Increased Risk of Anastomotic Leakage with Diclofenac Treatment after Laparoscopic Colorectal Surgery

Abstract

Background: Over a period our department experienced an unexpected high frequency of anastomotic leakages. After diclofenac was removed from the postoperative analgesic regimen, the frequency dropped. This study aimed to evaluate the influence of diclofenac on the risk of developing anastomotic leakage after laparoscopic colorectal surgery. Methods: This was a retrospective case-control study based on 75 consecutive patients undergoing laparoscopic colorectal resection with primary anastomosis. In period 1, patients received diclofenac 150 mg/day. In period 2, diclofenac was withdrawn and the patients received an opioid analgesic instead. The primary outcome parameter was clinically significant anastomotical leakage verified at reoperation. Results: 1/42 patients in the no-diclofenac group compared with 7/33 in the diclofenac group had an anastomotic leakage after operation (p = 0.018). In a multivariate regressional analysis, none of the recorded factors were significantly associated with the frequency of anastomotical leakages when diclofenac treatment was omitted from the model. Conclusions: We found an increased number of clinically significant anastomotic leakages in patients receiving oral diclofenac for postoperative analgesia. There is an urgent need to test our hypothesis in prospective randomized clinical trials and to examine whether our findings can be extended to open surgery and to other NSAIDs.

Guidelines for Perioperative Care in Elective Colonic Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations

“…There have been clinical case series linking voltarol (150 mg, p.o. once a day) and celecoxib (cyclo-oxygenase (COX)-2 inhibitor) to an increased incidence of anastomotic dehiscence [173][174][175][176]. However, until more thorough studies addressing this question have been carried out, there is not sufficient evidence to stop using NSAIDS as a component of multimodal analgesia in the postoperative period.…”

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

“…In recent discussions regarding the effect of NSAIDs on anastomotic leakage rate [1,2,3], the focus has been on diclofenac and celecoxib, both of which exhibit a high and similar affinity for the COX-2 enzyme [13]. Of these, diclofenac is the most frequently used substance in experimental studies [8,9,14], but test doses have varied because no standard dose of diclofenac for animal studies has been established.…”

“…Due to the severity of this complication, factors that may affect the leakage rate have been studied extensively. Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs (NSAIDs) on the anastomotic leakage rate after colorectal surgery in humans [1,2,3]. Experimental studies have been applied to examine the effect of different medical substances on anastomotic healing [4,5,6].…”

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

“…However, the positive effects of selective COX-2 inhibition have subsequently been questioned, as any lesser rate of gastrointestinal adverse effects may have been outweighed by negative effects such as increased risk of cardiovascular events [11] . As regards to colorectal surgery, recent retrospective clinical studies have also indicated a negative effect on anastomotic healing [12][13][14] , as well as some, but not all, experimental investigations [15][16][17] . In these studies, COX-2 inhibitors in particular have been implicated, as these have been compared unfavourably with mostly COX-1 selective compounds; more specifically, the use of celecoxib and diclofenac compared to ibuprofen seemed to be associated with high leakage rates [12][13][14] .…”

“…As regards to colorectal surgery, recent retrospective clinical studies have also indicated a negative effect on anastomotic healing [12][13][14] , as well as some, but not all, experimental investigations [15][16][17] . In these studies, COX-2 inhibitors in particular have been implicated, as these have been compared unfavourably with mostly COX-1 selective compounds; more specifically, the use of celecoxib and diclofenac compared to ibuprofen seemed to be associated with high leakage rates [12][13][14] . This is of special note, as the classical NSAID diclofenac usually is classified as "weakly COX-2 selective" along with celecoxib, while ibuprofen is classified as "weakly COX-1 selective" [18] .…”