Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma

Pediatrics. 2020 Apr;145(4):e20190107. doi: 10.1542/peds.2019-0107. Epub 2020 Mar 12.


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 P 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; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Albuterol / administration & dosage*
  • Albuterol / antagonists & inhibitors
  • Albuterol / chemistry
  • Asthma / drug therapy*
  • Benzalkonium Compounds / administration & dosage*
  • Benzalkonium Compounds / adverse effects
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / antagonists & inhibitors
  • Bronchodilator Agents / chemistry
  • Child
  • Child, Preschool
  • Disease Progression
  • Drug Interactions
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Preservatives, Pharmaceutical / administration & dosage*
  • Preservatives, Pharmaceutical / adverse effects
  • Regression Analysis
  • Retrospective Studies


  • Benzalkonium Compounds
  • Bronchodilator Agents
  • Preservatives, Pharmaceutical
  • Albuterol