Evidence Report/Technology Assessment 

Number 111 

Wound-Healing Technologies: Low-Level Laser and 

Vacuum-Assisted Closure 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. 290-02-0026 

Prepared by: 

Blue Cross and Blue Shield Association 

Technology Evaluation Center Evidence-based Practice Center (EPC) 

Chicago, Illinois 

Investigators 

David J. Samson, Principal Investigator 

Frank Lefevre, M.D. 

Naomi Aronson, Ph.D., EPC Director 

AHRQ Publication No. 05-E005-2 

December 2004 
This report may be used, in whole or in part, as the basis for development of clinical practice 

guidelines and other quality enhancement tools, or a basis for reimbursement and coverage 

policies. AHRQ or U.S. Department of Health and Human Services endorsement of such 

derivative products may not be stated or implied. 

AHRQ is the lead Federal agency charged with supporting research designed to improve the 

quality of health care, reduce its cost, address patient safety and medical errors, and broaden access

to essential services. AHRQ sponsors and conducts research that provides evidence-based 

information on health care outcomes; quality; and cost, use, and access. The information helps 

health care decisionmakers—patients and clinicians, health system leaders, and policymakers—

make more informed decisions and improve the quality of health care services. 
ii

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Samson DJ, Lefevre F, Aronson N. Wound-Healing Technologies: Low-Level Laser and 

Vacuum-Assisted Closure. Evidence Report/Technology Assessment No. 111. (Prepared by the 

Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice 

Center, under Contract No. 290-02-0026.) AHRQ Publication No. 05-E005-2. Rockville, MD: 

Agency for Healthcare Research and Quality. December 2004. 
Preface 

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. This report on low-level laser and vacuum-assisted 

closure for wound healing was requested by the American Association of Health Plans. The 

reports and assessments provide organizations with comprehensive, science-based information 

on common, costly medical conditions and new health care technologies. The EPCs 

systematically review the relevant scientific literature on topics assigned to them by AHRQ and 

conduct additional analyses when appropriate prior to developing their reports and assessments. 

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

We welcome comments on this evidence report. They may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by email to epc@ahrq.gov. 

Jean Slutsky, P.A., M.S.P.H. 

Acting Director, Center for Outcomes and 

Evidence 

Agency for Healthcare Research and Quality 

Jean Slutsky, P.A., M.S.P.H. 

Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Carolyn M. Clancy, M.D. 

Director

Agency for Healthcare Research and Quality 

Kenneth S. Fink, M.D., M.G.A., M.P.H. 

Director, EPC Program

Agency for Healthcare Research and Quality 

Carmen Kelly, Pharm.D. 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 

The authors of this report are responsible for its content. Statements in the report 

should not be construed as endorsement by the Agency for Healthcare Research and 

Quality or the U.S. Department of Health and Human Services of a particular drug, 

device, test, treatment, or other clinical service.

iii
Acknowledgments

The research team would like to acknowledge the efforts of Kathleen M. Ziegler, Pharm.D., 

for clinical and technical input, editing, and layout; Claudia J. Bonnell, B.S.N., M.L.S., for 

information services; Maxine A. Gere, M.S., for general editorial assistance; Carol Gold-Boyd 

for administrative support; Tracey Perez, R.N., J.D., for program support; and Stacie Schilling 

Jones and Carmen Kelly, Pharm.D., of the Agency for Healthcare Research and Quality for 

advice as our Task Order Officers. 

iv
Structured Abstract 

Context: Chronic wounds are a major source of morbidity, disability, and mortality, having a 

significant impact on public health and healthcare resource expenditure. 

Objectives: To systematically review evidence on low-level laser therapy or vacuum-assisted 

closure on wound-healing outcomes. 

Data Sources: MEDLINE® (through June 8, 2004), EMBASE (through June 14, 2004), and the 

Cochrane Controlled Trials Register (through 2003) were searched. Primary published evidence 

was supplemented with recent meeting abstracts and clinical trial protocols. 

Study Selection: Included studies were randomized, controlled trials (RCTs) of one of the 

following comparison types: alternative intervention; incremental benefit; or placebo. Low-level 

laser trials had to include only chronic wounds, while vacuum-assisted closure trials could 

include various wound types. Trials were full-text journal articles reporting on at least one 

outcome of interest. Primary outcomes of interest were incidence of complete wound closure, 

time to complete closure, and adverse events. 

Data Extraction: Titles and abstracts were screened by a single reviewer. A second reviewer 

reviewed citations marked ineligible for full-text retrieval. Rater agreement was required to 

exclude citations. Following retrieval, one reviewer determined whether an article should be 

included, excluded, or discussed with another reviewer. One reviewer performed primary data 

abstraction; evidence tables were fact-checked by a second reviewer. 

Data Synthesis: For low-level laser therapy, 11 studies (n=413) met study selection criteria. For 

vacuum-assisted closure, 6 studies (n=135) met study selection criteria. Outcomes of interest 

were summarized in tables and synthesized across studies. 

Conclusions: Evidence was limited by poor trial quality. Concerns centered on: randomization 

adequacy; group comparability at baseline and follow-up; use of complete healing as the primary 

endpoint; adjustment for confounders; and intention-to-treat analysis. Sample sizes were 

generally small, making it difficult to find statistically significant differences between groups. 

The best available trial did not show a higher probability of complete healing at 6 weeks with the 

addition of low-level laser compared to sham laser treatment added to standard care. Study 

weaknesses were unlikely to have concealed existing effects. Future studies may determine 

whether different dosing parameters or other laser types may lead to different results. 

Vacuum-assisted closure trials did not find a significant advantage for the intervention on the 

primary endpoint, complete healing, and did not consistently find significant differences on 

secondary endpoints and may have been insufficiently powered to detect differences. Ongoing 

RCT protocols may provide better evidence on outcomes of interest. 

Given the sparse evidence for these two interventions, at the present time, it is not possible to 

find variables in these trials that may be associated with better results. 

v

Contents 

Evidence Report........................................................................................................................ 1 

Chapter 1. Introduction ............................................................................................................ 3 

Scope and Objectives ........................................................................................................ 3 

Clinical Overview.............................................................................................................. 3 

Types of Skin Wounds/Ulcers................................................................................ 3 

 Table 1 .................................................................................................................... 4 

Conventional Treatment of Chronic Skin Wounds................................................. 5 

 Figure 1................................................................................................................... 6 

 Table 2 .................................................................................................................... 7 

Emerging Treatments for Skin Wounds ................................................................. 8 

Methodologic Issues in Wound-Healing Research ........................................................... 9 

Confounding Factors in Healing and Treatment..................................................... 9 

Design of Randomized, Controlled Trials for Wound-Healing Treatments........... 9 

Chapter 2. Methods.................................................................................................................. 13 

Objective and Key Questions............................................................................................ 13 

 Low-Level Laser Treatment ................................................................................... 13 

 Vacuum-Assisted Closure....................................................................................... 13 

Search Strategy.................................................................................................................. 13 

Patients, Settings, Interventions, and Outcomes ............................................................... 14 

 Patient Populations.................................................................................................. 14 

 Practice Settings...................................................................................................... 15 

 Interventions/Technologies of Interest ................................................................... 15 

Outcomes of Interest............................................................................................... 16 

Study Selection Criteria..................................................................................................... 16

Methods of the Review...................................................................................................... 17 

Assessment of Study Quality ............................................................................................ 18 

Study Design Criteria.............................................................................................. 18 

Definition of Quality Ratings.................................................................................. 18 

 Table 3 .................................................................................................................... 19 

Technical Expert Panel and Peer Review.......................................................................... 20 

Chapter 3. Results....................................................................................................................21 

Part I: Low-Level Laser Therapy ...................................................................................... 21 

 Overview................................................................................................................. 21 

 Evidence Table 1..................................................................................................... 22 

 Evidence Table 2..................................................................................................... 24 

 Evidence Table 3..................................................................................................... 30 

 Evidence Table 4..................................................................................................... 34 

 Evidence Table 5..................................................................................................... 36 

 Evidence Table 6..................................................................................................... 39 

 Conclusions............................................................................................................. 42 

vii
Part II: Vacuum-Assisted Closure..................................................................................... 44 

Overview ........................................................................................................................... 44 

 Evidence Table 7..................................................................................................... 45 

 Evidence Table 8..................................................................................................... 46 

 Evidence Table 9..................................................................................................... 47 

 Evidence Table 10................................................................................................... 49 

 Evidence Table 11................................................................................................... 51 

 Evidence Table 12................................................................................................... 53 

 Evidence Table 13................................................................................................... 56 

 Evidence Table 14................................................................................................... 59 

 Conclusions............................................................................................................. 63 

 Evidence Table 15................................................................................................... 64 

Chapter 4. Discussion .............................................................................................................. 65 

 

References and Included Studies.............................................................................................. 67

Listing of Excluded Studies...................................................................................................... 71 

Excluded Studies, Laser Therapy...................................................................................... 71 

Excluded Studies, Vacuum-Assisted Closure ................................................................... 73 

List of Acronyms/Abbreviations............................................................................................... 75

Appendixes 

Appendix A. Exact Search Strings 

Appendix B. Technical Expert Panel (TEP) and Reviewers 

Appendixes are provided electronically at http://www.ahrq.gov/clinic/tp/woundtp.htm

viii
Introduction

Chronic wounds are a major source of

morbidity, lead to considerable disability, and are

associated with increased mortality; therefore,

they have a significant impact on public health

and the expenditure of healthcare resources.1

The incidence of chronic wounds in the

United States is approximately 5 to 7 million per

year,

1 and the annual costs for management of

these wounds is greater than $20 billion.2,3 In

addition, chronic wounds can lead to

complications, such as infections, contractures,

depression or limb amputation.4 These

complications are associated with a need for

assisted living and with higher mortality.5, 6

The objective of this report is to systematically

review the evidence on the outcomes of two

technologies for wound healing: low-level laser

therapy and vacuum-assisted closure. This report

addresses the following specific questions: 

1. In the treatment of chronic nonhealing

wounds, what are the outcomes of low-level

laser therapy for specific indications and

patient types 

• as a substitute for conventional therapy?

or

• as an adjunct to conventional therapy,

compared with conventional therapy

alone?

2. In the treatment of acute or chronic wounds,

what are the outcomes of vacuum-assisted

closure for specific indications and patient

types 

• as a substitute for conventional dressings?

and

• as an adjunct to conventional therapy,

compared with conventional therapy

alone? 

This report also provides an overview of

clinical and methodologic issues relevant to

evaluating the evidence on interventions for

wound healing. Many variables affect the course

of wound healing; so well-controlled, randomized

trials are necessary to reach conclusions on

treatment efficacy.

Skin wounds are a heterogeneous and complex

group of disorders with a wide variety of causes.7

Approximately 70 percent are classified as

pressure ulcers, diabetic ulcers, or vascular

ulcers.8,9 Vascular ulcers are further classified as

due to arterial or venous insufficiency. Other lessfrequent causes include inflammatory conditions,

malignancies, burns, and radiation injuries.8

Often the causes of wounds are multifactorial,

such as in the diabetic patient who has both

arterial insufficiency and peripheral neuropathy.8

Each wound type has distinct physiologic

characteristics and exists in a unique host

environment with varied clinical and psychosocial

factors.8

Wounds are often classified as acute or chronic.

Acute wounds are generally less than 8 weeks in

duration and have not yet completed the natural

healing cycle. Chronic wounds are defined as

wounds that have failed to proceed through an

orderly and timely process that produces

anatomic and functional integrity.

10 Chronic

wounds either require a prolonged time to heal,

Evidence Report/Technology Assessment

Number 111

Wound-Healing Technologies: Low-Level Laser and

Vacuum-Assisted Closure

Summary

Authors: Samson D, Lefevre F, Aronson N

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

do not heal completely, or recur frequently. A large number of

factors can impede wound healing and may predispose a

patient to the development of chronic wound(s).11,12 These

include both systemic factors (poor nutrition, metabolic

derangements, and drugs) and local factors (tissue hypoxia,

infection, and dry wound bed).13

Conventional treatment for established wounds incorporates

common principles that apply to the management of all

wounds, including debridement of necrotic tissue, maintenance

of a moist wound bed, and control of infection. These

common elements are combined with treatment modalities

targeted to each type of wound and the clinical characteristics

of the patient.14,15,16 Optimal treatment also entails

consideration of the appropriate intensity of treatment.17

Unfortunately, there are no widely accepted, standardized

protocols that define optimal standard treatment or the

appropriate intensity of treatment delivery.

Because treatment varies widely in clinical practice, it is

difficult to determine whether a patient has actually received an

adequate course of treatment, and whether a nonhealing

wound should truly be called “refractory.” In randomized,

controlled trials, a relatively large proportion of refractory

wounds heal with standard treatment (control arm). The large

number of factors that contribute to wound healing, and the

high degree of variability in wound characteristics, patient

characteristics, and treatment delivery result in many potential

confounding factors when attempting to measure treatment

effect. 

As a result of these multiple confounding factors, it is

difficult to interpret outcomes from single-arm trials that lack a

control group, since improvement may be due to factors other

than the specific intervention being tested. A concurrent

control group is necessary to permit measurement of a

treatment effect above that related to optimization of standard

treatment or due to the natural history of wound healing.

Randomized assignment to treatment group is essential in

maximizing the likelihood that confounding factors are equally

distributed across treatment groups. Ascertainment of

outcomes should be ideally performed by an independent,

blinded individual. 

The U.S. Food and Drug Administration (FDA) has

prepared a draft guidance document that offers information on

optimal design of trials to assess wound-healing interventions,

including patient selection and assessment, treatment

considerations, and definition of outcomes and outcomes

assessment.16 The principals set forth by the FDA have been

adapted in the development of the protocol for this systematic

review. In particular, outcome measurement should focus on

outcomes that are quantitative and clinically meaningful.4,11

The most important outcomes to be considered are (1) the

percent of patients with complete healing and (2) time to

complete healing. In some cases, particularly for vacuumassisted closure, the treatment may not be expected to result in

complete healing. Rather the treatment may be intended to

advance the wound to a stage where healing is possible, either

by continued conventional treatment or by surgical closure. 

Methods 

The objective of this evidence report is to systematically

review and synthesize the available evidence on the effectiveness

of low-level laser treatment and vacuum-assisted closure for

wound healing. Outcomes of interest were

• Primary outcomes

• incidence of complete wound closure

• time to complete closure

• adverse events

• Secondary outcomes

• facilitating surgical closure 

• need for debridement

• infections

• pain

• activities of daily living

• quality of life

• improved cosmesis

Other secondary outcomes abstracted were change in wound

size and transcutaneous oxygen tension (tcpO2); however, these

were considered to be of less clinical importance.

Electronic database searches were completed of MEDLINE®

(via PubMed®), EMBASE, and the Cochrane Controlled Trials

Register. The MEDLINE® search covered references entered

onto the database from January 1, 1966 through June 8, 2004.

The Cochrane Controlled Trials Register search was completed

in 2003, through issue number 4. The EMBASE search

covered references entered through June 14, 2004.

The search was limited to studies on human subjects with

English-language abstracts. When abstracts were missing, the

full-text article was retrieved for review if the title suggested it

might possibly meet the study selection criteria. Papers

published in foreign languages were reviewed if the Englishlanguage abstract appeared to meet inclusion criteria. Results

of the search and study selection were reviewed by the

Technical Expert Panel (TEP) for this project, in order to

identify additional studies. 
In addition, two companies that produce lasers used in

wound healing (Microlight Corporation of America and

Photothera), as well as the major producer of vacuum-assisted

closure devices (V.A.C.®, Kinetics Concepts Inc. [KCI]), were

contacted and were invited to submit evidence-based

information for the review. The specific request was for “lists of

published, randomized, controlled trials (RCTs), published

abstracts of RCTs within the past 2 years, and published articles

on study design, or protocols of any RCTs (published or in

progress).”

This systematic review selected only randomized, controlled

trials meeting the following criteria:

1. The trial must involve one of the following comparisons

of interventions 

a. Either low-level laser treatment or vacuum-assisted

closure, compared with other wound healing

interventions (alternative intervention trials).

b. Either low-level laser treatment or vacuum-assisted

closure in addition to standard wound care, compared

with standard wound care alone (incremental benefit

trials).

c. Either low-level laser treatment or vacuum-assisted

closure, compared with a sham intervention (placebo

trials).

2. For low-level laser treatment, patient selection criteria

must target those with chronic wounds. For vacuumassisted closure, patient selection may address those with

chronic wounds or other types of wounds. 

3. The trial must report on at least one of the outcomes of

interest.

4. The trial must be published as a full journal article and

not merely as a conference abstract.

Titles and abstracts were screened by a single reviewer who

marked each citation as either eligible for review as full-text

articles or ineligible for full-text review. A second reviewer

reviewed all citations marked as ineligible by the first reviewer.

An eligible rating was necessary from only one reviewer to place

a citation in the pool of those to be retrieved for full-text

review.

In reviewing full-text articles to determine eligibility for data

abstraction, a single reviewer determined whether each paper

should be (1) included in systematic review, (2) excluded from

systematic review, or (3) discussed with additional reviewer.

One reviewer performed primary data abstraction of all data

elements into the evidence tables, and a second reviewer

checked the evidence tables for accuracy. 

A procedure was established in case of disagreements that

could not be resolved between the two reviewers. In such cases,

the EPC Program Director was consulted and then, if

necessary, the relevant members of the TEP. 

This systematic review applies the general approach to

grading evidence developed by the U.S. Preventive Services

Task Force.18 Two independent reviewers rated study quality,

and disagreements in ratings were resolved by consensus.

Results

Low-level laser. Eleven studies19-29 met the study selection

criteria for Part I of this review, nine of which were rated poor

in quality,19-23, 26-29 while one was rated good quality25 and one

was rated fair.24

Seven studies (n=262) compared standard care plus placebo

with the combination of standard care and sham laser

therapy.19,21,22,23,26,27,29 Most of these patients had lower extremity

venous ulcers. Of the three studies that reported on complete

healing,19,26,27 one provides weak evidence of a higher rate of

healing for patients treated by machine-scanned laser versus

those receiving sham laser.19

Standard treatment alone versus standard treatment plus

laser was compared in three studies, which reported on a total

of 151 patients with pressure ulcers.24,25,28 All three studies

reported on complete healing. One of these was rated as good

in quality, and this higher-quality study did not show a higher

probability of complete healing at 6 weeks with the addition of

laser treatment,25 nor did it show benefit for any of the other

reported outcomes. Use of medical treatment plus ultraviolet

light with medical treatment plus low-level laser therapy was

compared in one study of six patients with chronic venous

ulcers.20 That study did not show a higher probability of

complete healing at 6 weeks with the addition of laser

treatment. 

Overall, the quality of this body of evidence is poor, and

does not permit definitive conclusions. However, the available

data suggest that the addition of laser therapy does not improve

wound healing, as the vast majority of comparisons in these

studies do not report any group differences in the relevant

outcomes. It is unlikely that the lack of significant differences

is the result of a type II error, since there are no trends or

patterns of outcomes that favor the laser group. 

Vacuum-assisted closure. This body of evidence is

insufficient to support conclusions about the effectiveness of

vacuum-assisted closure in the treatment of wounds. There are

only six trials that met the inclusion criteria for this review30-35

and the included trials were of small size and poor quality.

With the exception of one study of 54 patients with incomplete

followup,34 all studies included fewer than 25 patients. The

randomization method was clearly adequate in only one study.

34

No study made clear that groups were comparable on all three

3
4

key baseline characteristics (age, wound duration, wound size).

None provided group information about wound duration. A

single study adjusted for confounders in the data analysis35 and

another performed an intention-to-treat analysis.32

Some outcomes in the available trials show a significant

benefit for the vacuum-assisted closure group, while others do

not. Only one study30 gave data on the probability of complete

healing, showing no significant difference between groups. A

study reporting time to satisfactory healing33 also found no

significant difference between groups. One study found no

difference between vacuum-assisted closure and control in time

to readiness for surgical closure.34

Three studies reported on change in wound area,31,33,34 one of

which found a difference between vacuum-assisted closure and

control,34 while two did not.31,33 Among four studies addressing

change in wound volume,30,31,32,35 two found a significant

advantage for vacuum-assisted closure31,32 and two did not

achieve statistical significance.30,35 One study found significant

changes in wound width and depth for vacuum-assisted

closure32 and another found it only for depth.31 It is possible

that the lack of significant results in some or all of these trials

result from a type II error. In most cases, the numerical results

favor the vacuum-assisted closure group. Power calculations are

lacking for these trials, but their small size raises the possibility

that they are underpowered. 

Trial protocols provided by the manufacturer of the V.A.C.®

device (Kinetic Concepts, Inc., KCI) outline much larger trials

that are condition-specific and address many of the quality

problems found in the published studies. If implemented and

completed successfully as planned, these trials will provide

substantial advances in the evidence base for vacuum-assisted

closure therapy, and may allow more definitive conclusions on

the efficacy of vacuum-assisted closure.

Discussion

This systematic review focused on two specific interventions

for wound healing, but the issues raised in this discussion

should be applied broadly. Because of the large size of

populations with nonhealing and other types of wounds, the

impact on healthcare expenditures is considerable. Future

research should address how to improve the delivery of care,

quality of care, and outcomes of treatment of wounds in

various settings. There is potential to reduce the frequency of

nonhealing wounds and thus the overall costs of care. New

interventions have the potential to improve wound care, but

outcomes must be demonstrated in well-controlled randomized

trials. Strategies for reducing the occurrence of wounds in

various susceptible populations also have a place in the research

portfolio. Given significant costs of chronic wounds, future

comparisons of the cost-effectiveness of various strategies for

preventing wounds, managing wounds, and improving quality

of care would be of value to clinical decisionmakers. 

Availability of the Full Report

The full evidence report used to create this summary was

prepared for the Agency for Healthcare Research and Quality

by the Blue Cross and Blue Shield Association Technology

Evaluation Center Evidence-based Practice Center, under

Contract No. 290-02-0026. It is expected to be available in

December 2004. At that time, printed copies may be obtained

free of charge from the AHRQ Publications Clearinghouse by

calling (800)-358-9295. Inquiries should include a request for

Evidence Report/Technology Assessment No. 111, Wound

Healing Technologies: Low-Level Laser and Vacuum-Assisted

Closure. In addition, Internet users will be able to access the

report and this summary online through AHRQ’s Website at

www.ahrq.gov. 

