Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention

  • Review
  • Intervention

Authors


Abstract

Background

Indications for the use of negative pressure wound therapy (NPWT) are broadening with a range of systems on the market, including those designed for use on clean, closed incisions and skin grafts. Reviews have concluded that the evidence for the effectiveness of NPWT remains uncertain. However, this is a rapidly evolving therapy. Consequently, a systematic review of the evidence for the effects of NPWT on postoperative wounds expected to heal by primary intention is required.

Objectives

To assess the effects of NPWT on surgical wounds (primary closure or skin grafting) that are expected to heal by primary intention.

Search methods

We searched the following electronic databases to identify reports of relevant randomised clinical trials: the Cochrane Wounds Group Specialised Register (searched 11 November 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4); Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 4); Ovid MEDLINE (2005 to October Week 4 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 8 November 2011); Ovid EMBASE (2009 to 2011 Week 44); and EBSCO CINAHL (1982 to 04 November 2011). We conducted a separate search to identify economic evaluations.

Selection criteria

We included trials if they allocated patients at random and compared NPWT with any other type of wound dressing or compared one type of NPWT with a different type of NPWT.

Data collection and analysis

We assessed trials for their appropriateness for inclusion and for their quality. This was done by three review authors working independently, using pre-determined inclusion and quality criteria.

Main results

We included five trials with a total of 280 participants. Two trials involved skin grafts, two included orthopaedic patients undergoing arthroplasty and one included general and trauma surgery patients; all had unclear or high risk of bias. Four trials compared NPWT with a standard dressing and one trial compared two NPWT devices. There were no differences in the proportion of wounds completely healed; the incidence of seromas; or failed skin grafts. One trial (87 participants) compared a commercial negative pressure device (VAC® KCI, San Antonio, Texas) with a negative pressure system developed in the hospital (GSUC). The wound complication rate was lower in the GSUC group (VAC® 3/42; GSUC 0/45); the RR was 0.13 (95% CI 0.01 to 2.51). The mean cost to supply equipment for VAC® therapy was USD 96.51/day compared to USD 4.22/day for the GSUC therapy (P = 0.01). Labour costs for dressing changes were similar. Pain intensity score was also reported to be lower in the GSUC group when compared with the VAC® group (p = 0.02). One trial was stopped early because of a high incidence of fracture blisters in the NPWT group (15/24; 62.5%) compared with the standard dressing group (3/36; 8.3%)(RR 7.50; 95%CI 2.43 to 23.14).

Authors' conclusions

There is no evidence for the effectiveness of NPWT on complete healing of wounds expected to heal by primary intention. There are clear cost benefits when non-commercial systems are used to create the negative pressure required for wound therapy, with no apparent reduction in clinical outcome. Pain levels are also rated lower when hospital systems are compared with their commercial counterparts. The high incidence of blisters occurring when NPWT is used following orthopaedic surgery suggests that the therapy should be limited until safety in this population is established. Given the cost and widespread use of NPWT, there is an urgent need for suitably powered, high-quality trials to evaluate the effects of the newer NPWT products that are designed for use on clean, closed surgical incisions. Such trials should focus initially on wounds that may be difficult to heal, such as sternal wounds or surgeries for obese patients.

摘要

負壓傷口治療用於皮膚移植與手術傷口癒合

背景

負壓傷口治療(negative pressure wound therapy, NPWT)的適應症隨著市場上系統的多樣化而擴展,包含用於乾淨、封閉傷口與皮膚移植的照護。目前文獻回顧的結果,針對負壓傷口治療有效性之證據仍無法確定。然而,這是快速興起的治療方法。因此,針對負壓傷口治療對於促進術後傷口癒合效果的系統文獻回顧是必需的。

目標

評估負壓傷口治療對於手術傷口(主要為閉合性或皮膚移植)之效果。

搜尋策略

我們搜尋了下列電子資料庫以找出相關隨機臨床試驗的報告:考科藍傷口專業註冊試驗(搜尋至2011年11月11日); CENTRAL(The Cochrane Library 2011, Issue 4); Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 4);Ovid MEDLINE(2005年到2011年10月第4週); Ovid MEDLINE(進行中與其它非索引引用2011年11月8日);Ovid EMDASE(2009年到2011年第44週);以及EBSCO CINAHL(1982年到2011年11月4日)。我們進行分別的搜尋,以找出經濟評估(economic evaluations)。

選擇標準

若試驗以隨機方式分配病人,並比較負壓傷口治療與其它傷口敷料類型;或是比較不同的負壓傷口治療類型的試驗,納入本回顧中。

資料收集與分析

我們評估了試驗是否符合納入標準,並評估其研究品質。這個過程由3位作者使用預定的納入、及研究品質標準獨立作業完成。

主要結論

我們採用了5個試驗總共有280位參與者。2個試驗涉及皮膚移植,2個包含了進行關節置換的骨科病人,還有一個包含一般與創傷外科病人。所有的試驗都具有不確定的或高的偏差風險。4個試驗比較了負壓傷口治療與標準敷料,而1個試驗比較兩種負壓傷口治療裝置。這些研究的結果,在傷口完全癒合比例、血腫發生或皮膚移植失敗率方面,沒有差異。1個試驗(87名參與者)比較了商用負壓儀器(VAC® KCI, San Antonio, Texas)與醫院中發展出來的負壓系統(GSUC)。使用GSUC者,傷口併發症發生率較低(VAC® 3/42; GSUC 0/45;RR 0.1395% CI 0.01到2.51)。使用VAC®治療設備的平均成本為美金96.51/天,較GSUCUSD4.22/天高(P=0.01)。兩組在更換敷料的人力成本上類似。相較於VAC組,使用GSUC組之疼痛強度分數也較低(P=0.02)。一個試驗提早停止,因為在負壓傷口治療組中,骨折水泡(fracture blisters)的發生率較高(15/24;62.5%),與標準敷料群組相比(3/36;8.3%)(RR 7.50;95% CI 2.43到23.14)。

作者結論

沒有證據支持負壓傷口治療用於促進傷口癒合上的有效性。在採用非商業系統以建立傷口治療所需的負壓時,有明顯的成本益處,對臨床效果方面卻沒有明顯的降低。當醫院系統與類似的商業系統比較時,疼痛水準也較低。骨科手術後使用負壓傷口治療,發生水泡機率較高,這個研究結果顯示,除非在這個族群使用負壓傷口治療的安全性被建立,否則,此治療應被限制。在使用負壓傷口治療的成本與廣泛使用的前提下,有適當效力、高品質的試驗以評估其對於清淨、封閉式手術切口上使用的效果有急切的需要。此類試驗初期應著重在可能難以癒合的傷口上(如胸骨傷口),或肥胖病人的手術傷口上。

Plain language summary

Negative pressure wound therapy for acute surgical wounds.

Negative pressure wound therapy (NPWT) involves applying suction to healing wounds. NPWT has been used for many years for the treatment of chronic wounds, such as leg ulcers and bed sores. More recently, the device has been modified for use on clean surgical wounds, including skin grafts. We undertook a review of studies that have compared NPWT with other wound treatments. We found five trials which showed that evidence to support the use of NPWT to promote faster healing and to reduce complications associated clean surgery remains unclear.

總結

負壓傷口治療用於皮膚移植與手術傷口癒合

負壓傷口治療用於急性手術傷口治療。

負壓傷口治療涉及利用抽吸促進傷口癒合。負壓傷口治療已於慢性傷口治療中使用多年,像是下肢潰瘍與褥瘡。近來,儀器調整為可用於乾淨的手術傷口,包含皮膚移植。我們進行了系統性文獻回顧,進行使用負壓傷口治療與其它傷口治療之比較。我們找到5個試驗,結果顯示使用負壓傷口治療可促進手術乾淨傷口的癒合或降低併發症之證據仍不明確。

譯註

East Asian Cochrane Alliance 翻譯
翻譯由 台灣衛生福利部/台北醫學大學實證醫學研究中心 資助

Background

Description of the condition

It is estimated that between 187 and 281 million operations are carried out annually worldwide, equating to one operation each year for every 25 people (WHO 2009). This figure is higher in developed countries. For example, in Australia in 2008/09 it can be calculated from hospital statistics that there was one elective surgical procedure for every 12.4 people (Australian Institute of Health and Welfare 2010).

Surgical wounds, including skin grafts, generally heal by primary intention where the wound edges are brought together so that they are adjacent to each other. Wound closure is usually assisted using sutures (stitches), staples, adhesive tape or glue (Coulthard 2010) and healing begins within hours of closure (Rodero 2010). However, some types of surgical wounds, such as skin grafts (Culliford 2007) and sternal wounds (Schimmer 2008), are more difficult to heal due to their anatomical position or an increased likelihood of infection. So too are surgical wounds in certain types of patients, such as the morbidly obese (Waisbren 2010).

Failure of a wound to heal may be due to underlying patient characteristics such as age or medical conditions, including malnutrition, obesity, uncontrolled diabetes, cardiovascular disease, compromised immunity or infection (Baronski 2008). It may also be the result of dehiscence, or separation of the wound edges. Reasons for dehiscence are either technical, such as sutures breaking, cutting through tissue or knots slipping, or inadequate splinting (Baronski 2008) or related to patient factors, such as those listed above and particularly wound infection (Ortega 2010). Chronic obstructive pulmonary disease is a major risk factor for dehiscence in sternal surgery (Olbrecht 2006). The most serious complication of dehiscence is wound evisceration, where the wound completely separates, exposing the underlying organs (Harvey 2005).

Description of the intervention

Negative pressure wound therapy (NPWT) has been used to treat wounds since the late 1990s (Fleischmann 1997; Morykwas 1997). NPWT is recommended for a diverse range of lesions including open abdominal wounds (Stevens 2009), open fractures (Stannard 2009), skin graft donor sites (Chio 2010), acute burns (Molnar 2005), pressure ulcers (Mandal 2007), post-traumatic wounds (Kanakaris 2007), diabetic foot ulcers (Eneroth 2008), split-thickness skin grafts (Blume 2010), sternal wounds (Sjogren 2011) and, more recently, after clean surgery in obese patients (Dragu 2010). NPWT is used prophylactically following skin grafts and clean surgery to prevent a surgical site complication, in contrast to its more frequent use in wounds healing by secondary intention (left open to heal from the bottom up) such as chronic or infected wounds.

NPWT consists of a closed, sealed system that produces negative pressure (suction) to the wound surface. The wound is covered or packed with an open-cell foam or gauze dressing and sealed with an occlusive drape. Intermittent or continuous suction is maintained by connecting suction tubes from the wound dressing to a vacuum pump and liquid waste collector. Standard negative pressure rates range between 50 and 125 mm Hg (Ubbink 2008; Vikatmaa 2008). The longest established device is the vacuum-assisted closure ((VAC® KCI, San Antonio, Texas) system (Morykwas 1997) however alternatives have been developed and are being used (Llanos 2006; Mody 2008; Rozen 2008).         

