USE OF MAGNESIUM SULFATE IN CONTINUOUS INFUSION IN PATIENTS WITH SEVERE ACUTE ASTHMA, IN A PEDIATRIC EMERGENCY ROOM

Milton Gross, Patricia M Lago, Fernanda Chiaradia, Bianca Zandoná, Gabriela Biondo, João Carlos Santana, Paulo Roberto Carvalho

Summary:

Introduction: Asthma is a disease with important morbidity and that can lead to death in childhood. The use of intravenous magnesium sulfate has been indicated in cases refractory to the initial management with inhaled bronchodilators and corticosteroids.

Objective: To evaluate the use of magnesium sulfate in continuous infusion (50mg/kg/hour in 4 hours) in children with severe acute asthma.

Location: 10-bed pediatric emergency room, university hospital.

Patients: Children over 2 years old who received a continuous infusion of magnesium sulfate at a dose of 50mg/kg/hour in 4 hours.

Methods and main findings: Cross-sectional, prospective study. All patients with severe acute asthma were included in a study protocol. A total of 40 patients met the inclusion criteria, 60% male, with a median age of 3.0 years (2.8-4.3). All patients were monitored and followed by an emergency pediatrician during the 4 hours of infusion. There was no description of adverse events related to the magnesium sulfate. The modified Wood-Downes clinical score was applied and compared before and after the infusion and a significant clinical improvement was observed (p<0.001). The serum magnesium levels at the end of the infusion ranged from 3.3-5.8 mg/dL, suitable as therapeutic and without toxicity (median 4.0). The median length of stay in pediatric emergency was 2 days. Only 2 patients (5%) were transferred to the PICU.

Conclusions: On this study, the use of continuous magnesium sulfate proved to be well tolerated, leading to improved respiratory status, and can be considered as adjunctive therapy in the management of severe asthma.

Introduction:

Asthma is the most common chronic disease in childhood, affecting about 10% of all children, being responsible for a large number of visits to the pediatric emergency (1,2). Severe acute asthma is defined as an asthma attack that does not respond to conventional anticholinergic therapy, repeated doses of beta-agonists and corticosteroids, requiring hospitalization (3). There are some options for a second treatment scale, one of which is magnesium sulfate, intravenously (4,5).

Magnesium sulfate is a drug that affects both the muscles of the airway and reduces the inflammatory process. Its mechanism of action is due to its spasmolytic properties, that is, the serum ionized magnesium above the physiological levels produces a transient blockage of the calcium channels regulated by the N-methyl-D-aspartate receptor, generating muscle relaxation. Blocking the entry of calcium into the smooth muscle of the airway interferes with the contraction of the smooth muscle, inducing bronchodilation. In addition, magnesium sulfate has an effect in inhibiting the release of acetylcholine by the motor nerve terminals, inhibiting the release of histamine from mast cells, thus decreasing the production of mucus by the secretory glands (6-9).

Several studies have suggested the use of magnesium sulfate for the treatment of severe acute asthma attacks, in children who did not respond to standard treatment, in a single dose (25-100 mg/kg), intravenously and in bolus. However, despite having a rapid peak of action, its spasmolytic effect decreases abruptly due to rapid renal elimination, even when administered at high doses (12-14).

As a strategy to maintain a consistent therapeutic serum level to compensate for rapid renal elimination, some researchers have proposed the continued use of magnesium sulfate intravenously (14-20). In a recent study carried out by Irazuzta and collaborators, they demonstrated that the use of magnesium sulfate, at a dose of 50mg/kg/hour for 4 hours when compared to bolus treatment (50mg/kg/hour in 1 hour), had better results in the time of disease progression, improvement in lung function, reduction in the hospitalization rate and a better cost-benefit ratio (17). Likewise, Torres, studying patients in a pediatric ICU, described that the infusion of magnesium sulfate during the first hour of hospitalization in patients with severe asthma significantly reduced the percentage of children who required mechanical ventilation (18).

The aim of this study was to evaluate the use of continuous magnesium sulfate over 4 hours in patients with severe acute asthma, who were admitted to the pediatric emergency room by varying the clinical response of the serum magnesium level and the presence of adverse events after infusion of medication.

This cross-sectional, observational, prospective study was submitted to the Ethics Committee and was accepted and filed under the number 23635618.1.0000.5327. We evaluated all patients with severe acute asthma who received magnesium sulfate in continuous infusion, admitted to the pediatric emergency room in the period from April 2017 to October 2019. Patients at the time of magnesium sulfate prescription were included in the study protocol where the medical record number and medication administration date were recorded for future review of data from the electronic medical record. All children eligible for the study remained monitored and accompanied by emergency pediatricians during the infusion. The prescription of magnesium sulfate was the responsibility of the attending physician, following the care protocol of the unit. Serum magnesium was collected immediately after the end of the infusion.

Selection of patients:

All patients over 2 years of age with acute severe asthma who received magnesium sulfate in continuous infusion at a dose of 50mg/kg/hour for 4 hours were included. Patients with a previous history of nephropathy, heart disease, pneumopathies and genetic syndromes associated with pulmonary impairment were excluded. Also excluded were those who used the medication more than once and those who used other intravenous bronchodilator drugs concurrently.

Demographic data and outcomes:

Data were placed in a Microsoft Excel spreadsheet. The variables evaluated were age, gender, weight, height, serum magnesium dosage, presence of adverse events, presence of pneumonia, use of antibiotics, clinical evolution through the modified Wood-Downes severity score (picture 1). The outcomes analyzed were length of stay in the pediatric emergency, need for admission to a pediatric ward or PICU, use of ventilatory support and death (21,22).