Suggested Citation

Samson D, Lefevre F, Aronson N. Wound Healing

Technologies: Low-Level Laser and Vacuum-Assisted Closure.

Summary, Evidence Report/Technology Assessment No. 111.

(Prepared by the Blue Cross and Blue Shield Association

Technology Evaluation Center Evidence-based Practice Center,

under Contract No. 290-02-0026). AHRQ Publication No.

05-E005-1. Rockville, MD: Agency for Healthcare Research

and Quality. December 2004.

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26. Lundeberg T, Malm M. Low-power HeNe laser treatment of venous

leg ulcers. Ann Plast Surg 1991; 27(6):537-9. 

27. Malm M, Lundeberg T. Effect of low power gallium arsenide laser on

healing of venous ulcers. Scand J Plast Reconstr Surg Hand Surg

1991; 25(3):249-51.

28. Nussbaum EL, Biemann I, Mustard B. Comparison of

ultrasound/ultraviolet-C and laser for treatment of pressure ulcers in

patients with spinal cord injury. Phys Ther 1994; 74(9):812-23.

29. Santoianni P, Monfrecola G, Martellotta D, et al. Inadequated effect

of helium-neon laser on venous leg ulcers. Photodermatology 1984;

1245-9.

30. Ford CN, Reinhard ER, Yeh D, et al. Interim analysis of a prospective,

randomized trial of vacuum-assisted closure versus the healthpoint

system in the management of pressure ulcers. Ann Plast Surg 2002;

49(1):55-61.

31. Eginton MT, Brown KR, Seabrook GR, et al. A prospective

randomized evaluation of negative-pressure wound dressings for

diabetic foot wounds. Ann Vasc Surg 2003; 17(6):645-9.

32. Joseph E, Hamori CA, Bergman S, et al. A prospective randomized

trial of vacuum-assisted closure versus standard therapy of chronic

nonhealing wounds. Wounds 2002; 12(3):60-7.

33. McCallon SK, Knight CA, Valiulus JP, et al. Vacuum-assisted closure

versus saline-moistened gauze in the healing of postoperative diabetic

foot wounds. Ostomy Wound Manage 2000; 46(8):28-32, 34.

34. Moues CM, Vos MC, van den Bemd GJ, et al. Bacterial load in

relation to vacuum-assisted closure wound therapy: a prospective

randomized trial. Wound Repair Regen 2004; 12(1):11-7. 

35. Wanner MB, Schwarzl F, Strub B, et al. Vacuum-assisted wound

closure for cheaper and more comfortable healing of pressure sores: a

prospective study. Scand J Plast Reconstr Surg Hand Surg 2003;

37(1):28-33.

5
www.ahrq.gov

AHRQ Pub. No. 05-E005-1

December 2004

ISSN 1530-440X
Evidence Report

Chapter 1. Introduction 

Scope and Objectives 

Chronic wounds are a major source of morbidity, lead to considerable disability, and are 

associated with increased mortality; therefore, they have a significant impact on public health 

and the expenditure of healthcare resources (Petrie, Yao, and Eriksson, 2003). 

The incidence of chronic wounds in the U.S. is approximately 5 to 7 million per year (Petrie, 

Yao, and Eriksson, 2003), and the annual costs for management of these wounds is greater than 

$20 billion (Frykberg, Armstrong, Giurini et al., 2000; Harding, Morris, and Patel, 2002). In 

addition, chronic wounds can lead to complications, such as infections, contractures, depression, 

or limb amputation (Jeffcoate and Harding, 2003). These complications are associated with a 

need for assisted living and with higher mortality (Deery and Sangeorzan, 2001; Reiber, Boyko, 

and Smith, 1995). 

The objective of this report is to systematically review the evidence on the outcomes of two 

technologies for wound healing: low-level laser therapy and vacuum-assisted closure. This 

report addresses the following specific questions: 

1. In the treatment of chronic nonhealing wounds, what are the outcomes of low-level laser 

therapy for specific indications and patient types: 

• as a substitute for conventional therapy? or 

• as an adjunct to conventional therapy, compared with conventional therapy alone?

2. In the treatment of acute or chronic wounds, what are the outcomes of vacuum-assisted 

closure for specific indications and patient types: 

• as a substitute for conventional dressings? and 

• as an adjunct to conventional therapy, compared with conventional therapy alone?

This Introduction chapter provides an overview of clinical and methodologic issues relevant 

to evaluating the evidence on interventions for wound healing. Many variables affect the course 

of wound healing; so well-controlled, randomized trials are necessary to reach conclusions on 

treatment efficacy. 

Clinical Overview 

Wound healing progresses through well-recognized, pathophysiological stages, and those 

wounds that do not progress to healing as expected are considered to be chronic. Conventional 

treatment of wounds incorporates common principles for all wounds, along with specific 

treatment strategies targeted to wound type and overall clinical characteristics of the patient. 

Types of Skin Wounds/Ulcers

Skin wounds are a heterogeneous and complex group of disorders with a wide variety of 

causes (Table 1) (Pierce, 2001). Approximately 70 percent are classified as pressure ulcers, 

diabetic ulcers, or vascular ulcers (Stadelman, Digenis, and Tobin, 1998a; Valencia, Falabella, 

3 
Table 1. Classification of Skin Wounds

Types of skin wounds 

Pressure wounds 

o Decubitus ulcers 

o Neuropathic ulcers 

Inflammatory wounds 

o Autoimmune disorders 

o Primary cutaneous disorders 

Vascular insufficiency wounds

o Venous insufficiency 

o Arterial insufficiency

Malignant wounds 

o Primary cutaneous malignancies 

o Secondary cutaneous malignancies 

Miscellaneous wounds

o Burns 

o Radiation injury

o Frostbite 

o Vasculitic ulcers

o Spider bites 

Kirsner, et al., 2001). Vascular ulcers are further classified as due to arterial or venous 

insufficiency. Other less-frequent causes include inflammatory conditions, malignancies, burns, 

and radiation injuries (Valencia, Falabella, Kirsner, et al., 2001). Often the causes of wounds are 

multifactorial, such as in the diabetic patient who has both arterial insufficiency and peripheral 

neuropathy (Valencia, Falabella, Kirsner, et al., 2001). Each wound type has distinct physiologic 

characteristics, and exists in a unique host environment with varied clinical and psychosocial 

factors (Valencia, Falabella, Kirsner, et al., 2001). 

Wounds are often classified as acute or chronic. Acute wounds are generally less than 8 

weeks in duration and have not yet completed the natural healing cycle. Chronic wounds are 

defined as wounds that have failed to proceed through an orderly and timely process that 

produces anatomic and functional integrity (Lazarus, Cooper, Knighton, et al., 1994). Chronic 

wounds either require a prolonged time to heal, do not heal completely, or recur frequently. 

Phases of Wound Healing 

There are three phases of wound healing: (1) inflammatory, (2) proliferative, and (3) 

remodeling (Steed, 2003b; Harding, Morris, and Patel, 2002). These phases are distinct, but 

overlap in time during the healing process. 

During the inflammatory phase, neutrophils and macrophages enter the wound site. 

Neutrophils act primarily to prevent and respond to infection; macrophages release inflammatory 

mediators such as cytokines and growth factors (Henry and Garner, 2003), which clear the 

wound of devitalized tissue and set the stage for cellular regeneration. The proliferative phase 

begins after two or three days and is marked by a predominance of fibroblasts and endothelial 

cells. Fibroblasts secrete growth factors and extracellular matrix components that lead to tissue 

regeneration (Henry and Garner, 2003). Endothelial cells form the new blood vessels that are 

also necessary for tissue regeneration. The final phase is the remodeling phase, in which intact 

skin replaces scar tissue. This phase is characterized by continued cycles of new cellular 

component formation and degradation of the scar by proteases (Eming, Smola, and Krieg, 2002; 

Henry and Garner, 2003). 

4 
Wounds that heal properly progress through these phases in an orderly fashion within about 8 

weeks. Nonhealing wounds are often “stuck” in one of these stages, usually continued 

inflammation or proliferation (Douglass, 2003; Henry and Garner, 2003). A large number of 

factors can impede wound healing (Figure 1) and may predispose a patient to the development of 

chronic wound(s) (Williams and Barbul, 2003; Steed, 2003b). These include both systemic 

factors (e.g., poor nutrition, metabolic derangements, and drugs) and local factors (e.g., tissue 

hypoxia, infection, dry wound bed) (Stadelman, Digenis, and Tobin, 1998b). 

While the above paradigm is widely accepted in conceptualizing wound care, there are 

alternative frameworks that have been proposed. Mustoe (2004) addresses limitations of current 

wound-healing science by addressing unifying aspects of chronic wounds, rather than their 

differences. He proposes that most, if not all, chronic wounds share common features of (1) the 

cellular and systemic effects of aging, (2) repeated ischemia-reperfusion injury, and (3) bacterial 

colonization with the accompanying inflammatory response. In this model, treatment 

approaches logically address all three aspects of chronic wounds. 

Conventional Treatment of Chronic Skin Wounds 

Optimal management of wounds starts with prompt recognition and accurate diagnosis in 

order to properly treat wounds at the earliest stage possible. Early recognition depends on 

identification of patients at risk, education for appropriate patients, and proper surveillance (U.S. 

Food and Drug Administration, 2000). An accurate diagnosis can be made from the appearance 

of the wound and the patient’s risk factors in up to 75 percent of skin wounds (de Araujo, 

Valencia, Federman, et al., 2003). In some cases, specialized testing such as blood flow 

measurement is necessary (de Araujo, Valencia, Federman, et al., 2003; Valencia, Falabella, 

Kirsner, et al., 2001). 

Conventional treatment for established wounds incorporates common principles that apply to 

the management of all wounds, including debridement of necrotic tissue, maintenance of a moist 

wound bed, and control of infection (Table 2). These common elements are combined with 

treatment modalities targeted to each wound type and the clinical characteristics of the patient 

(Lionelli and Lawrence, 2003; Steed, 1998a; U.S. Food and Drug Administration, 2000) (Table 

2). Optimal treatment also entails consideration of the appropriate intensity of treatment (Ratliff,

Bryant, Dutcher, et al., 2002). For example, depending on the context, dressing changes may be

performed once a day or several times per day. Nutritional support can entail a wide variety of 

approaches that may differ considerably. Treatment regimens that are considered intensive often 

involve a multidisciplinary team of clinicians, nurses, therapists, and other ancillary staff. 

Unfortunately, there are no widely accepted, standardized protocols that define optimal standard 

treatment or the appropriate intensity of treatment delivery. 

For wounds that do not heal with conservative therapy, surgical intervention may be 

considered. Surgical restoration of adequate blood flow is the goal for wounds caused by 

vascular insufficiency. Arterial revascularization procedures are often curative; however, venous 

surgery is of uncertain benefit for this purpose (de Araujo, Valencia, Federman, et al., 2003; 

Valencia, Falabella, Kirsner, et al., 2001). 

Skin grafting can be performed for chronic, nonhealing skin wounds that are not amenable to 

surgical revascularization. Skin grafts are usually taken from a portion of intact skin of the same

individual (autograft), but may also be taken from a cadaveric source (allograft). The specific 

indications for skin grafting are not well standardized (Valencia, Falabella, Kirsner, et al., 2001). 

5 
Figure 1. Factors contributing to wound healing and chronic wound formation

(Source: Douglass 2003. Adapted with permission from the British Journal of Community Nursing.)

 Chronic Wound 

Drugs/toxins 

• Corticosteroids• Chemotherapy

Metabolic factors • Diabetes mellitus• Renal failure 

Nu• • 

Local factors • Reduced oxygen pressure

• Infection

• Denervation 

• Foreign bodies

• Hyperglycemia 

6 
Table 2. Overview of Components of Standard Care for Skin Wounds

Common treatments Wound-specific treatments 

Pressure ulcers Diabetic ulcers Vascular ulcers 

 Debridement of necrotic or 

infected tissue 

 Maintenance of a moist 

wound environment

 Control of infection, and  Nutritional support 

 Weight off-loading  Regular repositioning  Protective dressing(s)  Unna boot  Bowel/bladder care for 

patients at risk for contamination 

 Weight off-loading  Moisture permeable 

dressing 

 Blood glucose control  Unna boot 

 Moisture permeable 

dressing(s) 

For venous ulcers:  Compression therapy  Elevation of legs For arterial ulcers:  Establishment of 

adequate circulation 

      

7 
Also, skin grafting is not always successful, as the donor skin may not “take” at the graft site in 

up to 25 percent of cases (Valencia, Falabella, Kirsner, et al., 2001). In addition, the procedure is

associated with a substantial amount of morbidity, such as pain and wound infections (Jones and 

Nelson, 2000). A recent Cochrane review of skin grafting for venous ulcers found the available 

efficacy studies to be of poor methodologic quality and concluded that there was limited 

evidence on whether skin grafting improves the rate of healing (Jones and Nelson, 2003). 

Finally, amputation may be the treatment of last resort for wounds that fail all other methods, if 

the benefit of healing the wound outweighs the adverse effects of amputation. 

The setting in which wounds are treated varies widely, from home treatment to specialized 

wound treatment centers. This may influence the specific treatment modalities used and/or the 

intensity of treatment provided. In clinical practice, there is a high degree of variability in wound 

treatment, and there is evidence that standard wound care deviates substantially from optimal 

treatment (ECRI, 2000). Thus, patients who present with nonhealing wounds may not have 

received similar prior care. It is possible that many of these “nonhealing” wounds may actually 

heal with an adequate trial of optimal care. The variability in prior care is also a concern for 

clinical trials, since this variability contributes to the heterogeneity of the study sample. 

Emerging Treatments for Skin Wounds 

Vacuum-assisted closure and low-level laser therapy are two potential alternatives for 

treating skin wounds. Low-level laser-assisted wound healing uses a low-energy, low-power, 

low-level laser, also known as a “cold” laser. It is hypothesized that delivery of low-energy laser 

therapy in this way may stimulate the physiologic process of wound healing, thus facilitating 

and/or accelerating the healing process. This physiologic rationale is supported by in vitro 

studies, and some animal models (Basford, Hallman, Sheffield, et al., 1986; Kana, Hutchenreiter, 

Haina, et al., 1981; Robinson, Garden, Taute, et al., 1987). 

Lasers used in wound-healing applications include the gallium-aluminum (GaAl), galliumarsenide (GaAs), and helium-neon (HeNe) laser. The power of these lasers ranges from 0.001 

watts (1 mW) to 0.05 watts (50 mW), producing minimal heating of tissue. These low-energy 

lasers do not damage tissue directly, as do high-energy lasers that are used to ablate or vaporize 

tissue. Critical aspects of laser treatment delivery include the wavelength, power density 

(mW/cm2

), and energy density (Joules/cm2). Variability in these parameters may lead to 

variation in tissue response to treatment (Eells, Henry, Summerfelt, et al., 2003). 

Vacuum-assisted closure uses negative pressure to assist wound healing. Negative pressure 

drains fluid from the wound, thus removing the substrate for growth of microorganisms. 

Negative pressure may also accelerate granulation tissue formation and promote angiogenesis 

(Lionelli and Lawrence, 2003). The mechanical stimulation of cells by tensile forces may also 

play a role, by increasing cellular proliferation and protein synthesis (Morykwas and Argenta, 

1997). 

The technique involves application of a sterile, open-pore foam dressing directly on the 

wound. The wound is then sealed with an occlusive drape in order to create a closed, controlled 

environment. A fenestrated vacuum tube is attached to the wound dressing, and connected to a 

collection device. Negative pressure is applied at 50–125 mm/Hg, resulting in a decrease in the 

local interstitial pressure, and effluent from the wound is drawn out into the collection device 

(Lionelli and Lawrence, 2003; Morykwas and Argenta, 1997). Initially, the vacuum pressure is 

applied continuously. As the amount of drainage decreases, the vacuum may subsequently be 

8
applied on an intermittent basis (Morykwas and Argenta, 1997). The vacuum dressing is usually

changed at approximately 48-hour intervals (Morykwas and Argenta, 1997). 

Both the lasers used in wound healing and vacuum-assisted closure devices have been 

cleared for marketing by the U.S. Food and Drug Administration’s (FDA's) 510(k) process, a 

regulatory mechanism that does not require submission of data from controlled efficacy trials. 

There are a variety of other emerging treatments for skin wounds that are in various stages of 

development and FDA approval/clearance (Bennett, Griffiths, Schor, et al., 2003; Cross and 

Mustoe, 2003; Eming, Smola, and Krieg, 2002; Lionelli and Lawrence, 2003; Petrie, Yao, and 

Eriksson, 2003). These include: topical growth factors; bioengineered skin products; electrical 

stimulation; therapeutic ultrasound; novel dressings (e.g., hydrocolloids, alginates); hyperbaric 

oxygen; and gene therapy. However, discussion of these technologies is outside the scope of this 

evidence report. 

Methodologic Issues in Wound-Healing Research 

Confounding Factors in Healing and Treatment 

 

As summarized in Figure 1, many factors influence wound healing (Harding, Morris, and 

Patel, 2002). Local factors include severity of wound (size/depth), viability of surrounding 

tissue, or the presence of infection or a foreign body. Systemic factors include age, functional 

status, nutritional status, and comorbid illnesses, such as diabetes and/or renal disease. The large 

number of factors that contribute to wound healing, and the high degree of variability in wound 

characteristics, patient characteristics, and treatment delivery result in many potential 

confounding factors when attempting to measure treatment effect. 

Since treatment varies widely in clinical practice, it is difficult to determine whether a patient

has actually received an adequate course of treatment, and whether a nonhealing wound should 

truly be called “refractory.” In randomized, controlled trials, a relatively large proportion of 

“refractory” wounds heal with standard treatment (i.e., control arm). In two recent randomized, 

controlled trials of bioengineered skin substitute versus standard care (Falanga, Margolis, 

Alvarez, et al., 1998; Veves, Falanga, Armstrong, et al., 2001), 38 percent and 49 percent of 

“refractory” wounds, respectively, healed completely in the standard-care arm. Even in wounds 

present for at least 1 year (Falanga and Sabolinski, 1999), a substantial minority (19 percent) 

healed with standard treatment. 

As a result of these multiple confounding factors, it is difficult to interpret outcomes from

single-arm trials that lack a control group, since improvement may be due to factors other than 

the specific intervention being tested. A concurrent control group is necessary to permit 

measurement of a treatment effect above that related to optimization of standard treatment or due 

to the natural history of wound healing. Randomized assignment to treatment group is essential 

in maximizing the likelihood that confounding factors are equally distributed across treatment 

groups. 

Design of Randomized, Controlled Trials for Wound-Healing 

Treatments 

The FDA has prepared a draft guidance document that outlines difficulties in conducting 

trials to assess the effectiveness of interventions for wound healing. This document offers 

9
guidance in optimal design of such trials (U.S. Food and Drug Administration, 2000). The 

principals set forth by the FDA are summarized here and have been adapted in the development 

of the protocol for this systematic review. 

Patient selection. The study population should ideally consist of patients with one particular 

type of skin wound, because of the different pathophysiology of each wound type and potential 

differences in response to therapy. A standardized definition of an adequate course of optimal 

care should be used in order to enroll a clinically refractory population. Alternatively, a run-in 

treatment period in which all patients receive an adequate course of optimal care may be utilized 

in order to exclude patients who heal with optimal standard care. This ensures that patients who 

enter the study are truly refractory to standard care. 

Specific enrollment criteria that exclude conditions known to impede healing, such as very 

deep wounds or immunosuppression, may be helpful in reducing variability in measured 

outcomes. This may aid in determining the specific effect of treatment, but may also lead to 

reduced generalizability.

Patient assessment. Thorough assessment prior to treatment is important in accurately 

characterizing the features of the wound and in measuring potential confounders of outcome. 

Accurate recording of wound size, depth, and duration are important, since these are major 

predictors of healing (de Araujo, Valencia, Federman, et al., 2003). 

Wounds can be measured by a variety of objective means, including direct tracing, 

planimetry, and stereophotogrammetry (ECRI, 2000). Wound imaging by photographic methods 

may also aid in the objective measurement of wounds. Other objective measures such as 

transcutaneous oxygen tension (tcpO2), ankle/brachial index, and microfilament testing may also 

be helpful in assessing the baseline wound characteristics. 

A thorough assessment and measurement of other potential confounding variables should be 

performed at baseline and at followup time points. These include patients’ clinical and 

demographic characteristics, comorbid medical conditions, and prior treatment received.

Treatment issues. Double-blinding of treatment is the optimal study design to minimize bias in 

treatment delivery and outcome assessment. A sham placebo should be considered in the control 

arm to allow for double-blinding. However, double-blinding may be difficult for some devices, 

especially for a therapy such as vacuum-assisted closure. The difficulties of double-blinding 

need to be balanced against the benefit in minimizing bias in interpreting the trial outcomes. 

Researchers should ensure that high-quality standard treatment is delivered to the control 

group. “High-quality” treatment means that all of the main modalities of standard care from

wound treatment guidelines are included (Table 2). No definitive standard treatment guidelines 

exist, but there are guidelines that incorporate modalities of standard care (e.g., from the Wound 

Ostomy and Continence Nurses Society [www.wocn.org]). 

It is also important to ensure that standard treatment modalities are identical between groups 

in order to avoid performance bias. The experimental treatment arm should not include 

additional elements of standard care that are not delivered to the control group. The 

experimental treatment arm should not incorporate a greater intensity of standard care than the 

control arm. The importance of equal intensity of care was demonstrated in a prior multicenter 

trial of platelet-derived growth factor for chronic wounds (Cross and Mustoe, 2003). In this 

10
study, the rate of healing was significantly higher in centers that incorporated more frequent 

debridement (Cross and Mustoe, 2003). 

An adequate followup period is required to demonstrate durability of response and adverse 

effects. It is recommended that patients remain enrolled in studies for at least 3 months 

following initiation of treatment (U.S. Food and Drug Administration, 2000). This is the 

minimum amount of time required to evaluate the number of healed wounds that recur. Some

experts recommend an even longer minimum duration. For example, Steed (2003b) recommends

that the minimum duration of a clinical trial include a run-in period of standard care, followed by 

20 weeks of treatment, and an additional 12 weeks of followup. 

