Intrathecal Hydromorphone Versus Intrathecal Morphine for Postcesarean Delivery Analgesia: A Randomized Noninferiority Trial

BACKGROUND: Spinal anesthesia with intrathecal morphine is often the preferred anesthetic modality for elective cesarean delivery. Side effects and drug shortages, however, prompted researchers to look into intrathecal hydromorphone as an alternative. These studies established the effective analgesic dose for 90% of patients (ED90) for both opioids for postcesarean analgesia, yet failed to demonstrate the superiority of morphine over hydromorphone. Nonetheless, the noninferiority of hydromorphone has yet to be determined. METHODS: In this noninferiority randomized blinded clinical trial, 126 patients undergoing elective cesarean delivery under spinal anesthesia received either morphine 150 µg or hydromorphone 75 µg (ED90). The primary outcome was the between-group difference of the mean Numeric Rating Scale (NRS) pain score (0–10) for the first 24 hours after cesarean delivery, with a preestablished threshold for noninferiority of 1. This 24-hour NRS pain score was defined as a single number obtained at the 24 hours postcesarean delivery interview, based on participant’s recall of their overall pain experience during this period. Secondary outcomes included differences in NRS pain scores every 6 hours, cumulative 24 hour opioid consumption, time-to-first opioid request, quality of recovery as measured by the Obstetric Quality of Recovery Score-11 (ObsQoR-11), frequency of interventions for side effects, and Apgar scores. RESULTS: The mean (standard deviation [SD]) of the 24-hour NRS pain score was 4.0 (1.7) for morphine and 3.6 (1.5) for hydromorphone (between-group difference –0.46 (95% confidence interval [CI], –1.0 to 0.1). Given that the upper limit of the 95% CI did not exceed 1, noninferiority of hydromorphone was established. No statistically significant differences were found in mean (SD) 24 hour oral morphine consumption (morphine: 4.2 mg (6.5) vs hydromorphone: 4.1 (8.0) mg; P = .98), median [interquartile range {IQR}] ObsQoR-11 score (morphine: score 87 [75–97.5] vs hydromorphone: score 90 [80–96.5]; P = .51), median [IQR] time to first opioid request (morphine: 10.2 [3.2–15.5] h versus hydromorphone: 6.2 [3.1–12.4] h; P = .35), or proportion of patients requiring interventions for opioid-related pruritus (morphine: 0.316 (variance 0.216) vs hydromorphone: 0.321 (variance 0.218) ( P = .96) and opioid-related nausea and vomiting (morphine: 0.333 (variance 0.222) vs hydromorphone: 0.393 (variance 0.238) ( P = .51). CONCLUSIONS: Intrathecally, hydromorphone is noninferior to morphine for analgesia after elective cesarean delivery when using the previously established ED90 for both opioids (morphine: 150 µg versus hydromorphone: 75 µg); hydromorphone provides effective analgesia and may be a suitable alternative to morphine.