Effectiveness of treatments for propranolol toxicity: a systematic review of current approaches and evidence

PURPOSE: Propranolol, a non-selective beta-blocker characterized by high lipid solubility, is extensively prescribed for cardiovascular and central nervous system disorders. Nevertheless, it is frequently implicated in intentional overdoses due to its central nervous system penetration and membrane-stabilizing properties, often resulting in life-threatening bradycardia, hypotension, seizures, and cardiac arrest. This systematic review aimed to assess the efficacy of the current medical and mechanical interventions employed in the management of propranolol toxicity. METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, CENTRAL, and Google Scholar for studies published between 1965 and March 18, 2025. Search terms included "propranolol toxicity," "glucagon," "high-dose insulin therapy," "lipid emulsion," "calcium," and "extracorporeal life support." Studies were included if they confirmed propranolol toxicity, evaluated at least one therapeutic intervention, and reported the clinical or hemodynamic outcomes. Expert opinions, narrative reviews, and letters to the editor were excluded from the analysis. RESULTS: A total of 92 studies were included, comprising observational studies, case series, detailed case reports, preclinical animal experiments, and animal control trials. Glucagon emerged as the most frequently utilized pharmacologic agent, followed by high-dose insulin euglycemic therapy (HDIET), intravenous lipid emulsion (ILE), inotropes, and calcium salts. Mechanical interventions such as extracorporeal life support (ECLS), pacing, and hemoperfusion have been reported in severe or refractory cases. The quality of evidence varied, with most studies limited by design heterogeneity, small sample sizes, and a lack of randomized controlled trials. CONCLUSION: Multiple interventions, including glucagon, HDIET, ILE, calcium, and ECLS, have demonstrated benefits in managing propranolol toxicity. However, owing to the low level of evidence and wide variability in patient presentations and treatment protocols, no single therapy exhibits universal efficacy. Individualized multimodal treatment remains essential, and high-quality clinical studies are necessary to establish standardized evidence-based protocols.