John S. Steinberg

Clinical approach to wounds: Débridement and wound bed preparation including the use of dressings and wound-healing adjuvants

Summary: This is a clinical review of current techniques in wound bed preparation found to be effective in assisting the wound-healing process. The process begins with the identification of a correct diagnosis of the wound’s etiology and continues with optimizing the patient’s medical condition, including blood flow to the wound site. Débridement as the basis of most wound-healing strategies is then emphasized. Various débridement techniques, including surgery, topical agents, and biosurgery, are thoroughly discussed and illustrated. Wound dressings, including the use of negative pressure wound therapy, are then reviewed. To properly determine the timing of advance therapeutic intervention, the wound-healing progress needs to be monitored carefully with weekly measurements. A reduction in wound area of 10 to 15 percent per week represents normal healing and does not mandate a change in the current wound-healing strategy. However, if this level of wound area reduction is not met consistently on a weekly basis, then alternative healing interventions should be considered. There is a growing body of evidence that can provide guidance on the appropriate use of such adjuvants in the problem wound. Several adjuvants are discussed, including growth factor, bioengineered tissues, and hyperbaric medicine.

Negative pressure wound therapy for at-risk surgical closures in patients with multiple comorbidities: a prospective randomized controlled study.

Purpose:The purpose of this study is to evaluate the effect of Negative Pressure Wound Therapy (NPWT) on closed surgical incisions. We performed a prospective randomized controlled clinical trial comparing NPWT to standard dry dressings on surgical incisions. Methods:Patients presenting to a high-volume wound center were randomized to receive either a V.A.C. (KCI, San Antonio, TX) or a standard dry dressing over their incision at the conclusion of surgery. These were primarily high-risk patients with multiple comorbidities. The 2 groups were compared, and all incisions were evaluated for infection and dehiscence postoperatively. Results:Eighty-one patients were included for analysis. Thirty-seven received dry dressings, and 44 received NPWT. Seventy-four of these underwent lower extremity wound closure. Average follow-up was 113 days. There were no differences in demographic, preoperative, and operative variables between groups; 6.8% of the NPWT group and 13.5% of the dry dressing group developed wound infection, but this was not statistically significant (P = 0.46). There was no difference in time to develop infection between the groups. There was no statistical difference in dehiscence between NPWT and dry dressing group (36.4% vs 29.7%; P = 0.54) or mean time to dehiscence between the 2 groups (P = 0.45). Overall, 35% of the dry dressing group and 40% of the NPWT group had a wound infection, dehiscence, or both. Of these, 9 in the NPWT group (21%) and 8 in the dry dressing group (22%) required reoperation. Conclusions:There is a significant rate of postoperative infection and dehiscence in patients with multiple comorbidities. There was no difference in the incidence of infection or dehiscence between the NPWT and dry dressing group. This study is registered with ClinicalTrials.gov. The unique registration number is NCT01366105.

The impact of negative-pressure wound therapy with instillation compared with standard negative-pressure wound therapy: a retrospective, historical, cohort, controlled study.

Background: Negative-pressure wound therapy with instillation is a novel wound therapy that combines negative pressure with instillation of a topical solution. Methods: This retrospective, historical, cohort-control study examined the impact of negative-pressure wound therapy with and without instillation. Results: One hundred forty-two patients (negative-pressure wound therapy, n = 74; therapy with instillation, 6-minute dwell time, n = 34; and therapy with instillation, 20-minute dwell time, n = 34) were included in the analysis. Number of operative visits was significantly lower for the 6- and 20-minute dwell time groups (2.4 ± 0.9 and 2.6 ± 0.9, respectively) compared with the no-instillation group (3.0 ± 0.9) (p ⩽ 0.05). Hospital stay was significantly shorter for the 20-minute dwell time group (11.4 ± 5.1 days) compared with the no-instillation group (14.92 ± 9.23 days) (p ⩽ 0.05). Time to final surgical procedure was significantly shorter for the 6- and 20-minute dwell time groups (7.8 ± 5.2 and 7.5 ± 3.1 days, respectively) compared with the no-instillation group (9.23 ± 5.2 days) (p ⩽ 0.05). Percentage of wounds closed before discharge and culture improvement for Gram-positive bacteria was significantly higher for the 6-minute dwell time group (94 and 90 percent, respectively) compared with the no-instillation group (62 and 63 percent, respectively) (p ⩽ 0.05). Conclusion: The authors’ results suggest that negative-pressure wound therapy with instillation (6- or 20-minute dwell time) is more beneficial than standard negative-pressure wound therapy for the adjunctive treatment of acutely and chronically infected wounds that require hospital admission. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Negative-pressure wound therapy with instillation: international consensus guidelines.

