Continuous infusion of magnesium sulfate: an adjuvant therapy to treat acute severe asthma.Daniele de Avila Dalmora (1), Patricia Miranda Lago (1), Jordana Vaz Hendler (2), João Carlos Batista Santana (1), Liane Esteves Daudt (1)Affiliation:Universidade Federal Rio Grande do Sul (Medicine School)Hospital de Clinicas de Porto AlegreCorresponding Author:Profa. Patricia Miranda LagoEmail: [email protected] OF INTERESTSThe authors declare that there is no conflict of interest.To editorAsthma is a significant cause of morbidity and mortality, particularly in severe cases. In such instances, the use of intravenous magnesium sulfate has emerged as an adjuvant therapy to help manage acute exacerbations, that are unresponsive to first-line treatments. While the efficacy of magnesium sulfate in improving symptoms in asthmatic patients has been well documented, the assessment of its potential side effects in pediatric patients is limited.By investigating the side effects of continuous magnesium sulfate 6 hours infusion in a pediatric emergency department in Southern Brazil, the authors aim was to determine if treatment could be a good and safe option in severe cases.This case series study was submitted to and approved by the Ethics Committee, with registration number 23635618.1.0000.5327. All parents of children participating in the study signed an informed consent document. There were no losses during the research period. The investigation was carried out from June 2022 to May 2023, in the Emergency Department (14 beds) of a public, general and university hospital from Porto Alegre.Throughout the period of continuous magnesium sulfate infusion, all selected children were closely monitored and accompanied by emergency pediatricians. The magnesium sulfate prescription was carried out by the attending physician in accordance with the unit’s care protocol. The initial therapy management included oxygen administration via nasal catheter or Venturi mask based on saturation and/or respiratory dysfunction, single-dose oral prednisolone, and rescue nebulization with salbutamol and ipratropium, during 1 to 2 hours. The patients who didn’t improve, received the continuous infusion of 50 mg/kg/h dose of magnesium sulfate for 6 hours, with a maximum daily dosage of 8000 mg. The blood sample was collected immediately after the completion of the infusion to assess the serum magnesium levels. The asthma crise severity was classified by the modified Wood-Downes score.Patients between 3 and 14 years old with acute severe asthma were included in the study. Children who had nephropathy, heart disease, chronic pneumopathies excluding asthma, and genetic syndromes associated with pulmonary involvement were excluded.The data was collected and recorded using the institutional REDCap (Research Electronic Data Capture) system. The variables evaluated included age, gender, weight, height, serum magnesium levels, presence of side effects, presence of pneumonia, viral infection and clinical evolution assessed using the modified Wood-Downes severity score (Figure 1). The outcomes analyzed were the length of stay in the pediatric emergency room, time of oxygen supplementation, need for admission to a pediatric intensive care unit (PICU), use of ventilatory support and mortality.The authors analyzed the data using IBM SPSS Statistics version 20.0. The Kolmogorov-Smirnov test was used to assess the normality of variables. Categorical variables were presented as percentages and compared using the χ2 test. Continuous variables without asymmetrical distribution were expressed as medians and compared using the Mann-Whitney or Kruskal-Wallis tests.The study included a total of 42 patients that met the inclusion criteria, among them, 24 males (57.1%) and 18 females (42.9%). The patients mean age was 5.7 years old, with a range from 3 to 12 years. The BMI calculations showed that none of the patients were overweight or obese (BMI 17.5±2.6). Before the administration of continuous magnesium sulfate infusion for 6 hours, the score values ranged from 3 to 5 (median 4 ). And after 6-hour infusion, the scores decreased significantly to a range from 3 to 1 (median 2 ) (p < 0.001) (Table 1).There was important clinical improvement after 6 hours infusion in 30 patients (72%), as assessed by variations in the clinical severity score, with a reduction of at least 1 point. However, 12 patients (28%) did not respond to magnesium sulfate, even with adequate serum levels. There was no difference regarding the age, BMI, gender, virus detection or pneumonia, comparing responsive and unresponsive children. The study methodology considered as unresponsive all patients that necessitated more than once magnesium infusion, received multiple therapies like intravenous salbutamol, had no improvement in clinical scores, required intensive care in the Pediatric Intensive Care Unit (PICU) and/or ventilatory support.The magnesium serum level after infusion was 4.7 mg/dl (no difference between respond or not). The length of stay median in the pediatric emergency department was 2 days, with an interquartile range of 2 to 4. It is important to mention that none of the patients required respiratory support.Concerning to the side effects, no events were reported during or after the 6-hour intravenous infusion of magnesium sulfate, as nausea, drowsiness, vision changes, muscle weakness or other neurological symptoms, hypotension, respiratory distress, arrhythmia, and burning sensation or redness in the application route. There were no statistical differences between cardiac frequency and systolic blood pressure during infusion (2,4 and 6 hours), but a significant reduction in respiratory rate was detected (Figure 1).The asthma management in the emergency service necessitates prompt action to reverse symptoms and avoid respiratory failure. The standard therapy approach involves repeated administration of bronchodilators and corticosteroids, but in some cases, it is not enough for clinical improve. An Intravenous magnesium sulfate had been employed in cases of acute severe asthma that do not respond to initial management (1,2)The Magnesium sulfate induces muscle relaxation, leading to bronchodilation, and presents a rapid onset of action. To maintain a sustained relaxation effect, continuous infusion is required, otherwise its use is limited by its short half-life of 2.7 hours. In the asthma treatment, the Magnesium can be administered as a single-dose bolus. However, to obtain a prolonger effect, the administration via continuous infusion emerged as an attempt to compensate for its rapid renal elimination (3-6).This case series that evaluated 42 patients with acute severe asthma treated with a 6-hour infusion of magnesium sulfate showed clinical response by an improved Wood-Downes severity score at the end of the infusion as described by Gross and Irazuzta, and no side effects, that wasn’t study yet for other authors (3,4).It is important observed that this research is a case series performed in a single center, with a limited number of patients. Despite the study limitations, the results corroborate findings of other researches in the medical literature (3-6). The use of continuous infusion of magnesium sulfate for 6-hours emerged as an interesting treatment option to the management of acute severe asthma, showing safety as analyzed by the side effects, and resulting in better clinical outcomes. The authors believe that further multicenter and randomized studies with larger sample size are recommended to confirm efficacy and safety.FIGURE 1 Evolution of vital signs during the infusion
