NSAID Risks & Dosing

Ketorolac Side Effects
Hernández-Diáz and coworkers,[9] in a carefully written epidemiologic analysis, concludes that for every 100,000 people per year taking NSAIDs, there will be 300 GI-related deaths, 5 liver-related, 4 renal-related, and an undetermined (data are unclear) number of congestive heart failure (CHF)-related deaths. The risks for acute liver failure, renal failure, and CHF were estimated to be double baseline. These numbers were based only on prescription NSAID use.

Additionally, in a study looking at NSAIDs, García Rodriguez and associates[10] found that NSAID users overall had a 4.4% increased relative risk of serious GI events compared with non-users. From this same study, they developed a relative risk (RR) value for GI side effects as compared with non-use of NSAIDs and demonstrated that the RR for ketorolac was 24.7.

Is a single parenteral dose of ketorolac associated with clinically relevant side effects?

Cawthorn and colleagues,[11] in a retrospective analysis of perioperative ketorolac administration (15 mg or 30 mg single IV pushes) and rates of postoperative bleeding in patients who underwent reduction mammoplasty, demonstrated that patients who received ketorolac were at increased risk of requiring surgical re-exploration for hematoma evacuation (RR = 3.6; 95% confidence interval [CI], 1.4-9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3-3.6). The authors concluded that a single perioperative IV dose of ketorolac was associated with a greater than 3-fold increase in the likelihood of requirement for surgical hematoma evacuation.

Bean-Lijewski and colleagues[12] conducted a double-blind, placebo-controlled trial evaluating the effect of ketorolac as a single IM dose of 0.75 mg/kg on bleeding time and postoperative pain in children, and demonstrated prolongation of bleeding time by 53 +/- 75 seconds (P = .006).

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Singer and coworkers[13] conducted a similar trial for evaluating the effect of a single 60-mg IM dose of ketorolac on 4-hour bleeding time in healthy volunteers. The results showed that bleeding time was increased from a mean baseline time of 3 minutes 34 seconds (+/- 1 min 20 sec) to a mean 4-hour postinjection time of 5 minutes 20 seconds (+/- 3 min 8 sec).The mean prolongation of bleeding time was 1 minute 46 seconds (50% increase with 95% CI, 25%-75%).

And Gallagher and colleagues[14] conducted a chart review of 169 patients undergoing tonsillectomy who were administered ketorolac. They demonstrated a postoperative hemorrhage rate of 10.1% in comparison to a rate of 2.2% in patients given opioids.

The limited amount of available data demonstrates no evidence to support giving ketorolac in doses greater than 10 mg, as well as significant rates of postoperative hemorrhage and prolongation of bleeding time after a single supra-analgesic dose of parenteral ketorolac. Prospective randomized trials comparing different doses of ketorolac given to ED patients are needed to further evaluate the lack of analgesia in doses greater than 10 mg.


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