Introduction

The Centers for Disease Control and Prevention1 defines diabetes mellitus as a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. The most common type of diabetes is type 2, previously called non-insulin-dependent diabetes mellitus or adult-onset diabetes. The prevalence of diabetes is significant; the American Diabetes Association2 stated that 25.8 million individuals in the United States had diabetes in 2011, representing 8.3% of the population. The cost of diabetes mellitus was last determined to be $174 in 2007, but better diagnostic tools, better health care leading to longevity, and better reporting methodology lead to far greater projected costs per year for the future. It is believed that approximately $1 in $10 health care dollars in 2010 were attributable to diabetes mellitus. Indirect costs include increased factors such as absenteeism, reduced productivity, and lost productive capacity due to disease-associated morbidity and mortality.

Diabetes mellitus is associated with a plethora of comorbid conditions including diabetic foot ulcers.3 Diabetic foot ulcers are a major reason for hospitalization and limb loss.4 Neuropathy is a major contributing factor to the development of these ulcers; it is associated with chronic hyperglycemia and changes in the microvasculature leading to progressive damage to the sensory fibers that normally signal impending foot damage, and an increased risk of unperceived foot ulcers. The average lifetime risk of developing a foot ulcer is as high as 25%,4 and foot ulcers and related complications account for approximately 16% of all hospital admissions and 23% of all hospital days among diabetic patients.3

Healing of a diabetic foot ulcer involves the well-established processes of inflammation, granulation tissue formation and epithelialization, and finally maturation of the scar tissue to provide stable restoration of skin and tissue integrity.5 Topical therapy for diabetic wounds focuses on standard moist wound therapy (SMWT) as the normative course of treatment, based on a major study in 1962 that definitively established that a clean moist, occluded wound healed more rapidly than a wound left open to the air.6 Thus, moist wound therapy is the standard to which other treatments are compared or supplemented.7

Negative pressure wound therapy (NPWT) has been described in the literature since the 1940s, but vacuum-assisted closure (VAC) systems (one type of NPWT) has been used in the treatment of open wounds on an anecdotal basis and in small studies since the 1980s.8 The basic components of VAC devices include an open-cell polymer foam dressing that conforms to the wound bed, a transparent film sheet used to seal the dressing, a plastic drainage tube attached to a collection reservoir and a vacuum pump that provides intermittent or continuous pressure, ranging from -25 mmHg through -200 mmHg.9 The negative pressure causes contraction of the dressing and deformation of the cells in the wound bed, which has been shown to stimulate neo-angiogenesis and granulation tissue formation. In addition, the negative pressure provides removal of wound exudate and reduces edema, which promotes perfusion.9 This type of wound treatment is performed in a variety of health care settings, including acute care, home care, long-term acute care, outpatient, and some long-term care settings, but is always monitored (either directly or indirectly) by a health care provider who checks the wound progress by tracking the removal of fluid, the size of the wound, progress in granulation tissue formation, and who intervenes should there be any adverse effects.

Case studies and small comparative studies have been reported that compare wound healing outcomes for patients managed with NPWT to those managed with SMWT.10 However, recommendations for changes in routine management of diabetic foot ulcers require demonstrated benefit across multiple studies with larger numbers of patients, and specifically studies involving diabetic foot ulcers. It is also important to consider the cost of treatment in comparison to outcomes, since VAC is considerably more expensive than SMWT. Nonetheless, VAC therapy may prove to be more cost-effective than SMWT, if VAC therapy provides a significant reduction in healing time and overall resource utilization. This literature review was undertaken to address the following questions: (1) Is NPWT clinically more effective than SMWT for wound healing in patients with a diabetic foot ulcer, (2) is NPWT more effective than SMWT in patients with a diabetic foot ulcer, with regard to promotion of faster wound closure rate, and (3) is NNPWT more effective than SMWT in patients with a diabetic foot ulcer, with regard to safety and reduction in secondary complications?

Methods

A review of the major nursing journal databases PubMed and OVID from 2000 to 2010 was completed using the key words "vacuum assisted closure," "negative pressure wound therapy," "diabetic wounds," and "standard moist wound therapy." Criteria for inclusion in this review included randomized clinical trials involving patients with diabetic foot ulcers and which comparing NPWT to SMWT. A total of 6 studies were found, and 4 met inclusion criteria.

