What is the initial management of a patient with propranolol overdose who presents with symptomatic bradycardia?

Management of Propranolol Overdose with Bradycardia

Glucagon 50-150 mcg/kg IV bolus followed by continuous infusion at 1-5 mg/hour is the first-line antidote for propranolol-induced bradycardia and hypotension, as it bypasses beta-receptor blockade to exert direct inotropic and chronotropic effects. 1

Immediate Assessment and Stabilization

• Assess for signs of hemodynamic compromise including altered mental status, hypotension (systolic BP <80-90 mmHg), acute heart failure, or shock—these indicate life-threatening toxicity requiring immediate intervention. 2
• Maintain airway patency and assist ventilation if needed, provide supplemental oxygen if hypoxemic, establish cardiac monitoring, obtain IV access, and perform 12-lead ECG. 2
• If ingestion was recent (within 1-2 hours), perform gastric lavage taking care to prevent pulmonary aspiration, followed by activated charcoal administration. 1, 3

First-Line Antidote: Glucagon

• Administer glucagon 50-150 mcg/kg (typically 3-10 mg) as IV bolus over 1-2 minutes, as this is the FDA-recommended first-line treatment for propranolol overdose with superior efficacy compared to atropine or catecholamines. 1
• Follow the bolus immediately with continuous glucagon infusion at 1-5 mg/hour, titrating to achieve adequate heart rate (target ≥60 bpm) and blood pressure (systolic ≥90 mmHg). 1
• Glucagon works by activating adenylyl cyclase independent of beta-receptors, producing positive inotropic and chronotropic effects even when beta-receptors are completely blocked. 1, 4
• Monitor for glucagon-induced nausea and vomiting; have suction readily available to prevent aspiration. 4

Second-Line Pharmacologic Interventions

If Bradycardia Persists Despite Glucagon

• Atropine 0.5-1 mg IV may be attempted (repeat every 3-5 minutes up to maximum 3 mg total), though it is often ineffective in propranolol overdose because the bradycardia results from direct myocardial depression rather than vagal tone. 1, 2
• Isoproterenol infusion 2-10 mcg/min can be used for refractory bradycardia, as it provides direct beta-agonist effects that may partially overcome receptor blockade at high doses. 1
• Transcutaneous pacing should be initiated immediately if pharmacologic measures fail to restore adequate heart rate in hemodynamically unstable patients, serving as a bridge to transvenous pacing if needed. 2

If Hypotension Persists Despite Glucagon

• Dopamine 5-20 mcg/kg/min IV infusion provides both inotropic and vasopressor effects, though response may be blunted due to beta-receptor blockade. 1, 3
• Avoid epinephrine as it may provoke uncontrolled hypertension due to unopposed alpha-adrenergic stimulation when beta-receptors are blocked. 1
• Norepinephrine 0.1-0.5 mcg/kg/min may be more effective than dopamine for severe hypotension, providing alpha-mediated vasoconstriction. 3

Advanced Rescue Therapies for Refractory Shock

High-Dose Insulin Euglycemia (HIE) Therapy

• Initiate insulin infusion at 1 unit/kg/hour IV with concurrent dextrose 0.5 g/kg/hour (typically D50W at 25-50 mL/hour) to maintain euglycemia (glucose 100-200 mg/dL) in patients with cardiogenic shock unresponsive to glucagon and vasopressors. 3
• Insulin enhances myocardial contractility by improving calcium handling and myocardial glucose uptake, independent of beta-receptors. 3
• Monitor blood glucose every 15-30 minutes initially, then hourly once stable; monitor potassium every 2 hours and replace aggressively (target K+ 4-5 mEq/L). 3
• Continue HIE therapy for 24-48 hours or until hemodynamic stability is achieved and propranolol levels decline. 3

Intravenous Lipid Emulsion (ILE) Therapy

• Administer 20% lipid emulsion 1.5 mL/kg IV bolus over 1 minute (typically 100 mL for 70 kg patient) for cardiac arrest or severe refractory shock despite glucagon and HIE. 3
• Follow with continuous infusion at 0.25 mL/kg/min (approximately 400 mL over 30-60 minutes), and repeat bolus after 5 minutes if cardiac arrest persists. 3
• Lipid emulsion creates an intravascular "lipid sink" that sequesters lipophilic propranolol, reducing free drug concentration at cardiac tissue. 3
• Maximum recommended dose is 10 mL/kg over the first 30 minutes; monitor for lipemia and pancreatitis. 3

Mechanical Circulatory Support

• Intra-aortic balloon pump (IABP) or veno-arterial extracorporeal membrane oxygenation (VA-ECMO) should be considered for refractory cardiogenic shock or cardiac arrest requiring prolonged CPR (>30-60 minutes) despite maximal pharmacologic therapy. 5, 6
• IABP provides hemodynamic support by augmenting diastolic blood pressure and reducing afterload, serving as a bridge to recovery as propranolol is metabolized. 5
• VA-ECMO via femoral vein-femoral artery cannulation provides complete cardiopulmonary support and has successfully rescued patients with massive propranolol overdose unresponsive to all other measures. 6

Management of Specific Complications

Seizures

• Administer benzodiazepines (lorazepam 2-4 mg IV or diazepam 5-10 mg IV) as first-line treatment for propranolol-induced seizures, which result from CNS toxicity due to propranolol's high lipophilicity. 7
• Seizures indicate severe toxicity and are associated with poor prognosis, particularly when combined with cardiac arrest. 7

Bronchospasm

• Treat with isoproterenol or aminophylline rather than standard beta-agonist bronchodilators, which will be ineffective due to beta-receptor blockade. 1
• Aminophylline 6 mg/kg IV over 20-30 minutes provides bronchodilation through phosphodiesterase inhibition. 2

Monitoring and Disposition

• Continuously monitor ECG, blood pressure, oxygen saturation, and neurological status throughout treatment. 1
• Measure serum propranolol levels if available, though management is guided by clinical response rather than specific levels. 3
• All patients with propranolol overdose require ICU admission for continuous cardiac monitoring and potential need for advanced interventions. 2
• Propranolol has a half-life of 3-6 hours, but clinical effects may persist 12-24 hours or longer in massive overdose; continue supportive care and monitoring until complete resolution. 7

Critical Pitfalls to Avoid

• Do not delay glucagon administration while attempting atropine or standard vasopressors—glucagon is the specific antidote and should be given immediately. 1, 4
• Do not use epinephrine for hypotension as it may cause severe hypertension due to unopposed alpha effects. 1
• Do not assume neurological findings (including unreactive pupils) indicate irreversible brain injury—these may be drug effects and can completely resolve with supportive care. 6
• Time from ingestion to treatment is the most critical prognostic factor—patients presenting within 1-2 hours have significantly better outcomes than those with delayed presentation. 7
• Cardiac arrest within the first hour post-ingestion indicates massive overdose (typically >4-8 grams) and requires immediate aggressive intervention including consideration of mechanical circulatory support. 5, 7