Outcomes and outcome measurement. Outcome measurement should focus on outcomes that 

are quantitative and clinically meaningful (Jeffcoate and Harding, 2003; Steed, 2003b). The 

most important outcomes to be considered are: (1) the percent of patients with complete healing; 

and (2) time to complete healing. 

Other outcomes that may also be clinically meaningful are: (1) facilitating surgical wound 

closure; (2) change in wound size; (3) improved cosmesis; (4) improved activities of daily living; 

(5) improved quality of life; (6) pain; (7) transcutaneous oxygen tension; (8) infections; and (9) 

need for debridement. 

In some cases, particularly for vacuum-assisted closure, the treatment may not be expected to 

result in complete healing. Rather, the treatment may be intended to advance the wound to a 

stage where healing is possible, either by continued conventional treatment or by surgical 

closure. These goals represent intermediate treatment outcomes. If the overall treatment 

strategy is successful, the benefit of these intermediate outcomes will ultimately be reflected in 

improved rates of complete healing. The intermediate outcome states are more difficult to 

measure, but are likely partly represented by the secondary outcomes of wound size and 

facilitation of surgical closure. 

Outcome assessment should also include measurement of adverse events that result from the 

treatment or from the natural history of the disorder. These include: (1) local adverse effects 

(pain, discharge, dermatitis); (2) immune reactions; (3) infections; (4) limb amputations; and (5) 

discontinuation from treatment, including assessment of whether discontinuation is a result of the 

treatment. 

Ascertainment of outcomes should be ideally performed by an independent, blinded 

individual. This is especially important in situations where patients and/or treating physicians 

are not blinded to treatment. 

11

Chapter 2. Methods 

This report is the product of a systematic review of the evidence on the outcomes of two 

technologies for wound healing: low-level laser therapy and vacuum-assisted closure. The 

protocol for this review was designed prospectively as much as possible to define: study 

objectives; search strategy; patient populations of interest; study selection criteria; outcomes of

interest; data elements to be abstracted and methods for abstraction; and methods for study 

quality assessment. 

This chapter of the report describes the objectives, key questions, and search strategies used 

to find articles; the criteria and methods for selecting eligible articles; the methods for data 

abstraction; the methods for quality assessment; and finally, the peer review and technical 

assistance received during the project. 

Objective and Key Questions 

The objective of this evidence report is to systematically review and synthesize the available 

evidence on the effectiveness of low-level laser treatment and vacuum-assisted closure for 

wound healing. To achieve this objective, the following key questions will be addressed: 

Low-Level Laser Treatment 

In the treatment of chronic, nonhealing wounds, what are the outcomes of low-level laser therapy 

for specific indications and patient types: 

a) as a substitute for standard therapy; or 

b) as an adjunct to standard therapy, compared with standard therapy alone? 

Vacuum-Assisted Closure 

In the treatment of various wounds, what are the outcomes of vacuum-assisted closure for 

specific indications and patient types: 

a) as a substitute for standard dressings; and 

b) as an adjunct to standard therapy, compared with standard therapy alone?

Search Strategy 

Electronic database searches were completed of MEDLINE® (via PubMed), EMBASE, and 

the Cochrane Controlled Trials Register. The MEDLINE® search covered references entered 

onto the database from January 1, 1966 through June 8, 2004. The Cochrane Controlled Trials 

Register search was completed in 2003, through issue number 4. The EMBASE search covered 

references entered through June 14, 2004. For detailed search terms, please refer to Appendix 

A.1

The search was limited to studies on human subjects with English-language abstracts. Papers 

published in foreign languages were reviewed if the English-language abstract appeared to meet 

 1

 Appendixes will be provided electronically at http://www.ahrq.gov/clinic/tp/woundtp.htm 

13
inclusion criteria. Results of the search and study selection were reviewed by the Technical 

Expert Panel for this project, in order to identify additional studies. 

In addition, two companies that produce lasers used in wound healing (Microlight 

Corporation of America and Photothera), as well as the major producer of vacuum-assisted 

closure devices (V.A.C.®, Kinetic Concepts Inc. [KCI]), were contacted and were invited to 

submit evidence-based information for the review. The specific request was for “lists of 

published, randomized, controlled trials (RCTs), published abstracts of RCTs within the past 2 

years, and published articles on study design, or protocols of any RCTs (published or in 

progress).” 

In some cases, device approval applications to the U.S. Food and Drug Administration 

(FDA) contain data from randomized, controlled efficacy trials. If available, such trials should be 

sought by the literature search. However, lasers used in wound healing and vacuum-assisted 

closure devices have been cleared for marketing by the FDA's 510(k) process, a regulatory 

mechanism that does not require submission of data from controlled efficacy trials. 

Patients, Settings, Interventions, and Outcomes 

Patient Populations 

Low-level laser treatment. With respect to low-level laser treatment, chronic wounds may be 

classified in a variety of ways. The simplest way is to distinguish between cutaneous ulcers and 

burns. However, a more comprehensive classification system places chronic wounds into these 

categories:

• pressure ulcers 

• metabolic disorders (e.g., diabetes mellitus)

• vascular insufficiency 

• inflammatory disorders 

• malignancies 

• infections 

• miscellaneous (e.g., burns) 

Vacuum-assisted closure. The review for vacuum-assisted closure addressed: 

• chronic wounds (as above) 

• acute wounds 

• traumatic wounds 

• subacute wounds 

• dehisced wounds 

• partial thickness burns 

• diabetic ulcers 

• pressure ulcers 

• flaps 

• grafts 

14
Study populations with both acute and chronic wounds will be examined carefully with 

respect to the duration of the wound and the types of interventions that have been performed 

prior to treatment with low-level laser therapy or vacuum-assisted closure. Some wounds may 

be described as refractory; that term should be defined as specifically as possible in terms of the 

types and duration of previous treatments. Similarly, the term “chronic” should be defined in as 

much detail as possible. 

Practice Settings 

Low-level laser treatment and vacuum-assisted closure may be used in the following settings: 

• Surgical centers 

• Hospitals 

• Specialized wound care centers 

• Nursing or rehabilitation facilities 

• Physicians' offices 

• Physical therapy offices 

• Homes 

Interventions/Technologies of Interest 

Standard care. Standard wound care is multifactorial. Among its components are: 

• Debridement 

• Dressings 

• Topical or systemic medications 

• Compression 

• Skin grafting 

• Skin equivalents 

• Improved nutrition 

• Convalescence 

• Physical therapy 

• Treatment of underlying disorder 

Low-level laser treatment. This review will focus on lasers that have been described as lowenergy, low-power, low-level or “cold” lasers. The power of these lasers ranges from 0.001 

watts (1 mW) to 0.05 watts (50 mW), producing minimal heating of tissue. Lasers used in 

wound healing applications include the gallium-aluminum (GaAl), gallium-arsenide (GaAs) and 

helium-neon (He-Ne) laser. Characteristics of laser treatment that would be of interest include 

laser type, intensity (measured in Joules per square centimeter of wound surface [Joules/cm2

]), 

duration of each session, frequency of sessions, and overall duration of treatment. Other prior 

and concurrent treatments will be examined in detail. 

Vacuum-assisted closure. The vacuum-assisted closure technique involves application of a 

sterile, open-pore foam dressing directly on the wound, which is then sealed with an adhesive 

15
drape, thus converting an open wound to a closed, controlled wound. An evacuation tube, 

embedded in the dressing, feeds into a collection canister. When subatmospheric pressure is 

applied, effluent from the wound is drawn out. Attention will be paid to the degree of negative 

pressure applied, frequency of dressing changes, and duration of use of the vacuum device. 

Other prior and concurrent treatments will be examined in detail. 

Outcomes of Interest 

In general, outcomes should be standard, valid, reliable and clinically meaningful. A 2000 

draft guidance document produced by the FDA (U.S. Food and Drug Administration, 2000) 

stated that wound healing outcomes should focus on the probability or speed of achieving 

complete wound closure. Intermediate outcomes such as wound size are problematic because of 

uncertainty about the validity of measurement techniques and clinical meaningfulness. 

• Primary outcomes: 

 incidence of complete wound closure 

 time to complete closure

 adverse events 

• Secondary outcomes 

 facilitating surgical closure 

 need for debridement 

 infections 

 pain 

 activities of daily living 

 quality of life 

 improved cosmesis 

Other secondary outcomes abstracted were change in wound size and transcutaneous oxygen 

tension (tcpO2); however, these were considered to be of less clinical importance. 

Study Selection Criteria 

As noted in the Introduction chapter of this Report, randomized, controlled trials are 

necessary to adequately assess the effectiveness of wound-healing interventions. Wound care 

entails multiple treatment factors, and it can be very difficult to attribute an effect to a specific 

factor. In addition, confounding could occur due to differences in patient characteristics and the 

quality and type of treatment factors. Randomization is the best method to assemble treatment 

groups that are comparable on known and unknown patient confounders. 

This systematic review will select only randomized, controlled trials meeting the following 

criteria: 

16
1) The trial must involve one of the following comparisons of interventions 

a) Either low-level laser treatment or vacuum-assisted closure, compared with other wound 

healing interventions (alternative intervention trials). 

b) Either low-level laser treatment or vacuum-assisted closure in addition to standard wound 

care, compared with standard wound care alone (incremental benefit trials). 

c) Either low-level laser treatment or vacuum-assisted closure, compared with a sham

intervention (placebo trials). 

2) For low-level laser treatment, patient selection criteria must target those with chronic 

wounds. For vacuum-assisted closure, patient selection may address those with chronic 

wounds or other types of wounds (see “Patient Populations,” above). 

3) The trial must report on at least one of the outcomes listed above under “Outcomes of 

Interest.”

4) The trial must be published as a full journal article and not merely as a conference abstract. 

Any citation lacking an abstract was excluded if the article was published in a non-Englishlanguage journal. Otherwise, when abstracts were missing, the full-text article was retrieved for 

review if the title suggested it might possibly meet the study selection criteria. 

For low-level laser, the searches found 482 references: 435 were excluded on the first screen, 

47 were retrieved, 11 met selection criteria and were abstracted, and 36 were excluded on the 

second screen. For vacuum-assisted closure, the searches found 467 references: 416 were 

excluded on the first screen, 51 were retrieved, six met selection criteria and were abstracted, and 

45 were excluded on the second screen. 

Methods of the Review 

Search results were stored in ProCite® databases. Titles and abstracts were screened by a 

single reviewer who marked each citation as either eligible for review as full-text articles or 

ineligible for full-text review. A second reviewer reviewed all citations marked as ineligible by 

the first reviewer. Agreement between raters was necessary to exclude a citation from full-text 

review. An “eligible” rating was necessary from only one reviewer to place a citation in the pool 

of those to be retrieved for full text review. 

In reviewing full-text articles to determine eligibility for data abstraction, a single reviewer 

determined whether each paper should be either: (1) included in systematic review; (2) excluded 

from systematic review; or (3) discussed with additional reviewer. 

Evidence tables were developed in Microsoft Excel® and Microsoft Word®. One reviewer 

performed primary data abstraction of all data elements into the evidence tables, and a second 

reviewer checked the evidence tables for accuracy. 

A procedure was established in case of disagreements that could not be resolved between the 

two reviewers. In such cases, the EPC Program Director was consulted and then, if necessary, 

the relevant members of the Technical Expert Panel. 

17
Assessment of Study Quality 

This systematic review applies the general approach to grading evidence developed by the 

U.S. Preventive Services Task Force (Harris, Helfand, Woolf, et al., 2001). Two independent 

reviewers rated study quality and disagreements in ratings were resolved by consensus. 

Following are the study design criteria and rating definitions developed by Harris and colleagues.

Study Design Criteria 

• Initial assembly of comparable groups: adequate randomization, including concealment 

and whether potential confounders (e.g., other concomitant care, patient characteristics) 

were distributed equally among groups 

• Maintenance of comparable groups (includes attrition, crossovers, adherence, 

contamination) 

• Important differential loss to followup or overall high loss to followup 

• Measurements: equal, reliable, and valid (includes masking of outcome assessment) 

• Clear definition of interventions 

• All important outcomes considered 

• Analysis: adjustment for potential confounders, intention-to-treat analysis 

Definition of Quality Ratings

In applying the Harris rating system to the studies selected for this systematic review, several 

rules were followed. To conclude that a study achieved initial assembly of comparable groups, it 

had to use an adequate randomization method and had to have equal distribution of confounders. 

Adequate randomization was defined as either central randomization or use of opaque envelopes 

(concealment). For the purposes of this review, equal distribution of confounders was defined as 

a minimal difference (less than 20%) in mean values between groups on age, wound duration and 

wound size. Low loss to followup and maintenance of comparable groups was defined as loss 

less than 20% of the initial sample and no differential loss to followup between groups. 

To consider measurements reliable, valid and equal, the article had to provide a clear 

description of wound measurement methods that appeared reproducible. Examples include use 

of photographic or digital transfer of wound tracings and/or use of computer software to 

calculate wound size. Liquid or plaster used to measure wound volume was also acceptable. 

Use of a blinded outcome assessor was also necessary to fully satisfy this quality dimension. 

Clear, detailed descriptions of both control and treatment interventions were sought. Analysis of 

results was considered appropriate if the investigators adjusted for confounders and analyzed by 

intention-to-treat, which was defined as analyzing all randomized patients or no more than 5% 

loss of the initial sample. See Table 3 for the quality criteria and ratings system applied to the 

evidence tables in Chapter 3. 

Good. Meets all criteria: Comparable groups are assembled initially and maintained throughout 

the study (followup at least 80 percent); reliable and valid measurement instruments are used and 

applied equally to the groups; interventions are spelled out clearly; all important outcomes are 

18
considered; and appropriate attention to confounders in analysis. In addition, for RCTs, 

intention-to-treat analysis is used. 

Fair. Studies will be graded “fair” if any or all of the following problems occur, without the 

fatal flaws noted in the “poor” category below: Generally comparable groups are assembled 

initially but some question remains whether some (although not major) differences occurred with 

followup; measurement instruments are acceptable (although not the best) and generally applied 

equally; some but not all important outcomes are considered; and some but not all potential 

confounders are accounted for. Intention-to-treat analysis is done for RCTs. 

Poor. Studies will be graded “poor” if any of the following fatal flaws exists: Groups assembled 

initially are not close to being comparable or maintained throughout the study; unreliable or 

invalid measurement instruments are used or not applied at all equally among groups (including 

not masking outcome assessment); and key confounders are given little or no attention. For 

RCTs, intention-to-treat analysis is lacking. 

Table 3. Quality Rating Criteria and Ratings

Dimension Components Dimension Ratings Quality Ratings

Initial Assembly of 

Comparable Groups 

Adequate randomization 

(concealed or 

centralized) 

Yes = all components 

adequate, satisfied 

Good = All dimensions 

satisfied 

Equal distribution of 

confounders (at least 

age, wound size, wound 

duration) 

No = one or more 

component inadequate, 

not satisfied 

Fair = all dimensions 

satisfied or partially 

satisfied 

Low Loss to Followup, 

Maintenance of

Comparable Groups 

No differential loss to 

F/U or Low Overall Loss 

to F/U (>20%) 

Partial = one or more 

components adequate, 

none inadequate, partially

satisfied 

Poor = one or more 

dimension not satisfied 

Measurements

Reliable, Valid, Equal 

Clearly described, 

reproducible 

measurement 

? = unclear if any

components satisfied 

Blinded outcome

assessment 

Interventions 

Comparable/Clearly 

Defined 

Appropriate Analysis 

of Results 

Adjustment for 

Confounders 

Intention-to-treat

analysis (all randomized 

analyzed to 5% or less 

loss) 

19
Technical Expert Panel and Peer Review 

The development of this evidence report was subject to extensive expert review, including 

ongoing guidance from a Technical Expert Panel (TEP) and document review by the TEP. 

The draft report was also reviewed by a panel of external peer reviewers that included 

experts in anesthesiology, dermatology, nursing, otolaryngology and orthopedic surgery, 

physical therapy, plastic and reconstructive surgery, podiatry, therapeutic laser technology, and 

undersea and hyperbaric medicine. Reviews were also solicited from the American Academy of 

Wound Management, the Association for the Advancement of Wound Care, and Wound, 

Ostomy and Continence Nurses Society. Comments were elicited from external peer reviewers 

using a structured comment form, compiled, and submitted with a description of comment 

disposition to the Agency for Healthcare Research and Quality (AHRQ). Appendix B lists the 

members of the Technical Expert Panel and external peer reviewers.2

 2

 Appendixes will be provided electronically at http://www.ahrq.gov/clinic/tp/woundtp.htm 

20
Chapter 3. Results 

Part I: Low-Level Laser Therapy 

The first part of this chapter reviews evidence on the following questions: 

In the treatment of chronic nonhealing wounds, what are the outcomes of low-level laser 

therapy for specific indications and patient types: 

a) as a substitute for standard therapy; or 

b) as an adjunct to standard therapy, compared with standard therapy alone? 

Overview

The only previous systematic reviews available on the use of laser therapy for wound healing 

have been produced by a single group in the United Kingdom (Flemming and Cullum, 2003; 

Cullum, Nelson, Flemming et al. 2001; Flemming, Cullum and Nelson, 1999). These reviews 

found no supportive evidence for a benefit of low level laser therapy in healing of venous leg 

ulcers. All 4 studies abstracted by these reviews are included in the present review. 

Among excluded studies, 3 were randomized controlled trials. Two were excluded because 

they did not select patients with chronic wounds (Lagan, Clements, McDonough, et al., 2001; 

Fernando, Hill, and Walker, 1993). The third study reported only on an outcome that was not of 

interest to this review, skin temperature (Schindl, Heinze, Schindl et al., 2002). Four 

comparative studies published in foreign languages were excluded. One German study was 

excluded because it did not select patients with chronic wounds (Zimmerman, 1990). Three 

Russian studies were examined by a Russian reader who determined that subjects were not 

assigned to groups randomly (Babadzhanov and Sultanov, 1998; Gostishchev, Vertianov, 

Novochenko, et al., 1987; Gostishchev, Vertianov, Shur, et al., 1985). No other nonrandom

comparative studies published in English were found. All other excluded studies were case 

series or case reports. 

Review of search results identified a total of 11 studies (n=413; (Bihari and Mester, 1989; 

Crous and Malherbe, 1988; Franek, Krol, and Kucharzewski, 2002; Iusim, Kimchy, Pillar, et al., 

1992; Lagan, McKenna, Witherow, et al., 2002; Lucas, Coenen, and De Haan, 2000; Lucas, van 

Gemert, and de Haan, 2003; Lundeberg and Malm, 1991; Malm and Lundeberg, 1991; 

Nussbaum, Biemann, and Mustard, 1994; Santoianni, Monfrecola, Martellotta, et al., 1984) that 

met study selection criteria for low-level laser therapy (Evidence Table 1). 

Details about studies meeting selection criteria are provided in Evidence Tables 2–5, each of 

which is divided into three subsets. The “A” subsets include seven studies with placebo controls, 

the “B” subsets contain three studies assessing the effects of low-level laser therapy plus 

standard treatment versus standard treatment alone, and the “C” subsets describe one study 

comparing the use of ultraviolet light and low-level laser therapy. Evidence Table 2 presents 

patient characteristics. Evidence Table 3 focuses on treatment details. Evidence Table 4 

describes outcomes assessment. Evidence Table 5 provides results. Information shown in 

Evidence Tables 1–5 served as the basis for study quality ratings. Study quality ratings are 

included in Evidence Table 6 (See Table 3, Chapter 2, Methods, for study quality criteria and 

ratings). 

21 
Evidence Table 1. Summary of Low-Level Laser Therapy Studies 

Study

n Randomized 

Patient Selection Control (Cx) Treatment (Tx) Comparable Characteristics Alloca- tion 

TxDescription 

Wound Measure-ment 

CompHeali

Franek, Krol, and Kucharzewski, 2002 

65; Cx1: 22; Cx2: 22; Tx: 21 

LE venous ulcers 

Cx1: SC+sham Cx2: SC 

SC+laser Yes: age, size 

No: duration 

random Cx, Tx

clear 

Digital, planimetrySW 

NR 

Lagan, McKenna, Witherow, et al., 2002 

15; Cx: 7; Tx: 8

Chronic LE venous ulcers 

SC+sham SC+laser ?: age, size, 

duration 

random Cx, Tx

clear 

Digital, SW, blind 

NR 

Malm and Lundeberg, 1991 

42; Cx: 21; Tx: 21 

LE venous ulcers 

SC+sham SC+laser Yes: age, size 

?: duration 

random Cx, Tx

clear 

Tracings, blind 

Tx=C

Lundeberg andMalm, 1991 

46; Cx: 23; Tx: 23 

LE venous ulcers 

SC+sham SC+laser Yes: age, size 

?: duration 

random Cx, Tx

clear 

Tracings, blind 

Tx=C

Bihari and Mester, 1989 

45; Cx: 15; Tx1: 15; Tx2: 15 

Resistant LE ulcers 

SC+sham Tx1: SC+hand

laser; Tx2; SC+machine laser 

?: age, size, duration 

random Cx, Tx

clear 

Blind Tx1=C

Tx2>C

Santoianni, Monfrecola, Martellotta, et al., 1984 

>28 Chronic

LE venous ulcers 

SC+laser misdirection 

Tx1: SC+1 J laser; Tx2: SC+4 J laser 

?: age, size, duration 

random Cx, Tx

clear 

Photos, tracings 

NR 

Iusim, Kimchy, Pillar, et al., 1992 

21; Cx: 7, Tx1: 8; Tx2: 6 

Resistant postop wounds 

SC+sham Tx1: SC+red

laser; Tx2: SC+IR laser 

Yes: age, size ?: duration 

random Cx, Tx

clear 

Photos NR 

Lucas, van Gemert, and deHaan, 2003 

86; Cx: 47; Tx: 39 

Pressure ulcers 

SC SC+Laser Yes: age, size,

duration 

Centrally random Cx, Tx clear Photos, tracing, blind Tx=C

Nussbaum, Biemann, and Mustard, 1994

20; Cx: 9 Tx1: 6 Tx2: 5 

Pressure ulcers 

SC Tx1: SC+Laser; Yes: age, 

Tx2: SC+US/UV duration 

No: size 

random Cx, Tx

clear 

Digital, blind 

Tx1=CTx2=CTx2>T

22 
Evidence Table 1. Summary of Low-Level Laser Therapy Studies (continued) 

Study

n Randomized 

Patient Selection Control (Cx) Treatment (Tx) Comparable Characteristics Alloca- tion 

TxDescription 

Wound Measurement Comp

Heali

Lucas, Coenen, and De Haan, 2000 

16 Cx: 8 Tx: 8

Pressure ulcers 

SC SC+Laser Yes: age,

duration, size 

random Cx, Tx

clear 

Photos, tracing, blind 

Tx=C

Crous and Malherbe, 1988

6 Cx: 3 Tx: 3

Chronic LE venous ulcers 

SC+UV SC+Laser ?: age, duration, 

size 

random Cx, Tx

clear 

Photos, blind 

NR 

Abbreviations: See end of Report

23 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics 

A. Placebo-Controlled Studies

Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Franek, Krol, and Kucharzewski, 2002; Bytom, Poland 

Cx1: compressive/ topical therapy+ sham laser Cx2: compressive/ topical therapyTx:compressive/ topical therapy+ laser 

symptomatic venous crural ulceration; chronic venousinsufficiency;ABI > 0.8, Doppler US ruled out arterial component 

65

Cx1: 22 Cx2: 22 Tx: 21 

Cx1: mn

65, rng 41-88 

Cx1: 10 M, 12 F

Cx2: mn 66, rng 43-86 Tx: mn 65, rng 44-80 

Cx2: 3 M, 19 FTx: 4 M, 17 F 

Cx1: mn 30 mo, rng 1 wk - 18 yrCx2: mn 51 mo, rng 4 mo - 16 yrTx: mn 41 mo, rng 2 wk - 24 yr

Cx1sq c0.4Cx2rng Tx: rng 

Lagan, McKenna, Witherow, et al., 2002; Ulster, UK 

Cx: standard nursing care +sham laser Tx: standard nursing care +laser 

15 pts with 16chronic venous/ mixed venous/ arterial ulcers; recruited from specialized outpatient leg ulcer clinic; age 30-85; able to attend weeklyassessment; no current/ previous laser; 

grossly infected wounds; medications contraindicatedfor laser; noncompliant pts; active/ suspected carcinoma; photosensitive skin; contraindications for laser; referral source requests particular treatment 

15 Cx: 7 Tx: 8

Cx+Tx: mn

69.9, SD 13.8 

Cx+Tx: 5 M, 10 F

Cx+Tx: mn 11.3 mo, SD 8.5 

24 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics (continued)

A. Placebo-Controlled Studies (cont’d) Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Malm and Lundeberg, 1991; Stockholm, Sweden 

Cx: standard conservative treatment +sham laser Tx: standard conservative treatment +laser 

venous leg ulcers 

skin allergy to standard treatment, peripheral arterial disease,rheumatoid arthritis, diabetes mellitus, traumatic venous ulcer, ankle pressure< 75 mmHg 

42 Cx: 21Tx: 21 

10 Cx: 6 Tx: 4(2 allergy to paste bandage, 7 unable to attend laser treatment regularly, 1 excessivepain) 

Cx: mn 61, rng 46-76 Tx: mn 60, rng 43-77 

Cx: 9 M, 12 F Tx: 10 M, 11 F

Cx: 

cm, Tx: 4-5

Lundeberg andMalm, 1991; Stockholm, Sweden 

Cx: standard treatment +sham laser Tx: standard treatment +laser 

venous leg ulcers 

skin allergy to standard treatment, peripheral arterial disease,rheumatoid arthritis, diabetes mellitus, traumatic venous ulcer 

46 Cx: 23Tx: 23 

12 Cx: 4 Tx: 8(4 allergy topaste bandage, 2 excessivepain, 6 unable to attend regularly) 

Cx: mn 54, rng 41-69 Tx: mn 62, rng 49-73 

Cx: 9 M, 14 F Tx: 8 M, 15 F 

Cx: 

cm, Tx: 

25 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics (continued)

A. Placebo-Controlled Studies (cont’d) Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Bihari and Mester, 1989; Budapest, Hungary 

Cx: adjuvant therapy +sham laser Tx1: adjuvant therapy +hand-held laser Tx2: adjuvant therapy +machinescanned laser 

crural ulcers proven resistant to conventionaltherapy ('torpid'ulcers) 

45

Cx: 15Tx1: 15 Tx2: 15 

Santoianni, Monfrecola, Martellotta, et al., 1984; Naples, Italy

Cx: compresses + laser pointed away from wound Tx1:compresses + laser 1 J/sq cmTx2:compresses + laser 4 J/sq cm

chronic venousleg ulcers; hospitalized 

≥30 2-23 mo

26 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics (continued)

A. Placebo-Controlled Studies (cont’d) Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Iusim, Kimchy, Pillar, et al., 1992; Haifa 

Cx: regular treatment +placebo Tx1: regular treatment + red light laser Tx2: regular treatment +infrared light laser 

Postoperative wounds resistant to conventional therapy: neuropathic foot ulcer, pressuresores, venous ulcers, diabeticfoot, amputation/ other surgerywith delayed wound healing

21 pts: Cx: 

7, Tx1: 8 Tx2: 6; 31 wounds: Cx: 11, Tx1: 9, Tx2: 11 

Cx: mn 

74.5, rng 60-87Tx1: mn71.1, rng 57-85Tx2: 74.5, rng 44-88 

Cx: 4 M, 4 F Tx1: 3 M, 4 F Tx2: 4 M, 2 F 

resistant to conventional therapy 

Cx: cm, Tx10.1-Tx2rng 

27 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics (continued)

B. Studies of Incremental Effect over Standard TreatmentStudy Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Lucas, van Gemert, and deHaan, 2003; Amsterdam, Netherlands 

Cx: consensustherapies Tx: consensus therapies + lowlevel laser therapy 

Consecutive pts, stage III (full-thickness, into subcutaneous/fat layer) decubitus ulcers, 3 nursing homes; 1 wound/pt; noage restriction

Wound area >30 sq cm; wound completelyoccluded byeschar; wound duration > 1 yr;diabetic pts withserious metabolic disorders; terminally ill pts 

86 Cx: 47Tx: 39 (19/105 refused consent) 

5 Cx: 3 (1 died, 1 hospitalized, 1 stage IV) Tx: 2(1 died, 1 stage IV) 

Cx: mn 83.5, SD 8.9, med 85, rng 49-100 Tx: mn81.3, SD 9.6, med 82, rng 49-94 

Cx: 18 M, 29 FTx: 14 M, 25 F

Cx: mn 3.3 wk,SD 5.1, med 2, rng 0.5-30, msg 3 Tx: mn 2.9, SD4, med 2, rng 0.5-22, msg 3 

Cx: mm100 500 - 8 Tx: 396100500 

Nussbaum, Biemann, and Mustard, 1994;Toronto, Canada 

Cx: standard treatment alone Tx1: standard treatment +laser Tx2: standard treatment +US/ UV-C 

hospitalized, spinal cord injury, skin wound 

20 pts

Cx: 9 Tx1: 6 Tx2: 5; 22 woundsCx: 9 Tx1: 7 Tx2: 6 

4 Cx: 3 Tx1: 1 (2 transferred to acute care hospitals, 2 elected surgical closure) 

Cx: mn 36, rng 15-46 Tx1: mn42, rng 30-61 Tx2: mn42.2, rng 26-59

Cx: 5 M, 1 F Tx1: 5 M, 1 F Tx2: 6 M, 0 F 

> 6 wk: Cx: 4 Tx1: 6 Tx2: 6; < 1 wk: Cx: 2 Tx1: 0 Tx2: 0 

Cx: cm, 3.3 Tx10.9 Tx20.9 

28 
Evidence Table 2. Low-Level Laser Therapy, Patient Characteristics (continued)

B. Studies of Incremental Effect over Standard Treatment (cont’d)Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Lucas, Coenen, and De Haan, 2000; Amsterdam, Netherlands 

Cx: consensustreatment Tx: consensus treatment +LLLT

consecutive pts, stage III pressure ulcers, 4 nursing homes 

Wounds > 30 sqcm, wounds completelyoccluded byeschar, constant/ invariable ulceration > 1 yr, diabetics with serious metabolic disorders, terminal pts 

16 Cx: 8 Tx: 8

Cx: med

88, rng 72-95 

Cx: 0 M, 8 F 

Tx: med 87.5, rng 73-92

Tx: 2 M, 6 F 

(wk) Cx: med 3, rng 1-10Tx: med 3, rng 1-9 

Cx: mmTx: 9-5

C. Laser Treatment versus Ultraviolet Light Study Comparison Inclusion Exclusion

n, Randomized n, Withdrew Age Gender Wound Duration Wo

Crous and Malherbe, 1988

Cx: medical treatment +ultraviolet lightTx: medical treatment +laser 

Distal lower extremitychronic venousulcers; 5 of 6 hospitalized 

6

Cx: 3 Tx: 3

Cx: rng 70-

79 

Cx: 2 M, 1 F 

Tx: rng 65-77 

Tx: 1 M, 2 F 

Cx: rng 0.4-30 yrTx: rng 6-12 yr

29 
Evidence Table 3. Low-Level Laser Therapy, Treatments 

A. Placebo-Controlled Studies

Study Allocation Comparison Control Treatment

Treatment 

Regimen 

Franek, Krol, 

and 

Kucharzewski, 

2002; Bytom, 

Poland 

groups established 

at random, Cx1 

and Tx groups in 

Dermatology Ward 

of same hospital, 

Cx2 group treated 

in different hospital 

Cx1: compressive/ 

topical therapy +

sham laser 

Cx2: compressive/ 

topical therapy

Tx: compressive/ 

topical therapy +

laser 

compressive: single layer 

elastic dressings; topical: 

baths of potassium 

permanganate, 0.1% 

copper sulfate,

compresses with colistins, 

fibrolaan, 

chloramphenicol and 

gentamicin under a 

dressing; changed every

few days; sham: radiation 

absorbing system in laser

GaA1As 810 nm, 4 J/sq 

cm, 65 mW; duration of 

treatment adjusted to 

ulcer size keeping dose 

constant 

5x/wk, mn 

4.5-5.0 wk

Lagan, 

McKenna, 

Witherow, et 

al., 2002; 

Ulster, UK 

prepared random 

allocation listing

held by the 

physical therapist 

delivering the 

sham/laser 

treatment, only 

unblinded party, 

played no other 

role in the trial 

Cx: standard nursing 

care + sham laser 

Tx: standard nursing 

care + laser 

standard nursing care: 

cleansing with water, 

debridement, dressings 

and/or compression 

bandaging; sham laser: 

nonemitting array

Biotherapy 3ML system 

(Omega Laser Systems, 

UK) GaA1As 660-950 nm, 

12 J/sq cm, 532 mW, 

noncontact technique, 

unit maintained 0.5 cm 

from surface 

1x/wk, 4 wk

Malm and 

Lundeberg, 

1991; 

Stockholm, 

Sweden 

Randomized by

permuted blocks 

Cx: standard 

conservative 

treatment + sham 

laser 

Tx: standard 

conservative 

treatment + laser, 

conservative wound care: 

cleaning with saline, 

paste bandage, elastic 

bandage at 15-25 mmHg; 

exercise program given 

on instruction sheet; 

sham laser: light removed

Irradia GaAs, 904 nm, 

1.96 J/sq cm, 4 mW; laser 

held perpendicular to 

wound for 10 min 

2x/wk, 12 

wk

Lundeberg and

Malm, 1991; 

Stockholm, 

Sweden 

Assigned 

randomly, by

permuted blocks 

Cx: standard 

treatment + sham 

laser 

Tx: standard 

treatment + laser 

Cleansing with saline, 

paste bandage followed 

by support bandage, 

exercise program 

HeNe, 632.8 nm, 4 J/sq 

cm, 6 mW 

2x/wk, 12 

wk

30 
Evidence Table 3. Low-Level Laser Therapy, Treatments (continued)

A. Placebo-Controlled Studies (cont’d) 

Study Allocation Comparison Control Treatment

Treatment 

Regimen 

Bihari and 

Mester, 1989; 

Budapest, 

Hungary 

randomly divided 

into groups by age 

Cx: adjuvant therapy 

+ sham laser 

Tx1: adjuvant therapy

+ hand-held laser 

Tx2: adjuvant therapy

+ machine-scanned 

laser 

adjuvant therapy: 

compressive bandages, 

antibiotics; sham: 

noncoherent nonpolarized

filtered light 

Hand-held Lasotronic 

HeNe; machine scanned 

Lasotronic HeNe/pulsed 

infrared, 904 nm, 4800 

Hz, 4 J/sq cm 

1x/wk, 9 mo

Santoianni, 

Monfrecola, 

Martellotta, et 

al., 1984; 

Naples, Italy

pts randomly

assigned to laser 

group or control 

group; if single 

ulcer < 5 cm, 

whole ulcer 

irradiated, if single 

ulcer > 5 cm, 1 

half irradiated, 

other half kept as 

control; if bilateral 

ulcers, < 30% 

difference in area, 

1 irradiated, 1 

used as control

(within subjects?) 

Cx: compresses + 

laser pointed away

from wound 

Tx1: compresses + 

laser 1 J/sq cm

Tx2: compresses + 

laser 4 J/sq cm

no surgery; antiseptic 

compresses changed 

2x/d

Valfivre LCS 25 HeNe

632.8 nm, 1 or 4 J/sq cm, 

25 mW, beam expander 

to cover entire wound 

6 d/wk, > 1 

mo 

Iusim, Kimchy, 

Pillar, et al., 

1992; Haifa, 

Israel 

randomly allocated Cx: regular treatment + placebo 

Tx1: regular treatment+red light laser 

Tx2: regular treatment+infrared light 

laser 

patients continued to 

receive regular local and 

general treatment (Milton, 

Rivanol, Neomycin, 

H2O2, Synto, Dermalar) 

Biobeam red light (660 

nm, 7.5-18 mW); infrared 

light (940 nm, 2.7-25 

mW), 7 min on continuous 

wave, 7 min on pulsed 

wave, focused on single 

point 

7 min cont, 

7 min 

pulsed, daily

31 
Evidence Table 3. Low-Level Laser Therapy, Treatments (continued)

B. Studies of Incremental Effect over Standard Treatment

Study Allocation Comparison Control Treatment

Treatment 

Regimen 

Lucas, van 

Gemert, and 

de Haan, 2003; 

Amsterdam, 

Netherlands 

randomly assigned 

by central 

computerized 

telephone service; 

minimization 

performed on 

wound size 

category and 

treatment center 

Cx: consensus

therapies 

Tx: consensus 

therapies+low level 

laser therapy 

consensus therapies, 

daily over 6 wk, based on

NPUAP 

recommendations: pt info/ 

instruction, wound 

cleansing, simple moist 

dressings, frequent 

position alteration 

Combilaser C-501 GaAs, 

904 nm, 1 J/sq cm, 12 x 8 

mW, irradiated area 12 sq 

cm, 125 sec, no 

corticosteroids/

concurrent adjunctive 

interventions; probe at < 1 

mm from center of wound 

surface 

5x/wk, 6 wk

Nussbaum, 

Biemann, and 

Mustard, 1994;

Toronto, 

Canada 

Randomly

assigned 

Cx: standard 

treatment alone

Tx1: standard 

treatment+laser

Tx2: standard 

treatment+US/ UV-C 

standard wound care: 

cleansing 2x/d with

Hygeol, Jelonet moist 

dressings, avoidance of 

lying or sitting on existing 

ulcers; participation in

rehabilitation program 

plastic covered Intelect 

800 cluster probe; 820 nm 

laser diode, 4 J/sq cm, 15 

mW, treatment time 35 

sec; probe in contact with 

wound; one exposure for 

small wounds; central and 

perimeter application for 

large wounds 

3x/wk, to 

closure 

Lucas, 

Coenen, and 

De Haan, 

2000; 

Amsterdam, 

Netherlands 

randomly assigned Cx: consensus

treatment 

Tx: consensus 

treatment+LLLT

consensus treatment: 

information/instruction, 

cleansing, simple moist 

dressings, frequent 

position alteration, no 

additional medication 

(corticosteroids), no 

concurrent physical 

therapy 

Combilaser C-501 GaAs, 

904 nm, 830 Hz, 1 J/sq 

cm, 8 mW, exposure time 

2 min 5 sec 

5x/wk, 6 wk

32 
Evidence Table 3. Low-Level Laser Therapy, Treatments (continued)

C. Laser Treatment Versus Ultraviolet Light 

Study Allocation Comparison Control Treatment

Treatment 

Regimen 

Crous and 

Malherbe, 

1988 

Randomly referred Cx: ultraviolet light 

Tx: laser

Medical treatment: 

dressings using saline, 

Granuflex and betadine, 

ultraviolet light, dose E4 

for necrotic tissue, dose 

E1 for granulation tissue 

Medical treatment, M3-UP 

scanning laser, 16 cm 

from ulcer, beam 

diameter 2 cm wider than 

ulcer, 1.4 mW, 10 min 

3x/wk, 4 wk

33 
Evidence Table 4. Low-Level Laser Therapy, Outcome Assessment 

A. Placebo-Controlled Studies

Study

Primary 

Outcomes 

Secondary

Outcomes 

Wound 

Measurement Observer F/U

Unit of

Analysis 

Intentionto-Treat? 

Franek, Krol, 

and 

Kucharzewski, 

2002; Bytom, 

Poland 

Wound area, 

volume, 

suppurative 

area, 

granulation 

area 

planimetry, traced

transparency, 

digitizing tablet 

4.5 -

5.0 wk

Pt ?

Lagan, 

McKenna, 

Witherow, et 

al., 2002; 

Ulster, UK 

wound surface 

area 

visual 

analogue 

scale pain 

traced on sterile

transparency by

one investigator

following

debridement; 

digitizing tablet; 

photography 

analysis of wound 

surface area

measurements

completed under 

blinded conditions 

1, 2, 3, 

4, 8, 12 

wk

pt ?

Malm and 

Lundeberg, 

1991; 

Stockholm, 

Sweden 

time to 

complete 

healing 

rate of 

healing 

tracings tracings identified by

code number to 

exclude observer 

bias 

12 wk pt no 

Lundeberg and

Malm (1991); 

Stockholm, 

Sweden 

time to 

complete 

healing 

rate of 

healing 

tracings tracings identified by

code number to 

exclude observer 

bias 

12 wk pt no 

Bihari and 

Mester, 1989; 

Budapest, 

Hungary 

independent trained

technician unaware 

which therapy pts 

received 

9 mo pt ? 

Santoianni, 

Monfrecola, 

Martellotta, et 

al., 1984; 

Naples 

epithelialization photographs, traced

transparencies

30 d no

Iusim, Kimchy, 

Pillar, et al., 

1992; Haifa 

complete 

healing, wound

area 

photographs 20 d pt (wound) ? 

34 
Evidence Table 4. Low-Level Laser Therapy, Outcome Assessment (continued) 

B. Studies of Incremental Effect over Standard Treatment

Study

Primary 

Outcomes 

Secondary

Outcomes 

Wound 

Measurement Observer F/U

Unit of

Analysis 

Intentionto-Treat? 

Lucas, van 

Gemert, and 

de Haan, 2003; 

Amsterdam, 

Netherlands 

absolute, 

relative

wound area

reduction 

Incidence 

stage IV, 

Norton Score

1:1 Polaroid; traced 

transparency 

Independent 

evaluator outlined 

wound on

transparency, area 

determined by

another blinded

evaluator 

6 wk pt ?, used last 

observation 

carried 

forward for 

Cx, not for 

Tx

Nussbaum, 

Biemann, and 

Mustard, 1994;

Toronto, 

Canada 

healing rate time to 

complete 

healing 

traced on 

transparency, 

digitizer tablet, stylus 

pen 

tracings made by 1 

investigator blinded 

to group assignment 

< 20 

wk, to 

complete 

healing 

wound ?

Lucas, 

Coenen, and 

De Haan, 

2000; 

Amsterdam, 

Netherlands 

wound area Complete 

healing 

1:1 Polaroid, outlined 

perimeter, 

transposed to 

transparency 

investigator blinded 

to clinical details

measured wound 

area 

6 wk pt ? 

C. Laser Treatment versus Ultraviolet Light 

Study

Primary 

Outcomes 

Secondary

Outcomes 

Wound 

Measurement Observer F/U

Unit of

Analysis 

Intentionto-Treat? 

