Tag Archives: Negative pressure wound therapy

Pressure distribution under Wound VAC® therapy vs tie-over bolster dressing

by Justin D. Guiliana DPM1*, Yvonne Cha DPM1, Brent H. Bernstein DPM2

The Foot and Ankle Online Journal 12 (3): 8

Split thickness skin grafts (STSG) are a widely accepted technique for wounds, however the incorporation of the graft to the wound can be easily affected by multiple factors such as the patient’s comorbidities but also the dressing type and its pressure distribution. Securing a newly applied skin graft effectively can often be a difficult task however, a tie-over bolster dressings and the use of negative pressure wound therapy using reticulated open-cell foam (NPWT/ROCF) as delivered by V.A.C.® Therapy (KCI Licensing, Inc., San Antonio, TX) are widely accepted dressings for securing grafts.  The purpose of this study was to compare sub-graft pressure distribution between NPWT/ROCF and tie-over bolster dressing where an experimental graft model was created to compare sub-graft pressure underneath the two dressings. It was found that peak pressure under the NPWT/ROCF graft was 14 pounds per square inch (psi) with a uniform, circular imprint. Peak pressure under the tie-over bolster dressing was 27 psi with three distinct bands of pressure and very low to no pressure distribution between the higher bands of pressure. In this study, NPWT/ROCF appears to have a better uniform pressure distribution compared to the tie-over dressing, which may be related to improved STSG incorporation into the wound.

Keywords: negative pressure wound therapy, pressure distribution, split–thickness skin graft, STSG,  tie-over bolster dressing, VAC® therapy

ISSN 1941-6806
doi: 10.3827/faoj.2018.1203.0008

1 – Resident, St. Luke’s Podiatry, Bethlehem, PA
2 – St. Luke’s Podiatry, Bethlehem, PA
* – Corresponding author: jguiliana28@gmail.com

Securing newly applied skin grafts to wounds of the lower extremity continues to be a challenge. In order for a split thickness skin graft (STSG) to achieve optimal healing, it requires immobilization of the graft to prevent infection, hematoma, and desiccation. Achieving all three components for successful split-thickness skin graft take has been difficult due to possible complexity in the contour of the soft tissue, and uneven pressure distribution [1].

Traditionally, tie over bolster dressings were applied over STSG to achieve immobilization on the wound in order to achieve optimal healing. However, negative pressure wound therapy using reticulated open-cell foam (NPWT/ROCF) as delivered by V.A.C.® is becoming a more common choice in wounds that have irregularity in the contour of the soft tissue. NPWT/ROCF allows a more uniform pressure distribution on the STSG that are implemented on soft tissue irregularities. This study shows different pressure distributions between tie over bolster dressings, and NPWT/ROCF and to observe the correlation between graft take, and pressure distribution [1].


Comparative Evaluation of Pressure Distribution under NPWT/ROCF vs. Tie-over Dressings

An experimental graft model was created to compare the sub–graft pressure distribution under a compressed NPWT/ROCF dressing and a tie–over bolster dressing.  A circular, full-thickness wound was made in a porcine extremity (Figure 1A). A tactile sensing system sensor (Tekscan Pressure Measurement System 4.11F, Tekscan, Inc, South Boston, MA) was trimmed to the wound shape and placed in the base of the wound (Figures 1A-C) to measures static pressure distribution. The pressure sensing system uses specialized software and thin, flexible sensors that accommodate most contours and provide accurate local pressure readings.

A human cadaveric mesh STSG was trimmed to the wound size and placed over the sensor (Figure 1D). Figures 2A and 2B show examples of the NPWT/ROCF and tie-over dressings, respectively. The graft/surface interface pressures were measured 1) without a dressing, 2) with a tie-over dressing utilizing 3-0 monofilament nylon suture over a moist cotton ball bolster, and 3) under the NPWT/ROCF dressing at a continuous pressure of -125 mmHg. A non-adherent interface dressing was placed directly over the STSG on all models.


Analysis of Pressure Distribution beneath NPWT/ROCF vs. Tie-Over Dressing Techniques in Porcine Wound Model

The peak pressure under the STSG without a dressing was 6 psi with a uniform, circular implant (Figure 3C). The peak pressure measured under the graft with a tie–over dressing was 27 psi with three distinct bands of pressure and zero to very low pressure distributions between the higher bands of pressure (Figure 3B). The white area indicated no pressure reading. The peak pressure measured underneath the graft with NPWT/ROCF was 14 psi with a uniform circular imprint (Figure 3A). 

Figure 1 (A) Circular, full-thickness wound created in a porcine extremity. (B) Tactile sensing system sensor used to measure subgraft pressure. (C) Tactile sensing system sensor trimmed to wound shape and placed in the base of the wound. (D) Human cadaveric meshed STSG trimmed to the wound size and placed over the sensor.

Figure 2 (A) Tie-over bolster dressing applied over the STSG and pressure sensor. (B) NPWT/ROCF dressing applied over the STSG and pressure sensor.

Figure 3 (A) Pressure under STSG with NPWT/ROCF dressing (14 psi with a uniform circular imprint). (B) Pressure under STSG with tie-over dressing (27 psi with three distinct bands of pressure and no to very low pressure distributions between the higher bands of pressure). (C) Pressure under STSG with no dressing (6 psi with uniform, circular imprint).


In many practices, NPWT/ROCF after adequate debridement has become a powerful workhorse in STSG management, particularly in cases of patients with comorbidities or wounds in difficult anatomic locations. The even distribution of pressure aids in immobilization, restriction of shearing to the graft, and prevention of seroma or hematoma formation. Distinct bands of low to no pressure displayed beneath the tie-over dressing in the porcine model indicate a lack of continuous contact between the dressing and graft, thus depriving areas of the graft from the beneficial effects of the dressing.

Our scientific findings dovetail similarly with the histological findings observed in a scientific study by Simman et al. [2]. In a comparative porcine model, NPWT/ROCF showed decreased wound edema, faster narrowing of the separation plane between the graft and recipient wound bed, and earlier termination of the acute inflammatory reaction as compared to a bolster dressing on postoperative days 3, 5, 7, 9, and 11. Authors proposed that a decrease in edema and plane of separation could increase oxygen and nutrient delivery to tissue, leading to accelerated healing [2]. The higher peak pressure observed with the tie-over dressing (27 psi) versus NPWT/ROCF (14 psi) in our study is notable. Further scientific studies would be appropriate to determine optimum pressure at the interface of the wound graft in various patients and wound types. 

The current authors postulate that mechanical factors played a critical role in outcome.  The micromechanical force exerted by the negative pressure and compressed open-cell foam has been shown to cause individual cell deformation and increased proliferation and granulation tissue formation [3]. Following NPWT/ROCF application to cells in an in vitro model, Wilkes et al., [4] reported a change in cell morphology, with cells appearing thicker and with an organized actin cytoskeleton. 

Disclosure: Dr. Brent H Bernstein serves as a consultant to KCI-Acelity Company, however no research financial support or funding was received for the study in this paper.


  1. Stone P, Prigozen J, Hofeldt M, Hass S, DeLuca J, Flaherty S. Bolster versus negative pressure wound therapy for securing split-thickness skin grafts in trauma patients. Wounds 16(7):219-223, 2004.
  2. Simman R, Forte R, Silverberg B, Moriera-Gonzalez A, Williams F. A comparative histological study of skin graft take with tie-over bolster dressing versus negative pressure wound therapy in a pig model: a preliminary study. Wounds 16(2):76-80, 2004.
  3. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP. Vacuum 275 assisted closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg 114(5):1086-1096, 2004. 
  4. Wilkes RP, McNulty AK, Feeley TD, Schmidt MA, Kieswetter K. Bioreactor for Application of Subatmospheric Pressure to Three-Dimensional Cell Culture. Tissue Eng 13(12):3003-3010, 2007.

