Abstract: We included 35 trials (13,872 adult participants). Seven included studies were at low risk of bias. We identified eight studies as awaiting classification since we could not obtain the full texts, and had insufficient information to include or exclude them. We included data from 24 trials for quantitative synthesis. The results of meta-analyses showed that nitrous oxide-based techniques increased the incidence of pulmonary atelectasis (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18 to 2.10, P = 0.002), but had no effects on the inhospital case fatality rate, the incidence of pneumonia, myocardial infarction, stroke, severe nausea and vomiting, venous thromboembolism, wound infection, or the length of hospital stay. The sensitivity analyses suggested that the results of the meta-analyses were all robust except for the outcomes of pneumonia, and severe nausea and vomiting. Two trials reported length of intensive care unit (ICU) stay but the data were skewed so were not pooled. Both trials reported that nitrous oxide-based techniques had no effects on the length of ICU stay. We rated the quality of evidence for two outcomes (pulmonary atelectasis, myocardial infarction) as high, four outcomes (inhospital case fatality rate, stroke, venous thromboembolism, length of hospital stay) as moderate, and three (pneumonia, severe nausea and vomiting, wound infection rate) as low. Given the evidence from this Cochrane review, the avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting. Since there are eight studies awaiting classification, selection bias may exist in our systematic review.

Plain-language summary: We examined the evidence available up to 17 October 2014. We included 35 trials involving 13,872 adult participants, all of whom were randomized to either receive nitrous oxide or no nitrous oxide. The trials covered a variety of situations during general anaesthesia. We found that general anaesthesia with nitrous oxide increased the risk of pulmonary atelectasis (i.e. failure of the lungs to expand fully). When we restricted the results to the highest quality studies only, we found evidence that nitrous oxide may potentially increase the risk of pneumonia and severe nausea and vomiting. However, nitrous oxide had no effect on the patients' survival, the incidence of heart attack, stroke, wound infection, the occurrence of blood clots within veins, the length of hospital stay, or the length of intensive care unit stay. The evidence related to survival of participants was of moderate quality because we did not have enough data. The evidence related to some harmful effects, such as failure of the lungs to expand fully and heart attack, was of high quality, while for other harmful effects, such as stroke and the occurrence of blood clots within veins, the evidence was of moderate quality. For others, such as pneumonia, severe nausea and vomiting, and wound infection, the evidence was of low quality. The evidence related to the length of time spend in hospital was of moderate quality. The avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting.