Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia

Study Overview
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Brief Summary
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Morphine is usually used for pain relief after cesarean delivery. However, sometimes it is not available, the patient might be allergic to morphine or intolerant to its side effects. Hydromorphone, another drug from the same class, might be used alternatively, but we need to prove that it is not inferior to morphine.

Detailed Description
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Spinal or intrathecal (IT) morphine is the most commonly used opioid for post-cesarean delivery analgesia. Factors that contribute to its widespread use include a favorable pharmacokinetic profile with duration of action up to 24 hours, ease of administration (during spinal block for surgical anesthesia) and low cost. Most providers administer 100 to 200 mcg of IT morphine for cesarean delivery analgesia with excellent analgesic results. Nevertheless, subarachnoid use of morphine is not without adverse events. While dose-dependent respiratory depression is the most worrisome complication, other side effects such as pruritus, nausea, vomiting and urinary retention can be bothersome during early puerperium. Furthermore, shortages of preservative free morphine in the United States has led clinicians to seek a reasonable alternative. For the last 20 years, spinal hydromorphone has been successfully used for chronic pain associated with neoplasms. Its use for post-cesarean analgesia has been successfully reported. However, data regarding its efficacy in the IT space for post-cesarean analgesia is scarce. In the past, doses of 40 to 100 mcg have been reported to provide adequate postoperative pain relief with minimal side effects. In a recent study, the Effective Dose in 90% of patients has been established for both Hydromorphone and Morphine to be 75 mcg and 150 mcg, respectively. No prospective studies have been conducted to specifically establish non-inferiority of hydromorphone when compared to morphine for post- cesarean analgesia. In addition, while all opioids share the same side effect profile, the frequency of those events are unknown for IT hydromorphone. The current proposal is a blinded randomized controlled trial of intrathecal hydromorphone versus morphine in term pregnant women undergoing elective cesarean deliveries under spinal anesthesia.

Official Title
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Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia: A Non-Inferiority Trial

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Spinal Hydromorphone
* Drug: Spinal Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years; American Society of Anesthesiologist's Physical Status (ASA-PS) < 3; Term pregnancy (> 37 weeks gestational age); Elective cesarean delivery; Spinal Anesthesia; Exclusion Criteria: Documented allergy or severe intolerance to opioids; Intra-operative conversion to a general anesthetic technique; Chronic pain syndrome with baseline pain levels >3 on a visual analogue scale (0-10 cm); History of opioid use during this pregnancy; Allergy or intolerance to NSAIDS or acetaminophen; Morbid obesity- Body Mass Index (BMI) >40.

Ages Eligible for Study
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Minimum Age: 18 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: Institutional Research Ethics Board Approval was obtained (Western Research Ethics Board 111264). Term pregnant women presenting to the Obstetric Care Unit at Victoria Hospital for an elective cesarean delivery will be approached for recruitment. Consenting participants will be randomly assigned to receive either 75 mcg of hydromorphone or 150 mcg of morphine at the time of their spinal anesthetic. Randomization will be achieved through a simple computerized randomization technique (use of random numbers list for allocation).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spinal Hydromorphone<br>For the intervention group, 75 mcg of hydromorphone will be added to the spinal anesthetic mixture as a one-time injection prior to cesarean delivery. | Drug: Spinal Hydromorphone<br>* 75 mcg of hydromorphone will be prepared in a non-identifiable syringe by central hospital pharmacy. The resulting solution will then be added to the spinal anesthetic mixture(fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)<br>|
| Active Comparator: Spinal Morphine<br>For the control group,150 mcg of preservative-free morphine will be added to the spinal anesthetic mixture as a one-time injection prior to cesarean delivery. | Drug: Spinal Morphine<br>* 150 mcg of morphine will be prepared in a non-identifiable syringe by central hospital pharmacy.The resulting solution will be added to the spinal anesthetic mixture (fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Average Numeric Rating Score (0-10 , where 0=no pain and 10= maximum pain) during the first 24 hours. | This is defined as the between- group difference in the average pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee 24 hours after spinal anesthesia. | 24 hours after spinal anesthesia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in NRS pain scores at specific time points in the first 24 hours. | This is defined as the between- group difference in the mean pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee immediately after surgery (in the Post-Anesthesia Care Unit) and at 6, 12, 18 and 24 hours after spinal anesthesia. | immediately after surgery (in PACU), 6, 12 and 18 hours after spinal anesthesia is given. | 
| Time-to-first oral opioid analgesic request | This is defined as the length of time between spinal anesthesia and the first time the subject requested additional opioid analgesia, up to 24 hours from the spinal anesthesia. | Measured in hours from the time of spinal anesthetic until patient request for prescribed oral opioid analgesia, up to 24 hours from the spinal anesthetic . | 
| Nausea and/or Vomiting that required treatment. | Nausea/Vomiting episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia | Absolute number of treatments required in the 24-hour time frame. | 
| Pruritus that required treatment. | Pruritus episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia | Absolute number of treatments required in the 24-hour time frame. | 
| Respiratory Depression | Respiratory Rate measured in breaths/minute) | In post-anesthesia care unit (PACU), 6, 12, 18 and 24 hours after spinal anesthesia | 
| Apgar Scores | Neonatal Apgar scores at 1 and 5 minutes in a 1-10 interval scale | 1 and 5 minutes after birth. | 
| Difference in Opioid Consumption in the first 24 hours | This is defined as the between-group difference in the total amount of Oral Morphine Equivalents consumed in the first 24 hours after spinal anesthesia is given. | 24 hours after spinal anesthesia. | 
| Obstetric Quality of Recovery Score ObsQoR-11 | 11-item questionnaire applied to subjects 24 hours after spinal anesthesia. Measured in a 0-110 scale | 24 hours after spinal anesthesia. |