How the intervention might work

In humans, the wound healing process is regarded as occurring in three consecutive and overlapping stages: inflammation, new tissue formation and remodelling (Gurtner 2008). The precise way in which NPWT may aid this process is not clear. Experimental evidence suggests that NPWT may assist wound healing by increasing local blood flow and granulation tissue and, reducing bacterial contamination, oedema and exudate. There may be other changes to the microenvironment of the wound (Banwell 2003). One of the basic theoretical principles underpinning the development of NPWT is that it increases perfusion or blood flow, but this has been recently challenged. In an experimental study, using healthy volunteers local blood flow decreased as suction pressure increased (Kairinos 2009).

Why it is important to do this review

Wounds that fail to heal may cause considerable distress to patients and impact negatively on the physical, social, emotional and economic aspects of their life (Andersson 2010). Investigations into interventions to avoid wound breakdown are therefore important. NPWT was approved by the American Food and Drug Administration (FDA) for the treatment of non-healing wounds in 1995 (Kloth 2002). More recently, a multi-national expert working group has issued guidelines for the use of the therapy for diabetic foot ulcers, complex leg ulcers, pressure ulcers, dehisced sternal wounds, open abdominal wounds and traumatic wounds (Expert Working Group 2008). While NPWT has become an accepted part of modern wound healing techniques, there have also been reports of severe adverse events associated with the therapy. Problems have included stomal dehiscence (Steenvoorde 2009), extraperitoneal bladder leakage (Heuser 2005), necrotising fasciitis (Citak 2010), bleeding after cardiac surgery (Petzina 2010) and pain (Apostoli 2008) and anxiety (Keskin 2008). Communiqués issued in 2009 by the FDA reported six deaths and 77 injury reports associated with the use of NPWT. The information sheets contained warnings and recommendations for consumers and healthcare practitioners about use of the treatment in certain circumstances (FDA 2009a; FDA 2009b).

Although several reviews of NPWT have been published, none has focused specifically on postoperative wounds expected to heal by primary intention (Gregor 2008; Ubbink 2008; Vikatmaa 2008); nor have any included an economic analysis. In addition, although publication bias has been noted, both in terms of the majority of trials being funded by manufacturers (Vikatmaa 2008) and premature termination of studies (Gregor 2008), no sub-analyses to control for these potential biases have been conducted. Recent reviews have concluded that the evidence for the effectiveness of NPWT remains uncertain, however, this is an evolving therapy and the indications for its use are widening. Consequently, a systematic review to summarise evidence on the effects of NPWT on the healing of surgical wounds healing by primary intention is required.

Objectives

To assess the effects of NPWT on surgical wounds (including skin grafts) that are expected to heal by primary intention.

Methods

Criteria for considering studies for this review

Types of studies

We included only randomised controlled trials (RCTs) that evaluated the effects of NPWT on the healing of surgical wounds. Surgical wounds included split skin grafts, full skin grafts or any primary wound closure. This criterion encompassed comparative full and partial economic evaluations conducted within the framework of eligible RCTs (i.e. cost-effectiveness analyses, cost-utility analyses, cost-benefit analyses and cost-analyses). We did not include trials of skin graft donor sites or wounds that were unable to be closed immediately because of damaged tissue (for example in severe trauma), infection or chronicity. Cross-over trials and quasi-randomised studies, e.g. treatment allocation alternate or by date of birth, were also ineligible.

Types of participants

We included trials involving people of any age, and in any care setting, involving the use of NPWT for surgical wounds healing by primary intention.

Types of interventions

The primary intervention was NPWT delivered by any mode (for example vacuum-assisted closure [(VAC® KCI, San Antonio, Texas] or simple closed-system suction drainage) delivered continuously or intermittently over any time period. The comparison interventions were any standard dressing (for example gauze) or any advanced dressing (for example hydrogels, alginates, hydrocolloids); or comparisons between different negative pressure devices.

Types of outcome measures

Primary outcomes
  • Proportion of surgical wounds healing by primary intention that completely heal (surgical wounds may include split skin grafts, full skin grafts or any primary wound closure).

  • Mortality.

  • Adverse events - including wound complications (such as wound infection, dehiscence, haematoma, seroma, fracture blisters and graft loss).

Secondary outcomes
  • Time to complete healing.

  • Pain (measured by any valid pain assessment instrument)

  • Quality of life (measured by any valid assessment instrument).

  • Cost (including: utility scores representing health-related quality of life; treatment costs per patient per wound; costs of health practitioner time or visits; costs of hospital stay for wound healing; procedure costs to treat adverse events, infections or complications; costs of hospital stay resulting from adverse events and complications; incremental cost per life year gained; incremental cost per quality adjusted life year (QALY) and cost-benefit ratio.

Search methods for identification of studies

Electronic searches

We searched the following electronic databases to identify reports of relevant randomised clinical trials: 

  • the Cochrane Wounds Group Specialised Register (searched 11 November 2011);

  • the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4);

  • Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 4);

  • Ovid MEDLINE (2005 to October Week 4 2011);

  • Ovid MEDLINE (In-Process & Other Non-Indexed Citations 8 November 2011);

  • Ovid EMBASE (2009 to 2011 Week 44);

  • EBSCO CINAHL (1982 to 4 November 2011).

We used the following search strategy in the Cochrane Central Register of Controlled Trials (CENTRAL):

#1 MeSH descriptor Negative-Pressure Wound Therapy explode all trees
#2 MeSH descriptor Suction explode all trees
#3 MeSH descriptor Vacuum explode all trees
#4 ("negative pressure" or negative-pressure or TNP):ti,ab,kw
#5 (sub-atmospheric or subatmospheric):ti,ab,kw
#6 ((seal* NEXT surface*) or (seal* NEXT aspirat*)):ti,ab,kw
#7 (wound NEAR/3 suction*):ti,ab,kw
#8 (wound NEAR/3 drainage):ti,ab,kw
#9 ((foam NEXT suction) or (suction NEXT dressing*)):ti,ab,kw
#10 ((vacuum NEXT therapy) or (vacuum NEXT dressing*) or (vacuum NEXT seal*) or (vacuum NEXT assist*) or (vacuum NEAR closure) or (vacuum NEXT compression) or (vacuum NEXT pack*) or (vacuum NEXT drainage) or VAC):ti,ab,kw
#11 ("vacuum assisted closure technique" or VAC):ti,ab,kw
#12 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11)
#13 MeSH descriptor Surgical Wound Infection explode all trees
#14 MeSH descriptor Surgical Wound Dehiscence explode all trees
#15 surg* NEAR/5 infect*:ti,ab,kw
#16 surg* NEAR/5 wound*:ti,ab,kw
#17 surg* NEAR/5 site*:ti,ab,kw
#18 surg* NEAR/5 incision*:ti,ab,kw
#19 surg* NEAR/5 dehisc*:ti,ab,kw
#20 wound* NEAR/5 dehisc*:ti,ab,kw
#21 (#13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20)
#22 (#12 AND #21)

The search strategies for Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL can be found in Appendix 1; Appendix 2 and Appendix 3 respectively. We combined the Ovid MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision) (Lefebvre 2011). We combined the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2011).

We conducted separate searches to identify economic evaluations in the following electronic databases:

  • NHS Economic Evaluation Database (The Cochrane Library 2011, Issue 3);

  • Ovid MEDLINE (1948 to July Week 3 2011);

  • Ovid MEDLINE (In-Process & Other Non-Indexed Citations 28 July 2011);

  • Ovid EMBASE (1980 to 2011 Week 29);

  • EBSCO CINAHL (1982 to 20 July 2011)

We used economics filters developed by Centre for Reviews and Dissemination (CRD 2010) in combination with terms to describe the condition and intervention in Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL searches (see Appendix 4; Appendix 5 and Appendix 6 respectively). We did not restrict any of the above searches with respect to language, date of publication or study setting.

We searched the following clinical trials registries for details of relevant protocols and contacted the relevant research team:

  • Clinical trials.gov;

  • World Health Organization (WHO) International Clinical Trials Registry Platform;

  • Australian and New Zealand Clinical Trials Registry;

  • Current Controlled Trials.

Searching other resources

We checked the citation lists of papers identified by the above strategies for further reports of eligible studies. We contacted corresponding authors of identified studies and the manufacturers and distributors of devices used to deliver NPWT, such as Vacuum-Assisted Closure ((VAC® KCI, San Antonio, Texas); SNaP® Wound Care System Dressing, Spiracur Inc; Venrturi™ Avanti and Venturi™ Compact (Talley Group, England); RENASYS EZ*; and Smith & Nephew. We contacted experts in the field to ask for information about any unpublished studies.

Data collection and analysis

Selection of studies

JW, WC and MS independently reviewed titles and abstracts identified through the search process. We retrieved full reports of all potentially relevant trials for further assessment of eligibility based on the inclusion criteria. Differences of opinion were settled by consensus. There was no blinding of study authorship.

Data extraction and management

We extracted the following data using a pre-designed checklist:

  • methods (number eligible and randomised, adequacy of randomisation, allocation concealment, blinding, completeness of follow-up);

  • participant characteristics and exclusions;

  • type of surgery;

  • setting;

  • study dates;

  • interventions;

  • number of participants per group

  • information about ethics approval, consent and conflict of interest; and

  • outcomes

We resolved discrepancies through discussion. One review author (JW) entered data into the Review Manager software (RevMan 2011) and the other review authors checked data for accuracy. If information regarding any data was unclear, we attempted to contact study authors of the original reports to provide further details.

Assessment of risk of bias in included studies

Two review authors independently assessed the eligible trials (JW and KS) using the Cochrane Collaboration tool for assessing risk of bias (Higgins 2011). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues which may potentially bias the study (see Appendix 7 for details of the criteria on which the judgement was based). We assessed blinding and completeness of outcome data for each outcome separately. We completed a 'Risk of bias' table for each eligible study. We resolved disagreements between review authors by consensus. We contacted investigators of included trials to resolve any ambiguities. We were to have reported bias, and more generally study limitations within economic evaluations, using the checklist from the NICE Guidelines Manual (NICE 2009). We have presented assessment of risk of bias using a 'Risk of bias' summary figure, which shows all the judgements in a cross-tabulation of study by entry.

Measures of treatment effect

For individual trials, we extracted the numbers with an event for each treatment group and used them to calculate the risk ratio (RR) with its 95% confidence interval (CI). For statistically significant effects, we calculated number needed to treat (NNT) or number needed to harm (NNH) from the risk difference. For continuous outcomes, we extracted the mean and standard deviation (SD) and calculated the mean difference (MD) or, if the scale of measurement differed across trials, the standardised mean difference (SMD), each with its 95% CI.

Economic analyses

We were to have undertaken the following economic analysis but no studies provided suitable data. However the methods remain detailed here in the event that future updates of this review identify economic data.

