Beta-adrenergic-blocking agents are widely used for the treatment of hypertension, arrhythmias, angina pectoris, heart failure, migraine headaches, and glaucoma. Beta-blocker poisoning is a common cause of drug-induced cardiogenic shock in the United States. Many patients with beta-blocker overdose will have underlying cardiovascular diseases or will be taking other cardioactive medications, both of which may aggravate beta-blocker overdose. Of particular concern are combined ingestions with calcium blockers or tricyclic antidepressants. A variety of beta blockers are available, with various pharmacologic effects and clinical uses (Table II-15).

Excessive beta-adrenergic blockade is common to overdose with all drugs in this category. All beta blockers antagonize beta₁ adrenoreceptors, decreasing heart rate and cardiac contractility. Some nonselective beta blockers also antagonize beta₂ receptors, which can result in bronchoconstriction, hypoglycemia, and hyperkalemia. Although beta receptor specificity is seen at low doses, it is lost in overdose.

1. Propranolol, acebutolol, and other agents with membrane-depressant (quinidine-like) effects further depress myocardial contractility and conduction and may be associated with ventricular tachyarrhythmias. Propranolol is also lipid soluble, which enhances brain penetration and can cause seizures and coma.
2. Pindolol, acebutolol, and penbutolol, agents with partial beta agonist activity, may cause tachycardia and hypertension.
3. Sotalol, which also has type III antiarrhythmic activity, prolongs the QT interval in a dose-dependent manner and may cause torsade de pointes and ventricular fibrillation.
4. Labetalol and carvedilol have combined nonselective beta- and alpha-adrenergic-blocking actions, and nebivolol is a selective beta₁ antagonist with vasodilating properties not mediated by alpha blockade. With these drugs, direct vasodilation can contribute to hypotension in overdose.
5. Pharmacokinetics. Peak absorption occurs within 1-4 hours but may be much longer with sustained-release preparations. Volumes of distribution are generally large. Elimination of most agents is by hepatic metabolism, although nadolol, atenolol, and carteolol are excreted unchanged in the urine and esmolol is rapidly inactivated by red blood cell esterases (see also Table II-63).

The response to beta-blocker overdose is highly variable, depending on underlying medical disease or other medications. Susceptible patients may have severe or even fatal reactions to therapeutic doses. There are no clear guidelines, but ingestion of only 2-3 times the therapeutic dose (see Table II-15) should be considered potentially life-threatening in all patients.

The pharmacokinetics of beta blockers varies considerably, and duration of poisoning may range from minutes to days.

1. Cardiac disturbances, including first-degree heart block, hypotension, and bradycardia, are the most common manifestations of poisoning. High-degree atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs such as propranolol. The ECG usually shows a normal QRS duration with increased PR intervals, but QRS widening can occur with membrane-depressant beta blocker intoxication. QT prolongation and torsade de pointes can occur with sotalol.
2. Central nervous system toxicity, including convulsions, coma, and respiratory arrest, is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs.
3. Bronchospasm is most common in patients ingesting nonselective beta blockers and with pre-existing asthma or chronic bronchospastic disease.
4. Hypoglycemia and hyperkalemia may sometimes occur.

Is based on the history of ingestion, accompanied by bradycardia and hypotension. Other drugs that may cause a similar presentation after overdose include sympatholytic and antihypertensive drugs, digitalis, and calcium channel blockers.

1. Specific levels. Measurement of beta-blocker serum levels may confirm the diagnosis but does not contribute to emergency management and is not routinely available. Metoprolol, labetalol, and propranolol may be detected in comprehensive urine toxicology screening.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, arterial blood gases, and 12-lead ECG and ECG monitoring.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat coma, seizures, hypotension, hyperkalemia, and hypoglycemia (p 37) if they occur.
   3. Glucagon (see B.1. below) is the first-line treatment of bradycardia. Atropine, 0.01-0.03 mg/kg IV, may be ineffective as beta blocker-associated bradycardia is not due to increased vagal tone. Isoproterenol (see p 544) is often ineffective because of beta blockade. Cardiac pacing may also be tried.
   4. Treat bronchospasm with nebulized bronchodilators.
   5. Continuously monitor the vital signs and ECG for at least 6 hours after ingestion.
2. Specific drugs and antidotes
   1. Give glucagon 5-10 mg IV (children 0.05-0.15 mg/kg) over 1-2 minutes for bradycardia resistant to basic supportive measures and repeat as needed. Start an infusion at the dose at which hemodynamics improve (see Glucagon).
   2. Administer calcium chloride 10%, 10 mL (0.1-0.2 mL/kg) IV, or calcium gluconate 10%, 20-30 mL (0.3-0.4 mL/kg) IV, and repeat every 5-10 minutes as needed. Calcium may reverse beta blocker-associated depression of cardiac contractility but does not affect sinus node depression or peripheral vasodilation, and has variable effects on AV nodal conduction.
   3. High-dose insulin euglycemic therapy (HIET) has shown benefit and relative safety in case reports and case series (see Insulin). Potential complications include hypoglycemia and hypokalemia, requiring close monitoring.
   4. Give sodium bicarbonate, 1-2 mEq/kg for wide-complex QRS conduction delay and associated hypotension caused by membrane-depressant beta blocker poisoning (eg, propranolol).
   5. Treat significant QT prolongation and polymorphic ventricular tachycardia (torsades de pointe) from sotalol poisoning with magnesium and pharmacologic (isoproterenol) or mechanical overdrive pacing. Correction of hypokalemia is also important.
   6. Vasopressors are often needed to manage shock from beta blocker overdose. Extraordinarily high doses may be required for refractory shock; however, ischemia (eg, limb or bowel) is a potential complication. HIET should be used before high-dose pressors. Epinephrine (IV infusion started at 1-4 mcg/min and titrated to effect) may be useful. Phosphodiesterase inhibitors have also been reported to be beneficial in case reports.
   7. Intravenous lipid emulsion therapy (ILE) may be helpful in overdose of lipophilic beta blockers such as propranolol, but a survival benefit in humans has not been established. ILE may impede ongoing laboratory analysis and can complicate use of certain extracorporeal life support circuits.
   8. Consider mechanical life support including intra-aortic balloon pump, cardiopulmonary bypass, or extracorporeal membrane oxygenation (ECMO) for refractory shock.
3. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Consider whole-bowel irrigation for large ingestions involving sustained-release formulations.
4. Enhanced elimination. Most beta blockers, especially the more toxic drugs such as propranolol, are highly lipophilic and have large volumes of distribution. For those with a relatively small volume of distribution coupled with a long half-life or low intrinsic clearance (eg, acebutolol, atenolol, nadolol, and sotalol), hemodialysis may be effective. Hemodialysis has also been shown to be effective for atenolol intoxication and should be considered especially in the setting of renal impairment.