Crous and 

Malherbe, 

1988 

ulcer size

(perimeter 

and area) 

Photography Physiotherapist not

involved with the 

investigation 

pt

35 
Evidence Table 5. Low-Level Laser Therapy, Results 

A. Placebo-Controlled Studies

Study Comparison Complete Healing Wound Area

Franek, Krol, 

and 

Kucharzewski, 

2002; Bytom, 

Poland 

Cx1: compressive/ 

topical therapy +

sham laser 

Cx2: compressive/ 

topical therapy

Tx: compressive/ 

topical therapy +

laser 

f/u average rate of change in relative area 

(%/wk): 

Cx1: 15 Cx2: 9 Tx: 16 (NS) 

average rate of change of relative 

suppurative area (%/wk): 

Cx1: 19 Cx2: 20 Tx: 9 (NS) 

Lagan, 

McKenna, 

Witherow, et 

al., 2002; 

Ulster, UK 

Cx: standard nursing 

care + sham laser 

Tx: standard nursing 

care + laser 

(% change): 

4 wk: Cx mn –23 Tx mn–26 

8 wk Cx mn -7 Tx mn –45.1 

SEM 20.6 SEM 16.6 

12 wk Cx mn +11.6 Tx mn –61.3 

SEM 41.2 SEM 15.6 

 (p=0.14) 

Malm and 

Lundeberg, 

1991; 

Stockholm, 

Sweden 

Cx: standard 

conservative 

treatment + sham 

laser 

Tx: standard 

conservative 

treatment + laser, 

12 wk

 Cx Tx

Dropped 6/21 4/21 

Healed 11/21 13/21 

Not healed 4/21 4/21 

Life-table analysis NS 

(% change/wk): NS 

Lundeberg and

Malm, 1991; 

Stockholm, 

Sweden 

Cx: standard 

treatment + sham 

laser 

Tx: standard 

treatment + laser 

12 wk

 Cx Tx

Dropped 4/23 8/23 

Healed 3/23 4/23 

Not healed 16/23 11/23 

Life-table analysis NS 

(% of original ulcer size): 

Cx: mn 49, SD 12 

Tx: mn 48, SD 9 (NS) 

36 
Evidence Table 5. Low-Level Laser Therapy, Results (continued)

A. Placebo-Controlled Studies (cont’d)

Study Comparison Complete Healing Wound Area

Bihari and 

Mester, 1989; 

Budapest, 

Hungary 

Cx: adjuvant therapy 

+ sham laser 

Tx1: adjuvant therapy

+ hand-held laser 

Tx2: adjuvant therapy

+ machine-scanned 

laser 

 Cx Tx1 Tx2 

Dropped 2/15 

Complete 5/15 10/15 12/15 

Improved 3/15 4/15 2/15 

No change 3/15 1/15 1/15 

Worse 2/15 0/15 0/15 

Complete healing: 

RR (95% CI) Tx1:Cx: 2.0 (0.9, 4.5) 

RR (95% CI) Tx2:Cx: 2.4 (1.1, 5.1) 

Santoianni, 

Monfrecola, 

Martellotta, et 

al., 1984; 

Naples, Italy

Cx: compresses + 

laser pointed away

from wound 

Tx1: compresses + 

laser 1 J/sq cm

Tx2: compresses + 

laser 4 J/sq cm

(area epithelialized, sq cm, ulcer < 5 cm): 

Cx: n=14, mn 3.3, SD 2.13 

Tx1: n=9, mn 3.21, SD 3.15 (p<0.95) 

Tx2: n=5, mn 4.52, SD 3.49 (p<0.5) 

(area epithelialized, ulcer > 5 cm, by half, 

control vs. laser): 

Tx1: n=7, mn (SD) 2.99 (2.55) vs. 2.3 (1.94) 

(NS) 

Tx2: n=10, mn (SD) 3.03 (4.47) vs. 3.22 

(4.25) (NS) 

Iusim, Kimchy, 

Pillar, et al., 

1992; Haifa, 

Israel 

Cx: regular treatment 

+ placebo 

Tx1: regular 

treatment + red light 

laser 

Tx2: regular 

treatment + infrared 

light laser 

Cx: 3/11 

Tx1: 3/9 

Tx2: 4/11 

(% change): 

Cx: mn -41 

Tx1: mn -89 (p=0.0345) 

Tx2: mn -58 (p=0.46) 

37 
Evidence Table 5. Low-Level Laser Therapy, Results (continued)

B. Studies of Incremental Effect over Standard Treatment

Study Comparison Complete Healing Wound Area

Lucas, van 

Gemert, and de

Haan, 2003; 

Amsterdam, 

Netherlands 

Cx: consensus

therapies 

Tx: consensus 

therapies + low level 

laser therapy 

 Cx Tx

N 43/47 36/39 

Complete 15/43 18/36 

Incomplete 26/43 12/36 

Larger 2/43 6/36 

(sq mm), Cx n=47/47, Tx n=36/39 

absolute improvement: 

 Cx Tx

Mn 138 48 

SD 270 394 (p=0.23) 

relative improvement (%): 

 Cx Tx

Mn 34 5 

SD 204 194 (p=0.42) 

LN improvement: 

 Cx Tx

mn 2.3 2.6 

SD 2.2 2.6 (p=0.59) 

Nussbaum, 

Biemann, and 

Mustard, 1994;

Toronto, 

Canada 

Cx: standard 

treatment alone

Tx1: standard 

treatment + laser 

Tx2: standard 

treatment + US/ UVC 

 Cx Tx1 Tx2 

Mn wks to 7.0 11.0 4.2 

complete 

healing 

(% change/wk): 

Cx: - 32.4 Tx1: -23.7 Tx2: -53.5 

(p=0.032, Tx2 better than Tx1, Tx1 not 

different from Cx; Tx2 not different from Cx)

Lucas, Coenen, 

and De Haan, 

2000; 

Amsterdam, 

Netherlands 

Cx: consensus

treatment 

Tx: consensus 

treatment + LLLT

6 wk: 

 Cx Tx

Complete 4/8 3/8 

(% change): 

Cx: med 95 

Tx: med 83 (p=0.47) 

C. Low-Level Laser Treatment, Results, Laser Treatment versus Ultraviolet Light

Study Comparison Complete Healing Wound Area

Crous and 

Malherbe, 1988

Cx: medical 

treatment + ultraviolet 

light 

Tx: medical treatment 

+ laser 

(% change):

Cx: mn -34, SD 21 

Tx: mn -50, SD 7 

38 
Evidence Table 6. Study Quality Ratings, Low-Level Laser Therapy

Study Yr

Initial Assembly of Comparable Groups

Low Loss toFollowup,Maintenance of Comparable Groups

Measurements Reliable, Valid, Equal 

Interventions Comparable/ Clearly Defined 

AppropriateAnalysis ofResults 

Overall Rating 

Franek, Krol, and Kucharzewski 2002 No Yes No Yes No PoorLagan, McKenna, Witherow, et al. 2002 ? Yes Yes Yes Partial PoorMalm and Lundeberg 1991 ? No Partial Yes No Poor Lundeberg and Malm 1991 ? No Partial No No Poor Bihari and Mester 1989 ? Yes Partial Yes Partial Poor Santoianni, Monfrecola, Martellotta, et al. 

1984 ? ? No Yes No Poor

Iusim, Kimchy, Pillar, et al. 1992 No Yes No No Partial PoorLucas, van Gemert, and de Haan 2003 Yes Yes Yes Yes Yes GoodNussbaum, Biemann, and Mustard 1994 ? No Yes Yes No PoorLucas, Coenen, and De Haan 2000 Partial Yes Yes Yes Yes FairCrous and Malherbe 1988 ? Yes Partial Yes Partial Poor 

39 
Placebo-controlled studies. Of the 11 studies meeting study selection criteria, seven studies 

enrolling 262 patients compared standard treatment plus sham low-level laser versus standard 

treatment plus active low-level laser (Bihari and Mester, 1989; Franek, Krol, and Kucharzewski, 

2002; Iusim, Kimchy, Pillar, et al., 1992; Lagan, McKenna, Witherow, et al., 2002; Lundeberg 

and Malm, 1991; Malm and Lundeberg, 1991; Santoianni, Monfrecola, Martellotta, et al., 1984). 

Six of seven studies included patients with primarily lower extremity venous ulcers, while the 

seventh (Santoianni, Monfrecola, Martellotta, et al., 1984) selected a heterogeneous group of 

patients with diabetes or peripheral vascular disease. 

Study quality. Overall study quality ratings were poor for all seven placebo-controlled studies 

(Evidence Table 6). None of these seven studies demonstrated that groups were comparable on 

all three critical baseline characteristics: age, wound size and wound duration (Evidence Table 

2). Randomization methods were poorly described. High loss to followup was common. It was 

rare for studies to use both reliable and valid measurement techniques and blinded outcome 

assessors. Less than half of the studies reported on the main outcome, complete healing, and 

none made it clear that analysis was by intention-to-treat and controlled for confounders. 

It is unclear whether any study assembled groups that were comparable on a sufficient range 

of key baseline patient characteristics. The study by Franek, Krol, and Kucharzewski (2002) 

assembled a control group receiving compressive and topical therapy plus sham low-level laser 

treatment that had a shorter mean wound duration (30 months) than the group receiving standard 

care plus active low-level laser therapy (41 months). The other six placebo-controlled studies 

did not provide comparisons between groups on wound duration at baseline. The studies by 

Franek, Krol, and Kucharzewski (2002), Malm and Lundeberg (1991), Lundeberg and Malm

(1991), and Iusim, Kimchy, Pillar, et al. (1992) enrolled patient groups of comparable mean age, 

as well as comparable wound size. 

In order for this review to describe the randomization method as adequate, the article had to 

state either that central randomization was performed or opaque (concealed) envelopes were 

employed. None of the seven placebo-controlled studies satisfied this quality component. Loss 

to followup exceeded 20 percent of the initial sample size in two studies: Malm and Lundeberg 

(1991) and Lundeberg and Malm (1991). Description of treatment and control procedures was 

clear in all cases. 

Wound measurement was assumed to be reliable and valid if the article described use of 

photographic or digital transfer of wound tracings and/or use of computer software to calculate 

wound size. The studies by Franek, Krol, and Kucharzewski (2002) and Lagan, McKenna, 

Witherow, et al. (2002) satisfied this quality component. Data abstraction also sought 

information on whether a blinded observer performed outcome assessment. Blinded outcome

assessors were used by Lagan, McKenna, Witherow, et al. (2002), Malm and Lundeberg (1991), 

Lundeberg and Malm (1991), and Bihari and Mester (1989). In only one study (Lagan, 

McKenna, Witherow, et al., 2002) was it clear that investigators used both blinded assessment 

and measurement that was reliable and valid. 

None of these articles stated whether statistical analyses used adjustment procedures to deal 

with baseline confounding variables. Intention-to-treat analysis was performed by Lagan, 

McKenna, Witherow, et al. (2002), Bihari and Mester (1989), and Iusim, Kimchy, Pillar, et al. 

(1992). The primary endpoint, complete healing, was reported in three studies: Malm and 

Lundeberg (1991), Lundeberg and Malm (1991), and Bihari and Mester (1989). Analysis of 

40 
results was considered appropriate if both adjustment for confounders and intention-to-treat 

analysis was carried out. None of these studies satisfied both components. 

Complete healing. Three of seven studies reported data on the primary outcome specified for 

this systematic review, complete healing. Using the GaAs laser, Malm and Lundeberg (1991, 

n=42) performed a life-table analysis of time to complete healing by 12 weeks and found no 

significant difference between groups. Lundeberg and Malm (1991, n=46) used the HeNe laser 

and similarly found no differences between groups on life-table analysis at 12 weeks. Selecting 

three groups of 15 subjects each, Bihari and Mester (1989) compared a sham low-level laser 

group with one group treated with a hand-held HeNe laser and another group treated with a 

machine-scanned HeNe/pulsed infrared laser. Results favored the hand-held laser group over 

sham, but the difference was not statistically significant: the relative risk and 95 percent 

confidence interval (RR, 95 percent CI) of complete healing at 9 months was 2.0 (0.9–4.5). 

Results were significant in the machine-scanned laser group (RR=2.4, 95 percent CI: 1.1–5.1); 

however, two control patients were excluded from the analysis. If they had achieved complete 

healing, the results would not be statistically significant. None of the available studies provides 

clear evidence that use of laser treatment leads to a higher probability of complete healing, 

compared with sham treatment. 

Change in wound area. Six of seven studies reported on this outcome. At 12 weeks’ followup, 

Franek, Krol, and Kucharzewski (2002) found no significant differences between groups on 

either the mean rate of change in relative area or in the mean rate of change of relative 

suppurative area. Lagan, McKenna, Witherow, et al. (2002) found no difference between groups 

on percent change in wound area at 12 weeks. Malm and Lundeberg (1991) reported no 

difference between groups in rate of wound area change over 12 weeks. Lundeberg and Malm

(1991) found that the average percent change at 12 weeks did not differ between groups. 

Santoianni, Monfrecola, Martellotta, et al. (1984) observed no differences between groups in the 

area epithelialized. Iusim, Kimchy, Pillar, et al. (1992) compared sham low-level laser with one 

group treated by red light laser and another treated with infrared light laser. By percent change 

in area at 20 days, the red light laser performed significantly better than sham, which did not 

differ from the infrared laser group. Only one of six studies reported a significant advantage 

favoring low-level laser treatment over sham. 

Other outcomes. Franek, Krol, and Kucharzewski (2002) reported that the rate of change in 

relative defect volume was better in the standard treatment alone arm versus the low-level laser 

arm. Lagan, McKenna, Witherow, et al. (2002) found that visual analog scale pain did not differ 

between groups. 

Studies without a placebo control. Three studies enrolling 151 patients compared patients 

receiving standard treatment alone with those undergoing standard treatment plus low-level laser 

(Lucas, van Gemert, and de Haan, 2003; Lucas, Coenen, and De Haan, 2000; Nussbaum, 

Biemann, and Mustard, 1994). All three selected patients with pressure ulcers. 

Study quality. Both the Lucas, van Gemert, and de Haan (2003) and the Lucas, Coenen, and De 

Haan (2000) studies showed that groups were comparable on age, wound size and wound 

duration. The groups in the study by Nussbaum, Biemann, and Mustard (1994) were comparable 

41 
on age and wound duration, but not on wound size. The Lucas, van Gemert, and de Haan (2003) 

study stated that central randomization was used, while the other two studies provided 

insufficient details about the randomization technique. Loss to followup exceeded 20 percent of 

the initial sample in the Nussbaum, Biemann, and Mustard (1994) study. Wound measurement 

was reliable and valid in all three studies and blind outcome assessors were used in all. Both 

control and treatment interventions were clearly described in all three studies. The Lucas, van 

Gemert, and de Haan (2003) and the Lucas, Coenen, and De Haan (2000) studies analyzed 

results by intention-to-treat, while Nussbaum, Biemann, and Mustard (1994) did not; neither did 

it mention use of adjustment for confounders. 

The Lucas, van Gemert, and de Haan (2003) study was the only study that met all five 

quality dimensions and received an overall good rating. The earlier study by Lucas, Coenen, and 

De Haan (2000) met all but one of the quality dimensions, and received an overall fair rating. 

The main detail lacking from this study was an adequate description of the randomization 

procedure. The Nussbaum, Biemann, and Mustard (1994) study was given an overall poor 

quality rating. Randomization was poorly described, wound size differed between groups, loss 

to followup was high and appropriate analysis of results was not carried out. 

Complete healing. All three studies reported on complete healing, but none provide support that 

use of laser therapy results in a higher probability of complete healing as compared to standard 

treatment alone. Lucas, van Gemert, and de Haan (2003) did not show a higher probability of 

complete healing at 6 weeks with laser. In the study by Nussbaum, Biemann, and Mustard 

(1994), patients receiving low-level laser treatment had a higher mean number of weeks to 

complete healing than standard treatment alone, by a followup as high as 20 weeks, but no 

statistical test result was provided. Lucas, Coenen, and De Haan (2000) observed that four of 

eight control patients and three of eight low-level laser patients achieved complete healing by 6 

weeks. 

Change in wound area. In Lucas, van Gemert, and de Haan (2003), no significant differences 

between groups were observed for absolute improvement, relative improvement or natural logtransformed improvement. Nussbaum, Biemann, and Mustard (1994) found that the rate of 

wound size change for laser was not better than that of control. Lucas, Coenen, and De Haan 

(2000) found no significant difference between groups in percent change of wound area. 

Other outcomes. Lucas, Coenen, and De Haan (2000) assessed the Norton wound scale and 

found no differences between groups. These authors also found no difference between groups in 

the incidence of stage IV pressure ulcers.

Studies comparing ultraviolet light and low-level laser therapy. One study of only six 

patients with chronic leg venous ulcers compared use of medical treatment plus ultraviolet light 

with medical treatment plus laser therapy (Crous and Malherbe, 1988). The overall study quality 

rating was poor. It is unclear whether the two groups of three subjects were comparable on age, 

wound duration or wound size. The randomization procedure was inadequately described. 

Interventions were clearly described. Wound measurement was performed with photographs and 

a blinded observer. Adjustment for confounders was not mentioned. Results were given for all 

randomized patients. Complete healing was not reported. 

The article reported on percent change in wound area and wound perimeter. The mean 

change in area in the ultraviolet light group was 34 percent, compared with 50 percent for low42 
level laser. Mean change in perimeter was 18 percent for ultraviolet light and 27 percent for 

low-level laser. No statistical test results were reported, but t-tests performed for this systematic 

review did not find statistically significant differences between groups. 

Conclusions 

Eleven studies (Bihari and Mester, 1989; Crous and Malherbe, 1988; Franek, Krol, and 

Kucharzewski, 2002; Iusim, Kimchy, Pillar, et al., 1992; Lagan, McKenna, Witherow, et al., 

2002; Lucas, Coenen, and De Haan, 2000; Lucas, van Gemert, and de Haan, 2003; Lundeberg 

and Malm, 1991; Malm and Lundeberg, 1991; Nussbaum, Biemann, and Mustard, 1994; 

Santoianni, Monfrecola, Martellotta, et al., 1984) met the study selection criteria for Part I of this 

review, nine of which were rated poor in quality (Bihari and Mester, 1989; Crous and Malherbe, 

1988; Franek, Krol, and Kucharzewski, 2002; Iusim, Kimchy, Pillar, et al., 1992; Lagan, 

McKenna, Witherow, et al., 2002; Lundeberg and Malm, 1991; Malm and Lundeberg, 1991; 

Nussbaum, Biemann, and Mustard, 1994; Santoianni, Monfrecola, Martellotta, et al., 1984), 

while one was rated good quality (Lucas, van Gemert, and de Haan, 2003) and one was rated fair 

(Lucas, Coenen, and De Haan, 2000). 

Seven studies (n=262) compared standard care plus placebo with the combination of standard 

care and sham laser therapy (Bihari and Mester, 1989; Franek, Krol, and Kucharzewski, 2002; 

Lagan, McKenna, Witherow, et al., 2002; Iusim, Kimchy, Pillar, et al., 1992; Lundeberg and 

Malm, 1991; Malm and Lundeberg, 1991; Santoianni, Monfrecola, Martellotta, et al., 1984). 

Most of these patients had lower extremity venous ulcers. Of the three studies that reported on 

complete healing (Bihari and Mester, 1989; Lundeberg and Malm, 1991; Malm and Lundeberg, 

1991), one provides weak evidence of a higher rate of healing for patients treated by machinescanned laser versus those receiving sham laser (Bihari and Mester, 1989). 

Standard treatment alone versus standard treatment plus laser was compared in three studies, 

which reported on a total of 151 patients with pressure ulcers (Lucas, Coenen, and De Haan, 

2000; Lucas, van Gemert, and de Haan, 2003; Nussbaum, Biemann, and Mustard, 1994). All 

three studies reported on complete healing. One of these was rated as good in quality, and this 

higher quality study did not show a higher probability of complete healing at 6 weeks with the 

addition of laser treatment (Lucas, van Gemert, and de Haan, 2003), nor did it show benefit for 

any of the other reported outcomes. Use of medical treatment plus ultraviolet light with medical 

treatment plus low-level laser therapy was compared in one study of six patients with chronic 

venous ulcers (Crous and Malherbe, 1988). That study did not show a higher probability of 

complete healing at 6 weeks with the addition of laser treatment. 

Overall, the quality of this body of evidence is poor, and does not permit definitive 

conclusions. However, the available data suggests that the addition of laser therapy does not 

improve wound healing, as the vast majority of comparisons in these studies do not report any 

group differences in the relevant outcomes. It is unlikely that the lack of significant differences 

is the result of a type II error, since there are no trends or patterns of outcomes that favor the 

laser group. 

43 
Part II: Vacuum-Assisted Closure

The second part of this chapter reviews evidence on the following questions: 

In the treatment of various wounds, what are the outcomes of vacuum-assisted closure for 

specific indications and patient types: 

a) as a substitute for standard dressings; and 

b) as an adjunct to standard therapy, compared with standard therapy alone?

Overview

A single previous systematic review is available on the use of vacuum-assisted closure for 

treating chronic wounds (Evans and Land, 2003). The authors concluded that the 2 small trials 

(Joseph, Hamori, Bergman, et al., 2000; McCallon, Knight, Valiulus, et al., 2000) that met their 

selection criteria offer weak evidence that vacuum-assisted closure is more efficacious than 

moist dressings. They noted that small sample sizes and methodological limitations require that 

the results of these 2 studies be interpreted with extreme caution. While Evans and Land 

restricted themselves to chronic wounds, the present review is broader in focus. Both studies 

reviewed in that report are also included here. 

Two randomized trials on the use of vacuum-assisted closure are excluded from the current 

review (Buttenschoen, Fleischmann, Haupt, et al., 2001; Genecov, Schneider, Morykwas, et al., 

1998) because they provided data only on outcomes that were not of interest to this review. The 

former reported on immune response markers and the latter gave data on skin biopsies. Two 

comparative studies published in Chinese were reviewed by a Chinese reader and found to be 

nonrandomized (Huang, Yao, and Huang, 2003; Yao, Huang, and Ma, 2002). No other 

nonrandomized comparative studies published in English were found. All other excluded studies 

were case series or case reports. 

Six studies using vacuum-assisted closure met study selection criteria, with a collective total 

of 135 patients (Eginton, Brown, Seabrook, et al., 2003; Ford, Reinhard, Yeh, et al., 2002; 

Moues, Vos, van den Bemd, et al., 2004; Joseph, Hamori, Bergman, et al., 2000; McCallon, 

Knight, Valiulus, et al., 2000; Wanner, Schwarzl, Strub, et al., 2003). Details about these studies 

are given in Evidence Tables 7–12; information in these tables served as the basis for study 

quality ratings, which may be viewed in Evidence Table 13. Evidence Table 7 summarizes the 

included studies. Evidence Table 8 presents patient inclusion and exclusion criteria. Evidence 

Table 9 shows patient characteristics. Evidence Table 10 gives details of treatment. Evidence 

Table 11 includes information on how outcomes were assessed. Evidence Table 12 depicts 

results. 

