Abstract: Twenty-six studies, randomising 2959 women, were included in this review. Inhaled analgesia versus a different type of inhaled analgesia  Pain relief was measured using a Visual Analogue Scale (VAS) from 0 to 100 mm where 100 corresponds to the most relief. Pain intensity was measured using a VAS from 0 to 100 mm, where 0 corresponds to no pain at all and 100 corresponds to the worst pain. The highest score for pain relief is the most positive in contrast to 'pain intensity' in which the higher score is more negative.   Flurane derivatives were found to offer better pain relief than nitrous oxide in first stage of labour as measured by a lower pain intensity score (average mean difference (MD) 14.39, 95% confidence interval (CI) 4.41 to 24.37, three studies, 70 women), also a higher pain relief score for flurane derivatives compared with nitrous oxide (average MD -16.32, 95% CI -26.85 to -5.79, two studies, 70 women). Substantial heterogeneity was found in the analyses of pain intensity (P = 0.003) and in the analysis of pain relief (P = 0.002).These findings should be considered with caution because of the questionable design of the included cross-over trials. More nausea was found in the nitrous oxide group compared with the flurane derivatives group (risk ratio (RR) 6.60 95% CI 1.85 to 23.52, two studies, 98 women). Inhaled analgesia versus placebo or no treatment  Placebo or no treatment was found to offer less pain relief compared to nitrous oxide (average RR 0.06, 95% CI 0.01 to 0.34, two studies, 310 women; MD -3.50, 95% CI -3.75 to -3.25, one study, 509 women). However, nitrous oxide resulted in more side effects for women such as nausea (RR 43.10, 95% CI 2.63 to 706.74, one study, 509 women), vomiting (RR 9.05, 95% CI 1.18 to 69.32, two studies, 619 women), dizziness (RR 113.98, 95% CI 7.09 to 1833.69, one study, 509 women) and drowsiness (RR 77.59, 95% CI 4.80 to 1254.96, one study, 509 women) when compared with placebo or no treatment. There were no significant differences found for any of the outcomes in the studies comparing one strength versus a different strength of inhaled analgesia, in studies comparing different delivery systems or in the study comparing inhaled analgesia with TENS. Due to lack of data, the following outcomes were not analysed within the review: sense of control; satisfaction with childbirth experience; effect on mother/baby interaction; breastfeeding; admission to special care baby unit; poor infant outcomes at long-term follow-up; or costs. Inhaled analgesia appears to be effective in reducing pain intensity and in giving pain relief in labour. However, substantial heterogeneity was detected for pain intensity. Furthermore, nitrous oxide appears to result in more side effects compared with flurane derivatives. Flurane derivatives result in more drowsiness when compared with nitrous oxide. When inhaled analgesia is compared with no treatment or placebo, nitrous oxide appears to result in even more side effects such as nausea, vomiting, dizziness and drowsiness. There is no evidence for differences for any of the outcomes comparing one strength verus a different strength of inhaled analgesia, comparing different delivery systems or comparing inhaled analgesia with TENS.

Plain-language summary: In this review of 26 randomised controlled trials of 2959 women, the effectiveness and safety of inhaled analgesia as pain relief for women in labour were studied. It was found that inhaled analgesia may help relieve pain during labour but women have to be informed about the side effects, such as nausea, vomiting, dizziness and drowsiness. Inhaled analgesia may help relieve labour pain without adversely increasing operative delivery rates (forceps or vacuum extraction, caesarian section), or affecting neonatal well being. Flurane derivatives were found to be slightly more effective than nitrous oxide for the reduction of pain and for pain relief although nitrous oxide also helped to relieve pain when compared with no treatment. Women who used nitrous oxide were more likely to experience nausea compared with flurane derivatives. When nitrous oxide was compared with no treatment or placebo, nitrous oxide resulted in side effects such as nausea, vomiting, dizziness and drowsiness. There was no information for satisfaction with childbirth experience or sense of control in labour in these studies and further research on these two important outcomes would be helpful.