Effectiveness of nitrous oxide as analgesia for pediatric patients in the Emergency Department: a systematic review

Introduction
Untreated acute pain in children at the Emergency Department could not only lead to long term negative effects but also adversely impact procedures. Nitrous oxide can be helpful in pain management due to the promise to provide effective relief of mild to moderate anxiety and pain. The objective of this systematic review was to critically appraise current best evidence regarding effectiveness of the use of nitrous oxide for pain management compared to local anesthesia in pediatric patients at the Emergency Department undergoing painful minor procedures.
Methods
We searched Embase, MEDLINE and Cochrane at the 7th of September 2021 for eligible clinical trials with pediatric patients at the Emergency Department treated with nitrous oxide compared to local anesthesia. There were no restrictions in dates of publication and only studies published in English were included. The following inclusion criteria were defined beforehand: children between 0 and 18 years of age undergoing painful minor procedures, treatment with nitrous oxide, at the Emergency Department and pain as outcome. Studies that compared nitrous oxide or nitrous oxide combined with a local anesthetic to Procedural Sedation and/or Analgesia were excluded. Risk of bias for individual studies was evaluated according to the Cochrane Handbook and quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation system.
Results
Seven studies in which a total of 371 patients were included comparing i) nitrous oxide to a local anesthetic or ii) nitrous oxide combined with a local anesthetic, to the same local anesthetic. Two studies showed nitrous oxide was equally effective in pain treatment as local anesthetics. Five studies showed nitrous oxide combined with a local anesthetic is more effective in reducing pain than a local anesthetic alone in pediatric patients at the Emergency Department undergoing painful minor procedures, but two studies only for a certain age range. In all seven studies no major adverse effects were reported. Quality of evidence was low due to risk of bias, inconsistency, indirectness and imprecision. Due to methodological inconsistencies and clinical heterogeneity, a meta-analysis was not possible.
Conclusions
Based on available evidence nitrous oxide is as effective as local anesthetics for pain management and nitrous oxide in combination with a local anesthetic is more effective in reducing pain than a local anesthetic alone in pediatric patients at the Emergency Department undergoing painful minor procedures. Nitrous oxide can be used in pediatric patients without major adverse events.
In daily clinical practice nitrous oxide can have an important contribution in pain management but for a maximum effective Procedural Sedation and/or Analgesia in pediatric patients at an Emergency Department it should always be combined with a local anesthetic.