Intrathecal Morphine for Labor Pain

Overseen By Naveed Siddiqui, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Must not be taking: Intramuscular morphine, Fentanyl

Disqualifiers: Chronic pain, Opioid use disorder, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

182 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had intramuscular morphine within 12 hours or more than 200 mcg of fentanyl in the last 4 hours before participating.

What data supports the effectiveness of the drug intrathecal morphine for labor pain?

Research shows that intrathecal morphine provides effective pain relief during labor, with most patients experiencing significant pain reduction. Although some side effects like itching and nausea were reported, they were manageable and did not affect the infants' condition. ^{1 2 3 4 5}

Is intrathecal morphine safe for use in humans?

Intrathecal morphine has been used safely in humans for labor pain, with studies showing no major side effects in mothers or newborns. However, some common side effects include itching, nausea, vomiting, urinary retention, and drowsiness, which can be managed with other medications. Serious adverse events are rare but can occur if the dose is too high. ^{1 2 5 6 7}

How does the drug intrathecal morphine differ from other treatments for labor pain?

Intrathecal morphine is unique because it is administered directly into the spinal fluid, providing effective pain relief during labor without prolonging labor or causing major side effects for mothers or newborns. This method reduces the need for additional pain medications and has a slow onset with prolonged duration, minimizing systemic absorption and protecting the fetus. ^{1 2 3 5 8}

What is the purpose of this 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.

Research Team

Naveed Siddiqui, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

This trial is for women in labor who need pain relief. They should not have any health conditions that would make an epidural risky, such as bleeding disorders or infection at the injection site.

Inclusion Criteria

I want pain relief for labor and have no issues preventing spinal or epidural.

I am 18 or older, pregnant for the first time with one baby, and at least 37 weeks along.

My last cervical check showed dilation of 6 cm or less.

Exclusion Criteria

My spinal pain treatment has not failed.

I have chronic pain, opioid use disorder, diabetes before pregnancy, sleep apnea, severe obesity, or my baby has abnormalities.

Participants will be excluded from further analysis if labour lasts less than 2 hours

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or morphine as part of the intrathecal component of combined spinal epidural for labor analgesia

24 hours

Continuous monitoring during labor

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of breakthrough pain, satisfaction, and adverse effects

24 hours

Post-delivery assessment

Treatment Details

Interventions

• Intrathecal Morphine

Trial Overview The study tests if adding a small dose of morphine to the spinal part of an epidural (CSE) can better prevent breakthrough pain during labor compared to using saline solution (placebo). It's a double-blinded study, so neither patients nor doctors know who gets morphine.

Participant Groups

Group I: Morphine Active Control 1 Intervention

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).

Group II: Placebo Placebo Group 1 Intervention

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).

Intrathecal Morphine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Approved in European Union as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Approved in Canada as Morphine for:

• Severe chronic pain
• Acute pain
• Labor analgesia
• Perioperative analgesia for intra-abdominal, intra-thoracic, and orthopedic surgery
• Perioperative analgesia for Cesarean section

Who Is Running the Clinical Trial?

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Lead Sponsor

Trials

132

Recruited

11,400+

Findings from Research

In a study involving 49 women receiving intrathecal morphine for labor pain, it was found to significantly reduce the need for nitrous oxide and postpartum pain medication, indicating its effectiveness in pain management.

The use of 0.5 mg intrathecal morphine was shown to be safe, with no prolongation of labor or major side effects for mothers or newborns, making it a viable alternative to traditional intravenous analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal morphine as analgesia for labor pain. Edwards, RD., Hansel, NK., Pruessner, HT., et al.[2016]

Intrathecal injections of morphine (0.5 mg or 1 mg) provided excellent pain relief during labor for 93% of the 30 healthy women studied, with analgesia lasting 6-8 hours after administration.

