Effect of diclofenac on cyclooxygenase-2 levels and early breaking strength of experimental colonic anastomoses and skin incisions.
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).


CONCLUSIONS
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.
Department of Surgical Gastroenterology D, Center for Perioperative Optimization, University of Copenhagen, Herlev Hospital, Herlev, Denmark. madkle01@heh.regionh.dk
M
M
Klein
P-M
PM
Krarup
J
J
Burcharth
M S
MS
Ågren
I
I
Gögenur
L N
LN
Jorgensen
J
J
Rosenberg
D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000139:chemically induced* / Q000201:enzymology; D000818:Animals; D001696:Biomechanical Phenomena; D003082:Colectomy; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D062109:Dermatologic Surgical Procedures; D004008:Diclofenac / Q000009:adverse effects*; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat