CORTICOSTEROIDS IN ACUTE RESPIRATORY FUNCTION

	To the Editor :

We read with interest the review by Jantz and Sahn entitled "Corticosteroids in acute respiratory failure" (1) that appeared in the October 1999 issue of the Journal. In this review, the authors examined the data and rationale for the use of corticosteroids (CCS) in conditions that cause acute respiratory failure. Of special interest for us is the section on status asthmaticus. In this section, on the basis of an incomplete literature search, the authors state that "[parenteral] corticosteroids should be use in all patients admitted to the ICU for status asthmaticus." However, the evidence they refer to does not support this recommendation. The authors found almost equal number of positive and negative trials that include children and adults with acute asthma presenting to an acute care setting, usually an emergency department (ED). However, evidence about the use of inhaled CCS in acute asthma was ignored (2). Under these circumstances, analysis is problematic because of selection bias, and the limited number of studies included, and because some of them had "nonexperimental" designs.

In contrast, we recently performed an evidence-based evaluation of the use of CCS in adults who presented to the ED with acute asthma (3). All studies were randomized, controlled trials conducted in an emergency care setting and included patients with asthma whose acute exacerbations were the primary reason for assessment. The results show that parenteral administration of CCS probably requires from 6 to 24 h to improve pulmonary function. On the other hand, pulmonary function is improved 1 to 3 h after treatment with inhaled CCS. The data also show the difficulty in making definitive conclusions about the effect of CCS on admission rates in the ED; one review of six studies demonstrated a 32% decrease in hospital admissions associated with CCS use, but a separate analysis involving only high quality studies found no benefit. Intravenous and oral CCS appeared to have similar effects on lung function. Finally, there was a tendency towards improvement in pulmonary function with medium and high doses; however, the evidence does not support the use of very high doses.

In summary, the Jantz and Sahn section on status asthmaticus is an example of an overview of primary studies that have not been identified or analyzed in a systematic way. In contrast, a systematic review limits bias, and its conclusions are more reliable and accurate.

Departamento de Emergencia, Hospital Central de las F.F.A.A., Montevideo, Uruguay

CARLOS RODRIGO

Unidad de Cuidado Intensivo, Asociación Española de Socorros Mutuos, Montevideo, Uruguay

1. Jantz, M. A., and S. A. Sahn. 1999. Corticosteroids in acute respiratory failure. Am. J. Respir. Crit. Care Med. 160: 1079-1100 [Free Full Text].

2. Rodrigo, G., and C. Rodrigo. 1998. Inhaled flunisolide for acute severe asthma. Am. J. Respir. Crit. Care Med. 157: 698-703 [Abstract/Free Full Text].

3. Rodrigo, G., and C. Rodrigo. 1999. Corticosteroids in the emergency department therapy of acute adult asthma: an evidence-based evaluation. Chest 116: 285-295 [Abstract/Free Full Text].

	From the Authors:

In our manuscript, we attempted to provide an overview of studies using corticosteroids in treating status asthmaticus (1). We did not perform a meta-analysis of all published studies or describe the details of each study given the space limitations. In the meta-analysis by Rodrigo and Rodrigo (2), which was published after our paper was submitted, the studies by Younger and colleagues (3), and Pierson and coworkers (4) were not included. Both of these randomized double-blind trials demonstrated a beneficial effect of corticosteroids compared with placebo. In addition, a randomized, double-blind study by Lin and colleagues (5), published after our article was submitted, also noted improvement in spirometry compared with placebo. In contrast to the results of Rodrigo and Rodrigo (2), a meta-analysis by Rowe and coworkers (6) concluded that corticosteroids are efficacious in treating acute exacerbations of asthma. A difficulty with the assessment of the literature regarding the treatment of acute asthma with corticosteroids is that the vast majority of studies have been conducted in the emergency department (ED) or the outpatient setting, making extrapolation to the intensive care unit (ICU) problematic. The meta-analysis by Rodrigo and Rodrigo employed trials that studied patients in the emergency department (ED) setting. Little data exists regarding treatment of patients with status asthmaticus who require admission to the ICU for respiratory failure. However, we believe that clinical experience and the data that does exist currently warrant their use in these critically ill patients (7).

We read with interest the article by Rodrigo and Rodrigo describing their randomized, double-blind trial of high dose flunisolide (1 mg every 10 min) delivered via metered-dose inhaler (MDI) versus placebo in addition to 400 µg of salbutamol via MDI every 10 min for 3 h in patients treated in the ED (8). Their data demonstrated improvement in spirometry by 90-120 min. Given the pharmacologic effects of corticosteroids, it is unclear why inhaled corticosteroids should have a more rapid onset of activity and clinical improvement compared with parenteral corticosteroids. We agree with Drs. Rodrigo and Rodrigo that additional studies comparing inhaled and parenteral corticosteorids for treating asthma in the ED are warranted. For treating patients with asthma and respiratory failure requiring admission to the ICU, we would not recommend using a MDI-based corticosteroid regimen over a parenteral regimen until more studies have been conducted. Before inhaled corticosteroids are utilized in mechanically ventilated patients, studies would been to be done to characterize aerosol delivery of the corticosteroid in the mechanicaly ventilated patient. In addition, the cost of a high-dose inhaled corticosteroid regimen, both in terms of drug costs and respiratory therapist time, may be greater with the inhaled rather than the parenteral or oral route.

MICHAEL A. JANTZ

STEVEN A. SAHN

Division of Pulmonary and Critical Care Medicine

Allergy and Clinical Immunology

Medical University of South Carolina

Charleston, South Carolina

1. Jantz, M. A., and S. A. Sahn. 1999. Corticosteroids in acute respiratory failure. Am. J. Respir. Crit. Care Med. 160: 1079-1100 .

2. Rodrigo, G., and C. Rodrigo. 1999. Corticosteroids in the emergency department therapy of acute adult asthma: an evidence-based evaluation. Chest 116: 285-295 .

3. Younger, R. E., P. S. Gerber, H. G. Herrod, R. M. Cohen, and L. V. Crawford. 1987. Intravenous methylprednisolone efficacy in status asthmaticus of childhood. Pediatrics 80: 225-230 [Abstract/Free Full Text].

4. Pierson, W. E., C. W. Bierman, and V. C. Kelley. 1974. A double-blind trial of corticosteroid therapy in status asthmaticus. Pediatrics 54: 282-288 [Abstract/Free Full Text].

5. Lin, R. Y., G. R. Pesola, L. Bakalchuk, G. T. Heyl, A. M. Dow, C. Tenenbaum, A. Curry, and R. E. Westfal. 1999. Rapid improvement of peak flow in asthmatic patients treated with parenteral methylprednisolone in the emergency department: a randomized controlled study. Ann. Emerg. Med. 33: 487-494 [Medline].

6. Rowe, B. H., J. L. Keller, and A. D. Oxman. 1992. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Ann. Emerg. Med. 10: 301-310 .

7. Leatherman, J.. 1994. Life-threatening asthma. Clin. Chest Med. 15: 453-479 [Medline].

8. Rodrigo, G., and C. Rodrigo. 1998. Inhaled flunisolide for acute severe asthma. Am. J. Respir. Crit. Care Med. 157: 698-703 .