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Communications to the Editor |

Status Asthmaticus in Children : Evidence-Based Recommendations FREE TO VIEW

Gustavo J. Rodrigo, MD; Carlos Rodrigo, MD
Author and Funding Information

Affiliations: Hospital Central de las FF.AA. Asociación Española 1a de Socorros Mutuos Montevideo, Uruguay,  University of Kentucky Children’s Hospital Lexington, KY

Correspondence to: Gustavo J. Rodrigo, MD, Departamento de Emergencia, Hospital Central de las FF.AA. Av. 8 de Octubre 3020, Montevideo 11600, Uruguay; e-mail: gurodrig@adinet.com.uy.



Chest. 2002;121(2):667-669. doi:10.1378/chest.121.2.667
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To the Editor:

We read with interest the review by Werner, entitled “Status Asthmaticus in Children,”1 that appeared in the June 2001 issue of CHEST. In this nonsystematic review, we found that important statements are not evidence based.

Werner examined the data and rationale for the use of corticosteroids (CCS) in children with acute asthma. On the basis of an incomplete literature search, the author stated, “There does not appear to be a role for aerosolized steroids in acute severe asthma in children.” As a result, all the evidence about the use of inhaled CCS in acute asthma was ignored. Most of this is new literature (mid-1990s), and its quality is very high. Therefore, Edmonds et al2 conducted a systematic review of the literature with meta-analysis to determine the benefit of inhaled CCS for the treatment of patients with acute asthma managed in the emergency department. On the basis of six randomized controlled trials (six adult, two pediatric), the authors found that patients treated with inhaled CCS were less likely to be admitted to the hospital (odds ratio, 0.33; 95% confidence interval, 0.17 to 0.64); additionally, they demonstrated a significant improvement in FEV1 at 2 h of treatment.

In the section on anticholinergics, Werner appropriately stated that“ anticholinergics are now an integral part of the treatment of acute asthma in children.” However, a “recommended dose” of 250 to 500μ g at 6-h intervals does not seem acceptable. On the contrary, there is strong evidence that supports the use of high and increasing doses of inhaled anticholinergics (ipratropium bromide) added toβ 2-agonists in the treatment of children and adults with acute asthma.37 Examination of the protocols reveals that repeated doses of nebulized ipratropium bromide were usually administered as 250 to 500 μg per dose every 20 min or four puffs (80 μg) every 15 to 20 min via metered-dose inhaler and spacer. So, routine emergency department treatment of acute severe asthma involves repeated doses of β2-agonists and ipratropium bromide administered over the first hour.

Werner recommended the use of “high-flow supplemental oxygen”; the assertion that “in the absence of preexisting chronic pulmonary disease, there is no evidence that oxygen will suppress the respiratory drive,” supported with a reference from 1980, would be considered with caution. On the contrary, there are data showing that the administration of 100% oxygen to acutely ill asthmatics can result in respiratory depression with carbon dioxide retention, particularly in patients with severe airway obstruction.8

Finally, two Uruguayan physicians, Rosello and Pla,9 first reported the treatment of acute asthma with parenteral magnesium sulfate in 1936.

Werner, HA (2001) Status asthmaticus in children: a review.Chest119,1913-1929. [PubMed] [CrossRef]
 
Edmonds, ML, Camargo, CA, Pollack, CV, et al Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). The Cochrane Library (Issue 2). 2001; Update Software. Oxford, UK:.
 
Plotnick, LH, Ducharme, FM Should inhaled anticholinergics be added to β2-agonists for treating acute childhood and adolescent asthma? A systematic review.BMJ1998;317,971-977. [PubMed]
 
Rodrigo, G, Rodrigo, C, Burschtin, O A meta-analysis of the effects of ipratropium bromide in adults with acute asthma.Am J Med1999;107,363-370. [PubMed]
 
Rodrigo, GJ, Rodrigo, C First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department.Am J Respir Crit Care Med2000;161,1862-1868. [PubMed]
 
Qureshi, F, Pestian, J, Davis, P, et al Effect of nebulized ipratropium on the hospitalization rates of children with asthma.N Engl J Med1998;339,1030-1035. [PubMed]
 
Benito Fernández, J, Mintegui Raso, S, Sánchez Echaniz, J, et al Eficacia de la administración precoz de bromuro de ipratropio nebulizado en niños con crisis asmática.An Esp Pediatr2000;53,217-222. [PubMed]
 
Chien, JW, Ciufo, R, Novak, R, et al Uncontrolled oxygen administration and respiratory failure in acute asthma.Chest2000;117,728-733. [PubMed]
 
Rosello, JC, Pla, JC Sulfato de magnesio en la crisis de asma.Prensa Med Argent1936;23,1677-1680
 
To the Editor:

I appreciate the thoughtful comments by Rodrigo and Rodrigo on my review of severe asthma in children. Rodrigo and Rodrigo disagree with my statement that, currently, there is no role for inhaled corticosteroids in treatment of acute, severe asthma in children. Should inhaled steroids be added to, or even replace, parenteral steroids in children with status asthmaticus? No literature exists to support such practice. They cite a recent meta-analysis in the Cochrane library on the benefits of inhaled steroids.1 Careful review of this analysis confirms that current recommendations on the use of corticosteroids in children with life-threatening asthma do not need to be changed. The analysis included three heterogeneous pediatric studies, none of which enrolled children with severe asthma. The majority of studies in this analysis compared inhaled corticosteroids to placebo, not to parenteral steroids. When comparing inhaled steroids to parenteral steroids, the meta-analysis found no difference. Parenteral steroids remain the avenue of choice in children with acute, severe asthma.

Rodrigo and Rodrigo further state that the recommended dose of 250 to 500 μg ipratropium q6h is insufficient. They quote five articles to support their assertion. Of these articles, four are available in the English language.25 None of them, including their own, supports their statement. None of these reports compared routine ipratropium doses to higher doses, nor did they compare more frequent to less frequent application. The only article attempting to address this issue is by Schuh et al.6In this double-blinded, three-armed trial, the investigators administered ipratropium to asthmatic children and compared the effects of 250 μg administered three times within an hour, 250 μg as a single dose, and placebo. The group receiving three doses experienced the greatest improvement in pulmonary function. Davis et al7had shown nicely that the dose-response curve for ipratropium in asthmatic children flattens between 75 μg and 250 μg. The maximal response of inhaled ipratropium develops over 30 to 90 min, and may persist for > 4 h.8 In summary, we know that ipratropium is better for severely asthmatic children than no ipratropium. It has not been shown that doses > 500 μg are necessary. It may be beneficial to start treatment with three doses of ipratropium every 20 min, then repeat it every 4 to 6 h.

Rodrigo and Rodrigo disagree with the statement regarding suppression of respiratory drive by administration of supplemental oxygen. There is no evidence at all to indicate that otherwise normal children experience respiratory depression with administration of oxygen. The report quoted by Rodrigo and Rodrigo offers an interesting observation in adult asthmatics (mean age, 43 years), in whom oxygen administration leads to a mean increase in Paco2 by 2.3 mm Hg.9It is nearly impossible to establish cause and effect from these data: bronchodilators were withheld during the observation period, and no attempt was made to see if the small trend would reverse after withdrawal of oxygen. Oxygen administration is a crucial element of first-line treatment of the asthmatic child. Children have less oxygen reserve compared to adults, as their resting oxygen consumption may be two to three times that of an adult.10 Unfounded fear may lead to misguided withholding of oxygen for the child with asthma.

We still have much to learn about pediatric asthma. It differs from adult asthma in many respects, such as etiology, epidemiology, and pathophysiology. Not all knowledge gained from adult asthmatics can be transferred readily to the pediatric patient.

References
Edmonds, M, Camargo, C, Pollack, C, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). 2001; Update Software. Oxford, UK:.
 
Rodrigo, GJ, Rodrigo, C First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department.Am J Respir Crit Care Med2000;161,1862-1868. [PubMed]
 
Rodrigo, G, Rodrigo, C, Burschtin, O A meta-analysis of the effects of ipratropium bromide in adults with acute asthma.Am J Med1999;107,363-370. [PubMed] [CrossRef]
 
Qureshi, F, Pestian, J, Davis, P, et al Effect of nebulized ipratropium on the hospitalization rates of children with asthma.N Engl J Med1998;339,1030-1035. [PubMed]
 
Plotnick, LH, Ducharme, FM Should inhaled anticholinergics be added to β2agonists for treating acute childhood and adolescent asthma? A systematic review.BMJ1998;317,971-977. [PubMed]
 
Schuh, S, Johnson, DW, Callahan, S, et al Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.J Pediatr1995;126,639-645. [PubMed]
 
Davis, A, Vickerson, F, Worsley, G, et al Determination of dose-response relationship for nebulized ipratropium in asthmatic children.J Pediatr1984;105,1002-1005. [PubMed]
 
Hardman, J Gilman, A Limbird, L eds.Goodman and Gilman’s the pharmacological basis of therapeutics 9th ed.1996 McGraw-Hill. New York, NY:
 
Chien, JW, Ciufo, R, Novak, R, et al Uncontrolled oxygen administration and respiratory failure in acute asthma.Chest2000;117,728-733. [PubMed]
 
LaFarge, CG, Miettinen, OS The estimation of oxygen consumption.Cardiovasc Res1970;4,23-30. [PubMed]
 

Figures

Tables

References

Werner, HA (2001) Status asthmaticus in children: a review.Chest119,1913-1929. [PubMed] [CrossRef]
 
Edmonds, ML, Camargo, CA, Pollack, CV, et al Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). The Cochrane Library (Issue 2). 2001; Update Software. Oxford, UK:.
 
Plotnick, LH, Ducharme, FM Should inhaled anticholinergics be added to β2-agonists for treating acute childhood and adolescent asthma? A systematic review.BMJ1998;317,971-977. [PubMed]
 
Rodrigo, G, Rodrigo, C, Burschtin, O A meta-analysis of the effects of ipratropium bromide in adults with acute asthma.Am J Med1999;107,363-370. [PubMed]
 
Rodrigo, GJ, Rodrigo, C First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department.Am J Respir Crit Care Med2000;161,1862-1868. [PubMed]
 
Qureshi, F, Pestian, J, Davis, P, et al Effect of nebulized ipratropium on the hospitalization rates of children with asthma.N Engl J Med1998;339,1030-1035. [PubMed]
 
Benito Fernández, J, Mintegui Raso, S, Sánchez Echaniz, J, et al Eficacia de la administración precoz de bromuro de ipratropio nebulizado en niños con crisis asmática.An Esp Pediatr2000;53,217-222. [PubMed]
 
Chien, JW, Ciufo, R, Novak, R, et al Uncontrolled oxygen administration and respiratory failure in acute asthma.Chest2000;117,728-733. [PubMed]
 
Rosello, JC, Pla, JC Sulfato de magnesio en la crisis de asma.Prensa Med Argent1936;23,1677-1680
 
Edmonds, M, Camargo, C, Pollack, C, et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma (Cochrane Review). 2001; Update Software. Oxford, UK:.
 
Rodrigo, GJ, Rodrigo, C First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department.Am J Respir Crit Care Med2000;161,1862-1868. [PubMed]
 
Rodrigo, G, Rodrigo, C, Burschtin, O A meta-analysis of the effects of ipratropium bromide in adults with acute asthma.Am J Med1999;107,363-370. [PubMed] [CrossRef]
 
Qureshi, F, Pestian, J, Davis, P, et al Effect of nebulized ipratropium on the hospitalization rates of children with asthma.N Engl J Med1998;339,1030-1035. [PubMed]
 
Plotnick, LH, Ducharme, FM Should inhaled anticholinergics be added to β2agonists for treating acute childhood and adolescent asthma? A systematic review.BMJ1998;317,971-977. [PubMed]
 
Schuh, S, Johnson, DW, Callahan, S, et al Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.J Pediatr1995;126,639-645. [PubMed]
 
Davis, A, Vickerson, F, Worsley, G, et al Determination of dose-response relationship for nebulized ipratropium in asthmatic children.J Pediatr1984;105,1002-1005. [PubMed]
 
Hardman, J Gilman, A Limbird, L eds.Goodman and Gilman’s the pharmacological basis of therapeutics 9th ed.1996 McGraw-Hill. New York, NY:
 
Chien, JW, Ciufo, R, Novak, R, et al Uncontrolled oxygen administration and respiratory failure in acute asthma.Chest2000;117,728-733. [PubMed]
 
LaFarge, CG, Miettinen, OS The estimation of oxygen consumption.Cardiovasc Res1970;4,23-30. [PubMed]
 
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