Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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Higher-Dose Intravenous Magnesium Therapy for Children With Moderate to Severe Acute Asthma

Ciarallo L, Brousseau D, Reinert S.

Arch Pediatr Adolesc Med. 2000;154:979-983. [abstract] [full-text]

Reviewed by Mara Chavolla, MD, St. Louis Children's Hospital, Washington University School of Medicine

Review posted July 23, 2001

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I. What is being studied?:

The study objective:

To evaluate the efficacy of a 40 mg/kg dose of IV Magnesium sulfate for moderate to severe asthma exacerbation in pediatric patients. The hypothesis was that pediatric patients with acute asthma exacerbation would have improved pulmonary function tests (PFTs) and peak expiratory flow rates (PEFR) with a single higher dose of IV Mg sulfate given in the emergency department (ED).

The study design:

Double-blind placebo-controlled trial.

The patients included:

Thirty patients aged 6 to 17.9 years with an acute asthma exacerbation who required 3 nebulized bronchodilator treatments while in the ED, with PEFR less than 70% of the predicted value.

The patients excluded:

Patients were excluded if febrile (body temperature higher than 38.5 C), if they had used theophylline within the previous week or had a history of cardiac, renal or pulmonary disease other than asthma.

The interventions compared:

The patients were randomized to receive intravenous Mg sulfate (40 mg/kg, max. 2 gm) in a 100 cc of NS solution or an equivalent volume of NS solution (placebo).

The outcomes evaluated:

Primary outcomes: Changes in PEFR, serial clinical asthma scores, blood pressure (BP), deep tendon reflexes and PFT's during the infusion and for additional 90 minutes following therapy.

A secondary outcome measure was the ED disposition (home vs hospital admission).

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes, block randomization was used to assign the patients to each group.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes, all of the discharged patients completed a follow-up telephone call. The rest were the ones admitted to the hospital.

Of interest, 8 of the 38 patients initially enrolled were excluded due to unacceptable spirometry effort. Although randomization occurred after this point, this is a significant fraction of the initial number eligible.

Were patients analyzed in the groups to which they were randomized?

Yes, there was no crossover of patients between the two groups.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Yes, the patients were randomly assigned by the investigational drug pharmacist, the magnesium and saline placebo solutions were prepared by the hospital pharmacy, the physicians on the medical team were blind to the patient's magnesium status. Volume and labeling of the placebo and the active treatment were indistinguishable.

4. Were the groups similar at the start of the trial?

Yes, there were no significant differences on demographic characteristics as well as therapy (steroids and beta agonist) before the start of the study infusion. There were no differences in the baseline magnesium levels as well as baseline PFT's and PEFR's between the two groups.

5. Aside from the experimental intervention, were the groups treated equally?

Almost. All patients received steroids before the infusion was started, although the time between receiving the corticosteroids (orally or IV) was longer for the IV Mg group (33.6 +/- 28.2 minutes) than for the placebo group (27.4 +/-19.8 minutes). No p value was given to this time difference. There were no significant differences between the two groups in the amount or timing of nebulizations given in the ED before or during the infusion.

III. What were the results?

1. How large was the treatment effect?

There was significant improvement in the PFT's and PEFR's as well as the asthma scores in the IV magnesium patient group at all the analyzed time points (p < 0.001), with the greatest improvement at the end of the study period (110 minutes after the infusion). A comparison of the absolute change in percent predicted FEV1 and PEFR between the two groups showed a 25% improvement at 110 minutes on both values for the experimental group compared to a modest increment of less than 5% for both values in the control group.

When compared to the previous study with a lower IV Mg sulfate dose (25 mg/kg) the percentage of improvement from baseline in the PEFR at 110 minutes was about 20% higher for the higher dose (80% change in this high IV magnesium trial vs 60% change in the lower dose study) (1).

All of the placebo group patients required hospitalization and only half of the IV magnesium group was admitted (8/16).

	Admitted to the hospital	No admission	Total
Experimental	8	8	16
Control	14	0`	14
Total	22	8	30

Relative Risk Reduction (RRR) = 0.5
Absolute risk reduction (ARR) = 0.5
Number needed to treat (NNT) = 2 or 2 patients treated to prevent 1 additional event).

2. How precise was the estimate of the treatment effect?

Although statistically significant responses occurred in treated and control patients, confidence intervals were not provided for the changes in PFT's and PEFR's. The ARR of hospitalization was 0.5 with a calculated 95% CI of 0.24, 0.76. The NNT of 2 had 95% CI's of 1 and 4.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Not directly. All patients less than 6 years were excluded as well as the patients with asthma exacerbation so severe that prevented them from doing PFT's; two important characteristics of patients admitted to the PICU. However, for patients with moderate asthma exacerbation treated in the ED this may be an important therapeutic measure to prevent hospitalization. Due to the limited treatment options for the severely ill asthmatics admitted to the PICU and the potential to show even larger effects at lower PEFR's, IV magnesium sulfate may be a useful resource for the patients admitted to the PICU. Further studies are needed.

2. Were all clinically important outcomes considered?

Yes, the impact of IV magnesium therapy on PFT's, asthma clinical scores and disposition was assessed, with a 3 day follow-up for discharged patients to prevent underestimation of exacerbation or hospital admissions shortly after ED discharge.

3. Are the likely treatment benefits worth the potential harms and costs?

There were no differences in deep tendon reflexes and systolic blood pressure throughout the study period. There is no mention of the cost of the therapy, but if it can reduce hospitalizations in asthma patients it may be a very cost-effective therapy in the ED.

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References

1. Ciarallo, L, Sauer, AH, Shannon, MW. Intravenous magnesium therapy for moderate to severe pediatric asthma: Results of a randomized, placebo-controlled trial. J Pediatr 1996; 129: 809-14. [abstract] [PedsCCM EB Journal Club review]

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