Magnesium sulphate for treating children up to two years old with bronchiolitis

Review question

We investigated the effectiveness and safety of magnesium sulphate for treating children up to two years old with acute bronchiolitis.

Background

Acute bronchiolitis is caused by a virus, and mostly affects children up to two years old. This condition blocks small airways in the lungs, causing coughing, wheezing, and breathing difficulties. Usual treatment involves supportive care, which includes providing adequate fluids and humidified oxygen. Children with bronchiolitis may need intensive care treatment.

Search date

Evidence is current to 30 April 2020.

Study characteristics

We included four studies (564 children) conducted in Qatar, Turkey, Iran, and India. Three studies included children with moderate to severe bronchiolitis. Studies compared magnesium sulphate, given via a tube into a vein (intravenous), or as a fine inhaled spray (nebulised), with a dummy treatment (known as a placebo – something that looks like magnesium sulphate treatment), medicines to open the airways (salbutamol or epinephrine), a salt water solution (hypertonic saline), or no treatment.

Study funding sources

One study received funding from a hospital and one from a university; two studies did not report funding sources.

Key results

There was not enough evidence to know if intravenous or nebulised magnesium sulphate, either alone or combined with other treatments, improved bronchiolitis outcomes in children up to two years old. We could not determine if magnesium sulphate reduced deaths, unexpected medical problems during treatment, time spent in hospital, or illness severity (based on doctors' clinical assessment scores). Time taken to recovery was not measured.

Certainty of the evidence

Overall, we are very uncertain of the results.

Authors' conclusions: 

There is insufficient evidence to establish the efficacy and safety of magnesium sulphate for treating children up to two years of age with acute bronchiolitis. No evidence was available for time to recovery, duration of mechanical ventilation and intensive care unit stay, or pulmonary function. There was no information about adverse events for some comparisons. Well-designed RCTs to assess the effects of magnesium sulphate for children with acute bronchiolitis are needed. Important outcomes, such as time to recovery and adverse events should be measured.

Read the full abstract...
Background: 

Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment involves adequate hydration, humidified oxygen supplementation, and nebulisation of medications, such as salbutamol, epinephrine, and hypertonic saline. The effectiveness of magnesium sulphate for acute bronchiolitis is unclear.

Objectives: 

To assess the effects of magnesium sulphate in acute bronchiolitis in children up to two years of age.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, and two trials registries to 30 April 2020. We contacted trial authors to identify additional studies. We searched conference proceedings and reference lists of retrieved articles. Unpublished and published studies were eligible for inclusion.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs, comparing magnesium sulphate, alone or with another treatment, with placebo or another treatment, in children up to two years old with acute bronchiolitis. Primary outcomes were time to recovery, mortality, and adverse events. Secondary outcomes were duration of hospital stay, clinical severity score at 0 to 24 hours and 25 to 48 hours after treatment, pulmonary function test, hospital readmission within 30 days, duration of mechanical ventilation, and duration of intensive care unit stay.

Data collection and analysis: 

We used standard methodological procedures expected by Cochrane. We used GRADE methods to assess the certainty of the evidence.

Main results: 

We included four RCTs (564 children). One study received funding from a hospital and one from a university; two studies did not report funding sources. Comparator interventions differed among all four trials. Studies were conducted in Qatar, Turkey, Iran, and India. We assessed two studies to be at an overall low risk of bias, and two to be at unclear risk of bias, overall. The certainty of the evidence for all outcomes and comparisons was very low except for one: hospital re-admission rate within 30 days of discharge for magnesium sulphate versus placebo. None of the studies measured time to recovery, duration of mechanical ventilation, duration of intensive care unit stay, or pulmonary function.

There were no events of mortality or adverse effects for magnesium sulphate compared with placebo (1 RCT, 160 children). The effects of magnesium sulphate on clinical severity are uncertain (at 0 to 24 hours: mean difference (MD) on the Wang score 0.13, 95% confidence interval (CI) -0.28 to 0.54; and at 25 to 48 hours: MD on the Wang score -0.42, 95% CI -0.84 to -0.00). Magnesium sulphate may increase hospital re-admission rate within 30 days of discharge (risk ratio (RR) 3.16, 95% CI 1.20 to 8.27; 158 children; low-certainty evidence).

None of our primary outcomes were measured for magnesium sulphate compared with hypertonic saline (1 RCT, 220 children). Effects were uncertain on the duration of hospital stay in days (MD 0.00, 95% CI -0.28 to 0.28), and on clinical severity on the Respiratory Distress Assessment Instrument (RDAI) score at 25 to 48 hours (MD 0.10, 95% CI -0.39 to 0.59).

There were no events of mortality or adverse effects for magnesium sulphate, with or without salbutamol, compared with salbutamol (1 RCT, 57 children). Effects on the duration of hospital stay were uncertain (magnesium sulphate: 24 hours (95% CI 25.8 to 47.4), magnesium sulphate + salbutamol: 20 hours (95% CI 15.3 to 39.0), and salbutamol: 24 hours (95% CI 23.4 to 76.9)).

None of our primary outcomes were measured for magnesium sulphate + epinephrine compared with no treatment or normal saline + epinephrine (1 RCT,120 children). Effects were uncertain for the duration of hospital stay in hours (MD -0.40, 95% CI -3.94 to 3.14), and for RDAI scores (0 to 24 hours: MD -0.20, 95% CI -1.06 to 0.66; and 25 to 48 hours: MD -0.90, 95% CI -1.75 to -0.05).