Two Perioperative Ketorolac Dosing Regimens After Cesarean Delivery and Opioid Use: A Randomized Controlled Trial

OBJECTIVE: To evaluate an initial intravenous loading dose of ketorolac 60 mg compared with 30 mg immediately after cesarean delivery and postoperative opioid requirements. METHODS: This was a randomized, controlled, single-blind trial of pregnant individuals undergoing cesarean delivery under regional anesthesia at a large academic medical center between June 2022 and October 2023. Enrolled participants were randomized to receive an initial loading dose of 60 mg (intervention) or 30 mg (control) of intravenous ketorolac in the operating room at the end of surgery. Demographics, pregnancy, and surgical characteristics were collected. The primary outcome was morphine milligram equivalents (MMEs) in the first 24 hours after delivery. Secondary outcomes included MMEs postoperatively during the delivery admission, postpartum pain scores (scored 0–10) assessed with the Defense and Veterans Pain Rating Scale, and time from the end of cesarean delivery to first opioid administration. Summary statistics and bivariate analysis were performed. Outcomes were compared between the two study groups with the two-sample t test or the Wilcoxon rank-sum test as appropriate. RESULTS: Of 418 patients screened for eligibility, 92 were enrolled and randomized to receive a 60-mg (n=46) or 30-mg (n=46) loading dose of intravenous ketorolac. Baseline characteristics were similar between the two groups. The median opioid consumption in the first 24 hours postoperatively was 7.5 MMEs (interquartile range 0–15 MMEs) in the intervention group and 7.5 MMEs (interquartile range 0–22.5 MMEs) in the control group ( P =.02). Participants receiving a 60-mg ketorolac load used an average of 15 MMEs (interquartile range 0–37.5 MMEs) postoperatively during the delivery admission compared with 30 MMEs (interquartile range 7.5–54.5 MMEs) in the 30-mg dose group ( P =.043). The intervention group had a longer time interval between the end of surgery to first opioid administration (15 [3–25] vs 2.75 [2–5] hours, P =.002), as well as lower pain scores on admission to the postpartum unit (3 [0–5] vs 5 [3–6], P <.001). No treatment-related adverse effects were observed in either group. CONCLUSION: An initial loading dose of 60 mg compared with 30 mg of intravenous ketorolac after cesarean delivery resulted in lower postoperative opioid use without an increase in treatment-related adverse events. However, the effect size was small, and future studies may better address the clinical utility of ketorolac loading dose. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05248984.