We will present a tabled analysis of the identified economic data in accordance with current guidance on the use of economics methods in the preparation of Cochrane Reviews (Shemilt 2011). We will classify economic evaluation according to the framework in Drummond et al (Drummond 2005). We will tabulate the main characteristics and results of the identified economic evaluation studies and augment these with a narrative description. This will discuss the methods used and compare the key results of those studies.

The results of cost-effectiveness studies are likely to vary according to the particular circumstances of each study. For example, the comparator treatment, such as standard care, may differ for different types of wounds and in different settings. Our analysis will place the results of the economic studies in context and will entail a discussion of scenarios that are likely to lead to the most cost-effective use of as well as the least cost-effective use.

Costs

All substantial costs that are observed to differ between patients administered the NPWT and patients administered standard care are intended to be captured and reported as part of the economic analysis. 

We will report unit costs along with the currency and price year in each original study. These costs will then be converted to 2011 values by applying implicit price deflators for GDP of that currency and then converted into the currency most frequently observed in the articles reviewed using GDP Purchasing Power Parities (Shemilt 2010). This will allow readers of the review to make meaningful comparisons between costs in studies that may have been conducted in different countries and at different times.

The main costs are likely to be those associated with the NPWT itself, specialist and other practitioner costs as measured by time or number of visits, potential cost-savings from a change in the number of bed days in hospital, and costs stemming from differing rates of adverse events and complications (including procedures initiated due to the failure of wounds to heal, such as amputation). The key cost drivers will be identified from the studies included. This will enable users of the review to gain a clear understanding of the nature of resource use associated with negative pressure wound therapy.

Outcomes

The primary trial outcome (proportion of wounds healed) and secondary outcome (time to complete healing) are relevant to the economic analysis as they may indicate a difference in the number of hospital bed days and specialist time required and a possible improvement in quality of life for the patient.

We will examine information on the change in health-related quality of life (HR-QoL) via utilities measured by a multi-attribute utility instrument (MAUI) or other approaches (such as the time trade-off, standard gamble) where possible. Ideally these data will be reported in trials for both the group treated with NPWT and a control group receiving the comparator wound care. The utility data will need to be assessed for comparability and representativeness considering issues such as the types of wounds included, the patient populations, timing of the baseline point and follow-up collection, the MAUI used and the algorithm for scoring the MAUI. We will present discussion of the potential impact on HR-QoL attributable to the intervention as part of the analysis.

If differences can be observed in the rates of adverse events, wound infections and complications resulting from the treatment of the wound, we will discuss the economic implications as part of the economic analysis.

Unit of analysis issues

We did not anticipate any unit of analysis issues, cross over trials were excluded and cluster randomised trials were not expected for this type of intervention.

Dealing with missing data

In the event that we obtained missing data from authors, we planned an available-case analysis, based on the numbers of patients for whom outcome data were known. We also planned best-case and worst-case analyses. In the event of missing standard deviations (SD) we planned imputation from other studies or, where possible, calculation from standard errors (SE) using the formula SD = SE x √¯N , where these were available (Higgins 2011).

Assessment of heterogeneity

We assessed heterogeneity visually and by using the Chi2 test with significance being set at P < 0.10. In addition, we investigated the degree of heterogeneity by calculating the I2 statistic (Higgins 2011). We planned to explore potential causes of significant heterogeneity (> 30%) and use a random-effects approach to the analysis but this was not necessary.

Assessment of reporting biases

If sufficient studies were identified we planned to assess reporting bias using funnel plots (Higgins 2011).

Data synthesis

Where studies were clinically similar and outcome measurements comparable, we pooled results using a fixed-effect model and reported the pooled estimate together with its 95% CI. We conducted a narrative review of eligible studies where statistical synthesis of data from more than one study was not possible or considered not appropriate, for example if the I2 statistic was above 60%. There were no time-to-event data so estimates of hazard ratios (HR) and 95% confidence intervals (CI) were not required (Altman 2001).

Subgroup analysis and investigation of heterogeneity

We planned to analyse potential sources of heterogeneity using the following subgroup analyses:

  1. type of setting (community, hospital, inpatient, outpatient);

  2. type of negative pressure device (vacuum-assisted closure ((VAC® KCI, San Antonio, Texas), RENASYS systemTM (Smith & Nephew, UK), Chariker-Jeter gauze-based negative pressure systems (V1STA, Versatile-1 and EZ-Care; Smith & Nephew, Inc.);

  3. type of surgery (traumatic wounds, reconstructive procedures, other post-surgical wounds);

  4. type of comparison dressing (saline gauze, Jelonet, hydrocolloid, foam, alginate); and

  5. intermittent versus continuous negative pressure.

Sensitivity analysis

We planned to perform sensitivity analyses to explore the effect of the following criteria:

  1. concealment of allocation (allocation adequately concealed versus not reported or inadequate);

  2. duration of follow-up (no stated follow-up versus any follow-up; follow-up for < 4 weeks versus 4 weeks or greater); and

  3. type of randomisation (truly randomised with adequate method of generating the randomisation sequence versus not reported).

Results

Description of studies

See Characteristics of included studies; Characteristics of excluded studies and Characteristics of ongoing studies.

Results of the search

Interventions search

Electronic searches yielded 356 references of which we excluded 346 because they did not meet one or more of our inclusion criteria. We retrieved the remaining 10 full-text papers for inspection. Of these, we included five papers, with results from five trials (Chio 2010; Dorafshar 2011; Howell 2011; Llanos 2006; Pachowsky 2011). A search of trial registry platforms identified 17 protocols related to NPWT. Eleven of these planned to investigate chronic wounds and were ineligible. Of the six remaining trials, five named investigators and one named the company (KCI) as the investigator. We attempted contact with the five study authors, three of whom did not respond. The investigator of one of the remaining protocols stated that the planned start date for the trial was in early 2011 (Chan 2011), we are still attempting to contact another author (Graves 2011). Regarding the company trial, KCI advised us that the trial will not be conducted. No patients were enrolled in the study, all sites were closed and all site payments reconciled. No reason was provided for terminating the study. We sent emails to all the manufacturers mentioned in our search strategy. We were advised of one animal study but identified no further human trials meeting our inclusion criteria.

Economic analysis search

Electronic searches yielded 115 references, none of which met our inclusion criteria.

Included studies

Types of participants

A total of 280 participants were enrolled in the five included trials (Chio 2010; Dorafshar 2011; Howell 2011; Llanos 2006; Pachowsky 2011). Participants in two trials underwent skin grafts. Chio 2010 investigated the forearm donor site among 54 patients undergoing a radial forearm free flap. Llanos 2006 enrolled 60 burns patients who had split-thickness skin grafts to their burn site. Of the remaining trials, Dorafshar 2011 recruited 87 patients with acute wounds resulting from trauma, surgery or dehiscence; Howell 2011 included 60 patients undergoing a total knee arthroplasty who were obese and at risk of infection and Pachowsky 2011 enrolled patients with closed surgical wounds after a total hip arthroplasty. Three trials were conducted in the USA (Chio 2010; Dorafshar 2011; Howell 2011) one in Chile (Llanos 2006) and one in Germany (Pachowsky 2011).

Types of interventions

In two trials (Chio 2010; Howell 2011), the negative pressure device, vacuum-assisted closure (VAC® KCI, San Antonio, Texas) set to -125 mmHg was compared to a standard dressing. The comparison standard dressing in the Chio 2010 trial consisted of sterile surgical foam, cut to size and wrapped in Adaptic dressing whereas wounds in the Howell 2011 trial were covered with a sterile gauze dressing that was secured with a perforated, stretchable cloth tape. Pachowsky 2011 used the PREVENA TM system (KCI, San Antonio, Texas) for the intervention treatment and a dry wound dressing as the control treatment. By contrast, Llanos 2006 used the hospital's central aspiration system at a pressure of 80 mmHg to achieve a vacuum. The comparison dressing was identical but no pressure was applied to the aspiration tubing. Dorafshar 2011 compared two negative pressure systems, (VAC® KCI, San Antonio, Texas and GSUC). The intervention dressing 'GSUC', was a locally developed system based on a gauze dressing moistened with 0.9% normal saline and sealed with an occlusive cover. A red rubber catheter was placed in the middle of the dressing and attached to continuous wall suction at 75 to 80 mm Hg.

Types of outcomes

Two comparisons are included; the first is negative pressure closure versus standard dressing. Incidence of adverse events was the only pre-specified primary outcome for this review reported in all studies for this comparison (Chio 2010; Howell 2011; Llanos 2006; Pachowsky 2011). Adverse events included wound blisters and deep wound infection (Howell 2011), seromas (Pachowsky 2011) and other wound complications. For example Chio 2010 defined wound complications as a combination of skin graft failure and tendon exposure. We also included "need for re-covering procedure" as a wound complication in the Llanos 2006 trial. Outcomes were measured in the Chio 2010 trial two weeks after surgery, in the Llanos 2006 study, outcome data were measured when wounds were uncovered, four days post surgery, Howell 2011 followed patients up for 12 months and in the Pachowsky 2011 trial, ultrasound examinations were conducted on day five and day 10 post surgery. The second comparison was one negative pressure closure versus another negative pressure closure (GSUC versus VAC® KCI, San Antonio, Texas). One trial was included in this comparison (Dorafshar 2011). Outcomes of interest to this review included adverse events, pain and cost.

Other outcomes, such as median graft loss, percentage of graft loss, time from grafting to hospital discharge and rates of change in surface area and wound volume, were reported by trialists, but these data were not included in our pre-specified primary or secondary outcomes.

Excluded studies

Five trials were excluded (Hu 2009; Johannesson 2008; Kim 2007; Moues 2004; Moues 2007). The intervention dressing in one trial was not a negative pressure device (Johannesson 2008); one was not a randomised controlled trial (Kim 2007); and three did not include acute wounds (Hu 2009; Moues 2004; Moues 2007). Two further trials included both chronic and acute wounds but results were not presented separately and, despite attempts to contact authors, no further information could be obtained (Braakenburg 2006; Moisidis 2004), these studies are currently classified as awaiting assessment as we continue in our efforts to obtain further information.

Risk of bias in included studies

See Figure 1 for a risk of bias summary.

Figure 1.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Sequence generation

Three of the five investigators described some form of process to generate the random allocation list. A computer-based random number generator was used in two trials (Chio 2010; Llanos 2006) and a web-based random number generator in the third (Dorafshar 2011). In the two other studies (Howell 2011; Pachowsky 2011) how the sequence was generated was not specified.

Allocation concealment

The method used for allocation concealment was unclear in the Chio 2010; Dorafshar 2011 and Howell 2011 trials. In the Dorafshar 2011 study, participants were allocated to their group "by drawing a previously prepared card", however, it was unclear if cards were concealed until the point of randomisation. "Blinded envelopes" were used in the Howell 2011 trial, we have assumed that 'blinded' indicated opaque however, we have been unable to confirm this with the author. Allocation in the Llanos 2006 study was not concealed since the theatre nurse allocated patients from a randomised list and the next allocation would have been predictable.

Blinding

Participants and personnel

The appearance of dressings was dissimilar in the Chio 2010; Dorafshar 2011; Howell 2011 and Pachowsky 2011 trials, so blinding was impossible. Dressings were identical in the Llanos 2006 trial and both groups had tubing attached to a suction apparatus. However, patients and staff would almost certainly have been aware if suction was activated.

Outcome assessment

Outcome measurement was not blinded in two of the trials (Chio 2010; Dorafshar 2011) and in the Howell 2011 trial it was unclear if whether outcome assessment was blinded. Ultrasound was used to assess outcomes in the Pachowsky 2011 trial but whether the ultrasonographer was blind to allocation was not stated. However, in the Llanos 2006 study, assessment was by photographs and the person assessing the photographs was "masked to which intervention the patient had received".

Incomplete outcome data

All participants were included in the analyses of four trials (Dorafshar 2011; Howell 2011; Llanos 2006; Pachowsky 2011). Four (7.4%) participants were unavailable for follow-up in the Chio 2010 trial, all of whom were assigned to the negative pressure group therefore Chio 2010 was deemed to be at high risk of attrition bias.

Selective reporting

All of each study's pre-specified outcomes, as defined in the papers, were reported in the results. No published protocol was available for four trials (Chio 2010; Howell 2011; Llanos 2006; Pachowsky 2011). In the Dorafshar 2011 trial, measures reflected the pre-defined outcomes listed in the published protocol (NCT00724750). However, the study began in 2006 but the protocol was first published in July 2008, so there is a potential for study characteristics to have changed before or during the study.

Other potential sources of bias

A manufacturer funded the Howell 2011 trial, which also contained unequal numbers in each arm of the trial. This trial was stopped early due to an unacceptably higher rate of blisters among patients in the negative pressure group. The Pachowsky 2011 trial was also manufacturer funded and one of the authors received conference funding from the manufacturer of the trial intervention.

Effects of interventions

Comparison 1: Negative pressure wound therapy versus standard dressing (four trials, 189 participants)

Primary
Proportion of surgical wounds healing by primary intention that completely heal

Results for this outcome were not provided by either Chio 2010; Llanos 2006 or Pachowsky 2011. All of the wounds in the Howell 2011 trial healed.

Mortality

Although not directly reported, results indicate that no participant died during any of the trials (Chio 2010; Howell 2011; Llanos 2006; Pachowsky 2011).

Adverse events

Four trials of 189 participants reported data for this outcome (Chio 2010; Howell 2011; Llanos 2006; Pachowsky 2011). Adverse events were reported in two trials involving skin loss following grafting and were pooled Chio 2010; Llanos 2006). There was no statistically significant difference between groups for this outcome (NPWT 13/53 24.5%; standard dressing 24/57 42.1%); the RR was 0.61 (95% CI 0.33 to 1.13) Analysis 1.1. In the Howell 2011 trial, fracture blisters and deep wound infections were included as adverse events. Significantly more fracture blisters were observed in the NPWT group (15/24; 62.5%) when compared with the standard dressing group (3/36;8.3%); RR 7.50 (95% CI 2.43 to 23.14; p = 0.0005) Analysis 1.2. In the same study, one deep wound infection occurred in each group Howell 2011. The adverse events reported in the Pachowsky 2011 trial were seromas but there was no significant difference between the groups. In the NPWT group 4/9 (44.9%) participants developed a seroma compared with 9/10 (90%) participants in the standard dressing group; RR 0.09 (95% CI 0.01 to 1.03) Analysis 1.3 (p = >0.05).

Secondary
Time to complete healing

In the Howell 2011 trial, there was no reported difference in time to wound closure between groups (negative pressure 4.3 days; static pressure 4.1 days). Neither of the other three trials provided data for this outcome (Chio 2010; Llanos 2006; Pachowsky 2011).

Pain

Results for this outcome were not provided by any of the authors (Chio 2010; Howell 2011; Llanos 2006; Pachowsky 2011).

Quality of life

None of the included studies provided measures for this outcome.

Cost

None of the included studies provided measures for this outcome.

Comparison 2: One negative pressure closure method (GSUC) versus another negative pressure closure method (VAC® KCI, San Antonio, Texas) (one trial 87 participants)

Primary
Proportion of surgical wounds healing by primary intention that completely heal

There were no data for this outcome.

Mortality

Although not directly reported, results at follow-up indicate that none of the participants died during the study.

Adverse events

In their study of 87 participants, Dorafshar 2011 reported a higher adverse rate in the VAC® therapy group, all of these were haematomas (VAC® 3/42; GSUC 0/45); the odds ratio (OR) was 0.13 (95% CI 0.01 to 2.51); P = 0.18) (Analysis 2.1).

Secondary
Time to complete healing

There were no data for this outcome.

Pain

Pain before, during and after dressing changes was reported to be lower in the GSUC group when compared to the VAC® group (P = 0.02) (Dorafshar 2011).

Wound complications
Quality of life

Quality of life was not measured in this trial.

Cost

One within-trial cost analysis was undertaken by Dorafshar 2011, who reported that the mean cost of supply equipment for VAC® therapy was USD 96.51/day compared to USD 4.22/day for the GSUC therapy (P = 0.01). The daily labour costs to change the dressings were USD 21.18/day for GSUC versus USD 25.55/day for VAC® (P = 0.11). Overall, there was a greater than fourfold increase in costs in the VAC® group.

Discussion

Summary of main results

Wound healing

This systematic review examined the evidence from randomised controlled trials (RCTs) that focused on the effectiveness of negative pressure wound therapy for acute surgical wounds. Evidence is limited, with only five small trials of 280 participants meeting the inclusion criteria. Although negative pressure wound therapy (NPWT) is being widely used and is supported for use for a range of surgical applications (Krug 2011) there is no evidence to support or refute the effectiveness of NPWT to improve healing rates or to reduce time to complete healing from this review. Our pre-defined primary outcome, 'the proportion of wounds that completely heal', may be a useful measure for chronic wounds, where NPWT is widely used. However, it has become clear to us that this outcome is not appropriate for surgery that is expected to heal by primary intention; most clean surgical wounds will completely heal in a relatively short time. Moreover, determining when a surgical incision is 'completely healed' is difficult. Consequently, wound healing should not be included as a primary outcome for future updates.

Adverse events

Trials included in this review included orthopaedic surgery, skin grafts and general surgery. With the exception of two trials involving skin graft survival, clinical heterogeneity and dissimilar outcomes prevented pooling results. Two trials were suggestive of a benefit of NPWT for skin graft survival (Chio 2010; Howell 2011) and one for the prevention of seromas (Pachowsky 2011) but all of these trials were at unclear or high risk of bias, reducing confidence in the results. Conversely, increased harm through the use of NPWT was shown in one trial (Howell 2011). This was the formation of skin blisters around the edge of the NPWT dressing. In this trial, the dressing-associated blister rate was 63% in the NPWT group (Howell 2011), which compares poorly with rates between 2.4% to 26% in other recent trials where modern wound dressings have been used for postoperative orthopaedic wounds (Abuzakuk 2006; Koval 2007; Ravenscroft 2006; Ravnskog 2011) and was the reason for early termination of the trial. It is unclear why skin blisters occur following orthopedic surgery but may be due postoperative swelling, leading to sheer or friction when the securing tape is stretched (Ravenscroft 2006).

It is also unclear which system should be used to deliver the therapy. Although there is substantial literature related to wound healing using the vacuum-assisted closure (VAC® KCI, San Antonio, Texas) system (Morykwas 1997), our review failed to support the use of a commercial device for acute wounds. The systems are very expensive and our results suggest that alternative, cheaper methods may be as effective. For example, in one trial where the VAC® system was compared to a standard dressing, there was a 10% reduction in wound complications in the VAC® group (Chio 2010). However, in a similar study, where negative pressure was achieved using the hospital's aspiration system, the wound complication rate in the negative pressure group was 23% less than in the standard dressing group (Llanos 2006). Although the difference was not statistically significant in either trial, the results may be reassuring to those who cannot afford the expense of hiring the equipment required for VAC® and similar commercial systems. Additional evidence for the safety of a hospital-devised system was provided in the most recent trial where the VAC® system was directly compared with a method based on a sealed gauze dressing and the hospital's wall suction (Dorafshar 2011). In that study, there was no difference in the wound complication rate between the two groups.

Cost

When compared to a commercial system of delivering NPWT, equipment costs were four times lower when a hospital-based system was used (USD 25.40/day compared to USD 110.06/day). This was due entirely to higher equipment cost for the commercial product; the cost for labour to change the dressings was similar (Dorafshar 2011). Although these results are from only one trial, until equipment costs from commercial manufactures are substantially reduced, additional studies are unlikely to change this finding. In attempts to find ways around these costs, innovative attempts to develop hospital-based systems are increasing (Mody 2008; Perez 2010; Rozen 2008; Shalom 2008).

Pain

In one study pain levels during and after dressing changes were significantly lower in the hospital-based negative pressure group (Dorafshar 2011). However, the hospital-based device used continuous suction at 75 to 80 mm Hg, whereas the VAC® system was set between 75 to 125 mm Hg, which may account for the reported difference in perceived pain.

Overall completeness and applicability of evidence

Indications for the use of NPWT in closed surgery are broadening (DeCarbo 2010; Pachowsky 2011) with a range of new systems on the market, including those designed for use on clean, closed wounds (Allen 2011). However, studies eligible for inclusion in our review represented a relatively narrow focus; there were two skin graft trials, one trial that included patients with acute wounds from trauma or surgery and two others that recruited patients undergoing a planned total knee or hip arthroplasty. The largest trial enrolled 87 patients. Negative pressure levels varied between trials and between device types, with hospital aspiration systems generally using a lower pressure than the VAC®) system. Whether different pressures produce different outcomes is unclear from our results but animal studies indicate that performance is similar across the range of pressures used in the trials we included (Morykwas 2001). Another limitation was a variation in the follow-up times, which ranged from the fourth postoperative day (Llanos 2006) to 12 months post surgery (Howell 2011). Finally, included trials were geographically limited; three were conducted in North America, one in South America and one in Germany, further restricting the external validity of results. In light of these limitations, there remains uncertainty about whether NPWT should be used at all for closed surgical wounds, unless there are reasons to believe that the wound may be difficult to heal. There are also important questions about the use of NPWT for orthopaedic surgery; the one trial in this category was terminated early because of high blister rates.

Quality of the evidence

Limitations in study design and implementation

Risk of bias was assessed according to six domains: sequence generation; allocation concealment; blinding; selective outcome reporting, incomplete follow-up and other potential biases. Our assessments of the risk of bias for a number of these domains in all of the included studies showed limitations in study design and implementation, these have been reported elsewhere in the review Figure 1. Of particular concern, in a study where blinding of the intervention is difficult or impossible, was uncertainty about allocation concealment and outcome assessment blinding. Accordingly, the quality of the evidence was considered unclear for all of the outcomes.

