r

c i ty

IMPLANTING SURGEON(s) 1 ast name

s t reet

state zip

f i rst

last name first

(indicate surgeon(s)' position by placing the appropriate number in box)

attending staff thoracic resident other resident

other (specify)

] c

numbe r street

J L city state zip

III. SPECIMEN AND HANDLING

1. SURGICAL PAT HOLOGY . . . (Comp l ete this section if specimen is a surgically

explanted valve; if not, go to AUTOPSY section, p. 23)

SURGICAL EXP LANTAT I ON DATE

SURGICAL PATHOLOGY NUMBER

month day year

HOSPITAL ELXE name

numbe r ] [

I

city

st reet

state zip

73 8
SPECIMEN HANDLING - ENTIRE SPECIMEN

(Indicate your handling sequency by numbering each step in your

examination process in the order in which you performed them)

M A

PHOTOGRAPHY

COLD (SUB-FREEZING) STORAGE

Fl XATI ON FORMALDEHYDE

GLUTERALDEHYDE

OTHER (specify)

RADIOGRAPHY

PHYSICAL MEASUREMENTS (also see cross pathology section)

BLOOD CULTURE

TISSUE CULTURE

ELECTRON MICROSCOPY

SCANN I NG

TRANSM I SS I ON

SUE STAINS

H 5 E PAS

PAS DIGESTED

TR I CHROME

OIL RED "0"

OTHER (specify)

CONGO RED

MUC I N ELASTIC TISSUE

P T A H

ADDITIONAL STUDIES PERFORMED VES

STUDY

mon th

1

I TATF 1 ! i day year

2. AUTOPSY

DATE OF DEATH

PLACE OF DEATH

m c

month day

numbe r

HOSPITAL

HOME

year

c i ty

I I OTHER (spec : fy,

7 3 3

street

rn m

q

state

PUBLIC AREA

OFFICE

'P
EX PLANT I NG SURGEON^

(Indicate surgeon(s)' position by placing appropriate number in box)

attending staff I

[ thorac i c resident other resident

other (specify)

IND I CAT i ON FOR EXPLANTAT I ON (more than one may be indicated; please number

each in order of priority)

RED CELL HEMOLYSIS

PARAVALVAR LEAK

MATERIALS FAILURE

HIGH PRESSURE GRADIENT

THROMBUS / TISSUE OVERGROWTH

EMBOLISM

INFECTIOUS ENDOCARDITIS

OTHER (specify)

SURGICAL PATHOLOGIST(s) 1

2.

! r

L ... (Indicate patholog i st (s) 1 position by placing appropriate number in box)

attending staff pathology resident I j other resident

other (specify)

SPECIMEN DEFINITION

MAT

INTACT VALVE

VALVE CAGE ONLY

OCCLUDER (POPPET) ONLY

VALVE WITH SURROUNDING TISSUE

OTHER (specify)

740
DEATH WITNESSED

DEATH WITNESSED BY 1

YES NO

(Indicate witness 1 relationship to patient by placing appropriate

number in box)

SPOUSE

PHYSICIAN

PARAMEDIC

NURSE

FRI END

FAMILY MEMBER

CO-WORKER

OTHER (specify)

AUTOPSY DATE AUTOPSY NUMBER

mon th

PATHOLOGIST(s) 1.

2.

day yea r

J

(Indicate pathol og i s t (s ) position by placing appropriate number in box)

ATTENDING STAFF | CORONER (OR STAFF)

OTHER (specify)

RES IDENT

CLINICAL IMPRESSION OF CAUSE OF DEATH

PRIMARY CARDIAC DISEASE IMMEDIATE CAUSE OF DEATH

CARDIAC DISEASE CONT I R I BUT I NG FACTOR BUT NOT PRIMARY CAUSE OF DEATH

DEATH NOT RELATED TO CARDIAC DISEASE

SPECIMEN DEFINITION

MAT

HEART WITH VALVE IMPLANTED

| VALVE WITH SURROUNDING TISSUE

.

I INTACT VALVE ONLY

OCCLUDER (POPPET) ONLY

VALVE WITHOUT OCCLUDER

| I I |_J OTHER (specify)

7 4 I
SPECIMEN HANDLING - ENTIRE SPECIMEN

M A

PHOTOGRAPHY

COLD (SUB-FREEZING) STORAGE

Fl XATION

FORMALDEHYDE

GLUTERALDEHYDE

OTHER (specify)

RADIOGRAPHY

PHYSICAL MEASUREMENTS

BLOOD CULTURES

TISSUE CULTURES

ELECTRON MICROSCOPY

SCANN ING TRANSMISSION

iSUE STAINS

H £- E PAS

PAS DIGESTED

TR I CHROME

OIL RED "0"

OTHER (specify)

