Use of intravenous aminophylline in addition to the standard first-line treatment in children and adolescents with an acute asthma exacerbation: a systematic review and meta-analysis of randomised controlled trials

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Abstract
Importance: The role of intravenous aminophylline in acute asthma in childhood is unclear. Objectives: To assess the safety and efficacy of intravenous aminophylline for asthma in children. Methods: From 1966 to May 2024, we searched MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Central Register of Controlled Trials. We included only randomised controlled trials testing standard treatment in combination with aminophylline and followed the international guidelines for conducting systematic reviews. The outcomes measured were morbidity, escalation of care, length of hospital stay, adverse events, mortality and lung functions. We used the random-effects model for data analysis and the fixed-effects model to evaluate heterogeneity. Results: Nine studies (466 participants) fulfilled our a priori eligibility criteria. No significant difference was found in post-treatment asthma severity score (mean difference (MD)=0.13, 95% CI −0.79 to 1.06, I 2 =0 %), hospitalisation rate (risk ratio (RR)=0.66, 95% CI 0.27 to 1.59, I 2 =0 % ), paediatric intensive care unit admission (RR=0.73, 95% CI 0.51 to 1.05, I 2 =0%), intubation rate (RR=0.09, 95% CI 0.01 to 1.64, p=0.1) or length of hospital stay (MD=−3.62, 95% CI −13.05 to 5.82, I 2 =31%). Emesis (RR=3.52, 95% CI 2.04 to 6.06, I 2 =0%) and nausea (RR=4.92, 95% CI 2.41 to 10.06, I 2 =0%) occurred more in the aminophylline group. One study showed improved lung function in the aminophylline group, while others showed no difference. Conclusion: This review showed limited evidence of the benefit of intravenous aminophylline in managing asthma in most preventilation severity parameters. However, lowering the intubation rate and improving lung function deserve more attention. PROSPERO registration number: CRD42023405234.

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