Volume 28 Number 4

Clinical question

What is the best available evidence for enzymatic debridement to promote complete healing and/or improvement in wound bed condition in pressure injuries (PIs)?

Summary

Evidence from three randomised controlled trials (RCTs),^1-4 two^{1, 4} of which were included in a network meta-analysis,⁵ provided Level 1 evidence supporting use of a collagenase to debride PIs to promote complete healing.^1-5 Level 2⁶ and Level 3^{7, 8} evidence suggested use of a collagenase to debride PIs was associated with superior improvements in the wound bed condition compared with sharp⁶ or autolytic debridement.^{7, 8} Level 1 evidence^{9, 10} found no difference between a collagenase and other types of enzymatic debridement for achieving PI healing. Expert opinion (Level 5) suggested that the urgency of debridement,^11-15 vascularisation of the wound bed,¹⁶ type of non-vitalised tissue to be debrided,¹⁷ the patient’s tolerance of the treatment,^{18, 19} and financial cost^{1, 3, 20, 21} are all considerations when selecting a method for debriding PIs. This evidence supported a Grade B recommendation (a weak recommendation).²²

Clinical practice recommendations 

Enzymatic debridement can be used to remove devitalised tissue from pressure injuries in the presence of adequate vascularisation and in the absence of a need for rapid removal of non-viable tissue (Grade B).

Sources of evidence 

This summary was conducted using methods published by the Joanna Briggs Institute.^22-24 The summary is based on a literature search combining search terms related to PIs and enzymatic debridement. Searches were conducted in CINAHL, Medline, the Cochrane Library and Google Scholar for evidence published up to November 2019 in English. Levels of evidence for intervention studies are reported in the table below. (1 = high)

Background

Debridement is the process of removing devitalized tissue (e.g. necrotic tissue or bacteria/biofilm) from the wound bed. One method of debriding a wound is enzymatic debridement—the use of exogenous enzymes that digest proteins (collagen and/or fibrin) in necrotic tissue.⁵ Enzymes used for debridement include general proteolytics (active against a broad range of protein matter), fibrinolytics (active against fibrin) and collagenases (selective action against collagen).^{19, 28} Collagenase ointment appears to act on lower levels of necrotic tissue, working from the bottom of the wound bed up.²⁵  Papain-based enzymatic debriding agents act from the top of the wound down, and act against all protein that contains cysteine,¹⁷ working best in the presence of urea.^{17, 25} 

Evidence

Evidence from primarily pre-1980s studies reporting positive impact of enzymatic debridement for chronic wounds (some studies including PIs) is summarised in narrative in two systematic reviews.^{18, 25} Both reviews^{18, 25} reported primarily low level evidence at high risk of bias outlining the clinical benefits of enzymatic debriding agents, with some small studies offering  favourable comparisons to placebo treatment. These studies provided early support for using enzymes to debride chronic wounds more slowly and with generally low levels of pain²⁵ (both Level 1).

Enzymatic debridement to promote complete healing

• A network meta-analysis of RCTs⁵ (two RCTs,^{1, 4} n = 61 participants in total) showed collagenase ointment was associated with an increase in complete healing within up to 16 weeks compared with advanced wound dressing (risk ratio [RR] = 2.12, 95% confidence interval [CI] 1.06 to 4.22), with 176 more PIs per 1,000 likely to heal. However, the studies were at high risk of bias and certainty in the result was low⁵ (Level 1). 
• In an RCT at high risk of bias  (n = 27 PIs),^{2, 3} collagenase ointment was associated with an increase in complete healing within 84 days compared with autolytic debridement using a hydrogel (collagenase 69% versus autolysis 21%, p = 0.02),^{2, 3} as well as faster healing rates² (Level 1).
• An early RCT²⁶ (n = 17 PIs) at high risk of bias reported a non-specific fibrinolytic (streptokinase/streptodornase) was associated with slower healing than autolytic debridement using a hydrogel, but the difference was not significant. In most countries, this treatment has been superseded by contemporary enzymatic debriding agents²⁶ (Level 1). 
• In a cohort study at high risk of bias (n = 434 PIs),²⁷ collagenase ointment was associated with statistically significantly higher rates of healing by 12 months compared with sharp debridement (collagenase 22% versus sharp debridement 11%, hazard ratio [HR] = 1.85, 95% CI 1.28 to 2.68, p = 0.001)²⁷ (Level 2). However, healing rates in both groups were low and may not be clinically significant.  

Enzymatic debridement to promote improvement in the wound bed condition 

• In a cohort study at low risk of bias (n = 114),⁶ collagenase ointment was associated with significantly greater improvements in overall score (p = 0.022) and in necrotic tissue score (p = 0.0001) on the Bates-Jensen Wound Assessment Tool (BWAT) compared to wounds receiving sharp debridement. There was no significant difference in change in wound surface area between the two debridement methods. Both groups received concurrent negative pressure wound therapy⁶ (Level 2). 
• In a case-controlled study at low risk of bias (n = 557 PIs), collagenase ointment was associated with improved granulation by 12 months compared to autolytic debridement using medicinal honey (collagenase 100% granulation versus honey 38%, odds ratio [OR] =  1.384, 95% CI 1.057 to 1.812, p = 0.018).⁷ This finding was supported by an observational study at low risk of bias that reported treatment of PIs (n = 46,054) with collagenase ointment was associated with requiring fewer follow-up visits compared to medicinal honey, including lower rates of hospital readmission (OR = 0.86, 95% CI 0.80 to 0.94, p = 0.0002)⁸ (both Level 3). 

Comparisons between different types of enzymatic debridement 

• Two RCTs,^{9, 10} both at moderate risk of bias, showed no significant difference in healing outcome measures between collagenase ointment and debridement with papain-urea (n = 26 PIs)⁹ and debridement using a fibrinolytic (n = 78 PIs)¹⁰  (both Level 1). 

Considerations for use

The following points should be considered when performing enzymatic debridement:

• Adequate wound bed vascularity should be established before performing debridement¹⁶ (Level 1).
• In limbs/heels with poor vascularity or ischemia, dry stable eschar should usually be left undisturbed, except when infection is suspected. When infection is suspected, consult an appropriate medical practitioner^11-16 (Levels 1 and 5).
• Enzymatic debridement is appropriate when the need to remove devitalised tissue is not clinically urgent. In the presence of extensive necrotic tissue, crepitus, flatulence or signs of advanced cellulitis or sepsis, more rapid methods of debridement (e.g. surgical/sharp debridement) should be performed^11-15 (Level 5).
• Papain-urea could be selected when excessive necrotic tissue is present and collagenase could be selected for wound beds containing excessive fibrous tissue or mixed non-viable tissue¹⁷ (Level 5).
• Individuals may experience pressure injury pain and/or burning sensations from enzymatic debridement. Diluting the enzymatic agent in hydrogel might help reduce pain¹⁹ (Level 5) and maintain a moist healing environment¹⁸ (Level 1).
• Economic analyses^{1, 3, 20, 21} suggest that enzymatic (collagenase) debridement is associated with lower financial costs than using sharp debridement,²¹ autolytic debridement with medicinal honey (although the difference was not statistically significant)²⁰  or using  an advanced wound dressing only.^{1, 3}
• Manufacturer instructions should always be followed, including when selecting a compatible wound dressing to apply²⁹ (Level 5).

Author(s)

Wound Healing and Management Unit
Curtin University (WHAM@Curtin)

References

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