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Meta-Analysis
. 2015 Nov 6;2015(11):CD008984.
doi: 10.1002/14651858.CD008984.pub2.

Nitrous oxide-based techniques versus nitrous oxide-free techniques for general anaesthesia

Rao Sun  1 , Wen Qin Jia, Peng Zhang, KeHu Yang, Jin Hui Tian, Bin Ma, Yali Liu, Run H Jia, Xiao F Luo, Akira Kuriyama
Affiliations
Meta-Analysis

Nitrous oxide-based techniques versus nitrous oxide-free techniques for general anaesthesia

Rao Sun et al. Cochrane Database Syst Rev. .

Abstract

Background: Nitrous oxide has been used for over 160 years for the induction and maintenance of general anaesthesia. It has been used as a sole agent but is most often employed as part of a technique using other anaesthetic gases, intravenous agents, or both. Its low tissue solubility (and therefore rapid kinetics), low cost, and low rate of cardiorespiratory complications have made nitrous oxide by far the most commonly used general anaesthetic. The accumulating evidence regarding adverse effects of nitrous oxide administration has led many anaesthetists to question its continued routine use in a variety of operating room settings. Adverse events may result from both the biological actions of nitrous oxide and the fact that to deliver an effective dose, nitrous oxide, which is a relatively weak anaesthetic agent, needs to be given in high concentrations that restrict oxygen delivery (for example, a common mixture is 30% oxygen with 70% nitrous oxide). As well as the risk of low blood oxygen levels, concerns have also been raised regarding the risk of compromising the immune system, impaired cognition, postoperative cardiovascular complications, bowel obstruction from distention, and possible respiratory compromise.

Objectives: To determine if nitrous oxide-based anaesthesia results in similar outcomes to nitrous oxide-free anaesthesia in adults undergoing surgery.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014 Issue 10); MEDLINE (1966 to 17 October 2014); EMBASE (1974 to 17 October 2014); and ISI Web of Science (1974 to 17 October 2014). We also searched the reference lists of relevant articles, conference proceedings, and ongoing trials up to 17 October 2014 on specific websites (http://clinicaltrials.gov/, http://controlled-trials.com/, and http://www.centerwatch.com).

Selection criteria: We included randomized controlled trials (RCTs) comparing general anaesthesia where nitrous oxide was part of the anaesthetic technique used for the induction or maintenance of general anaesthesia (or both) with any general anaesthesia using a volatile anaesthetic or propofol-based maintenance of anaesthesia but no nitrous oxide for adults undergoing surgery. Our primary outcome was inhospital case fatality rate. Secondary outcomes were complications and length of stay.

Data collection and analysis: Two review authors independently assessed trial quality and extracted the outcome data. We used meta-analysis for data synthesis. Heterogeneity was examined with the Chi² test and by calculating the I² statistic. We used a fixed-effect model if the measure of inconsistency was low for all comparisons (I² statistic < 50%); otherwise we used a random-effects model for measures with high inconsistency. We undertook subgroup analyses to explore inconsistency and sensitivity analyses to evaluate whether the results were robust. We assessed the quality of evidence of the main outcomes using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.

Main results: 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.

Authors' conclusions: 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.

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Conflict of interest statement

Rao Sun: none known. Wen Qin Jia: none known. KeHu Yang: none known. Jin Hui Tian: none known. Bin Ma: none known. Yali Liu: none known. Run H Jia: none known. Peng Zhang: none known. Xiao F Luo: none known. Akira Kuriyama: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
4
4
Funnel plot of comparison: 1 Nitrous oxide‐based versus nitrous oxide‐free, outcome: 1.6 Severe nausea and vomiting.
1.1
1.1. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 1 Inhospital case fatality rate.
1.2
1.2. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 2 Pneumonia.
1.3
1.3. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 3 Pulmonary atelectasis.
1.4
1.4. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 4 Myocardial infarction.
1.5
1.5. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 5 Stroke.
1.6
1.6. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 6 Severe nausea and vomiting.
1.7
1.7. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 7 Venous thromboembolism.
1.8
1.8. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 8 Wound infection rate.
1.9
1.9. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 9 Length of hospital stay.
1.10
1.10. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 10 Inhospital case fatality rate: type of surgery.
1.11
1.11. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 11 Pneumonia: type of surgery.
1.12
1.12. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 12 Pulmonary atelectasis: type of surgery.
1.13
1.13. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 13 Myocardial infarction: type of surgery.
1.14
1.14. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 14 Stroke: type of surgery.
1.15
1.15. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 15 Severe nausea and vomiting: type of surgery.
1.16
1.16. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 16 Wound infection rate: type of surgery.
1.17
1.17. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 17 Length of hospital stay: type of surgery.
1.18
1.18. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 18 Inhospital case fatality rate: concentrations of inhaled nitrous oxide.
1.19
1.19. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 19 Stroke: concentrations of inhaled nitrous oxide.
1.20
1.20. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 20 Severe nausea and vomiting: concentrations of inhaled nitrous oxide.
1.21
1.21. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 21 Length of hospital stay: concentrations of inhaled nitrous oxide.
1.22
1.22. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 22 Inhospital case fatality rate: techniques used in the nitrous oxide‐free group.
1.23
1.23. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 23 Pneumonia: techniques used in the nitrous oxide‐free group.
1.24
1.24. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 24 Pulmonary atelectasis: techniques used in the nitrous oxide‐free group.
1.25
1.25. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 25 Myocardial infarction: techniques used in the nitrous oxide‐free group.
1.26
1.26. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 26 Stroke: techniques used in the nitrous oxide‐free group.
1.27
1.27. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 27 Severe nausea and vomiting: techniques used in the nitrous oxide‐free group.
1.28
1.28. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 28 Wound infection rate: techniques used in the nitrous oxide‐free group.
1.29
1.29. Analysis
Comparison 1 Nitrous oxide‐based versus nitrous oxide‐free, Outcome 29 Length of hospital stay: techniques used in the nitrous oxide‐free group.
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Update of

References

References to studies included in this review

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References to studies awaiting assessment

Adams 1994 {published data only}
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References to other published versions of this review

Yang 2011
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