Is there a difference in the adverse effect profile or the analgesic effect between ketorolac and d

Fråga: Is there a difference in the adverse effect profile or the analgesic effect between ketorolac and diclofenac, administered intravenously for the treatment of postoperative pain? According to the questioner, there have been concerns over the safety of ketorolac.

Sammanfattning: We have found no evidence in published literature for a difference between diclofenac and ketorolac in the treatment of postoperative pain, either with respect to analgesia or side-effects.

Svar: Ketorolac and diclofenac are two non-steroidal antiinflammatory drugs (NSAID). Several studies have been performed to compare the effects of diclofenac and ketorolac in different clinical settings. Below are presented data from randomised, clinical trials on patients undergoing major surgery.

The analgesic effect of ketorolac, diclofenac and either placebo or ketoprofen were compared in three double blind, randomised studies, including 102, 85 and 30 major surgery patients, respectively. All three studies were designed to detect a significant difference in postoperative opioid consumption, but no such difference could be shown. Daily doses of ketorolac were between 60-120 mg and of diclofenac 75-150 mg. No serious adverse events occurred in any of the studies, and no differences were seen in reported, minor side-effects (1-3). Variables of hemostasis were only measured in the smallest of the above mentioned studies, where no differences could be detected in e.g. platelet adhesion, bleeding time or blood loss. However, these side-effect data lack power analyses, and are therefore not conclusive.

The safety issue of ketorolac was in focus of a recently performed, prospective, randomised, multicenter population study, including 11245 patients, which compared the safety of ketorolac with either diclofenac or ketoprofen in the treatment of postoperative pain. The study was sponsored by the manufacturer of ketorolac and was initiated on a recommendation from regulatory agencies. Median doses varied between study sites in different countries; 40-100 mg for ketorolac, 75-150 mg for diclofenac and 200-400 mg for ketoprofen. The main outcome was a composite measure of death, increased surgical bleeding or gastrointestinal bleeding, which occurred in a total of 139 patients. No differences were seen between ketorolac and the two comparators, either together or separately, for any separate or composite outcome (4).