Effects of high neuromuscular blocking agent dose on post-operative respiratory complications in infants and children

Background: This study evaluated the association between neuromuscular blocking agent dose and post-operative respiratory complications in infants and children. Methods: Data from 6507 general anaesthetics provided to children aged 0-10 years undergoing surgery were analysed to examine the effects of neuromuscular blocking agent dose on post-operative respiratory complications (primary endpoint) and secondary endpoints. Confounder-adjusted analyses addressed age, surgical duration, and comorbidity burden. Results: In confounder-adjusted analyses, high doses of neuromuscular blocking agents were associated with higher risk of post-operative respiratory complications (OR 2.27; 95% CI 1.12-4.59; P =.022). The effect was modified by age (P-for-interaction =.016) towards a more substantial risk in infants ≤1 year (OR 3.84; 95% CI 1.35-10.94; P =.012), by duration of surgery (P-for-interaction =.006) towards a higher difference in odds for surgeries <90 minutes (OR 4.25; 95% CI 1.19-15.18; P =.026), and by ASA physical status (P-for-interaction =.015) with a greater effect among patients with higher operative risk (ASA >1: OR 3.17; 95% CI 1.43-7.04; P =.005). Neostigmine reversal did not modify the association between neuromuscular blocking agents and post-operative respiratory complications (P-for-interaction =.38). Instrumental variable analysis confirmed that high doses of neuromuscular blocking agents were associated with post-operative respiratory complications (probit coefficient 0.25; 95% CI 0.04-0.46; P =.022), demonstrating robust results regarding concerns of unobserved confounding. Conclusions: High dose of neuromuscular blocking agents is associated with post-operative respiratory complications. We have identified subcohorts of paediatric patients who are particularly vulnerable to the respiratory side-effects of neuromuscular blocking agents: infants, paediatric patients undergoing surgeries of short duration, and those with a high ASA risk score.