Low dose intrathecal morphine for post-cesarean analgesia with scheduled multimodal pain regimen: a prospective, randomized, open blinded end-point study

Abstract

Background: The intrathecal morphine dose in combination with multimodal analgesia providing optimal pain management post-cesarean delivery while minimizing side effects has not been determined. We performed a prospective, randomized, open blinded end-point study comparing intrathecal morphine 50 μg vs. 100 μg combined with scheduled intravenous ketorolac and oral acetaminophen for post-cesarean delivery analgesia.

Methods: Participants received intrathecal hyperbaric bupivacaine 12 mg, fentanyl 15 µg and a randomized dose of intrathecal morphine 50 μg vs. 100 μg followed by intravenous ketorolac 30 mg every six hours and oral acetaminophen 1000 mg every eight hours for the first 24 hours. Oral oxycodone and intravenous morphine were administered based on pain scores. The primary outcome was time to first analgesic request (opioid rescue dose) in the first 24 hours, analyzed using intent to treat and the hypothesis of non-inferiority using a log-rank testing approach and assuming a non-inferiority margin of a hazard ratio of 1.65.

Results: There were 201 participants randomized to intrathecal morphine 50 μg vs. 100 μg. The median time to first rescue dose was 23.5 hours postoperatively for the 50 μg cohort (95% CI 15.2, 28.3) and 22.9 hours postoperatively with the 100 μg cohort (95% CI 13.8, 28.2). The probability of requesting an opioid rescue dose was similar between the two treatment groups during the first 24 hours. Postoperative pruritus, nausea, vomiting, total opioids used, pain at rest and with ambulation, and time to first ambulation were not different between the two cohorts.

Conclusion: With ketorolac and acetaminophen, intrathecal morphine 50 μg was not inferior to 100 μg evaluating time to first opioid rescue dose and opioid use over time. There were no differences in secondary outcomes.

Keywords: Intrathecal morphine; Opioid side effect profile; Post-cesarean multimodal analgesia; Post-cesarean pain management; Spinal anesthesia.