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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Morphine | Active Comparator | 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). |
|
| Placebo | Placebo Comparator | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intrathecal morphine | Drug | morphine 100 mcg, included in the intrathecal component of combined spinal epidural (CSE). |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Naveed Siddiqui, MD | Contact | 416-586-5270 | naveed.siddiqui@uhn.ca |
| Name | Affiliation | Role |
|---|---|---|
| Naveed Siddiqui, MD | MOUNT SINAI HOSPITAL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mount Sinai Hospital | Recruiting | Toronto | Ontario | M5G1X5 | Canada |
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| ID | Term |
|---|---|
| D048949 | Labor Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| D000077330 | Saline Solution |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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| Saline solution (placebo) | Other | normal saline 0.2 ml added to the intrathecal component of combined spinal epidural (CSE). |
|
|
| 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 |
| D006571 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |