More than 4 million births occur in the United States each year; in 2008, there were 4,247,694 births.1 A 2002 review of labor pain management in United States hospitals—stratified by number of yearly births and size of hospital—found that, among women who gave birth in 1997, 21 to 50 percent received epidural analgesia (hereafter epidural), 5 to 11 percent received combined spinal-epidural analgesia, 40 to 56 percent received parenteral analgesia, and 2 to 13 percent received paracervical or spinal analgesia. Ten to 17 percent of women did not receive any form of analgesia.2 The 2006 Listening to Mothers II survey found that 86 percent of 1,573 responding women reported using one or more types of medication for pain relief during labor; 76 percent used epidural or spinal analgesia/anesthesia, 22 percent received narcotics, 3 percent received general anesthesia, and 3 percent used nitrous oxide.3 Although limited by reliance on women's self-report, this survey provides data on the relative use of each method in the United States.3 Given that so few facilities offer nitrous oxide, a survey intended to provide national estimates of medication use may not provide accurate numbers.

Use of inhaled nitrous oxide is a common option for labor pain management in several countries outside the United States. A 2002 systematic review on the topic, the most recent source available, cites evidence that nitrous oxide is used in the United Kingdom by approximately 50 to 75 percent of women and in Finland by approximately 60 percent of women.4 In one study, 65 percent of women in Sweden received nitrous oxide for labor pain in 1991,5 and a 1995 survey of hospitals in Ontario, Canada, found that nitrous oxide was available for labor pain analgesia in 75 percent of responding hospitals.6 Nitrous oxide is also commonly used for labor analgesia in Australia and New Zealand.4 Five centers in the United States are known to currently provide nitrous oxide as an option for labor pain management: the Birth Center at the University of California San Francisco (UCSF) Medical Center; the University of Washington Hospital in Seattle; St. Joseph Regional Medical Center in Lewiston, ID; Okanogan Douglas Hospital in Brewster, WA; and Vanderbilt University Medical Center in Nashville, TN (which began offering nitrous oxide in June 2011 after this review was under way). The UCSF practices have been described in the literature, including contraindications, preparation of the patient, and the documentation and competency requirements for midwives.7 The UCSF model uses a mixture of 50 percent nitrous oxide and 50 percent oxygen that is self-administered by the patient after initial instruction on use and potential side effects. No related publications or descriptions of the option used at the University of Washington Hospital, St. Joseph Regional Medical Center, Okanogan Douglas Hospital, or Vanderbilt University could be located in the literature. A significant barrier to use in the United States is limited availability of equipment to blend and deliver a mixture of nitrous oxide and oxygen for self-administration by laboring women.

Nitrous Oxide as a Labor Pain Management Option

Nitrous oxide, sometimes called “laughing gas” because it can produce euphoria, is an inhalational anesthetic and analgesic gas. Nitrous oxide has been used in dental care since the mid-1800s8 and is commonly used for this indication today. Use of nitrous oxide during labor began in the late 1800s, and equipment for self-administration was introduced by Minnitt in England in 1934.4

The mechanism of action of nitrous oxide is thought to be an increased release of endorphin, dopamine, and other natural pain relievers in the brain, which modulate pain stimuli by way of descending spinal cord nerve pathways.9-10 Nitrous oxide does not completely relieve the pain of labor but instead creates “diminished pain, or a continued awareness of pain without feeling bothered by it.”11 Nitrous oxide also has an anti-anxiety effect, which may be helpful if laboring women are restless and doubt their ability to cope, emotions that are not uncommon especially during transition (the end of the first stage of labor, see Figure 1 for an overview of the stages of labor).

Figure 1 depicts the three stages of labor. The first stage of labor includes uterine contractions that cause the dilation (opening) and effacement (thinning) of the cervix. The first stage is often divided into early labor, active labor, and transition, corresponding to the level of dilation of the cervix. Contraction frequency, duration, and intensity increase as the first stage progresses. The second stage of labor begins when the cervix is completely dilated to 10 centimeters. Uterine contractions continue during the second stage, with the woman pushing to help the fetus down and out of the birth canal. The second stage of labor ends with the birth of the baby, at which point the third stage of labor begins. During the third stage, the uterus contracts and the woman may need to push to assist in the removal of the placenta. The third stage of labor concludes with the delivery of the placenta.

Figure 1

Stages of labor.

Nitrous oxide in a 50/50 mix, which can be mixed with a blender device (e.g., Nitronox®) or premixed (e.g., Entonox®), is the most common concentration of nitrous oxide administered for labor pain management, although some literature addresses varying concentrations of nitrous oxide in oxygen.12-13 Nitrous oxide is usually self-administered via a facemask or mouthpiece on an intermittent basis, beginning about 30 to 60 seconds before each contraction.14 Some literature addresses continuous vs. self-administered/intermittent administration.15-16

A variety of pain management methods are available for the pain women experience during the different stages of labor. See Table 1 for the labor pain management methods found in studies in this review. Epidural analgesia is the most commonly used method in the United States17 and may block pain entirely. Although epidurals are more effective for pain relief than other pain management methods, epidurals are associated with increased risk of assisted (vacuum or forceps) vaginal birth, use of oxytocin, maternal hypotension, motor blockade, urinary retention, maternal fever, and cesarean for fetal distress.18 In addition, the second stage of labor can be longer in women who have epidurals than in women who receive other pain management methods.19 Women who have epidurals must have additional monitoring and may need confinement to bed, which limits mobility and options for positioning, and placement of a Foley catheter. Epidural placement is an invasive procedure that can have uncommon but clinically significant complications such as spinal headache.20 Catastrophic complications, such as epidural hematoma and epidural abscess, are very rare but do occur.20

Table 1. Labor pain management methods used in studies included in this review.

Table 1

Labor pain management methods used in studies included in this review.

Although nitrous oxide would not be expected to be as effective for analgesia as an epidural because of the differences in their mechanism of action, nitrous oxide has other benefits including that it is inexpensive and noninvasive. Nitrous oxide has a rapid onset and end of action. Thus women who do not like nitrous oxide or find it inadequate for pain management can easily discontinue its use and switch to another method, unlike epidurals and systemic opioids that diminish gradually over a much longer time period. Mobility and options for positioning are not limited nor does nitrous oxide require additional monitoring and potential anesthesia-related interventions (e.g., bladder catheterization). Women self-administer nitrous oxide, which allows them to control the amount they need.21 Nitrous oxide may not be an ideal method for women who want maximum pain relief, but it could be preferable to other pharmacologic pain management methods for women who want increased mobility with less intervention and monitoring. Nitrous oxide might also be useful when a woman wants to delay use of epidural analgesia until later in labor, when epidural anesthesia is not immediately available (e.g., in hospitals that do not have in-house anesthesia staff and must call in an anesthesia provider), when a woman arrives at the hospital too far along in labor to allow for an epidural to be placed and take effect, and when a woman finds epidural analgesia ineffective or inadequate.

One concern with nitrous oxide use is the potential for the gas to escape into the room and potentially affect health care workers as well as other individuals present with laboring women. For this reason, there are multiple organizations responsible for regulation of the use of nitrous oxide and factors other than clinical outcomes are important to decisionmaking about its use (see Appendix F for a description of regulatory considerations). Room ventilation systems and scavenging systems that remove waste gases are used to reduce exposure to caregivers and others present for labor. Equipment capable of scavenging provides constant negative pressure so that the woman's exhalations, which contain nitrous oxide, are captured and removed from the room and facility.14

Identifying the appropriate outcome measure by which to assess nitrous oxide is challenging. Nitrous oxide is not intended to provide the extent of pain relief expected with epidural. Rather than a head to head comparison of effectiveness, the benefits of nitrous oxide rest on women's satisfaction and safety of the approach for the woman and her fetus/newborn.