Indirectness of evidence

The review was limited by a lack of conformity; in both the experimental and the control intervention. For example the negative pressure device varied between studies as did the control dressing. Consequently, the evidence was restricted to indirect comparisons between these varied interventions. Additionally, the review aimed to assess NPWT for acute surgical wounds but the type of surgeries were limited. As a result, the evidence may be regarded as indirect for other types of surgery. Finally, direct evidence of the effect of the intervention on wound infection or dehiscence, arguably the most important adverse outcomes of surgery, was reported in only one study. Taken together, these limitations restrict confident decision making in regards to the use of NPWT for acute wounds.

Unexplained heterogeneity or inconsistency of results

The only outcome which could be pooled was an assessment of skin graft survival. Consequently, we were unable to evaluate the effects of the intervention across studies.

Imprecision of results

In the only pooled outcome, confidence intervals were quite narrow but only two small studies of skin graft failure were included Analysis 1.1. Of the other, single study outcomes, only one showed evidence of effect. In this trial, where NPWT was more likely to cause fracture blisters than the standard dressing, we have included the confidence intervals to indicate the high level of uncertainty around the effect size Analysis 1.2.  Further research is therefore very likely to have an important impact on the confidence of the estimate of effect for all of the measured outcomes and is likely to change the estimate.

Publication bias

We feel confident that our comprehensive electronic searches identified all existing, published randomised controlled trials addressing the review question, helping to limit bias in the review process. However, most of the trials identified through a search of the Clinical Trial Registries have not been published and we were unable to track down any information about them. Moreover, the scant contribution of the five included trials, in the face of such wide use of NPWT, is unusual. These two factors may or may not indicate publication bias.

Potential biases in the review process

Clearly described procedures were followed to prevent potential bias in the review process. A careful literature search was conducted and the methods we used were transparent and reproducible. None of the authors has any conflict of interest. It is possible that trials published in journals that were outside of our search strategy may have been missed.

Agreements and disagreements with other studies or reviews

Our results are consistent with the most recent evidence-based recommendations for the use of NPWT, which cover a range of applications, including NPWT for acute wounds (Krug 2011). The systematic review by Ubbink 2008 was published before three of our included trials were undertaken; their review also included an earlier trial that we had excluded from our review (Moisidis 2004) so results are not comparable. However, our findings are in agreement with other non-randomised studies that show that NPWT may reduce wound complications (Blume 2010; DeCarbo 2010; Kim 2007). Other randomised (Hu 2009) and non-randomised studies have also shown a marked cost benefit when non-commercial applications were compared with commercial products (Rozen 2008; Shalom 2008). In one of these studies, a net saving per patient was USD 2603 (Rozen 2008).

Authors' conclusions

Implications for practice

Evidence for the effectiveness of negative pressure wound therapy (NPWT) for complete healing of acute wounds remains unclear, as does the effect of NPWT on time to complete healing. Rates of graft loss may lower when NPWT is used, but hospital-based products are as effective in this area as commercial applications. There are clear cost benefits when non-commercial systems are used to create the negative pressure required for wound therapy, with no reduction in clinical outcome. Pain levels are also rated lower when hospital systems are compared with their commercial counterparts. The high incidence of blisters occurring when NPWT is used following orthopaedic surgery suggests that the therapy should be limited until safety in this population is established.

Implications for research

There is an urgent need for suitably powered, high-quality trials to evaluate the effectiveness of the newer NPWT products, which are designed for use on clean, closed surgical incisions. Such trials should focus initially on wounds that may be difficult to heal, such as sternal wounds or surgeries on obese patients. Given the large cost differences between products, further trials comparing different types of NPWT are also justified. Full economic evaluations, including those associated with the NPWT itself, specialist and other practitioner costs as measured by time or number of visits, potential cost-savings from a change in the number of bed days in hospital, and costs stemming from differing rates of adverse events and complications (including procedures initiated due to the failure of wounds to heal, such as amputation) need to be included. This will enable users of any future review to gain a clear understanding of the nature of resource use associated with negative pressure wound therapy. To facilitate assessment, future trials that combine different types of conditions (acute, sub-acute and chronic) should present results of each condition group separately. It may also be useful to test NPWT at various pressures.

Acknowledgements

The authors would like to thank the peer referees: Wounds Group editors - Kurinchi Gurusamy, Dirk Ubbink, Gill Worthy and referees - Fausto Biancari, Susanne Cunliffe, Patricia Davies, Jo Dumville, Ian Schemilt and copy editor Jenny Bellorini.

The NHMRC has provided funding for this review from its Centre of Research Excellence Scheme, which funds one or more of the authors.

Data and analyses

Download statistical data

Comparison 1. Negative pressure versus standard dressing
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Adverse events2110Risk Ratio (M-H, Random, 95% CI)0.61 [0.33, 1.13]
2 Fracture blisters1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
3 Seroma1 Odds Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Negative pressure versus standard dressing, Outcome 1 Adverse events.

Analysis 1.2.

Comparison 1 Negative pressure versus standard dressing, Outcome 2 Fracture blisters.

Analysis 1.3.

Comparison 1 Negative pressure versus standard dressing, Outcome 3 Seroma.

Comparison 2. Negative pressure GSUC versus negative pressure VAC
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Adverse events187Risk Ratio (M-H, Fixed, 95% CI)0.13 [0.01, 2.51]
Analysis 2.1.

Comparison 2 Negative pressure GSUC versus negative pressure VAC, Outcome 1 Adverse events.

Appendices

Appendix 1. Ovid MEDLINE effectiveness search strategy

1 exp Negative-Pressure Wound Therapy/
2 exp Suction/
3 exp Vacuum/
4 (negative pressure or negative-pressure or TNP).tw.
5 (sub-atmospheric or subatmospheric).tw.
6 ((seal* adj surface*) or (seal* adj aspirat*)).tw.
7 (wound adj2 suction*).tw.
8 (wound adj5 drainage).tw.
9 ((foam adj suction) or (suction adj dressing*)).tw.
10 (vacuum assisted closure technique or VAC).tw.
11 ((vacuum adj therapy) or (vacuum adj dressing*) or (vacuum adj seal*) or (vacuum adj closure) or (vacuum adj compression) or (vacuum adj pack*) or (vacuum adj drainage) or (suction* adj drainage)).tw.
12 or/1-11
13 exp Surgical Wound Infection/
14 exp Surgical Wound Dehiscence/
15 (surg* adj5 infect*).tw.
16 (surg* adj5 wound*).tw.
17 (surg* adj5 site*).tw.
18 (surg* adj5 incision*).tw.
19 (surg* adj5 dehisc*).tw.
20 (wound* adj5 dehisc*).tw.
21 (wound* adj5 dehisc*).tw.
22 or/13-21
23 12 and 22
24 randomized controlled trial.pt.
25 controlled clinical trial.pt.
26 randomized.ab.
27 placebo.ab.
28 clinical trials as topic.sh.
29 randomly.ab.
30 trial.ti.
31 or/24-30
32 (animals not (humans and animals)).sh.
33 31 not 32
34 23 and 33
35 (2005* or 2006* or 2007* or 2008* or 2009* or 2010*).ed.
36 34 and 35

Appendix 2. Ovid EMBASE effectiveness search strategy

1 exp suction drainage/
2 exp vacuum assisted closure/
3 (negative pressure or negative-pressure or TNP).tw.
4 (sub-atmospheric or subatmospheric).tw.
5 ((seal* adj surface*) or (seal* adj aspirat*)).tw.
6 (wound adj2 suction*).tw.
7 (wound adj5 drainage).tw.
8 ((foam adj suction) or (suction adj dressing*)).tw.
9 (vacuum assisted closure technique or VAC).tw.
10 ((vacuum adj therapy) or (vacuum adj dressing*) or (vacuum adj seal*) or (vacuum adj closure) or (vacuum adj compression) or (vacuum adj pack*) or (vacuum adj drainage) or (suction* adj drainage)).tw.
11 or/1-10
12 exp Surgical Wound Infection/
13 exp Surgical Wound Dehiscence/
14 (surg* adj5 infection*).tw.
15 (surg* adj5 wound*).tw.
16 (surg* adj5 site*).tw.
17 (surg* adj5 incision*).tw.
18 (surg* adj5 dehisc*).tw.
19 (wound* adj5 dehisc*).tw.
20 or/12-19
21 11 and 20
22 Clinical trial/
23 Randomized controlled trials/
24 Random Allocation/
25 Single-Blind Method/
26 Double-Blind Method/
27 Cross-Over Studies/
28 Placebos/
29 Randomi?ed controlled trial$.tw.
30 RCT.tw.
31 Random allocation.tw.
32 Randomly allocated.tw.
33 Allocated randomly.tw.
34 (allocated adj2 random).tw.
35 Single blind$.tw.
36 Double blind$.tw.
37 ((treble or triple) adj blind$).tw.
38 Placebo$.tw.
39 Prospective Studies/
40 or/22-39
41 Case study/
42 Case report.tw.
43 Abstract report/ or letter/
44 or/41-43
45 40 not 44
46 animal/
47 human/
48 46 not 47
49 45 not 48
50 21 and 49
51 (2009* or 2010* or 2011*).em.
52 50 and 51

Appendix 3. EBSCO CINAHL effectiveness search strategy

S22 S12 and S21
S21 S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20
S20 TI wound* N5 dehisc* or AB wound* N5 dehisc*
S19 TI surg* N5 dehisc* or AB surg* N5 dehisc*
S18 TI surg* N5 incision* or AB surg* N5 incision*
S17 TI surg* N5 site* or AB surg* N5 site*
S16 TI surg* N5 wound* or AB surg* N5 wound*
S15 TI surg* N5 infection* or AB surg* N5 infection*
S14 (MH "Surgical Wound Dehiscence")
S13 (MH "Surgical Wound Infection")
S12 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11
S11 TI ( foam suction or suction dressing* or suction drainage ) or AB ( foam suction or suction dressing* or suction drainage )
S10 AB vacuum therapy or vacuum dressing* or vacuum seal* or vacuum closure or vacuum compression or vacuum pack or vacuum drainage
S9 TI vacuum therapy or vacuum dressing* or vacuum seal* or vacuum closure or vacuum compression or vacuum pack or vacuum drainage
S8 TI wound N5 drainage or AB wound N5 drainage
S7 TI wound N5 suction* or AB wound N5 suction*
S6 TI ( seal* N1 surface* or seal* N1 aspirat* ) or AB ( seal* N1 surface* or seal* N1 aspirat* )
S5 TI ( sub-atmospheric or subatmospheric ) or AB ( sub-atmospheric or subatmospheric )
S4 TI ( negative pressure or negative-pressure or TNP ) or AB ( negative pressure or negative-pressure or TNP )
S3 (MH "Negative Pressure Wound Therapy")
S2 (MH "Vacuum")
S1 (MH "Suction+")

Appendix 4. Ovid MEDLINE economics search strategy

1 exp Negative-Pressure Wound Therapy/
2 exp Suction/
3 exp Vacuum/
4 (negative pressure or negative-pressure or TNP).tw.
5 (sub-atmospheric or subatmospheric).tw.
6 ((seal* adj surface*) or (seal* adj aspirat*)).tw.
7 (wound adj2 suction*).tw.
8 (wound adj5 drainage).tw.
9 ((foam adj suction) or (suction adj dressing*)).tw.
10 (vacuum assisted closure technique or VAC).tw.
11 ((vacuum adj therapy) or (vacuum adj dressing*) or (vacuum adj seal*) or (vacuum adj closure) or (vacuum adj compression) or (vacuum adj pack*) or (vacuum adj drainage) or (suction* adj drainage)).tw.
12 or/1-11
13 exp Surgical Wound Infection/
14 exp Surgical Wound Dehiscence/
15 (surg* adj5 infect*).tw.
16 (surg* adj5 wound*).tw.
17 (surg* adj5 site*).tw.
18 (surg* adj5 incision*).tw.
19 (surg* adj5 dehisc*).tw.
20 (wound* adj5 dehisc*).tw.
21 (wound* adj5 dehisc*).tw.
22 or/13-21
23 12 and 22
24 economics/
25 exp "costs and cost analysis"/
26 economics, dental/
27 exp "economics, hospital"/
28 economics, medical/
29 economics, nursing/
30 economics, pharmaceutical/
31 (economic* or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic*).ti,ab.
32 (expenditure* not energy).ti,ab.
33 value for money.ti,ab.
34 budget*.ti,ab.
35 or/24-34
36 ((energy or oxygen) adj cost).ti,ab.
37 (metabolic adj cost).ti,ab.
38 ((energy or oxygen) adj expenditure).ti,ab.
39 or/36-38
40 35 not 39
41 letter.pt.
42 editorial.pt.
43 historical article.pt.
44 or/41-43
45 40 not 44
46 Animals/
47 Humans/
48 46 not (46 and 47)
49 45 not 48
50 23 and 49

Appendix 5. Ovid EMBASE economics search strategy

1 exp suction drainage/
2 exp vacuum assisted closure/
3 (negative pressure or negative-pressure or TNP).tw.
4 (sub-atmospheric or subatmospheric).tw.
5 ((seal* adj surface*) or (seal* adj aspirat*)).tw.
6 (wound adj2 suction*).tw.
7 (wound adj5 drainage).tw.
8 ((foam adj suction) or (suction adj dressing*)).tw.
9 (vacuum assisted closure technique or VAC).tw.
10 ((vacuum adj therapy) or (vacuum adj dressing*) or (vacuum adj seal*) or (vacuum adj closure) or (vacuum adj compression) or (vacuum adj pack*) or (vacuum adj drainage) or (suction* adj drainage)).tw.
11 or/1-10
12 exp Surgical Wound Infection/
13 exp Surgical Wound Dehiscence/
14 (surg* adj5 infection*).tw.
15 (surg* adj5 wound*).tw.
16 (surg* adj5 site*).tw.
17 (surg* adj5 incision*).tw.
18 (surg* adj5 dehisc*).tw.
19 (wound* adj5 dehisc*).tw.
20 or/12-19
21 11 and 20
22 health-economics/
23 exp economic-evaluation/
24 exp health-care-cost/
25 exp pharmacoeconomics/
26 or/22-25
27 (econom* or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic*).ti,ab.
28 (expenditure* not energy).ti,ab.
29 (value adj2 money).ti,ab.
30 budget*.ti,ab.
31 or/27-30
32 26 or 31
33 letter.pt.
34 editorial.pt.
35 note.pt.
36 or/33-35
37 32 not 36
38 (metabolic adj cost).ti,ab.
39 ((energy or oxygen) adj cost).ti,ab.
40 ((energy or oxygen) adj expenditure).ti,ab.
41 or/38-40
42 37 not 41
43 exp animal/
44 exp animal-experiment/
45 nonhuman/
46 (rat or rats or mouse or mice or hamster or hamsters or animal or animals or dog or dogs or cat or cats or bovine or sheep).ti,ab,sh.
47 or/43-46
48 exp human/
49 exp human-experiment/
50 or/48-49
51 47 not (47 and 50)
52 42 not 51
53 21 and 52

Appendix 6. EBSCO CINAHL economics search strategy

S45 S22 and S44
S44 S40 NOT S43
S43 S19 NOT (S19 AND S42)
S42 MH "Human"
S41 MH "Animal Studies"
S40 S35 NOT S39
S39 S36 or S37 or S38
S38 PT commentary
S37 PT letter
S36 PT editorial
S35 S33 OR S34
S34 TI (cost or costs or economic* or pharmacoeconomic* or price* or pricing*) OR AB (cost or costs or economic* or pharmacoeconomic* or price* or pricing*)
S33 S29 OR S32
S32 S30 OR S31
S31 MH "Health Resource Utilization"
S30 MH "Health Resource Allocation"
S29 S23 NOT S28
S28 S24 or S25 or S26 or S27
S27 MH "Business+"
S26 MH "Financing, Organized+"
S25 MH "Financial Support+"
S24 MH "Financial Management+"
S23 MH "Economics+"
S22 S12 and S21
S21 S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20
S20 TI wound* N5 dehisc* or AB wound* N5 dehisc*
S19 TI surg* N5 dehisc* or AB surg* N5 dehisc*
S18 TI surg* N5 incision* or AB surg* N5 incision*
S17 TI surg* N5 site* or AB surg* N5 site*
S16 TI surg* N5 wound* or AB surg* N5 wound*
S15 TI surg* N5 infection* or AB surg* N5 infection*
S14 (MH "Surgical Wound Dehiscence")
S13 (MH "Surgical Wound Infection")
S12 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11
S11 TI foam suction or suction dressing* or suction drainage or AB foam suction or suction dressing* or suction drainage
S10 AB vacuum therapy or vacuum dressing* or vacuum seal* or vacuum closure or vacuum compression or vacuum pack or vacuum drainage
S9 TI vacuum therapy or vacuum dressing* or vacuum seal* or vacuum closure or vacuum compression or vacuum pack or vacuum drainage
S8 TI wound N5 drainage or AB wound N5 drainage
S7 TI wound N5 suction* or AB wound N5 suction*
S6 TI seal* N1 surface* or seal* N1 aspirat* or AB seal* N1 surface* or seal* N1 aspirat*
S5 TI sub-atmospheric or subatmospheric or AB sub-atmospheric or subatmospheric
S4 TI negative pressure or negative-pressure or TNP or AB negative pressure or negative-pressure or TNP
S3 (MH "Negative Pressure Wound Therapy")
S2 (MH "Vacuum")
S1 (MH "Suction+")

Appendix 7. Risk of bias criteria

1.  Was the allocation sequence randomly generated?

Low risk of bias

The investigators describe a random component in the sequence generation process such as: referring to a random number table; using a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.

High risk of bias

The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.

Unclear

Insufficient information about the sequence generation process to permit judgement of low or high risk of bias.

2.  Was the treatment allocation adequately concealed?

Low risk of bias

Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.

High risk of bias

Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non­opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear

Insufficient information to permit judgement of low or high risk of bias. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.

3.  Blinding - was knowledge of the allocated interventions adequately prevented during the study?

Low risk of bias

Any one of the following.

  • No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

  • Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

  • Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of others unlikely to introduce bias.

High risk of bias

Any one of the following.

  • No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.

  • Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.

  • Either participants or some key study personnel were not blinded, and the non-blinding of others likely to introduce bias.

Unclear

Any one of the following.

  • Insufficient information to permit judgement of low or high risk of bias.

  • The study did not address this outcome.

4.  Were incomplete outcome data adequately addressed?

Low risk of bias

Any one of the following.

  • No missing outcome data.

  • Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias).

  • Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.

  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.

  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size.

  • Missing data have been imputed using appropriate methods.

High risk of bias

Any one of the following.

  • Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups.

  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate.

  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size.

  • ‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.

  • Potentially inappropriate application of simple imputation.

Unclear

Any one of the following.

  • Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomised not stated, no reasons for missing data provided).

  • The study did not address this outcome.

5.  Are reports of the study free of suggestion of selective outcome reporting?

Low risk of bias

Any of the following.

  • The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way.

  • The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon)

High risk of bias

Any one of the following.

  • Not all of the study’s pre-specified primary outcomes have been reported.

  • One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified.

  • One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect).

  • One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.

  • The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear

Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.

6.  Other sources of potential bias

Low risk of bias

The study appears to be free of other sources of bias.

High risk of bias

There is at least one important risk of bias. For example, the study:

  • had a potential source of bias related to the specific study design used; or

  • had extreme baseline imbalance; or

  • has been claimed to have been fraudulent; or

  • had some other problem.

Unclear

There may be a risk of bias, but there is either:

  • insufficient information to assess whether an important risk of bias exists; or

  • insufficient rationale or evidence that an identified problem will introduce bias.

 

Appendix 8. Glossary of terms

TermDescription
DehiscenceWound dehiscence is a complication of surgery in which a wound breaks open along the line of the surgical incision.
GSUCGSUC is a system of negative pressure wound therapy. It is based on a gauze dressing moistened with 0.9% normal saline into which a red rubber catheter is inserted. The dressing is then sealed with an occlusive cover and continuous wall suction at 75 to 80 mm Hg is applied.
Negative pressure wound therapy (NPWT)NPWT is based on a closed sealed system that produces negative pressure to the wound surface. The wound is covered or packed with an open-cell foam or
gauze dressing and sealed with an occlusive drape. Intermittent or continuous suction is maintained by connecting suction tubes from the wound dressing to a vacuum pump and liquid waste collector. Standard negative pressure rates range between 50 and 125 mm Hg (Ubbink 2008; Vikatmaa 2008).
Risk ratio (RR)The risk ratio or relative risk (RR) is the probability that a member of a group who is exposed to an intervention will develop an event relative to the probability that a member of an unexposed group will develop that same event.

What's new

DateEventDescription
13 November 2013AmendedAcknowledgement added to the funders

History

Protocol first published: Issue 8, 2011
Review first published: Issue 4, 2012

DateEventDescription
16 May 2012Amendedadjustments to text

Contributions of authors

Contributions of editorial base:

Nicky Cullum: edited the protocol; advised on methodology, interpretation and protocol content. Approved the final review prior to submission.
Sally Bell-Syer: co-ordinated the editorial process. Advised on methodology, interpretation and content. Edited and copy edited the review.
Ruth Foxlee: designed the search strategy and edited the search methods section.