CONGO RED MUC IN ELASTIC TISSUE

P T A H

ADDITIONAL STUDIES PERFORMED yes NO

STUDY J DATE

month day

no

year
IV. PROSTHESIS EXAMINATION

I, OCCLUDER / LEAFLETS / CUSPS

IS OCC LUDER/LEAFLET/CUSP MOTION RESTRICTED? CH YES | | NO

IF YES, DESCRIPTION OF RESTRICTED OCCLUDER/LEAFLET/CUSP MOTION MAT

OCCLUDER/LEAFLET(s) IMMOBILIZED IN OPEN POSITION

OCCLUDER/LEAFLET(s) IMMOBILIZED IN CLOSED POSITION

OCCLUDER/LEAFLET(s) IMMOBILIZED IN INTERMEDIATE POSITION

FULL CLOSURE POSSIBLE, FULL OPENING IMPEDED

FULL OPENING POSSIBLE, FULL CLOSURE IMPEDED

BOTH FULL OPENING AND FULL CLOSURE TOTALLY OR PARTIALLY IMPEDED

CAUSE OF RESTRICTED OCCLUDER/LEAFLET/CUSP MOTION (if cusps or leaflets, indicate

number involved. You may check as many as applicable)

u

THROMBUS/TISSUE OVERGROWTH ON CAGE (rigid prostheses only)

THROMBUS/TISSUE OVERGROWTH IN PRIMARY FLOW ORIFICE

THROMBUS/TISSUE OVERGROWTH IN SECONDARY FLOW ORIFICE

THROMBUS/TISSUE OVERGROWTH ON OCCLUDER/LEAFLET(s ) /CUSPS

POST SURGICAL UNDE3RIDED TISSUE

I j UPSTREAM | | DOWNSTREAM

MURAL THROMBUS

LJ UPSTREAM

CUSP CALCIFICATION

CUSP VEGETATION

CUSP FIBROSIS

DOWNSTREAM

NUMBER OF CUSP(s) INVOLVED

NUMBER OF CUSP(s) INVOLVED

NUMBER OF CUSP(s) INVOLVED

SUTURE MATERIAL PROJECTING INTO PRIMARY ORIFICE

[j UPSTREAM I I DOWNSTREAM

DEFORMATION OF CAGE

STRUT, STENT, AND/OR HINGE FRACTURE

RETRACTION/FRAYING OF CLOTH

VALVE ALIGNMENT PROBLEM

VALVE SIZING PROBLEM

MISSHAPEN OCCLUDER

THROMBUS/TISSUE OVERGROWTH INTERFERES WITH COMPLETE EXAMINATION

UNDER MICROSCOPE

WITH ELECTRON MICROSCOPE

TO NAKED EYE WITH HAND LENS

OTHER (specify)

743
S THERE EVIDENCE OF OCCLUDER/ LEAF LET/ CUSP CHANGES? YES NO

IF YES,

M A

(you may check more than one)

SWELLING

SHRINKAGE

CUSP CALCIFICATION (b i op ros theses only)

CUSP FIBROSIS (b ioprostheses only)

DISTORTED SHAPE

Dl SCOLORATI ON CRACKING

PITTING (e.g. from corrosion)

SUBSURFACE INCLUSIONS (trans i 1 1 umi nate)

GROOVING (of disc occluder only)

NOTCHING (of disc occluder only)

OTHER (speci fy)

ADHERENT MATERIALS (are there thrombi, vegetat i on

,

' t i ssue , or other materials

present on occluder, leaflets, and/or cage?)

OCCLUDER/POPPET (rigid prostheses) MAT

FRIABLE THROMBUS

NON-FRIABLE THROMBUS

VERRUCUS VEGETATIONS

TISSUE OVERGROWTH

NOT FULLY EVALUATED

OTHER (specify)

LEAFLETS/CUSPS (bi-leaflet and b ioprostheses

)

MAT if CUSPS

FRIABLE THROMBUS

NON-FRIABLE THROMBUS

VERRUCUS VEGETATIONS

TISSUE OVERGROWTH

NOT FULLY EVALUATED

[ I I I I | I OTHER (specify)

7 44
CAGE MAT

FRIABLE THROMBUS

NON-FRIABLE THROMBUS

VERRUCUS VEGETATIONS

TISSUE OVERGROWTH

NOT FULLY EVALUATED

OTHER (specify)

2. VALVE FRAMEWORK MAT ^struts, stent, hinges, and muscle guard ring)

FRACTURE

SCRATCHING

PITTING

BENDING

FRAYED/TORN CLOTH

MISSING CLOTH

RETRACTED CLOTH

NOT FULLY EVALUATED

OTHER (specify)

3. SUTURE / TISSUE INTERFACE

T

SUTURE LINE

M A

INTACT

ENDOCARDITIS

BLIND SINUS PRESENT

ANEURYSM PRESENT

PARAVALVAR LEAK

VEGETATIONS

THROMBUS

TISSUE OVERGROWTH

CALCIFICATION

OTHER (specify)

CALCIFICATION

METHOD OF SUTURE PLACEMENT (check as many as applicable] MAT

INTERRUPTED

UN INTERRUPTED

MATTRESS

PURSE-STRING

OTHER (specify)

745
TYPE OF SUTURE MATERIAL (check as many as appropriate)

SILK

Wl RE MERS I LENE

PROLENE

DEXON

VICRO

OTHER (specify)

Mi A

TEVDEK

DACRON

NYLON

CHROMIC CATGUT

PLAIN CATGUT

COTTON

4. BASE RING

INFLOW FACE (includes fabric covering)

A r

u u

FRACTURE

SCRATCHING

PITTING

BENDING

FRAYED/TORN CLOTH

MISSING CLOTH

RETRACTED CLOTH

TISSUE I N GROWTH

OTHER (soecify)

% fabric area covered

with adherent tissue

OUTFLOW FACE (includes fabric covering) MAT

FRACTURE

SCRATCHING

PITTING

BENDING

FRAYED/TORN CLOTH

MISSING CLOTH

RETRACTED CLOTH

TISSUE INGROWTH

OTHER (specify)

/o fabric area covered

with adherent tissue

7

6
DEHISCENCE (PARAVALVAR LEAK)

1 - 5 mm

6 - 10 mm

11 - 20 mm

2 1 - 30 mm

30 - mm. ^50 mm

• NUMBER EACH DEHISCED AREA ON SKETCH BELOW: THEN, ACCORDING TO SIZE, P THE NUMBER OF EACH DEHISCED AREA IN THE APPROPRIATE BOX ABOVE.