Graft take rates in low-risk and high-risk patients with negative pressure wound therapy vs tie-over dressings

by Brent H Bernstein DPM1, Yvonne Cha DPM1*, Justin Guiliana DPM1

The Foot and Ankle Online Journal 12 (2): 6

Establishing a reliable method of securing skin grafts over wounds of the lower extremities remains a challenge, particularly in high-risk patients. Studies have reported on the use of negative pressure wound therapy using reticulated open-cell foam (NPWT/ROCF) as delivered by V.A.C.® Therapy (KCI Licensing, Inc., San Antonio, TX) as a bolster dressing over split- thickness skin grafts in various populations. The aim of this study was to compare take rates of lower extremity grafts in high-risk patients who received NPWT/ROCF versus tie-over dressings. We also retrospectively evaluated graft take rates in low-risk (no comorbidities) versus high-risk (≥1 comorbidity) graft patients who received post-graft NPWT/ROCF versus tie-over dressings. Forty-seven STSG patient records were analyzed. In the high-risk patient group, a significantly higher number of patients obtained ≥80% graft take rate in the NPWT/ROCF versus tie-over group (p=0.008). Graft take rates were similar between the two dressings in low-risk patients. In this study, NPWT/ROCF appears to improve STSG take compared to tie-over dressings in high-risk patients, which may be related to an improved contact zone between the graft and wound site.

Key words: negative pressure wound therapy, V.A.C. therapy, split-thickness skin graft

ISSN 1941-6806
doi: 10.3827/faoj.2018.1202.0006

1 – St. Luke’s University Health Network- Allentown, Pennsylvania
* – Corresponding author: yvonne0cha@gmail.com

Closure of lower extremity wounds remains a challenge in patients with considerable comorbidities. An ever-increasing number of closure options have prompted us to adopt a “reconstructive elevator” approach to our modern lower extremity practice (Figure 1). Typically in our practice, anatomic location, biomechanics and bony pressure points dictate plastic closure selection. Wounds with bone, joint, or tendon exposure without periosteum or paratenon larger than 0.5 cm in diameter are treated with flaps. Wounds located on the weight-bearing areas of the foot are typically treated with secondary intention or preferably cultured cellular grafts. In the literature, a split-thickness skin graft (STSG) is considered by some surgeons to be the preferred method of repair for moderate to large soft tissue defects on non-weight-bearing areas of the extremities [1-5].

Split-thickness skin grafting is a method of transposition of human skin (epidermal and a portion of the dermal layers) from a harvest to recipient site. The stages of STSG healing are: plasmatic imbibition, inosculation, and capillary ingrowth. A skin graft survives the first 48 hours through imbibition, or diffusion, of exudate through the host bed that supplies nutrients and removes waste products. The next step is inosculation, in which the graft develops connections with the recipient blood vessels. 

Figure 1 The “reconstructive elevator” approach to modern lower extremity practice.

Finally, capillary in-growth occurs when new vessels grow into the graft from the host bed and actively innervate the graft to establish blood supply [6, 7]. 

Patient comorbidities, such as diabetes mellitus (DM), lymphedema, and peripheral vascular disease (PVD) are known to impede wound healing [8], and can lead to graft failure. Other reasons for graft failure include ischemia, seroma/hematoma formation, fluid collection, shearing forces, infection, desiccation, and rejection. Reported skin graft failure rates vary dramatically, depending on wound etiology and a host of other factors. The method used to secure the graft can be a critical element in reducing opportunities for failure. Goals of a bolster dressing are to provide even pressure, immobilization and restriction of shearing to the graft, as well as prevent seroma or hematoma formation while providing a moist wound bed beneath the STSG [7]. 

During the past several years, adjunctive use of negative pressure wound therapy using reticulated open-cell foam (NPWT/ROCF) as delivered by V.A.C.® Therapy (KCI Licensing, Inc., San Antonio, TX) has become a well-established method of securing the graft to the recipient bed. NPWT/ROCF can act as both a temporizing bridge to STSG closure as well as the dressing over the STSG [4, 5, 8-12]. Obtaining successful graft take requires that the skin graft remain immobilized for 2-5 days or until revascularization occurs [13]. The compressed NPWT/ROCF foam maintains continuous, firm contact between the graft and wound bed while the negative pressure actively removes exudates and infectious material from the wound bed. Foam pliability allows relative movement of the wound surface without compromising pressure [4]. 

