Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review

Abstract

BackgroundCurrently, there is a lack of guidelines for the use of short-acting bronchodilators (SABD) in people admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), despite routine use in practice and risk of cardiac adverse events.AimTo review the evidence that underpins use and optimal dose, in terms of risk versus benefit, of SABD for inpatient management of AECOPD and collate the results for future guidelines.MethodsMedline, Embase, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and International Clinical Trials Registry Platform were searched (inception to November 2017) for published and ongoing studies. Included studies were randomised controlled trials or controlled clinical trials investigating the effect of SABD (β2-agonist and/or ipratropium) on inpatients with a diagnosis of AECOPD. This review was undertaken in accordance with PRISMA guidelines and a pre-defined protocol. Due to heterogeneous methodologies, meta-analysis was not possible so the results were synthesised qualitatively.ResultsOf 1378 studies identified, 10 met inclusion criteria. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser, and type of β2-agonist used. However, some evidence demonstrated significantly increased cardiac side effects with increased dosage of β2-agonist (45% versus 24%), P<0.05).ConclusionThis review identified a paucity of methodologically rigorous evidence evaluating use of SABD among AECOPD. The available evidence did not identify any additional benefits for participants receiving higher doses of short-acting β2-agonists compared to lower doses, or based on type of delivery method or β2-agonists used. However, there was a small increase in some adverse events for participants using higher doses of β2-agonists.Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0860-0) contains supplementary material, which is available to authorized users.

Future Trends in Nebulized Therapies for Pulmonary Disease

“…Diseases requiring inhalation therapies include asthma, bronchiectasis, COPD, CF, pneumonia, and ARDS [34][35][36]. Common nebulized medications used to treat these conditions include antibiotics [37,38], various bronchodilators, such as albuterol sulfate [39] and ipratropium bromide [40], and corticosteroids, such as budesonide [41].…”

<p>Nebulized Therapies in COPD: Past, Present, and the Future</p>

“…Nebulized short-acting bronchodilators are widely used for the management of patients with acute COPD exacerbations in the hospital setting. 43 Clinical studies of the nebulized SABAs albuterol sulfate and levalbuterol hydrochloride have demonstrated improvements in forced expiratory volume in 1 second (FEV 1 ) when compared with placebo. 44,45 No significant differences were observed between these two treatments in terms of efficacy, cost, occurrence of AEs, or hospitalizations.…”

Nonantibiotic Pharmacological Treatment of Severe Chronic Obstructive Pulmonary Disease Exacerbations

“…10 Both short-acting β-agonists and anticholinergic drugs are very common in clinical practice and not infrequently used in combination, particularly in the more severe cases, although in contrast with stable COPD, there is no evidence that their combination in AECOPD produces additional benefit. 11 Indeed, a study reviewing administrative data of a 3year period between 2010 and 2012 in the United States showed that only 5% of patients presenting with AECOPD did not receive a short-acting β-agonist, while 72% received a short-acting β-agonist and 46% received it in combination with a short-acting anticholinergic agent. 12 Importantly, the same study showed that most patients (81%) received systemic corticosteroids, and 92% were treated with antibiotics.…”

“…Inhaled, short-acting β-adrenergic agonists (e.g., salbutamol) are the mainstay of therapy for AECOPD because of their rapidity and efficacy in producing bronchodilation with increase in FEV1 and forced vital capacity (FVC), reduction in dynamic hyperinflation, and breathlessness. 1, 11 Although there is no clear evidence supporting nebulization versus metered dose inhalers (MDI), 13 nebulization is the method of choice in severe exacerbations, in critical care and always in intubated patients due to the perceived inability to coordinate inspiration with MDIs. A recent randomized controlled trial comparing air-versus oxygen-driven nebulizers in patients hospitalized for AECOPD showed that oxygen-driven nebulization determined the raise in transcutaneous PCO 2 by 3.4 versus 0.1 mm Hg of the air-driven nebulizer, while 40% of the patients had an tPCO 2 increase equal or greater than 4 mm Hg.…”

“…Interestingly, comparison between 2.5, 5, and 10 mg showed a similar incidence and extent of tachycardia and change in blood pressure for 2.5 and 5 mg, but a significantly early tachycardiac effect and decrease in blood pressure with the 10-mg regime. 11 The high prevalence of cardiac comorbidity in patients with COPD mandates for caution in the dose and frequency of administration of β-adrenergic agents. Indeed, tachycardia and cardiac arrhythmias may occur, particularly following the administration of multiple inhaled doses over a relatively short time.…”