TOTAL PERCENT OF VALVE PERIMETER DEHISCENCE

KEY: (diameter = 6 cm, ) SKETCH FINDINGS BELOW:

FIGURE 1

747
ESTIMATED REDUCTION IN PRIMARY FLOW ORIFICE AREA

TO APPROXIMATE SIZE AND NATURE OF THE REDUCTION IN THE ORIFICE, USE THE

TRANSPARENT TEMPLATE ATTACHED TO THE END OF TH i S FORM. SKETCH YOUR

FINDINGS ACCORDING TO THE KEY IN THE APPROPRIATE VALVE ORIFICE FIGURE.

KEY AORTIC VALVE

ESTIMATED TOTAL X REDUCTION

J//////\ THROMBUS

%A TISSUE OVERGROWTH

| VEGETATION

J OTHER (specify)

ESTIMATED TOTAL REDUCTION

MITRAL VALVE TRICUSPID VALVE

QH ESTIMATED TOTAL % REDUCTION ESTIMATED TOTAL % REDUCTION

FIGURE 2 74 8
OSTHESIS ORIENTATION

IN THE FOLLOWING FIGURE, SKETCH THE APPROPRIATE ORIENTATION OF THE IMPLANTED

PROSTHESIS (es). e. g., AN ARROW SHOULD POINT IN THE DIRECTION OF THE LARGE

ORIFICE, OR STRUT OR STENT POSITIONS SHOULD BE DRAWN IN.

PULMONIC VALVE

L. CORONARY A. -Q| ^AORTIC VALVE

MITRAL

VALVE

REFERENCE

1-TRICUSPID

| VALVE

FIGURE

GROSS PATHOLOGY - autopsy only

ART MEASUREMENTS

HEART WE IGHT

RIGHT VENTRICLE LENGTH (valve ring to internal apex)

RIGHT VENTRICLE THICKNESS (at midpoint of free wall)

VALVE RING CIRCUMFERENCE - TRICUSPID (natural valve)

VALVE RING CIRCUMFERENCE - PULMONIC (natural valve)

LEFT VENTRICLE LENGTH (valve ring to internal apex)

LEFT VENTRICLE THICKNESS (at midpoint of free wall)

VALVE RING CIRCUMFERENCE - MITRAL (natural valve)

VALVE RING CIRCUMFERENCE - AORTIC (natural valve)

AORTIC CIRCUMFERENCE (2cm. above prosthetic valve ring)

RIGHT CORONARY ARTERY OSTIUM (distance anove prosthetic

valve ring)

LEFT CORONARY ARTERY OSTIUM (distance above prosthetic

va 1 ve ring)

OTHER (specify)

OTHER (specify)

q.m

cm.

cm.

cm.

cm.

cm.

cm.

cm. cm.

cm.

cm

cm. cm. cm

749
TOPOGRAPHICAL SCHEMA OF THE HEART

SHOWING THE CORONARY VESSELS

(Sketch below onl y pericardial, epicardial, and graft findings)

Figure 4
PERICARDIUM / EPICARDiUM AND PERICARDIAL SAC

PERICARDITIS - CHRONIC

PERICARDITIS - ACUTE

ADHESIONS

EASILY LYSED

DENSE FIBROUS

FLUID

HEMORRHAGIC

CLEAR

CLOUDY

cc

cc

cc PAC I NG WIRES (show location on topographical sketch)

TEMPORARY

PERMANENT

IN THE FOLLOWING SECTION, ABBREVIATIONS ARE USED FOR HEADINGS: R A denotes RIGHT ATRIUM; L A denotes LEFT ATRIUM; R V denotes RIGHT

VENTRICLE; and L V denotes LEFT VENTRICLE. M, A, T, and P stand for

MITRAL. AORTIC, TRICUSPID, AND PULMONIC AS PREVIOUSLY NOTED

CHAM3ER SIZE

RA RV LA LV

APPEARS NORMAL

D I LATED

REDUCED IN SIZE

ENDOCARDIUM (A)

1 FOCAL F I BROS I S/TH I C KEN ! NG

2 DIFFUSE F I BROS I S/TH I CKEN I NG

3 MULTI-FOCAL FIBROSIS

4 FRIABLE THROMBUS

5 NON-FRIABLE THROMBUS

6 SEPTIC VEGETATION

7 BLAND VEGETATION

8 PACING W|RE(s)

75 I
VIEW OF CARDIAC FINDINGS

(Sketch or indicate below your intracardiac findings, coding each finding

with the corresponding letter and number found in the text

)

752
MYOCARDIUM (B)

RA RV LA LV

1 HYPERTROPHY/THICKENING

2 THINNING

3 FOCAL FIBROSIS

4 DIFFUSE FIBROSIS

5 MULT I -FOCAL FIBROSIS

6 FOCAL HEMORRHAGE

7 DIFFUSE HEMORRHAGE

8 MULTI -FOCAL HEMORRHAGE

9 ABSCESS

10 ACUTE INFARCTION _ _

11 HEALING INFARCTION _

1 2 HEALED INFARCTION

13 PERFORATION/RUPTURE

|4 SUTURES I I I | I I I CHORDAE TENDINEAE (C)

1 THICKENING

2 FUSION

3 SHORTENING j 4 RUPTURE

5 VEGETATIONS

6 SURGICAL REMOVAL | | I

PAPILLARY MUSCLES (Q)

1 THICKENING

2 THINNING

3 FIBROSIS

4 HEMORRHAGE

5 INFARCTION

6 ABSCESS

7 RUPTURE

8 SURGICAL REMOVAL | | |

FOR THE ABOVE INFORMATION, PLEASE SKETCH YOUR FINDINGS ON FIGURE 5 , FOUND

ON PAGE 38. INDICATE YOUR FINDING BY THE LETTER AND THE NUMBER OF THE

ABNORMALITY, AS CODED TO THE TERMS ABOVE.

753
NOTES OF SKETCHES (supplemental)

754
PLEASE SKETCH OR INDICATE

FINDINGS, AS APPROPRIATE.

'-'-^^vlJ- R CORONARY A. %

J-AORTIC VALVE

l-TRICUSPIO VALVE

ATURAL VALVES (E)

1 REPLACED BY PROSTHESIS

2 VALVE RING

a DILI TAT I ON b STENOSIS

C CALCIFICATION

d HEMORRHAGE e ABSCESS

f PERFORATION

g SUTURES

OTHER (specify)

3 VALVE CUSPS

a THICKENING

b CALCIFICATION

C RETRACTION/ROLLING

d BLAND VEGETATIONS e SEPTIC VEGETATIONS

f FUSION OF COMMISSURES

OTHER (speci fy)

755
M

ASCENDING AORTA / (p)

SINUS OF VALSALVA

1 RUPTURED ANEURYSM

2 UNRUPTURED ANEURYSM

3 INFECTIONS / ENDOCARDITIS

4 FATTY STREAKS

5 COMPLICATED LESIONS

6 CALCIFIED LESIONS

7 EMBOLIC FRAGMENT

OTHER (specify)

CORONARY ARTERIES AND BRANCHES

S IN THE FOLLOWING SECTION, THE COLUMN ABBREVIATIONS ARE AS FOLLOWS:

T denotes THROMBUS, E F, EMBOLIC FRAGMENT; F S, FATTY STREAKS;

F P, FIBROUS FLAQUES; COL, COMPLICATED LESIONS; CAL, CALCIFIED

LESIONS; AND %RED, PERCENT REDUCTION IN CROSS-SECTIONAL AREA IN THE MOST SEVERE SECTION OF ARTERIAL NARROWING.

CORONARY BRANCH

Right coronary arteries

1 00 OX I MA

L

2 MID

3 DISTAL

4 POSTERIOR DESCENDING

T EF FS FP COL CAL %Red.

n n h n r

i i

Left coronary arteries

5 MA I N 6 PROXIMAL LEFT ANTERIOR DESCENDING

I 7 MID LEFT ANTERIOR DESCENDING

8 APICAL LEFT ANTERIOR DESCENDING

9 F I RST DIAGONAL

|0 SECOND DIAGONAL

| | PROXIMAL CIRCUMFLEX

1 2 OBTUSE MARGINAL

| 3 DISTAL C IRCUMFLEX

1 4 POSTEROLATERAL

| 5 POSTERIOR DESCENDING

n P P

n

PLEASE MARK YOUR ABOVE FINDING ON THE SKETCH ON p. k2

756
FROM AUSTEN et a I Circulation '78

Figure 7

ON THE SKETCH ABOVE, PLEASE INDICATE YOUR FINDINGS CORRESPONDING TO THE COLUMN

ABBREVIATIONS ON p. 42. (EXAMPLE: EMBOLIC FRAGMENT OF PROXIMAL LAD SHOULD BE WRITTEN AS E F IN THE #6 AREA OF THE SKETCH).

75 7
BY-PASS GRAFT No. 1 (Indicate site of graft as Gl on coronary artery sketch

or topographical sketch,

FIBROUS INTIMAL PROLIFERATION

MEDIAL FIBROSIS

THROMBUS

FATTY STREAKS

FIBROUS PLAQUES

COMPLICATED LESIONS

CALCIFIED LESIONS

REDUCTION IN DIAMETER

OTHER (specify)

% ESTIMATED REDUCTION

BY-PASS GRAFT No. 2 Indicate site of graft as G2 on coronary artery sketch

or topographical sketch

FIBROUS INTiMAL PROLIFERATION

MEDIAL FIBROSIS

THROMBUS

FATTY STREAKS

FIBROUS PLAQUES

COMPLICATED LESIONS

CALCIFIED LESIONS

REDUCTION IN DIAMETER

OTHER (specify)

% ESTIMATED REDUCTION

BY-PASS GRAFT No. 3 Indicate site of graft as G3 on coronary artery sketch

or topographical sketch

FIBROUS INTIMAL PROLIFERATION

MEDIAL FIBROSIS

THROMBUS

FATTY STREAKS

FIBROUS PLAQUES

COMPLICATED LESIONS

CALCIFIED LESIONS

REDUCTION IN DIAMETER

OTHER (specify)

% ESTIMATED REDUCTION

758
f

: >T I MATED NARROWING OF CORONARY ARTERIES

AMPLE

TERY

TO APPROXIMATE THE EXTENT AND PERCENTAGE OF NARROWING OF THE CORONARY

ARTERIES, USE THE TRANSPARENT TEMPLATE ATTACHED TO THE END OF THIS FORM.

