From 1975 to 1995, hospitalization and death rates in children with asthma significantly increased. This increase occurred despite the presence of national treatment guidelines, improved efforts at patient education and a more aggressive approach to treatment. The mainstays of asthma therapy are corticos-teroids and beta agonists but, in the acute setting, these treatments are not always immediately effective and will not prevent hospital admission. Intravenous magnesium sulfate (IVMg) was first proposed as a treatment for asthma more than 60 years ago. It relaxes smooth muscle, reduces histamine-induced bronchospasm and has a rapid onset of action. Ciarallo and colleagues reported the first pediatric trial with this drug in 1996. They recently performed a follow-up study of magnesium therapy for pediatric asthma using higher doses of the drug than were used in their initial study.
Children were enrolled through the emergency departments of two children's hospitals. Entry criteria included age between six and 18 years, at least three nebulized treatments in the emergency department with albuterol or ipratropium (singly or combined), and a peak expiratory flow rate (PEFR) of less than 70 percent predicted. This last criterion qualified the children as having a moderate-to-severe exacerbation of asthma. All eligible children were given 2 mg per kg of intravenous methylprednisolone. They were then randomly assigned in a double-blind fashion to receive IVMg (40 mg per kg in 100 mL of normal saline) or an equivalent volume of normal saline (placebo) over 20 minutes. Serial clinical asthma scores along with PEFR, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded at 15-minute intervals for 90 minutes. Treatment with nebulized bronchodilators was continued at the discretion of the treating physician, and a second serum magnesium level was checked 30 minutes after the infusion was complete. Follow-up of children who were discharged from the emergency department was by telephone at 48 to 72 hours.
Of the 38 patients enrolled, 30 were eligible on the basis of spirometric criteria. Fourteen were assigned to the placebo group, and 16 were given IVMg. The baseline pulmonary function studies, oxygen saturation by pulse oximetry and use of home asthma therapies were consistent in all patients. The mean age of the children in the treatment group was about 11 years, and about 70 percent were male. The PEFR of the children given IVMg was significantly improved from baseline at the end of the infusion, at 20 minutes post-infusion and at 110 minutes post-infusion. A similar result was seen with the FEV1, which was most improved at 110 minutes post-infusion. In the placebo group, the changes from baseline in PEFR and FEV1 were minimal and not significant. Clinical asthma scores were significantly better in the IVMg group, although this result did not occur until 95 minutes post-infusion. At the end of the clinical assessment period, eight of the 16 children given IVMg were discharged from the emergency department to home. None required a repeat emergency department visit or hospital admission. All 14 children in the placebo group were admitted to the hospital for further treatment of their asthma.
The authors conclude from this study that IVMg, given as a single dose of 40 mg per kg, is a safe, rapidly acting and effective adjunct in the treatment of acute exacerbations of asthma in children. It should be considered for use in children with moderate to severe asthma who have not responded to nebulized bronchodilator therapy.