Use of inhaled/nebulised ipratropium bromide in addition to standard first-line treatment with inhaled/nebulised short-acting beta 2-agonist and systemic steroid in the management of acute asthma exacerbations: a systematic review and meta-analysis of randomised controlled trials

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Abstract
Background: The role of inhaled/nebulised ipratropium bromide (IB) in asthma is unclear. Aims: To assess the efficacy and safety of inhaled/nebulised IB for asthma management in children. Methods: We searched MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials and the Web of Science until July 2024. We included randomised controlled trials (RCTs) and followed international guidelines for reporting systematic reviews. Outcomes included morbidity, escalation of care, length of hospital stay, mortality, adverse events and lung function. Results: We included 24 studies (total participants n=3238). The hospitalisation rate (risk ratio (RR) 0.84, 95% CI 0.70 to 1.00, I ² 30%), hospital stay in hours (MD 1.75, 95% CI −0.87 to 4.36, I ² 15%) and paediatric intensive care (PICU) admission (RR 0.91, 95% CI 0.35 to 2.32, I ² 0%) were similar. The hospitalisation rate was lower in patients who received IB nebuliser (RR 0.76, 95% CI 0.64 to 0.90, I ² 0%). The asthma severity score was significantly better in the IB group (MD −0.38, 95% CI −0.63 to −0.12, I 2 59%). No serious adverse events were reported. Conclusion: This review found high-certainty evidence that the IB nebuliser leads to a lower hospitalisation rate. However, when inhaled/nebulised IBs were analysed together, the hospitalisation rate was similar, with moderate certainty evidence. IB improved asthma clinical scores, with low certainty evidence. No difference was reported in other prespecified outcomes. Considering the current evidence and safety profile, inhaled/nebulised IB needs to be considered as an additional treatment for acute asthma exacerbation. PROSPERO registration number: CRD42023405023.

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