So bored…my heart stopped beating: Beta Blocker Toxicity

A 54-year-old female with past medical history of HTN, CAD s/p two stents in 2013, and atrial fibrillation is brought in by EMS into the resuscitation bay. You notice she appears tired and weak but appears alert and mentating well. She reports an episode of syncope, and her daughter called EMS, who then noted she had a heart rate of 40 and a blood pressure of 76/55.

You’re helping put her on the monitor and simultaneously, a finger-stick is 125 mg/dL. Her mental status is unchanged, heart rate reads 38/regular, and her BP is 78/54 mm Hg. She is afebrile, not tachypneic, and saturating well on room air. You continue to ask her questions – she has had no trauma, recent travel, chest pain, focal weakness, numbness, tingling, or blurry vision prior to the episode. There are no previous episodes of syncope, seizure, toxic ingestion, and no known blood loss. She felt general weakness since the morning directly prior to her episode of syncope. Her remaining physical exam is unremarkable aside from slightly cold extremities. You quickly start a bolus of IV fluids, order basic labs including cardiac enzymes, and ask for an ECG.

As her daughter obtains her medication list, you do a quick bedside ultrasound. You note no pericardial or pleural effusion, good EF, and no D sign. You find out that she has been taking metoprolol at 200 mg BID. She states she missed a few doses over the last week, so she had been taking 2 pills (400 mg) twice a day for the last 3 days.

Here is the ECG:

1. What do you see on ECG?
  • Sinus Bradycardia with a rate of about 45/min, prolonged PR interval of 240 ms indicative of first degree AV Block


2. What is your differential diagnosis?
  • Beta Blocker Toxicity
  • Calcium Channel Blocker Toxicity
  • Inferior MI
  • Lyme Disease
  • Hypothyroidism
  • Hyperkalemia


3. How does beta blocker toxicity occur?

Beta-adrenergic receptors facilitate calcium entry into cardiac myocytes by activating cyclic AMP, which then facilitates opening of L-type calcium channels. Calcium is essential for cardiac contractility, action potential generation, and various other cellular processes.

Beta blockers act by inhibiting the opening of L-type calcium channels. Calcium channel blockers (CCBs) work in a similar fashion, maintaining the channel in a closed state, and resulting in a similar clinical picture.


4. What are the clinical signs and symptoms?

Beta blockers have both chronotropic (heart rate) and inotropic (contractility) effects. In large or excessive doses, this results in the classic findings of bradycardia and hypotension, conduction abnormalities, and can even lead to cardiogenic shock.(1) In addition, non-selective beta blockers, like propranolol and sotalol, affect B2 receptors as well, which can result in bronchospasm, decreased gluconeogenesis/glycogenolysis and increased lipolysis, leading to hypoglycemia. While B1-selective agents like metoprolol tend not to have these B2 effects at therapeutic doses, they lose their selectivity in excessive doses, resulting in effects similar to non-selective agents.(2)

Given a state of cardiovascular compromise and end organ hypoperfusion, mental status change is also common, and can include delirium, fatigue, or coma. Reports have also included seizures, specifically due to propranolol.(2)


5. How can you differentiate beta blocker vs. CCB toxicity?

Both beta-blockers and CCBs produce a very similar clinical picture. Calcium channel blocker toxicity can also result in hypotension, bradycardia, conduction abnormalities, mental status change, and cardiogenic shock. However, one key difference is that beta blockers generally predispose to hypoglycemia, while CCBs generally predispose to hyperglycemia. Calcium channel blockers inhibit calcium-mediated insulin release by pancreatic beta islet cells. During times of stress, myocytes rely more heavily on carbohydrate metabolism, and while glucose production may be increased, there may not be sufficient insulin to use the glucose produced. This can result in hyperglycemia, acidosis, and insulin deficiency in a state resembling DKA.(2)


For more information on CCB toxicity, check out this case based post on calcium channel antagonist poisoning: Hypotension and Bradycardia in the Poisoned Patient: Calcium Channel Antagonists



6. What should be your initial steps?
  • Initial resuscitation should focus on your ABCs. Patients can present with severely depressed mental status and may need intubation for airway protection.
  • 1-2 L fluid bolus and atropine are appropriate initial resuscitative measures, but may often fail. Patients are often euvolemic, and shock is usually due to direct cardiac toxicity. Thus, further measures should focus on improving bradycardia and myocardial contractility.(3)
  • Toxicity with beta blockers such as propranolol or labetalol can result in sodium channel antagonism, resulting in QRS widening on ECG. Consider sodium bicarbonate, 1-2 mEq/kg bolus for QRS>120 ms.(1,3)
  • Early contact with your poison control center is essential.



7. Is there a role for GI decontamination in beta blocker toxicity?
  • GI decontamination should be considered in all patients presenting within 1-2 hours of ingestion, as long as they are clinically stable and protecting their airway.
  • In beta blockers with sustained release formations, onset of toxicity can be greater than 12 hours after intake. Thus, GI decontamination may be beneficial even after the initial 1-2 hour window.(1)
  • A single dose of activated charcoal can be given for immediate release preparations within 1-2 hours after ingestion, and whole bowel irrigation can be considered for sustained release preparations prior to symptom onset. Once bradycardia and hypotension ensue, reduced GI function and ileus can occur, and whole bowel irrigation should be avoided.(3)


8. Despite atropine and a fluid bolus, your patient is still bradycardic and hypotensive, what can you try next?

  • Glucagon
    • It has both positive chronotropic and inotropic effects on the heart and allows for the production of cAMP needed in the presence of beta blockade
    • Initial dose is at 50-150 micrograms/kg, about 3-10 mg in a 70 kg individual. The effects in heart rate and blood pressure can be seen within minutes but may require repeated boluses. There is no established maximum dose, and a drip may be started based on the effective bolus, as the effect while rapid, is also short lived.(1)
    • Nausea and vomiting are common and dose related. Anti-emetics should be administered concurrently, especially to prevent aspiration. Transient hyperglycemia can also occur and rarely requires intervention.


