June 6, 2001

Postoperative Analgesic Effects of Celecoxib or Rofecoxib After Spinal Surgery

Reuben SS, Connelly NR. Anesthesia and Analgesia 2000;91:1221-8

Commentary by Raymond Sinatra M.D., Ph.D

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis at peripheral sites of tissue injury and in spinal cord. Non-selective agents including ibuprofen and ketorolac provide measurable postsurgical analgesia as well as useful opioid sparing effects. Unfortunately these agents also inhibit platelet function and may increase risks of postoperative blood loss. For this reason these agents are often discontinued or restricted in perioperative settings. In recent years highly selective cyclooxygenase -2 (COX 2) inhibitor agents, which inhibit synthesis of the prostaglandins that mediate pain and inflammation while sparing those that maintain platelet function and GI mucosal integrity, have been developed and advocated for use as post-surgical analgesics. This investigation by Rueben and Connelly tested the safety and analgesic effects of two commonly prescribed COX-2 inhibitors, Celecoxib and Rofecoxib for patients recovering from spinal fusion surgery. The model was particularly robust as this procedure is extremely painful and is commonly associated with significant blood loss.

Sixty patients undergoing elective decompressive lumbar laminectomy were randomized into three treatment groups and received in blinded fashion either Celecoxib 200 mg, Rofecoxib 50 mg or placebo pill, 1 hour prior to surgery. Patients received a standardized general anesthetic that included propofol, isoflurane and fentanyl (5 mcg/kg) Intraoperative blood loss was carefully measured. Postoperatively, all patients received IV-PCA morphine (2 mgq8min as needed). Pain intensity and cumulative morphine dose were measured at 4, 8, 12, 16, 20, and 24 hrs following surgery.

There were no intragroup differences with regard to duration of surgery or intraoperative blood loss. The cumulative dose of PCA morphine was significantly lower in the Rofecoxib group than placebo group at all observation intervals, and lower than the celecoxib group at intervals beyond 8hrs Patients in the Celecoxib group required less PCA morphine than the placebo group at the 4 and 8hr observation interval. No differences were noted after this time. (figure 1) When compared to placebo, pain intensity scores were lower in the Celecoxib group at 8 hrs and in the Rofecoxib group at 8, 12 and 16 hrs.

Selective COX-2 Inhibitors offer clinical benefits for patients recovering from major orthopedic procedures. Patients treated with either coxib did not experience increased blood loss, while benefiting from reductions in PCA morphine dose requirements and lower pain intensity scores. The fact that analgesic benefits were more prolonged in the Rofecoxib group may be attributed to its extended duration (24 hrs). It is conceivable that 1-2 additional doses of Celecoxib would have provided equivalent effectiveness, however this dose would exceed the manufacturers dose recommendation in this setting.

The major finding of this study is that coxibs, in contrast to non-selective NSAIDs, may be employed preemptively with a high degree of hemostatic safety. What remains unclear is whether coxibs (like non-selective NSAIDs) affect bone remodeling and risk failure of the spinal fusion. The authors may need to provide long-term fusion stability/failure data for patients enrolled into the protocol in order to satisfy these surgical concerns. Finally, the authors did not comment on whether reductions in morphine exposure translate into reductions in sedation, nausea, urinary retention and ileus. Improvements in opioid related morbidity would easily justify the costs associated with perioperative administration of coxibs.

ABSTRACT

Postoperative Analgesic Effects of Celecoxib or Rofecoxib After Spinal Surgery

AUTHORS:
Reuben SS, Connelly NR

SOURCE:
Anesthesia and Analgesia 2000;91:1221-8

ABSTRACT:
Nonsteroidal antiinflammatory drugs are recommended for the multimodal management of postoperative pain and may have a significant opioid-sparing effect after major surgery. The analgesic efficacy of the cyclooxygenase-2 nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, have not been evaluated after major orthopedic surgery. This study was designed to determine whether the administration of a preoperative dose of celecoxib or rofecoxib to patients who have undergone spinal stabilization would decrease patient-controlled analgesia (PCA) morphine use and/or enhance analgesia. We evaluated 60 inpatients undergoing spine stabilization by one surgeon. All patients received PCA morphine. The patients were divided into three groups. Preoperatively, they were given oral celecoxib 200 mg, rofecoxib 50 mg, or placebo. The outcome measures included pain scores and 24-h morphine use at six times during the first 24 postoperative h. The total dose of morphine and the cumulative doses for each of the six time periods were significantly more in the placebo group than in the other two groups. The morphine dose was significantly less in five of the six time intervals in the rofecoxib group compared with the celecoxib group. The pain scores were significantly less in the rofecoxib group than in the other two groups at two of the six intervals, and less than the placebo group in an additional interval. Although both rofecoxib and celecoxib produce similar analgesic effects in the first 4 h after surgery, rofecoxib demonstrated an extended analgesic effect that lasted throughout the 24-h study. We thus recommend that rofecoxib be used as a preoperative component of pain management that includes PCA morphine in patients undergoing spine stabilization surgery. Implications: The cyclooxygenase-2-specific nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, both demonstrate an opioid-sparing effect after spinal fusion surgery. Celecoxib resulted in decreased morphine use for the first 8 h after surgery, whereas rofecoxib demonstrated less morphine use throughout the 24-h study period.