A 2023 meta-analysis compared the efficacy and safety of low-dose (<30 mg) and high-dose (≥ 30 mg) ketorolac dosing strategies for acute pain relief in the emergency department (ED). A total of 5 randomized clinical trials (N= 627) comparing low-dose and high-dose ketorolac were identified for analysis. The upper age for the trials ranged from 55 to 70 years, while the sources of acute pain included renal colic, musculoskeletal, flank, abdominal, and headache-related pain. Of note, the dosing strategies between trials varied, with two trials using intramuscular ketorolac, and the remaining three trials using intravenous ketorolac. It was determined that low-dose parenteral ketorolac (15-20 mg) may have no difference in effect on pain scores than a higher dose of 30-90 mg (mean difference [MD] -0.05 mm; 95% confidence interval [CI] -4.91 mm to 5.01 mm). A low dose of ketorolac at 10 mg was also determined to have potentially no effect on pain scores compared to high-dose ketorolac (MD -1.56 mm; 95% CI -8.82 to 5.69). [1]
Additionally, low-dose ketorolac was found to require an increased need for rescue analgesia (relative risk [RR] 1.27; 95% CI 0.86 to 1.87) and without affecting the risk of pooled adverse events including nausea, headache, dizziness, and flushing (RR 0.84; 95% CI 0.54 to 1.33); no episodes of gastrointestinal bleeding or new renal dysfunction were reported in any of the reviewed trials. A post-hoc sensitivity analysis, which excluded high-dose comparators not seen in clinical practice, further confirmed no difference in pain scores between groups. The overall small sample size and low certainty of evidence reduced the validity of the analysis. As a result, heterogeneity was high (>50%) when reviewing pooled adverse events. This, and the exclusion of patients with a risk of NSAID-related adverse events (bleeding, peptic ulcer, renal dysfunction) decrease the generalizability of the data. Overall, it was determined that low-dose parenteral ketorolac is likely as safe and effective in relieving acute pain compared to high-dose parenteral ketorolac. However, it should be taken into consideration that patients receiving low doses may be more likely to require rescue medication. More extensive studies are necessary to further address the incidence of more serious adverse events that might occur due to high-dose ketorolac use in clinical practice. [1]