44 
Evidence Table 7. Summary of Vacuum-Assisted Closure Studies

Study

n Randomized

Patient Selection Control (Cx) Treatment (Tx) Comparable Characteristics Alloca- tion 

Treatment Description 

Wound Measure-ment 

CompHealin

Moues, Vos, van den Bemd, et al., 2004 

54; Cx: 25Tx: 29 

Fullthickness wounds 

SC/dressings V.A.C.® Yes: age; 

? size, duration

Random, envelopes 

Cx, Txclear 

Photocopies, SW 

NR 

Wanner, Schwarzl, Strub, et al., 2003 

22; Cx: 11; Tx: 11 

Pressure ulcers 

SC/dressings V.A.C.® Yes: age, size 

?: duration 

Random Cx, Tx

clear 

Saline volume

NR 

Joseph, Hamori, Bergman, et al., 2000 

24; Cx: 12; Tx: 12 

Nonhealing wounds 

SC/dressings V.A.C.® Yes: age

No: size ?: duration 

Random Cx, Tx

clear 

Plaster mold, blind 

NR 

Ford, Reinhard, Yeh, et al., 2002 

28 Pressure 

ulcers 

gel products V.A.C.® No: age 

?: size, duration 

Random Cx, Tx

clear 

Alginate mold, blind 

Tx=Cx 

Eginton, Brown, Seabrook, et al., 2003 

10 Diabetic 

foot wounds 

SC/dressings V.A.C.® ?: age, size, 

duration 

Random Cx, Tx

clear 

Digitalphotos, planimetrySW, blind 

NR 

McCallon, Knight, Valiulus, et al., 2000 

10; Cx: 5; Tx: 5

Nonhealing diabetic foot wounds 

SC/dressings V.A.C.® Yes: age 

?: size, duration 

Coin flip, then alternate 

Cx, Txclear 

Tracings, photos, biometric SW 

Tx=Cx 

45 
Evidence Table 8. Vacuum-Assisted Closure, Patient Selection Criteria 

Study Inclusion Exclusion

Moues, Vos, 

van den Bemd,

et al., 2004; 

Rotterdam 

Full-thickness wound that could not 

be closed immediately because of 

infection, contamination, or chronic 

character; type: trauma (2), 

infection (17), dehiscence (5),

pressure ulcer (20), miscellaneous 

(10) 

Malignant disease, deep fistulas, sepsis, active bleeding, 

uncontrolled diabetes, psychiatric patients, and unstable 

skin around the wound 

Wanner, 

Schwarzl, 

Strub, et al., 

2003; Nottwil, 

Switzerland 

all consecutive pts with a pressure 

sore in the pelvic region, deeper 

than grade 2 (at least into SC fat); 

paraplegics or tetraplegics 

pressure ulcer not in pelvic region (7); < grade 3 (3); lack 

of data (1); severe diarrhea (1) 

Joseph, 

Hamori, 

Bergman, et 

al., 2000; 

Boston 

chronic, nonhealing wounds (open 

wound, any site no closure ≥ 4 wk), 

recalcitrant to multiple prior 

treatments; setting: hospital (5), 

nursing home (9), home (10); 

wound type (Cx, Tx): dehisced (3, 

0); pressure (13, 12); pressurerecurrent (1, 2); radiated (0, 1); 

traumatic (1, 1); venous 

insufficiency (0,2) 

Infection; albumin < 3 g/dL; chronic disease requiring 

ongoing therapy for stabilization, uncontrolled diabetes, 

thyroid disease, hypertension; steroids, 

immunosuppressants, anticoagulants; pregnant/lactating; 

biopsy-proven osteomyelitis; uncooperative/unsuitable 

participant in dressing changes; malignant/neoplastic 

diseases in wound margin; fistulas to the wound 

Ford, 

Reinhard, Yeh,

et al., 2002; 

Boston 

Stage III-IV pressure ulcers, 21-80 

yo; > 4 wk; albumin > 2.0 g/dl; 

post-debridement ulcer volume 10–

150 mL 

fistulas to organs/body cavities; malignancy in wound; 

pregnant/lactating; Hashimoto thyroiditis; Graves disease; 

iodine allergy; systemic sepsis; electrical burn; radiation 

exposure; chemical exposure; cancer; connective tissue 

disease; chronic renal/pulmonary disease; uncontrolled 

diabetes; steroids/immunosuppressants; pacemaker; 

ferromagnetic clamps; recently placed orthopedic 

hardware 

Eginton, 

Brown, 

Seabrook, et 

al., 2003; 

Milwaukee 

diabetic foot wounds of size not 

expected to heal in 1 mo 

growth factors, hyperbaric oxygen < 30 d, untreated 

cellulitis, malignancy in wound, necrotic tissue, 

osteomyelitis, no insurance for VAC or f/u 

McCallon, 

Knight, 

Valiulus, et al., 

2000; 

Shreveport 

nonhealing (> 1 mo) diabetic foot 

ulceration; 18–75 yo; 

venous disease; active infections not resolved by initial 

debridement; coagulopathy

46 
Evidence Table 9. Vacuum-Assisted Closure, Patient Characteristics

Study Comparison

n, Randomized n, Withdrew Wound Duration Age Gender Wound Size Como

Moues, Vos, van den Bemd,et al., 2004; Rotterdam Full-thickness wound that could not be closed immediately 

Cx: standard moist dressingTx: V.A.C.®

54 Cx: 25Tx: 29 

< 4 wk: 8 

Cx, 12 Tx> 4 wk: 17 Cx, 17 Tx

Cx: mn 47.9, SD 17.0 Tx: mn 47.7, SD 19.6 

Cx: 14 M, 11 FTx: 21 M, 8 F

Wanner, Schwarzl, Strub, et al., 2003; Nottwil, Switzerland; Pelvic pressureulcers into SC fat 

Cx: traditional care Tx: V.A.C.®

22 Cx: 11Tx: 11 

Cx: mn 53, rng 

34-77Tx: mn 49, rng 25-73

Cx: 8 m, 3 FTx: 7 M, 4 F

(volume) Cx: mn 42 ml, SD 16, rng 5-68Tx: mn 50, SD 33, rng 3-132 

(Cx, Tvascudeplehypoahypopanemsteroi

Joseph, Hamori, Bergman, et al., 2000; Boston Nonhealing wounds (> 4 wk, 78%pressureulcers) 

Cx: standard wound care Tx: V.A.C.®

24 pts Cx: 12Tx: 12 36 wounds Cx: 18Tx: 18 

> 4 wk Cx: mn 49; 

Tx: mn 56 (p=0.17) 

Cx: 5 M, 7 FTx: 8 M, 4 F(p=0.18) 

(volume) UA=pt Cx: mn 24 cu cm Tx: mn 38 (p=0.08); 

47 
Evidence Table 9. Vacuum-Assisted Closure, Patient Characteristics (continued)

Study Comparison

n, Randomized n, Withdrew Wound Duration Age Gender Wound Size Como

Ford, Reinhard, Yeh,et al., 2002; Boston Full-thickness pressure ulcers

Cx: HealthpointSystem (gel products) Tx: V.A.C.®

28 pts 41 wounds 

6 (3 lost to followup, 1 noncompliant, 2 died) 

> 4 wk Cx: mn 54.4 

Tx: mn 41.7 

Eginton, Brown, Seabrook, et al., 2003; Milwaukee Diabetic foot wounds 

Crossover Cx: moist dressings 2 wkTx: V.A.C.® 2wk

10 pts 11 wounds 

4 (1 did not return for f/u, 1 coverage denied, 1 hyperbaric oxygen, 1 failed V.A.C.®) 

(length):

Cx+Tx: mn 7.7 cm, SD 1.6 (width): mn 3.5, SD 0.6(depth): mn 3.1, SD 0.9

McCallon, Knight, Valiulus, et al., 2000; Shreveport Nonhealing diabetic foot wounds 

Cx: salinemoistened gauze dressings Tx: V.A.C.®

10 Cx: 5 Tx: 5

> 1 mo Cx: mn 50.2, 

SD 8.7 Tx: mn 55.4, SD 12.8 

(area):

Cx: 20 sq cm Tx: 23 

48 
Evidence Table 10. Vacuum-Assisted Closure, Treatments 

Study Allocation Comparison Control Treatment

TR

Moues, Vos, van den Bemd,et al., 2004; Rotterdam Full-thickness wounds that could not be closed immediately 

Randomly assigned by patientpicking a closed envelope 

Cx: standard moist dressings Tx: V.A.C.®

Debridement before and during therapy when clinically needed; standard moist gauze, using: 0.9% saline, 0.2% nitrofuralam, 1% acetic acid, 2% sodium hypochlorite, changed 2x/day

Debridement before an duringtherapy when clinically needed; V.A.C.®; 125 mmHg continuous suction, wounds inspected and dressings changed every 48 hr

Usth

Wanner, Schwarzl, Strub, et al., 2003; Nottwil, Switzerland; Pelvic pressureulcers into SC fat 

Randomized Cx: traditional

care 

traditional care - 1 day after debridement, wet-to-dry/dry-to-wet dressings, Ringer's solution, changed 3x/d until granulationtissue, then 1-3x/d; closure with flap after 50% decrease in wound volume

Tx: V.A.C.®

V.A.C.®, <125 mmHg belowambient pressure; polyvinyl foam/transparent polyurethane dressing changed after 2-7 d (when canister full); closure with flap after 50% decrease in wound volume

Joseph, Hamori, Bergman, et al., 2000; Boston; Nonhealing wounds (> 4 wk, 78%pressureulcers) 

prospectively randomized: folders in 2 colors randomlyorganized in locked cabinet; after consent, folder picked for each wound 

Cx: standard wound care Tx: V.A.C.®

standard wound care: wet-to-moist (saline) gauze dressings changed 3x/d, not allowed to dry the wound bed, occlusive covering; nutritional assessment, supplements, multivitamin, debridement; pressure-relieving surface; frequent assessment, pressurereduction 

V.A.C.®, < 125 mmHg belowambient pressure; custom-cutfoam dressings with film drapechanged each 48 hr; nutritional assessment, supplements, multivitamin, debridement; pressure-relieving surface; frequent assessment, pressurereduction 

6 

Ford, Reinhard, Yeh,et al., 2002; Boston; Full-thickness pressure ulcers

random assignment; table of random letters (V, H) generated before trial began; 3 pts with 3 wounds each crossed over for 2nd 6-wkcourse of opposing treatment 

Cx: HealthpointSystem (gel products) Tx: V.A.C.®

debridement, Healthpoint System - gel products (Iodosorb, Iodoflex, Panafil); pts with substantial exudate received Iodosorb or Iodoflex, clean/granulating wounds received Panafil; dressings changed 1-2x/d

debridement, V.A.C.®, dressings changed 3x/wk

6 

49 
Evidence Table 10. Vacuum-Assisted Closure, Treatments (continued)

Study Allocation Comparison Control Treatment

TR

Eginton, Brown, Seabrook, et al., 2003; Milwaukee Diabetic foot wounds 

randomly assigned, random number generator: even numbers treated with V.A.C.®1st, odd numbers treated withmoist dressings 1st 

Crossover Cx: moist dressings 2 wkTx: V.A.C.® 2 wk

initial debridement, moist dressings, hydrocolloid gel, gauze, changed daily, 2 wk

initial debridement, V.A.C.®, - 125 mmHg continuous negative pressure, custom-cut foam dressings with transparent occlusive film changed > 3x/wk, 2 wk

2 

McCallon, Knight, Valiulus, et al., 2000; Shreveport Nonhealing diabetic foot wounds 

randomized by coin flip, then alternating groups 

Cx: salinemoistened gauzedressings Tx: V.A.C.®

debridement, physical therapy, saline-moistened gauze dressings, changed 2x/d; bedrest or strict nonweight bearing 

V.A.C.®, 125 mmHg continuous suction 1st 48 hr, then intermittent suction; dressing changed each 48 hr; bedrest or strict nonweight bearing 

50 
Evidence Table 11. Vacuum-Assisted Closure, Outcome Assessment 

Study Comparison Primary Outcomes

SecondaryOutcomes Wound Measurement Observer F/U

A

Moues, Vos, van den Bemd,et al., 2004; Rotterdam 

Cx: standard moist dressings Tx: V.A.C.®

Median time to reach “ready for surgical therapy” 

Wound surfacearea, bacterial load

Tracings onto polyethylene film, photocopying onto paper, computer software calculated area

Not blinded 

Wanner, Schwarzl, Strub, et al., 2003; Nottwil, Switzerland; Pelvic pressureulcer into sc fat 

Cx: traditional care Tx: V.A.C.®

time to 50% decrease inwound volume

ulcer covered with transparent 

sheet of elastic polymer, injected with saline until full, fluid volume measured 

21-56 d 

Joseph, Hamori, Bergman, et al., 2000; Boston; Nonhealing wounds (> 4 wk, 78%pressureulcers) 

Cx: standard wound care Tx: V.A.C.®

Time to target decline inwound volume

wound length, width, depth; wound biopsies 

Photography, dimensions, volume by alginate impression molds 

independent blinded observer, not involved indaily patient care 

6 wk w

Ford, Reinhard, Yeh,et al., 2002; Boston 

Cx: HealthpointSystem (gel products) Tx: V.A.C.®

complete healing wound length, 

width, depth, volume, bone biopsy

photography, dimensions, volume by plaster mold

blinded assessment 

3-10 mo w

Eginton, Brown, Seabrook, et al., 2003; Milwaukee Diabetic foot wounds 

Crossover Cx: moist dressings 2 wkTx: V.A.C.® 2wk

Rate of wound healing, dimensions, area, volume

digital photography, computerized 

planimetry software 

blinded evaluation, wound length, width, depth, volume

4 wk

51 
Evidence Table 11. Vacuum-Assisted Closure, Outcome Assessment (continued) 

Study Comparison Primary Outcomes

SecondaryOutcomes Wound Measurement Observer F/U

A

McCallon, Knight, Valiulus, et al., 2000; Shreveport 

Cx: salinemoistened gauze dressings Tx: V.A.C.®

time to closure/satisfactory healing (delayed primaryintention - surgical closure, or secondaryintention - granulation, epithelialization) 

rate, wound area 

tracings on acetate film, photography, area calculated bycomputer biometric software

52 
Evidence Table 12. Vacuum-Assisted Closure, Results 

Study Comparison F/U Complete Healing Wound Area Wound Volume Wound Moues, Vos, van den Bemd,et al., 2004; Rotterdam Full-thickness wound 

Cx: standard moist dressings (25)Tx: V.A.C.®(29) 

(time until “ready

for surgical therapy”): Cx: md 7.0, SEM 0.81 Tx: md 6.0, SEM 0.52 (p=0.19) 

(% change/d): Cx (n=13) mn 1.7, SEM 0.5 Tx: (n=15) mn 3.8, SEM 0.5 (p<0.05) 

Wanner, Schwarzl, Strub, et al., 2003; Nottwil, Switzerland; Pelvic pressureulcers into SC fat 

Cx: traditional care (11) Tx: V.A.C.®(11) 

21-56days 

(time to 50% drop in vol): 

Cx: mn 28 d, SD 7 Tx: mn 27 d, SD 10; (unadjusted p=0.9, adjusted p=0.2)

Joseph, Hamori, Bergman, et al., 2000; Boston; Nonhealing wounds (> 4 wk, 78%pressureulcers) 

Cx: standard wound care (12) Tx: V.A.C.®(12) 

6 wk (time to > 95% fall in vol): Cox 

Proportional Hazards Model significant predictors: VAC (p=0.046), initial tendon/bone exposure (p=0.05) (% change): Cx: mn 30; Tx: mn 78 (p=0.038) 

(% chanCx: -38; Tx: -46 ((% chanCx: -35 Tx: -63 ((% chanCx: -20 Tx: -66 (

53 
Evidence Table 12. Vacuum-Assisted Closure, Results (continued)

Study Comparison F/U Complete Healing Wound Area Wound Volume Wound Ford, Reinhard, Yeh,et al., 2002; Boston Full-thickness pressure ulcers

Cx: HealthpointSystem (gel products) Tx: V.A.C.®Cx+Tx (22) 

3-10 mo 

Cx: 2/15; Tx: 2/20 (8-10 wk) Tx:Cx RR = 0.75, 95%CI: 0.12, 4.73 

(% change): 

Cx: -42.1 Tx: -51.8 (p=0.46) 

(changeCx: mn -Tx: -36.9 (changeCx: -19.0 Tx: -40.0 (changeCx: -31.0 Tx: -33.6 

Eginton, Brown, Seabrook, et al., 2003; Milwaukee Diabetic foot wounds` 

Crossover, Cx:moist dressings 2 wk; Tx: V.A.C.® 2 wkCx+Tx (6) 

4 wk (% change): 

Cx: mn +5.9, SD 17.4 Tx: mn - 16.4, SD 6.2 (NS); 

(% change): Cx: mn -0.1, SD 14.7 Tx: mn -59, SD 9.7 (p<0.005) 

(% chanCx: mn +Tx: mn -(% chanCx: mn +Tx: mn – (% chanCx: mn –Tx: mn –

54 
Evidence Table 12. Vacuum-Assisted Closure, Results (continued)

Study Comparison F/U Complete Healing Wound Area Wound Volume Wound McCallon, Knight, Valiulus, et al., 2000; Shreveport Nonhealing diabetic foot wounds 

Cx: salinemoistened gauze dressings (5) Tx: V.A.C.® (5)

(time to

satisfactoryhealing): Cx: mn 42.8 d, SD 32.5 Tx: mn 22.8, SD 17.4 (NS); (delayed 1o

closure): Cx: 2/5; Tx: 4/5; (2o intention): Cx: 

3/5; Tx: 1/5 

(% change): Cx: mn +9.5, SD 16.9 Tx: mn -28.4, SD 24.3 (NS) 

55 
Evidence Table 13. Vacuum-Assisted Closure, Study Quality Ratings

Study Yr

Initial Assembly of Comparable Groups

Low Loss toFollowup,Maintenance of Comparable Groups

Measurements Reliable, Valid, Equal 

Interventions Comparable/ Clearly Defined 

AppropriateAnalysis ofResults 

Overall Rating 

Moues, Vos, van den Bemd, et al. 2004 Partial ? No Yes No PoorWanner, Schwarzl, Strub, et al. 2003 ? ? Partial Yes No PoorJoseph, Hamori, Bergman, et al. 2000 ? ? Yes Yes Partial PoorFord, Reinhard, Yeh, et al. 2002 ? No Yes Yes No PoorEginton, Brown, Seabrook, et al. 2003 ? No Yes Yes No PoorMcCallon, Knight, Valiulus, et al. 2000 ? ? No Yes No Poor

56 
All studies used the V.A.C.® (Kinetic Concepts, Inc., KCI) device. Three studies included 

patients who primarily had pressure ulcers (Wanner, Schwarzl, Strub, et al., 2003; Ford, 

Reinhard, Yeh, et al., 2002; Joseph, Hamori, Bergman, et al., 2000). Joseph, Hamori, Bergman, 

et al. (2000) selected patients with chronic (i.e., >4 weeks’ duration) nonhealing wounds of 

various etiologies, of which 78 percent were pressure ulcers. Pressure ulcers in the Ford, 

Reinhard, Yeh, et al. (2002) study were of 4 weeks duration or longer. Wanner, Schwarzl, Strub, 

et al. (2003) did not specify the duration of the pressure ulcers. Eginton, Brown, Seabrook, et al. 

(2003) included diabetic foot wounds not expected to heal within 1 month and McCallon, 

Knight, Valiulus, et al. (2000) selected diabetic foot wounds of more than 1 month duration. 

The comparison of interventions was conventional/standard wound care (mainly, moist 

dressings changed at least once daily) versus vacuum-assisted closure in five studies (Moues, 

Vos, van den Bemd, et al., 2004; Wanner, Schwarzl, Strub, et al., 2003; Joseph, Hamori, 

Bergman, et al., 2000; Eginton, Brown, Seabrook, et al., 2003; McCallon, Knight, Valiulus, et 

al., 2000). One study (Ford, Reinhard, Yeh, et al., 2002) compared vacuum-assisted closure with 

the Healthpoint® system, consisting of gel/pad products (Iodosorb®, IodoflexTM, Panafil®). 

Study quality. All six studies were rated poor in quality (Evidence Table 13). Only one study 

made it clear that an adequate randomization method was used (i.e., sealed envelopes in Moues, 

Vos, van den Bemd, et al., 2004). One study (McCallon, Knight, Valiulus, et al., 2000) used an 

allocation method that was probably inadequate to be considered true randomization: coin flip to 

assign the first patient, then alternating group assignment. 

No study indicated that groups were comparable on all three key baseline characteristics 

(age, wound duration, and wound size, see Evidence Table 9). Age was comparable between 

groups in these four studies: Moues, Vos, van den Bemd, et al. (2004); Wanner, Schwarzl, Strub, 

et al. (2003); Joseph, Hamori, Bergman, et al. (2000); and McCallon, Knight, Valiulus, et al. 

(2000). Vacuum-assisted closure patients were younger than control patients in the study by 

Ford, Reinhard, Yeh, et al. (2002). Wanner, Schwarzl, Strub, et al. (2003) assembled groups that 

were comparable in wound size. Wounds were smaller in the vacuum-assisted closure group 

than the control group in the study by Joseph, Hamori, Bergman, et al. (2000). None of the 

seven studies provided information on the comparability of groups with respect to wound 

duration. All studies gave clear descriptions of interventions. All studies also described reliable 

and valid measurement methods and three used blinded observers (Joseph, Hamori, Bergman, et 

al., 2000; Ford, Reinhard, Yeh, et al., 2002; Eginton, Brown, Seabrook, et al., 2003). One study 

(Ford, Reinhard, Yeh, et al., 2002) reported on the primary endpoint, complete healing, while 

McCallon, Knight, Valiulus, et al. (2000) provided data on time to satisfactory healing. Only 

Wanner, Schwarzl, Strub, et al. (2003) performed adjustment for confounders in the data 

analysis. Joseph, Hamori, Bergman, et al. (2000) provided the only intention-to-treat analysis. 

Complete healing. The proportion of patients who achieved complete healing was reported in 

only one study (Ford, Reinhard, Yeh, et al., 2002). In the control group receiving gel products 

for full-thickness pressure ulcers, two of 15 wounds had complete healing within 8–10 weeks, 

compared with two of 20 in the vacuum-assisted closure group. The relative risk of complete 

healing was 0.75 with a 95 percent confidence interval from 0.12 to 4.73. Although the 

numerical rate of complete healing was lower in the vacuum-assisted closure group, the 95 

percent confidence interval is quite wide and overlaps with 1.0, indicating a lack of statistical 

difference between groups. 

57 
McCallon, Knight, Valiulus, et al. (2000) defined a related outcome, “satisfactory healing,” 

as achieving definitive closure either by reaching a stage suitable for surgical intervention such 

as skin grafting (delayed primary intention) or by complete healing without surgical intervention 

(secondary intention). The mean time to satisfactory healing was 42.8 days in the control group 

and 22.8 days in the vacuum-assisted closure group, a difference that was not statistically 

significant in this study of 10 patients with diabetic foot wounds. Most of the vacuum-assisted 

closure wounds (4 of 5) were healed by delayed primary intention, while most of the control 

wounds (3 of 5) healed by secondary intention. 

