Colin R. Brown

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 30 mg, 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 IV morphine provided supplemental analgesia. RESULTS:Among 127 patients enrolled, morphine use during the first 24 h was significantly less in patients receiving 30 mg 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 30-mg ketorolac group used significantly less morphine than the placebo group. Summed pain intensity differences at 4 and 6 h significantly favored the 30-mg ketorolac group over the other groups. The rates of pyrexia and tachycardia were significantly lower in the ketorolac 30-mg 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.

Intranasal ketorolac for acute postoperative pain

Abstract Background: Efficacy and tolerability of intranasal ketorolac (SPRIX®) was assessed in abdominal surgery patients. Methods: Adult patients were randomly assigned to receive ketorolac 31.5 mg (n = 214) or placebo (n = 107) every 6 hr after surgery for 48 hr, then up to 4 times/day for up to 5 days. Morphine sulfate via patient controlled analgesia was available in both groups as needed. Results: Least square mean 6 hr summed pain intensity difference scores were significantly greater in the ketorolac group indicating better analgesic efficacy compared to placebo (117.4 vs. 89.9, p = 0.032; difference 27.6, 95% CI 2.5–52.7). Pain intensity difference indicated significantly better pain relief in the ketorolac group at 20 min after the first dose (p = 0.01). Morphine use over 48 hr decreased 26% in the ketorolac group compared to placebo (p = 0.004). Day 1 global pain control scores were significantly higher in the ketorolac group compared to placebo (p = 0.009). Quality of analgesia was rated significantly higher (p = 0.009) in the ketorolac group by 20 min after first dose. Adverse event and serious adverse event incidences were similar in both groups. Rhinalgia and nasal irritation, generally mild and transient in nature, occurred more frequently in the ketorolac group. Conclusion: Intranasal ketorolac was well tolerated and provided effective pain relief within 20 minutes with reduced opioid analgesia use. While IN ketorolac was assessed in an inpatient, conventional surgery setting in this study, IN ketorolac use may have more relevance for use in outpatient settings and ambulatory surgery or fast-track surgical procedures.

Hypnotic efficacy of diphenhydramine, methapyrilene, and pentobarbital

The antihistamines diphenhydramine and methapyrilene were compared with pentobarbital for hypnotic effect in two Veterans Administration Hospital populations using subjective‐response methods. In the first part of the study, 60 mg and 180 mg of pentobarbital were compared with 50 mg and 150 mg of diphenhydramine. A positive dose‐response relationship was obtained only for pentobarbital; neither dose of diphenhydramine was significantly different from 60 mg of pentobarbital for any response variable. In the second part of the study, 100 mg of pentobarbital, 50 mg of diphenhydramine, and 50 mg of methapyrilene were compared with placebo. One hundred mg of pentobarbital and 50 mg of diphenhydramine were significantly different from placebo, but 50 mg of methapyrilene was not.

Respiratory effects of hydromorphone in man.

The respiratory depressant efJeets of hydromorphone, a potent analgesie, were compared with morphine in a randomized double‐blind erossover study in human volunteers. Using a rebreathing technique, earbon dioxide response curves were plotted automatically with a speeial‐purpose analog computer. The respiratory depressant relative potency of hydromorphone to morphine over the total observation period was found to be 7.99 with lower and upper 95 per cent confidence limits of 5.44 and 10.69. Based on the displacement of the respiratory response curve, approximately 1.25 mg of hydromorphone is equivalent to 10 mg of morphine in our population of volunteers. For peak respiratorll depression, 0.95 mg of hydromorphone is equivalent to 10 mgoj morphine

The Oral Hypnotic Bioassay of Hydroxyzine and Pentobarbital for Nighttime Sedation

H YDR0XYZINE, an antihistamine, is extensively used as a tranquilizing agent for preoperative medication,’ as a tranquilizer in intensive care and coronary care units,2 in combination with narcotic agents for analgesia and sedation in minor surgical procedures,3 as a psychoactive agent in the management of neuroses and psychoses,4 and as a sedative for women in labor.5 Since it has a wide margin of safety, its usefulness as a nighttime sedative was examined in this study.

Double-Blind 12-Hour Comparison of Oral Bromfenac and Naproxen Sodium with Intramuscular Ketorolac for Postoperative Pain

Clinical Pharmacology & Therapeutics (1996) 59, 133–133; doi: 10.1038/sj.clpt.1996.32

Combined routes of administration to assay oral analgesia in postoperative pain.

To increase the sensitivity of the method for evaluating oral analgesics in postoperative patients, we designed a combined oral/parenteral bioassay. Drugs studied were parenteral morphine, parenteral propiram, and oral codeine at two dose levels each and oral propiram at four dose levels. Results from data on 308 patients suggest that future studies designed to establish the relative potencies of oral analgesics should use parenteral morphine as the standard in a combined oral/parenteral study because this approach provides a very sensitive measure of analgesia. Further, with one drug as the reference compound, results from many sources would be more readily compared.