Overdose on metoprolol
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Metoprolol Overdose: Clinical Manifestations, Toxicology, and Treatment
Introduction to Metoprolol Overdose
Metoprolol, a beta-1 adrenergic blocking agent, is commonly prescribed for conditions such as hypertension, heart failure, and arrhythmias. However, overdose of this medication can lead to severe and potentially fatal outcomes. This article synthesizes findings from multiple case reports and studies to provide a comprehensive overview of the clinical manifestations, toxicological findings, and treatment strategies for metoprolol overdose.
Clinical Manifestations of Metoprolol Overdose
Cardiovascular Effects: Bradycardia and Hypotension
One of the primary effects of metoprolol overdose is significant cardiovascular depression, leading to bradycardia (slow heart rate) and hypotension (low blood pressure). These symptoms can rapidly progress to cardiovascular collapse if not promptly managed . In severe cases, patients may develop cardiogenic shock, as illustrated in a pediatric case where a 14-year-old girl ingested a large dose of metoprolol and propafenone, leading to cardiac arrest and eventual death despite aggressive treatment.
Sudden Clinical Deterioration
Patients who overdose on metoprolol may experience sudden and rapid clinical deterioration. This necessitates close and careful monitoring, as the condition can worsen quickly, leading to life-threatening complications.
Neuropsychiatric Effects
Although less common, neuropsychiatric adverse reactions such as acute delirium and psychosis can occur in both young and elderly patients following metoprolol overdose. These symptoms typically resolve once the drug is discontinued.
Toxicological Findings in Metoprolol Overdose
Blood and Tissue Concentrations
Toxicological analysis of metoprolol overdose cases reveals varying concentrations of the drug in different body fluids and tissues. For instance, one fatal case reported metoprolol levels of 19.8 mg/L in blood, 83.1 mg/L in bile, 1.6 mg/L in urine, and 15.1 mg/L in vitreous humor. Another case documented levels of 4.7 mg/L in blood, 194 mg/L in urine, and 254 mg/L in bile. These findings highlight the importance of comprehensive toxicological screening in suspected overdose cases.
Metabolism and Elimination
In cases of overdose, the metabolism and elimination of metoprolol can be significantly impaired. For example, a pediatric patient exhibited a prolonged elimination half-life of 13.2 hours and a 70% decrease in clearance, indicative of a poor metabolizer phenotype.
Treatment Strategies for Metoprolol Overdose
Initial Management: Gastric Lavage and Antidote Therapy
Initial management of metoprolol overdose often includes gastric lavage to remove unabsorbed drug from the stomach, followed by administration of antidotes such as glucagon. Glucagon is traditionally considered a first-line antidote for beta-blocker overdose due to its ability to increase heart rate and blood pressure.
Advanced Therapies: Intravenous Lipid Emulsion and Hyperinsulinemia/Euglycemia
In cases where initial treatments are ineffective, advanced therapies such as intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) have shown promise. These therapies can help stabilize patients by improving myocardial function and reversing cardiovascular depression. For instance, a 59-year-old man who ingested a massive dose of metoprolol was successfully treated with ILE and HIE, leading to a return of spontaneous circulation and eventual recovery.
Extracorporeal Membrane Oxygenation (ECMO)
In extreme cases of refractory shock, extracorporeal membrane oxygenation (ECMO) may be required to provide circulatory support. This was demonstrated in a case where a patient ingested 7500 mg of metoprolol and required ECMO after failing to respond to conventional treatments.
Conclusion
Metoprolol overdose is a serious medical condition that can lead to severe cardiovascular and neuropsychiatric effects. Prompt recognition and aggressive management are crucial to improving patient outcomes. While initial treatments include gastric lavage and glucagon administration, advanced therapies such as ILE, HIE, and ECMO may be necessary in severe cases. Clinicians should be aware of the variable response to treatment and the importance of close monitoring in these patients.
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