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: Anastomotic dehiscence remains an important challenge for colorectal surgeons worldwide. Extensive research focused on performing a safe anastomosis is conducted with rats being the most used model when examining colorectal anastomoses. In daily clinical practice resorbable sutures are used when hand-sewn anastomoses are performed. However, in the experimental studies examining colorectal anastomoses, non-resorbable sutures have predominantly been used. The aim of this study was to compare a rapidly resorbable suture with a non-resorbable suture in experimental colorectal anastomoses. This was an experimental, prospective, case-control study using forty male Wistar rats. A colonic anastomosis was performed in a standardized fashion with either rapidly resorbable or non-resorbable suture. On the seventh postoperative day, the animals were sacrificed and the breaking strength of the anastomoses was measured. No suffering or poor wellbeing of the animals was registered. No animals died or were prematurely sacrificed. At tissue harvesting, no anastomotic leaks or signs of peritonitis were registered. The breaking strengths of the anastomoses were comparable in the two groups (median 2.175 (range 1.479-2.880) Newton vs. 2.267 (1.290-4.042) Newton (P = 0.256) for resorbable and non-resorbable sutures, respectively). We found no significant correlations between pre- to postoperative weight-loss and anastomotic strength. Non-resorbable suture was comparable with rapidly resorbable suture with regards to breaking strength of an experimental colonic anastomosis. Thus, absorbable suture can be used in experimental studies which then more easily can be compared to clinical practice.International Journal of Surgery (London, England) 02/2011; 9(4):332-4. DOI:10.1016/j.ijsu.2011.02.006 · 1.65 Impact Factor
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ABSTRACT: Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs indirectly reduce pain by inhibiting inflammation. Although beneficial for most surgical patients, animal studies and recent clinical studies suggest a harmful effect on new intestinal anastomoses by increasing the rate of leakage. NSAIDs may indirectly disturb anastomotic healing by inhibiting inflammation as an integrated part of the wound healing process in an early, critical phase after surgery. A literature review based on a structured search in PubMed of clinical and experimental studies investigating the effects of NSAIDs on anastomotic healing and leakage rates after intestinal surgery, as well as proposed mechanisms and effects studied in animal models. Three recent observational cohort studies (accumulated n = 882) indicate an increased rate of anastomotic leakages (15-21%) associated with cyclooxygenase-2 (COX-2) selective NSAIDs after intestinal surgery compared to the leakage rates in controls or historical cohorts (1-4%). Three prospective studies on related topics contain relevant data on NSAIDs and are compared to these studies. Several experimental animal studies support an increased risk for anastomotic leakage with the use of NSAIDs. The reported effects of NSAIDs on anastomotic healing suggest an increased risk for leakage. A better understanding of the complex interactions of NSAID-induced inhibition on anastomotic healing is a prerequisite for the safe use of NSAIDs. Until more data are available, a careful use of NSAIDs may be warranted in gastrointestinal anastomotic surgery.International Journal of Colorectal Disease 08/2011; 26(12):1501-9. DOI:10.1007/s00384-011-1285-6 · 2.42 Impact Factor
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ABSTRACT: 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. 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. 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. 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.European Surgical Research 02/2012; 48(2):73-8. DOI:10.1159/000336208 · 1.43 Impact Factor