Preemptive and Postsurgical Analgesia

As discussed earlier, the use of long-lasting analgesics before surgery may help to avoid the establishment of a sensitized state and result in diminished postoperative pain. Table 3 summarizes data on coxibs in preemptive and postsurgical analgesia. Some relevant details are presented here.

Table 3: Summary of COX-2-Selective Inhibitors Used in Preemptive and Postsurgical Studies

R = randomized; DB = double blind; PC = placebo controlled; PG = parallel group; AC - active comparator; TID = three times daily.

*P <.05.
†P <.001.
‡P <.0001.
§P <.0001 and P < .03, respectively.
¶P = .005.

In the ambulatory setting, preoperative rofecoxib (50 mg, n = 19), acetaminophen (2,000 mg, n = 16), or a combination of rofecoxib 50 mg plus acetaminophen 2,000 mg (n = 14), compared with a control group given vitamin C (500 mg, n = 19), were evaluated in patients undergoing ear, nose, and throat surgery.41 Patients took medication 30 minutes before surgery and the morning after surgery. For overall analgesic efficacy, preoperative rofecoxib was significantly more effective than either placebo or acetaminophen (P <.05); rofecoxib also decreased the need for rescue opioid (fentanyl). Notably, the addition of acetaminophen to rofecoxib did not significantly improve analgesic efficacy.(41)

In patients undergoing total knee arthroplasty, the safety and efficacy of the preoperative and postoperative administration of rofecoxib was evaluated.(42) All patients were required to discontinue NSAID use 10 days prior to surgery and for 7 days received no medication. Three days before surgery patients were randomized to either placebo (n = 11) or rofecoxib 25 mg (n = 10). Pain measurements at rest and while moving were made during the 7-day drug-free period and the 3 days leading up to surgery, and other hematologic variables were measured, including intraoperative blood loss and postoperative measures of hemoglobin, hematocrit, platelet count, prothrombin time, and international normalized ratio. Rofecoxib resulted in significantly improved pain scores on all measurements. There were no differences in intraoperative bleeding or the variables used to assess hemodynamic factors.(42)

Reuben and Connelly also investigated the preemptive use of rofecoxib 50 mg (n = 20) and celecoxib 200 mg (n = 20) compared with placebo (n = 20) in patients undergoing spinal fusion surgery.(43) At the end of the study, patients in the placebo group had significantly higher cumulative dosages of morphine than did patients in either the celecoxib group (P <.03) or the rofecoxib group (P < .0001) (Figure 3).(43) The morphine dosage was significantly lower for patients in the rofecoxib group at each measurement interval compared with placebo; patients in the celecoxib group consumed as much or more morphine in the last four of the six intervals as did patients in the placebo group. No significant increase in intraoperative bleeding in patients receiving either coxib was observed.(43)

Figure 3. PCA morphine consumption at each postoperative time interval in patients undergoing spinal fusion surgery who received preemptive analgesia with a COX- 2-selective inhibitor or placebo. Reprinted with permission from Reuben SS, Connelly NR. Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000; 91:1221-1225.43

Preliminary results from a study evaluating the effect of preoperative rofecoxib (25 mg and 50 mg) on postsurgical patient-controlled analgesia (PCA) morphine usage and measurements of effort-dependent pain found that patients randomized to rofecoxib 50 mg had significantly better visual analog scale (VAS) pain scores and consumed significantly less morphine than their counterparts in the other two study groups following elective abdominal surgery.(44) The rofecoxib 50 mg group also had superior pulmonary function relative to the other two groups.

Studies of coxibs for preemptive analgesia show that a single dose of rofecoxib or celecoxib before surgery diminished both postoperative pain and postsurgical morphine use. Rofecoxib was more effective than celecoxib for preemptive analgesia. Both drugs were similarly analgesic over the initial postoperative period, but one preoperative dose of rofecoxib provided enduring relief.

For postsurgical pain, rofecoxib 50 mg (given as 50 mg on day 1, then 25 or 50 mg on days 2 to 5) was superior to placebo (P <.05) and similar to naproxen for all single-dose measures of pain relief following orthopedic surgery (Table 3).(45) Furthermore, the rofecoxib 50-mg group used less narcotic analgesia (P = .005) and reported less pain on global evaluations (P = .041) than did the placebo group.

In another study of postorthopedic surgical pain, celecoxib (200 mg 3 times daily) compared with hydrocodone 10 mg plus acetaminophen 1,000 mg resulted in significantly lower maximum pain intensity, fewer doses of medication, and superior scores on the American Pain Society Patient Questionnaire (all P ² .013).(46) Fewer patients taking celecox-ib experienced adverse events compared with those taking hydrocodone plus acetaminophen (43% vs 89%; P <.001).(46)

Other known side effects of nonselective NSAIDs include inhibition of osteogenic activity in patients undergoing spinal fusion. Preclinical data showed that rofecoxib does not inhibit osteogenic activity. Currently, there is an ongoing double-blind controlled clinical trial to verify that rofecoxib does not interfere with spinal fusion. Additionally, a retrospective trial involving more than 300 patients who underwent spinal fusion surgery showed that rofecoxib was associated with a nonunion rate similar to that of placebo from a historical trial.(47)

Katz WA. Cyclooxygenase-2-selective inhibitors in the management of acute and perioperative pain. Cleve Clin J Med 2002;69:SI65-75.