Dear Editor:

I would like to highlight several key aspects of the Alvarez paper entitled, “A Prospective, Randomized, Comparative Study of Collagenase and Papain-Urea for Pressure Ulcer Debridement,” which was published in WOUNDS in October, 2002 [2002;14(8):293-301]. It is my hope to provide the readers with additional information, which may allow them to better understand the study outcomes and conclusions. I also wish to exemplify the importance of following manufacturer’s recommendations for product usage.

Proper product application. Alvarez, et al., assumed both Collagenase Santyl® Ointment (Smith & Nephew Inc., Largo, Florida) and Accuzyme® papain-urea ointment (Healthpoint Ltd., Ft. Worth, Texas) should be applied in the same manner, with papain-urea and collagenase applied over the entire surface of nonviable tissue. This is ideal for papain-urea, but is contrary to the manufacturer’s recommendations for collagenase. Papain-urea should be strictly applied to nonviable tissue. Collagenase, however, should be applied to the entire lesion and not be strictly confined to the nonviable tissue. Boxer, et al.,[1] states, “…necrotic tissue may be anchored to the wound surface by strands of undenatured collagen. Since necrotic tissue is an important cause of failure of the wound to heal, it is obvious that such binding must be severed before healing can occur. Until these collagen fibers are severed, debridement cannot take place, granulation is slowed, and no supportive base is available for epithelialization.”1 Collagenase works by severing nonviable collagen, and this can only be done by applying collagenase to the entire base of the lesion. Alvarez, et al., cite references from Rao,[2] Varma,[3] Boxer,[1] and Lee.[4] In each of these studies, collagenase was applied to the entire lesion and not confined strictly to the nonviable tissue. The clinical results reported in these studies with this method of application stand in stark contrast to the results reported in the Alvarez study when application of collagenase is restricted to just the top of necrotic tissue alone.

Based upon the previously mentioned studies, for optimal results, collagenase should be applied to the entire wound bed, thereby denaturing the collagen strands that anchor the necrotic tissue to the wound base. The papain-urea product was used correctly and according to product insert; however, the study assumed that collagenase should be used in the same manner and it should not.

The use of cover dressings. In the Alvarez study, the wounds treated with papain-urea and wounds treated with collagenase were covered with moistened gauze dressings. This is the proper protocol for application of papain-urea and will help create the most beneficial environment to foster papain-urea products; however, it is not proper protocol for collagenase. The active enzyme in the collagenase ointment is collagenase, which is a hydrophilic molecule. For ease of application, the enzyme is contained within a petrolatum base, which is considered hydrophobic. Since the active enzyme, collagenase, which is responsible for debridement, is hydrophilic and seeks moisture, the manufacturer has consistently recommended that a dry, sterile dressing be used to cover collagenase. If not, the formulation’s potency could be diluted as some of the enzyme could be drawn up to the moistened gauze, instead of towards the wound.

The results reported in Alvarez’s study for collagenase when used with a moist gauze dressing are clearly inconsistent with the results reported in past published randomized controlled studies when collagenase was used with a dry gauze dressing. Previously published studies show that much better results can be expected when collagenase is used according to manufacturer’s recommendations, which is to cover the entire lesion with collagenase and then cover the lesion with dry gauze.