Quality of Labour Epidural Analgesia With Intrathecal Morphine as a Component of Combined Spinal Epidural

Quality of Labour Epidural Analgesia With Intrathecal Morphine as a Component of Combined Spinal Epidural: a Double-blinded Randomized Control Trial

Neuraxial analgesia has shown to be the gold standard for effective labor pain relief, offering numerous benefits including enhanced pain control and maternal satisfaction. The methods to achieve neuraxial analgesia include lumbar epidural (LE), and combined spinal epidural (CSE). While LE may not consistently provide optimal pain relief, leading to frequent maternal requests for supplemental analgesics, CSE presents a promising advancement. This is due to the rapid onset of pain relief from intrathecal components, complemented by the longer-lasting effects of epidural medications. Intrathecal drugs have demonstrated the ability to offer more symmetrical blockades compared to epidurally administered medications. Nonetheless, some clinicians remain cautious about CSE due to the potential for increased pain when transitioning from spinal to less effective epidural analgesia. Long-acting opioids like morphine in the intrathecal space may mitigate this problem by providing transitional analgesia to the laboring parturient.

The primary aim of this randomized controlled trial is to provide evidence of whether the addition of 100 mcg of morphine in the intrathecal (spinal) component of CSE reduces the rate of breakthrough pain during labor.

Study Overview

• Status: Recruiting
• Conditions: Labor Pain
• Intervention / Treatment: Drug: Intrathecal morphine; Other: Saline solution (placebo)

Detailed Description

The addition of morphine to a combination of bupivacaine and lipophilic opioids (fentanyl) for the spinal component of CSE for labor analgesia has been shown to increase the duration of analgesia. A meta-analysis by Al-Kazwini and coworkers suggests a possible beneficial prolonging effect of adding morphine to spinal analgesia, however, the authors concluded that more adequately powered randomized controlled trials (RCTs) are required to determine the benefits and harms of intrathecal morphine (ITM).

This prolonged duration of action of ITM may reduce the need for frequent top-ups, which could alleviate nursing and anesthesiologist workload and enhance maternal satisfaction. An RCT conducted by Vasudevan and coworkers has concluded that the addition of 100 mcg ITM along with bupivacaine and fentanyl reduced the incidence of breakthrough pain in labor. Another dose-finding study comparing 50 and 100 mcg of ITM as a component of CSE labor analgesia concluded that 100 mcg of ITM significantly lowers the local anesthetic consumption and shorter duration of the first stage of labor without any significant difference in adverse effects. The RCT by Vasudevan et al. had a small sample size, enrolled mixed parity patients, and utilized continuous infusion for labor analgesia maintenance.

Hence, the investigators plan to conduct adequately powered RCT enrolling only primigravidae patients, which tend to have more prolonged labor than multiparous and programmed intermittent epidural bolus (PIEB) with patient-controlled epidural analgesia (PCEA) will be used, which is a more contemporary labor maintenance technique.

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Naveed Siddiqui, MD; Phone Number: 416-586-5270; Email: naveed.siddiqui@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Recruiting
      • Mount Sinai Hospital
      • Sub-Investigator: Ronald George, MD
      • Sub-Investigator: Kristi Downey, MSc
      • Contact: Naveed Siddiqui, MD; Phone Number: 416-586-5270; Email: naveed.siddiqui@uhn.ca
      • Sub-Investigator: Narinder Singh, MD
      • Sub-Investigator: Afsheen Nasir, MD
      • Sub-Investigator: Binu Jacob, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult (≥18 years) term primiparous (≥37 weeks) patients with live singleton pregnancy
• Patients who request labour analgesia and do not have any contraindications for neuraxial analgesia.
• Less than or equal to 6 cm cervical dilation during the last vaginal examination.

Exclusion Criteria:

• Patients who are expected to be discharged within 24 hours of delivery.
• Patients with chronic pain conditions, opioid use disorder, pre-gestational diabetes, obstructive sleep apnea, morbid obesity (BMI >40 kg/m2), or fetal abnormalities.
• Patients who have intramuscular morphine within 12 hours or fentanyl >200 mcg in the preceding 4 hours.
• Participants will be excluded from further analysis in case of spinal analgesic failure
• Participants will be excluded from further analysis if labour lasts less than 2 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine; 0.6 ml of 0.25% bupivacaine, fentanyl 10 mcg with morphine 100 mcg (total volume 1 ml) as intrathecal component of combined spinal epidural (CSE).	Drug: Intrathecal morphine; morphine 100 mcg, included in the intrathecal component of combined spinal epidural (CSE).; Other Names: Morphine
Placebo Comparator: Placebo; 0.6 ml of 0.25% bupivacaine, fentanyl 10 mcg with normal saline 0.2 ml (total volume 1 ml) as intrathecal component of combined spinal epidural (CSE).	Other: Saline solution (placebo); normal saline 0.2 ml added to the intrathecal component of combined spinal epidural (CSE).; Other Names: saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of breakthrough pain: questionnaire	The rate of breakthrough pain is defined as the ratio of the number of episodes of breakthrough pain during labour analgesia and the duration of epidural analgesia. An episode of breakthrough pain during labour analgesia was defined as subjective discomfort due to pain or pressure increasing during a contraction (rated as NRS ≥3/10), which was successfully treated with the manual administration of supplemental medications.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first episode of breakthrough pain in minutes	The amount of time in minutes to the first recorded episode of breakthrough pain, defined as subjective discomfort due to pain or pressure increasing during a contraction (rated as NRS ≥3/10), which was successfully treated with the manual administration of supplemental medications.	24 hours
Epidural medication consumption (milliliters)	The overall consumption of epidural medication throughout labour, in milliliters.	24 hours
Epidural pump settings: questionnaire	Any adjustments made to the programmed intermittent bolus settings of the epidural pump will be recorded.	24 hours
Presence of fetal heart rate anomalies: questionnaire	The presence of any fetal heart rate anomalies will be recorded	24 hours
Presence of Cesarean delivery: questionnaire	The presence of Cesarean delivery will be recorded	24 hours
Analgesic consumption post-delivery: questionnaire	Presence of analgesic consumption post-delivery will be recorded.	24 hours
Presence of pruritis: questionnaire	The presence of pruritis (yes or no) will be recorded.	24 hours
Presence of nausea: questionnaire	The presence of nausea(yes or no) will be recorded.	24 hours
Presence of vomiting: questionnaire	The presence of vomiting(yes or no) will be recorded.	24 hours
Presence of sedation: questionnaire	The presence of sedation(yes or no) will be recorded.	24 hours
Presence of respiratory depression: questionnaire	The presence of respiratory depression(yes or no) will be recorded.	24 hours
Apgar score at 1 minute	Apgar score recorded by the respiratory therapist, nurse or midwife at 1 minute of life.	1 minute
Apgar score at 5 minutes	Apgar score recorded by the respiratory therapist, nurse or midwife at 5 minutes of life.	5 minutes
Umbilical artery pH	Lab results for umbilical artery pH	24 hours
Umbilical vein pH	Lab results for umbilical vein pH	24 hours
Satisfaction: questionnaire	Post-delivery, patients will be asked how satisfied they were with their labour analgesia from 0-10, where 0 is no pain and 10 is the worst pain imaginable.	24 hours
Obstetric Quality of Recovery-10 (ObsQoR-10) score 24 hours	ObsQoR-10 score at 24 hours. There are 10 questions, and the results are tabulated out of 100. The higher the overall score out of 100, the better quality of recovery a patient is experiencing.	24 hours

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Investigators: Principal Investigator: Naveed Siddiqui, MD, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: CSE; intrathecal morphine; combined spinal epidural
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Labor Pain; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Sodium Compounds; Chlorides; Hydrochloric Acid; Morphine; Saline Solution; Sodium Chloride
• Other Study ID Numbers: 24-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No