Why we do what we do: Intravenous magnesium for asthma exacerbations

So you’ve thrown the kitchen sink at a child with a moderate to severe asthma exacerbation. And despite the large hematoma on their forehead from the concussive effect of the faucet ricocheting off their skull they’ve not improved. What’s a clinician to do? Give intravenous magnesium sulfate, that’s what you should do. Interestingly we learned that it was valuable when treating pregnant women with preeclampsia that also happened to have asthma (if that’s apocryphal let me know). If you want, you can also review stratification of asthma severity before moving on.

Let’s run down some of the evidence in chronological order (I won’t include every study – just some illustrative examples):

Skobeloff et al. JAMA, 1989

An early RCT, done in adults, that randomized 38 patients moderate to severe asthma exacerbations to get IV mag vs placebo. The authors noted that the Mag group had better improvement in peak flow and fewer Mag patients were admitted (7 for Mag vs 15 for placebo).

Green et al. Annals of Emerg Med, 1992

The authors randomized 120 consecutive patients in a block manner (alternating Mag vs placebo days) and failed to show a reduction in admission rate –  22% in Magnesium group (95%CI 13-32), 17% in control (95%CI 10-26), p = 0.523. I included this study because the physicians weren’t blinded to the randomization. Does this impact how you assess the validity of the study?

Bloch et al. Chest 1995

Another adults only trial, this time involving 135 patients. They also noted a decreased risk of admission, 35.3% in the placebo group and 25.4% in the Mag group (p = 0.21). When they broke it down to moderate (FEV1 <75% predicted) and severe (FEV1 <25% predicted) they noted that only the severe group had significantly reduced admission rates. Specifically they stated that in the severe patients “admission rates were 78.6% (11/14) for the placebo-treated group and 33.3% (7/21) for the magnesium-treated group (p = 0.009). For the moderate patients, admission rates were 22.4% (11/49) for the placebo-treated group and 22.2% (10/25) for the magnesium-treated group (p = 0.98).” This study built upon Skobeloff by including more patients and stratifying severity.

Ciarrallo et al. J. Pediatr, 1996

A study on kids? Now you’re talking. This RCT of kids 6 to 18 years with peak flow rates <60% predicted following 3 nebulized treatments included 31 kids (15 Mag vs 16 placebo). The dose was 25mg/kg IV over 20 minutes – more on the dose in a little bit. The Mag group had higher serum Mag levels (only mean 1.3), and a better improvement in % increase in expected peak flow. They also noted that 27% of IV mag were discharged home vs 0% placebo; p = 0.03.

Ciarrallo et al. Arch Pediatr Adolescent Medicine

Ciarrallo followed up earlier work by going with a higher dose of IV Mag (40mg/kg) – more is better! This RCT involved 30 children age 6 to 18 that needed 3 back to back nebs (albuterol alone or combo of albuterol/ipratropium). They excluded febrile patients, as well as those with cardiac, renal or non-asthma pulmonary disease and theophylline use in the last week. Patients got IV Mag or placebo. The authors noted a reduced risk of admission 50% IV mag (8/16) vs 100% placebo (14/14); p=0.02, and improved respiratory scores at approximately one and a half hours (mean asthma score 1.4 for IV mag and 2.5 placebo; p<0.001). The small numbers limited the generalizability, but it was a start.

Let’s get meta

So, out of the 5 aforementioned studies, 4 showed a reduced risk of admission and improved pulmonary function or clinical asthma scores. Two are more germane to Pediatric Emergency Medicine as they included children. To better draw conclusions we’d need a meta analysis… And here you go, it’s from Rowe et al. in 2000. Overall the authors examined 7 studies with 665 patients and concluded the following: