S. Yauw1, R. Lomme1, H. Van Goor1 1Radboud University Medical Center,Department of Surgery,Nijmegen, Gelderland, Netherlands
Introduction:
Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with anastomotic leakage in humans and animals, but pathophysiological mechanisms are unknown. Diclofenac causes leakage of anastomoses in the ileum and proximal colon, but not in the distal colon of the rat, suggesting a role for the ileal and proximal colonic content in NSAID induced leakage. Other studies suggest an increase of bile toxicity by specific NSAIDs, causing small intestinal damage. In this experiment we determined if changes in bile composition are relevant in diclofenac induced leakage.
Methods:
An anastomosis was constructed in the ileum of four groups of male Wistar rats in which all bile was diverted and replaced either by ‘control bile’(B-) or ‘diclofenac bile’(B+) from donor rats. Two groups received diclofenac (3mg/kg/day) orally (O) from day 0 until sacrifice on day 3: group O+B+ (n=11) and O+B- (n=8), and two groups did not receive oral diclofenac: O-B+ (n=10) and O-B- (n=11). Primary outcomes were anastomotic leakage and leak severity score (0=clean, 1= small abscess, 2=pus, 3= dehiscence/peritonitis). Secondary outcomes were bursting pressure and breaking strength. Excretion of diclofenac in bile was determined with HLPC.
Results:
Leak rates were equally high in group O+B+ (10/11), group O+B- (7/8) and group O-B+ (9/10), and lower in group O-B- (3/11; p=0.020 vs. O+B+). Leak severity score decreased orderly from group O+B+ (2.4±1.0) to O+B- (1.9±1.1; p=0.625*) to O-B+ (1.2±0.8; p=0.021*) to O-B- (0.3±0.5;p<0.001*) (*compared to O+B+ with ANOVA). Bursting pressure results corresponded with leak severity scores, breaking strength was similar among groups. Diclofenac molecules were detected with HPLC in bile starting from 1 hour after administration.
Conclusion:
Diclofenac (metabolites) in bile seems to increase anastomotic leakage rates. The effect appears inferior to the effect of oral diclofenac, though it may explain the reduced effect of diclofenac on distal colon anastomoses in the rat.