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Published on: May 4, 2021
Inhaled nitrous oxide for painful procedures in children and youth: a systematic review and meta-analysis
Naveen Poonai1,2,3,4, Christopher Creene5, Ariel Dobrowlanski5
1Department of Pediatrics, Schulich School of Medicine and Dentistry, London, ON, Canada. naveen.poonai@lhsc.on.ca.
Insights
Nitrous oxide (N₂O) is effective for managing pediatric procedural pain and distress, particularly when combined with topical anesthetics for IV insertion and laceration repair. Adverse effects are less common with N₂O alone compared to combinations with other sedatives.
Area of Science:
- Pediatric Emergency Medicine
- Pain Management
- Anesthesiology
Background:
- Procedural pain and distress are significant challenges in pediatric emergency care.
- Nitrous oxide (N₂O) is a widely used inhaled agent for procedural sedation and analgesia.
- Evidence synthesis is needed to guide the optimal use of N₂O for specific pediatric procedures.
Approach:
- Systematic review and meta-analysis of 30 trials involving pediatric participants (0-21 years).
- Inclusion of studies reporting distress or pain during emergency department procedures.
- Assessment of N₂O efficacy using meta-analysis and qualitative classifications (favorable, neutral, unfavorable) where meta-analysis was not feasible.
- Evaluation of risk of bias and quality of evidence using established tools (Cochrane Risk of Bias, GRADE).
Key Points:
- Nitrous oxide (70%) combined with eutectic mixture of local anesthetics (EMLA) was superior to EMLA alone for reducing pain during IV insertion.
- N₂O demonstrated favorable outcomes for distress and pain during laceration repair compared to lidocaine, oxygen, and midazolam.
- N₂O showed neutral efficacy against ketamine for laceration repair and against various agents for fracture reduction, lumbar puncture, and urethral catheterization.
- Adverse effects like nausea, agitation, and vomiting were reported, with lower incidence when N₂O was used alone versus in combination with other sedating agents (midazolam, fentanyl).
Conclusions:
- Sufficient evidence supports the recommendation of nitrous oxide combined with topical anesthetics for IV insertion and laceration repair in children.
- The combination of N₂O with other sedating agents increases the frequency of adverse effects.
- N₂O is a valuable tool for managing pediatric procedural pain and distress, with safety considerations regarding co-administration.
Objectives:
The objective of this study was to synthesize indication-based evidence for N2O for distress and pain in children.
Study Design:
We included trials of N2O in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting N2O or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.
Results:
We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% N2O (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I2 = 0%) and 50% N2O plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I2 = 43%) were superior to EMLA. 50% N2O was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I2 = 15%). For distress and pain during laceration repair, N2O was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), N2O was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), N2O was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), N2O was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), N2O plus EMLA was "favorable" versus N2O and EMLA alone. Common adverse effects of N2O included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with N2O alone (278/1147 (24.2%)) versus N2O plus midazolam (48/52 (92.3%)) and N2O plus fentanyl (123/201 (61.2%)).
Conclusions:
There is sufficient evidence to recommend N2O plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.
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