Early administration of corticosteroids in acute asthma

Early administration of corticosteroids in acute asthma


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EARLYADMINISTRATIONOF CORTICOSTEROIDSIN ACUTE ASTHMA To the Editor:--We read the original contribution by Lin and colleagues a that appeared in the November 1997 issue. The authors concluded that "severe acute asthma does not preferentially respond to intravenous methylprednisolone treatment within the first hour of presentation to the ED." However, the data showed the opposite. The reason is type II statistical error. In this way, the peak expiratory flow rate (PEFR) improvements tended to be less in the methylprednisolone group than in the saline group; there was a difference between mean PEFRs of approximately 50 L/see in favor of saline treatment (P = .072), and there is a high probability that this difference would have been significant with a larger sample size. In accordance with these results, the main conclusion of this clinical trial would be that the early administration of methylprednisolone has a detrimental effect on acute asthma patients. However, this conclusion is not supported by the literature. Based on a meta-analysis of the effectiveness of steroids in acute asthma, Rowe et al 2 concluded that steroid use reduces the incidence of relapse in discharged patients and improves pulmonary function, albeit slowly (after 6 to 12 hours). This time delay fits with the concept that the beneficial action of corticosteroids develops via the synthesis of new proteins through gene induction. More recently, in a randomized controlled trial, we found that early administration of parenteral corticosteroids does not improve pulmonary function in the first 6 hours of treatment. 3 Finally, there is some evidence that suggests that inhaled corticosteroids can have early therapeutic effects (at 2 hours). 4 This rapid response suggests a nonimmunological, topical antiinflammatory effect) Therefore, before considering infrequent conditions that could explain these findings (aspirin hypersensitivity or an unpredictable effect of the preservative), we should ask us if this result is a consequence of an unsuccessful randomization process (eg, a significant difference in acute symptom duration between the groups at presentation (2.0 v 5.9 days, P < .05). GUSTAVORODRIGO,MD

Emergency Medicine Department Military Hospital CARLOSRODRIGO, MD

Intensive Care Unit Asociaci6n Espafiola la de Socorros Mutuos Montevideo, Uruguay

References 1. Lin RY, Pesola GR, Westfal RE, et al: Early parenteral corticosteroid administration in acute asthma. Am J Emerg Med 1997;15:621 625 2. Rowe BH, Keller JL, Oxman AD: Effectiveness of steroid therapy in acute asthma: A meta-analysis. Am J Emerg Med 1992;10: 301-310 3. Rodrigo C, Rodrigo G: Early administration of hydrocortisone in the emergency room treatment of acute asthma: A controlled clinical trial. Respir Med 1994;88:755-761 4. Rodrigo G, Rodrigo C: Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 1998; 157:698-703 5. McFadden ER: Inhaled glucocorticoids and acute asthma: therapeutic breakthrough or non-specific effect? (Editorial) Am J Respir Crit Care Med 1998;157:677-678

The author replies:---Rather than speculate on the possible results of a hypothetically larger study, we prefer to focus on the actual findings of our study. 1 Our analysis of covariance did not show a significant effect of acute symptom duration. That speaks against the suggestion that this could have explained the (nonsignificant) difference observed between corticosteroid and placebo

patients. We believe that with multiple baseline characteristics being tabulated, it should not he unexpected that one or two baseline differences will be noted by chance occurrence. We concur with Rodrigo and Rodrigo that the literature predominantly shows that corticosteroids should enhance mad not diminish the bronchodilator responses in asthmatics. It is interesting that they report a possible rapid response to flunisolide in acute asthmatic patients. In an earlier study of continuous nebulization with albuterol, we noted that patients reporting triamcinolone use had faster bronchodilator responses than those who did not report using inhaled corticosteroids. 2 Upon reviewing an interventional study by Fanta et al,3 we noted that the study showed a bronchodilator enhancement with corticosteroids in acute asthma patients who did not initially respond to bronchodilators. In our recent study, 1 we did not select patients in this manner. We speculated that a significant proportion of our patients responded maximally to initial bronchodilators and, thus, could not show any further benefit with additional agents such as corticosteroids. With this in mind, we designed a follow-up study on corticosteroids in patients with asthma who did not respond adequately to initial bronchodilator therapy. We are in the process of analyzing these data and hope to shed further light on the issue of the timing of the effects of corticosteroid treatment in acute asthma. ROBERTV. LIN, MD, MS

Department of Medicine St. Vincent's Hospital-NYMC New York, NY

References 1. Lin RY, Pasoli E, Westfall R, et al: Early parental corticosteroid administration in acute asthma. Am J Emerg Med 1997; 15:621-625 2. Lin RY, Sauter D, Newman T, et al: An association between the reported use of inhaled triamcinolone and differential short term responses to aerosolized albuterol in emergency department asthmatics. Chest 1994; 106:452-457 3. Fanta CH, Rossing TH, McFadden ER Jr: Glucocorticoids in acute asthma. Am J Med 1983;74:845-851

ENDOTRACHEALADMINISTRATIONOF FLUMAZENIL To the Editor:--The role of the benzodiazepine antagonist flumazenil in managing the patient who presents obtunded after a drug overdose remains controversial. 1-4The potential benefit to the patient, namely, improving the level of consciousness and avoiding endotracheal intubation0 must be balanced by the potential risks, including benzodiazepine withdrawal and unmasking the proconvulsant effects of coingestants. Only a few authors recommend the routine use of flumazenil in cases of unknown drug ingestion. 1'2 Most references suggest using flumazenil only when it is certain that no proconvulsant agents (ie, cyclic antidepressants or cocaine) were ingested and that the patient is not chronically taking benzodiazepines) Some authors advocate avoiding flumazenil altogether when treating comatose patients suspected of mixed drug overdose. 4 Flumazenil is usually administered intravenously, at doses starting at 0.1 to 0.2 rag. In the March issue of the journal, Palmer et aP reported that flumazenil can be administered effectively via an endotracheal tube. Their study found that therapeutic blood levels of flnmazenil were obtained 1 minute after the endotracheal administration of 1.0 mg of drug diluted in 10 cc of saline. The study population consisted of six patients undergoing elective surgery, none of whom were maintained on benzodiazepines or cyclic antidepressants. While the authors of this study have proven to us that we can give flumazenil by the endotracheal route, I see no good reason why we would give it this way to patients presenting after drug overdose. The cardiovascular toxicity resulting from benzodiaz-