Comparative Effectiveness of Ketorolac Dosing Strategies for Emergency Department Patients With Acute Pain
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STUDY OBJECTIVES: Ketorolac is a commonly used nonopioid parenteral analgesic for treating emergency department (ED) patients with acute pain. Our systematic review aims to summarize the available evidence by comparing the efficacy and safety of differing ketorolac dosing strategies for acute pain relief in the ED. METHODS: The review was registered on PROSPERO (CRD42022310062). We searched MEDLINE, PubMed, EMBASE, and unpublished sources from inception through December 9, 2022. We included randomized control trials of patients presenting with acute pain to the ED, comparing ketorolac doses less than 30 mg (low dose) to ketorolac doses more than or equal to 30 mg (high dose) for the outcomes of pain scores after treatment need for rescue analgesia, and incidence of adverse events. We excluded patients in non-ED settings, including postoperative settings. We extracted data independently and in duplicate and pooled them using a random-effects model. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool and the overall certainty of the evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. RESULTS: This review included 5 randomized controlled trials (n=627 patients). Low-dose parenteral ketorolac (15 to 20 mg), as compared to high-dose ketorolac (≥30 mg), probably has no effect on pain scores (mean difference 0.05 mm lower on 100 mm visual analog scale, 95% confidence interval [CI] -4.91 mm to +5.01 mm; moderate certainty). Further, low-dose ketorolac at 10 mg may have no effect on pain scores compared to high-dose ketorolac (mean difference 1.58 mm lower on 100 mm visual analog scale, 95% CI -8.86 mm to +5.71 mm; low certainty). Low-dose ketorolac may increase the need for rescue analgesia (risk ratio 1.27, 95% CI 0.86 to 1.87; low certainty) and may have no difference on rates of adverse events (risk ratio 0.84, 95% CI 0.54 to 1.33; low certainty). CONCLUSION: In adult ED patients with acute pain, parenteral ketorolac given at doses of 10 mg to 20 mg is probably as effective in relieving pain as doses of 30 mg or higher. Low-dose ketorolac may have no effect on adverse events, but these patients may require more rescue analgesia. This evidence is limited by imprecision and is not generalizable to children or those at higher risk of adverse events.
