Intravenous Methadone Versus Intrathecal Morphine for Analgesia Following Cesarean Delivery

• Intravenous line (IV) Methadone (Drug): Subjects will receive standardized spinal anesthesia without intrathecal morphine (intrathecal 1.6-2 mL 0.75% bupivacaine + dextrose, 15 mcg fentanyl) and intravenous methadone (0.2mg/kg total body weight up to max dose of 20 mg, with saline added to make total volume 2 mL) The Intravenous line (IV) methadone will be administered after cord clamping and administration of uterotonics with the dose of medication divided into 4 equal aliquots each administered 5 minutes apart.
• Intrathecal Morphine (Drug): Subjects will receive standardized spinal anesthesia with intrathecal morphine 150 micrograms and no methadone (2cc dose of IV normal saline) The Intravenous line (IV) saline will be administered after cord clamping and administration of uterotonics with the dose of medication divided into 4 equal aliquots each administered 5 minutes apart.

Primary outcomes

• Total Opioid Consumption [24 hours post-delivery, 48 hours post-delivery]: Total opioid consumption (Morphine Milligram Equivalent) of either intrathecal opiate or intravenous methadone at 24-48 hours after delivery.

Secondary outcomes

• Obstetric Quality of Recovery-10 (ObsQoR-10) Scoring Tool [24 hours, 48 hours, 7 days]: The Obstetric Quality of Recovery-10 (ObsQoR-10), is a patient-reported 10-item questionnaire used to assess quality of recovery following spinal administration of pain medication. Patients rate each recovery item on a scale of 0 to 10, with 0 = worst possible recovery and 10 = best possible recovery. Total score ranges from 0-100 with higher scores indicating a better recovery after childbirth.
• Numeric Rating Scale (NRS) Pain Score at Rest [12 hours, 24 hours, 36 hours, 48 hours, 7 days]: A Numeric Rating Scale (NRS) for pain is a patient-reported item regarding the level of pain experienced at rest and is measured on a Likert scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable". Higher scores indicate worse pain.
• Numeric Rating Scale (NRS) for Movement-evoked Pain [12 hours, 24 hours, 36 hours, 48 hours, 7 days]: A Numeric Rating Scale (NRS) score for movement-evoked pain is a patient-reported item regarding the level of pain experienced with provoking maneuvers such as cough, inspiration/expiration, sitting up, knee flexion, hip flexion, rolling over in bed, and walking. The NRS is measured on a Likert scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable". Higher scores indicate worse pain.
• Numeric Rating Scale (NRS) for Pain in Previous 24 Hours [12 hours, 24 hours, 36 hours, 48 hours, 7 days]: A Numeric Rating Scale (NRS) score for highest level of pain is a patient-reported item regarding the level of pain experienced in the last 24 hours. The NRS is measured on a Likert scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain imaginable". Higher scores indicate worse pain.
• Pruritus [12 hours, 24 hours, 36 hours, 48 hours]: The severity of pruritus post spinal administration will be patient-reported on a 0-10 rating scale where 0 = none and 10 = severe. Higher scores indicate worse pruritus.
• Richmond Agitation Sedation Scale (RASS) [12 hours, 24 hours, 36 hours, 48 hours]: The Richmond Agitation Sedation Scale (RASS) will be used to assess the level of alertness and agitated behavior in patients. The patient's level of consciousness and sedation are rated by care provider, ranging from a combative state (+4) to an unarousable state (-5), with a "calm and alert" score at 0, with higher scores indicating more agitated behavior.
• Nausea [12 hours, 24 hours, 36 hours, 48 hours]: The severity of nausea post spinal administration will be patient-reported on a 10-point scale where 0 = no nausea and 10 = worse nausea imaginable. Higher scores indicate worse nausea.
• Patient Health Questionnaire-9 (PHQ-9) Score [7 days]: The Patient Health Questionnaire-9 (PHQ-9) is a nine-item self-administered questionnaire used to screen for depression severity. Each item is scored from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27, with higher scores indicating more severe depressive symptoms. The outcome was measured as the number of subjects who experienced minimal symptoms (score range 0-4), mild symptoms (score range 5-9), moderate symptoms (score range 10-14), moderately severe symptoms (score range 15-19) or severe symptoms (score range 20-27).
• Global Health State [24 hours, 48 hours, 7 days]: The Global Health State will be measured via Visual Analogue Scale to gauge the patient's overall assessment of their health on a scale from 0 (worst health imaginable) to 100 (best health imaginable). Higher scores indicate better health.

Sex: Female, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* English-speaking
* Age over 18 years old
* Scheduled cesarean delivery

Exclusion Criteria:

* Any contraindication to the administration of a spinal technique for anesthesia
* History of intolerance or adverse reaction to opioid medications
* History of chronic pain, opioid use >30 OME/day, or substance use disorder
* History of obstructive sleep apnea, chronic obstructive pulmonary disease, or respiratory compromise (SpO2 <92% on room air, or has a pre-existing oxygen requirement)
* History of liver or kidney failure
* Diagnosis of pre-eclampsia with current pregnancy
* Depression requiring more than one medication
* Planned use of CSE technique
* BMI >50.0 kg/m2
* ASA status IV, V
* No prior history of an ECG demonstrating QTc > 440ms
* Surgical complication requiring conversion to general anesthesia

Participant flow

Outcome results

• Total Opioid Consumption (Primary), Median, Morphine Milligram Equivalent: Spinal Anesthesia With Intravenous Methadone 22.5 (15.0 to 45.0); Spinal Anesthesia With Intrathecal Morphine 0 (0 to 7.5) (p 0.002)
• Obstetric Quality of Recovery-10 (ObsQoR-10) Scoring Tool (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 83 (69 to 91); Spinal Anesthesia With Intrathecal Morphine 80 (77 to 89) (p 0.76)
• Numeric Rating Scale (NRS) Pain Score at Rest (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 3 (2 to 5); Spinal Anesthesia With Intrathecal Morphine 1.5 (0 to 3) (p 0.013)
• Numeric Rating Scale (NRS) for Movement-evoked Pain (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 6 (4 to 7); Spinal Anesthesia With Intrathecal Morphine 3 (2 to 5) (p 0.06)
• Numeric Rating Scale (NRS) for Pain in Previous 24 Hours (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 6 (4 to 8); Spinal Anesthesia With Intrathecal Morphine 4.5 (4 to 6) (p 0.10)
• Pruritus (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 0 (0 to 3); Spinal Anesthesia With Intrathecal Morphine 3.5 (2 to 6) (p 0.037)
• Richmond Agitation Sedation Scale (RASS) (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 0 (0 to 0); Spinal Anesthesia With Intrathecal Morphine 0 (0 to 0)
• Nausea (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 3 (0 to 5); Spinal Anesthesia With Intrathecal Morphine 2 (0 to 7) (p 0.70)
• Patient Health Questionnaire-9 (PHQ-9) Score (Secondary), Count of participants, Participants: Spinal Anesthesia With Intravenous Methadone 8; Spinal Anesthesia With Intrathecal Morphine 13
• Global Health State (Secondary), Median, score on a scale: Spinal Anesthesia With Intravenous Methadone 55 (45 to 75); Spinal Anesthesia With Intrathecal Morphine 68 (57.5 to 83) (p 0.23)

Adverse events

Time frame: Adverse events were collected from the time of informed consent through study completion, approximately 1 week.

Other adverse events by term

• Study Protocol (PDF, 2025-08-10)

• Emily E Sharpe, M.D., Principal investigator, Mayo Clinic