Results

Patients in all 4 studies had chronic or acute diabetic foot wounds although the severity and precursor condition (partial foot amputation) varied.4,7,11,12 Patient demographics (age, ethnic group, etc) and exclusion criteria varied from study to study. For example, Etoz11 excluded patients who had arterial insufficiency as evidenced by absence of pedal pulses; this was not an exclusion criterion in the other 3 studies. The only exclusion criteria that were consistent for all 4 studies were ulcer malignancy, current treatment with corticosteroids or radiotherapy, underlying osteomyelitis, sepsis, pregnancy, and nursing mothers.4,7,11,12

Prior to treatment assignment in all 4 studies, wounds were debrided of nonviable tissue.4,7,11,12 In 3 of the studies, systemic antibiotic therapy was given to all patients for prophylaxis following surgical debridement.4,7,11,12 Patients were randomly assigned to the experimental intervention (VAC) or SMWT in all studies. No studies were identified in which NPWT techniques other than VAC were used. The amount of continuous negative pressure was -125 mmHg, according to standard treatment guidelines. Dressing changes varied from every 24 hours to every 48 hours to 3 times per week.4,7,11,12

Patients in the comparison groups received SMWT. However, variations in SMWT were noted. Patients in the Etoz study received traditional moist saline dressings changed twice a day,11 while participants in the study by Blume and colleagues7 received advanced dressings (predominantly hydrogels and alginates) according to guidelines published by the Wound, Ostomy and Continence Nurses Society and institutional protocols. Comparison group patients in the Armstrong and colleagues4 study also were managed with advanced wound dressings (alginates, hydrocolloids, foams, or hydrogels); the attending clinician selected the specific dressing based on standardized guidelines and an individualized assessment of wound status. In the study by Sepulveda and colleagues,12 the specific dressing was chosen according to the saturation of the secondary bandage. If the bandage presented a rate of saturation lower than 50%, the wound was dressed with a hydrocolloid gel, tulle (woven gauze) impregnated with a petrolatum emulsion, and a bandage. In contrast, if the saturation of the dressing was greater than 50%, the wound was covered with an alginate and a bandage.

Question 1: Is NPWT more effective than SMWT for wound healing in patients with a diabetic foot ulcer?

The evidence from these studies suggests that NPWT using a VAC system promotes healing of diabetic foot ulcers, and in some cases, complete reepithelialization.4,7,11,12 In the study by Blume and colleagues,7 the proportion of ulcers with complete closure was significantly greater (P = .007) for patients receiving NPWT as compared to SMWT. Similarly, in the study by Armstrong and colleagues,4 a higher percentage of patients healed with NPWT than with the control treatment, 56% versus 39% (P = .040). Etoz11 also observed a significant difference in the number of days required for complete or near complete granulation of the wound bed without any infection, 11.25 days for patients receiving NPWT and 15.7 days for those receiving SMWT (P = .05). In the study by Sepulveda and colleagues,12 90% granulation took 18.6 days for patients managed with NPWT versus 32.3 days for patients managed with SMWT (P = .007).

The endpoints were similar in all studies. In the Blume7 study, the primary endpoint was complete ulcer closure, defined as 100% reepithelialization. Sepulveda and colleagues12 defined the endpoint as 90% granulation, and although Etoz did not define the endpoint definitely by complete granulation, he noted that the criteria for the end point was no sign of inflammation and readiness for surgical closure almost complete granulation with no signs of inflammation.11 However, not all patients in these studies reached the treatment endpoints; this was particularly true of the patients managed with SMWT. In the Armstrong and colleagues,4 study patients were treated until wounds were healed or until completion of the 112-day period of active treatment.

Considered collectively evidence from these 4 studies suggests that NPWT is clinically more effective than SMWT for wound healing in patients with a diabetic foot ulcer. Specifically, more patients experienced wound improvement or complete wound closure when managed with NPWT as opposed to SMWT.4,7,11,12

Question 2: Is NPWT more effective than SMWT in patients with a diabetic foot ulcer, with regard to promotion of faster wound closure rate?

It has been reported that NPWT decreases bacterial colonization and interstitial edema. It also increases capillary blood flow and removes fluid from the wound, which is hypothesized to promote rapid formation of granulation tissue required for wound closure. Furthermore, NPWT reduces wound surface area by the traction force of negative pressure and increases mitotic activity among cells responsible for collagen synthesis and epithelial resurfacing.9

Etoz11 measured wound surface area every 48 hours in patients in both the treatment and comparison groups; wound therapy was continued until the wound bed was almost completely granulated and there was no sign of inflammation. Before treatment, the mean wound surface area was not significantly different between the experimental and control groups. However, within 1 week there was an increased amount of granulation tissue and a decreased amount of nonviable tissue among wounds in the NPWT group. At study endpoint, the mean wound surface area decreased 20.4 cm² (range, 88.6-109.0 cm²) in the NPWT group versus a men decrease of 9.5 cm² (range, 85.3-94.8 cm²) in the control group; this difference was statistically significant (P = .032).