Declarations of interest

Prof Scuffham is the director of a unit contracted to the Australian Department of Health and Ageing to undertake external evaluations of industry submissions to the PBAC.
Joan Webster, Monica Stankiewicz, Karen Sherriff, Wendy Chaboyer - none declared.

Sources of support

Internal sources

  • Royal Brisbane and Women's Hospital, Australia.

    Time to conduct review

  • Griffith University, Australia.

    Time to conduct review

External sources

  • NIHR/Department of Health (England), (Cochrane Wounds Group), UK.

Differences between protocol and review

We added one intervention: comparisons between different negative pressure devices.

The list of abstracted data was expanded to include:

  • study dates;

  • number of participants per group;

  • information about ethics approval, consent and conflict of interest.

In trials of skin grafts, graft failure is an important outcome. We failed to include this as either a primary or secondary outcome but believe, for future updates that skin graft failure should be included. We also failed to include length of hospital stay, which is important for any economic analysis. Consequently, graft failure and length of hospital stay have been included as additional outcomes post hoc.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Chio 2010

Methods

Study design: randomised controlled trial
Ethics and informed consent: ethics approved and consent obtained

Sample size calculation: yes

ITT analysis: patients analysed in groups to which they were assigned but 4 participants, who did not present for follow-up, were not included in the analysis

Participants Location: Columbus, Ohio, USA
Mean age Group 1: 62.1;Mean age Group 2: 58.1
Inclusion criteria: patients scheduled to undergo radial forearm free flap
Exclusion criteria: none stated
Interventions

Aim/s: to evaluate the effectiveness of negative pressure dressings compared with static pressure dressings in the prevention of graft failure
Intervention/s in both groups: "In all subjects, iodine petroleum–impregnated gauze rolls were placed over the skin graft in the inter-tendon spaces, followed by coverage with a sheet of Adaptic nonadherent dressing (Johnson & Johnson, Langhorne, PA).

Dressings in both treatment groups were left in place for a total of six days, after which all dressings were then taken down, and the donor site dressed with Adaptic and circumferential gauze roll for a total of two weeks".

Group 1 (NPD) intervention: "foam specifically designed for use with the negative pressure device (V.A.C. device; KCI, San Antonio, TX) was cut and the arm covered with an occlusive dressing. The vacuum device was attached and activated intraoperatively and set to –125 mmHg with adequate seal verified. No immobilizing splint was used".

Group 2 (SPD) intervention: "a piece of sterile surgical foam cut to size and wrapped in Adaptic dressing was secured over the recipient bed followed by placement of a volar wrist-immobilizing splint".
Study date/s: March 2007 to August 2009

Outcomes

Measures:

  1. Graft failure

  2. Percentage of area of skin graft failure

  3. Adverse events

Validity of measure/s: quantitative measurements of the donor site were accomplished with the aid of a 1 x 1 cm grid transparency, which was laid over the donor site. The exact borders of the skin graft were then traced onto the overlying grid with a permanent marker.

Time points: follow-up at 2 weeks post surgery (N.B. graft failure was also measured at 1 month post surgery but it was unclear if those from the 2-week follow-up had been included in this measure)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Evidence: Quote "A randomization schedule, created by a biostatistician using a random number generator".

Comment: blocking not mentioned

Allocation concealment (selection bias)High risk

Evidence: Quote "We had a list of the randomization schedule, and pts were assigned to either group based on the order of their surgery" (personal, email communication).

Comment: surgeons aware of the next assignment

Blinding of participants and personnel (performance bias)
All outcomes
High risk

Evidence for participants: not described

Comment: difference in appearance of dressings made blinding impossible

Evidence for personnel: not described

Comment: difference in appearance of dressings made blinding impossible

Blinding of outcome assessment (detection bias)
All outcomes
High risk

Evidence: Quote "Evaluators at the time of the postoperative visits were not blinded as to which treatment arm the subjects belonged".

Comment: correspondence with the author confirmed that "evaluators" were investigators

Incomplete outcome data (attrition bias)
All outcomes
High risk

Evidence: Quote"Four subjects 4/54 (all of whom belonged to the NPD group) were lost to the first postoperative follow-up and were thus excluded from final analysis because no postoperative data could be recorded for these subjects. Of the remaining 50 Ss, only 32 patients (16 subjects in SPD group and 16 subjects in NPD group) returned for their second postoperative visit".

Comment: only data from the first postoperative visit has been included

Unequal distribution of 'drop outs' (15% in negative pressure group; 0% in static pressure group)

Selective reporting (reporting bias)Low risk Comment: all the pre-specified clinical outcomes are presented in Table 2. Adverse events are reported in the Results section. Measures reflect the aims of the intervention and the pre-defined outcomes. A published protocol was not available.
Other biasLow risk

Evidence: the authors report: Quote "Competing interests: None. Sponsorships: None".

Comment: no other potential biases were identified

Dorafshar 2011

Methods

Study design: randomised controlled trial
Ethics and informed consent: ethics approved and consent obtained

Sample size calculation: yes

ITT analysis: yes

Participants

Location: University of Chicago Medical Center, IL, USA
Mean age Group 1: 53;Mean age Group 2: 54
Inclusion criteria: patients admitted to University of Chicago Medical Center,18 years of age, with acute wounds resulting from trauma, dehiscence, or surgery
Exclusion criteria:

Systemic sepsis caused by wound infection
Grossly necrotic wounds
Malignancy in the wound
Wounds with untreated osteomyelitis
Patients with allergy to sulfamylon and Dakin’s (sodium hypochlorite) solution
Patients with severe peripheral vascular disease

Interventions

Aim/s: Quote "The primary objective was to compare the efficacy of VAC and GSUC with respect to changes in wound size. Secondary objectives were to compare associated costs of the dressings, the ease of application, and the pain associated with each dressing change".
Intervention/s in both groups: Quote "Patients had ad lib access to analgesics administered via PCA or a nurse".

Group 1 (GSUC) intervention: Quote "In the GSUC arm, a gauze dressing (Kerlix 4.5 inch roll, Covidien, Mansfield MA) moistened with 0.9% normal saline was applied to the wounds, a red rubber catheter (C.R. Bard, Covington, GA) was placed in the center of the dressing, and the dressing was then sealed with an occlusive cover
(Ioban Antimicrobial Incise Drape, 3M, St Paul, MN). Continuous wall suction at 75 to 80 mm Hg was applied and the dressings were changed daily".

Group 2 (VAC) intervention: Quote "In the VAC arm, GranuFoam black sponge (KCI, San Antonio, TX) was applied to the wounds and sealed with an occlusive plastic cover; continuous suction at 75 to 125 mm Hg was initiated and the dressing was changed every 48 hours, as recommended by VAC therapy guidelines. All components of the dressing were obtained from Kinetics Concepts, Inc.
Study date/s: October 2006 to May 2008

Outcomes

Measures:

  1. Rate of change in surface area between groups (expressed as the rate of change %/day)

  2. Rate of change in wound volume between groups (expressed as the rate of change %/day)

  3. Cost/day

  4. Pain measured using a 0 to 10 linear analogue scale and reported as the "sum of pain intensity differences"

  5. Wound complications

  6. Adverse events

Validity of measure/s:

  1. "Wound size was calculated using the Xakellis and Frantz method: wound surface area = length X width X 0.783; wound volume area = area X depth X 0.327".

  2. Pain was self reported and measured "according to the 0 to 10 linear analogue scale immediately before, during, and after removal of the dressing. The sum of pain intensity differences (SPID) was used to facilitate comparison of pain levels between the 2 groups. The SPID score was calculated using the formula: (pain during - pain before) + (pain after - pain during)."

Time points: data collected up to day 7 were included in the analyses

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk Evidence: Quote "The randomization sequence was generated from the Web site http://www.randomization.com".
Comment: blocking not mentioned
Allocation concealment (selection bias)Unclear risk Evidence: Quote "On enrolment, patients were then randomized to either GSUC or VAC therapy in a 1:1 ratio by drawing a previously prepared card".
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Evidence for participants: Quote "The 2 methods of SAWT were obviously and visibly different, so it was impossible to blind either the therapists or the patients to the method of treatment".

Evidence for personnel: Quote "The 2 methods of SAWT were obviously and visibly different, so it was impossible to blind either the therapists or the patients to the method of treatment".

Blinding of outcome assessment (detection bias)
All outcomes
High risk

Evidence: Quote "A senior therapist who was highly experienced with both VAC and GSUC changed all of the dressings.

We tried to minimize bias by using therapists who were not participating in the study to gather and record data”

Comment: the therapist was not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low risk Evidence: Quote "An intention-to-treat analysis was performed for all of the primary and secondary outcomes. Forty-five patients in the GSUC group and 42 patients in the VAC group were included in the analyses."
Selective reporting (reporting bias)Low risk Comment: all the pre-specified clinical outcomes are presented in Tables 3 and 4. Complications and adverse events are reported in the results section. Measures reflect the aims of the intervention and the pre-defined outcomes listed in the published protocol (NCT00724750), which was sighted.
Other biasUnclear risk

Evidence: the study began in 2006 but the protocol was Quote "First Received on July 25, 2008" at ClinicalTrials.gov

Comment: potential for study characteristics to have changed before or during the study

Howell 2011

Methods

Study design: randomised controlled trial
Ethics and informed consent: not reported

Sample size calculation: yes

ITT analysis: all participants completed the study

Participants Location: NYU Hospital for Joint Disorders, New York, NY, USA
Mean age Group 1: not reported;Mean age Group 2: not reported
Inclusion criteria: patients undergoing unilateral or bilateral primary TKA who were obese (BMI > 30), who met criteria of increased risk for postoperative wound drainage and who were prescribed enoxaparin sodium for deep venous thrombosis (DVT) prophylaxis
Exclusion criteria: patient refusal to participate in the study, revision TKR, prior knee surgery (except arthroscopy), and patients with documented diabetes mellitus were excluded from the study
Interventions

Aim/s: to compare the number of days to dry wound between a negative pressure dressings group compared with static pressure dressings group
Intervention/s in both groups: "All patients received three doses of peri-operative intravenous antibiotics and were maintained on subcutaneous DVT prophylaxis for 30 days after surgery".

Group 1 (NPD) intervention: "Subsequent to the closure of the surgical incision, a negative pressure dressing (VAC Therapy, Kinetic Concepts Inc., San Antonio, Texas) was applied under sterile conditions. A medical grade open cell polyurethane ether foam (pore size of 400--600 micrometers) was cut into the shape of a rectangle approximately 5 cm in width and a length sufficient to cover the entire linear wound. The knee was held in 151 of flexion, and the foam was secured over the incision by the application of a specialized adhesive drape, provided in the VAC Therapy system. An evacuation tube with side ports was embedded within the reticulated foam, allowing negative pressure to be applied equally over the entire wound bed. The foam-evacuation tube complex attached to a programmable vacuum pump applied a 125 mmHg continuous vacuum pressure to the wound.

