title: Nimesulide 90 mg orally twice daily does not influence postoperative morphine requirements after major chest surgery.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Royal College of Surgeons, St. James's Hospital, Dublin, Ireland.
authors.forename: Donal F
authors.initials: DF
authors.lastname: Harney
authors.forename: Michelle
authors.initials: M
authors.lastname: Dooley
authors.forename: Brendan
authors.initials: B
authors.lastname: Harhen
authors.forename: Niall
authors.initials: N
authors.lastname: McGuiness
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Connail
authors.initials: C
authors.lastname: McCrory
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Noreen P
authors.initials: NP
authors.lastname: Dowd
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D000284:Administration, Oral; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000517:prevention & control*; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases / Q000134:cerebrospinal fluid; D013249:Sternum / Q000601:surgery*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013908:Thoracotomy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D015121:6-Ketoprostaglandin F1 alpha; D009020:Morphine; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide