Skip to main content Accessibility help

Does perioperative administration of rofecoxib improve analgesia after spine, breast and orthopaedic surgery?

  • G. Riest (a1), J. Peters (a1), M. Weiss (a1), J. Pospiech (a2), O. Hoffmann (a3), M. Neuhäuser (a4), M. Beiderlinden (a1) and M. Eikermann (a1) (a5)...



Background and objective: Data on the effectiveness of cyclooxygenase 2 inhibitors in postoperative pain therapy vary widely. We tested in a prospective, placebo-controlled, randomized, double-blind trial the hypotheses that perioperative (i.e. preoperative and postoperative) administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after spine, breast and orthopaedic surgery. Methods: Five hundred and forty patients scheduled for spine, breast or orthopaedic surgery were randomly assigned to receive in combination with postoperative morphine via patient controlled analgesia pump for 4 days either rofecoxib 50 mg administered perioperatively, rofecoxib 50 mg administered only postoperatively, or placebo. Primary outcome criteria were pain score at rest (numeric rating scale 0–4) and morphine consumption. Results: Perioperative rofecoxib significantly decreased pain score 0 (0–1) vs. 1 (0–2) (median (interquartile range)), and morphine consumption 18 (6–33) vs. 22.5 (12–38) compared with placebo. In contrast, rofecoxib when administered only postoperatively did not significantly improve analgesic effects or side-effects at time of assessment of the main criteria (24 h after skin closure), but during the follow-up period at 48 h and 72 h after skin closure pain scores and morphine consumption were improved compared to placebo. The analgesic effects of rofecoxib were independent from the type of surgery. Conclusions: Perioperative administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after orthopaedic, breast and spine surgery. However, the benefit of preoperative administration of the cyclooxygenase 2 inhibitor seems to be only moderate, suggesting that early postoperative administration may be a useful alternative approach. There is no evidence that the type of surgery influences analgesic effects of cyclooxygenase 2 inhibitors.


Corresponding author

Correspondence to: M. Eikermann, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, D-45122 Essen, Germany. Sleep Disorders Research Program, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, 02115 MA, USA. E-mail:; Tel: +1 617 278 0063; Fax: +1 617 732 7337


Hide All


Simanski C, Neugebauer E. Postoperative pain therapy. Chirurg 2003; 74: 254274.
Hopf HW, Weitz S. Postoperative pain management. Arch Surg 1994; 129: 128132.
Cherny N, Ripamonti C, Pereira J et al. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 2001; 19: 25422554.
Ashburn MA, Caplan A, Carr DB et al. Practice guidelines for acute pain management in the perioperative setting. Anesthesiology 2004; 100: 15731581.
Cashman J, McAnulty G. Nonsteroidal anti-inflammatory drugs in perisurgical pain management. Mechanisms of action and rationale for optimum use. Drugs 1995; 49: 5170.
Rusy LM, Houck CS, Sullivan LJ et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg 1995; 80: 226229.
Moiniche S, Romsing J, Dahl JB, Tramer MR. Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesth Analg 2003; 96: 6877.
Reuben SS, Connelly NR. Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000; 91: 1222112225.
Reuben SS, Bhopatkar S, Maciolek H, Joshi W, Sklar J. The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002; 94: 5559.
Buvanendran A, Kroin JS, Tuman KJ et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003; 290: 24112418.
Sinatra RS, Shen QJ, Halaszynski T, Luther MA, Shaheen Y. Preoperative rofecoxib oral suspension as an analgesic adjunct after lower abdominal surgery: the effects on effort-dependent pain and pulmonary function. Anesth Analg 2004; 98: 135140.
Ott E, Nussmeier NA, Duke PC et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125: 14811492.
Malan Jr TP, Marsh G, Hakki SI, Grossman E, Traylor L, Hubbard RC. Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty. Anesthesiology 2003; 98: 950956.
Tang J, Li S, White PF et al. Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology 2002; 96: 13051309.
Karamanlioglu B, Turan A, Memis D, Ture M. Preoperative oral rofecoxib reduces postoperative pain and tramadol consumption in patients after abdominal hysterectomy. Anesth Analg 2004; 98: 10391043.
Koizuka S, Saito S, Obata H et al. Oral etodolac, a COX-2 inhibitor, reduces postoperative pain immediately after fast-track cardiac surgery. J Anesth 2004; 18: 913.
Reynolds LW, Hoo RK, Brill RJ, North J, Recker DP, Verburg KM. The COX-2 specific inhibitor, valdecoxib, is an effective, opioid-sparing analgesic in patients undergoing total knee arthroplasty. J Pain Symptom Manage 2003; 25: 133141.
Barton SF, Langeland FF, Snabes MC et al. Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery. Anesthesiology 2002; 97: 306314.
Romsing J, Moiniche S. A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain. Acta Anaesthesiol Scand 2004; 48: 525546.
Hawkey CJ. COX-2 inhibitors. Lancet 1999; 353: 307314.
Joshi W, Connelly NR, Reuben SS, Wolckenhaar M, Thakkar N. An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management. Anesth Analg 2003; 97: 3538.
Huang JJ, Taguchi A, Hsu H, Andriole Jr GL, Kurz A. Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial. J Clin Anesth 2001; 13: 9497.
O'Hanlon DM, Thambipillai T, Colbert ST, Keane PW, Given HF. Timing of preemptive tenoxicam is important for postoperative analgesia. Can J Anaesth 2001; 48: 162166.
Katz J. Preemptive analgesia: importance of timing. Can J Anesth 2001; 48: 105114.
Steffen P, Seeling W, Reiser A, Rockemann M, Georgieff M. Differential indications for non-opioids for postoperative analgesia III. Analgesic effect of perioperative administration of metamizole plus diclofenac after spinal anesthesia. Anasthesiol Intensivmed Notfallmed Schmerzther 1997; 32: 496501.
Celik JB, Tuncer S, Reisli R, Sarkilar G, Celik C, Akyurek C. A comparative study of the effect of rofecoxib (a COX-2 inhibitor) and naproxen sodium on analgesic requirements after abdominal hysterectomy. Arch Gynecol Obstet 2003; 268: 297300.
Bekker A, Cooper PR, Frempong-Boadu A, Babu R, Errico T, Lebovits A. Evaluation of preoperative administration of the cyclooxygenase-2 inhibitor rofecoxib for the treatment of postoperative pain after lumbar disc surgery. Neurosurgery 2002; 50: 10531057.
Meyer R. Rofecoxib reduces perioperative morphine consumption for abdominal hysterectomy and laparoscopic gastric banding. Anaesth Intens Care 2002; 30: 389390.
Romsing J, Moiniche S, Mathiesen O, Dahl JB. Reduction of opioid-related adverse events using opioid-sparing analgesia with COX-2 inhibitors lacks documentation: a systematic review. Acta Anaesthesiol Scand 2005; 49: 133142.
Apfelbaum JL, Gan TJ, Zhao S, Hanna D, Chen C. Reliability and validity of the perioperative opioid-related symptom distress scale. Anesth Analg 2004; 99: 699709.
Bauer P. Multiple testing in clinical trials. Statist Med 1991; 10: 871890.
Breitfeld C, Peters J, Vockel T, Lorenz C, Eikermann M. Emetic effects of morphine and piritramide. Br J Anaesth 2003; 91: 218223.
Casarett D, Karlawish J, Sankar P, Hirschman K, Asch DA. Designing pain research from the patient's perspective: What Trial End Points Are Important to Patients With Chronic Pain? Pain Med 2001; 2: 309316.
Katz N. Reporting of clinical trials of analgesia. J Thorac Cardiovasc Surg 2003; 127: 605.
Oberholzer-Gee F, Inamdar NS. Merck's recall of rofe-coxib – a strategic perspective. N Engl J Med 2004; 351: 21472149.
Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Donaldson III WF, Evans CH. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1996; 21: 271277.
Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Evans CH. Herniated cervical intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1995; 20: 23732378.
Svensson CI, Yaksh TL. The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol 2002; 42: 553583.
Gan TJ, Lubarsky DA, Flood EM et al. Patient preferences for acute pain treatment. Br J Anaesth 2004; 92: 681688.
Kissin I. Preemptive analgesia. Why its effect is not always obvious. Anesthesiology 1996; 84: 10151019.
Kissin I. Preemptive analgesia. Anesthesiology 2000; 93: 11381143.
Farlow M, Potkin S, Koumaras B, Veach J, Mirski D. Analysis of outcome in retrieved dropout patients in a rivastigmine vs. placebo, 26-week, Alzheimer disease trial. Arch Neurol 2003; 60: 843848.


Related content

Powered by UNSILO

Does perioperative administration of rofecoxib improve analgesia after spine, breast and orthopaedic surgery?

  • G. Riest (a1), J. Peters (a1), M. Weiss (a1), J. Pospiech (a2), O. Hoffmann (a3), M. Neuhäuser (a4), M. Beiderlinden (a1) and M. Eikermann (a1) (a5)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.