The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery

BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain without increasing bleeding when administered before surgery. METHODS: We randomly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule: 1) placebo at induction, at wound closure, and 12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after induction (post)., Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale. Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated. RESULTS: Postoperative pain scores were less in the pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between the pre and post groups, nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0, vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but this was also only significant for the pre group (P = 0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was only significant for the pre group (P 0.05). Twenty-four hour consumption of morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg); both were significantly less than in the control group (47 +/- 27 mg, P < 0.001). CONCLUSIONS: Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia. There was a trend towards improved analgesia immediately after surgery with preincision administration, consistent with the expected time course of nonsteroidal antiinflammatory drug's effect. Perioperative parecoxib administration, consisting of two injections spaced 12 h apart, improved postoperative analgesia over the first 24 h without increasing bleeding.