The VAC Therapy dressing remained in place for a 48-hour period, after which time clean, dry gauze dressings were applied and changed on daily basis until the wound was dry".

Group 2 (SPD) intervention: "Patients in the control arm had their surgical wound covered in the operating room with a sterile, dry gauze dressing that was held in place with a perforated, stretchable cloth tape. This initial dressing remained in place for 48 hours after which time clean, dry gauze dressings were applied and changed on a daily basis until the wound was dry."
Study date/s: not stated

Outcomes

Measures:

  1. Days to dry wound

  2. Deep wound infection

  3. Blister formation

Time points: patients followed for 12 months post surgery

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk Comment: not described
Allocation concealment (selection bias)Low risk Evidence: Quote “randomized with blinded envelopes to either the treatment with negative pressure wound therapy group or a control group using sterile gauze"
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Evidence: not described

Comment: difference in appearance of dressings made blinding impossible

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk Evidence: not described
Incomplete outcome data (attrition bias)
All outcomes
Low risk Evidence: 51 patients were randomised and 51 completed the study
Selective reporting (reporting bias)Low risk Comment: the pre-specified clinical outcomes are presented in Table 1. A post hoc analysis of blister occurrence is shown in Table 2. Infection rates are reported in the results section. No published protocol was found.
Other biasUnclear risk

No baseline data are presented. In addition, groups contained unequal numbers, which may indicate undisclosed losses in one group

The study was supported by KCI, the manufacturer of the negative pressure device

Llanos 2006

Methods

Study design: randomised, double-blind controlled trial
Ethics and informed consent: ethics approved and consent obtained

Sample size calculation: yes

ITT analysis: yes

Participants Location: Burn & Plastic Surgery Unit, Santiago, Chile
Mean age Group 1: 34 (20 to 52);Mean age Group 2: 34.5 (19 to 58)
Inclusion criteria: Quote "all patients who were admitted at the hospital with acute traumatic injuries and skin loss, which hindered primary closure, underwent a surgical cleaning of their wound, and had a quantitative biopsy culture performed on their wound. Those patients whose biopsy culture had a bacterial count lower than 100,000 colony forming units per gram of tissue and who had given informed consent to enter the study were recruited".
Exclusion criteria: those who Quote "had burns that covered 20%, or more, of their total body surface; were polytraumatized; had surgical contraindications because of medical, anesthetic (serious associated pathology), or surgical cause (hypoalbuminemia or systemic infection); or were enlisted in other clinical trials".
Interventions

Aim/s:

Primary: to determine if the negative pressure closure diminishes the area loss of the skin grafts

Secondary: to determine if 1) the negative pressure closure shortens hospital stay, or if secondary wound coverage procedures are needed; and 2) to determine if there is a relation between the area loss of the skin graft and the total grafted surface.
Intervention/s in both groups: Quote"The graft was covered with a single layer of paraffin gauze dressing (Jelonet, Smith & Nephew, England); then, 3 sheets of polyurethane (high-density foam, Nuris Luisa, Santiago, Chile) with a fenestrated silicone drainage tube between the layers was placed over the gauze and covered with a transparent adhesive dressing (Op site, Smith & Nephew) providing the vacuum seal. We used a double layer under the tube to prevent pressure ulcers at the bed of the suction tube.

Group 1 (NPC) intervention: Quote "The suction tube was connected to the central aspiration system at a pressure of −80 mm Hg, and the integrity of the vacuum seal was tested and reinforced with cotton dressing and an elastic gauze bandage if necessary".

Group 2 (Control) intervention: the control group Quote "only differed from the active group in that it lacked a connection to the central aspiration system (i.e., negative pressure vacuum)".
Study date/s: May 2003 to October 2004

Outcomes

Measures:

  1. Area loss of skin graft in cm2

  2. Need for re-grafting

  3. Length of hospital stay

  4. Complications

Validity of measure/s: Quote "Digital photographs, without flash, were taken from a distance of 40 cm from the wound to evaluate the areas of loss at the moment of uncovering the graft. Afterward, these images were analyzed with the Autocad (Autodesk, Inc, 2001, Fremont, CA) software, measuring the loss in cm2".

Time points: fourth postoperative day

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk Evidence: Quote "Treatment assignment was performed using computer-generated random numbers in permuted blocks of 6".
Allocation concealment (selection bias)High risk

Evidence: Quote "The treatment allocation of each patient was performed by the nurse of the operating room who knew the corresponding assignment".

Comment: follow-up correspondence with the author indicated Quote "the theatre nurse had a list of randomization with computer generated random numbers". So allocation was not concealed.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Evidence for participants: not described

Comment: dressings were identical. The only difference was that dressing in the NPC group were connected to an 'active' suction device. Potential for participant to notice this.

Evidence for personnel: Quote "The corresponding treatment was notified to the surgeon only once the skin graft had been performed so that the surgeon did not modify his technique according to the assignation of treatment".

Comment: once surgery was completed, other personnel would have been aware of group assignment (active suction or not). Whether this would have affected outcomes is unclear.

Blinding of outcome assessment (detection bias)
All outcomes
Low risk Evidence: Quote "The person in charge of measuring the areas in the photographic register was masked to which intervention the patient had received. That way, at the moment of evaluating the photograph, this person did not know whether or not the patient had undergone NPC. In addition, the data analyst was masked to the groups of intervention at the moment of analyzing the results".
Incomplete outcome data (attrition bias)
All outcomes
Low risk Evidence: Quote "All the patients were analyzed in the group to which they were assigned, adhering to the intention-to-treat principle". "In our study, there were no drop-outs, drop-ins, or noncompliant patients. Furthermore, no patients refused to take part in the study".
Selective reporting (reporting bias)Low risk Comment: all the pre-specified clinical outcomes are presented in Table 2 and in Figures 4 and 5. Adverse events are reported in the Results section. Measures reflect the aims of the intervention and the pre-defined outcomes. A published protocol was not available.
Other biasLow risk

Evidence: Quote "The authors have no conflicts of interest with any of the manufacturing companies of the products used in the present study".

Comment: no other potential biases were identified

Pachowsky 2011

  1. a

    BMI: body mass index; DVT: deep venous thrombosis; ITT: intention-to-treat; SPID: sum of pain intensity differences; TKR: Total knee replacement; TKA: Total knee arthroplasty.

Methods

Study design: randomised controlled trial
Ethics and informed consent: ethics approved and consent obtained

Sample size calculation: no

ITT analysis: yes

Participants Location: University hospital in Erlangen, Germany
Mean age Group 1: 70.0 (SD 11.01);Mean age Group 2: 66.2 (SD 17.83)
Inclusion criteria: Quote "consecutive patients who were scheduled for a total hip arthroplasty (THA) for osteoarthritis of the hip were randomised".
Exclusion criteria: Not stated
Interventions

Aim/s:

Primary : to evaluate the effect of NPWT on postoperative seroma

Secondary :
Intervention/s in both groups: Quote"The surgical intervention was identical for both groups. All patients received two Redon drains, one in the deep area of the wound close to the prostheses and one above the closed fascia. The postoperative physiotherapy and mobilisation was also identical for both groups. Both groups received perioperative prophylaxis with antibiotics either Augmentin (amoxicillin trihydrate with potassium clavulanate) or ciprofloxacin".

Group 1 (NPWT) intervention: Quote "The NPWT group was treated with a PREVENA™ system (KCI, San Antonio, USA). The PREVENA system was left on the wound for five days including the day of surgery.".

Group 2 (Control) intervention: the control group received Quote "the standard wound dressing of our department, consisting of a dry wound coverage".
Study date/s: Not stated

Outcomes

Measures:

  1. Incidence of seroma (by ultrasound)

  2. Amount of wound drainage in the Redondrain canisters

  3. Duration of prophylactic antibiotics

  4. Secretion from the wound

Validity of measure/s: Quote "All patients underwent an ultrasound (Zonare, Z.one Ultra SP 4.2, Erlangen, ZONARE Medical Systems, Inc., Mountain View, USA) of the wound".

Time points: fifth and 10th post-operative days

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Evidence for participants: not described

Comment: difference in appearance of dressings made blinding impossible

Evidence for personnel: not described

Comment: difference in appearance of dressings made blinding impossible

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskDressings were left in place for five days. The ultrasound was performed on day five. It is unclear if the person performing the ultrasound was aware of the allocated group.
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll enrolled patients were accounted for in the analyses
Selective reporting (reporting bias)Unclear riskResults for outcomes identified in the methods section were reported. The protocol was not sighted.
Other biasUnclear risk

Evidence: Quote "Matthias H. Brem gave scientific presentations for KCI. The PREVENATM wound treatment system was provided by KCI free of charge."

One patient in the NPWT group removed the Redon drain by himself on the first postoperative day

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Hu 2009Acute, sub-acute and chronic wounds were included. Acute wounds were defined as those that had been 'open' for less than 1 week.
Johannesson 2008The intervention dressing was not a continuous negative pressure device.
Kim 2007The study was not a randomised controlled trial.
Moues 2004No acute wounds were included.
Moues 2007No acute wounds were included.

Characteristics of studies awaiting assessment [ordered by study ID]

Braakenburg 2006

MethodsRandomised controlled trial
Participants65 patients with chronic and acute wounds
InterventionsVacuum-assisted closure versus static pressure dressing
OutcomesPain, antibiotic use, wound and granulation surface measurement
NotesResults of chronic and acute wounds presented together. Details of acute wounds alone requested from investigator.

Moisidis 2004

MethodsRandomised controlled trial
Participants22 patients with chronic, sub-acute and acute wounds (10 with acute wounds)
InterventionsVacuum-assisted closure versus static pressure dressing
OutcomesEpithelialisation, proportion of graft take
NotesResults of chronic and acute wounds presented together. Details of acute wounds alone requested from investigator.

Characteristics of ongoing studies [ordered by study ID]

Chan 2011

Trial name or titleA prospective randomised controlled trial of negative pressure suction dressing and early mobilisation in the management of lower leg skin grafts
MethodsRandomised controlled trial
ParticipantsPatients with lower leg wounds requiring split skin grafting for primary closure, e.g. post planned skin lesion removal or trauma
InterventionsNegative pressure dressing versus static pressure dressing
OutcomesPrimary: graft success at day 5 to 7 when dressing is removed. Secondary: graft success at 6-week follow-up.
Starting dateEarly 2011
Contact information Mark.Wade@waitematadhb.govt.nz; richard.martin@waitematadhb.govt.nz
Notes 

Graves 2011

Trial name or titleIncisional wound vac in obese patients
MethodsRandomised controlled trial
ParticipantsObese patients after standard closure of trauma-related, operative orthopaedic incisions
InterventionsNegative pressure dressing versus static pressure dressing
OutcomesDrainage from incisional wound
Starting dateEstimated December 2010
Contact informationMatthew Graves (mgraves@umc.edu); Lori Smith (lsmith6@umc.edu)
NotesInvestigator contacted. Awaiting response.

Ancillary