SKETCH YOUR FINDINGS SIMILAR TO THE EXAMPLE SHOWN AND INDICATE THE ARTERY IN QUESTION.

ARTERY

l i

1 1 PERCENT OCCLUSION

r

PERCENT CCCLUS I ON |_

1 1 J

"

TERY ARTERY

PERCENT OCCLUSION

FIGURE 3

PERCENT OCCLUSION
VI. HISTOPATHOLOGY

1. TISSUE OVERGROWTH

2. VEGETATIONS

3. REPRESENTATIVE SECTIONS

(Interventricular septum as reference point)

a. 12 o'clock 1

b. 3 o'clock

c. 6 o'clock

d. 9 o'clock

4. OTHER, describe

7S0
VII. SUMMARY SHEET

Please summarize below your key findings according to the Systematized

Nomenclature of Medicine (SNOMED)

ETIOLOGY

'OROGRAPHIC FINDINGS

MORPHOLOGIC FINDINGS

Dl SEASE

PROCEDURES

Signed M . D

Date

7S 1
ORIFICE MEASUREMENT TEMPLATE

USE THIS TRANSPARENT TEMPLATE TO APPROXIMATE AND MARK

THE OBSERVED REDUCTION IN PRIMARY FLOW ORIFICE AND REDUCTION

(NARROWING) OR CORONARY ARTERIES. SKETCH YOUR F1NDINCS

ON 32 AND 44 OF THE EVALUATION FORM.

USE EITHER FIGURE (OR BOTH) TO APPROXIMATE ACTUAL SIZE

762 -
Appendix C

Evaluation Protocols*

This protocol was designed for the evaluation of retrieved, expanded

teflon graft material , G0RE-TEXR

.

Docume n tation

Every returned sample we receive is logged into the Histology Logbook.

A histological log number is written on each specimen container received.

The log number corresponds to the date the specimen arrived in Histology and

the number of specimens logged in on that particular day. For example, the

first specimen logged in on May 21, 1980, would receive the log number

5-2180-1. In addition to the histology log number, all the information sent

with the specimen is recorded into the histology logbook. Any information

needed which is not included with the specimen is requested with a thank

you letter.

To identify each sample for the gross photographic documentation, a typed

I.D. label with the histology log number, patient's name and surgeon's name

is prepared.

The following equipment is used to photograph the returned samples:

1. Photo table with 4-BBA number 1 daylight bulbs and adjustable

camera holder.

2„ 35mm Canon AT-1 camera with Canon 100mm Macro lens,

3. Kodachrome KPA 40, Type A professional transparency film.

4. Dissecting tray, eye dropper, forceps, scissors, green sponge-cloths, mm ruler, latex gloves and safety glasses.

The specimens usually arrive in a fixative of either cacodylate buffer or

10% formalin. For protection, gloves and safety glasses are worn during photograph preparation. The specimen is removed from the container with forceps

with care to avoid disrupting the gross appearance. To insure that the tissue

does not dry and become damaged, it is periodically moistened with fixative.

*Provided by Ms. B. Boyce, W.L. Gore Associates Inc., 1505 N. Fourth St. Flagstaff, Arizona 86002

imiimMHhiuii*>iwwWB
The moisture also highlights the specimen for a quality photograph. The

specimen is placed on a green sponge-cloth in the dissecting tray. The I.D.

label is placed directly below the sample and the ruler directly above the

sample. A picture of the graft outer surface appearance is taken first.

If possible, a transverse picture is taken to demonstrate the appearance of

the lumen. The graft is then cut along its longitudinal axis and pinned

open to expose the luminal surface. Each photograph is taken in duplicate,

a slide for the analysis and one slide for the gross photograph notebook.

When a specimen is too small to photograph with the 35mm camera, a Nikon

SM-10 Stereoscope with a Nikon M-35 FA 35mm camera is used, For lighting the

subject, an MK 11 Fiber Optic light is used. This scope allows up to 40 power

magnification, which is especially beneficial for small diameter grafts.

Gross Examination

a) All GORE-TEX graft specimens submitted to the Histology laboratory for

evaluation are inspected grossly, following a standard method of examination.

The length of the graft segment is measured and expressed in centimeters or

millimeters. Host vessel attachment, if present, is noted

and the respective proximal and distal host vessel segments are examined for

evidence of intimal hyperplasia, pannus extension, suture line dehiscence, etc.

The graft outer surface is thai considered, and tissue attachement, or

lack thereof, is noted. When tissue is present, relative degree of attachment

is determined with a needle probe inserted between the tissue and the graft

outer surface. A subjective determination of tissue attachment is concluded

from the force necessary to pull a portion of tissue away from the graft outer

surface. Any evidence of hematoma is also noted.