Common side effects included pruritus (80%), nausea or vomiting (53%), urinary retention (43%), and drowsiness (43%), but these were manageable with naloxone, which did not compromise pain relief or cause significant respiratory depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal administration of hyperbaric morphine for the relief of pain in labour. Abboud, TK., Shnider, SM., Dailey, PA., et al.[2019]

In a study of 13 healthy women in active labor, an intrathecal injection of 1.0 mg morphine provided acceptable or good pain relief for 85% of the participants, with analgesia onset occurring within 15-45 minutes and lasting until delivery.

The morphine injection was associated with mild side effects in 85% of patients, such as pruritus and nausea, but did not negatively impact the infants, as indicated by low plasma morphine concentrations in both mothers and umbilical cords.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal administration of morphine for the relief of pains in labour and estimation of maternal and fetal plasma concentration of morphine. Hée, P., Stampe Sørensen, S., Bock, JE., et al.[2019]

Intrathecal opioids, particularly morphine sulfate, are effective for managing pain during the first stage of labor but do not effectively control pain during the second stage.

While intrathecal morphine provides long-lasting pain relief, it is associated with a high incidence of side effects, prompting research into optimal dosing to maximize pain relief while minimizing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal opioids for the control of pain experienced during labor and in the post-cesarean section period. Pellegrini, JE.[2005]

In a study involving 10 primiparous patients, intrathecal morphine sulfate provided effective pain relief during the first stage of labor without compromising the bearing down reflex, indicating its efficacy as an analgesic.

The use of intrathecal morphine was associated with minimal side effects, primarily mild peri-oral itching in some patients, and no adverse effects were observed in the infants, suggesting a safe alternative to epidural anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose intrathecal morphine sulphate as sole analgesic for pain of labour in combination with elective forceps delivery. A report of 10 cases. Kadieva, VS., Boezaart, AP.[2014]

In a case series of six patients who received an incorrect dose of intrathecal morphine (1 mg/ml instead of 50 mcg/ml), four experienced serious adverse events, primarily respiratory depression and somnolence, highlighting the risks associated with dosing errors in pain management.

A systematic review of 63 cases indicated that serious adverse events after intrathecal morphine typically occur within 2 to 24 hours post-injection, with respiratory depression being life-threatening at doses exceeding 900 mcg, but naloxone did not compromise analgesia, suggesting a need for careful monitoring and dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. Koning, MV., Reussien, E., Vermeulen, BAN., et al.[2022]

A case of temporary, completely reversed motor and sensory paralysis occurred after administering 1.6 mg of morphine sulfate intrathecally, suggesting a rare side effect of the medication.

The paralysis may not be due to direct damage from the medication itself, but rather linked to cardiovascular changes that happen as a result of effective pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary motor and sensory paralysis associated with intrathecal administration of morphine. Kleiner, LI., Krzeminski, J., Rosenwasser, RH.[2019]

Intrathecal injection of morphine provided effective pain relief for labor in 20 women, with complete analgesia achieved within 15-60 minutes and lasting up to 11 hours, without affecting sensory or motor function.

While mild systemic side effects like nausea and itching were common, they were generally manageable, and the analgesic effects were attributed to morphine's action on spinal opiate receptors, ensuring minimal impact on the fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal injection of morphine for obstetric analgesia. Baraka, A., Noueihid, R., Hajj, S.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intrathecal morphine as analgesia for labor pain. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Intrathecal administration of hyperbaric morphine for the relief of pain in labour. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Intrathecal administration of morphine for the relief of pains in labour and estimation of maternal and fetal plasma concentration of morphine. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Intrathecal opioids for the control of pain experienced during labor and in the post-cesarean section period. [2005]

5. South Africa pubmed.ncbi.nlm.nih.gov

Low-dose intrathecal morphine sulphate as sole analgesic for pain of labour in combination with elective forceps delivery. A report of 10 cases. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Temporary motor and sensory paralysis associated with intrathecal administration of morphine. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Intrathecal injection of morphine for obstetric analgesia. [2019]