Subcutaneous Methadone for Cesarean Analgesia: a Non Inferiority Study Using QoR-10

Overview

This study aims to evaluate whether subcutaneous methadone provides postoperative analgesia that is non-inferior to that achieved with intrathecal morphine in women undergoing cesarean delivery under neuraxial anesthesia. The primary outcome will be the quality of postoperative recovery, assessed using the QoR-10 score during the first 24 hours after surgery. Secondary outcomes will include postoperative pain intensity, opioid consumption, incidence of adverse effects, and maternal satisfaction. This trial seeks to determine whether subcutaneous methadone could represent an alternative analgesic strategy within multimodal analgesia protocols for cesarean delivery.

Effective postoperative analgesia following cesarean delivery is a fundamental component of maternal recovery and patient satisfaction. Current international recommendations, including the most recent 2026 update from the PROSPECT Working Group, emphasize that neuraxial morphine remains the gold standard for postoperative analgesia. These guidelines also highlight the strong evidence supporting multimodal analgesia strategies, including the routine use of paracetamol and dexamethasone as adjuncts to improve analgesic outcomes and postoperative recovery. Despite its efficacy, intrathecal morphine may be associated with dose-dependent adverse effects, such as pruritus, nausea, vomiting, and respiratory depression. For this reason, there remains ongoing clinical interest in identifying alternative analgesic strategies that provide comparable efficacy with a more favorable safety profile. Methadone is a long-acting opioid that also exhibits N-methyl-D-aspartate (NMDA) receptor antagonist properties, which may enhance analgesia and reduce postoperative opioid requirements. There is evidence supporting its use in cesarean delivery when administered intravenously. In particular, a randomized trial demonstrated that intravenous methadone provides effective postoperative analgesia following cesarean delivery. However, other routes of administration have not been adequately evaluated in this setting. The subcutaneous route may offer several potential advantages, including ease of administration, predictable absorption, and sustained systemic drug exposure, which could make it a practical alternative in obstetric analgesia. To date, subcutaneous methadone has not been evaluated nor directly compared with intrathecal morphine, which remains the current standard for post-cesarean analgesia.