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 (31.5 mg) [DOSAGE ERROR CORRECTED] 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 > or =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 ( approximately 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 pruritus. 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.

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain.

BACKGROUND: We evaluated the safety and efficacy of multiple doses of intranasal ketorolac tromethamine (ketorolac) for postoperative pain. METHODS: This was a double-blind, placebo-controlled study in patients undergoing major surgery who were randomized to receive intranasal ketorolac, 10 mg or 31.5 mg, [DOSAGE ERROR CORRECTED]or placebo every 8 h for 40 h. After surgery, patients with pain intensity of at least 40 on a 100-mm visual analog scale were assessed at 30 min and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h after receiving the study drug. Patient-controlled i.v. morphine provided supplemental analgesia. RESULTS: Among 127 patients enrolled, morphine use during the first 24 h was significantly less in patients receiving 31.5 mg [DOSAGE ERROR CORRECTED] of ketorolac (37.8 mg) than in the placebo group (56.5 mg) and in the 10-mg ketorolac group (54.3 mg). Over 48 h, the 31.5-mg ketorolac [DOSAGE ERROR CORRECTED] group used significantly less morphine than the placebo group. Summed pain intensity differences at 4 and 6 h significantly favored the 31.5-mg ketorolac [DOSAGE ERROR CORRECTED]group over the other groups. The rates of pyrexia and tachycardia were significantly lower in the ketorolac 31.5-mg [DOSAGE ERROR CORRECTED]group than in the placebo group. Other adverse events were reported with similar frequency in all treatment groups and most were considered unrelated to treatment. CONCLUSION: Thirty milligrams of intranasal ketorolac demonstrated significant analgesic efficacy compared to 10 mg of intranasal ketorolac and placebo.