Beta blocker poisoning
- Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT
Fermin Barrueto, Jr, MD, FACEP, FAAEM, FACMT
- Clinical Associate Professor
- University of Maryland School of Medicine
- Section Editor
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Emergency Medicine (Adult and Pediatric)
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
Beta adrenergic antagonists (beta blockers) have been in clinical use for more than 30 years, and are employed in the management of a range of disorders, including hypertension, ischemic heart disease, heart failure, arrhythmias, migraine headache, tremor, portal hypertension, and aortic dissection. Although safe for most patients when taken as prescribed, beta blocker toxicity is associated with significant morbidity and mortality. In 2006, there were 9041 single beta blocker exposures reported to poison centers in the United States. Of these, there were 613 moderate or major adverse outcomes and four deaths .
Complications following beta blocker overdose are related to excessive beta adrenergic blockade, and occasionally the proarrhythmic (membrane-stabilizing) activity of these agents on cardiac conduction . Ingestion of other cardioactive agents in association with beta blockers increases mortality following overdose [2,3]. Common and potentially dangerous coingestions include calcium channel blockers, cyclic antidepressants, and neuroleptics .
An overview of beta blocker intoxication will be presented here. A summary table to facilitate emergent management is provided (table 1). A general approach to an adult patient with possible drug intoxication, and an overview of adverse effects of beta blockade, are discussed separately. (See "General approach to drug poisoning in adults" and "Major side effects of beta blockers".)
Receptor types and general mechanism — There are at least three distinct types of beta receptors:
●Beta 1, which are found primarily in heart muscle. Activation of these receptors results in an increase in heart rate, contractility, atrioventricular (AV) conduction, and a decrease in AV node refractoriness.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila) 2007; 45:815.
- Love JN, Howell JM, Litovitz TL, Klein-Schwartz W. Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity. J Toxicol Clin Toxicol 2000; 38:275.
- Vucinić S, Joksović D, Jovanović D, et al. Factors influencing the degree and outcome of acute beta-blockers poisoning. Vojnosanit Pregl 2000; 57:619.
- Taboulet P, Cariou A, Berdeaux A, Bismuth C. Pathophysiology and management of self-poisoning with beta-blockers. J Toxicol Clin Toxicol 1993; 31:531.
- Samuels TL, Uncles DR, Willers JW, et al. Logging the potential for intravenous lipid emulsion in propranolol and other lipophilic drug overdoses. Anaesthesia 2011; 66:221.
- Love JN. Acebutolol overdose resulting in fatalities. J Emerg Med 2000; 18:341.
- Link MS, Foote CB, Sloan SB, et al. Torsade de pointes and prolonged QT interval from surreptitious use of sotalol: use of drug levels in diagnosis. Chest 1997; 112:556.
- Vlahovic-Palcevski V, Milic S, Hauser G, et al. Toxic epidermal necrolysis associated with carvedilol treatment. Int J Clin Pharmacol Ther 2010; 48:549.
- Reith DM, Dawson AH, Epid D, et al. Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol 1996; 34:273.
- Neuvonen PJ, Elonen E, Vuorenmaa T, Laakso M. Prolonged Q-T interval and severe tachyarrhythmias, common features of sotalol intoxication. Eur J Clin Pharmacol 1981; 20:85.
- Love JN, Litovitz TL, Howell JM, Clancy C. Characterization of fatal beta blocker ingestion: a review of the American Association of Poison Control Centers data from 1985 to 1995. J Toxicol Clin Toxicol 1997; 35:353.
- Lifshitz M, Zucker N, Zalzstein E. Acute dilated cardiomyopathy and central nervous system toxicity following propranolol intoxication. Pediatr Emerg Care 1999; 15:262.
- Mégarbane B, Deye N, Malissin I, Baud FJ. Usefulness of the serum lactate concentration for predicting mortality in acute beta-blocker poisoning. Clin Toxicol (Phila) 2010; 48:974.
- Love JN, Enlow B, Howell JM, et al. Electrocardiographic changes associated with beta-blocker toxicity. Ann Emerg Med 2002; 40:603.
- Rennyson SL, Littmann L. Brugada-pattern electrocardiogram in propranolol intoxication. Am J Emerg Med 2010; 28:256.e7.
- Soni N, Baines D, Pearson IY. Cardiovascular collapse and propranolol overdose. Med J Aust 1983; 2:629.
- Hofer CA, Smith JK, Tenholder MF. Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options. Am J Med 1993; 95:431.
- Ashraf M, Chaudhary K, Nelson J, Thompson W. Massive overdose of sustained-release verapamil: a case report and review of literature. Am J Med Sci 1995; 310:258.
- Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol 2003; 41:595.
- Boyd R, Ghosh A. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose. Emerg Med J 2003; 20:266.
- Lee J. Glucagon use in symptomatic beta blocker overdose. Emerg Med J 2004; 21:755.
- Holger JS, Engebretsen KM, Obetz CL, et al. A comparison of vasopressin and glucagon in beta-blocker induced toxicity. Clin Toxicol (Phila) 2006; 44:45.
- Love JN, Hanfling D, Howell JM. Hemodynamic effects of calcium chloride in a canine model of acute propranolol intoxication. Ann Emerg Med 1996; 28:1.
