'Laughing Gas' Eases Pain in Early Labor, Review Shows

By Nancy Walsh

Inhaled analgesia -- using nitrous oxide or a flurane-derivative -- is a useful option for women in labor, particularly for those who are unable or unwilling to undergo more invasive analgesic procedures, a Cochrane review determined.

Inhaling nitrous oxide -- commonly called laughing gas -- was associated with greater pain relief than placebo or no treatment during the first stage of labor, with an average mean difference of −3.50 (95% CI −3.75 to −3.25) on a Visual Analog Scale (VAS) of pain, according to Trudy Klomp, MSc, of the Midwifery Academy of Amsterdam in the Netherlands, and colleagues.

In turn, administration of a flurane-derivative agent led to more pain relief than the nitrous oxide, with a mean treatment effect of −16.32 (95% CI −26.85 to −5.79) on VAS, the researchers reported in the Cochrane Database of Systematic Reviews 2012.

Inhaled analgesia during labor has been used for more than 150 years, with nitrous oxide being the most commonly used agent, most likely because it is easy to administer, has minimal toxicity, and has no effect on uterine contractility.

While the use of epidural analgesia has become increasingly popular, it increases costs and is not without side effects, so other options are desirable, according to Klomp and colleagues.

"Even in hospitals with full-time obstetric anesthesia coverage, no one may be available to place an epidural, provide another highly effective method of labor analgesia, or provide a labor-intensive nonpharmacological method to help the woman in pain," the authors observed.

Because reliable data are sparse regarding the safety and efficacy of inhaled anesthesia during labor, whether with nitrous oxide or flurane derivatives such as enflurane or isoflurane, Klomp's group searched the literature, identifying 26 randomized trials that included 2,959 women planning a vaginal birth.

A total of 18 of the studies had a parallel design, while the remainder were crossover studies, and sample sizes ranged from 18 to 509.

When the researchers compared outcomes in women using nitrous oxide with those for women using flurane derivatives, they found that in three crossover studies that included 70 women, pain intensity during the first stage of labor was lower among women using the flurane agents, with an average mean difference of 14.39 (95% CI 4.41 to 24.37).

However, there was considerable heterogeneity in these studies (I2=42%), the researchers noted.

In two studies that assessed maternal satisfaction with pain relief during the first and second stages of labor for the flurane derivatives or nitrous oxide, no differences were reported, with a risk ratio of 0.97 (95% CI 0.80 to 1.18).

In studies that considered the safety of nitrous oxide versus flurane derivatives, there were no differences in the need for assisted vaginal birth (RR 0.71, 95% CI 0.44 to 1.15).

There were no differences in drowsiness or blood loss between the groups, although less amnesia was seen with nitrous oxide.

However, nitrous oxide was associated with more nausea compared with the flurane derivatives (RR 6.60, 95% CI 1.85 to 23.52).

No differences were seen between nitrous oxide and the flurane derivatives in low Apgar scores or neurologic adaptive capacity scores, and the scarcity of data on these newborn outcomes precluded any conclusions being made in these areas, the researchers noted.

In two studies that compared inhaled analgesia with placebo or no treatment, women receiving 30% to 50% nitrous oxide experienced less pain (RR 0.06, 95% CI 0.01 to 0.34).

There also were no differences in rates of assisted vaginal births or cesarean sections among women receiving inhaled analgesia versus controls.

However, women receiving nitrous oxide experienced more nausea (RR 43.10, 95% CI 2.63 to 706.74) drowsiness (RR 77.59, 95% CI 4.80 to 1,254.96), and dizziness (RR 113.98, 95% CI 7.09 to 1,833.69).

One study that included 20 women compared inhaled nitrous oxide with transcutaneous electrical nerve stimulation, and found no difference in pain intensity or satisfaction with pain relief.

The authors of the review concluded that inhaled analgesia with the flurane derivatives during the first stage of labor provided greater pain relief with less nausea than nitrous oxide.

However, nitrous oxide can be easily self-administered, while the flurane derivatives must be given by an anesthesia professional.

Klomp and colleagues cautioned that their findings should be interpreted with care, because they analyzed the data from the crossover studies as though the trials had been parallel in design, which could lead to high risk of bias.

They also noted that many of the included studies had small sample sizes and blinding was difficult, because some of the flurane derivatives have distinct odors.

Overall, none of the included studies were free from bias, and in more than half, the quality of reporting was rated as poor.

The authors concluded that further randomized studies are needed to more fully explore the efficacy of inhaled analgesia, and should include outcomes such as the women's sense of control and satisfaction with the childbirth experience.

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