Inhaled Nitrous Oxide and Labor Analgesia

• Sponsor: Ya'aqov Abrams (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01738672
• Collaborator: University of Pittsburgh (Other)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Hypothesis: The administration of nitrous oxide for labor analgesia will decrease the labor epidural anesthesia rate by 15%.

Specific Aim: To determine if nitrous oxide can be an effective alternative technique for the provision of labor analgesia at Magee-Womens Hospital.

Condition or Disease	Intervention/Treatment	Phase
Labor Pain	Drug: Inhaled nitrous oxide	Phase 2

Detailed Description

Inhalational anesthetic agents have been used since the mid 1800s to help alleviate pain associated with labor. James Simpson and John Snow initially utilized ether and chloroform respectively in 1847 and 1853. Stanislav Klikovich followed in his predecessors footsteps and successfully administered nitrous oxide for labor analgesia in 1881. Although many inhalational agents have been considered for labor analgesia since that time, the administration of nitrous oxide has been refined over the last century and remains a common practice for obstetrical anesthesia today. Since that time, nitrous oxide has been found to be an effective labor analgesia for many women, although providing less pain relief compared then a labor epidural, it has been found to be safe for the mother, baby, and health care providers.

Nitrous oxide is currently used by 60% of laboring women in the United Kingdom, 50% of women who deliver in Australia and nearly 50% of all parturients in Canada and Finland. This compares to a recent article which reported that only two United States hospitals routinely offer nitrous oxide for labor analgesia as the majority of laboring women request an epidural. The epidural rate in the Unites States averages nearly 90% compared to only 14-38% in other parts of the world.

Nitrous oxide is an easy to administer non-flammable, odorless inhalational agent that produces both analgesia and anxiolysis. It is believed the mechanism of action of nitrous oxide is through the release of endogenous opioid peptides into the periaqueductal gray area of the midbrain which stimulates descending noradrenergic pathways resulting in analgesia. These pathways modulate pain in the dorsal horn of the spinal cord through alpha-2 adrenoreceptors. Anxiolytic effects are thought to be caused by inhibition of N-methyl-D-aspartate (NMDA) receptors. In a Swedish study involving 1,997 parturients utilizing inhaled nitrous oxide as the sole anesthetic for labor analgesia, 37.6% of participants reported effective pain relief.

Currently, the rate of labor epidural analgesia at Magee Womens Hospital is approximately 90%. There are many advantages to the use of nitrous oxide for labor analgesia compared to an epidural. Complications associated with labor epidural analgesia can include infection, bleeding, headache, and wet-tap. These complications can result in a prolonged hospital stay that is not associated with the use of nitrous oxide for labor analgesia.

One of the biggest advantages of the use of nitrous oxide for labor analgesia is the significantly lower cost to administer compared to an epidural. In a recent article in the Birth journal, it was noted that the use of nitrous oxide is far less expensive and much simpler than epidural analgesia and does not result in complications requiring additional treatments and prolonged hospital stays. The use of nitrous could have major financial benefits for both Medicaid and private insurance companies. In 2004, the largest cost for these insurance entities was the cost to care for pregnant and laboring women which was reported to cost $41 billion. The most significant cost savings would be the reduction in anesthesia services. Currently average cost per patient for anesthesia staff coverage is 728 dollars. Average re-imbursement for a labor epidural placement is 385 dollars. Nitrous oxide does not require anesthesia staff to implement, saving health care dollars. After the initial investment of the nitrous oxide machine, the only additional cost would be the tubing and mask for the patient and the nitrous oxide and oxygen E-cylinders for delivery.

With Nitrous oxide having many qualities that make it an attractive choice for labor analgesia, many anesthesia providers are questioning its limited use in the United States. It is speculated that it may be cultural issue and that women make decisions regarding labor analgesia based on learned experiences of family and friends, many of whom have not heard of or used nitrous oxide to cope with labor pains. Another reason may be that some authors argue that nitrous oxide is an orphan drug with no pizzazz for professional groups or companies to profit from its use as it causes environmental and occupational hazards which limit its use. No definitive opinion exists to answer this question. Finally, some authors suggest its use is limited due to the disadvantages of nitrous oxide, which include the possibility to cause mood alterations, euphoria, impaired mentation, dysphoria, inappropriate behaviors and nausea and vomiting. These side effects are limited through a number of fail-safe mechanisms built into the nitrous oxide machine which includes the delivery of at least 30% oxygen and 3 liters of fresh gas flow. In addition the proper use includes self administration under direct supervision of a trained provider while the nitrous oxide is in use.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Inhaled Nitrous Oxide and Labor Analgesia
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitrous Oxide Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia.	Drug: Inhaled nitrous oxide; Administration of nitrous oxide for labor analgesia; Other Names: N2O Nitronox Entonox

Outcome Measures

Primary Outcome Measures

1. Labor Pain [At baseline, and at 1 hour after initiation of nitrous oxide]

   Participant reported pain score, using a numerical rating scale (NRS) ranging from no pain (0) to severe pain (10).

Other Outcome Measures

1. Anxiety [At baseline, and at 1 hour after initiation of nitrous oxide]

   Participant reported anxiety score, using a numerical rating scale (NRS) ranging from no anxiety (0) to severe anxiety (10).

2. Nausea [At baseline, and at 1 hour after initiation of nitrous oxide]

   Participant reported nausea score, using a numerical rating scale (NRS) ranging from no nausea (0) to severe nausea (10).

3. Emesis [During administration of nitrous oxide]

   Participant reported emesis (yes or no).

4. Participant Satisfaction [24 hours after delivery]

   Participant reported score of satisfaction with nitrous oxide for labor analgesia, using a numerical rating scale (NRS) ranging from completely dissatisfied (0) to completely satisfied (100).

5. Crossover To Epidural [Initiation of nitrous oxide to completion of delivery.]

   Participants crossing over from nitrous oxide to epidural.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• all women of childbearing age (including children aged 14 years and above)who are pregnant

• parturients who request labor analgesia of family medicine investigators certified in the use of nitrous oxide for labor analgesia at Magee-Women's Hospital

• informed verbal and written consent

Exclusion Criteria:

• coexisting medical conditions that are contraindications to the use of nitrous oxide (i.e. recent eye or ear surgery, history of Meniere's disease, history of vitamin B-12 deficiency)

• history of severe nausea and vomiting

• history of chronic pain

• inability to hold a facemask

• impairment of consciousness or intoxication at time of delivery

• received intravenous opioids within two hours prior to initiation of nitrous oxide

• impaired oxygenation (ex: lung cysts, pneumothorax, pulmonary hypertension, or pulmonary edema) with a room-air pulse oximetry reading less than 95%

• hemodynamic instability

• non-reassuring fetal heart rate tracing

• inability to read, write and understand the English language enough to complete all survey questionnaires and pain assessment scales.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Ya'aqov Abrams
• University of Pittsburgh

Investigators

• Principal Investigator: Ya'aqov Abrams, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ya'aqov Abrams, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01738672
• Other Study ID Numbers: PRO11090221
• First Posted: Nov 30, 2012
• Last Update Posted: Nov 21, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Ya'aqov Abrams, Assistant Professor, University of Pittsburgh: Nitrous oxide; labor and delivery; analgesia
• Additional relevant MeSH terms: Labor Pain; Nitrous Oxide; Entonox

Study Results

Participant Flow

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Period Title: Overall Study
STARTED	16
COMPLETED	11
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Overall Participants	16
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	30
Sex: Female, Male (Count of Participants)
Female	16 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Labor Pain
Description	Participant reported pain score, using a numerical rating scale (NRS) ranging from no pain (0) to severe pain (10).
Time Frame	At baseline, and at 1 hour after initiation of nitrous oxide

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	16
Baseline	8.88 (0.97)
1 hour after initiation of nitrous oxide	8.18 (1.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitrous Oxide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	t-test, 2 sided
	Comments

2. Other Pre-specified Outcome

Title	Anxiety
Description	Participant reported anxiety score, using a numerical rating scale (NRS) ranging from no anxiety (0) to severe anxiety (10).
Time Frame	At baseline, and at 1 hour after initiation of nitrous oxide

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	15
Baseline	2.50 (3.54)
1 hour after initiation of nitrous oxide	2.00 (3.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitrous Oxide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	t-test, 2 sided
	Comments

3. Other Pre-specified Outcome

Title	Nausea
Description	Participant reported nausea score, using a numerical rating scale (NRS) ranging from no nausea (0) to severe nausea (10).
Time Frame	At baseline, and at 1 hour after initiation of nitrous oxide

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	16
Baseline	0.25 (0.58)
1 hour after initiation of nitrous oxide	0.46 (1.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nitrous Oxide
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	t-test, 2 sided
	Comments

4. Other Pre-specified Outcome

Title	Emesis
Description	Participant reported emesis (yes or no).
Time Frame	During administration of nitrous oxide

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	16
Number [participants experiencing emesis]	1 6.3%

5. Other Pre-specified Outcome

Title	Participant Satisfaction
Description	Participant reported score of satisfaction with nitrous oxide for labor analgesia, using a numerical rating scale (NRS) ranging from completely dissatisfied (0) to completely satisfied (100).
Time Frame	24 hours after delivery

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	3
Median (Full Range) [units on a scale]	90

6. Other Pre-specified Outcome

Title	Crossover To Epidural
Description	Participants crossing over from nitrous oxide to epidural.
Time Frame	Initiation of nitrous oxide to completion of delivery.

Outcome Measure Data

Analysis Population Description

Data are included for all participants from which they were collected.

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
Measure Participants	15
Number [participants]	8 50%

Adverse Events

Arm/Group Title	Nitrous Oxide
Arm/Group Description	Parturients who request labor analgesia will be offered inhaled nitrous oxide for labor analgesia. Inhaled nitrous oxide: Administration of nitrous oxide for labor analgesia
All Cause Mortality
	Nitrous Oxide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nitrous Oxide
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Nitrous Oxide
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Cardiac disorders
Sinus Bradycardia	1/16 (6.3%)
Sinus Tachycardia	3/16 (18.8%)
Gastrointestinal disorders
Nausea	3/16 (18.8%)
Vomiting	1/16 (6.3%)
General disorders
Pain	16/16 (100%)
Psychiatric disorders
Anxiety	7/16 (43.8%)
Vascular disorders
Hypertension	2/16 (12.5%)
Hypotension	3/16 (18.8%)

Limitations/Caveats

The study was limited by its small size. Additionally, because all participants were recruited from Family Medicine clinics in Pittsburgh, these results may not be generalizable to other populations of pregnant women.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.