  • Calcium
    • Can be used for both beta blocker and CCB toxicity, but evidence (although limited) is more substantial for its use in CCB toxicity.(1)
    • Can be given as calcium gluconate or calcium chloride, however calcium chloride contains more mEq of calcium per dose.
    • Large doses of calcium are required for effect to take place
    • Initial dosing can be 0.6 mL/kg bolus of 10% calcium gluconate or 0.2 mL/kg of 10% calcium chloride.(1)
    • If an effect on BP is seen, a drip can be started at 0.6-1.5 mL/kg/hour calcium gluconate or 0.2-0.5 mL/kg/hr calcium chloride.
    • The goal of serum-ionized calcium is two times the normal level.


  • High-Dose Insulin
    • While the exact mechanism of insulin’s action in beta-blocker toxicity is not clear, we know that insulin provides metabolic support to the heart in a state of carbohydrate metabolism during stress/toxicity. It provides metabolic substrate for cardiac cells, and improves function without increasing cardiac work. This is in contrast to glucagon, calcium, or epinephrine, which improve contractility but also increase fatty acid metabolism and increase cardiac workload.(1)
    • While no randomized, controlled trials exist, multiple cases report significant improvements in heart rate and blood pressure with high-dose insulin, following single and multi-drug ingestions of beta blockers and CCBs.(4,5,6)
    • An initial bolus of 1 U/kg can be given along with a 25 g of dextrose (not necessary if blood sugar greater than 400 mg/dL)
    • An insulin drip should then be started at 0.5 U/kg/hr, with a dextrose infusion of 0.5 g/kg/hr, with euglycemia as the goal, defined as blood sugar 100-250, mg/dL; frequent bedside glucose monitoring os required.
    • Use a central line for dextrose administration in order to provide more concentrated solutions and avoid fluid overload.
    • Monitor potassium


  • Catecholamines
    • There is no one proven beta adrenergic agonist that is superior to others, and all have been used for beta blocker overdose.
    • However, considering pharmacology, norepinephrine and epinephrine could be considered first-line, as they have both alpha and beta agonist properties and may improve contractility as well as peripheral vascular resistance.(1)


  • Intralipid Emulsion Therapy
    • In theory, intravascular lipids can catch free plasma medications, resulting in lower plasma drug concentration.
    • Some cases have reported a positive response within one hour of administration,(6,7) and therapy may be considered as an adjunct when hypotension is unresponsive to other therapies.(3)
    • Initial dosing can be a loading dose of 1.5 mL/kg of 20% lipid emulsion, followed by a 0.25-0.5mL/kg/min drip.


  • Hemodialysis
    • Most beta blockers are lipophilic, highly protein-bound, mainly undergo hepatic metabolism, and will not be effectively dialyzed.(1)
    • The exceptions are atenolol, nadolol, and sotalol, which are less than 25% protein bound, and undergo renal metabolism. Dialysis can be beneficial in these cases.


  • Cardiac Pacing
    • Transcutaneous or transvenous pacing may be required when further measures fail.
    • Even with transvenous pacing, blood pressure may not improve significantly, as the myocardium lacks intracellular calcium needed to maintain contractility; this is especially true for CCB toxicity. Optimal pacing rate is 50-60/min, lower than usual, in order to give myocytes adequate time to build intracellular calcium during diastole.(1)


  • Extracorporeal Membrane Oxygenation (ECMO) may be considered for refractory cases



7. What is your patient's ultimate disposition?
  • In short, your patient might require more than one agent to achieve hemodynamic stability.
  • Ultimate disposition depends on the patient’s hemodynamic status, however all patients should be admitted for further treatment/observation for at least 24 hours. This should be in a setting with close cardiac monitoring and capacity for quickly treating hemodynamic compromise.


For a case based example of beta blocker toxicity, check out Dr. Kendall’s EM-Critical Care conference presentation:

EM Critical Care: Beta Blocker Toxicity



(1) Kerns, W. Management of B-Adrenergic Blocker and Calcium Channel Antagonist Toxicity. Emerg Med Clinics of North America, 2007;(25), 2:309-33

(2) Weinstein R.S.: Recognition and management of poisoning with beta-adrenergic blocking agents. Ann Emerg Med 1984; 13: 1123-1131

(3) Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. British Journal of Clinical Pharmacology. 2016 Mar; 81(3):453-61.

(4) Greene SL, Gawarammana I, Wood DM, Jones AL, Dargan PI.Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective observational study. Intensive Care Med 2007;33: 2019–24.

(5) St-Onge M, Dubé PA, Gosselin S, Guimont C, Godwin J, Archambault PM, Chauny JM, Frenette AJ, Darveau M, Le sage N, Poitras J, Provencher J, Juurlink DN, Blais R. Treatment for calcium channel blocker poisoning: a systematic review. Clinical Toxicology, 2014; 52: 926–44.

(6) Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with hyperinsulinemic euglycemia therapy and intravenous lipid emulsion. European Journal of Emergency Medicine, 2011; 18: 121–3.

(7) Dolcourt BA, Aaron CK. Intravenous fat emulsion for refractory verapamil and atenolol induced shock: a human case report. (Abstract). Clinical Toxicology 2008; 46: 619–20.



















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