While many studies have reported on the use of NPWT/ROCF over STSGs, its relative efficacy versus traditional tie-over bolster dressings has been debated in the literature. We hypothesized that the use of NPWT/ROCF creates an improved contact zone between the graft and wound site as compared to tie-over dressings, which may result in higher graft take rates. We further hypothesized that among high-risk patients with known comorbidities, application of NPWT/ROCF over STSGs on lower extremity wounds leads to higher graft take rates compared to tie-over dressings. To test these hypotheses, we performed a retrospective cohort analysis examining skin graft take rates of high-risk patients treated with NPWT/ROCF versus tie-over cotton bolster dressings. 

Patients and Methods

We retrospectively reviewed the charts of consecutive patients who received an STSG procedure performed by the leading author as primary surgeon between March 1994 and May 2007. Records were divided into four groups: 1) High-risk NPWT/ROCF, 2) High-risk tie-over bolster, 3) Low-risk NPWT/ROCF and 4) Low-risk tie-over bolster. Patients were considered high-risk if they had any of the following comorbidities: DM, end-stage renal disease (ESRD), contralateral lower-extremity amputation, lymphedema, smoking, peripheral nerve disorders, spinal cord injuries (SCI) or disorders, PVD, venous insufficiency, immunocompromised, or connective tissue disorders. A hospital IRB Waiver of Authorization was obtained to perform this retrospective data analysis, based on its minimal risk level to patients. All tie-over bolster and NPWT/ROCF dressings were similarly fashioned and placed by the same surgeon. Tie-over patients were treated with a post-graft bolster dressing consisting of normal saline soaked absorbent cotton balls and tied over the graft using 3-0 monofilament nylon sutures. 

Figure 2 NPWT application diagram.

STSGs in the NPWT/ROCF-treated groups were covered with an available (eg, ADAPTIC®) porous non-adherent layer, an NPWT/ROCF dressing and semi-permeable drape with tubing. The tubing was connected to the subatmospheric pressure unit with -125mmHg applied for 3-5 days (Figure 2). The authors’ medical records, digital photograph archives, and surgical logs were reviewed, and percentage of graft take at 14 days post-operative was recorded for each patient. Total number patients with ≥80% and ≥50% graft take were compared between both treatment arms for both high- and low-risk groups. Fisher’s exact two-tailed test was utilized to compare the groups by percentage of graft take.


Forty-seven patients met the study inclusion criteria. 15 patients in the NPWT/ROCF group and 21 in the tie-over group were classified as high-risk. There were 5 patients in the NPWT/ROCF group and 6 patients in the tie-over group that were classified as low-risk. 

Frequencies of patient comorbidities are listed in Table 1. Wound etiologies in the low-risk patient group included traumatic wounds, post-debridement wounds from necrotizing fasciitis or bites, post-lesion excision sites, and decubitus ulcers. 

Table 1 Graft rate take rate.

There was a significant difference between the two treatment arms of high-risk patients that achieved a graft take rate ≥80%: 13 of 15 for the NPWT/ROCF group versus 9 of 21 for the tie-over group (p=0.008) (Table 1). The number of patients in the high-risk cohort that achieved ≥50% graft take was also significantly lower in the tie over patient group (14/21) versus the NPWT/ROCF group (15/15; p=0.027). Complete graft failure (0% graft take) was reported in the remaining 7 tie-over and 1 NPWT/ROCF high-risk patients. The average percent graft take rates for high-risk patients in the NPWT/ROCF versus tie-over groups were 90.3% vs. 55.2%, respectively. When subgrouped by comorbidities, the average graft take rate in the NPWT/ROCF-treated patients was higher than the tie-over patients in each of the subgroups, but the difference was not significant, owing to low populations in all subcategories (Table 1). All low-risk NPWT/ROCF and tie-over patients achieved a graft take rate of 80% or greater (Table 2). 


The retrospective analysis demonstrated significantly improved STSG take rates and survival in high-risk patients who received NPWT/ROCF, compared to traditional tie-over dressings. Our graft take rates in both the high- and low-risk NPWT/ROCF groups—90.3% and 100%, respectively—mirror that which is reported in the literature [14-16]. In 1997, Argenta and Morykwas first demonstrated effective use of NPWT/ROCF as a bolster for STSGs on a variety of acute and chronic wounds [14]. Blackburn et al [15] showed a ≥95% STSG take rate with the use of NPWT/ROCF on contoured wounds in complex anatomic regions. 

