From the Guidelines
Glucagon is the most effective drug to increase heart rate in a patient with propranolol overdose presenting with sinus bradycardia and syncope. The recommended dose is 3-10 mg IV with infusion of 3-5 mg/h, as suggested by the 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay 1. Glucagon works by activating adenylyl cyclase through a G-protein coupled receptor pathway, which increases intracellular cyclic AMP (cAMP) levels - the same second messenger system activated by beta-adrenergic receptors. This mechanism allows glucagon to bypass the beta-receptor blockade caused by propranolol, effectively increasing heart rate and cardiac contractility. Some key points to consider when administering glucagon include:
- Monitoring for potential side effects such as nausea, vomiting, and hyperglycemia
- Continuous cardiac monitoring, blood pressure measurements, and blood glucose checks during treatment
- Being aware that other sympathomimetic drugs like epinephrine or dobutamine may be ineffective in beta-blocker overdose due to their dependence on functional beta receptors. It is crucial to prioritize the patient's morbidity, mortality, and quality of life when making treatment decisions, and glucagon has been shown to be effective in this context 1.
From the FDA Drug Label
Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a propranolol overdose Glucagon should be administered as 50 mcg/kg to 150 mcg/kg intravenously followed by continuous drip of 1 mg/hour to 5 mg/hour for positive chronotropic effect.
The most effective drug to increase heart rate in a patient with propranolol overdose, sinus bradycardia, and syncope, by stimulating the same second messenger system activated by beta (β)-adrenergic receptors, is glucagon. Glucagon stimulates the same second messenger system as ß-adrenergic receptors, increasing heart rate and contractility. It should be administered as 50 mcg/kg to 150 mcg/kg intravenously, followed by a continuous drip of 1 mg/hour to 5 mg/hour for a positive chronotropic effect 2.
From the Research
Treatment Options for Propranolol Overdose
To increase heart rate in a patient with propranolol overdose, sinus bradycardia, and syncope, by stimulating the same second messenger system activated by beta (β)-adrenergic receptors, the following drugs can be considered:
- Glucagon: It increases heart rate and myocardial contractility, and improves atrioventricular conduction, bypassing the beta-adrenergic receptor site 3, 4, 5.
- Aminophylline: It increases cyclic AMP, reversing the otherwise lethal effects of a propranolol overdose in dogs 6.
- Amrinone: It also increases cyclic AMP, but the recovery of heart rate and systemic arterial blood pressure is slower compared to aminophylline 6.
- Forskolin: It increases cyclic AMP, but the recovery of heart rate and systemic arterial blood pressure is slower compared to aminophylline 6.
Mechanism of Action
These drugs stimulate the same second messenger system activated by beta (β)-adrenergic receptors by increasing cyclic AMP, which leads to an increase in heart rate and myocardial contractility.
Clinical Evidence
Studies have shown that glucagon is effective in reversing the cardiovascular depression caused by beta-blocker overdose, including propranolol 3, 4, 5. Aminophylline, amrinone, and forskolin have also been shown to be effective in increasing heart rate and systemic arterial blood pressure in dogs with propranolol overdose 6.
Dosage and Administration
The dosage and administration of these drugs vary, with glucagon typically given as a 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response 3. Aminophylline, amrinone, and forskolin dosages are also variable, but have been shown to be effective in increasing heart rate and systemic arterial blood pressure in dogs with propranolol overdose 6.