Background: Negative-pressure wound therapy with instillation is increasingly utilized as an adjunct therapy for a wide variety of wounds. Despite its growing popularity, there is a paucity of evidence and lack of guidance to provide effective use of this therapy. Methods: A panel of experts was convened to provide guidance regarding the appropriate use of negative-pressure wound therapy with instillation. A face-to-face meeting was held where the available evidence was discussed and individual clinical experience with this therapy was shared. Follow-up communication among the panelists continued until consensus was achieved. The final consensus recommendations were derived through more than 80 percent agreement among the panelists. Results: Nine consensus statements were generated that address the appropriate use of negative-pressure wound therapy with instillation. The question of clinical effectiveness of this therapy was not directly addressed by the consensus panel. Conclusion: This document serves as preliminary guidelines until more robust evidence emerges that will support or modify these consensus recommendations.

The role of chronic and perioperative glucose management in high-risk surgical closures: a case for tighter glycemic control.

Background: The exact risk that poor glucose control introduces to patients undergoing surgical closure has yet to be fully defined. Methods: The authors retrospectively analyzed a prospectively collected database of patients seen at their wound care center to evaluate the effects of chronic and perioperative glucose control in high-risk patients undergoing surgical wound closure. Hemoglobin A1c and blood glucose levels for the 5 days before and after surgical closure were recorded and compared with the primary endpoints of dehiscence, infection, and reoperation. Univariate and multivariate analyses were performed. Results: Seventy-nine patients had perioperative glucose levels and 64 had hemoglobin A1C levels available for analysis. Preoperative and postoperative hyperglycemia (defined as any blood glucose measurement above 200 mg/dl) as well as elevated A1C levels (above 6.5 percent or 48 mmol/ml) were significantly associated with increased rates of dehiscence (odds ratio, 3.2, p = 0.048; odds ratio, 3.46, p = 0.028; and odds ratio, 3.54, p = 0.040, respectively). Variability in preoperative glucose (defined as a range of glucose levels exceeding 200 points) was significantly associated with increased rates of reoperation (odds ratio, 4.14, p = 0.025) and trended toward significance with increased rates of dehiscence (p = 0.15). In multivariate regression, only perioperative hyperglycemia and elevated A1c were significantly associated with increased rates of dehiscence. Conclusions: In primary closure of surgical wounds in high-risk patients, poor glycemic control is significantly associated with worse outcomes. Every effort should be made to ensure tight control in both the chronic and subacute perioperative periods. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Functional limb salvage in the diabetic patient: the use of a collagen bilayer matrix and risk factors for amputation.

Background: The diabetic foot ulcer presents a therapeutic challenge with a high rate of limb infection and extremity amputation. Adequate debridement and stable coverage of exposed structures are paramount to preserving limb length. The authors reviewed their use of a collagen bilayer matrix in the diabetic population for the preservation of functional limb length. Salvage rates were stratified with patient comorbidities of severe peripheral arterial disease and/or persistent infection. Methods: A retrospective review was performed of all consecutive patients who underwent application of Integra by the senior authors (J.S.S., C.E.A.) for lower extremity salvage between January of 2004 and December of 2008. Results: A total of 105 patients with 121 separate wounds were analyzed. Patient age ranged from 22 to 80 years (mean, 58 years). The average wound size was 25.9 cm2 in the diabetic population. Average follow-up was 325 days, and average number of operations before closure was 1.28. In the diabetic population, of the 59 patients identified as low risk for amputation, 10 (17 percent) progressed to amputation. Of the 28 patients identified as high risk for amputation, 15 (54 percent) progressed to amputation. In the nondiabetics, 31 patients were classified as low risk for amputation, and one (3 percent) went on to an amputation. Conclusions: Use of a collagen bilayer matrix appears to be a viable option for reconstruction and stable closure in the diabetic patient at low risk for amputation, with risk based on available blood supply and evidence of infection. In the diabetic patient at high risk for amputation, however, the rate of salvage may not be improved with the use of Integra.

Best‐practice algorithms for the use of a bilayered living cell therapy (Apligraf®) in the treatment of lower‐extremity ulcers

Tissue‐engineered skin substitutes such as Apligraf® have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard‐to‐heal wounds since 1998, Apligraf® has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound‐healing technologies, such as tissue‐engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf®, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf® treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user‐friendly direction simplifying both patient selection and appropriate use of Apligraf® within the context of good wound‐healing practice.

Débridement of the noninfected wound

The utility of wound débridement has expanded to include the management of all chronic wounds, even in the absence of infection and gross necrosis. Biofilm, metalloproteases on the wound base, and senescent cells at the wound edge irreversibly change the physiology of wound healing and contribute to a pathologic, chronic inflammatory environment. The objective of this review is to provide surgeons with a baseline understanding of the processes of débridement in the noninfected wound.

Wound Care: Biofilm and Its Impact on the Latest Treatment Modalities for Ulcerations of the Diabetic Foot

Biofilm is an increasingly important topic of discussion in the care of the chronic diabetic foot wound. Treatment modalities have focused on biofilm reduction or eradication through debridement techniques, topical therapies, negative pressure therapy, and ultrasound. In addition, advanced wound healing modalities, such as bioengineered alternative tissues, require optimal wound bed preparation with specific consideration of biofilm reduction before their application. Although fundamental principles of diabetic wound care still apply, critical thought must be given to biofilm before implementing a treatment plan for the closure of these complex wounds.

Confirmatory data from EU study supports Apligraf for the treatment of neuropathic diabetic foot ulcers.

INTRODUCTION A study of 72 subjects conducted in the European Union and Australia assessed the safety and efficacy of Apligraf (Organogenesis, Inc, Canton, Massachusetts), a bilayered cell therapy composed of living keratinocytes and living fibroblasts in the treatment of non-infected, diabetic foot ulcers (DFU). The design and patient population of this study were similar to a 208-subject United States study (Veves et al., 2001), which led to FDA approval of Apligraf for the treatment of DFU. EU patient outcomes were compared and contrasted to established US-based patient outcome parameters. METHODS Subjects with a non-infected neuropathic diabetic foot ulcer present for at least two weeks were enrolled in these prospective, multicenter, randomized, controlled, open-label studies that compared Apligraf used in conjunction with standard therapy (sharp debridement, standard wound care, and off-loading) against standard therapy alone. RESULTS The design, conduct, and patient populations of the EU and US studies were comparable. Pooling of data was able to be performed because of the similarity and consistency of the two studies. Efficacy and safety results remained consistent across studies independent of mean ulcer duration that was significantly longer in the EU study (21 months, compared to 10 months in the US). Reported adverse events through 12 weeks were comparable across treatment groups in the two studies. Multiple efficacy measures consistently demonstrated superiority of Apligraf treatment over control treated groups in both studies. Combining the data from both studies, 55.2% (80/145) of Apligraf subjects had complete would closure by 12 weeks, compared to 34.3% (46/134) of Control subjects (P = 0.0005; Fishers exact test), and Apligraf subjects had a significantly shorter time to complete wound closure (P = 0.0004; log-rank test). CONCLUSIONS Both the EU and US studies exhibited superior efficacy and comparable safety for subjects treated with Apligraf compared to control treated subjects. The similar outcomes of the two studies provide robust, consistent evidence of the benefit of Apligraf in treating geographically disparate DFU patient populations.