60 Inhaled nitrous oxide for distressing procedures in children: a systematic review
Bibliographic record
Abstract
Abstract Background Inhaled nitrous oxide (N2O) is a potentially effective agent for pain and procedural distress in children but questions remain regarding indication specific effectiveness. Objectives Our objective was to synthesize the evidence for N2O in children and youth regarding procedural distress, pain, and adverse events (AEs). Design/Methods We performed electronic searches of MEDLINE, EMBASE, Google Scholar, CINAHL, conference proceedings, and trial registries. We included randomized trials of N2O in children and youth 0-21.99 years that reported procedural distress or pain. Methodological rigor and quality of evidence were evaluated using the Cochrane Collaboration’s Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Where meta-analysis wasn’t possible, we summarized results using Tricco et al.’s classification system of “favorable” or “unfavorable” (p<0.05), or “neutral” (p>0.05). Results We included 29 trials, involving 2,404 children aged 3 weeks-21 years. The overall quality of evidence for distress and pain was “low” and “moderate”, respectively. For venous cannulation (n=12), three meta-analyses were possible: A) pain was significantly lower with 70% N2O versus eutectic mixture of local anesthetics (EMLA) (mean difference: -16.5; 95% CI: -28.6 to -4.4; p=0.008; 85 participants; 3 trials; I2= 0%); B) pain was not significantly different with 50% N2O alone versus EMLA (mean difference: -0.4; 95% CI: -1.2 to 0.3; p=0.26; 65 participants; 2 trials; I2= 15%); C) combination 50% N2O plus EMLA was significantly better than EMLA alone (mean difference: -1.2; 95% CI: -2.1 to -0.3; p=0.007; 65 participants; 2 trials; I2= 43%). For pain and distress during laceration repair (n=5), N2O was deemed “favorable” versus subcutaneous lidocaine, oxygen, or oral midazolam, but “neutral” versus intravenous ketamine. For pain and distress during fracture reduction (n=3), N2O was deemed “neutral” versus combination intramuscular meperidine plus promethazine, intravenous lidocaine, or combination intravenous ketamine plus midazolam. For pain and distress during lumbar puncture (n=1), N2O was deemed “favorable” versus oxygen. Higher concentrations of N20 were associated with more AEs per participant: 6.7% (1/15), 13.7% (64/468), and 25.3% (56/221) with 30%, 50%, and 70% N2O, respectively. The most common AEs were nausea and agitation (both 3.5% [40/1128]). There were no AEs requiring resuscitative measures. Conclusion N2O is a potentially effective agent for reducing procedural distress and pain in children, although high quality evidence is lacking. Most data exist for venous cannulation where safety and efficacy at reducing pain are optimized with combining 50% N2O and topical anesthetic cream. For laceration repair, there is considerably less data. Still, N2O appears to be superior to oral midazolam but equivalent to intravenous ketamine.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.011 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".