Increased Scheduled Intravenous Ketorolac After Cesarean Delivery and Its Effect on Opioid Use: A Randomized Controlled Trial

Abstract

Objective: To evaluate the efficacy of scheduled ketorolac in reducing opioid use after cesarean delivery.

Methods: This was a single-center, randomized, double-blind, parallel-group trial to assess pain management after cesarean delivery with scheduled ketorolac compared with placebo. All patients undergoing cesarean delivery with neuraxial anesthesia received two doses of 30 mg intravenous ketorolac postoperatively and then were randomized to receive four doses of 30 mg of intravenous ketorolac or placebo every 6 hours. Additional nonsteroidal anti-inflammatory drugs were held until 6 hours after the last study dose. The primary outcome was total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients who used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and serum creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) provided 80% power to detect a population mean difference in MME of 32.4, with an SD for both groups of 68.7 after accounting for protocol noncompliance.

Results: From May 2019 to January 2022, 245 patients were screened and 148 patients were randomized (74 per group). Patient characteristics were similar between groups. The median (quartile 1-3) MME from arrival in the recovery room until postoperative hour 72 was 30.0 (0.0-67.5) for the ketorolac group and 60.0 (30.0-112.5) for the placebo group (Hodges-Lehmann median difference -30.0, 95% CI -45.0 to -15.0, P <.001). In addition, participants who received placebo were more likely to have numeric rating scale pain scores higher than 3 out of 10 ( P= .005). The mean±SD decrease from baseline hematocrit to postoperative day 1 was 5.5±2.6% for the ketorolac group and 5.4±3.5% for the placebo group ( P =.94). The mean±SD postoperative day 2 creatinine was 0.61±0.06 mg/dL in the ketorolac group and 0.62±0.08 mg/dL in the placebo group ( P =.26). Participant satisfaction with inpatient pain control and postoperative care was similar between groups.

Conclusion: Compared with placebo, scheduled intravenous ketorolac significantly decreased opioid use after cesarean delivery.

Clinical trial registration: ClinicalTrials.gov , NCT03678675.