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Table of Contents
Authors: Matthew Murphy, MD, Emergency Medicine Resident, Lehigh Valley Health Network; and Bryan G. Kane, MD, FACEP, Medical Staff President and Emergency Medicine Associate Program Director, Professor of Medicine, Lehigh Valley Health Network
The COVID-19 pandemic caused problems for the care of bronchospasm. Because nebulizers aerosolize the virus, metered-dose inhalers (MDIs) are preferred for COVID-19 and other respiratory infections.1,2 The increased demand for MDIs during the pandemic, however, caused a worldwide shortage of these devices.3,4 Fortunately, intramuscular options for treating bronchospasm that show similar efficacy are available as alternatives.5
Epinephrine and terbutaline are injectable β2-agonists.6,7 They have similar efficacy when given subcutaneously.8-10 One prospective study showed that intramuscular terbutaline improved subjective symptoms and respiratory rates in patients with acute asthma exacerbations, although to a lesser extent than nebulized albuterol.11 A later retrospective study showed similar patient outcomes between nebulized albuterol and subcutaneous terbutaline.12
Cardiac effects of terbutaline are generally minor. Slightly higher rates of tachycardia have been observed after injected terbutaline versus injected epinephrine.13 A prospective study did not find elevations in troponin levels with terbutaline when it was used acutely.14 Notably, the study included a small cohort of 29 critically ill children and described ECG changes during intravenous infusions of terbutaline. The highest level of evidence on the use of terbutaline in children at present is a 2017 systematic review on the safety of pediatric asthma medications.15 This review found a total of 11 reported adverse drug reactions with terbutaline (4 with intravenous infusion and 7 with oral administration). No adverse drug events were identified with subcutaneous injection. The subcutaneous terbutaline injection site most frequently studied is the deltoid. Recommended dosing of terbutaline for asthma varies from 0.25 to 0.5 mg subcutaneously in the deltoid. When administered intramuscularly, terbutaline has been associated with tremor or restlessness.16
Another alternative to inhaled bronchodilators is injected epinephrine. A 1988 study did not identify a relationship between age and ventricular dysrhythmia in asthmatic patients treated with subcutaneous epinephrine.17 A more recent systematic review and meta-analysis compared epinephrine by any route with selective β2-agonists by any route for the treatment of asthma.18 There was no significant difference in clinical improvement, although epinephrine had more adverse events. For adults, intramuscular injection of epinephrine in the thigh has been demonstrated to lead to significantly higher peak plasma levels compared to intramuscular or subcutaneous injection in the upper extremity.19 The superiority of intramuscular over subcutaneous injection for epinephrine has also been demonstrated in children.20 The dosage of epinephrine varies in the studies noted. One advantage of using 0.3 mg of 1:1000 epinephrine (0.15 mg for pediatrics) is staff familiarity with this dosage because it is also used in the treatment of anaphylaxis.
Based on available evidence, injected terbutaline or epinephrine appears to be a viable alternative to nebulized bronchodilators for acute bronchospastic exacerbations during times when supply chains are low or aerosolization must be avoided.
