Nitrous Oxide + Oxygen for Induced Labor

Overseen By Olivia Sher, MPH

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Maimonides Medical Center

Must not be taking: Magnesium sulfate, Opioids

Disqualifiers: Malignant hyperthermia, Vitamin B12 deficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 15 minutes

162 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized controlled trial aims to compare the effectiveness of nitrous oxide versus oxygen in facilitating the successful placement of a Foley balloon catheter for cervical ripening and induction of 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 participate if you are using magnesium sulfate or have used intravenous or intramuscular opioids within 4 hours before the trial.

Is nitrous oxide with oxygen safe for use during labor?

Nitrous oxide mixed with oxygen is generally considered safe for women in labor, their newborns, and healthcare workers. While there are some concerns about potential risks, such as effects on the brain and cardiovascular system, studies have shown it to be a safe option for pain management during childbirth. ^{1 2 3 4 5}

How does the drug nitrous oxide with oxygen differ from other treatments for induced labor?

Nitrous oxide with oxygen is unique because it is a noninvasive inhaled option for pain relief during labor, unlike more common methods like epidurals or IV medications. It has been used for over 100 years in many countries, providing effective pain relief without the need for needles or significant medical intervention. ^{6 7 8 9 10}

What data supports the effectiveness of the drug nitrous oxide with oxygen for induced labor?

Research shows that nitrous oxide mixed with oxygen is effective for pain relief during labor, with most women experiencing satisfactory pain control without affecting their consciousness or the baby's health. It is a noninvasive option that has been used worldwide for over 100 years, providing a safe alternative to more invasive pain relief methods like epidurals. ^{2 6 10 11 12}

Are You a Good Fit for This Trial?

This trial is for pregnant patients who are at term or have a medical need for early delivery and require a Foley balloon catheter for cervical ripening. Participants must be able to self-administer nitrous oxide safely, speak English, and not have conditions like vitamin B12 deficiency, history of malignant hyperthermia, recent opioid use, contraindications to nitrous oxide, non-reassuring fetal heart patterns, gas-trapping conditions or be under 35 weeks gestation.

Inclusion Criteria

I am pregnant and can have a balloon placed in my cervix.

Patients admitted to labor and delivery for induction of labor (term inductions, medically indicated preterm inductions)

Exclusion Criteria

Vitamin B12 deficiency

History of malignant hyperthermia

I have not used any IV or IM opioids in the last 4 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either nitrous oxide or oxygen during Foley balloon placement for cervical ripening and induction of labor

15 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Nitrous oxide
• Oxygen

Trial Overview The study is testing the effectiveness of using nitrous oxide (laughing gas) versus oxygen in helping with the placement of an intracervical balloon catheter used to prepare the cervix for labor induction. It's a randomized controlled trial where participants will receive either nitrous oxide or oxygen randomly.

How Is the Trial Designed?

Group I: Nitrous Oxide Experimental Treatment 1 Intervention

Patients in the intervention arm will receive an inhalant of 50% nitrous/50% oxygen intended to target pain relief for the duration of their foley ballon placement.

Group II: Oxygen Placebo Group 1 Intervention

Patients in the control arm will receive an inhalant of 100% oxygen for the duration of their foley balloon placement.

Nitrous oxide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia
• Emergency department analgesia

Approved in European Union as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia

Approved in Canada as Nitrous Oxide for:

• Procedural sedation for mild to moderate pain
• Labor analgesia
• Dental anesthesia

Who Is Running the Clinical Trial?

Maimonides Medical Center

Lead Sponsor

Trials

72

Recruited

15,400+

Published Research Related to This Trial

Inhalation of nitrous oxide mixed with oxygen (50%:50%) provides better analgesia during labor compared to oxygen alone, enhancing maternal comfort without affecting labor duration or bleeding volume.

This method is deemed safe and effective for pain relief in labor, maintaining good mental and physical condition for pregnant women, as shown in a study involving 200 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study: the effects of inhaling nitrous oxide for analgesia labor on pregnant women and fetus]. Ou, X., Li, B., Du, H.[2013]

In a study of 34 women using nitrous oxide for labor analgesia, 91.18% reported low pain scores (0-1), indicating that it is an effective pain relief option during childbirth.

Nitrous oxide did not negatively impact respiratory or circulatory functions, labor progress, neonatal health (Apgar scores), or increase postpartum bleeding, suggesting it is a safe choice for obstetric analgesia when oxygen levels are properly managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of nitrous oxide in labor analgesia]. Wang, B., Zhang, X., Wei, L.[2013]

In a study of 6242 women who delivered vaginally, those who used nitrous oxide alone reported similar levels of satisfaction with their anesthesia care as those who received neuraxial analgesia, despite lower reports of analgesic effectiveness.

The findings suggest that factors other than pain relief, such as the overall experience of care, contribute to maternal satisfaction during labor, indicating that nitrous oxide can be a viable option for pain management in labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous Oxide During Labor: Maternal Satisfaction Does Not Depend Exclusively on Analgesic Effectiveness. Richardson, MG., Lopez, BM., Baysinger, CL., et al.[2018]

Inhalation of 50% nitrous oxide in oxygen significantly improved pain relief during labor compared to a control group, with an effectiveness rate of 80.9% versus 0.9%.

