Authors' objectives: The objective for the present report, is to systematically summarize published results on effectiveness using nitrous oxide in a paediatric setting for small, but painful hospital procedures. Safety issues for both the patients and health personnel exposed to nitrous oxide will also be reviewed.

Authors' results and conclusions: Literature search: We included 22 randomized controlled trials for the analyses of effect and safety of children. We also included 15 non-randomized controlled trials (19 articles) to document safety concerns of health personnel exposed to waste nitrous oxide. For the records only, we made a table of another 58 non-randomized controlled trials reporting results on safety of anaesthetic gases to health personnel, where nitrous oxide most likely is a part of the gas. :Effectiveness of nitrous oxide We have shown that health personnel or patients had a higher satisfaction level, lower distress or anxiety, and higher success rate when N2O was used compared to the placebo group. However, when other sedatives were used, N2O showed no benefit. Further, the pain level was lower using N2O compared to midazolam and/or ketamine, but not to EMLA or placebo. The certainty of evidence were from low to moderate, mostly due to lack of blinding and imprecision of the results. Most evident results was the reduced recovery time using N2O over other active drugs, not surprisingly as N2O has a very rapid onset and offset time. The certainty of evidence were high due to the pronounced differences in time and the objectivity in the outcome. Safety of nitrous oxide: Fifteen studies (19 articles) reported data on adverse events. Of 525 patients sedated with N2O, independent of hospital procedure or control group, none of the adverse events reported met the U.S. Food and Drug Administration’s definition of a serious adverse events. In particular, none of the study participants experienced serious cardiac or respiratory events (including oxygen below saturation level). Nausea, vomiting, restlessness, and euphoria were the most common adverse events observed in the N2O group. Health personnel exposed to waste N2O only, did not have an increased odds ratio for spontaneous abortion for none of the levels of N2O exposure (low exposure (OR=0.89; 95%CI=0.67, 1.19), high exposure (OR=1.18; 95%CI=0.84, 1.66) and unknown exposure (OR=1.30; 95%CI=0.43, 3.88)). However, there were a dose dependent increase in the odds ratio for reduced fertility in N2O exposed health care personnel (low exposure: OR=0.79; 95%CI=0.48, 1.30; high exposure: OR=3.48; 95%CI=1.99, 6.08). Further, the adjusted rate of congenital abnormalities in children was higher in N2O exposed women than in the control group (5.5±0.95, N=579 vs 3.6±0.34, N=2882). The certainty of the effect estimate was very low for all results. Sister chromatid exchange, micronuclei formation, DNA breaks and reactive oxygen species were methods to study the genotoxic effect of N2O exposure. The four included studies did not report evidence to reveal a potential genotoxic effect of N2O in the given settings (both dental offices and operating rooms). This was also true for the three included studies of neurological toxicity of N2O and for the four included studies of the effect of N2O on B12 metabolism. Conclusion: The results show that nitrous oxide can be used for sedation of children without serious adverse events. The most noticeable advantage by using N2O is the short restitution compared to other sedation methods which shortens the whole procedure and may streamline hospital procedures in children. The present technology assessment shows that midwives and dental personnel exposed to N2O compared to no exposure, did not increase the risk of spontaneous abortion or, at low exposure, reduced fertility. High exposure showed reduced fertility. The risk for congenital abnormalities born by exposed mothers (concentration or exposure degree not known) was higher than in non-exposed mothers. It is important to understand that these results are generated from data based on self-reporting questionnaires. Also, information about level of exposure were inadequate. No sufficient evidence were shown to draw conclusions of the toxic effect of N2O on DNA or cellular mechanisms. There were no studies on negative effects on reproductive health for health personnel in a setting where N2O were used for sedation of children for small hospital procedures. The personnel included in the present studies, were expected to have a more or less continuous exposure to N2O during their work hours. For personnel working with N2O sedation of children for small hospital procedures the exposure is expected to be significantly lower than the health care workers in the studies where toxic effects were reported, justified by two reasons. First, the concentration of N2O is expected to be lower because the access to better scavenging and ventilation systems; and second, the net exposure time would be lower as the procedure time (maximum 30 minutes per procedure) and the number for the hospital procedures per health worker per week would be relatively few (personal communication).

Authors' methods: We performed a Health Technology Assessment on effectiveness and safety of nitrous oxide for sedation in children in accordance with the handbook "Slik oppsummerer vi forskning", by Norwegian Institute of Public Health. We found literature from both hospital and dental settings. As our commissioner represents a hospital settings, we decided to narrow our report to only include efficiency assessment of literature covering a hospital setting. However, in the assessment of safety for health personnel, we included results also from dental setting.

Project Status: Completed

Year Published: 2018

URL for published report: https://www.fhi.no/en/publ/2018/Effectiveness-and-safety-of-nitrous-oxide-as-sedation-regimen-in-children-an-HTA/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo