Effect of diclofenac on cyclooxygenase-2 levels and early breaking strength of experimental colonic anastomoses and skin incisions.
ABSTRACT Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs on the anastomotic leakage rate after colorectal surgery.
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.
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).
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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ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDS) are an integral component of the postoperative analgesic regimen, particularly in enhanced recovery protocols for elective colorectal resections. They are administered to reduce opioid requirements and mitigate the side effects of narcotics on the gastrointestinal tract. Recently however, there have been reports in the literature that have raised the possibility of an association between the use of NSAIDS and an increased risk of colorectal anastomotic leaks (AL).1–4.The therapeutic effects of NSAIDS are due to their inhibition of the enzyme cyclooxygenase (COX) that occurs as two main isoforms, COX-1 and COX-2. This inhibition results in the decreased synthesis of prostanoids which are important mediators of inflammation and pain. NSAIDS are categorized based on the extent of inhibition of these isoforms as being either COX-2 selective or non-selective. However, the potency and selectivity of the different commercially available NSAIDS diJournal of Gastrointestinal Surgery 06/2014; · 2.36 Impact Factor
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ABSTRACT: Many studies have been conducted on colorectal anastomotic leakage to reduce the incidence of anastomotic leakage. However, how to precisely determine if the bowel can withstand the pressure of a colorectal anastomosis experiment, which is called anastomotic bursting pressure, has not been determined. A task force developed the experimental animal hollow organ mechanical testing system to provide precise measurement of the maximum pressure that an anastomotic colon can withstand, and to compare it with the commonly used method such as the mercury and air bag pressure manometer in a rat colon rupture pressure test. Forty-five male Sprague-Dawley rats were randomly divided into the manual ball manometry (H) group, the tracing machine manometry pressure gauge head (MP) group, and the experimental animal hollow organ mechanical testing system (ME) group. The rats in each group were subjected to a cut colon rupture pressure test after injecting anesthesia in the tail vein. Colonic end-to-end anastomosis was performed, and the rats were rested for 1 week before anastomotic bursting pressure was determined by one of the three methods. No differences were observed between the normal colon rupture pressure and colonic anastomotic bursting pressure, which were determined using the three manometry methods. However, several advantages, such as reduction in errors, were identified in the ME group. Different types of manometry methods can be applied to the normal rat colon, but the colonic anastomotic bursting pressure test using the experimental animal hollow organ mechanical testing system is superior to traditional methods.International Journal of Surgery (London, England) 10/2013; · 1.44 Impact Factor
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ABSTRACT: Enhanced recovery programs following colorectal resection recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as part of multimodal analgesia. The present study aimed to assess whether postoperative NSAID use increased the risk of anastomotic leak. A systematic review of published literature was performed for studies comparing anastomotic leak following NSAID administration versus control. Meta-analysis was conducted for studies in human patients and experimental animal models. The primary endpoint was anastomotic leak. The final analysis included 8 studies in humans and 12 experimental animal studies. Use of NSAIDs was significantly associated with anastomotic leak in humans (8 studies, 4,464 patients, odds ratio [OR] 2.14; p < 0.001). This effect was seen with nonselective NSAIDs (6 studies, 3,074 patients, OR 2.37; p < 0.001), but not with selective NSAIDs (4 studies, 1,223 patients, OR 2.32; p = 0.170). There was strong evidence of selection bias from all clinical studies, with additional inconsistent definitions and outcomes assessment. From experimental animal models, anastomotic leak was more likely with NSAID use (ten studies, 575 animals, OR 9.51; p < 0.001). Bursting pressures at day 7 were significantly lower in NSAID versus controls (7 studies, 168 animals, weighted mean difference -35.7 mmHg; p < 0.001). Emerging data strongly suggest that postoperative NSAIDs are linked to anastomotic leak, although most studies are flawed and may be describing pre-existing selection bias. However, when combined with experimental data, these increasing concerns suggest caution is needed when prescribing NSAIDs to patients with pre-existing risk factors for leak, until more definitive evidence emerges.World Journal of Surgery 03/2014; · 2.23 Impact Factor