Cesarean Section Pain
Conditions
Keywords
cesarean section, methadone, intratecal morphine, recovery, maternal satisfaction
Brief summary
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.
Detailed description
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.
Interventions
DRUGMethadone 0.15 mg/kg
Subcutaneous methadone administered for postoperative analgesia following cesarean delivery under neuraxial anesthesia.
DRUGmorphine
Intrathecal morphine administered during neuraxial anesthesia for postoperative analgesia following cesarean delivery.
Sponsors
Clinica Alemana de Santiago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
A sample size calculation was performed for a non-inferiority study with two parallel groups and 1:1 allocation, using the total Obs-Quality of Recovery-10 score as the primary outcome, analyzed as a continuous variable. The non-inferiority margin was set at 8 points, defined as the maximum clinically acceptable difference to consider the intervention not inferior to the control. The estimation assumed a common standard deviation of 15.2 points, based on preliminary data, a one-sided significance level of 0.025, and 80% statistical power. Under the assumption of no true differences between groups, the calculated sample size was 58 patients per group. Accounting for a 10% rate of loss to follow-up or incomplete data, the final sample size was adjusted to 64 patients per group, for a total of 128 patients.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery-10 (QoR-10) score at 24 hours | 24 hours | cesarean delivery. The QoR-10 is a validated patient-reported outcome measure ranging from 0 to 100, with higher scores indicating better recovery. The study is designed to assess noninferiority of subcutaneous methadone compared to intrathecal morphine using a predefined noninferiority margin of 8 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain intensity | Up to 24 hours after surgery | Pain intensity measured using a numerical rating scale (0-10) at rest and during movement. |
| Opioid consumption | Up to 24 hours after surgery | Total opioid consumtion within the first 24 hours after cesarean section, converted to morphine oral equivalents |
| adverse effects | 24 hours | incidence of nausea, vomiting, pruritus, somnolence, respiratory deppresion within 24 hours |
Contacts
CONTACTJAVIERA VARGAS, MD, MSc
Outcome results
None listed