Division of Pediatric Pulmonology, Department of Pediatrics, College of Medicine,
Division of Pediatric Pulmonology, Department of Pediatrics, College of Medicine.
Pediatrics. 2020 Apr;145(4). doi: 10.1542/peds.2019-0107. Epub 2020 Mar 12.
The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations.
We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A value <.05 was considered significant.
A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; < .001).
BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization.
用于制备持续雾化溶液的沙丁胺醇滴管瓶含有防腐剂苯扎氯铵(BAC)。BAC 本身已被证明会引起支气管痉挛。我们假设 BAC 会降低急性哮喘发作患者沙丁胺醇的治疗效果。
我们进行了一项回顾性队列研究,比较了接受持续雾化沙丁胺醇治疗且含有和不含有 BAC 的<18 岁患者的临床结局。对于主要终点(持续沙丁胺醇雾化的持续时间),我们通过生存曲线的 Kaplan-Meier 估计值比较了两组,进行了对数秩检验差异,并使用多变量 Cox 回归调整了基线特征。 <.05 被认为具有统计学意义。
共有 477 名患者纳入分析(236 名暴露于 BAC,241 名对照)。BAC 组的持续雾化时间明显长于对照组(中位数分别为 9 小时和 6 小时;24 小时时,15.7%需要持续雾化,而对照组为 5.8%)。对照组在任何特定时间停止持续雾化的可能性高 79%(风险比 1.79;95%置信区间:1.45 至 2.22; <.001),停止额外呼吸支持的可能性高 43%(风险比 1.43;95%置信区间:1.16 至 1.75; <.001)。
BAC 是一种功能性的沙丁胺醇拮抗剂,与持续雾化沙丁胺醇治疗时间延长和额外的呼吸支持有关,这表明不含防腐剂的沙丁胺醇制剂在持续雾化治疗中更安全。