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Debridement: Enzymatic

Debridement: Enzymatic

Debridement: Enzymatic



  • Enzymatic debridement is the topical application of a manufactured formulation using proteolytic compounds to facilitate removal of devitalized tissue and debris from the wound bed [1]
  • Several enzymatic debridement agents have been removed from the United States healthcare market due to issues ranging from safety (cross-sensitivity anaphylaxis), lack of efficacy, and indiscriminate tissue selectivity [1]
  • Clostridial collagenase ointment (Santyl®) is the only Food and Drug Administration (FDA) approved enzymatic debriding agent in the US, and as such, further discussion is limited to this pharmaceutical product


  • Clostridial collagenase ointment (CCO) is a painless method to remove devitalized tissue and debris from the wound bed traditionally used in patients who were unable to tolerate surgical debridement due to co-morbidities, bleeding risk and pain management issues or lack consistent access to a clinician skilled in the surgical option [2] [3] [4]
  • Choosing a debridement method selection is a complex process based on [2]:
    • Patient and wound specific characteristics
    • Setting in which the patient is receiving care
    • Skill set of the practitioner administering and managing the debridement
  • Recent literature supports using CCO in a synergy with conservative sharp debridement and other mechanical methods to achieve superior outcomes (e.g. time to complete debridement) as compared to conservative sharp debridement/mechanical method alone [5][6][7]

How the intervention works

  • Necrotic tissue is mostly comprised of denatured collagen
  • CCO acts selectively hydrolytically cleaves denatured collagen in seven different areas of the collagen strand that anchors devitalized tissue to the wound bed [8]
  • Published reports suggest CCO reduces inflammatory markers in diabetic foot ulcers (DFU) and may enhance cellular migration, proliferation and angiogenic abilities as cleaving multiple sites of the collagen strand may release peptides and matrix sections necessary for wound healing [9]
  • Complete debridement of visible necrotic tissue reported range is 7- 42 days [10][11]
  • CCO should be stopped when granulation tissue is well established, though complete epithelialization with continued used has also been reported [7][8][12] 

Classifications or types of enzymatic debridement (if any)

  • Only one enzymatic debriding agent is available in the United States and Canada


  • CCO is indicated for removal (debridement) of devitalized tissue in chronic dermal wounds and severe burns as a part of a comprehensive management process that includes addressing wound etiology and optimizing the health status of the patient
  • Wounds with devitalized tissue (pressure ulcers, burns, venous ulcers, diabetic foot ulcers, traumatic wounds, surgical wounds, vascular wounds, burns, wounds associated with vasculitic/inflammatory etiologies such as pyoderma gangrenosum) with or without adjunctive sharp debridement
  • Patients who are non-operative candidates, prolonged bleeding times, immunocompromised, minimally to autolytic methods of debridement are optimal candidates for CCO treatment if no systemic infection.
  • Debridement can be achieved in wounds with bioburden (critical colonization) when used in conjunction with compatible antimicrobial/antiseptic agents. [13]
  • Combining surgical sharp debridement with CCO as a treatment strategy has been shown to achieve improved reductions in wound surface areas [5][6][7]


  • CCO is contraindicated in patients that are hypersensitive to collagenase or white petrolatum. White petrolatum serves as the inactive vehicle agent for collagenase
  • Patients with systemic clinical infection should undergo surgical debridement when possible

Evidence and Recommendations

  • Most Clinical Practice Guidelines available at the National Guideline Clearing House (www.guideline.gov) support the use of enzymatic debridement as one method to remove devitalized tissue

Risks and Complications

  • Reported side effects have included: pain, burning, or irritation at site of application
  • Hypersensitivity is rare
  • Local and systemic infection is a potential complication in any wound and not limited to those receiving CCO


  • CCO requires a prescription
  • Applied daily  
  • Available in 30 and 90-gram tubes
  • Dosage is based on both wound size and size of dispensed drug
  • Calculated approximate dosing using the following formula for a 30-gram tube: length x width of wound/2; 90-gram tube formula is: length x width of wound/3 based on the length of the prescription
  • Use a dosing calculator for accuracy (see calculator - external link)
  • Some specialty pharmacies offer prescription templates for providers, calculate dose and drop ship with direct delivery to the patient’s home

