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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a small amount of morphine to the spinal pain relief method during labor can reduce breakthrough pain. Breakthrough pain occurs when pain suddenly returns despite pain relief. The trial compares two groups: one receives morphine with their spinal pain relief, and the other receives a placebo (a treatment with no active pain relief). This trial suits first-time mothers who are at least 37 weeks pregnant, have requested pain relief for labor, and have a cervix dilation of 6 cm or less. As an unphased trial, it offers participants the chance to contribute to important research that could enhance pain management during labor.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that intrathecal morphine can effectively relieve labor pain. However, controlled clinical trials have not provided much detailed information about its safety in people. Some studies suggest that intrathecal morphine may control pain better than other methods, such as continuous epidural anesthesia.

It's important to note that opioids, including morphine, can sometimes cause side effects like nausea, vomiting, and drowsiness. Prospective trial participants should discuss any safety concerns with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard pain management options for labor, such as epidurals using just local anesthetics and opioids like fentanyl, the treatment using intrathecal morphine introduces morphine directly into the spinal fluid. This approach is unique because it combines morphine with bupivacaine and fentanyl in a combined spinal epidural (CSE), potentially offering more effective and longer-lasting pain relief during labor. Researchers are excited about this treatment as it could enhance pain control while reducing the need for additional analgesics and interventions, offering a more streamlined and efficient option for labor pain management.

What evidence suggests that intrathecal morphine is effective for labor pain?

Research shows that adding a small amount of morphine to the spinal part of combined spinal epidural (CSE) techniques can improve pain relief during labor. In this trial, participants in the morphine arm will receive this addition, which reduces the need for extra pain medication and makes sudden pain easier to manage. Spinal morphine provides longer-lasting pain control. Studies also suggest it offers better pain relief than other methods, such as epidural ropivacaine infusion. While earlier studies used higher doses, the current focus is on smaller, safer doses to minimize side effects while still providing effective pain relief. ^{1 2 3 5 6}

Who Is on the Research Team?

Naveed Siddiqui, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

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.

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

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

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.

Patients who are expected to be discharged within 24 hours of delivery

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1949078/

Single-dose intrathecal analgesia to control labour pain Early studies with high doses (2 mg) showed good analgesia that lasted 8 hours, but there were many side effects.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0885392400002049

Evidence-Based Review of the Literature on Intrathecal ... Few studies of intrathecal hydromorphone for pain have been performed, and there have been no controlled trials. It is likely that intrathecal hydromorphone is ...

3. bjanaesthesia.org.uk bjanaesthesia.org.uk/article/S0007-0912(17)35532-0/fulltext

Intrathecal morphine reduces breakthrough pain during ... The addition of small dose of morphine to the spinal component of the CSE technique improved the effectiveness of epidural labour analgesia and reduced the need ...

4. jaclinicalreports.springeropen.com jaclinicalreports.springeropen.com/articles/10.1186/s40981-015-0005-6

Intrathecal morphine versus epidural ropivacaine infusion for ... The results of this study suggest that ITM is better than CSEA-EDA for anesthesia following CD with regard to pain control.

5. link.springer.com link.springer.com/article/10.1007/s00228-020-02880-6

Single dose epidural hydromorphone in labour pain One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus.

6. mayoclinic.org mayoclinic.org/healthy-lifestyle/labor-and-delivery/in-depth/labor-and-delivery/art-20049326

Labor and delivery: Pain medications Opioids don't offer great relief from labor pain. They typically don't work for pain during delivery. They can cause nausea, vomiting and drowsiness. These ...