Comorbidity High risk tie-over group  High risk NPWT/ROCF Group 
n Average % take 80% graft take (n) ≥50% graft take (n) n Average % take  ≥80% graft take (n) ≥50% graft take (n)
DM, ESRD, contralateral lower extremity amputation, PVD 14 57.9 6 4 13 93.1 12 1
SCI/peripheral neuropathy/congenital spinal cord lesion 0 n/a n/a n/a 0 n/a n/a n/a
Venous insufficiency 6 58.3 3 2 1 95 1 0
Connective tissue disorder/immunocompromised 0 n/a n/a n/a 1 50 0 0
smoker 1 0 0 1 0 n/a n/a n/a
total 21 55.2 9 7 15 90.3 13 1

Table 2 Comorbidity and graft rate take rate.

A consecutive case series of 61 STSG patients revealed a significant decrease in repeated STSGs for the NPWT/ROCF group as compared to the bolster dressing group, suggesting improved graft survival with adjunctive use of NPWT/ROCF [19]. Our patients have experienced other advantages of NPWT/ROCF reported in the literature, such as enhanced patient mobility, shorter hospital stay, and an earlier return to daily activities while the dressing is in place [2, 15, 17]. 

Our study’s similar graft take rates between the two treatment arms of the low-risk population somewhat support outcomes of other clinical studies that have reported no significant difference in STSG take rates between NPWT/ROCF and tie-over dressing groups [3, 18-19]. Moisidis et al [18] performed a prospective, blinded, randomized controlled trial comparing NPWT/ROCF to standard bolster dressings on 22 adult inpatients with wounds requiring skin grafting. There were no differences in quantitative graft take between the two groups, but NPWT/ROCF had a significantly better qualitative graft take as compared to the standard bolster dressing [18]. In a retrospective chart review, Stone et al also found similar graft take rates between NPWT/ROCF and bolster dressings in 40 trauma patients who underwent soft tissue loss and fasciotomies [3]. Our study results appear to suggest prudent use of NPWT/ROCF in low-risk patients, although the small sample sizes clearly warrant further study. 

This study has several limitations including its small size, retrospective nature, and lack of randomization and blinding. Unobserved covariates which could also account for differences in graft take, such as wound size, duration, or type of wound treatment prior to grafting, may also distort the conclusions of the study. Also, the author believes that as his practice changed from utilizing the tie-over dressing to the use of NPWT/ROCF over time, perhaps an improvement in surgical technique could have occurred as well over this period of time. This improvement in technique could have allowed an improved success in the latter portion of the cohort when NPWT/ROCF was utilized more often. 

To the authors’ knowledge, this study is the first to delineate between high- and low-risk patient populations in comparing NPWT/ROCF versus tie-over bolster treatment over STSGs. Our results suggest that the presence of patient comorbidities may be an important consideration when choosing a bolster dressing. Combining high and low-risk populations within cohorts may underestimate the utility of NPWT/ROCF in high-risk populations. Our preliminary results are promising and suggest that NPWT/ROCF may be a more efficacious dressing versus traditional tie-over dressings in high-risk patients whereby reliably uniform contact between the graft and dressing is critical to successful graft take.


