Benzalkonium Chloride: A Bronchoconstricting Preservative in Continuous Albuterol Nebulizer Solutions

Prabhakaran, Sreekala; Abu-Hasan, Mutasim; Hendeles, Leslie

doi:10.1002/phar.1929

Cited by 14 publications

(5 citation statements)

References 16 publications

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“…Other studies have suggested that β2 -adrenoceptor agonists induced bronchospasm may be related to inhalant excipients (propellants and surfactants), preservatives (benzalkonium bromide), osmotic pressure, and/or pH [1,8] . Benzalkonium bromide has been mentioned several times in preservatives [13][14][15] , and ededidine disodium has also been reported [16] .In this case, the patient used terbutaline sulfate nebulizate, which does not contain preservatives and excipients, but its excipients contain ededine disodium [1] , which may be the cause of bronchospasm. In addition, osmotic pressure of nebulized uids can cause bronchoconstriction, hypertonic buffers have been shown to cause the release of histamine from normal human basophils and mast lung cells, and both hypotonic or hypertonic saline solutions can induce bronchoconstriction [1] .…”

Section: Discussionmentioning

confidence: 99%

Tremor and Paradoxical bronchospasm caused by Terbutaline

Wang¹,

Liu²,

Liang³

et al. 2023

Preprint

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Background Common adverse reactions of terbutaline include skeletal muscle tremor, headache,tachycardia, palpitations, hypokalemia and so on.Bronchospasm caused by terbutaline is rarely reported. This article reports one case of severe bronchospasm caused by nebulized terbutaline sulfate inhalation therapy. Case presentation A 51-year-old female patient was admitted to hospital with acute bronchitis.The main complaints were cough, sputum and wheezing. She has no history of drug or food allergies. On the day of admission, terbutaline nebulization treatment immediately caused limb tremor and bronchospasm. After glucocorticoid, aminophylline, non-invasive respiratory support and other symptomatic treatments,the patient improved on the 4th day. Conclusion The mechanism of terbutaline leading to bronchospasm is still unclear. The tert-butylline on the chemical structure of terbutaline may bind to proteins to produce IgE-mediated bronchospasm, The excipient ededidine disodium and the osmotic pressure of the nebulized diluent may also lead to bronchospasm. During the clinical treatment, hypotonic nebulizing dilutions should be avoided, and close monitor should be taken in case ofpossible fatal bronchospasm.

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Section: Discussionmentioning

confidence: 99%

Tremor and Paradoxical bronchospasm caused by Terbutaline

Wang¹,

Liu²,

Liang³

et al. 2023

Preprint

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“…Although there is substantial evidence that BAC induces bronchospasm in clinical pharmacology studies of patients with stable asthma 7 and there are a few recent case reports regarding difficulty weaning children exposed to BAC from continuous nebulized albuterol, 8,9 this is the first study comparing the clinical outcomes of specifically pediatric patients with asthma exacerbation receiving continuous albuterol nebulization with an albuterol formulation containing BAC compared to a formulation that is preservative free. Previous studies have demonstrated that the effect of BAC nebulized in the airways of patients with stable asthma was dose dependent, cumulative, and more pronounced in patients with greater baseline airway reactivity.…”

Section: Discussionmentioning

confidence: 99%

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma

Pertzborn¹,

Prabhakaran²,

Abu-Hasan³

et al. 2020

Pediatrics

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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.

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“…Cases of paradoxical bronchospasm during nebulization treatment for asthma have been reported and attributed to BAC [83, 84], prompting calls for its removal from the available formulations [85, 86]. On the other hand, paradoxical bronchospasm has been documented even in response to bronchodilators themselves [87–89] as well as other compounds added to nebulization solution [90, 91], and even biologically inactive substances such as saline and distilled water [92, 93], underscoring the limited value of anecdotal evidence especially with respect to common multifactorial conditions such as asthma.…”

Section: Discussionmentioning

confidence: 99%

Methodological evaluation of human research on asthmagenicity and occupational cleaning: a case study of quaternary ammonium compounds (“quats”)

LaKind

Goodman

2019

Allergy Asthma Clin Immunol

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In this paper, we review methodological approaches used in studies that evaluated the association between occupational exposure to quaternary ammonium compounds (quats) and occupational asthma. This association is of interest because quats are a common active ingredient of disinfectants and have been linked to work-related asthma in some circumstances. However, any evidence-based assessment of an exposure-outcome association needs to consider both strengths and limitations of the literature. We focus on publications cited by various US and international organizations. Eighteen investigations included in the review fall into two broad categories: case reports and challenge studies of individual patients and population studies that examined the association between quats and asthma occurrence in groups of subjects. We evaluated these studies guided by questions that address whether: exposure data on specific quat(s) and other agents that may cause asthma were included, new asthma cases were differentiated from asthma exacerbation, and information on respiratory sensitivity versus irritation was given. We also assessed consistency across studies. Studies of individual patients, particularly those that provided detailed information on challenge test results, document cases of asthma induced by exposure to quats. By contrast, studies of occupational groups with the highest potential for quats exposure (e.g., cleaners and farmers) do not consistently report increased incidence of asthma due specifically to quats. The unresolved methodological issues include: poor understanding of exposure pathways considering that quats are non-volatile, lack of quantitative data allowing for identification of an asthmagenicity threshold, insufficient information on whether quats are sensitizers or act via dose-dependent irritation or some other mechanism, and inability to quantify risk of new-onset asthma attributable to quats. Another important area of uncertainty is the lack of information on the specific quats being used. There is also a lack of data capable of distinguishing the effects of quats from those of other chemical and biological workplace exposures. The current state-of-the-science does not allow a proper assessment of the potential link between quats and occupational asthma.

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Benzalkonium Chloride: A Bronchoconstricting Preservative in Continuous Albuterol Nebulizer Solutions

Cited by 14 publications

References 16 publications

Tremor and Paradoxical bronchospasm caused by Terbutaline

Tremor and Paradoxical bronchospasm caused by Terbutaline

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma

Methodological evaluation of human research on asthmagenicity and occupational cleaning: a case study of quaternary ammonium compounds (“quats”)

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