The GORE-TEX graft assumes a tan or off-white appearance after days or

weeks of implantation. Any wall discoloration, such as a red or dark-brown

continuous or mottled appearance is recorded. A careful examination of the

entire graft luminal surface is performed. If clot is present, clot consistency,

7GA
attachment, color and thickness is recorded. Near the anastomoses, the luminal

surface is checked for evidence of pannus extension, and the suture line is

examined for evidence of tissue overgrowth. If the appearance of the graft

is consistent along its length, one representative longitudinal section is

taken. If both anastomoses are present or if the luminal or outer surface

matrices differ along the length of the graft, several longitudinal sections

are taken. Transverse sections are taken if clot is present on the luminal

surface to determine degree of occlusion of the lumen.

Also, transverse sections are taken of GORE-TEX grafts used as A-V

fistulae for dialysis, if the graft presents with a pseudoaneurysm. With a

transverse section, the pseudoaneurysm capsule can be visualized.

b) Occasionally grafts are returned with questions regarding the mechanical

integrity of the graft material. In these instances, the graft sample is

placed in a potassium dichromate solution** and all organic matter is digested

from the specimen, 1/2-12 hrs. The sample is thoroughly rinsed in distilled

water, dried, and submitted to our Quality Control department.

A destructive water entry pressure (WEP) test is performed on the sample.

The test consists of subjecting the graft to a initial water entry pressure

of 2 psi, then increasing the pressure .2 psi/minute until the graft leaks.

A minimum WEP of 3.0 psi is required for confirmation of structural integrity.

All findings are recorded and reported to the surgeon who submitted the sample.

Microscopic Examination

The sections taken at gross examination are processed for standard paraffin

sections, using alcoholand toluene in the tissue processor.

**A sulphuric acid - potassium dichromate mixture used for cleaning laboratory

glassware (e.g. Dichrol). The digestion is carried out at room temperature.

7SG
The GORE-TEX graft is cut with an American Optical "820" Spencer

Microtome. The majority of grafts are cut at 6 microns thickness.

Standard microtome knives are used. Disposable microtome blades are

not recommended as they are not sharp enough to cut proper ribbons

from specimens which contain graft material. A 7203 Thomas Fanz

Microtome Knife Sharpener is utilized and is one of the most important

reasons for obtaining good tissue slides. The blades must be sharpened

frequently to keep them at the peak of perfection for high performance.

The blades are also honed on a leather strop for final fine finish.

The following routine stains are ssed for the sections:

H & E Milligan's Trichrome

Ledrum's Acid Picro-Mal 1 ory Fibrin

Occasionally we are asked to do special stains. These consist mainly of

Dahl's Calcium, Brown & Brenn Bacteria, Verhoeff's Elastin, & Hall's Bilirubin.

These are requested either by the party who sends us the specimen or by our

laboratory technician upon gross examination of the specimen. Vie use these

particular stains because they are the best we have found to use with our

graft material. The sections are examined in a routine manner, progressing

from host vessel characteristics (if the host vessel is present), the suture

line, graft outer surface, interstitial space (wall) to the luminal surface.

The host vessel examination includes looking for evidence of hemorrhaging

or hematoma formation in the adventitia, medial calcification, intimal hyperplasia near the suture line, presence or absence of the endothelium and assessment of the relative health of the vessel. The suture line is examined for

possible clot formation, pannus extension or endothelial cell overgrowth.

Tissue necrosis around suture material is also assessed.

7GG
Examination of the graft outer surface includes determination of the

degree of tissue attachment, and penetration of tissue through the reinforcing

material and into the graft wall. Both H & E and Trichrome stained sections

are examined. Any cellular response is noted. If indicated by the appearance

of the tissue, the Brown and Brenn bacterial stain or Dahl 's calcium stain are

performed on sections to check for sepsis or calcification.

Graft wall contents are investigated using sections stained with H & E,

Trichrome, Fibrin and when applicable, bacterial, calcium and bilirubin stains.

The graft wall is specifically examined for fibroblastic infiltration, collagen

production, infiltration of blood elements, bacterial colonization, and uniformity

of wall filling,

A microscopic examination of the luminal surface is performed to assess

deposition of blood elements, including fibrin, erythrocytes and neutrophilic

leukocytes, or tissue extension from the host vessels. Attachment of luminal

surface matrices is assessed by noting degree of matrix penetration into the

graft interstitial spaces. If clot is present, a relative assessment of the

age of the clot is performed based on clot constituents. Clusters or

erythrocytes and leukocytes represent post-removal or post-mortem clot,

while laminated fibrin is indicative of pre-mortem deposition. Measurements of any luminal surface matrix are recorded as is degree of surface

covered by the matrix. Sections stained with the usual stains (H & E, Trichrome and Fibrin) are examined. If pannus extensions are present, a section

stained with Verhoeff's Elastin stain is examined for presence of elastic

tissue.

Histological observations are summarized, and the analysis and summary

are recorded on a standard form (see attached).

When scanning electron microscopy is performed on sections of a returned

graft sample, light microscopy observations are correlated with scanning electron microscopy observations in a combined summary.

7B7
Scanning Electron Microscopy

A representative sample of each specimen analysed is examined by SEM.

The specimens are cut, placed in a divided process basket, and immersed in a

Wheaton dish of cacodylate buffer and refrigerated for 24 hours.

The specimens are then washed with a continuous flow of distilled water

for 3-4 hours, to remove the cacodylate buffer solution.

The specimens are then dehydrated by sequentially immersing in 50%, 70%,

80%, 95%, and 100% ethanol solutions. This is followed by immersion in a 50%

ethanol/50% amyl acetate solution and then by immersion in 100% amyl acetate.

The specimen is then dried for examination in the SEM with a CO^ critical point

dryer. For fatty specimens immersion in chloroform is included prior to

critical point drying.

For examination of transverse sections the specimen may be freeze-fractured

in liquid nitrogen after critical point drying. Specimens are examined using an

Amray 1000A scanning electron microscope employing a tungsten filament.

The entire flow surface of the sample is scanned using double display CRT's

with a one to four magnification ratio. The usual magnifications are 200X

and 800X, or 500X and 2000X. The host vessel is scanned to determine the

composition of material and/or tissue on the flow surface. The host vessel

endothelial layer is often sloughed during specimen implantation or removal,

and scanning electron microscopy can sometimes determine the areas of regeneration of this layer. The degree of confluence of the endothelial cells is noted

as well as the areas of extension over the suture line onto the graft luminal

surface. Other material or tissue composition of the graft flow surface is

noted. Any areas of exposed graft luminal surface are scanned to determine

if any material, cells or tissue appear to be penetrating the interstices.

The specimen is changed to an approximate 90 degree orientation to the beam

to determine the thickness of the material and/or tissue on the flow surface.

7S8
Any abnormalities of the specimen such as bacteria or

artifacts due to specimen preparation, are also noted. The wall interstices

are not routinely scanned. The graft structure usually shows a smeared appearance when sectioned with a cutting instrument. Freeze fracturing, which prevents structural smearing, is not usually performed due to the large number

of specimens processed.

A low magnification (approximately 6x-20x) micrograph is taken to show

the overall view of the sample and to indicate the sites of the higher magnification micrographs. These higher magnification micrographs are usually taken

between 500 X and 2000X, as this is the magnification range that appears to

best demonstrate the cell tissue and/or material type. Polaroid type 52 film

is used for all micrographs. The micrographs are treated with Blair spray

fix, workable matte fixative (Blair Art Products, Inc., Memphis, Tenn.) rather

than the Polaroid jelly. The jelly is messy, caustic, reflects light which

interferes with the observation of the micrograph and takes a long time to dry.

To date, micrographs up to 2 1/2 years old and treated with Blair spray fix

reveal no discoloration or other abnormalities. A duplicate set of 35mm slides

are taken of each micrograph, one set for our files and one set for the surgeon.

A combined summary of scanning electron microscope and light microscope

observations is included with the completed analyses.

7G9
N9

W. L . GORE Be ASSOCIATES, INC

MEDICAL PRODUCTS DIVISION

P.O. DRAWER NUMBER 1 FLAGSTAFF, ARIZONA 86002

1505 NORTH FOURTH STREET DOCK NUMBER 2 PHONE: 602/526-3030 TWX: 910/972-0960

RETURNED CLINICAL SAMPLE EVALUATION

Gore No. Date:

SAMPLE IDENTIFICATION:

LOT No. SERIAL No.

RETURNED FROM:

PATIENT IDENTIFICATION:

AGE OF PATIENT:

REMOVAL DATE:

SITE:

SAMPLE HISTORY

SEX: IMPLANT DATE:

IMPLANT DURATION:

REASON FOR IMPLANTATION:

PATIENT CONDITION AFTER IMPLANTATION:

REASON FOR REMOVAL:

PATIENT CONDITION AFTER GRAFT REMOVAL:

770

JEWARK, DELAWARE • FLAGSTAFF, ARIZONA • MUNICH, WEST GERMANY • DUNFERMLINE, SCOTLAND
[ETURNED CLINICAL SAMPLE EVALUATION

age 2.

ROSS SAMPLE OBSERVATIONS:
RETURNED CLINICAL SAMPLE EVALUATION

Page 3.

HISTOLOGICAL OBSERVATIONS:
W. I_. GORE 3c ASSOCIATES. INC

MEDICAL PRODUCTS DIVISION

P.O. DRAWER NUMBER 1 FLAGSTAFF, ARIZONA 86002

1505 NORTH FOURTH STREET DOCK NUMBER 2 RETURNED SAMPLE EVALUATION

PHONE: 602/526-3030 TWX: 910/972 0960

ore No. Animal 1.0. GORE-TEX® Type:

ETURNED FROM:

WIPLE HISTORY:

ROSS SAMPLE OBSERVATIONS:

STOLOGICAL OBSERVATIONS.

TE: 773 SIGNED:

GORE-TEX is a trademark of W. L. Gore & Associates, Inc. NEWARK. DELAWARE • ELKTON. MARYLAND FLAGSTAFF, ARIZONA • MUNICH, WEST GERMANY • DUNFERMLINE, SCOTLAND

MPGHIS Oi
Testing Procedure*

This protocol was designed for the mechanical evaluation of weft

knit graft material in the form of small samples, which precludes fabric

testing.