- Sakurai H, Kei M, Matsubara K, et al. Cardiogenic shock triggered by verapamil and atenolol: a case report of therapeutic experience with intravenous calcium. Jpn Circ J 2000; 64:893.
- Sim MT, Stevenson FT. A fatal case of iatrogenic hypercalcemia after calcium channel blocker overdose. J Med Toxicol 2008; 4:25.
- Kerns W 2nd, Schroeder D, Williams C, et al. Insulin improves survival in a canine model of acute beta-blocker toxicity. Ann Emerg Med 1997; 29:748.
- Holger JS, Engebretsen KM, Fritzlar SJ, et al. Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity. Clin Toxicol (Phila) 2007; 45:396.
- Pertoldi F, D'Orlando L, Mercante WP. Electromechanical dissociation 48 hours after atenolol overdose: usefulness of calcium chloride. Ann Emerg Med 1998; 31:777.
- Avery GJ 2nd, Spotnitz HM, Rose EA, et al. Pharmacologic antagonism of beta-adrenergic blockade in dogs. I. Hemodynamic effects of isoproterenol, dopamine, and epinephrine in acute propranolol administration. J Thorac Cardiovasc Surg 1979; 77:267.
- Burns MJ, Linden CH. Insulin for beta-blocker toxicity. Ann Emerg Med 1997; 30:711.
- Page C, Hacket LP, Isbister GK. The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: a case report. J Med Toxicol 2009; 5:139.
- Lyden AE, Cooper C, Park E. Beta-Blocker Overdose Treated with Extended Duration High Dose Insulin Therapy. J Pharmacol ClinToxicol 2014; 2:1015. http://www.jscimedcentral.com/Pharmacology/pharmacology-2-1015.pdf (Accessed on June 16, 2014).
- Cole JB, Stellpflug SJ, Ellsworth H, et al. A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock. Clin Toxicol (Phila) 2013; 51:201.
- Jovic-Stosic J, Gligic B, Putic V, et al. Severe propranolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: a case report. Clin Toxicol (Phila) 2011; 49:426.
- Stellpflug SJ, Harris CR, Engebretsen KM, et al. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Clin Toxicol (Phila) 2010; 48:227.
- Doepker B, Healy W, Cortez E, Adkins EJ. High-dose insulin and intravenous lipid emulsion therapy for cardiogenic shock induced by intentional calcium-channel blocker and Beta-blocker overdose: a case series. J Emerg Med 2014; 46:486.
- Donovan KD, Gerace RV, Dreyer JF. Acebutolol-induced ventricular tachycardia reversed with sodium bicarbonate. J Toxicol Clin Toxicol 1999; 37:481.
- Shanker UR, Webb J, Kotze A. Sodium bicarbonate to treat massive beta blocker overdose. Emerg Med J 2003; 20:393.
- Snook CP, Sigvaldason K, Kristinsson J. Severe atenolol and diltiazem overdose. J Toxicol Clin Toxicol 2000; 38:661.
- Hurwitz MD, Kallenbach JM, Pincus PS. Massive propranolol overdose. Am J Med 1986; 81:1118.
- Kulling P, Eleborg L, Persson H. Beta-adrenoceptor blocker intoxication: epidemiological data. Prenalterol as an alternative in the treatment of cardiac dysfunction. Hum Toxicol 1983; 2:175.
- Lane AS, Woodward AC, Goldman MR. Massive propranolol overdose poorly responsive to pharmacologic therapy: use of the intra-aortic balloon pump. Ann Emerg Med 1987; 16:1381.
- Frierson J, Bailly D, Shultz T, et al. Refractory cardiogenic shock and complete heart block after unsuspected verapamil-SR and atenolol overdose. Clin Cardiol 1991; 14:933.
- DeLima LG, Kharasch ED, Butler S. Successful pharmacologic treatment of massive atenolol overdose: sequential hemodynamics and plasma atenolol concentrations. Anesthesiology 1995; 83:204.
- Love JN, Howell JM, Klein-Schwartz W, Litovitz TL. Lack of toxicity from pediatric beta-blocker exposures. Hum Exp Toxicol 2006; 25:341.
- Belson MG, Sullivan K, Geller RJ. Beta-adrenergic antagonist exposures in children. Vet Hum Toxicol 2001; 43:361.
- Love JN, Sikka N. Are 1-2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med 2004; 26:309.
- Wax PM, Erdman AR, Chyka PA, et al. beta-blocker ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005; 43:131.
- Receptor types and general mechanism
- CELLULAR TOXICOLOGY
- TOXICITY OF SPECIFIC AGENTS
- CLINICAL FEATURES OF OVERDOSE
- Physical findings
- LABORATORY EVALUATION
- Laboratory studies
- DIFFERENTIAL DIAGNOSIS
- Acute stabilization and overview of therapy
- Approach to the selection of specific therapies
- - Severely symptomatic patients
- - Mildly symptomatic patients
- - Asymptomatic patients
- Specific therapies
- - Glucagon
- - Calcium
- - Vasopressor (catecholamine)
- - Insulin and glucose
- - Lipid emulsion therapy
- - Gastrointestinal (GI) decontamination
- - Other therapies
- Pediatric considerations
- ADDITIONAL RESOURCES
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS