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沙丁胺醇持续治疗联合苯扎氯铵在儿童重症哮喘住院治疗中的应用。

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma.

机构信息

Division of Pediatric Pulmonology, Department of Pediatrics, College of Medicine,

Division of Pediatric Pulmonology, Department of Pediatrics, College of Medicine.

出版信息

Pediatrics. 2020 Apr;145(4). doi: 10.1542/peds.2019-0107. Epub 2020 Mar 12.

DOI:10.1542/peds.2019-0107
PMID:32165556
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7111532/
Abstract

BACKGROUND AND OBJECTIVES

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景和目的

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。

方法

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。

结果

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)。

结论

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。

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本文引用的文献

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Safety and effectiveness of albuterol solutions with and without benzalkonium chloride when administered by continuous nebulization.连续雾化给药时含和不含苯扎氯铵的沙丁胺醇溶液的安全性和有效性。
Am J Health Syst Pharm. 2018 Nov 15;75(22):1791-1797. doi: 10.2146/ajhp180154. Epub 2018 Oct 3.
2
Paradoxical bronchospasm from benzalkonium chloride (BAC) preservative in albuterol nebulizer solution in a patient with acute severe asthma. A case report and literature review of airway effects of BAC.一名急性重症哮喘患者因沙丁胺醇雾化溶液中苯扎氯铵(BAC)防腐剂引发矛盾性支气管痉挛。BAC气道效应的病例报告及文献综述
Respir Med Case Rep. 2017 Mar 6;21:39-41. doi: 10.1016/j.rmcr.2017.03.005. eCollection 2017.
3
Benzalkonium Chloride: A Bronchoconstricting Preservative in Continuous Albuterol Nebulizer Solutions.
苯扎氯铵:持续雾化沙丁胺醇溶液中的一种支气管收缩性防腐剂。
Pharmacotherapy. 2017 May;37(5):607-610. doi: 10.1002/phar.1929. Epub 2017 May 9.
4
Safety and effectiveness of continuous aerosolized albuterol in the non-intensive care setting.非重症监护环境下持续雾化吸入沙丁胺醇的安全性和有效性。
Pediatrics. 2014 Oct;134(4):e976-82. doi: 10.1542/peds.2014-0907.
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Pulmonary function response to EDTA, an additive in nebulized bronchodilators.肺功能对雾化支气管扩张剂中的添加剂乙二胺四乙酸(EDTA)的反应。
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Effect of inhaled preservatives on asthmatic subjects. II. Benzalkonium chloride.吸入性防腐剂对哮喘患者的影响。II. 苯扎氯铵。
Am Rev Respir Dis. 1990 Jun;141(6):1405-8. doi: 10.1164/ajrccm/141.6.1405.