Effects of cyclooxygenase inhibition on anastomotic healing following large bowel resection in a rabbit model—a randomized, blinded, placebo-controlled trial

Neuß, H.; Raue, W.; Müller, Verena; Weichert, Wilko; Schwenk, W.; Mall, Julian W.

doi:10.1007/s00384-009-0643-0

Cited by 26 publications

(19 citation statements)

References 33 publications

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“…Recently, non‐steroidal anti‐inflammatory drugs (NSAIDs) have been suggested as a potential factor in the development of anastomotic leakage8–15. NSAIDs are increasingly being used in fast‐track surgery programmes to optimize pain control and to reduce opioid usage16, 17.…”

Section: Introductionmentioning

confidence: 99%

“…However, inhibition of cyclo‐oxygenase (COX) interferes with normal processes important for wound repair and healing of intestinal anastomoses20. Experimental studies have shown inferior anastomotic healing following treatment with NSAIDs8–13. Two retrospective clinical studies reported a potential detrimental effect of NSAIDs on anastomotic leakage14, 15.…”

Section: Introductionmentioning

confidence: 99%

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Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

Gorissen

Benning

Berghmans

et al. 2012

British Journal of Surgery

187

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

Gorissen

Benning

Berghmans

et al. 2012

British Journal of Surgery

187

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“…Furthermore, retrospective studies [5,6,7] have drawn attention to the possible detrimental effects of the NSAIDs on the anastomotic leakage rate after colorectal resection. The underlying mechanisms have been investigated in several experimental studies, but with conflicting results [8,9,10,11,12,13]. Considerable variation in dosage can explain the different results.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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“…It was demonstrated that the COX-2 level was indeed significantly reduced without clearly impacting on breaking strength of the colonic anastomoses or incisional wounds. In a recent study, Neuss et al [25] also failed to show a detrimental effect of NSAID on breaking strength of experimental colonic anastomoses. NSAID doses varied greatly in the previous studies showing detrimental effects of COX-2 inhibition [7,8,9,17].…”

Section: Discussionmentioning

confidence: 99%

Effect of Diclofenac on Cyclooxygenase-2 Levels and Early Breaking Strength of Experimental Colonic Anastomoses and Skin Incisions

Klein

Krarup

Burcharth³

et al. 2010

Eur Surg Res

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Background: Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs on the anastomotic leakage rate after colorectal surgery. Methods: An experimental, randomized, placebo-controlled prospective study on 32 male Wistar rats was carried out. We examined the effect of diclofenac 4 mg/kg/day on the cyclooxygenase-2 (COX-2) enzyme in the anastomotic tissue and on the breaking strength of anastomotic and incisional wounds. The operation was performed with colonic resection and hand-sewn anastomosis. After 3 days, the rats were sacrificed and the breaking strength and the COX-2 content of the anastomosis were measured. Results: There was a significantly reduced level of COX-2 in the rats treated with diclofenac (p = 0.001); no significant differences in any of the breaking strength measurements and no significant correlation between COX-2 levels and breaking strength of the anastomotic or incisional wounds could be found (p = 0.073 and p = 0.727). Conclusion: This study for the first time showed that a diclofenac dose of 4 mg/kg/24 h was sufficient to reduce the level of COX-2 enzymes in the anastomotic tissue in rats. This inhibition of the inflammatory response did not lead to reduced breaking strength of either anastomotic or incisional wounds. Whether there is a detrimental effect of COX inhibition on colorectal anastomoses in the clinical setting remains controversial.

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Effects of cyclooxygenase inhibition on anastomotic healing following large bowel resection in a rabbit model—a randomized, blinded, placebo-controlled trial

Abstract: The application of Valdecoxib does not influence anastomotic healing or new vessel formation in the anastomotic region following large bowel resection.

Cited by 26 publications

References 33 publications

Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery

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

Effect of Diclofenac on Cyclooxygenase-2 Levels and Early Breaking Strength of Experimental Colonic Anastomoses and Skin Incisions

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