After receipt of the retrieved graft (not fixed in formalin) the

graft is cleaned by the following procedure:

Materials :

Terg-A-Zyme - 7.5 g/liter water.

Cleaning Procedure :

1) The explanted grafts are handled using plastic gloves.

2) Fill beaker with distilled water, drop in spin bar and place

beaker on hotplate. Start bar spinning slowly and turn heat

on low. Optimum temperature is 120°F (50°C).

3) Weigh the appropriate amount of Terg-A-Zyme into disposable

weighing tin and pour it into the spinning water.

4) When Terg-A-Zyme has dissolved put graft into solution,

5) Change Terg-A-Zyme solution every 2 hours until water is clean

and tissue is soft. Rinse graft when changing solutions, rubbing

graft between fingers under running water.

6) When tissue has become soft hold graft under running water and

carefully strip tissue away from graft by using tweezers. Put

tissue in plastic bag for disposal. When graft is clean rinse

thoroughly to remove any Terg-A-Zyme.

Evaluation :

The identity of the graft is checked by visual examination and a

filament count of the yarns. Stitch density was measured by counting the

number of stitches in each direction using a 1 cm eye piece micrometer.

If the sample was a complete cylinder, the diameter was measured and the

*Provided by Ms. K. Botzko, USCI Surgical Products, Box M, Billerica, MA, 01821

77 A
total number of stitches around the circumference counted, Individual

yarns were unravelled from the graft and were used for tensile tests.

The tests were performed on a Tineus 01 sen tensile tester using air

grips with a 5 cm spacing at 50mm/min crosshead speed.

775
Dacron Graft Evaluation Protocol*

The following flow diagram illustrates the evaluation program used

for the evaluation of retrieved Dacron grafts. The specific tests which

are conducted on any graft are based upon the reason for the return of the

graft as well as the size and condition of the sample when received by Meadox.

HISTOLOGICAL

PREPARATION

RECOVERED DACRON GRAFT

10 - 50 X MICROSCOPE

1. MACRO

2. MICRO

(50-100X)

EXAMINE GROSS SPECIMEN

OBTAIN PHOTOGRAPHIC

RECORD V

ENZYME DIGESTION REMC\T TISSUF

FROM FABRIC

FABRIC PORTION V

IDENTIFY

COMPOSITION:

1. INFRARED

2. SOLUBILITY

CHARACTERIZE

STRUCTURE

PHYSICAL TESTS: TENSILE STRENGTH BURST STRENGTH

POROSITY

PHOTOGRAPHIC RECORD MACRO

SEM

YARN-

-

FILAMENT COUNT

FILAMENT CROSS- SECTION

TENSILE

STRESS/STRAIN

PROPERTIES

FABRIC-

-

IDENTIFY CONSTRUCTION

*Provided by Dr. S. Weinberg, Director of Research, Meadox Medicals, 103

Bauer Dr., P.O. Box 530, Oakland, New Jersey 07436

776

-ft U.S. GOVERNMENT PRINTING OFFICE : 1981 O—336-652
j.H4A 'REV- 2-8C)

U.S. DEPT. OF COMM.

(BIBLIOGRAPHIC DATA

I.HEET (See instructions)

1. PUBLICATION OR

REPORT NO. NBS SP 601

2. Performing Organ. Report No 3. Publ ication Date

January 1981

TITLE AND SUBTITLE

^mplant Retrieval: Material and Biological Analysis

Proceedings of a Conference held at the National Bureau of Standards,

paithersburg, MD 20234, May 1-3, 1980

j\UTHOR(S)

f\1 1 an Weinstein, Donald Gibbons, Stanley Brown, and William Ruff, Editors

PERFORMING ORGANIZATION (If joint or other than NBS, see instructions) | 7. Contract/Grant No.

(national bureau of standards

Department of commerce

washington, d.c 20234

8. Type of Report & Period Covered Final

illPONSORING ORGANIZATION NAME AND COMPLETE ADDRESS (Street. City. State. ZIP)

[food and Drug Administration, National Heart, Lung and Blood Institute, National

institute for Arthritis, Metabolism and Digestive Diseases, National Institute for

jSandi capped Research, Veterans Administration, and the American Society for Testing

; and Materials

^SUPPLEMENTARY NOTES

Uibrary of Congress Catalog Card Number: 80-600194

I

| Document describes a computer program; SF-185, FIPS Software Summary, is attached.

1 iABSTRACT (A 200-word or less factual summary of most significant information. If document includes a significant

I bibliography or literature survey, mention it here)

This book contains the proceedings of a conference on implant retrieval and

alysis as well as a report on a workshop concerned with implant retrieval systems,

enty-six invited papers that were presented at the conference are included. Four

ibject areas are specifically addressed: bulk phenomena, release phenomena, interice phenomena, and information utilization. Implants of both orthopaedic type and

rdiovascular type were considered at the conference. Data on the failure modes of

plants were presented. Specific consideration of biocompatability problems was

eluded. Several operating data/information systems were described in detail. Rec- mendations were made in the workshop concerned with uniformity and standardization

information systems dealing with implant retrieval data.

1 jKEY WORDS (Six to twelve entries; alphabetical order; capitalize only proper names; and separate key words by semicolons)

Analysis; biological ; cardiovascular; implants; metals; orthopaedic; polymers;

retrieval

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