Finding the Right Dose: New PECARN Study Reveals Target Levels for IV Magnesium in Pediatric Asthma

Background

Pediatric asthma exacerbations represent a significant burden on emergency departments, with over 1.2 million ED visits and 110,000 hospitalizations annually in the United States. While many treatment options exist for the emergency care of asthma (such as albuterol, ipratropium bromide, and corticosteroids), some children continue to have persistent symptoms and require hospitalization despite these treatments. Intravenous (IV) magnesium sulfate is a potential adjunct treatment, but evidence regarding its appropriate dose and efficacy has been limited. This pharmacology study was part of the broader IMPACT-ED trial (Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department), which was designed as a pilot study examining the role of IV magnesium in pediatric acute asthma exacerbations [1].

Study Question

This 2025 Journal of Clinical Pharmacology publication focuses on the pharmacokinetics of IVMg in children with asthma, providing detailed models that describe how the drug is processed in the body. It also defines the concentration-effect relationships, linking magnesium levels to both therapeutic efficacy and potential safety concerns in pediatric asthma management [2].

Study Design

This prospective, double-blind, placebo-controlled study, as part of the IMPACT-ED trial [1], enrolled 49 children (ages 2-17) with a moderate-severe asthma exacerbations across 3 PECARN sites:

  • Participants were randomly assigned to receive one of the following:
    • Placebo (0.9% NaCl solution)
    • IVMg 50 mg/kg (maximum 2g)
    • IVMg 75 mg/kg (maximum 3g)
  • Monitoring
    • Blood samples were collected at the following time points:
      • Prior to drug administration
      • 20-40 minutes after infusion started
      • 90-150 minutes after infusion started
    • Asthma severity was assessed using the Pediatric Respiratory Assessment Measure (PRAM) at the following time points:
      • Before drug infusion
      • 20-40 minutes after infusion started
      • 120 minutes after infusion started
    • Blood pressure was monitored frequently:
      • Within 10 minutes before infusion
      • Every 10 minutes after infusion started until 90 minutes
      • Again at 120 minutes after infusion started

Key Findings

The study found that improvements in PRAM scores were significantly associated with total magnesium exposure in the bloodstream over time (measured as “area under the concentration-time curve” or AUC0-2h, which represents the total amount of magnesium in the bloodstream over the 2-hour period). Key findings include:

Finding: A target threshold of total magnesium AUC0-2h >63.1 mg·h/L was identified:

  • Provided >80% sensitivity (but low specificity ~40%) for achieving meaningful improvement in asthma symptoms
  • Reached by 50% of children receiving 75 mg/kg dose
  • Reached by 40% of children receiving 50 mg/kg dose

Safety outcomes:

  • Hypotension was uncommon.
    • Hypotension was observed in only 2 kids (out of 31) receiving magnesium and 2 kids (out of 18) in the placebo group.
    • None had poor perfusion.
    • None received any specific treatment for the hypotension beyond a single fluid bolus.
  • No relationship was found between magnesium concentration and blood pressure changes.
  • Both doses (50 and 75 mg/kg) appeared safe based on blood pressure monitoring.

Caution

This was a pilot study with a relatively small sample size (49 children), so findings need validation in larger trials.

Take home messages

  1. This study suggests, for the first time, a specific serum magnesium exposure target (total serum magnesium AUC0-2h >63.1 mg·h/L) that correlates with clinical improvement in moderate-severe pediatric asthma exacerbations.No significant drop in blood pressure was observed with either magnesium dose – Both 50 and 75 mg/kg were well-tolerated in the ED setting. More research is warranted to understand the best dose. We have a pharmacokinetics model for future research.

Why is this important for patients and caregivers

  • Previous research never found what dose of intravenous magnesium is most effective. This study helps physicians and pharmacists start to understand what that dose should be.
  • Magnesium is commonly used in asthma exacerbations but some providers worry that it can cause hypotension. We need more studies to understand its safety and this small study proves we can safely study magnesium in a larger trial.

References

  1. Johnson MD, Shihabuddin BS, Barney BJ, et al.; IMPACT‐ED Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN). Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department (IMPACT-ED), a pilot randomized trial. Acad Emerg Med. 2025 Mar 17. doi: 10.1111/acem.70006. Epub ahead of print. PMID 40095736
  2. Rower JE, Johnson MD, Zorc JJ, et al. Pharmacokinetics and Pharmacodynamics of Intravenous Magnesium Sulfate in Pediatric Acute Asthma Exacerbations. J Clin Pharmacol. Published online January 7, 2025. doi:10.1002/jcph.6179. PMID 39775569

Julia Magaña, MD

Julia Magaña, MD

University of California, Davis

Michael Johnson, MD MS

Michael Johnson, MD MS

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University of Utah

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