ANOLIN, MARC EDRIANN T.

BSNGROUPCA01

Enzymatic Wound Debridement

Mikel Gray Janet Ramundo Journal of Wound, Ostomy and Continence Nursing June 2008 Volume 35 Number 3 Pages 273 - 280

Abstract Background: Clinical experience and existing research strongly support debridement as a necessary component of wound bed preparation when slough or eschar is present. Multiple techniques are available, but the indications for each technique and their efficacy are not clearly established. There is little evidence to guide the clinician in the selection of a safe, effective debridement method for the patient with a chronic wound. Objectives: We sought to identify evidence related to the efficacy of enzymatic debriding agents collagenase and papain-urea in the removal of necrotic tissue from the wound bed and its impact on wound healing. Search Strategy: A systematic review of electronic databases was undertaken using key words: (1) debridement, (2) enzymatic debridement, (3) collagenases, (4) papain, (5) urea, and (6) papain-urea. All prospective and retrospective studies that compared enzymatic debridement using collagenase or papain-urea (with and without chlorophyllin) on pressure ulcers, leg ulcers, or burn wounds were included in the review. All studies that met inclusion criteria and were published between January 1960 and February 2008 were included. Results: Collagenase ointment is more effective than placebo (inactivated ointment or petrolatum ointment) for debridement of necrotic tissue from pressure ulcers, leg ulcers, and partial-thickness burn wounds. Limited evidence suggests that a papain-urea-based ointment removes necrotic material from pressure ulcers more rapidly than collagenase ointment, but progress toward wound healing appears to be equivocal. Limited evidence suggests that treatment of partial-thickness burn wounds in children with collagenase ointment may require an equivocal time to treatment with surgical excision and that combination treatment may reduce the need for surgical excision. Insufficient evidence was found to determine whether collagenase ointment removes necrotic tissue from leg ulcers more or less rapidly than autolytic debridement enhanced by a polyacrylate dressing. Implications for Practice: Enzymatic debriding agents are an effective alternative for removing necrotic material from pressure ulcers, leg ulcers, and partial-thickness wounds. They may be used to debride both adherent slough and eschar. Enzymatic agents may be used as the primary technique for debridement in certain cases, especially when alternative methods such as surgical or conservative sharp wound debridement (CSWD) are not feasible owing to bleeding disorders or other considerations. Many clinicians will select enzymes when CSWD is not an option. Clinical

experience strongly suggests that combined therapy, such as initial surgical debridement followed by serial debridement using an enzymatic agent or enzymatic debridement along with serial CSWD, is effective for many patients with chronic, indolent, or nonhealing wounds.

Questions 1. Does enzymatic debridement using the agent collagenase remove necrotic debris from the wound bed and promote wound healing in pressure ulcers, leg ulcers, or burn wounds? 2. Does enzymatic debridement using the agent papain-urea remove necrotic debris from the wound bed and promote wound healing in pressure ulcers, leg ulcers, or burn wounds? Introduction

Debridement is defined as removal of foreign material and devitalized or contaminated tissue from

the wound bed until surrounding healthy tissue is exposed.1 Multiple techniques are used to debride wounds; the most common techniques are surgical, conservative sharp, mechanical, high-pressure fluid irrigation, ultrasonic mist, autolysis, enzymatic, larval therapy, and autolysis.2,3 Enzymatic debridement is the application of exogenous enzymes to the wound bed in order to degrade necrotic tissue without harming viable, granulation tissue. Debridement is considered a necessary component of wound bed preparation, especially in chronic, nonhealing, or indolent wounds considered to be stalled in the inflammatory phase of wound healing.3 Limited evidence exists that directly links debridement to wound healing.4,5In addition, expert opinion and clinical experience overwhelmingly support its necessity when the wound bed contains necrotic tissue in the form of yellow slough or black eschar. Existing research provides a rational basis for debridement as a component of wound bed preparation in order to (1) reduce the inflammatory cytokines, fibronectin, and metalloproteinases produced when a wound is chronically inflamed owing to the presence of necrotic tissue; (2) promote DNA synthesis and growth of keratinocytes that are inhibited by production of these inflammatory products; and (3) reduce bacterial bioburden associated with necrotic tissue in the wound bed.6-10 Enzymatic debridement is frequently used either alone or in combination with other techniques such as surgical debridement, to remove necrotic tissue and promote wound healing.3,12 It can be used in patients with infected or contaminated wounds, patients on anticoagulant therapy when surgical debridement is not feasible, and on either yellow slough or black eschar. Enzymatic debriding agents are typically applied daily or twice daily depending on the agent. They are applied directly to the wound bed and may produce a transient stinging sensation that some patients find distressing. Some patients may be hypersensitive to the enzyme or another component within its delivery vehicle. Clinicians are advised to cleanse the wound and to cross-hatch black eschar before applying an enzymatic debriding agent. The purpose of this Evidence-Based Report Card is to identify and review existing evidence concerning the effectiveness of 2 enzymes, collagenase and papain-urea, for debriding pressure ulcers, leg ulcers, or diabetic foot ulcers. Based on the existing research, the primary outcome we selected was time required to remove visible necrotic material from the

