Intranasal Ketorolac for Postoperative Pain: A Phase 3, Double‐blind, Randomized Study

Objective.  Analgesic efficacy and tolerability of intranasal (IN) ketorolac was evaluated in postoperative patients in a randomized, double‐blind, placebo‐controlled study. Methods.  Patients received IN ketorolac (30 mg) or placebo three times daily for up to 5 days, with access to morphine by patient controlled analgesia (PCA). Patients in a single‐dose phase were removed from PCA 3 hours prior to the first study dose the day after surgery, and received a single IN ketorolac or placebo dose when visual analog scale scores were ≥40. Results.  Three hundred patients (N = 199 ketorolac, N = 101 placebo) were enrolled following primarily hysterectomies (135/300, 45%) and hip replacements (100/300, 33%); 189 (N = 115 ketorolac, N = 74 placebo) entered the single‐dose phase. Mean age was 52 years (range 19–81) and 69% of patients were women. The primary efficacy endpoint, the single‐dose summed pain intensity difference score at 6 hours, was significantly higher in the ketorolac group compared with placebo (83.3 vs 37.2, P  < 0.007), indicating greater pain reduction with ketorolac. Morphine use was reduced by 34% in the ketorolac group compared with the placebo group. The incidence of adverse events (∼98%) was similar in the two groups. The most common adverse events in both groups were nausea and vomiting. There was a trend in the ketorolac group for a lower incidence of opioid‐related side effects such as constipation and pruritis. Nasal irritation occurred more frequently with ketorolac vs placebo (24% vs 2%). Conclusion.  IN ketorolac was well tolerated and effective in treating moderate‐to‐severe postoperative pain in inpatients; the convenience of IN dosing suggests that its usefulness in the ambulatory care setting should be evaluated.