Effects of avoidance versus use of neuromuscular blocking agents for facilitation of tracheal intubation in children and infants

Citation:

Christensen MI, Creutzburg A, Vested M, Nørskov AK, Lundstrøm LH, Afshari A. Effects of avoidance versus use of neuromuscular blocking agents for facilitation of tracheal intubation in children and infants. Eur J Anaesthesiol. 2026;43:1–14. doi:10.1097/EJA.0000000000002358. (PROSPERO: CRD42024518195)

Study at a glance

- Design: Systematic review + pairwise random-effects meta-analysis (Mantel–Haenszel RR) of paediatric RCTs; trial sequential analysis (TSA) for the primary outcome; GRADE Summary of Findings.

- Search: MEDLINE, EMBASE, CENTRAL, BIOSIS, Web of Science, CINAHL + registries (ClinicalTrials.gov, WHO ICTRP, CTIS, EudraCT) and other sources; last search 8 July 2025.

- Population/setting: Patients <18 years undergoing oral or nasal tracheal intubation with direct or video laryngoscopy, in any setting (OR and NICU included).

- Comparison: Avoidance of NMBAs (placebo/other drugs/no NMBA for intubation conditions) vs use of NMBAs (any NMBA, dose, duration).

- Included evidence: 47 RCTs overall; primary outcome (difficult tracheal intubation) reported by 30 trials (n=2,276).

Key results (avoidance vs use of NMBAs)

1) Difficult tracheal intubation (primary)

- Pooled effect: RR 3.47 (95% CI 2.52–4.77), P<0.00001; k=30; I²=18%.

- Absolute risks (SoF): 61/1000 with NMBA use vs 212/1000 with NMBA avoidance (≈151 more/1000; 95% CI 93–231 more).

- Aggregate events: 249/1197 (20.8%) vs 66/1079 (6.1%).

- TSA: α-spending adjusted RR 3.68 (95% CI 2.22–6.11); required information size reached.

2) Failed intubation

- Pooled effect: RR 4.70 (95% CI 2.36–9.35), P<0.0001; k=20; I²=0%.

- Absolute risks (SoF): 12/1000 with NMBA use vs 57/1000 with NMBA avoidance (≈45 more/1000; 95% CI 16–101 more).

- Aggregate events: 33/682 (4.8%) vs 9/747 (1.2%).

3) Serious adverse events (≥1 SAE)

- Pooled effect: RR 0.63 (95% CI 0.33–1.21), P=0.17; k=47; I²=0%.

- Absolute risks (SoF): 15/1000 with NMBA use vs 10/1000 with NMBA avoidance (≈6 fewer/1000; CI includes benefit and harm).

- Aggregate events: 13/1630 (0.8%) vs 22/1456 (1.5%); events were rare.

4) Upper airway discomfort or injury

- Pooled effect: RR 1.12 (95% CI 0.40–3.16), P=0.83; I²=37%.

- Detailed event totals were in Supplementary Material (not in the provided PDF), so absolute effects are uncertain.

Robustness / sensitivity highlights

- No important subgroup differences for difficult intubation by trial risk-of-bias strata (P=0.83) or by age (0–2 vs ≥2 years; P=0.64).

- Post hoc: effect on difficult intubation remained >3 across publication eras; excluding neonatal opioid-only trials minimally changed RR (3.47 → 3.31).

Quality / certainty (as reported/appraised)

- GRADE: Difficult intubation = Moderate certainty; Failed intubation = Moderate; SAEs = Very low. (Upper airway outcome: not clearly GRADEd in accessible materials; effect estimate very imprecise.)

- Review-level appraisal: AMSTAR 2 = Critically low confidence (notably no excluded-studies table; no formal publication-bias assessment). ROBIS overall risk of bias = High.

Practical takeaway

- Across paediatric RCTs, avoiding NMBAs substantially increases the risk of difficult and failed tracheal intubation (moderate-certainty evidence).

- Differences in serious adverse events and upper airway injury/discomfort remain uncertain because events are rare and estimates are imprecise (very low/low certainty), and the review has methodological reporting gaps that reduce confidence in safety conclusions.