In the study by Armstrong and colleagues,4 the rate of wound healing, based on the time to complete closure, was faster in the NPWT group than in the control group (P = .005), and the rate of granulation tissue formation, based on the time to 76% to 100% formation in the wound bed, was faster in the NPWT group than in the control group (P = .002).

The reduction in wound surface area over a defined period of time reflects the rate at which the ulcer is healing. Though not reaching complete closure, Blume and colleagues7 reported that the surface area of the wounds in the NPWT group was smaller than wounds in the SMWT group (P = .032).7 A significant difference in size on day 28 (change of 4.32 cm² vs 2.53 cm², P = .021) was also noted and the time to 75% closure was significant (54 vs 84 days) (P = .014). In summary, the data from these studies suggest that NPWT using a VAC system promotes more rapid closure of diabetic foot ulcers than SMWT.4,7,11,12

Question 3: Is NPWT more effective than SMWT in patients with a diabetic foot ulcer, with regard to safety and reduction in secondary complications?

Secondary complications associated with diabetic foot ulcers vary, but most commonly involve various infectious complications and wound deterioration resulting in amputation. Wound complications in the studies reviewed were typical for diabetic foot ulcers and included wound infections, cellulitis, osteomyelitis, edema, and the need for amputation.

Blume and colleagues7 found significantly fewer secondary amputations for patients assigned to the NPWT treatment group versus those treated with SWMT (4.1% vs 10.2% P < .035). In contrast, Armstrong and colleagues4 found no significant differences in secondary amputation rates when comparing NPWT and SMWT (3% vs 11%, P = .6). The relative risk ratio (0:225) indicated that patients treated with NPWT were less likely than control patients to undergo secondary amputation. However, this finding must be viewed with caution in light of the 95% confidence interval (0.05-1.1).

Blume and colleagues7 evaluated differences between MPWT and SMWT groups at 6 months (incidence of wound infections, edema, cellulitis, and osteomyelitis) and found no statistically significant differences. Armstrong's group4 also found no significant differences in the frequency and severity of adverse events among the 2 groups (42% vs 54%, P = .875).

Apelqvist and colleagues13 examined the data collected in the Armstrong4 study and noted that significantly more surgical procedures including debridement were performed in the SMWT group than in the NPWT group (120 vs 43, P < .001). This finding suggests that recurrence of nonviable tissue was more likely among the group managed with SMWT, which is consistent with the results of Etoz,11 who reported that the NPWT group had increased granulation tissue and decreased nonviable tissue when compared to the SMWT group. Edema of the extremities diminished in patients in both groups, as did the surface area of diabetic foot ulcers (P = .05).11

Discussion

Findings from these 4 studies suggest that outcomes using NPWT via a VAC system were favorable when compared to the SMWT in the treatment of diabetic foot ulcers. Specifically, the data suggest that VAC therapy promotes faster reduction in wound surface area through granulation tissue formation and reepithelialization, reduces time to healing, and may reduce the incidence of infectious complications (Table 1).

TABLE 1. Summary Results of Studies Reviewed

These data also indicate that NPWT is associated with no more adverse side effects than SMWT. Nevertheless, NPWT should be implemented as one element of a comprehensive management program that includes effective offloading of plantar surface ulcers and tight glucose control in addition to local wound care. As noted by all the investigators, surgical debridement is an essential "first step" in local wound care and should be initiated prior to using NPWT. NPWT can then be used either to promote primary wound healing or to prepare a wound for surgical closure.

Further research is needed to address limitations of these studies that do not control for age, sex, race, and type and severity of the diabetic foot wound. Refining the demographic variables as well as narrowing the type of diabetic foot wound might lead to better criteria for the use of VAC. Further research is also needed to address resource utilization and costs that might lead to more informed decisions on where and when to use the VAC. Finally areas of investigation should address the efficacy of NPWT systems other than VAC and should explore situations in which NPWT is and is not likely to be as effective.

Key Points

* Evidence from 4 randomized controlled trials suggests that NPWT using a VAC system is more effective than SMWT in promoting the healing of diabetic foot wounds.

* Evidence from 4 randomized controlled trials suggests that NPWT using a VAC system is more effective than SMWT in promoting faster healing of diabetic foot wounds.

Recommendations for Clinical Practice

1. NPWT should be considered as one of multiple options in a comprehensive treatment plan for patients with diabetic foot ulcers.

2. The condition of any wound requiring medical management should be comprehensively assessed with regard to underlying causes, systemic factors, and conditions at the wound in order to develop a plan of care that should be continually reassessed to determine if progress toward healing is being made.

Conclusion

Findings from these studies provide evidence that NPWT is safe and effective for management of diabetic foot ulcers. Nevertheless, NPWT should be implemented as one element of a comprehensive management program that includes effective offloading of plantar surface ulcers and tight glucose control in addition to local wound care.

References