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Relevant Article

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Motov S, Yasavolian M, Likourezos A, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Annals of Emergency Medicine, 2017;70:177-184.

Background

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Intravenous (IV) ketorolac is a very commonly used nonsteroidal anti-inflammatory drug (NSAID) for pain control in the emergency department (ED). This goal of this study was to determine if there was a significant different in pain relief between traditional and lower doses of ketorolac.

Methods

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The study was a randomized, double blind trial performed in a large-volume urban ED. Patients between 18 and 65 years of age who presented to the ED with acute pain rated ≥5 on a 10-point scale were eligible for inclusion in the study. Exclusion criteria were pregnancy, a history of gastrointestinal hemorrhage, renal or hepatic insufficiency, allergies to NSAIDs, and unstable vital signs. There were 240 patients randomized into three groups, with 80 patients each assigned to receive 10, 15 or 30mg of IV ketorolac. Follow up pain scores were recorded 30 minutes after administration. Statistical analysis was performed using linear regression and ANOVA to determine a p-value for the change in pain scores. A power analysis determined that a sample of 78 subjects per group provided at least 80% power to detect a minimal clinically significant difference of at least 1.3 at 30 minutes with an alpha of 0.05; subjects available for analysis at the 30-minute mark in the 10, 15, and 30 mg groups were 79, 80, and 80, respectively.

Results

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Analysis of the data showed roughly equal reduction in pain scores between the three groups. The mean absolute reduction in pain scores were 2.5, 2.4 and 3.0 for the 10, 15 and 30mg groups, which was found to be not statistically significant. The most commonly reported adverse effects included dizziness, headache and nausea with no significant different in prevalence between the groups.

Relevance to Emergency Medicine

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This article is highly relevant to the practice of emergency medicine, largely because of how commonly we use ketorolac to treat pain. The FDA recommends dosing of 30mg IV or 60mg IM.1 However, previous studies have indicated that lower doses may have the same efficacy as the recommended doses.2,3 This high-quality study by Motov, et al. adds additional evidence to support a lower dose.4 The study was limited, as the authors point out, by its size and lack of long term follow up, so uncommon and serious adverse effects including renal insufficiency or GI bleeding, were not assessed.

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Even without hard evidence of a decrease in serious adverse effects, it is certainly safe, and probably safer, to use a lower dose of IV ketorolac.

References

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Food and Drug Administration (FDA). Ketorolac Tromethamine. Hospira. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/074802s038lbl.pdf. Accessed June 4, 2017.
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Staquet  MJ. A Double-blind Study with Placebo Control of Intramuscular Ketorolac Tromethamine in the Treatment of Cancer Pain. Journal of Clinical Phramcology, 1989:29:1031–1036.
[PubMed: 2689472]
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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
[PubMed: 9620101]
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Motov  S, Yasavolian  M, Likourezos  A, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Annals of Emergency Medicine, 2017;70:177–184.
[PubMed: 27993418]