  1. Llanos S, Danilla S, Barraza C, Hernandez I, Nava E, Diaz J. Effectiveness of negative pressure closure in the integration of split thickness skin grafts: a randomized, double-masked, controlled trial. Ann Surg 244(5):700-705, 2006. 
  2. Chang KP, Tsai CC, Lin TM, Lai CS, Lin SD. An alternative dressing for skin graft immobilization: negative pressure dressing. Burns 27(8):839-42, 2001. 
  3. Stone P, Prigozen J, Hofeldt M, Hass S, DeLuca J, Flaherty S. Bolster versus negative pressure wound therapy for securing split-thickness skin grafts in trauma patients. Wounds 16(7):219-223, 2004. 
  4. Schneider AM, Morykwas MJ, Argenta LC. A new and reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg 102(4):1195-1198, 1998. 
  5. Repta R, Ford R, Hoberman L, Rechner B. The use of negative-pressure therapy and skin grafting in the treatment of soft-tissue defects over the Achilles tendon. Ann Plast Surg 55(4):367-70, 2005. 
  6. Warriner RA. Wound assessment. In Wound Care Practice, pp75-100, edited by PJ Sheffield, APS Smith, CE Fife. Best Publishing Company, Flagstaff, 2004. 
  7. Gupta S, Gabriel A, Shores J. The perioperative use of negative pressure wound therapy in skin grafting. Ostomy Wound Manage 50(4A Suppl):32-34, 2004. 
  8. Armstrong DG, Lavery LA, Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 366(9498):1704-1710, 2005. 
  9. Eginton MT, Brown KR, Seabrook GR, Towne JB, Cambria RA. A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds. Ann Vasc Surg 17(6):645-649, 2003. 
  10. Morris GS, Brueilly KE, Hanzelka H. Negative pressure wound therapy achieved by vacuum-assisted closure: Evaluating the assumptions. Ostomy Wound Manage 53(1):52-57, 2007. 
  11. Carson SN, Overall K, Lee-Jahshan S, Travis E. Vacuum-assisted closure used for healing chronic wounds and skin grafts in the lower extremities. Ostomy Wound Manage 50(3):52-58, 2004. 
  12. Isago T, Nozaki M, Kikuchi Y, Honda T, Nakazawa H. Skin graft fixation with negative-pressure dressings. J Dermatol 30(9):673-678, 2003. 
  13. Rudolph R, Ballantyne DL, Jr. Skin Grafts. In Plastic Surgery, pp 221-274, edited by JG McCarthy, Saunders, Philadelphia, 1990. 
  14. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 38(6):563-576, 1997. 
  15. Blackburn JH, Boemi L, Hall WW et al. Negative pressure dressings as a bolster for skin grafts. Ann Plast Surg 40(5):453-457, 1998. 
  16. Molnar JA, DeFranzo AJ, Marks MW. Single-stage approach to skin grafting the exposed skull. Plast Reconstr Surg 105(1):174-177, 2000. 
  17. Sposato G, Molea G, Di CG, Scioli M, La R, I, Ziccardi P. Ambulant vacuum- assisted closure of skin-graft dressing in the lower limbs using a portable mini- VAC device. Br J Plast Surg 54(3):235-237, 2001. 
  18. Moisidis E, Heath T, Boorer C, Ho K, Deva AK. A prospective, blinded, randomized, controlled clinical trial of topical negative pressure use in skin grafting. Plast Reconstr Surg 114(4):917-922, 2004. 
  19. Scherer LA, Shiver S, Chang M, Meredith JW, Owings JT. The vacuum assisted closure device: A method of securing skin grafts and improving graft survival. Arch Surg 137(8):930-934, 2002.

EBMR: Comparison of Negative Pressure Wound Therapy using Vacuum-Assisted Closure with Advanced Moist Wound Therapy in the Treatment of Diabetic Foot Ulcers

Evidence Based Medicine Review

Blume P., Walters J., Payne W., Ayala J., and Lantis J.

Diabetes Care 31:631-636, 2008

Michael Turlik, DPM

The Foot & Ankle Journal 1 (12): 5

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.  It permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ©The Foot & Ankle Journal (www.faoj.org)


This was a multi-center randomized controlled efficacy trial of 342 diabetic subjects who were followed for a minimum of 112 days. The study was performed across 37 diabetic foot clinics and hospitals principally in the United States. The primary outcome was complete ulcer closure. There was a thorough description of the method of randomization as well as, concealment allocation. Subjects and investigators were not blinded and it was unclear if data collectors and analysts were blinded. Safety and effectiveness analysis was conducted by the company sponsoring the study.


A sample size calculation was carried out with the expectation of a 20% difference between groups (Absolute Risk Reduction). Enough subjects were enrolled in the study to satisfy the sample size calculation. Baseline data examination reveals no difference between groups. Data from the primary outcome were analyzed as intention to treat as well as, per protocol. Efficacy of the intervention was reported as statistically significant both for intention to treat and per protocol analysis favoring the vacuum assisted closure method. Point estimates were reported for the primary outcome but 95% confidence intervals were not reported.


