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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December 2004

ISSN 1530-440X