The use of nitrous oxide also resulted in a lower cesarean section rate (11.6% vs 19.3%) and a shorter active labor phase (153 minutes vs 187 minutes), while showing no severe side effects for mothers or babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study on efficacy and safety of labor analgesia with inhalation of nitrous oxide in oxygen]. Su, F., Wei, X., Chen, X., et al.[2013]

Inhaled nitrous oxide (N2O) has been effectively used for over 100 years as a noninvasive pain relief option during labor, but it remains underutilized in the United States.

The article reviews the safety and efficacy of nitrous oxide compared to epidural and IV pain medications, suggesting it could be a valuable alternative for laboring women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide for labor analgesia. Hellams, A., Sprague, T., Saldanha, C., et al.[2018]

Nitrous oxide is considered safe for use during labor, showing no significant adverse effects for mothers, newborns, or healthcare workers, based on a systematic review of 11 randomized controlled trials.

While nitrous oxide is not the most potent option for labor pain relief, it provides adequate analgesia for many women, making it a viable choice for labor analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide for relief of labor pain: a systematic review. Rosen, MA.[2022]

Nitrous oxide (N2O) labor analgesia, when administered as a 50% blend with oxygen and self-administered by the mother, is considered safe for mothers, neonates, and caregivers during childbirth.

Concerns about potential long-term effects of N2O exposure, such as brain damage or addiction risks, are largely based on high-dose exposure scenarios and do not apply to the controlled use of N2O/O2 during labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and risks of nitrous oxide labor analgesia: a review. Rooks, JP.[2018]

Nitrous oxide (N2O) has become a popular and safe option for labor analgesia in the United States, with its use increasing from only 3 centers in 2011 to several hundred by 2020.

While N2O may not provide as strong pain relief as epidurals, it offers benefits such as increased patient control and mobility during labor, contributing to overall satisfaction among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous Oxide for Labor Analgesia: What We Know to Date. Broughton, K., Clark, AG., Ray, AP.[2021]

Nitrous oxide mixed with oxygen is a safe and effective pain management option for laboring women, gaining popularity in the U.S. as a minimal sedation alternative.

At the University of New Mexico Hospital, nurses now oversee the administration of nitrous oxide during childbirth, including for women with opioid dependence, following established guidelines that address education, cost, and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiating Intrapartum Nitrous Oxide in an Academic Hospital: Considerations and Challenges. Migliaccio, L., Lawton, R., Leeman, L., et al.[2018]

Nitrous oxide (N2O) has been effectively used for over 30 years at the University of California at San Francisco for labor analgesia, with many women reporting it provides significant pain relief during labor.

Despite its effectiveness, N2O is not widely available in the United States, highlighting a need for broader implementation and consideration of its clinical and environmental safety in medical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide for labor analgesia: expanding analgesic options for women in the United States. Collins, MR., Starr, SA., Bishop, JT., et al.[2022]

In a study involving 50 patients, nitrous oxide combined with intramuscular pethidine significantly affected oxygen saturation levels compared to no analgesia, indicating potential risks for maternal and fetal oxygenation during labor.

The findings suggest that nitrous oxide should be avoided for pain relief in labor if there are concerns about the mother's or baby's oxygen levels, as it may compromise their physiological reserves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled oximetric evaluation of inhalational, opioid and epidural analgesia in labour. Zelcer, J., Owers, H., Paull, JD.[2019]

Isoflurane mixed with nitrous oxide and oxygen can condense at relatively low temperatures, which could affect its effectiveness for pain relief during labor if not properly stored; for example, condensation occurs at 3.1°C at a pressure of 8.7 MPa.

To ensure proper mixing after phase separation, the mixture should be stored horizontally at room temperature for 24 hours or rolled mechanically, which helps restore the mixture's effectiveness for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase behaviour of premixed 0.25% isoflurane in 50% nitrous oxide and 50% oxygen. Tunstall, ME., Ross, JA.[2019]

Citations

1. China pubmed.ncbi.nlm.nih.gov

[Clinical study: the effects of inhaling nitrous oxide for analgesia labor on pregnant women and fetus]. [2013]

2. China pubmed.ncbi.nlm.nih.gov

[Application of nitrous oxide in labor analgesia]. [2013]

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

Nitrous Oxide During Labor: Maternal Satisfaction Does Not Depend Exclusively on Analgesic Effectiveness. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[Clinical study on efficacy and safety of labor analgesia with inhalation of nitrous oxide in oxygen]. [2013]

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

Nitrous oxide for labor analgesia. [2018]

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

Nitrous oxide for relief of labor pain: a systematic review. [2022]

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

Safety and risks of nitrous oxide labor analgesia: a review. [2018]

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

Nitrous Oxide for Labor Analgesia: What We Know to Date. [2021]

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

Initiating Intrapartum Nitrous Oxide in an Academic Hospital: Considerations and Challenges. [2018]

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

Nitrous oxide for labor analgesia: expanding analgesic options for women in the United States. [2022]

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

A controlled oximetric evaluation of inhalational, opioid and epidural analgesia in labour. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Phase behaviour of premixed 0.25% isoflurane in 50% nitrous oxide and 50% oxygen. [2019]