Where Have All the Enzymes Gone?

Reference: Ramundo J, Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs. 2008;35(3):273–280.

Rationale: Debriding necrotic tissue is an important step in wound care. Indications and efficacy are not clearly established for the major methods used. Scant evidence guides the selection of safe, effective, debriding modalities for chronic wounds.

Objective: Identify and review evidence relating to use of collagenase or papain-urea enzymatic debridement formulations for necrotic tissue removal (NTR) and healing efficacy on leg ulcers, pressure ulcers, or burns.

Methods: MEDLINE, CINAHL, Cochrane databases, and Google Scholar were searched from January 1960 through February 2008 for prospective and retrospective controlled clinical trials comparing either collagenase or papain-urea formulations with other debridement modalities on leg ulcers, pressure ulcers, or burns. Studies were included if NTR and/or healing outcomes were reported. Case studies, case series, and pre-clinical studies were excluded.

Results: Five randomized controlled studies (RCTs), all using gauze dressings impregnated with petrolatum-based ointment containing bacterially-derived collagenase, showed over a 2- to 4-week period that collagenase removed necrotic tissue faster than placebo ointment or gum, but did not improve healing rates for patients with pressure ulcers (n = 14), leg ulcers (n = 30), pressure or leg ulcers (n = 47), or burns (n = 77). One small study reported faster healing in burns debrided with collagenase with added topical polymyxin B sulfate compared to silver sulfadiazine with no debridement (n = 15).

In studies comparing enzymes to other debridement modalities on chronic wounds, collagenase-impregnated gauze dressings removed necrotic tissue from venous leg ulcers faster than 0.5% trypsin/chymotrypsin, but more slowly from pressure ulcers than papain-urea, and more slowly than autolysis using a Ringers-moistened polyacrylate dressing: 20% NTR (n = 15; P > 0.05) compared to 10% NTR with collagenase (n = 27) during the first 14 days of use on venous ulcers.

A comparison-cohort study found debridement times similar for 78 children with partial-thickness burns managed using collagenase alone compared to 41 subjects combining it with surgical excision or receiving surgical excision alone. Patients receiving only collagenase debridement experienced fewer transfusions and shorter hospital stays, but 17 of an additional 29 patients started on only collagenase debridement experienced infections.

The only RCT on papain reported more visible NTR and granulation tissue formation during weeks 2, 3, or 4 of debridement on pressure ulcers using papain combined with urea in a hydrophilic ointment vehicle compared to collagenase in petrolatum ointment in long-term care. There was no significant difference in healing rates (n = 26).

Authors’ Conclusions: Enzymatic agents may be used as the primary technique for debriding certain cases, especially if surgical or conservative sharp wound debridement is not feasible.

Reference: Dryburgh N, Smith F, Donaldson J, Mitchell M. Debridement for surgical wounds. Cochrane Database Syst Rev. 2008;(3):CD006214.

Rationale: Infected surgical wounds are often debrided in hopes of expediting wound healing. No consensus guides the choice of surgical, mechanical, enzymatic, or autolytic debridement methods for infected surgical wounds.

Objective: Review evidence to determine effects of different debridement methods on the rates of healing and/or debridement of infected surgical wounds.

Methods: Authors searched databases of the Wounds Group Specialized Trials Register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, MEDLINE, EMBASE, and CINAHL) for surgical wound debridement studies reporting time to complete debridement and/or time to complete healing following debridement. Two authors independently reviewed data from each study, which was extracted and summarized in a systematic review.

Results: Five small RCTs qualified for inclusion. All RCTs reported the time to complete debridement. The only statistically significant effects were in two RCTs of low methodological quality. One RCT reported complete wound debridement in 5 days. The wounds were dressed twice daily with gauze soaked in 20-mL streptokinase/streptodornase enzymatic ointment (n = 7) compared to 13.5 days when dressed with saline-soaked wet-to-dry gauze (n = 11; P < 0.05). The other RCT reported complete debridement in 8.1 days for infected appendectomy or bowel surgery wounds using dextranomer beads (an autolytic debridement modality discontinued in all countries except South Africa [n = 10]) compared to 11.6 days using mechanical debridement with Eusol ribbon gauze containing chlorinated lime and boric acid solution (n = 10; P < 0.05). Outcome measures were too different to qualify for meta-analysis. The other RCTs reported no differences in complete debridement or healing time between dextranomer beads and either 0.1% chloramine soaked pads, polymer foam dressing, or 10% aqueous polyvinylpyrrolidone.

Authors’ Conclusions: More adequately powered, methodologically sound RCTs that assess valid measures of healing, debridement time, patient quality of life, and cost effectiveness of modern modalities are needed to support clinical decisions regarding debridement modalities.

While debridement is recognized as a vital aspect of chronic and acute wound care, questions remain. Which modality works best on a specific wound type? Studies comparing enzymes are small and rarely control for differences in vehicle, enzymatic activity units, or topical dressing effects. Papain, the last enzyme with more debriding activity than collagenase, is no longer available. Enzymatic or autolytic debridement gently debride chronic or acute wounds with similar speed in the course of 2 to 4 weeks, disproving the myth that enzymatic is faster than autolytic debridement. The only study that compares these two debriding modalities was too small for twice the NTR with autolytic debridement at 2 weeks to be statistically significant. Would debridement be faster if enzymatic debridement were combined with autolytic debridement with, for example, a hydrogel or under moisture-retentive dressings? Only autolytic debridement with a hydrogel has evidence that it improves healing outcomes compared to mechanical debridement with gauze.¹ Is this true only for diabetic foot ulcers? Early surgical debridement improves survival in severely burned patients,² but as described above, may increase the need for transfusions or length of stay in patients with partial-thickness burns. How can one avoid these complications without increasing risk of infection? Mechanical debridement with wet-to-dry gauze is substandard practice, which causes pain and damages healthy tissue.³ Which of these results, if any, generalize to all wounds? Why doesn’t faster debridement hasten healing?

It remains true⁴ that there are no RCTs comparing debridement with no debridement of surgical wounds to test the belief that NTR improves outcomes. Except for autolytic debridement of diabetic foot ulcers with hydrogels, there is insufficient evidence that clearly points to one modality that works best to optimize outcomes on a specific wound type and how to address complications such as infection, pain, blood, and tissue loss. We owe it to patients to go beyond reporting NTR to validate clinical healing, quality of life, and the economic benefits of wound debridement modalities.