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A SYSTEMATIC REVIEW OF THE LITERATURE TO ESTABLISH THE

BENEFITS OF NEGATIVE PRESSURE WOUND THERAPY IN THE
TREATMENT OF DIABETIC FOOT ULCERATION.

Objectives and search strategy.

In this paper I reviewed the reported benefits of Negative Pressure Wound Therapy
(NPWT) in the diabetic foot ulcer treatment. NPWT has been used in the treatment of
ulcer of different origin since last 30 years or so. It was not until recently that this
technique has been employed in the treatment of diabetic ulcer (mostly leg ulcer). To
assess the benefit of this technique over the traditional treatment methods, a
comprehensive search of the online literature has been undertaken by using Eduserv
Athens, Pubmed and Medline. Selections of literature were specific to those related to
diabetic ulcer, but some selective reference is made to non-diabetic wounds.

Beneficial:

Three multicentric, RCT identified benefits in use of NPWT in the healing of diabetic
foot ulcer. Two of these studied on foot ulcer as such and one on ulcer after partial
amputation for diabetic foot ulcer.

Concern:

None of the reported papers mentioned any adverse effect of using NPWT, though some
paper were concerned about the optimal negative pressure to be used or whether negative
pressure used should be continuous or intermittent and if there are any significant
difference between these two methods. One review expressed potential publication bias
as a result of lack of access to unpublished study result data (Frank et al, 2008).

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Introduction:

Diabetic wound fail to heal due a complex combination of factors e.g. local oedema
which prevent effective oxygenation and nutrient exchange. Hyperglycaemia complicates
the situation by acting as a substrate for infection. NPWT deliver sub atmospheric
pressure (either intermittent or continuous) to a wound at 50-175 mmHg (optimum
setting 125 mmHg) (Sibbald et al. 2003). In this therapy, an open wound is turned into a
controlled, closed wound while removing excess fluid from the wound bed, and thus
enhancing circulation and disposal of cellular waste from the lymphatic system (Fleck et
al, 2004). Other benefits of NPWT are, providing a moist wound environment
(Morykwas et al, 1997), removing slough (Zarogen et al, 2001) potentially decreasing
wound bacterial burden (Morykwas et al, 1997), reducing oedema and third-space fluids,
increasing blood floe to the wound (Argenta et al, 1997), increasing growth factors, and
promoting white cells and fibroblasts within the wound. In addition to all these good
effect, NPWT which is a mechanical stress to the wound, may kick start healing
(Morykwas and Argenta, 1997).
Most of the study reviewed, used a commercial vacuum assisted closure device (VAC and
KCI), which are available in the market since 1995. Most of the ongoing studies are
being sponsored by these two companies too.

Early research paper on NPWT:

Though these were not specifically mentioned about diabetic foot ulcer, I decided to
mention about these 5 papers published in Russian medical literature. These are the
earliest papers published on NPWT. Two of these papers were published in 1986, one in
1987, and one each in 1991 and 1998. Kostiuchenok et al (1986), discusses the failure of
surgical debridement to significantly reduce microbial counts in the tissue of purulent
wound. They mentioned of using vacuum method for the preparation of persistent
nonhealing wounds and trophic ulcers autografting this study included 221 subjects with
purulent wounds of various aetiologies. They divided the subjects into 3 groups. 22

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subjects were given vacuum treatment before and after surgical debridement, group 2 of
94 subjects received treatment only after surgical debridement and control group of 105
subjects were treated with only surgical debridement. An external funnel device (25 mm
to 30 mm in diameter) was used to apply negative pressure. A pressure of -100 mm Hg
was applied after tightly applied against the wound and moved along the entire wound
area, which removed foreign bodies, blood clots and detritus. Treatment time was 5 to 10
minutes. Treatment was discontinued once no visible contamination was left in the
wound and brisk capillary haemorrhage appeared over the wound surface. Biological
analysis of the microbe count per 1 g of wound tissue (Davydov et al, 1988) was
performed after the vacuum treatment. The authors concluded that negative pressure
treatment of purulent wound in combination with surgical debridement significantly
reduced the bacterial burden within the wound and resulted in improved wound healing.

Recent ones:

Blume et al, (2008) of Yale University Scholl of Medicine, studied 342 patients with
diabetic foot ulcers who were randomised to negative pressure wound therapy or
advanced moist wound therapy for up to 112 days. This was a multicentric randomised
controlled trial. Mean age of 58 years and 79% were male. Aim of this study was to
evaluate safety and clinical efficacy of NPWT compared with advanced moist wound
therapy (AMWT) to treat diabetic foot ulcer. Complete ulcer closure was defined as skin
closure without drainage or dressing requirement. These patients were followed at 3 and
9 months. A greater proportion of foot ulcer achieved complete ulcer healing with NWPT
(73 of 169, 43.2%) than with AMWT (48 of 166, 28.9%) within the 112 days of active
treatment phase (p=0.007). Median time for 100% wound closure was 96 days in the
NPWT group; no such estimate was possible in the AMWT groups. NPWT patients also
experienced significantly (p=0.035) fewer secondary amputation. Safety assessment did
not find any significant difference between the two groups e.g. infection, cellulites, and
osteomyelitis at 6 months. Out come of this study appears to be in favour of NPWT (safe
and more efficacious) than AMWT for the diabetic foot ulcer treatment.

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Joseph et al. (2000) compared the VAC system with standard saline WM dressings in a
group of 24 patients with chronic, non-healing wounds in a prospective randomised trial.
These patients failed multiple medical and surgical wound treatment before trying the
negative pressure trial. At the end of the trial, histologically, the VAC wounds showed
angiogenesis and healthy tissue growth (64%), whereas in the WM group, 81% displayed
inflammation and fibrosis.

One small study was done by McCallon et al (2000) with 10 patients having diabetic foot
ulcer. The treatment options were allocated by a coin flip and then alternately to either
vacuum therapy or saline gauze changed twice daily. Throughout the study, patients were
non-weight bearing. The outcome was determined either healed or ready for surgical
closure or grafting. The vacuum group attained the target after 22.8 days of treatment
compared to 42.8 days with the gauze group. Wound size was reduced to 28% (+/-24)
with the vacuum group, whereas increased to 10% (+/-17) with standard care. Statistical
analysis of the significance was not possible as it was not mentioned whether values were
means or medians, and standard errors or standard deviations. There are problem with
this study as the treatment allocation was done by an open method and there is a lack of
base line wound measurement, which question the decrease or increase in wound size
after the application of treatment options.

Armstrong et al. (2005) looked at whether NPWT improves the proportion and rate of
wound healing after partial foot amputation in diabetic patients. This was a large multi-
centre randomised intention-to-treat trial, involving 162 patients. NPWT was delivered
through the VAC therapy system, and control patients received standard moist wound
care according to the consensus guidelines. In the VAC group more patients achieved
complete wound closure during 16-week assessment (56% compared with 39% in the
control group). This study also found that patients who presented with 0-15% granulation
at baseline, reached 76-100% granulation faster in VAC group than in the control group
(median 42 days versus median 84 days).

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 A retrospective study was done to assess amputation rate in diabetic foot ulcer patients by
comparing the negative pressure wound therapy with traditional wound therapy. This was
a comparative study done in USA between commercial payer (n=3,524) and Medicare
(n=12,795) patients and was analyzed retrospectively. Patients were divided into groups
of Negative Pressure Wound Therapy and control or traditional therapy. Incidence of
amputation in Negative Pressure Wound Therapy groups was lower in Medicare sample
(35%) and commercial payer sample (34%) then the traditional therapy group.
Amputation rates increased progressively with increasing wound debridement depth in
both control groups, but this increasing trend did not occur in the NPWT groups (Robert
et al, 2007).

Study Wound type Number of Therapy control results Comments

done by participants used
Blume Diabetic Foot 342 116 days WMWT Complete wound No data or
healed: 43.2% comments
2008 Ulcer NPWT
(73/169) vs. on 7
28.9% (48/166) patients
Armstron Diabetic Foot 162 with 16 weeks of MWT Complete wound More
closure: 56% vs. chronic
g 2005 Ulcer partial foot vacuum
39% ulcer in
amputation therapy control
group
wounds
Joseph Mixed wounds 24 people VAC MWT Reduction in Data not
wound volume: presented
2000 with 36 changed Changed
78% vs. 30% about
wounds every 48 3 times reduction of
wound
hrs. a day
volume.
McCallon Diabetic Foot 10 patients Vacuum Saline Healed or ready Open
for surgical method of
2000 Ulcer therapy gauze
closure/grafting: allocating
changed 22.8 days vs. 42.8 the
days treatment
twice
option
daily

Table 1: Characteristics of studies.

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Cost NWPT group Conventional therapy (moist gauze) group

Material expenses £277±£153 £10±£7

(p<0.0001)
Nursing expenses £22±£21 £54±£39

Hospitalisation costs £1,195±£708 £1,648±£893

Total costs £1,494±£869 £1,714±£925

Table 2: cost effectiveness of two studies. (Kirby, 2007)

Conclusion:

People with diabetes are at risk of developing foot ulcers. Aim of diabetes treatment is to
control the glycaemia and to prevent development of complications. Even if all the
measures are followed to prevent complications, a number of patients develop ulcer and
become chronic or non-healing. To prevent these foot ending up to amputation, more
effective wound healing technique are needed to be found out.

NPWT is one of the techniques that can be employed for this purpose. The concept of
NPWT is not new one, though using it to treat diabetic foot ulcer are quite recent. Based
on current available clinical experience and trial evidence, NPWT are suitable to be used
for ulcer that are complex, poor healing response and of higher rate of complications.
Good quality evidence is not available in favour of vacuum therapy in healing pressure
ulcers or mixed populations of wounds. There is some evidence that post-amputation foot
wound of diabetic patients heal rapidly by using NPWT. In case of simple diabetic foot
ulcers there is no high quality evidence of an effect on healing. Cost effectiveness
analysis of two studies found that vacuum therapy is associated with lower staff costs and
higher material cost when compared with the traditional or regular formulary dressing.

To be used routinely, this technique need to be tried and tested with more large

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prospective controlled trial (to prove its worth and superiority over the existing
techniques). The question be solved may not be whether NPWT is beneficial in wound
healing or not. Effectiveness of this technique has been documented by numerous case
studies. Determination of parameters for pressure intensity, duration of treatment, interval
between treatment, mode of application, and timing of application will allow clinicians to
provide the most efficient and cost effective therapy.

Reference:
1. Frank Peinemann, Natalie McGauran, Stefan Sauerland and Stefan Lange. Negative
pressure wound therapy: potential publication bias caused by lack of access to
unpublished study results data. 2008; 8, 4
2. Sibbald RG, Mahoney J; V.A.C. Therapy Canadian Consensus Group.A consensus
report on the use of vacuum-assisted closure in chronic, difficult to-heal wounds. Ostomy
Wound Manage 2003; 49 (11): 52-66.
3. Fleck CA, Frizzell LD. When negative is positive: a review of negative pressure
wound therapy. Wound Care 2004; 3(4): 20-5.
4. Morykwas MJ, Argenta LC, Shelton-Brown EI, et al. Vacuum-assisted closure: a
new method for wound control and treatment: animal studies and basic foundation. Ann
Plast Surg. 1997; 38:553-562.
5. Zarogen A. Nutritional assessment and intervention in the person with a chronic
wound. In: Krasner DL, Rodeheaver GT, Sibbald RG, eds. Chronic Wound Care: A
Clinical Source Book for Healthcare Professionals, Third Edition. Wayne, Pa.; Health
Management Publications, Inc.; 2001:117-126.
6. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound
control and treatment: clinical experience. Ann Plast Surg. 1997; 38:563-577.
7. Davydov YA, Larichev KG, et al.: The bacteriological and cytological assessment
of vacuum therapy of purulent wound. Vestnik Khirugii. 1988: 10: 48-52.
8. Peter A. Blume, Jodi Walters, Wyatt Payne, Jose Ayala, John Lantis : Comparison of
Negative Pressure Wound Therapy Using Vacuum-Assisted Closure With Advanced
Moist Wound Therapy in the Treatment of Diabetic Foot Ulcers. Diabetes Care 2008;

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31:631-636.
9. Joseph E, Hamori CA, Bergman S, et al. A prospective randomised trial of vacuum-
assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 2000;
12(3): 60-7.
10. Armstrong DG, Lavery LA; Diabetic Foot Study Consortium. Negative pressure
wound therapy after partial diabetic foot amputation: a multicentre, randomised
controlled trial. Lancet 2005; 366: 1704-10.
11. Robert G. Frykberg, and David V. Williams, Negative-pressure wound therapy and
diabetic foot amputations: A retrospective study of payer claims data. Journal of the
American Podiatric Medical Association. 2007; 97 (5). 351-359.
12. Michael Kirby. Negative pressure wound therapy. The British Journal of Diabetes
and Vascular Disease. 2007; 7 (5). 230-234.