From the Guidelines
Metoprolol overdose can be effectively reversed with glucagon, which is the recommended treatment according to the most recent guidelines 1. The recommended dose is 1-5 mg IV glucagon given as a bolus, followed by an infusion of 1-5 mg/hour if needed. This approach is particularly useful when managing severe bradycardia or hypotension caused by metoprolol overdose or adverse reactions. In addition to glucagon, supportive measures should include:
- Intravenous fluids for hypotension
- Atropine (0.5-1 mg IV) for bradycardia
- Possibly vasopressors like norepinephrine or epinephrine for persistent hypotension Cardiac monitoring is essential throughout the reversal process. Glucagon works by activating adenylyl cyclase through a non-beta receptor pathway, increasing intracellular cAMP levels and restoring cardiac function independently of the blocked beta receptors. This mechanism makes it effective even when beta receptors are occupied by metoprolol. For less severe cases, simply discontinuing metoprolol and monitoring the patient may be sufficient, as the drug's half-life is approximately 3-7 hours. It's worth noting that other treatments such as high-dose insulin, lipid emulsion, and extracorporeal life support may be considered in refractory cases, but the evidence for these treatments is not as strong as it is for glucagon 1. The most recent guidelines from the American Heart Association recommend glucagon as the first-line treatment for beta-blocker overdose, including metoprolol 1.
From the FDA Drug Label
OVERDOSAGE ... There is no specific antidote ... Clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care. ... In shock resulting from inadequate cardiac contractility, consider administration of dobutamine, isoproterenol or glucagon.
Metoprolol reversal is not directly supported by a specific antidote. Management of overdose is primarily symptomatic. In cases of shock due to inadequate cardiac contractility, medications like dobutamine, isoproterenol, or glucagon may be considered 2.
From the Research
Metoprolol Reversal
- Metoprolol is a moderately lipophilic β-blocker that can cause direct myocardial depression leading to bradycardia, hypotension, and cardiovascular collapse in overdose 3
- Treatment of metoprolol overdose includes intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) therapies, which have been shown to be effective in reversing the toxic effects of metoprolol 3
- The use of ILE and HIE therapies in the treatment of β-blocker overdose is increasing, and clinicians should be aware of their dosing strategies and indications 3
Mechanism of Action
- Metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used in the treatment of heart failure (HF) and atrial fibrillation (AF) 4
- The precise mechanisms of action of metoprolol in these diseases remain largely uncertain, but it has been shown to be effective in reducing mortality and morbidity in HF and AF 4
Treatment Guidelines
- There are no clear treatment guidelines available for β-blocker overdose, and the response to toxic concentrations is highly variable 3
- Guidelines on how to best switch to a different β-blocker are also lacking, but a practical approach to switching between commonly prescribed β-blockers has been proposed 5
Clinical Evidence
- Studies have shown that metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF 4
- Metoprolol CR has also been shown to be effective in maintaining sinus rhythm after cardioversion of atrial fibrillation 6
- The use of metoprolol in combination with repeated cardioversion has been shown to increase the proportion of patients in sinus rhythm during six months of follow-up 6