title: Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data.
abstract: OBJECTIVE
  To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.
  
  
  METHODS
  Cohort study based on data from a prospective clinical database and electronically registered medical records.
  
  
  METHODS
  Six major colorectal centres in eastern Denmark.
  
  
  METHODS
  2766 patients (1441 (52%) men) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009. Median age was 70 years (interquartile range 62-77).
  
  
  METHODS
  Postoperative use of NSAID (defined as at least two days of NSAID treatment in the first seven days after surgery).
  
  
  METHODS
  Frequency of clinical anastomotic leakage verified at reoperation; mortality at 30 days.
  
  
  RESULTS
  Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% v 5.1%; P<0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P<0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (v colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% v ibuprofen 4.1% v controls 3.2%; P=0.20).
  
  
  CONCLUSIONS
  Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.
authors.affiliation: Department of Surgery, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark. madsklein1@gmail.com
authors.forename: Mads
authors.initials: M
authors.lastname: Klein
authors.forename: Ismail
authors.initials: I
authors.lastname: Gögenur
authors.forename: Jacob
authors.initials: J
authors.lastname: Rosenberg
mesh_terms: D000368:Aged; D057868:Anastomotic Leak / Q000209:etiology* / Q000601:surgery; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000601:surgery*; D003107:Colorectal Surgery / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004008:Diclofenac / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D011184:Postoperative Period; D012086:Reoperation; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004008:Diclofenac; D007052:Ibuprofen