Picture 5: Correlation of the variation percentage of the Wood-Downes
clinical score with the serum magnesium level at the end of the 4-hour
continuous infusion of magnesium sulfate.
When comparing the serum magnesium level and a better clinical response,
assessed by varying the score (p = 0.392), no correlation was observed.
Using a cutoff point of serum magnesium level at 4.0, as suggested in
the literature as a therapeutic mean, no significant variation was
observed (p = 0.77) (Picture 5).
There were no reports of any adverse events during and after the
intravenous magnesium sulfate infusion in 4 hours, researching the
description of nausea, drowsiness, vision changes, muscle weakness,
hypotension, respiratory distress, arrhythmia and burning sensation and
redness in the application route.
The average length of stay in the pediatric emergency was 2 days. Only 2
(5%) patients required transfer to the PICU, but without the need for
ventilatory support. There was no correlation between the length of stay
in the pediatric emergency and the variation in the clinical score (p =
0.242). None of the patients in the study died.
Discussion:
The management of asthma in the emergency room must be fast and
organized due to the reversibility possibility of the condition and the
potential risk of progression to respiratory failure (3). The classic
treatment includes repeated inhaled beta-adrenergics and
corticosteroids. In acute and severe cases, magnesium sulfate has been
used intravenously after failure to respond to initial management.
Magnesium produces smooth muscle relaxation inducing bronchodilation and
has a rapid peak of action, but is also rapidly eliminated by the
kidney, which restricts its use. In order to prolong the effect of
magnesium sulfate, maintaining a compatible therapeutic level to
compensate for the rapid elimination, Irazuzta et al. suggested the
continuous infusion of this medication (16,19,20).
The present study evaluated children who were admitted to the pediatric
emergency room with severe acute asthma and who used a continuous
infusion of magnesium sulfate for 4 hours, at a dose of 50mg/kg/hour. It
was possible to observe that there was a significant clinical
improvement after the end of the infusion, the serum magnesium level
ranged from 3.3 to 5.6 mg/dL, very close to the levels described in the
literature as therapeutic (around 4.0 mg/dL). No patient experienced
adverse events (8).
The beneficial effect of magnesium sulfate on asthma is well known, but
few studies have been conducted in children. In a 2016 Cochrane review,
only 5 studies with a more robust methodology were identified, where the
authors concluded that intravenous magnesium sulfate could reduce the
need for hospital admission in patients with moderate to severe asthma,
refractory to the initial treatment. In our study, a significant
clinical improvement was observed after 4 hours of infusion, assessed by
varying the clinical severity score and only 2 out of 40 patients did
not respond to magnesium sulfate, even with an adequate serum level,
requiring transfer to PICU (16).
The normal concentration of serum magnesium in humans is 1.8 to 2.3 mg /
dL. It is the fourth most abundant mineral in the body, it acts as a
cofactor in more than 300 enzymatic reactions, it is necessary for the
synthesis of proteins, including DNA and RNA. The ideal level of serum
magnesium for the treatment of wheezing exacerbations in childhood is
not well established in the literature. Several studies have reported
achieving therapeutic efficacy with serum concentrations between 3 and 5
mg/dL, corroborating the data found in this study in which the median
serum magnesium was 4.3 (3.9-4.6) after 4 hours of infusion (13-20).
The toxicity of magnesium sulfate has already been well evidenced in
obstetric and anesthetic studies, mainly associated with the treatment
of eclampsia, however there is little description outside these
contexts. The side effects of magnesium sulfate are known to be dose
dependent. Symptoms such as nausea, flushing, drowsiness, changes in
vision and muscle weakness are more common when serum magnesium
concentrations exceed 9 mg/dL. On the other hand, Graft and
collaborators observed that the maintenance of serum magnesium levels
between 4 and 6 mg/dL are effective in avoiding clinical signs of
toxicity (15). From the data found in this study, we can observe that
the use of magnesium sulfate by continuous infusion in 4 hours at a dose
of 50mg/kg/hour raises the serum magnesium level to therapeutic values,
non-toxic however (14,15,19).
Our study has limitations because it is a case series without a control
group. Associated with this, it is a review of electronic medical
records, subject to some interpretation bias, mainly in the subjective
data described, however we try to minimize this fact by using only one
reviewer researcher. Despite these restrictions, the results obtained
corroborate with the data presented in the literature so far, showing
that magnesium sulfate in continuous infusion could be useful in the
treatment of severe acute asthma safely. New studies, ideally
multicentric, randomized and with a larger sample size, can contribute
to a deeper knowledge on the subject.
Conclusion:
Based on this study, we concluded that the use of continuous intravenous
magnesium sulfate at a dose of 50mg/kg/hour in 4 hours can be a
satisfactory adjuvant therapy in the setting of severe acute asthma in
children. Associated with the advantage of a good clinical response,
magnesium sulfate was shown to be safe, maintaining a non-toxic and
therapeutic serum level, with no adverse events observed.
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