Clinical Review

Inhaled nitrous oxide for labor analgesia: Pearls from clinical experience

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No oversight by an anesthesiologist is required

The Centers for Medicare and Medicaid Services (CMS) produced a clarification statement for definitions of “anesthesia services” (42 CFR 482.52)9 that may be offered by a hospital, based on American Society of Anesthesiologists (ASA) definitions. CMS, consistent with ASA guidelines, does not define moderate or conscious sedation as “anesthesia,” thus direct oversight by an anesthesiologist is not required. Furthermore, the definition of “minimal sedation,” which is where 50% concentration delivery of inhaled nitrous oxide would be categorized, also does not meet this requirement by CMS.

Illustration: Kimberly Martens for OBG Management

Women who use inhaled nitrous oxide for labor pain typically are satisfied with its use

The use of analog pain scale measurements may not be appropriate in a setting where dissociation from pain might be the primary beneficial effect. Measurements of maternal satisfaction with their analgesic experience support this. The experiences at Vanderbilt University and Brigham and Women’s Hospital show that, while pain relief is limited, like reported in systematic reviews, maternal satisfaction scores for labor analgesia are not different among women who receive inhaled nitrous oxide analgesia, neuraxial analgesia, and those who transition from nitrous to neuraxial analgesia. In fact, published evidence supports extraordinarily high satisfaction in women who plan to use inhaled nitrous oxide, and actually successfully do so, despite only limited degrees of pain relief.10,11 Work to identify the characteristics of women who report success with inhaled nitrous oxide use needs to be performed so that patients can be better selected and informed when making analgesic choices.

Animal research on inhaled nitrous oxide may not translate well to human neonates

A very recent task force convened by the European Society of Anaesthesiology (ESA) addressed some of the potential concerns about inhaled nitrous oxide analgesia.12 Per their report:

“the potential teratogenic effect of N2O observed in experimental models cannot be extrapolated to humans. There is a lack of evidence for an association between N2O and reproductive toxicity. The incidence of health hazards and abortion was not shown to be higher in women exposed to, or spouses of men exposed to N2O than those who were not so exposed. Moreover, the incidence of congenital malformations was not higher among women who received N2O for anaesthesia during the first trimester of pregnancy nor during anaesthesia management for cervical cerclage, nor for surgery in the first two trimesters of pregnancy.”

There is a theoretical concern of an increase in neuronal apoptosis in neonates, demonstrated in laboratory animals in anesthetic concentrations, but the human relevance of this is not clear, since the data on animal developmental neurotoxicity is generally combined with data wherein potent inhalational anesthetic agents were also used, not nitrous oxide alone.13 The analgesic doses and time of exposure of inhaled nitrous oxide administered for labor analgesia are well below those required for these changes, as subanesthetic doses are associated with minimal changes, if any, in laboratory animals.

No labor analgesic is without the potential for fetal effects, and alternative labor analgesics such as systemic opioids in higher doses also may have potential adverse effects on the fetus, such as fetal heart rate effects or early tone, alertness, and breastfeeding difficulties. The low solubility and short half-life of inhaled nitrous oxide contribute to low absorption by tissues, thus contributing to the safety of this agent. Nitrous oxide via inhalation for sedation during elective cesarean has been reported to show no adverse effects on neonatal Apgar scores.14

Modern equipment keeps occupational exposure to nitrous oxide safe

One retrospective review of women exposed to high concentrations of inhaled nitrous oxide reported reduced fertility.15 However, the only effects on fertility were seen when nitrous was used without scavenging equipment, and in high concentrations. Moreover, that study examined dental offices, where nitrous was free flowing during procedures—quite a different setting than the intermittent inhalation, demand-valve modality as is used during labor—and when using appropriate modern, FDA-approved equipment, and scavenging devices. Per the recent ESA task force12:

“Members of the task force agreed that, despite theoretical concerns and laboratory data, there is no evidence indicating that the use of N2O in a clinically relevant setting would increase health risk in patients or providers exposed to this drug. With the ubiquitous availability of scavenging systems in the modern operating room, the health concern for medical staff has decreased dramatically. Properly operating scavenging systems reduce N2O concentrations by more than 70%, thereby efficiently keeping ambient N2O levels well below official limits.”

The ESA task force concludes: “An extensive amount of clinical evidence indicates that N2O can be used safely for procedural pain management, for labour pain, and for anxiolysis and sedation in dentistry.”12

Two important reminders

Inhaled nitrous oxide has been a central component of the labor pain relief menu in most of the rest of the world for decades, and the safety record is impeccable. This agent has now had extensive and growing experience in American maternity units. Remember 2 critical points: 1) patient selection is key, 2) analgesia is not like that provided by regional anesthetic techniques such as an epidural.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

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