Nimesulide 90 mg Orally Twice Daily Does Not Influence Postoperative Morphine Requirements After Major Chest Surgery

Abstract

Cyclooxygenase 2 inhibition has proven analgesic efficacy in a variety of surgical procedures. We postulated that perioperative cyclooxygenase 2 inhibition significantly reduces postoperative morphine requirements after major thoracic surgery and investigated the site of this potential analgesic effect. Ninety-two patients participated in this single-center, double-blind, randomized, placebo-controlled, parallel-group trial. Patients between the ages of 18 and 80 yr undergoing a thoracotomy or median sternotomy were randomized to receive either nimesulide or placebo in combination with a standard analgesic regimen perioperatively. Nimesulide was administered orally the evening before surgery and at 12-h intervals for 5 days postoperatively. The primary efficacy variables were morphine consumption and pain scores for the first 48 h postoperatively. The secondary efficacy variable was the effect of nimesulide on cyclooxygenase activity in cerebrospinal fluid (CSF). Pain scores at rest or with movement, and total morphine consumption for the first 48 h postoperatively, were not statistically different between the groups. The mean difference in total morphine consumption up to 48 h postoperatively between the nimesulide and placebo group was a 9.0 mg reduction (95% CI: -28.9 to 10.9 mg) (P = 0.37). Adjusted mean (se) CSF 6-keto-PGF1alpha (6-keto-PGF1alpha) concentrations increased by 54.7 (25.7) pg/mL from preoperatively to Day + 2 postoperatively in the placebo group, whereas adjusted mean (se) CSF 6-keto-PGF1alpha concentration decreased by 0.6 pg/mL (18.2 pg/mL) in the nimesulide group. These changes were not statistically different between the groups (P = 0.095). Nimesulide, at a dose of 90 mg twice daily in combination with a standard analgesic regimen, does not influence pain scores, morphine requirements, or CSF prostaglandin levels after major thoracic surgery.