Ketorolac in the era of cyclo-oxygenase-2 selective nonsteroidal anti-inflammatory drugs: a systematic review of efficacy, side effects, and regulatory issues.

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The recent introduction of oral COX-2 selective NSAIDs with potential for perioperative use, and the ongoing development of intravenous formulations, stimulated a systemic review of efficacy, side effects, and regulatory issues related to ketorolac for management of postoperative analgesia. To examine the opioid dose sparing effect of ketorolac, we compiled published, randomized controlled trials of ketorolac versus placebo, with opioids given for breakthrough pain, published in English-language journals from 1986-2001. Odds ratios were computed to assess whether the use of ketorolac reduced the incidence of opioid side effects or improved the quality of analgesia. Depending on the type of surgery, ketorolac reduced opioid dose by a mean of 36% (range 0% to 73%). Seventy percent of patients in control groups experienced moderate-severe pain 1 hour postoperatively, while 36% of the control patients had moderate to severe pain 24 hours postoperatively. Analgesia was improved in patients receiving ketorolac in combination with opioids. However, we did not find a concomitant reduction in opioid side effects (e.g., nausea, vomiting). This may be due to studies having inadequate (to small) sample sizes to detect differences in the incidence of opioid related side effects. The risk for adverse events with ketorolac increases with high doses, with prolonged therapy (>5 days), or invulnerable patients (e.g. the elderly). The incidence of serious adverse events has declined since dosage guidelines were revised. Ketorolac should be administered at the lowest dose necessary. Analgesics that provide effective analgesia with minimal adverse effects are needed.