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Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay Asociación Española Primera en Socorros Mutuos, Montevideo, Uruguay
Correspondence to: Gustavo J. Rodrigo, MD, Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, Av 8 de Octubre 3020, Montevideo 11600, Uruguay; e-mail: gurodrig{at}adinet.com.uy
To the Editor:
We read with interest the article by Silverman et al that was recently published in CHEST (August 2002)1 regarding the administration of magnesium sulfate to adult patients with acute severe asthma. This well-done multicenter study demonstrated that the administration of 2 g IV magnesium sulfate only improves pulmonary function when administered as an adjunct to standard therapy (ie, nebulized ß-agonists and IV corticosteroids) in a very select subgroup of patients (ie, those with FEV1 < 20% of predicted). On the contrary, the study found that magnesium did not decrease the hospitalization rate. However, Noppen,2 in an editorial comment appearing in the same issue of CHEST as the study, asserted that "IV magnesium therapy certainly should be added to conventional treatment."2 , p 397
We disagree with that statement. In our opinion, the study by Silverman et al has a critical limitation: the standard therapy used. Thus, in the last decade it has been demonstrated that the administration of anticholinergic agents to acute asthma patients who have been treated with ß-agonists improves pulmonary function and reduces the hospitalization rate. The use of multiple doses of ipratropium bromide (IB) seems indicated in the emergency department treatment of children and adults who have acute severe asthma. Studies have reported a substantial reduction in hospital admissions and significant differences in lung function favoring the combined treatment.3 4 5 6 7 8 Recently, this evidence has been included in the management guidelines of asthma exacerbation.9 Silverman et al1 recognized that the magnitude of the response to magnesium would differ if additional interventions (eg, nebulized IB) were used, and claim for studies that consider this type of protocol.
A few years ago, we studied the effects of high and cumulative doses of salbutamol and IB in the treatment of patients with acute severe asthma (ie, FEV1 <50% of predicted; n = 180).7
In a double-blind, randomized, controlled trial, we compared a regimen of salbutamol alone to salbutamol combined with IB (both drugs were administered through a metered-dose inhaler and spacer at rate of 4 puffs every 10 min). One hundred thirty patients (72% of total sample) had an FEV1 
30% of predicted. After 3 h of treatment, subjects who had received IB had an overall 20.5% greater improvement in peak expiratory flow and a 48.1% greater improvement in FEV1 compared with control subjects. The patients who were the most likely to benefit from the combined treatment were those with more severe obstruction (ie, FEV1 30% of predicted). At the end of the protocol (3 h), there was a statistical reduction in the hospital admission rate. In Table 1
, we compared the FEV1 values from our study7
(only patients with FEV1 30% of predicted) with those of the Silverman et al1
at arrival (0 min) and at the end of the protocol (our study, 180 min; Silverman et al, 240 min). The data showed the following: (1) similar baseline values in the two studies; (2) patients in our study who had received salbutamol and IB had significant FEV1 improvements at the end of the protocol in the three subgroups of patients, and, on the contrary, only patients with the lowest initial FEV1 (ie, < 20% of predicted) who had been treated with magnesium presented a significant improvement in pulmonary function; and (3) the ratio between the mean final differences of both studies favors our study in all subgroups studied.
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* Brussels, Belgium
Correspondence to Marc Noppen, MD, PhD, FCCP, Head, Interventional Endoscopy Unit, Academic Hospital AZ-VUB Jette 101, Laarbecklaan, B 1090 Brussels, Belgium; e-mail: marc.noppen{at}az.vub.ac.be
To the Editor:
I thank Drs. Rodrigo and Rodrigo for their comment on the article by Silverman et al,1 and on my accompanying editorial.2 I acknowledge their suggestion that anticholinergics might or should have been added to standard therapy in the study by Silverman et al1 ; however, my editorial suggestion that IV magnesium sulfate should be added to standard therapy in the severest cases of acute severe asthma was not solely based on the article by Silverman et al,1 but mainly on two recently published meta-analyses, stating that "... magnesium sulfate appears to be safe and beneficial for patients who present with severe acute asthma. Practice guidelines need to be changed to reflect these results."3 The study by Silverman et al,1 in my view, corroborates these suggestions.
In fact, when confronted with a patient with very severe acute asthma, with pending respiratory insufficiency and mechanical ventilation, every physician in the world will try anything at hand to avoid this. Magnesium sulfate is widely available, safe, cheap, and proven useful in these very severe cases.3 4 I therefore see no reason not to use IV magnesium sulfate in these circumstances.
References
* Long Island Jewish Medical Center, New Hyde Park, NY
Correspondence to: Robert Silverman, MD, Department of Emergency Medicine, Long Island Jewish Medical Center, 270-05 76th Ave, New Hyde Park, NY 11042; e-mail: aresilv{at}aol.com
To the Editor:
We appreciate the comments on our article that was published in CHEST (August 2002),1 since inhaled ipratropium bromide has been shown by Rodrigo and Rodrigo2 to be useful in adults with severe acute asthma. The methodologies used by previous ipratropium studies involving adults were not sufficient, nor were the results of smaller clinical trials able to document this.3 4 We did not use ipratropium bromide in our protocol because the findings of Rodrigo and Rodrigo2 were published after our study enrollment had been completed.
It is difficult to predict whether the apparent benefit of magnesium would have differed had we added multiple-dose ipratropium to our treatment protocol. It is also difficult to predict whether the results from the ipratropium study would have differed had Rodrigo and Rodrigo2 used magnesium as part of their standard treatment protocol. Since the mechanisms of action of the two agents appear to differ, the benefits might be, to some extent, additive. It is also possible that some patients would respond better to one agent than to the other. The best way to address these questions is through a clinical trial in which a given population (eg, those with an FEV1 < 25% or 30% of predicted) would be randomized to receive ipratropium, magnesium, or a combination of the two interventions.
Regarding the comment that the benefit of magnesium is limited to patients with an FEV1 < 20% of predicted, it is difficult to select a precise cutoff that will predict the response to therapy. We presented data by three subgroups to conveniently represent what our regression analysis had demonstrated, which was that the lower the baseline FEV1, the greater the response to magnesium. We identified an FEV1 of 25% of predicted as an important reference point based on data from an earlier study.5
Had we used block randomization techniques or a larger number of patients, we might have been able to identify a more exact treatment threshold. When the data are plotted out, as the FEV1 moves toward 25% of predicted, magnesium appears to be less effective, and when the baseline FEV1 is > 25% of predicted, magnesium does not appear to be effective at all. For this reason, we are comfortable recommending that magnesium be considered when the initial FEV1 approximates 25% of predicted.
Finally, the observations that both ipratropium and magnesium appear to be beneficial only when there is severe obstruction, as measured by FEV1, presents an important clinical challenge. It is our impression that many patients who are routinely treated in the emergency department do not undergo pulmonary function tests (either FEV1 or peak expiratory flow rate) before treatment. Since FEV1 or peak expiratory flow rate cannot be estimated accurately based on the patient’s appearance, some patients will be undertreated (or overtreated) unless pulmonary function tests are performed. We urge that clinicians adhere to National Asthma Education and Prevention Program guidelines in assessing acutely ill patients in the emergency department.6
References
This article has been cited by other articles:
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  G. J. Rodrigo, B. H. Rowe, M. Blitz, and S. Blitz There is no evidence to support the use of aerosolized magnesium for acute asthma. Chest, July 1, 2006; 130(1): 304 - 306. [Full Text] [PDF]
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