Original ContributionsContinuous Versus Intermittent Nebulization of Salbutamol in Acute Severe Asthma: A Randomized, Controlled Trial*
Introduction
There is general agreement that nebulization of β2-agonists is the mainstay of therapy in patients with acute asthma,1, 2 and inhalation represents the route of choice.3, 4, 5, 6 Bronchodilator inhalation allows the deposition of high doses of β2-agonists directly to the bronchial receptors, producing maximal bronchodilator effects with minimal systemic absorption and side effects. There is a consensus that frequent intermittent nebulizations (3 in the first hour) are appropriate,1, 2, 6, 7, 8, 9 but continuous nebulization is also proposed.1, 2 Frequent administration of bronchodilators is thought to dilate the proximal bronchial tree, thereby allowing further distal deposition of subsequent bronchodilator treatments, which produces sustained bronchodilation and prevents bronchospastic rebounds.10, 11, 12, 13 All these benefits also might be obtained with continuous nebulization of bronchodilators.13, 14, 15, 16, 17, 18 Recent studies comparing intermittent and continuous nebulization of β2-agonists suggested that the latter might carry some advantages.14, 15 However, these studies focused on pulmonary function change and did not assess clinically relevant endpoints such as the improvement of the clinical condition and the rate of hospitalization or relapse. Moreover, beneficial effects were not found on an intention-to-treat basis and were apparent only when a retrospective post hoc analysis was performed on the subset of the patients exhibiting the most severe bronchial obstruction.14, 15 In addition, in one study the regimen of intermittent nebulization did not conform to that currently recommended for frequent administration of β2-agonists.14
Finding a better way to administer β2-agonists might be of utmost importance because severe bronchoconstriction and acute severe asthma has been well identified as the leading cause of mortality in asthma.19 Accordingly, we designed this prospective, randomized, double-blind study to test the hypothesis that an equal total dose of salbutamol nebulized continuously induces a greater bronchodilator effect and clinical improvement than intermittent nebulization in acute severe asthma.
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Materials and methods
All consecutive patients who presented to the emergency department of our hospital, a tertiary teaching hospital, with acute exacerbation of asthma between March 1996 and June 1997 were screened. The following criteria were required for inclusion in the study: a measured peak expiratory flow (PEF) of less than 50% predicted in association with 2 of the following clinical criteria of severity: heart rate 120 beats/min or greater, respiratory rate greater than or equal to 30 breaths/min, pulsus
Results
During the study period, 102 consecutive patients presented to the ED with acute asthma, and 42 fulfilled the inclusion criteria and were randomly assigned to study treatment. Demographic and clinical characteristics of the study patients are shown in the Table.Mean PEF was 24%±12% predicted. Hypoxemia was present in all patients with a mean PaO2/FIO2 ratio of 198±55 mm Hg, whereas hypercapnia was present in 35% of patients.
Twenty-one patients in each group were randomly assigned to receive
Discussion
In the present study, no appreciable difference was observed between continuous and intermittent nebulization of salbutamol in patients presenting to the ED with acute severe asthma in regard to spirometry (PEF), clinical symptoms (clinical score), or disposition (hospitalization rate). However, this was a small study with limited power to detect differences in failure and hospitalization rate. Accordingly, the decision to use intermittent or continuous nebulization should be made on the basis
Acknowledgements
We appreciate the review of the manuscript by Professor Laurent Brochard (Creteil, France). We also thank the physicians and nurses of the emergency department of F. Bourguiba Hospital, without whom this study would not have been possible.
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Address for reprints: Fekri Abroug, MD, Intensive Care Unit, CHU F. Bourguiba, Monastir 5000, Tunisia; 216 3 460672, fax 216 3 460678; E-mail [email protected].