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

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.

Inclusion criteria

• Women aged 18-45 years
• Singleton pregnancy at term (≥37 weeks of gestation)
• Scheduled for elective cesarean delivery
• Planned neuraxial spinal anesthesia
• Ability to understand and complete the QoR-10 questionnaire
• Provision of written informed consent

Exclusion criteria

• Emergency cesarean delivery
• Contraindication to neuraxial anesthesia
• Known hypersensitivity or allergy to methadone or morphine
• Chronic opioid use or opioid dependence