Intramuscular Promethazine Added to IV Ondansetron for the Prevention of Intrathecal Morphine-Induced Pruritus and Nausea After Cesarean Delivery: A Randomized Controlled Trial

Intrathecal morphine is commonly used to facilitate postoperative pain control after cesarean delivery (CD). However, pruritus, nausea, and vomiting are frequent medication-related side effects. We hypothesized that adding prophylactic intramuscular promethazine (IMP) would reduce intrathecal morphine-related pruritus and other side effects more effectively than standard care with ondansetron alone. In this single-center, double-blinded, randomized controlled trial of patients undergoing scheduled CD under spinal anesthesia with intrathecal morphine, all participants received standard care with prophylactic IV ondansetron prior to surgery and were randomly assigned to receive either IMP 25 mg or intramuscular saline placebo after umbilical cord clamping. Pruritus, nausea and vomiting, agitation, fatigue, and pain were assessed at one hour, four hours, and 24 hours postoperatively. Secondary outcomes included pain, the Sedation-Agitation Scale, and fatigue. Sixty-seven patients completed the protocol: 34 received IMP, and 33 received intramuscular saline placebo. Among the total population, 15% reported nausea or vomiting, and 63% reported pruritus. No differences were observed between patients receiving prophylactic IMP and those receiving saline placebo regarding pruritus, nausea, vomiting, agitation, fatigue, or pain at any time point. The addition of prophylactic IMP to standard care with prophylactic IV ondansetron did not reduce the incidence of intrathecal morphine-induced side effects after scheduled CD.