Scope of This Report

Most women in the United States use some type of medication for labor pain management. However, the option of using nitrous oxide to relieve labor pain is limited by its lack of availability. With such prevalent use of nitrous oxide during labor in other countries, increasing interest in this method in the United States, and potential advantages of this pain management method, such as being less expensive and invasive than widely used regional anesthesia, this review attempts to assess the effectiveness of nitrous oxide in managing labor pain and to identify potential factors that may influence its availability and use within the United States. Our Key Questions have been structured with this goal in mind. The primary outcomes for consideration, as identified by our technical expert panel, include the comparative effectiveness of nitrous oxide for the management of labor pain, the influence of nitrous oxide on women's satisfaction with their birth experience, the health system factors influencing its use within the United States, and any adverse effects associated with this intervention. With the rate of cesarean birth continuing to rise—32.3 percent of all U.S. births reported in 20081—it is also important to address whether the use of nitrous oxide during labor influences the route of birth in women initially intending a vaginal birth.

Key Questions

We have synthesized evidence in the published literature to address these Key Questions:

  1. What is the effectiveness of nitrous oxide when compared with other methods for the management of labor pain among women intending a vaginal birth?
  2. What is the comparative effectiveness of nitrous oxide on women's satisfaction with their birth experience and pain management?
  3. What is the comparative effectiveness of nitrous oxide on the route of birth?
  4. What is the nature and frequency of adverse effects associated with the use of nitrous oxide for the management of labor pain, including but not limited to:
    • Maternal adverse effects, such as nausea and vomiting, dreams, dizziness, unconsciousness, and postpartum complications.
    • Fetal/neonatal adverse effects, such as low Apgar scores and abnormal fetal cord blood gases.
    • Childhood adverse effects, such as drug dependency and developmental complications.
    • Adverse effects on health care providers and other individuals present for labor.
  5. What are the health system factors influencing the use of nitrous oxide for the management of labor pain, including but not limited to provider preferences, availability, setting, and resource utilization?

Organization of This Evidence Report

The following chapter describes our methods, including our search strategy, inclusion and exclusion criteria, approach to review of abstracts and full publications, and methods for extraction of data into evidence tables, and compiling evidence. We also describe our approach to grading the quality of the literature and to describing the strength of the literature.

In the Results chapter, we review the evidence identified by Key Question. We report the number and type of studies identified and we differentiate between total numbers of publications and unique studies to bring into focus the number of duplicate publications in this literature in which multiple publications are derived from the same study population. In the final chapter of the report we discuss the results and enlarge on the methodologic considerations relevant to each Key Question. We also outline the current state of the literature and challenges for future research on the use of nitrous oxide for the management of labor pains.

Uses of This Report

We anticipate this report will be of value to all health care providers who take care of women of childbearing age, including members of the American Congress of Obstetricians and Gynecologists; the Association of Women's Health, Obstetric and Neonatal Nurses; the American College of Nurse-Midwives; the American Association of Birth Centers; the American Society of Anesthesiologists; the Society for Obstetric Anesthesia and Perinatology; the American Association of Nurse Anesthetists; the American Academy of Family Physicians; and other clinical professional organizations. In addition, this review will be of use to the National Institutes of Health, Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and the Health Resources and Services Administration – all of which have offices or bureaus devoted to women's health issues. This report can bring providers up to date about the current state of evidence, and it provides an assessment of the quality of studies that aim to determine the outcomes of the use of nitrous oxide for the management of labor pain. It will be of interest to individual women and the general public because millions of women per year give birth in the United States, and the recurring need for women and their health care providers to decide among numerous options for labor pain management. This report will also be useful to facilities considering providing nitrous oxide for labor pain management. We also anticipate it will be of use to private sector organizations concerned with women's health, such as Childbirth Connection, the National Women's Health Network, and Our Bodies Ourselves.

Researchers can obtain a concise analysis of the current state of knowledge in this field. They will be poised to pursue further investigations that are needed to advance research methods, understand risk factors, develop options for labor pain management, and optimize the effectiveness and safety of clinical care for women in labor.