wound bed. Time to wound healing, the preferred outcome, was reported when available, but it was not measured in the majority of studies identified. Methods A systematic review of electronic databases MEDLINE and CINAHL (from January 1960 to February 2008) was undertaken using the following key words: (1) debridement, (2) enzymatic debridement, (3) collagenases, (4) papain, (5) urea, and (6) papain-urea. Boolean features of these databases were used to combine these terms with the following key words: (1) wound healing, (2) pressure ulcer, (3) varicose ulcer, (4) leg ulcer, and (5) diabetic foot. All prospective and retrospective studies that compared enzymatic debridement using collagenase or papain-urea (with and without chlorophyllin) on pressure ulcers, leg ulcers, or burn wounds were included in the review. Studies focusing on children and adults were included; studies reporting in vivo or in vitro model data were excluded. Prospective and retrospective case studies and multiple case series were excluded. Studies published in English and those with an English language abstract were included. The Cochrane Database for Systematic Reviews was searched using the key term debridement. The ancestry of review articles and research reports were searched for additional studies. Finally, the Web-based engine, Google Scholar, was searched using the key terms: (1) debridement, (2) enzymatic debridement, (3) collagenase, and (4) papain-urea. Question 1: Does enzymatic debridement using the agent collagenase remove necrotic debris from the wound bed and promote wound healing in pressure ulcers, leg ulcers, or burn wounds? Nine studies were identified that compared enzymatic debridement with a petrolatum-based ointment, placebo ointment, autolytic debridement, surgical excision, silver sulfadiazine, or alternative enzymatic agents (papain-urea and trypsin/chymotrypsin)13-22 (Table 1). Five randomized clinical trials were identified that compared collagenase derived from a bacterial source to a placebo comprising a heat-inactivated collagenase ointment or a petrolatum-based ointment never charged with the enzymatic agent. Collagenase Versus Placebo Boxer and coinvestigators13 compared two 0.5% collagenase preparations to a heat-inactivated ointment in 47 subjects with either pressure ulcers or leg ulcers. Collagenase was administered in a petrolatum-based ointment or as a hydrophilic gum that required hydration to achieve the desired concentration of 0.5%. The gum preparation also contained neomycin; the authors did not comment on what actions were taken to maintain the blind when the hydrophilic gum was administered. The majority of their study population had more than 1 ulcer, and analysis of results was based on 62 wounds. The volume of necrotic tissue at baseline was evaluated using an ordinal scale, where 1 indicated minimal debris in the wound bed with subclinical necrosis, 2 indicated a thin layer of necrotic tissue, 3 indicated a thick layer of necrotic tissue, and 4 indicated marked, heaped-up necrotic materials. No distinction between eschar and slough was indicated in the research report. The efficiency of debridement was indicated via an estimate of the percentage of reduction (varying from 0% to 100%) in wound area covered by necrotic tissue and changes in the thickness of necrotic tissue. The efficiency of debridement in level 1 wounds was evaluated based on the percentage of granulation tissue observed in the wound bed. Wounds were cleansed with sterile

water and water-soaked gauze, and the ointment or gum preparation was applied directly to the wound. Wounds were treated over variable time periods until complete debridement was obtained varying from 1 week to 14 weeks. Significantly more wounds (58/62, 94%) managed by the collagenase preparations achieved complete debridement as compared to 1 of 8 lesions (13%) in the wounds treated by the placebo ointment ( P < .01). No significant difference in the efficiency of debridement was noted when the collagenase ointment and collagenase gum with neomycin-treated wounds were compared. The researchers reported that no hypersensitivity reactions occurred. No clinically relevant adverse side effects occurred; some subjects treated with collagenase over a period of multiple weeks developed mild erythema adjacent to the wound that subsided when application of the enzymatic agent was discontinued. Wound healing outcomes were not reported.

REACTION: --It is a good thing to know that doctors nowadays have more innovative ways of concealing and treating wounds of humans. Debridement has been incorporated into a conceptual framework focusing on Wound Bed Preparation. This framework was originally described and subsequently refined by Schultz and colleagues.11 It is based on a synthesis of research and clinical experience on the management of indolent or nonhealing (chronic) wounds. Wound Bed Preparation focuses on 4 factors that must be addressed when formulating a treatment plan for a chronic wound, collectively referred to using the acronym TIME, where "T" indicates nonviable or deficient tissue, "I" indicates infection or inflammation, "M" indicates moisture imbalance, and "E" indicates a nonadvancing or undermined wound edge. While widespread agreement exists concerning the necessity of debridement in wounds with grossly visible necrotic tissue, less agreement exists concerning the optimal technique for removing slough or eschar from the wound.3 Selecting the optimal technique for debriding a specific wound is influenced by multiple factors, including the type and volume of necrotic tissue, the presence of underlying infection or bacterial bioburden, wound size, pain associated with the technique, presence of comorbid conditions including sepsis, vascularity of the wound and adjacent tissue, patient preference, and cost. It may also be impacted by access to providers, particularly in home care and long-term care.