The manufacturer of the wound closure vacuum assisted device (KCI) supported the study. It was not indicated if the study was registered. The primary author has received payments from the manufacturer for speaking engagements. No other disclosures were noted for other authors or investigators. The article has been marked as an advertisement by the publisher.


The study contains several well described methodological techniques to limit bias, randomization, concealment allocation, and intention to treat analysis. However, due to the nature of the study investigators and subjects were unable to be blinded.

Although unblinded studies are associated with an increased treatment effect this is less likely when the primary outcome is objective such as resolution of an ulcer as opposed to soft measurements such as patient reported outcomes. [1] However, no mention was made regarding blinding of data collectors and analyzers.

The data from the study was analyzed by the company funding the study. This may be perceived as a potential source of bias, it is more reassuring to the reader when the data is analyzed by a neutral third party. The results of the primary outcome were presented as intention to treat and per protocol. It appears the author chose to assign the worst case scenario for the data lost to follow-up for the ITT analysis. Both methods were statistically significant however differed in their point estimate. Was this study clinically significant? The authors expected a 20% difference (ARR) between groups when they calculated their sample size. If the 20% difference is to be accepted as a clinically significant result then the result of the primary outcome using the intention to treat analysis was not clinically significant but only statistically significant. The per protocol analysis was both clinically and statistically significant. Furthermore, it is difficult to analyze the results with only point estimates and not 95% confidence intervals (CI). Why 95% CI were reported for secondary measures and not the primary outcome was unclear.

There appears to be a fairly high loss to follow-up in both arms of the study (approximately 30% per treatment arm). The prognosis for subjects lost to follow-up is thought to be different than the patients who remain in the study. [2] This loss of data may compromise the randomization sequence. Did the loss of follow-up effect the results of the study? The strength of the inference drawn from the study is modified by the magnitude of the difference between the intention to treat and per protocol analysis. It would have been instructive for the reader if the authors addressed this point during their discussion of the results.

Interpretation the study’s results would be better understood with a clear clinically important difference stated by the authors and with 95% CI reported about the point estimate of the primary outcome.

Using the data from this study 95% CI can be calculated for the Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT) for both the intention to treat and per protocol analysis. [3] (table 1)

Table 1

The ARR only exceeds 20% during the per protocol analysis. The lower end of the 95% CI for both ITT and PP is greater than 0 which is consistent with a statistically significant result. Although the point estimate (ARR) for the intention to treat analysis is less than 20% , a risk reduction of more than 20% cannot be ruled out by evaluating the upper end of the 95% CI and would suggest a larger study is necessary or less loss of follow-up.

The NNT is a more clinician friendly metric to access efficacy in studies with dichotomous outcomes. The NNT for both are similar 5 (PP) and 8 (ITT) however, the upper limit of the 95% CI or worse case scenario is 12 (PP) and 24 (ITT). This appears to be a large difference.

Although the use of the vacuum assisted closure appears to be more efficacious the magnitude of the effect is unclear and the inference reduced. It is up to the reader to determine if the loss to follow-up, lack of blinding and lack of clinical significance reduces the inference of the results of this study.

In addition, since the study was designed as an efficacy rather than an effectiveness study, generalizing the results to clinical practice should be undertaking with caution.

The safety data were presented as treatment related rates at six months. However, the trial evaluated treatment until day 112 or ulcer closure by any means. It would be informative to the reader to review the data on safety prior and post intervention termination. There have been two meta-analysis published this year for vacuum assisted closure and diabetic foot ulcers this year. [4,5]


1. Woods L, Egger M, Lotte Gluud L, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 336 (March): 601 – 605, 2008.
2. Montori VM, Guyatt GH. Intention-to-treat principle. Can Med Assoc J 165 (10): 1339 – 1341, 2001.
3. Graphpad. http://www.graphpad.com/quickcalcs/NNT1.cfm Accessed 11/3/2008.
4. Gregor S, Maegle M, Sauerland S, Krahn JF, Peinemann F, Lange S. Negative pressure wound therapy a vacuum of evidence? Arch Surg 143 (2): 189 – 196, 2008.
5. Bell G, Forbes A. A systematic review of the effectiveness of negative pressure wound therapy in the management of diabetes foot ulcers. Int Wound J 5 (2): 233 – 242, 2008.

© The Foot & Ankle Journal, 2008