Intravenous Bronchodilators in Pediatric Critical Asthma: A Systematic Review and Network Meta-Analysis

Abstract

Introduction: Pediatric critical asthma is one of the most common pediatric illnesses in children admitted to the pediatric ward and pediatric intensive care unit (PICU). Adjunct intravenous (IV) bronchodilators are often used when initial management with systemic corticosteroids and inhaled short-acting beta agonists (SABA) fail to provide improvement in a patient's clinical condition. While the recent guidelines gave recommendations for the use of different IV bronchodilators compared to placebo, it did not include ranking on which one should be used as first-line or second-line agent. The aim of this network meta-analysis is to determine the effect of IV bronchodilators on patient-centered outcomes and rank medications based on their effectiveness in these outcomes.

Methods: A systematic review was conducted using three databases MEDLINE, Embase, and CINAHL to identify randomized control trials examining the use of IV magnesium sulfate (MgSO₄), IV methylxanthines (aminophylline or theophylline), IV SABA (salbutamol, terbutaline) in pediatric critical asthma patients. Bayesian network metanalytic framework was used to compare the interventions. Results are reported as odds ratio (OR) or mean difference (MD) and 95% Credible Interval (CrI).

Results: Twelve trials (n = 852) were included in the network meta-analysis. Largest reduction in hospital length of stay (LOS), PICU admission, and PICU LOS were noted with IV MgSO₄; (MD: -3.1 days, 95% CrI: -6.9 days to 0.13 days), (OR 0.21; 95% CrI 0.02, 1.3), and (MD: -4.0 days, 95% CrI: -7.1 days to -1.2 days) respectively. IV MgSO₄ was ranked first in three outcomes of interest with Surface Under the Cumulative Ranking curve (SUCRA) of 0.884 for hospital LOS, 0.919 for PICU admission, and 0.957 for PICU LOS. For preventing intubation, IV SABA was ranked the highest (SUCRA 0.995), but the only study with IV SABA had zero intubation events. In a sensitivity analysis that excluded studies with zero events, the intubation rate was lowest with IV MgSO₄ (OR 0.10; 95% CrI 0.003, 0.88) and it was ranked the best treatment (SUCRA 0.921).

Conclusions: In this network meta-analysis comparing different IV adjunct bronchodilators, IV MgSO₄ was ranked first followed by IV SABA, and then IV methylxanthines. Given these findings and the favorable safety profile, ease of use, and low cost, IV MgSO₄ appears most promising the first adjunct IV bronchodilator, however, further large high-quality trials are still needed before it can be endorsed as routine first-line agent.

Keywords: aminophylline; bronchodilator; children; critical asthma; magnesium sulfate; methylxanthines; network meta‐analysis; salbutamol; status asthmaticus; terbutaline.

FIGURE 1

Cumulative ranks and surface under the cumulative rank curve (SUCRA) for patient‐centered outcomes: (A) hospital length of stay, (B) intubation rate, (C) PICU admission rate, and (D) PICU length of stay. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Radial plot for surface under the cumulative rank curve (SUCRA) for patient‐centered outcomes. The SUCRA for the different interventions is grouped by the outcomes. Each bar is the SUCRA value on a scale of 1–100, representing SUCRA values of 0‐1. [Color figure can be viewed at wileyonlinelibrary.com]