Documentation requirements

  • A comprehensive wound assessment should be performed at least weekly, including wound measurements. Dosage should be adjusted accordingly

How to:

  • Effectiveness based on weekly reduction in devitalized tissue
  • Secondary outcome is often noted by a decrease in wound surface area

Practice Tips:

  • Use the MEND mneumonic
    • M – Moisture is needed to optimize effects. If wound bed is dry, cover with a damp saline gauze or petrolatum
    • E- Apply edge to edge of wound. Necrotic tissue can be visible and non-visible to the naked eye. CCO will not harm healthy appearing tissue in the wound bed
    • N – Apply nickel thick. This method approximates calculated dosing requirements
    • D – Daily application. Apply more often if dressing becomes soiled
  • While CCO can be used with other topical agents, collagenase activity can be impacted when used after or with other frequently used wound management agents including wound cleansers, topical antimicrobial and antibiotics
  • Educate fellow clinicians on MEND and avoiding severe potential enzymatic inhibition when used with other topical agents (see external video)
  • Be mindful that while iodine containing dressing will completely inactivate collagenase activity, the variety of silver dressings on the market vary in inhibiting collagenase. Many clinicians choose to use silver dressings to treat detrimental bioburden in the wound simultaneously with collagenase, sacrificing some activity as the gain in reducing bioburden outweighs the inhibition. A list of the variety of silver dressings impact on collagenase inhibition is available at "Products that inhibit collagenase enzymatic activity".[14] 

Patient Education for Clinicians

  • Educate on the MEND pneumonic
  • Assure patients/caregivers can perform dressing changes and identify early signs of wound deterioration
  • Inform patients/caregivers that wound drainage may increase as necrotic tissue liquifies

Coding, Coverage and Reimbursement

  • Co-pay assistance information is available on manufacturer’s website.
  • Discount cards are available from local sales representatives and through many specialty pharmacies
  • As CCO is the only available enzymatic debridement agent, it is on most Medicaid and third-party insurance formularies. Medicare Part D coverage is available.
  • Application of CCO in the office or clinic setting can be billed* using a debridement code: 97602.

*Services billed to third parties are not guaranteed reimbursement


Several studies have shown CCO having an economical advantage as compared to non-CCO selective debridement, medicinal honey, hydrogel, saline dampened gauze. [6][15][16][17] [18][19][20][21][22]

CMS Quality Measures

Currently lacking.

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NOTE: This is a controlled document. This document is not a substitute for proper training, experience, and exercising of professional judgment. While every effort has been made to ensure the accuracy of the contents, neither the authors nor the Wound Reference, Inc. give any guarantee as to the accuracy of the information contained in them nor accept any liability, with respect to loss, damage, injury or expense arising from any such errors or omissions in the contents of the work.


  1. Smith RG. Enzymatic debriding agents: an evaluation of the medical literature. Ostomy/wound management. 2008;volume 54(8):16-34.
  2. Waycaster C, Carter MJ, Gilligan AM, Mearns ES, Fife CE, Milne CT et al. Comparative cost and clinical effectiveness of clostridial collagenase ointment for chronic dermal ulcers. Journal of comparative effectiveness research. 2017;.
  3. Waycaster C, Milne CT et al. Clinical and economic benefit of enzymatic debridement of pressure ulcers compared to autolytic debridement with a hydrogel dressing. Journal of medical economics. 2013;volume 16(7):976-86.
  4. Thomas A., Thayer W. et al. Debridement of chronic wounds: A review of past & present treatment strategies. Today's Wound Clinic;8(5):1-7. . 2014;.
  5. Motley TA, Lange DL, Dickerson JE Jr, Slade HB et al. Clinical outcomes associated with serial sharp debridement of diabetic foot ulcers with and without clostridial collagenase ointment. Wounds : a compendium of clinical research and practice. 2014;volume 26(3):57-64.
  6. Tallis A, Motley TA, Wunderlich RP, Dickerson JE Jr, Waycaster C, Slade HB, Collagenase Diabetic Foot Ulcer Study Group. et al. Clinical and economic assessment of diabetic foot ulcer debridement with collagenase: results of a randomized controlled study. Clinical therapeutics. 2013;volume 35(11):1805-20.
  7. Jimenez JC, Agnew PS, Mayer P, Clements JR, Caporusso JM, Lange DL, Dickerson JE Jr, Slade HB et al. Enzymatic Debridement of Chronic Nonischemic Diabetic Foot Ulcers: Results of a Randomized, Controlled Trial. Wounds : a compendium of clinical research and practice. 2017;.
  8. Sheets AR, Demidova-Rice TN, Shi L, Ronfard V, Grover KV, Herman IM et al. Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing? PloS one. 2016;volume 11(7):e0159598.
  9. Galperin RC, Lange DL, Ramsay SJ, Shi L, Weedon KA, Hudson NM, Dickerson JE Jr, Cargill DI, Slade HB et al. Anti-inflammatory Effects of Clostridial Collagenase Results from In Vitro and Clinical Studies. Journal of the American Podiatric Medical Association. 2015;volume 105(6):509-19.
  10. Ozcan C, Ergün O, Celik A, Cördük N, Ozok G et al. Enzymatic debridement of burn wound with collagenase in children with partial-thickness burns. Burns : journal of the International Society for Burn Injuries. 2002;volume 28(8):791-4.
  11. Milne CT, Ciccarelli AO, Lassy M et al. A comparison of collagenase to hydrogel dressings in wound debridement. Wounds : a compendium of clinical research and practice. 2010;volume 22(11):270-4.
  12. Milne CT, Ciccarelli A, Lassy M et al. A comparison of collagenase to hydrogel dressings in maintenance debridement and wound closure. Wounds : a compendium of clinical research and practice. 2012;volume 24(11):317-22.
  13. McCallon SK, Weir D, Lantis JC 2nd et al. Optimizing Wound Bed Preparation With Collagenase Enzymatic Debridement. The journal of the American College of Clinical Wound Specialists. 2015;volume 6(1-2):14-23.
  14. Jovanovic A, Ermis R, Mewaldt R, Shi L, Carson D et al. The Influence of Metal Salts, Surfactants, and Wound Care Products on Enzymatic Activity of Collagenase, the Wound Debriding Enzyme Wounds.;volume 24(9):242-253.
  15. Gilligan, A.M., Carter, M.J., Waycaster, C., Fife, C.E. et al. Comparative effectiveness of clostridial collagenase ointment to medicinal honey for treatment of venous leg ulcers in outpatient care settings. Presented at: Wild on Wounds. September 2-5, Las Vegas, NV. . 2015;.
  16. Fife CE, Carter MJ et al. Wound Care Outcomes and Associated Cost Among Patients Treated in US Outpatient Wound Centers: Data From the US Wound Registry. Wounds : a compendium of clinical research and practice. 2012;volume 24(1):10-7.
  17. Bergemann R, Lauterbach KW, Vanscheidt W, Neander KD, Engst R et al. Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany. PharmacoEconomics. 1999;volume 16(4):367-77.
  18. Müller E, van Leen MW, Bergemann R et al. Economic evaluation of collagenase-containing ointment and hydrocolloid dressing in the treatment of pressure ulcers. PharmacoEconomics. 2001;volume 19(12):1209-16.
  19. Carter MJ, Gilligan AM, Waycaster CR, Schaum K, Fife CE et al. Cost effectiveness of adding clostridial collagenase ointment to selective debridement in individuals with stage IV pressure ulcers. Journal of medical economics. 2017;volume 20(3):253-265.
  20. Mearns, E.S., Liang, M., Limone, B., et al. et al. Cost-effectiveness of clostridial collagenase ointment compared with medicinal honey for treatment of pressure ulcers ClinicoEconomics and Outcomes Research; August 16 (9):485-489 . 2017;.
  21. Waycaster C, Milne C et al. Economic and clinical benefit of collagenase ointment compared to a hydrogel dressing for pressure ulcer debridement in a long-term care setting. Wounds : a compendium of clinical research and practice. 2013;volume 25(6):141-7.
  22. Motley TA, Gilligan AM, Lange DL, Waycaster CR, Dickerson JE Jr et al. Cost-effectiveness of clostridial collagenase ointment on wound closure in patients with diabetic foot ulcers: economic analysis of results from a multicenter, randomized, open-label trial. Journal of foot and ankle research. 2015;volume 8():7.
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