Low-Level Laser and Vacuum-Assisted Closure
Evidence Report/Technology Assessment: Number 111
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Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
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Introduction / Methods / Results / Discussion / Availability of Full Report / References
Authors: Samson D, Lefevre F, Aronson N.
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 health care 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:
- 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?
- As an adjunct to conventional therapy, compared with conventional therapy alone?
- 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?
- 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
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 less frequent
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
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
wounds either require a prolonged time to heal, 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
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,
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:
- The percent of patients with complete healing.
- Time to complete healing.
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.
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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.
- 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 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 (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
This systematic review selected only randomized, controlled
trials meeting the following criteria:
- The trial must involve one of the following comparisons
- Either low-level laser treatment or vacuum-assisted closure, compared with other wound healing interventions (alternative intervention trials).
- Either low-level laser treatment or vacuum-assisted closure in addition to standard wound care, compared with standard wound care alone (incremental benefit trials).
- Either low-level laser treatment or vacuum-assisted closure, compared with a sham intervention (placebo trials).
- 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.
- The trial must report on at least one of the outcomes of interest.
- 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
In reviewing full-text articles to determine eligibility for data
abstraction, a single reviewer determined whether each paper
- Included in systematic review.
- Excluded from systematic review.
- 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.
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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
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.
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 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.
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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 health care expenditures is considerable. Future
research should address how to improve the delivery of care,
quality of care, and outcomes of treatment of wounds in
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.
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Availability of 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. Printed copies may be obtained
free of charge from the AHRQ Publications Clearinghouse by
calling 1-800-358-9295. Inquiries should include a request for
Evidence Report/Technology Assessment No. 111, Wound
Healing Technologies: Low-Level Laser and Vacuum-Assisted
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a PDF File (1.5 MB). Plugin Software Help.
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AHRQ Publication Number 05-E005-1
Current as of December 2004