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 trial tests whether nitrous oxide (laughing gas) or oxygen provides better pain relief during the placement of a Foley balloon catheter, a device used to initiate labor. Participants will receive either a mix of nitrous oxide and oxygen or just oxygen. The trial seeks pregnant individuals scheduled for labor induction who can receive a Foley balloon catheter. Participants should not have certain medical conditions, such as an allergy to nitrous oxide or vitamin B12 deficiency. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to important research that could enhance labor induction methods.

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

Research has shown that nitrous oxide is generally safe for pain relief during labor. In past studies, women found it to be a safe option with little risk to the baby. The effects of nitrous oxide wear off quickly, offering an advantage over other pain relief methods used during labor. However, the pain relief it provides is often mild and might not significantly reduce pain for everyone.

No specific safety concerns are associated with using nitrous oxide during labor, but its pain relief may not be as strong as other options. Still, its short-lasting effects and safety make it a popular choice for those seeking minimal intervention. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard pain relief options for induced labor, which often involve epidurals or narcotics, the use of nitrous oxide for pain management is gaining attention. Researchers are excited about this approach because nitrous oxide, combined with oxygen, offers a fast-acting, non-invasive alternative that women can control. It provides pain relief without the need for an IV or additional interventions, allowing for greater mobility during labor. Plus, its effects wear off quickly, making it a flexible option that can be discontinued at any time if needed.

What evidence suggests that this trial's treatments could be effective for induced labor?

Research has shown that nitrous oxide can help relieve pain during labor. One study used a mix of 80% nitrous oxide and 20% oxygen, which eased pain without causing serious side effects. Many women have shared positive experiences using nitrous oxide for labor pain. However, some studies have found it didn't provide much more pain relief than a placebo in early labor. In this trial, participants in the experimental arm will receive an inhalant of 50% nitrous oxide and 50% oxygen, while those in the control arm will receive 100% oxygen. Overall, nitrous oxide may help shorten labor by a few hours, making it a promising option for managing pain during labor induction. ^{2 3 5 6 7}

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

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

History of malignant hyperthermia

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

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3594866/

Nitrous Oxide for Labor Analgesia: Expanding Analgesic ... Klikovich published the results of his study wherein he utilized 80% N2O with 20% oxygen in 25 laboring women, and demonstrated pain relief with no adverse ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1871519223001002

Women's perspectives of nitrous oxide for labour and ... The majority (86.3%) used N2O for pain relief in labour, 43.0% laboured spontaneously, and 50.6% experienced induction or augmentation of labour. Smaller ...

3. apsf.org apsf.org/article/safety-and-utility-of-nitrous-oxide-for-labor-analgesia/

Safety and Utility of Nitrous Oxide for Labor Analgesia One study found no decrease in pain scores with nitrous oxide compared to placebo in early labor,8 and use of nitrous oxide did not lead to a significant ...

4. oregon.gov oregon.gov/oha/HPA/DSI-HERC/EvidenceBasedReports/Nitrous%20Oxide%20for%20Labor%20Pain%20Mgmt.pdf

nitrous oxide use for labor pain The literature review found that the length of labor was consistently shorter (about 2 to 4 hours shorter) among Page 11 11 Nitrous Oxide Use for Labor Pain ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01738672

NCT01738672 | Inhaled Nitrous Oxide and Labor Analgesia Hypothesis: The administration of nitrous oxide for labor analgesia will decrease the labor epidural anesthesia rate by 15%.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32452155/

Nitrous Oxide Use During Labor: Satisfaction, Adverse Effects ... The purpose of this study was to investigate demographic characteristics, safety, and satisfaction in a cohort of parturients who used inhaled nitrous oxide (N ...

7. effectivehealthcare.ahrq.gov effectivehealthcare.ahrq.gov/sites/default/files/related_files/labor-nitrous-oxide_executive.pdf

Nitrous Oxide for the Management of Labor Pain Executive ... Our primary outcomes included pain management, satisfaction with pain management, satisfaction with birth experience, effect of nitrous oxide on the route of ...