Intrathecal Morphine for Cesarean Delivery

Study Overview
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Brief Summary
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This is a randomized double blinded non-inferiority study comparing the duration of pain relief when patients receive one of three doses of spinal morphine. Enrolled patients will be randomly assigned to receive either 50 mcg, 150 mcg, or 250 mcg. All patients will receive standardized postoperative care, including multimodal analgesia. The primary outcome will be the time until the patient requests additional opioid pain medications.

Detailed Description
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Prospective, randomized, double-blind, controlled trial, with a non-inferiority design. Patients will be randomly assigned to receive either intrathecal morphine 50 mcg, 150 mcg, or 250 mcg based on a pre-assigned randomization sequence. This medication will be administered as part of their spinal anesthesia for cesarean delivery. the patient, clinician who administers the spinal anesthesia, and investigator who follows the patient will all be blinded to the dose of medication. All patients will receive standard of care for cesarean delivery and routine nursing care. This includes: preoperative intravenous catheter placement with preoperative IV fluid, standard American Society of Anesthesiologists monitoring, and neuraxial anesthesia placement (either spinal or combined spinal epidural) in sterile fashion. Each patient will receive standard cesarean induction dose of intrathecal medication consisting of 1.5ml of 0.75% hyperbaric bupivacaine, fentanyl 25 mcg. At end of surgery, all patients will receive standard dose of ketorolac 30 mg IV and acetaminophen 1 gm IV and continue with redosing every 6 and 8 hours (respectively) for 24 hours. On arrival to PACU, all patients will receive standard nursing care with standard monitoring of side effects. On discharge from PACU, patients will be transferred to postpartum floor and receive standard nursing care and monitoring. Over the following 24 hours, the patient will receive all standard post-cesarean care. For treatment of breakthrough pain, medications will provided be per standard care: oxycodone 5-10 mg PO every four hours PRN for pain. If the patient is not comfortable after receiving oral oxycodone they will be assessed by an anesthesia provider for either regional nerve block or additional opioids, as a one-time dose or by patient controlled analgesia (PCA). For treatment for side effects, medications will provided be per standard care: ondansetron 4mg IV as first-line for nausea/vomiting, promethazine 6.25 mg IV or Haloperidol 0.5-1mg IV for refractory nausea/vomiting. Naloxone 0.04 mg IV for refractory pruritus.

Official Title
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Optimal Dose of Intrathecal Morphine for Postoperative Analgesia After Cesarean Delivery

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Morphine Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women (ASA 2) Between 18 and 45 years old Singleton term pregnancies Planned neuraxial anesthesia Exclusion Criteria: Refusal to participate Known allergy or contraindication to any medication used in the study Significant medical or obstetrical disease (ASA ≥ 3) Opioid use disorder Chronic pain syndrome Daily or near daily opioid use within last 3 weeks. Patient receiving a Monoamine oxidase inhibitors (MOAi)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 50 micrograms<br>Patients in this arm will receive 50 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery | Drug: Morphine Sulfate<br>* Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief<br>|
| Active Comparator: 150 micrograms<br>Patients in this arm will receive 150 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery | Drug: Morphine Sulfate<br>* Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief<br>|
| Active Comparator: 250 micrograms<br>Patients in this arm will receive 250 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery | Drug: Morphine Sulfate<br>* Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of pain relief | Time to patient request for first dose of oral rescue pain medicine | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores | Visual analogue pain scores reported by the patient. Scale measured on a line from 0 to 100 mm, with 0 representing 'no pain' and 100 representing 'worst possible pain' | 24 hours | 
| Quality of recovery | Quality of Recovery Score following Cesarean Delivery Questionnaire (ObsQoR-11). This is a multi-dimensional wellness scale ranging from 0 (worst) to 10 (best) along 12 axis items. | 24 hours | 
| Nausea | Incidence of nausea and vomiting requiring treatment with a medication | 24 hours | 
| Pruritus | Incidence of pruritus requiring treatment with a medication | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cesarean, morphine, multimodal analgesia