Facilitation of surgical closure. One study (Moues, Vos, van den Bemd, et al., 2004) reported 

on the time to readiness for surgical closure, among patients with full-thickness wounds of 

various etiologies. Log-rank test analysis of Kaplan-Meier time to readiness did not show any 

statistically significant differences between groups. The median time to readiness for surgical 

closure was 6 days for vacuum-assisted closure patients and 7 days for conventionally treated 

patients (p=0.19). 

Change in wound area. Two studies of diabetic foot wounds reported nonsignificant results 

favoring vacuum-assisted closure over moist dressings in percent change in wound area, and one 

study of full-thickness wounds reported a similar finding. Eginton, Brown, Seabrook, et al. 

(2003) used a crossover design in six patients who first had 2 weeks of either moist dressings or 

vacuum-assisted closure, then switched to the other for 2 weeks. The mean change in area was 

an increase of 5.9 percent for the control intervention and a decrease of 16.4 percent for vacuumassisted closure. In the study by McCallon, Knight, Valiulus, et al. (2000, n=10), the mean 

change in wound area in the control group was a gain of 9.5 percent, compared with a mean 

decrease of 28.4 percent in the vacuum-assisted closure group. In a subset of only 52 percent of 

the original group of patients with full-thickness wounds, Moues, Vos, van den Bemd, et al. 

(2004) found a significantly higher daily percent change in wound area among vacuum-assisted 

closure patients (3.8), compared with conventionally treated patients (1.7, p<0.05). 

Change in wound volume. Four studies have reported on changes in wound volume: all three 

studies of pressure ulcers and one study on diabetic foot wounds. Wanner, Schwarzl, Strub, et 

al. (2003) included 22 patients with pelvic pressure ulcers. The endpoint was time to 50 percent 

decrease in wound volume. The mean time for traditional care was 28 days, compared with 27 

days for vacuum-assisted closure. The unadjusted p value was 0.9, while adjustment for initial 

wound volume yielded a p value of 0.2. In the study by Ford, Reinhard, Yeh, et al. (2002) of 19 

patients with full-thickness pressure ulcers, after 3–10 months, the mean percent change in 

wound volume was –42.1 percent in the group receiving gel products and –51.8 percent in the 

vacuum-assisted closure group (p=0.46). The group of 24 patients with nonhealing wounds (78 

percent pressure ulcers) studied by Joseph, Hamori, Bergman, et al. (2000) were evaluated in two 

ways. First, the mean percent reduction in volume at 6 weeks was compared: 30 percent for 

standard wound care and 78 percent for vacuum-assisted closure (p=0.038). Second, a Cox 

proportional hazards model analysis found that use of vacuum-assisted closure and initial 

exposure of tendon or bone were significant predictors of time to greater than 95 percent 

reduction in volume. In the crossover study of six patients with diabetic foot wounds (Eginton, 

Brown, Seabrook, et al., 2003), the mean percent reduction in wound volume was 0.1 percent in 

the moist dressing phase and 59 percent in the vacuum-assisted closure phase (p<0.005). 

58 
Change in wound dimensions. Three studies report changes in length, width and depth of 

wounds, and two of the three studies report significant differences in favor of the vacuumassisted closure group for one or more of these outcomes. In the Ford, Reinhard, Yeh, et al. 

(2002) study of pressure ulcers, the mean changes (cm) for the gel product group and vacuumassisted closure group, respectively, were: –18.7 and –36.9 (length, p=0.10); –19.0 and –40.0 

(width, p=0.11); and –31.0 and –33.6 (depth, p=0.90). Mean percent change in the Joseph, 

Hamori, Bergman, et al. (2000) study of nonhealing wounds, for standard care and vacuumassisted closure, respectively, were: –38 and –46 (length, p=0.38); –35 and –63 (width, p=0.02); 

–20 and –66 (depth, p<0.001). In the crossover study by Eginton, Brown, Seabrook, et al. (2003) 

of diabetic foot wounds, the following comparisons of mean percent change values for moist 

dressings and vacuum-assisted closure, respectively, were observed: +6.7 and –4.3 (length, 

p>0.05); +2.4 and –12.9 (width, p>0.05); and –7.7 and –49 (depth, p<0.05). 

Complications. Two studies reported data on complications during wound treatment. Ford, 

Reinhard, Yeh, et al. (2002) reported two deaths (group assignments not specified) and one 

vacuum-assisted closure patient with diabetes, hypertension, vascular insufficiency and sepsis 

who required distal lower extremity amputation. More cases of pre-existing osteomyelitis 

improved in the vacuum-assisted closure group (37.5 percent) than in the group receiving gel 

products (0 percent), but the difference was not statistically significant (p=0.25). In the Joseph, 

Hamori, Bergman, et al. (2000) study, eight of 18 wounds treated with standard care developed 

complications, compared with three of 18 vacuum-assisted closure wounds (p=0.0028). 

Complications included: fistulas; wound infection; osteomyelitis; and calcaneal fractures. 

Biopsy results. The study comparing gel products and vacuum-assisted closure in 22 patients 

with full thickness pressure ulcers (Ford, Reinhard, Yeh, et al., 2002) reported quantitative 

biopsy results. The mean number of polymorphonuclear (PMN) leukocytes per high-powered 

field increased in the gel product group, but decreased in the vacuum-assisted closure group 

(p=0.13). Lymphocytes also increased in the gel product group and decreased in the vacuumassisted closure group (p=0.41). The mean number of capillaries declined in both groups, but to 

a slightly lesser extent in the vacuum-assisted closure group (p=0.75). 

Randomized trials in progress. KCI, the manufacturer of the V.A.C.® device, has shared 

protocol documents for 10 randomized trials in progress (Evidence Table 14). These protocols 

cover a wide variety of wound types, including burns, pressure ulcers, diabetic ulcers, traumatic 

and surgical wounds, venous stasis wounds, and diabetic wounds. Large sample sizes are 

planned, determined by power analyses. Sophisticated randomization techniques will be used in 

many trials. A wide range of outcomes will be assessed, often by a blinded observer. Plans to 

adjust for confounders in the analysis, if necessary, are common. Concerns remain about the 

criteria for allowable withdrawals, including: noncompliance; worsened condition;

complications; and treatment difficulties/failures. If such withdrawals are excluded from

analysis, it would constitute violation of the intention-to-treat principle. 

59 
Evidence Table 14. Vacuum-Assisted Closure, KCI Randomized Trials in Progress 

Study Patients Target n Randomization

AllowableWithdrawals Treatments Outcomes F/U

PlaAdmeCoers

MolnarWake Forest bilateral 2nd/3rd degree hand 

burns, 12-24 hrs post injury

by hand,

random fashion like toss of coin 

usual

institutional regimen, V.A.C.®, 48 hr 

photography, ROM, pinch/grip strength, need for surgery,general appearance 

30 d, 60 d 

Protocol VAC2001-01

stage III/IV pressure ulcer

258, power analysis 

by patient, standard tablesof random numbers, opaque envelopes 

investigator/ KCI discretion of noncompliance/worsening,complications, treatment difficulties or failure, reasons documented

WOCN guideline (1992) moist therapy; V.A.C.®; 84 d 

blinded, photography, bilayer tracing, complete closure (and time), facilitation of surgical closure, AEs, area, volume, pain 

84 d yes 

Protocol VAC2001-02

venous stasis ulcers, > 30 d duration, ABI 0.7-1.2 

258, power analysis 

by patient, standard tablesof random numbers, opaque envelopes 

investigator/ KCI discretion of noncompliance/worsening,complications, treatment difficulties or failure, reasons documented

WOCN guideline (1996, 1993) moist therapy; V.A.C.®; 112 d 

blinded, photography, bilayer tracing, complete closure (and time), area, AEs, pain, QOL, cost 

112 d yes 

Protocol VAC2001-04

draininghematoma, orthopedic surgical procedure following trauma 

258, power analysis 

by patient, central computerized randomization

investigator/ KCI discretion of noncompliance/worsening,complications, treatment difficulties; reasons documented

pressuredressings; V.A.C.®; 10 d 

incidence of draininghematomas, infections, wound dehiscence, AEs, QOL, cost 

12 mo yes 

60 
Evidence Table 14. Vacuum-Assisted Closure, Randomized Trials in Progress (continued) 

Study Patients Target n Randomization

AllowableWithdrawals Treatments Outcomes F/U

PlanAdjumenConers?

Protocol VAC2001-05

surgicallytreated calcaneus, tibial plateau, pilon fractures 

348, power analysis 

by patient, central computerized randomization

investigator/ KCI discretion of noncompliance/worsening,complications, treatment difficulties; reasons documented; data up to withdrawalincluded inanalysis 

standard care; V.A.C.®; to discharge 

drainage, wound healing,surgical revision, infection, wound dehiscence, AEs, QOL, cost 

12 mo yes 

Protocol VAC2001-06

open fractures 258, 

power analysis 

by patient, central computerized randomization

investigator discretion of noncompliance/worsening,complications, treatment difficulties; reasons documented; data up to withdrawalincluded inanalysis 

standard care, V.A.C.®; until ready for surgical closure 

postoperative AEs/complications, time to closure 

12 mo yes 

Protocol VAC2001-07

amputation wounds of the diabetic foot 

146, power analysis 

by patient, central computerized randomization,opaque envelopes 

investigator/ KCI discretion of noncompliance/worsening,complications, treatment difficulties or failure; reasons documented

guidelinebased care; V.A.C.®; 112 d 

complete closure (and time), facilitation of surgical closure, area, foot salvage, complications, QOL, cost 

38 wks yes 

61 
Evidence Table 14. Vacuum-Assisted Closure, Randomized Trials in Progress (continued) 

Study Patients Target n Randomization

AllowableWithdrawals Treatments Outcomes F/U

PlanAdjumenConers?

Protocol VAC2001-08

diabetic foot ulcers 

248, power analysis 

by patient, central computerized randomization,opaque envelopes 

investigator/KCIdiscretion of noncompliance/worsening,complications, treatment difficulties or failure; reasons documented

guidelinebased care; V.A.C.®; 112 d 

blinded, complete closure (and time), facilitation of surgical closure, area, foot salvage, complications, QOL, cost 

38 wks yes 

Protocol VAC2002-09

open chest wounds 

116, power analysis 

by patient, central computerized randomization

investigator/KCIdiscretion of noncompliance/worsening, complications, treatment difficulties or failure; reasons documented

guidelinebased moist therapy; V.A.C.®; 84 d 

blinded, facilitation of surgical closure, complications, pain, cost 

3 mo yes 

Protocol VAC2002-10

open abdominal wounds 

116, power analysis 

by patient, central computerized randomization

investigator/KCIdiscretion of noncompliance/worsening, complications, treatment difficulties or failure; reasons documented

guidelinebased moist therapy; V.A.C.®; 84 d 

blinded, facilitation of surgical closure, complications, pain, cost 

3 mo yes 

62 
KCI also furnished abstracts presented at the 2nd World Union of Wound Healing Societies, 

which met in Paris, France, July 8–12, 2004. While these abstracts provide too little detail for 

meaningful analysis in this systematic review, they are summarized in Evidence Table 15 to 

document the progress of ongoing randomized trials. 

Conclusions 

This body of evidence is insufficient to support conclusions about the effectiveness of 

vacuum-assisted closure in the treatment of wounds. There are only six trials that met the 

inclusion criteria for this review and the included trials were of small size and poor quality. With 

the exception of one study of 54 patients with incomplete followup, all studies included fewer 

than 25 patients. The randomization method was clearly adequate in only one study. No study 

made it clear that groups were comparable on all three key baseline characteristics (age, wound 

duration, wound size). None provided group information about wound duration. A single study 

adjusted for confounders in the data analysis and another performed an intention-to-treat 

analysis. 

Some outcomes in the available trials show a significant benefit for the vacuum-assisted 

closure group, while others do not. Only one study gave data on the probability of complete 

healing, showing no significant difference between groups. A study reporting time to 

satisfactory healing also found no significant difference between groups. One study found no 

difference between vacuum-assisted closure and control in time to readiness for surgical closure. 

Three studies reported on change in wound area; one of which found a difference between 

vacuum-assisted closure and control, while two did not. Among four studies addressing change 

in wound volume, two found a significant advantage for vacuum-assisted closure and two did not 

achieve statistical significance. One study found significant changes in wound width and depth 

for vacuum-assisted closure and another found it only for depth. It is possible that the lack of 

significant results in some or all of these trials result from a type II error. In most cases, the 

numerical results favor the vacuum-assisted closure group. Power calculations are lacking for 

these trials, but their small size raises the possibility that they are underpowered. 

The randomized, controlled trial protocols provided by KCI outline much larger trials that are 

condition-specific and address many of the quality problems found in the published studies. If 

implemented and completed successfully as planned, these trials will provide substantial 

advances in the evidence base for vacuum-assisted closure therapy, and may allow more 

definitive conclusions on the efficacy of vacuum-assisted closure. 

63 
Evidence Table 15. Abstracts Presented at the 2nd World Union of Wound Healing Societies, Paris, France; July 8–12, 2004

Abstract # Author 

Patient Selection n Cx Tx Tx=Cx

Tx>CxSignificant 

Tx>CxSignificant? Tx>Cx NS Comm

A001 Moues fullthickness 

wounds 

54 conventional 

moist gauze therapy 

VAC® area Surgical

closure 

publish

include

A016 Foo diabetic foot 25 moist

gauze dressing 

V.A.C.® area,

granulation tissue formation 

interim 

(target 40) 

D008 Molnar bilateral

thermal hand burns 

23 silver

sulfadiazine 

V.A.C.® volume

(14 d), range of motion 

volume (3 d, 5 d), edema 

interim

Wake Forest protoco

E008 Stannard draining

hematoma postsurgical stablization of skeletal trauma 

79 pressure

dressing 

V.A.C.® drainage 

time, surgical evacuation

interim

ProtocVAC2004 

E009 Stannard open reduction, internal 

fixation of high-risk fractures 

90 standard

postop dressings 

V.A.C.® drainage 

time to Grade 3/to wound sealing 

interim

ProtocVAC2005 

E010 Stannard open

fractures 

28 wet-tomoist 

dressings 

V.A.C.® deep 

infections, osteomyelitis, dehiscence 

interimProtocVAC2006 

64 
Evidence Table 15. Abstracts Presented at the 2nd World Union of Wound Healing Societies, Paris, France; July 8-12, 2004 (conti

Abstract # 

Author Patient

Selection

n Cx Tx Tx=Cx Tx>Cx

Significant 

Tx>CxSignificant? 

Tx>Cx NS 

Comme

E011 Payne diabetic foot

amputation wounds 

43 moist

dressings 

V.A.C.® wound

closure 

foot salvage interim; 

ProtocoVAC2007 

H013 Armstrong complex

diabetic foot ulcers 

46 moist

dressings 

V.A.C.® wound

closure 

area, volume

interim; 

ProtocoVAC2008 

P029 Vuerstaek recalcitrant

leg ulcers 

60 control V.A.C.® cleaning

time, healing time 

P036 Lantis venous

stasis leg ulcers 

split-thickness skin 

graft 

graft +V.A.C.® 

graft take, 

4-7 d, 90d 

prematustop 

X001 Niezgoda pressure

ulcers 

98 moist

wound healing 

V.A.C.® area, 

volume

interim; ProtocoVAC2001 

DD004 Bayer median

sternotomy wound 

8 moist

dressings 

V.A.C.® wound 

closure early; ProtocoVAC2009 

DD010 Orgill open

abdominal wounds 

30 moist

wound therapy 

V.A.C.® depth (4/5 

followup periods) 

wound 

closure 

interim; ProtocoVAC2010 

E012 Obdeijn acute and V.A.C.® 

chronic wounds 

35 hydrocolloids 

and alginates 

no data 

abstrac

65 
Chapter 4. Discussion 

Chronic wounds are a source of major disability, morbidity, and increased risk of mortality, 

and thus have a significant impact on the public health and the expenditure of health care 

resources. There are many factors that can impede wound healing and may predispose a patient 

to the development of chronic wounds. Local factors include severity of wound (area/depth), 

viability of surrounding tissue, presence of infection or foreign body. Systemic factors include 

age, functional status, nutritional status, and comorbid illnesses such as diabetes and/or renal 

disease. Moreover, in clinical practice, there is a high degree of variability in wound treatment, 

and evidence that standard wound care deviates substantially from optimal guidelines. Thus, 

patients who present with nonhealing ulcers may actually heal with an adequate trial of optimal 

care. 

Drawing on a draft U.S. Food and Drug Administration guidance document and other 

sources, this systematic review identified key features of trials that are necessary to provide good 

quality evidence on the effects of an intervention on wound healing. First, randomized 

controlled trials are required to control for the many confounding factors that affect the course of 

wound healing. Trials should be double-blinded or use independent blinded assessment of 

outcome if double-blinding is not feasible. The patient population should represent a single type 

of wound, since each type of wound has distinct physiologic characteristics, which may differ in 

their response to a particular therapy. Well-defined entry criteria or a run-in period of optimal 

treatment can establish whether a study population is refractory to best conventional care. The 

intensity and quality of care provided to study and control groups should differ only with respect 

to the use or absence of the intervention under study. The outcomes of greatest clinical 

significance are the percent of patients with complete healing and time to complete healing. 

Secondary outcomes such as wound size and facilitation of surgical closure are of interest, but 

are not sufficient. 

The evidence for this systematic review consisted of 11 (n=419) randomized, controlled trials 

of low-level laser therapy and six (n=135) randomized, controlled trials of vacuum assisted 

closure. Overall, these trials were of poor quality. All six of the vacuum-assisted closure studies 

were rated as poor quality. Nine of 11 laser studies were rated poor quality; one was rated good 

and another fair. Quality concerns center on: adequacy of randomization methods, the 

comparability of groups at baseline and followup, use of complete healing as the primary 

endpoint, adjustment for confounders, and intent-to-treat analysis. Sample sizes were generally 

small, making it difficult to find statistically significant differences between groups. As to 

results, the best available trial did not show a higher probability of complete healing at 6 weeks 

with the addition of low-level laser treatment care compared to sham laser treatment added to 

standard care. Weaknesses in the available low-level laser studies were not likely to have 

concealed existing effects. Future studies may determine whether different dosing parameters or 

use of lasers other than the helium-neon and gallium-arsenide types may lead to different results. 

Trials using the vacuum-assisted closure device did not find a significant advantage for the 

intervention on the primary endpoint, complete healing, and did not consistently find significant 

differences on secondary endpoints. The small vacuum-assisted closure studies may have been 

insufficiently powered to detect differences. Given the sparse evidence for these two wound 

healing interventions, it is not possible to find variables in these trials that may be associated 

with better results. 

65 
KCI, the manufacturer of the V.A.C.® device, has shared protocol documents for 10 

randomized trials in progress. These protocols cover a wide variety of wound types, including 

burns, pressure ulcers, diabetic ulcers, traumatic and surgical wounds, venous stasis wounds, and 

diabetic wounds. Large sample sizes are planned, determined by power analyses. Sophisticated 

randomization techniques will be used in many trials. A wide range of outcomes will be 

assessed, often by a blinded observer. Plans to adjust for confounders in the analysis, if 

necessary, are common. Concerns remain about the overly broad criteria for allowable 

withdrawals, including: noncompliance; worsened condition; complications; and treatment 

difficulties/failures. Excluding patients for these reasons may give an unrealistic sense of the 

effectiveness of vacuum-assisted closure therapy. However, if intention-to treat analyses are 

reported, these trials have the potential to substantially advance the evidence base for vacuumassisted closure therapy. 

It is notable that surprisingly large numbers of control patients achieved complete healing in 

these trials, implying that optimal conventional treatment is often not delivered. Of the 4 trials 

that reported on complete healing as an outcome, 24 of the total of 81 patients (30 percent) in the 

control arm had complete healing. Similar improvement in the control groups has been observed 

in randomized trials of other wound healing interventions. For example, in two recent trials of 

bioengineered skin substitute versus standard care, 38 percent and 49 percent of “refractory”

ulcers, healed completely in the standard care arm. Even in wounds present for at least 1 year, a 

substantial minority (19 percent) healed with standard treatment. 

This systematic review focused on two specific interventions for wound healing, but the 

issues raised in the discussion should be applied broadly. Due to the large size of populations 

with nonhealing and other types of wounds, the impact on healthcare expenditures is 

considerable. Future research should address how to improve the delivery of care, quality of 

care and outcomes of treatment of wounds in various settings. There is potential to reduce the 

frequency of nonhealing wounds and thus the overall costs of care. New interventions have the 

potential to improve wound care, but outcomes must be demonstrated in well-controlled 

randomized trials. Strategies for reducing the occurrence of wounds in various susceptible 

populations also have a place in the research portfolio. Given significant costs of chronic 

wounds, future comparisons of the cost-effectiveness of various strategies for preventing 

wounds, managing wounds and improving quality of care would be of value to clinical 

decisionmakers. 

66 
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not a randomized controlled trial 

Babadzhanov BR, Sultanov IA. [Combined therapy of 

trophic ulcers with protracted healing]. Khirurgiia (Mosk) 

1998; (4):42-5. 

non-relevant patient population 

Babapour R, Glassberg E, Lask GP. Low-energy laser

systems. Clin Dermatol 1995; 13(1):87-90. 

no primary data 

Basford JR. Low-energy laser treatment of pain and 

wounds: hype, hope, or hokum? Mayo Clin Proc 1986; 

61(8):671-5. 

no primary data 

Basford JR. Low-energy laser therapy: controversies and 

new research findings. Lasers Surg Med 1989; 9(1):1-5. 

no primary data 

Bulyakova NV, Zubkova SM, Azarova VS, et al. Effect of 

pulsed laser radiation on regeneration of injured muscles 

with different regeneration capacities and the state of the

thymus. Dokl Biol Sci 2002; 38265-70. 

non-relevant study question 

Chen WM . [He-Ne laser for wound]. Chinese Journal of

Physical Therapy 1994; 17(4):241. 

not a randomized controlled trial 

Cullum N, Nelson EA, Flemming K, et al. Systematic

reviews of wound care management: (5) beds; (6)

compression; (7) laser therapy, therapeutic ultrasound, 

electrotherapy and electromagnetic therapy. Health Technol 

Assess 2001; 5(9):1-221. 

no primary data 

Dolan MSTaVP. Experimental placebo controlled

investigation into infrared laser treatment of wound healing

in ulcers. 1988. 

not a published article 

Dolan MSTV, Pa SHJCM. Infra-red softlaser treatment of 

decubitus. Versus Tijdschrift Fysiotherapie 1989; 7(3):124-

40. 

not a randomized controlled trial 

Fernando S, Hill CM, Walker R. A randomised double 

blind comparative study of low level laser therapy 

following surgical extraction of lower third molar teeth. Br

J Oral Maxillofac Surg 1993; 31(3):170-2. 

non-relevant patient population 

Flemming K, Cullum N. Laser therapy for venous leg

ulcers. Cochrane Database Syst Rev 2000; (2):CD001182. 

no primary data 

Flemming KA, Cullum NA, Nelson EA. A systematic 

review of laser therapy for venous leg ulcers. J Wound 

Care 1999; 8(3):111-4. 

no primary data 

Gogia PP, Marquez RR. Effects of helium-neon laser on

wound healing. Ostomy Wound Manage 1992; 38(6):33, 

36, 38-41. 

not a randomized controlled trial 

Gostishchev VK, Vert'ianov VA, Novochenko AN, et al. 

[Use of low-intensity laser irradiation in the treatment of 

suppurative wounds]. Vestn Khir Im I I Grek 1987; 

138(3):61-3. 

not a randomized controlled trial 

Gostishchev VK, Vert'ianov VA, Shur VV, et al. [The 

helium-neon laser in the treatment of suppurative wounds].

Vestn Khir Im I I Grek 1985; 134(3):57-60. 

not a randomized controlled trial 

Howell RM, Cohen DM, Powell GL, et al. The use of low

energy laser therapy to treat aphthous ulcers. Ann Dent 

1988; 47(2):16-8. 

not a randomized controlled trial 

Juri H, Palma JA. CO2 laser in decubitus ulcers: a

comparative study. Lasers Surg Med 1987; 7(4):296-9. 

non-relevant intervention 

Koev K, Rousseva M, Zaprianov Z, et al. Experimental 

study on the effect of low intensity helium-neon laser 

radiation on the restorative processes in the front 

epithelium and substantia propria of the cornea. 2. After

nonperforative traumatic damage. Folia Med (Plovdiv) 

1991; 33(1):46-51. 

non-relevant study question 

Krol P, Franek A, Hunka-Zurawinska W, et al. [Laser's

biostimulation in healing or crural ulcerations]. Pol 

Merkuriusz Lek 2001; 11(65):418-21. 

not a randomized controlled trial 

Lagan KM, Clements BA, McDonough S, et al. Low 

intensity laser therapy (830nm) in the management of 

minor postsurgical wounds: a controlled clinical study.

Lasers Surg Med 2001; 28(1):27-32. 

non-relevant patient population 

71
Liu LW. [Ultraviolet or He-Ne laser therapy for 50 cases

with weapon wound]. Chinese Journal of Physical Therapy

1980; 3(1):44-6. 

not a randomized controlled trial 

Lucas C, Criens-Poublon LJ, Cockrell CT, et al. Wound 

healing in cell studies and animal model experiments by

Low Level Laser Therapy; were clinical studies justified? a

systematic review. Lasers Med Sci 2002; 17(2):110-34. 

no primary data 

Schindl A, Heinze G, Schindl M, et al. Systemic effects of

low-intensity laser irradiation on skin microcirculation in 

patients with diabetic microangiopathy. Microvasc Res

2002; 64(2):240-6. 

non-relevant outcome 

Schindl A, Schindl M, Schind L. Phototherapy with low 

intensity laser irradiation for a chronic radiation ulcer in a 

patient with lupus erythematosus and diabetes mellitus. Br 

J Dermatol 1997; 137(5):840-1.

not a randomized controlled trial 

Schindl A, Schindl M, Schon H, et al. Low-intensity laser

irradiation improves skin circulation in patients with 

diabetic microangiopathy. Diabetes Care 1998; 21(4):580-

4. 

non-relevant outcome 

Schindl A. Low-intensity laser irradiation improves skin 

circulation in patients with diabetic microangiopathy. 

Diabetes Care 1998; 21(4):580-4. 

non-relevant outcome 

Sliney D. Low level laser therapy wound treatment update. 

J Laser Appl 1999; 11(5):221-4. 

no primary data 

Zapryanov Z, Koev K, Tanev V, et al. An experimental 

study of the effect of low level helium-neon laser

irradiation on the reparative processes of the cornea after 

perforative injury. Folia Med (Plovdiv) 1990; 32(2):39-44 . 

non-relevant study question 

Zimmermann M. [Studies on the therapeutic efficacy of a

HeNe laser]. [German]. Deutsche Zeitschrift fur Mund-, 

Kiefer- und Gesichtschirurgie 1990; 14(4):313-9. 

non-relevant patient population 

72
Excluded Articles, Vacuum-Assisted Closure 

Azad S, Nishikawa H. Topical negative pressure may help

chronic wound healing. BMJ 2002; 324(7345):1100. 

no primary data 

Ballard K, Baxter H. Vacuum-assisted closure. Nurs Times 

2001; 97(35):51-2. 

not a randomized controlled trial 

Banwell P, Withey S, Holten I. The use of negative

pressure to promote healing. Br J Plast Surg 1998; 

51(1):79. 

no primary data 

Banwell PE. Topical negative pressure therapy in wound 

care. J Wound Care 1999; 8(2):79-84. 

no primary data 

Baxandall T. Tissue viability. Healing cavity wounds with 

negative pressure. Nurs Stand 1996; 11(6):49-51. 

not a randomized controlled trial 

Bonnema J, van Geel AN, Ligtenstein DA, et al. A 

prospective randomized trial of high versus low vacuum 

drainage after axillary dissection for breast cancer. Am J 

Surg 1997; 173(2):76-9. 

non-relevant comparison 

Buttenschoen K, Fleischmann W, Haupt U,, et al. The 

influence of vacuum-assisted closure on inflammatory

tissue reactions in the postoperative course of ankle 

fractures. Foot Ankle Surg 2001; 7(3):165-173. 

non-relevant outcom 

Collier M. Know how: vacuum-assisted closure (VAC). 

Nurs Times 1997; 93(5):32-3. 

not a randomized controlled trial 

Cooper SM, Young E. Topical negative pressure in the 

treatment of pressure ulcers. J Am Acad Dermatol 1999; 

41(2 Pt 1):280. 

no primary data 

Cooper SM, Young E. Topical negative pressure. Int J

Dermatol 2000; 39(12):896-8. 

no primary data 

de Vooght A, Feruzi G, Detry R, et al. Vacuum-assisted 

closure for abdominal wound dehiscence with prosthesis 

exposure in hernia surgery. Plast Reconstr Surg 2003; 

112(4):1188-9. 

not a randomized controlled trial 

Deaton WR Jr, Clutts GR. Use of negative pressure as a 

method of draining extensive wounds. Am Surg 1957; 

23(3):278-80. 

no primary data 

Deva AK, Siu C, Nettle WJ. Vacuum-assisted closure of a 

sacral pressure sore. J Wound Care 1997; 6(7):311-2. 

not a randomized controlled trial 

Dunlop MG, Fox JN, Stonebridge PA, et al. Vacuum

drainage of groin wounds after vascular surgery: a 

controlled trial. Br J Surg 1990; 77(5):562-3. 

not a vacuum-assisted wound healing device 

Duxbury MS, Finlay IG, Butcher M, et al. Use of a vacuum 

assisted closure device in pilonidal disease. J Wound Care 

2003; 12(9):355. 

not a randomized controlled trial 

Erdmann D, Drye C, Heller L, et al. Abdominal wall defect 

and enterocutaneous fistula treatment with the VacuumAssisted Closure (V.A.C.) system. Plast Reconstr Surg 

2001; 108(7):2066-8. 

not a randomized controlled trial 

Evans D, Land L. Topical negative pressure for treating 

chronic wounds. Cochrane Database Syst Rev 2001; 

(1):CD001898. 

no primary data 

Finnegan D. Pressure sores. 1. Positive living or negative 

existence? Nurs Times 1983; 79(24):51-2, 53. 

not a randomized controlled trial 

Genecov DG, Schneider AM, Morykwas MJ, et al. A 

controlled subatmospheric pressure dressing increases the 

rate of skin graft donor site reepithelialization. Ann Plast 

Surg 1998; 40(3):219-25. 

not a randomized controlled trial 

Giovanni UM, Demaria RG, Otman S, et al. Treament of 

poststernotomy wounds with negative pressure. Plast 

Reconstr Surg 2002; 109(5):1747. 

not a randomized controlled trial 

Greer S, Kasabian A, Thorne C, et al. The use of a 

subatmospheric pressure dressing to salvage a Gustilo 

grade IIIB open tibial fracture with concomitant

osteomyelitis to avert a free flap. Ann Plast Surg 1998; 

41(6):687. 

not a randomized controlled trial 

Greer SE. Whither subatmospheric pressure dressing? Ann 

Plast Surg 2000; 45(3):332-4; discussion 335-6. 

no primary data 

Harlan JW. Treatment of open sternal wounds with the 

vacuum-assisted closure system: a safe, reliable method. 

Plast Reconstr Surg 2002 ; 109(2):710-2. 

no primary data 

73
Heath T, Moisidis E, Deva A. A prospective controlled trial

of vacuum assisted closure (VAC) in the treatment of acute 

surgical wounds requiring split skin grafting. Fourth 

Australian Wound Management Association Conference 

2002; 41. 

unpublished 

Huang J, Yao YZ, Huang XK. [Treatment of open fracture 

by vacuum sealing technique and internal fixation]. 

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2003; 

17(6):456-8. 

not a randomized controlled trial 

Kalailieff D. Vacuum-assisted closure: wound care 

technology for the new millennium. Perspectives

(Montclair) 1998; 22(3):28-9. 

not a randomized controlled trial 

Kamolz LP, Andel H, Haslik W, et al. Use of

subatmospheric pressure therapy to prevent burn wound 

progression in human: first experiences. Burns 

2004;30(3):253-8. 

not a randomized controlled trial 

Kirby JP, Fantus RJ, Ward S, et al. Novel uses of a 

negative-pressure wound care system. J Trauma 2002; 

53(1):117-21. 

not a randomized controlled trial 

Kloth LC. 5 questions-and answers-about negative pressure 

wound therapy. Adv Skin Wound Care 2002; 15(5):226-9. 

no primary data 

McLean WC. The role of closed wound negative pressure 

suction in radical surgical procedures of the head and neck. 

Laryngoscope 1964; 7470-94. 

not a randomized controlled trial 

Mendez-Eastman S. Guidelines for using negative pressure 

wound therapy. Adv Skin Wound Care 2001; 14(6):314-22. 

no primary data 

Mendez-Eastman S. New treatment for an old problem: 

negative-pressure wound therapy. Nursing (Lond) 2002; 

32(5):58-63. 

no primary data 

Mullner T, Mrkonjic L, Kwasny O, et al. The use of 

negative pressure to promote the healing of tissue defects: a 

clinical trial using the vacuum sealing technique. Br J Plast 

Surg 1997; 50(3):194-9. 

not a randomized controlled trial 

Nelson RP, Merrill DC. Use of negative pressure suction in 

urology. Urology 1974; 4(5):574-6. 

not a randomized controlled trial 

Neubauer G, Ujlaky R. The cost-effectiveness of topical 

negative pressure versus other wound-healing therapies. J 

Wound Care 2003; 12(10):392-3. 

no primary data 

Nienhuijs SW, Manupassa R, Strobbe LJ, et al. Can topical 

negative pressure be used to control complex

enterocutaneous fistulae? J Wound Care 2003; 12(9):343-5. 

not a randomized controlled trial 

Patel CT, Kinsey GC, Koperski-Moen KJ, et al. Vacuumassisted wound closure. Am J Nurs 2000; 100(12):45-8. 

not a randomized controlled trial 

Philbeck TE Jr, Whittington KT, Millsap MH, et al. The 

clinical and cost effectiveness of externally applied 

negative pressure wound therapy in the treatment of 

wounds in home healthcare Medicare patients. Ostomy

Wound Manage 1999; 45(11):41-50. 

no primary data, Not counted for purposes of computing 

percent agreement. 

Prokuski L. Negative pressure dressings for open fracture 

wounds. Iowa Orthop J 2002; 2220-4. 

not a randomized controlled trial 

Saklani AP, Delicata RJ. Vacuum assisted closure system

in the management of enterocutaneous fistula. Postgrad 

Med J 2002; 78(925):699; author reply 699. 

not a randomized controlled trial 

Schaum KD. Medicare Part B negative pressure wound 

therapy pump policy. A partner for Medicare Part A PPS.

Home Healthc Nurse 2002; 20(1):57-8. 

no primary data 

Shaer WD. Inexpensive vacuum-assisted closure 

employing a conventional disposable closed-suction 

drainage system. Plast Reconstr Surg 2001; 107(1):292-3. 

not a randomized controlled trial 

Silvis RS, Potter LE, Robinson DW, et al. The use of 

continuous suction negative pressure instead of pressure 

dressing. Ann Surg 1955; 142(2):252-6. 

not a randomized controlled trial 

Skillman J, Kirkpatrick N, Coombes A, et al. Vacuum

Assisted Closure (VAC) dressing for skin graft application

following exenteration of the orbit. Orbit 2003; 22(1):63-5. 

not a randomized controlled trial 

Yao YZ, Huang XK, Ma XL. [Treatment of traumatic soft

tissue defect by vacuum sealing]. Zhongguo Xiu Fu Chong 

Jian Wai Ke Za Zhi 2002; 16(6):388-90. 

not a randomized controlled trial 

74
List of Acronyms/Abbreviations 

AE adverse events 

AHRQ Agency for Healthcare Research and Quality 

CI confidence interval 

cx control 

d day 

F female 

f/u followup 

FDA U.S. Food and Drug Administration 

GaAl gallium-aluminum 

GaAs gallium-arsenide 

HeNe helium-neon 

hr hour 

LLL low-level laser 

M male 

mn mean 

mo month 

NR not reported 

NS not significant 

PMN polymorphonuclear 

QOL quality of life 

rng range 

ROM range of motion 

SC standard care 

SC subcutaneous 

SD standard deviation 

SW software 

tcpO2 transcutaneous oxygen tension 

TEP: Technical Expert Panel 

tx treatment 

U.S. United States 

US ultrasound 

UV ultraviolet 

VAC vacuum-assisted closure 

wk week 

WOCN Wound, Ostomy and Continence Nurses Society 

yr year 

75
Appendix A. Exact Search Strings 

Electronic database searches using the following terms were completed of MEDLINE® (via 

PubMed), EMBASE, and the Cochrane Controlled Trials Register. The MEDLINE® search 

covered references entered onto the database from January 1, 1966 through June 8, 2004. The 

Cochrane Controlled Trials Register search was completed in 2003, through issue number 4. 

The EMBASE search covered references entered through June 14, 2004. 

The search was limited to studies on human subjects with English-language abstracts. Papers 

published in foreign languages were reviewed if the English-language abstract appeared to meet 

inclusion criteria. Results of the search and study selection were reviewed by the Technical 

Expert Panel (TEP) for this project, in order to identify additional studies. 

In addition, two companies that produce lasers used in wound healing were contacted 

(Microlight Corporation of America and Photothera), as well as the major producer of vacuumassisted closure devices (V.A.C.®, Kinetics Concepts Inc. [KCI]) and invited them to submit 

evidence-based information for the review. The specific request was for “lists of published, 

randomized, controlled trials (RCTs), published abstracts of RCTs within the past 2 years, and 

published articles on study design, or protocols of any RCTs (published or in progress).” 

Low-Level Laser Therapy 

For low-level laser therapy, the search is somewhat narrower than for vacuum-assisted closure 

because the question is limited to chronic, nonhealing wounds. 

A Medical Subject Headings ® (MeSH®) term, “laser therapy, low-level,” was introduced in 

2002. The following entry terms map to it: 

• Laser Therapies, Low-Level 

• Laser Therapy, Low Level 

• Low-Level Laser Therapies 

• Laser Irradiation, Low-Power 

• Irradiation, Low-Power Laser 

• Laser Irradiation, Low Power 

• Laser Therapy, Low-Power 

• Laser Therapies, Low-Power 

• Laser Therapy, Low Power 

• Low-Power Laser Therapies 

• LLLT 

• Laser Biostimulation 

• Biostimulation, Laser Low-Level 

• Laser Therapy Low Level 

• Laser Therapy Low-Power 

• Laser Irradiation Low Power 

• Laser Irradiation Low-Power 

• Laser Therapy Low Power 

• Laser Therapy 
The following text phrases will also be searched: 

• “low level laser” 

• “low power laser” 

• “low intensity laser” 

• “low energy laser” 

• “low level energy laser” 

• “low output laser” 

• “nonablative laser” 

• “cold laser” 

These terms related to wounds will be searched: 

• “skin ulcer[MeSH]” 

 “decubitus ulcer” 

 “foot ulcer” 

 “leg ulcer” 

 “varicose ulcer” 

 “diabetic foot” 

• “wound*” 

• “ulcer*” 

The intersection of the laser therapy terms and wound terms served as the initial pool of 

references. These were cross-referenced with the terms for randomized trials compiled by 

the Cochrane Collaboration (Clark and Oxman, 2003). 

Vacuum-Assisted Closure 

Searches on the terms below relate to vacuum-assisted closure: 

• “topical negative pressure” 

• “sub-atmospheric pressure therapy” (also “subatmospheric”) 

• “sub-atmospheric pressure dressing” (also “subatmospheric”) 

• “vacuum sealing” 

• “vacuum assisted closure” 

• “negative pressure dressing” 

• “negative pressure therapy” 

• “foam suction dressing” 

• “vacuum compression” 

• “vacuum pack” 

• “sealed surface wound suction” 

• “sealing aspirative therapy” 

These terms related to wounds will be searched: 
• “wound*” 

• “ulcer*” 

• “decubit*” 

• “incision*” 

• “dressing” 

• “free flap” 

• “skin graft*” 

• “skin transplantation” 

• “degloving injuries” 

• “degloving injury” 

Excluded terms: 

• “mechanical ventilation” 

• “ear pressure” 

• “venous pressure” 

• “hypertension” 

• “abortion” 

• “core needle” 

• “colonic anastomos*” 

The intersection of the vacuum-assisted closure terms and wound terms served as the initial pool 

of references. These were cross-referenced with the terms for randomized trials compiled by the 

Cochrane Collaboration (Clark and Oxman, 2003). 
Appendix B. Technical Expert Panel (TEP) and 

Reviewers 

Technical Expert Panel (TEP) 

David G. Armstrong, D.P.M., M.Sc., Ph.D.(c) 

Professor of Surgery 

Chair of Research and Assistant Dean 

Dr. William M. Scholl College of Podiatric Medicine at 

Rosalind Franklin University of Medicine and Science 

North Chicago, IL 

Sharon Baranoski, M.S.N., R.N., C.W.O.C.N., A.P.N., F.A.A.N. 

Administrator, Home Health and 

Administrative Director of Clinical Programs and Development 

Silver Cross Hospital 

Joliet, IL 

Harriet Williams Hopf, M.D. 

Associate Professor in Residence 

Department of Anesthesia and Perioperative Care and Surgery 

University of California, San Francisco 

San Francisco, CA 

Frank LoGerfo, M.D. 

William V. McDermott Professor of Surgery 

Harvard Medical School and 

Chief, Division of Vascular Surgery 

Beth Israel Deaconess Medical Center 

Boston, MA 

Harold R. Mancusi-Ungaro, Jr., M.D., F.A.C.S. 

Chief, Plastic Surgery 

Kaiser Permanente, Santa Rosa 

Santa Rosa, CA 

William S. Schwab, III, M.D., Ph.D. 

Chief of Geriatric Services 

Ohio Permanente Physician Group 

Willoughby, OH 

Nominee: American Association of Health Plans (AAHP; Partner Organization) 
External Peer Reviewers 

David Atkins, M.D., M.P.H. 

Chief Medical Officer 

Center for Outcomes and Quality 

Agency for Healthcare Research and Quality 

Rockville, MD 

Elise Berliner, Ph.D. 

Agency for Healthcare Research and Quality 

Rockville, MD 

Caroline Fife, M.D. 

Associate Professor of Anesthesiology 

Department of Anesthesiology 

The University of Texas-Houston Medical School and 

Director, Hermann Center for Wound Healing and Lymphedema Management 

Houston, TX 

Kenneth S. Fink, M.D., M.G.A., M.P.H. 

Director, Evidence-based Practice Centers (EPC) Program 

Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality 

Rockville, MD 

Carmen Kelly, Pharm.D. 

LT, U.S. Public Health Service 

Pharmacist Officer and 

EPC Task Order Officer 

Agency for Healthcare Research and Quality 

Rockville, MD 

Steven R. Kravitz, D.P.M. 

President 

American Podiatric Wound Care Association 

Richboro, PA 

Nominee: American College of Foot and Ankle Surgeons 

Wayne J. Schroeder, M.D. 

Vice President, Medical Director 

Kinetic Concepts, Inc. 

San Antonio, TX 
James Spencer, M.D. 

Assistant Attending 

The Mount Sinai Hospital and 

Associate Professor 

Mount Sinai School of Medicine 

Department of Dermatology 

New York, NY 

Nominee: Association for the Advancement of Wound Care 

Jackson Streeter, M.D. 

President and CEO 

PhotoThera, Inc. 

Carlsbad, CA 92008 

Pamela G. Unger, P.T. 

The Center for Advanced Wound Care 

Partner, Director of Clinical and Administrative Services 

Wyomissing, PA 

Stephanie Yates, R.N., M.S.N., C.W.O.C.N. 

Clinical Nurse Specialist 

Rex Healthcare 

Raleigh, NC 

Nominee: Wound Ostomy and Continence Nurses Society