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.

Summary
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.

References

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Catapano MS. The analgesic efficacy of ketorolac for acute pain. J Emerg Med. 1996;14:67-75. Abstract

Ducharme J. Acute pain management in adults. In: Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 8th ed. New York: McGraw-Hill; 2010.

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Minotti V, Betti M, Ciccarese G, Fumi G, Tonato M, Del Favero A. A double-blind study comparing two single dose regimens of ketorolac with diclofenac in pain due to cancer. Pharmacotherapy.1998,18:504-508.

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Peirce RJ, Fragen RJ, Pemberton DM. Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate postoperative pain. Pharmacotherapy. 1990;10(6 Pt 2):111S-115S.

Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6Pt 2):116S-121S.

Hernández-Díaz S, García-Rodríguez LA. Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. Am J Med. 2001;110 Suppl 3A:20S-7S. Abstract

García Rodríguez LA, Cattaruzzi C, Troncon MG, Agostinis L. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other non-steroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Arch Intern Med. 1998;158:33-39. Abstract

Cawthorn TR, Phelan R, Davidson JS, Turner KE. Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty. Can J Anaesth. 2012;59:466-472. doi:10.1007/s12630-012-9682-z. Epub 2012 Mar 21.

Bean-Lijewski JD, Hunt RD. Effect of ketorolac on bleeding time and postoperative pain in children: a double-blind, placebo-controlled comparison with meperidine. J Clin Anesth. 1996;8:25-30. Abstract

Singer AJ, Mynster CJ, McMahon BJ. The effect of IM ketorolac tromethamine on bleeding time: a prospective, interventional, controlled study. Am J Emerg Med. 2003;21:441-443. Abstract

Gallagher JE, Blauth J, Fornadley JA. Perioperative Ketorolac tromethamine and postoperative hemorrhage in cases of tonsillectomy and adenoidectomy. Laryngoscope. 1995;105:606-609. Abstract

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