Effect of Postoperative Diclofenac on Anastomotic Healing, Skin Wounds and Subcutaneous Collagen Accumulation: A Randomized, Blinded, Placebo-Controlled, Experimental Study

Abstract

Background: Retrospective studies have drawn attention to possible detrimental effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the anastomotic leakage rate after colorectal resection. In this study, we examined the effects of the NSAID diclofenac on the breaking strength of an experimental colonic anastomosis and a skin incision as well as subcutaneous collagen accumulation. Methods: This was a randomized, blinded, placebo-controlled experimental study in 60 male Wistar rats treated with diclofenac 4 mg/kg/day or placebo. In each rat, a colonic anastomosis was performed and an expanded polytetrafluoroethylene (ePTFE) tube was placed subcutaneously. Incisional and anastomotic wound breaking strength and hydroxyproline content in the ePTFE tubes were measured 7 days after the operation. Results: We found no significant differences in any of the breaking strength measurements, but showed a median 38% reduction in hydroxyproline deposition as a result of diclofenac treatment (p = 0.03). In the placebo group, subcutaneous collagen deposition tended to correlate positively with skin incisional but negatively with anastomotic bio-mechanical strength. Conclusion: Postoperative diclofenac treatment significantly inhibited collagen deposition in subcutaneous granulation tissue. Anastomotic strength and skin wound strength were not significantly affected. The ePTFE model is suitable for assessing the effect of various drugs on collagen formation and thus on wound healing.

NSAID administration post colorectal surgery increases anastomotic leak rate: systematic review/meta-analysis

“…NSAIDs, yet distal colonic anastomoses show no detrimental effects 29 . Furthermore, looking at the two studies which found no increased risk of leakage following NSAID administration, both examined distal colonic anastomoses exclusively 27,28 . Their negative findings fall in line with the location dependent findings of other studies, and cannot be generalized to state that there is no association between NSAID use and anastomotic leakage elsewhere in the gastrointestinal tract.…”

Ketorolac Use and Postoperative Complications in Gastrointestinal Surgery

“…In animal studies, diclofenac use has been associated with reductions in anastomotic tensile strength, bursting pressure, and hydroxyproline deposition. 22–24 …”

Multicentre observational cohort study of NSAIDs as risk factors for postoperative adverse events in gastrointestinal surgery

“…These clinical findings are supported by animal studies that have demonstrated that NSAID use following bowel anastomosis may be associated with decreased anastomotic strength and increased leak rates 7 8. NSAIDs are implicated in reducing collagen synthesis and hydroxyproline deposition during the healing process.…”