Emergency Treatment of Asthma… 2

Emergency Treatment of Asthma… 2

Emergency Treatment of Asthma... 2

Emergency Treatment of Asthma

To the Editor:

In the article by Lazarus (Aug. 19 issue), 1 the author provides a comprehensive and balanced review of the emergency treatment of asthma but does not discuss the controversy around the use of epinephrine for acute severe asthma exacerbations. 2 The National Asthma Education and Prevention Program guidelines 3 restrict the use of subcutaneous epinephrine to the prehospital setting whenever nebulized short-acting β2 -adrenergic agonists are not available. Nonetheless, some authors propose its use as a last chance to avoid intubation. 4 The beta- and alpha-adrenergic effects of epinephrine induce bronchodilation but could also limit airway edema. Furthermore, epinephrine improves the partial pressure of oxygen (which may paradoxically be worsened by β2 -adrenergic agonists in some patients 4 ), and it has been hypothesized that patients with particular genetic variations in the adrenoreceptors may have a more favorable response to epinephrine, even if β2 -adrenergic agonists fail. 4 The safety of epinephrine has been reevaluated, suggesting that its use may be less dangerous than previously surmised. 2,5 We would be interested in knowing Lazarus’s opinion about the use of nebulized or systemic epinephrine in adults with acute severe asthma refractory to β2 -adrenergic agonists who are otherwise healthy.

Stefano Franchini, M.D.
Alessandro Marinosci, M.D.
Gabriella Cicenia, M.D.
San Raffaele Scientific Institute, Milan, Italy
franchini. stefano@hsr. it

No potential conflict of interest relevant to this letter was reported.

Smith D. Riel J. Tilles I. Kino R. Lis J. Hoffman JR. Intravenous epinephrine in life-threatening asthma. Ann Emerg Med 2003;41:706-711
CrossRef | Web of Science | Medline

National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma: full report 2007. (http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf .)

Papiris SA. Manali ED. Kolilekas L. Triantafillidou C. Tsangaris I. Acute severe asthma: new approaches to assessment and treatment. Drugs 2009;69:2363-2391
CrossRef | Web of Science | Medline

Putland M. Kerr D. Kelly AM. Adverse events associated with the use of intravenous epinephrine in emergency department patients presenting with severe asthma. Ann Emerg Med 2006;47:559-563
CrossRef | Web of Science | Medline

To the Editor:

The patient described by Lazarus, a woman with a history of recent admissions to the intensive care unit for asthma and poor compliance with prescribed therapy, is a candidate for intramuscular glucocorticoid therapy in the emergency department. A Cochrane review on the use of glucocorticoids to prevent relapse after asthma exacerbations concluded that oral and intramuscular glucocorticoids could be equally beneficial, on the basis of two studies that compared intramuscular dexamethasone (10 mg) and intramuscular methylprednisolone (240 mg) versus placebo. 1 A small, randomized, double-blinded, controlled trial comparing relatively low dose intramuscular triamcinolone diacetate (40 mg) versus oral prednisone (40 mg, once daily for 5 days) showed similar relapse rates in the two groups. 2 In our practice, an inner-city emergency department with over 100,000 visits per year by adults, many of whom are indigent, we often successfully use a depot injection of triamcinolone acetonide (120 mg) in patients who are unlikely to fill a prescription for oral glucocorticoids. We are unaware of studies comparing relapse rates among patients treated with intramuscular glucocorticoids versus those treated with inhaled glucocorticoids.

Thomas Chi, M.D.
Richard Sinert, M.D.
SUNY Downstate Medical Center, Brooklyn, NY
tjc1977@hotmail. com

No potential conflict of interest relevant to this letter was reported.

Rowe BH. Spooner C. Ducharme F. Bretzlaff J. Bota G. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev 2007;3:CD000195-CD000195

Schuckman H. DeJulius DP. Blanda M. Gerson LW. DeJulius AJ. Rajaratnam M. Comparison of intramuscular triamcinolone and oral prednisone in the outpatient treatment of acute asthma: a randomized controlled trial. Ann Emerg Med 1998;31:333-338
CrossRef | Web of Science | Medline

The author replies: Franchini and colleagues ask an important question about the role of epinephrine in the management of asthma exacerbations in the emergency department. Unfortunately, there are few answers. There is a rationale for the use of drugs with alpha-adrenergic vasoconstrictor activity. They reduce the thickness of the tracheal mucosa in dogs 1 and decrease microvascular leakage of the airways in guinea pigs. 2 In humans, intravenous phenylephrine, an α1 -adrenergic agonist, decreases airway resistance in subjects with severe asthma. 3 However, it is a leap from these proof-of-concept studies to clinical use, and the evidence does not support the use of epinephrine for treatment of asthma exacerbations. Randomized trials comparing nebulized epinephrine with nebulized albuterol have failed to show a difference in efficacy, and a meta-analysis of six studies showed no advantage of nebulized epinephrine over albuterol or terbutaline. 4 Franchini and colleagues cite studies that suggest the risks of intravenous epinephrine are less than previously believed. However, the studies were retrospective, lacked an active comparison treatment, were small, and were generally restricted to young patients. These safety studies do suggest that it may be ethically feasible to conduct randomized, controlled trials to examine the efficacy of subcutaneous, intravenous, or nebulized epinephrine in patients with acute severe asthma that has not responded to standard treatment. If mucosal edema is indeed the cause of the failure to respond, then nebulized epinephrine may be more effective in this group of patients, and may be associated with less risk, than systemic epinephrine. Until studies testing this hypothesis are completed, there is no evidence to support the routine use of epinephrine for asthma exacerbations. Clinicians who choose to use epinephrine in highly selected patients with severe exacerbations that have not responded to conventional treatments should consider the risk versus the benefit of this approach, should use low doses, and should monitor patients carefully for adverse events.

Chi and Sinert make an important point: many patients treated in the emergency department for asthma cannot (for financial or other reasons) or do not take glucocorticoids as prescribed at discharge. Intramuscular glucocorticoids are effective in children and adults to prevent relapse; however, since data are not sufficient to choose one route of administration, intramuscular glucocorticoids should probably be reserved for patients at high risk for nonadherence.

Stephen C. Lazarus, M.D.
University of California, San Francisco, San Francisco, CA
lazma@ucsf. edu

Since publication of his article, the author reports no further potential conflict of interest.

Laitinen LA. Robinson NP. Laitinen A. Widdicombe JG. Relationship between tracheal mucosal thickness and vascular resistance in dogs. J Appl Physiol 1986;61:2186-2193
Web of Science | Medline

Boschetto P. Roberts NB. Rogers DF. Barnes PJ. Effect of antiasthma drugs on microvascular leakage in guinea pig airways. Am Rev Respir Dis 1989;139:416-421
CrossRef | Web of Science | Medline

Grandordy BM. Paiva de Carvalho J. Regnard J. et al. The effect of intravenous phenylephrine on airway calibre in asthma. Eur Respir J 1995;8:624-631
Web of Science | Medline

Rodrigo GJ. Nannini LJ. Comparison between nebulized adrenaline and beta2 agonists for the treatment of acute asthma: a meta-analysis of randomized trials. Am J Emerg Med 2006;24:217-222
CrossRef | Web of Science | Medline

Citing Articles

Matthew A. Waxman, Tyler W. Barrett, David L. Schriger. (2012) A Tale of Two Steroids. Annals of Emergency Medicine59. 147-155


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