Beta-blocker and calcium channel blocker overdose

Also known as Beta-blocker poisoning · Calcium channel blocker poisoning · CCB overdose · High-dose insulin euglycaemia therapy (HIET)

Beta-blocker (BB) and calcium channel blocker (CCB) overdose are life-threatening poisonings with high mortality (4 of 15 patients died in an Australian CCB series; verapamil or diltiazem doses over 300 mg carry a significant risk of death). Both cause: bradycardia, hypotension, AV block, and (CCBs) hyperglycaemia from inhibited insulin secretion. Pathophysiology: BBs block beta-adrenergic receptors (reduced cAMP → reduced inotropy/chronotropy). CCBs block L-type calcium channels (reduced calcium influx → reduced inotropy, vasodilation, impaired pancreatic insulin release). Management: ABCDE plus specific antidotes added to standard ACLS. Key treatments: (1) IV calcium (chloride or gluconate, repeated as required). (2) High-dose insulin euglycaemia therapy (HIET — insulin 1 U/kg bolus plus 0.5 to 1 U/kg/h infusion, titrated up to 10 U/kg/h, with dextrose to maintain euglycaemia). (3) Vasopressors — noradrenaline and/or adrenaline are consensus first-line. (4) Glucagon (moderate inotropic benefit, mainly in BB overdose). (5) Intravenous lipid emulsion for refractory toxicity. (6) VA-ECMO for refractory shock or arrest.

low19 referencesUpdated 26 July 202623 min readVerification in progress

The one-line answer

Beta-blocker and calcium-channel-blocker overdose produce toxin-induced cardiogenic shock that specific antidotes must be added to standard ACLS to reverse — the problem is receptor or channel blockade, not vagal tone. Both bring bradycardia, hypotension, and AV block; CCB overdose adds hyperglycaemia (calcium-channel blockade inhibits pancreatic insulin secretion), the single bedside discriminator from BB. Escalate early and in order: IV calcium and high-dose insulin euglycaemia therapy (1 U per kg bolus plus 0.5 to 1 U per kg per hour, titrated up to 10 U per kg per hour — first-line consensus therapy alongside noradrenaline and/or adrenaline), glucagon (moderate inotropic benefit, mainly in BB overdose), intravenous lipid emulsion for refractory lipophilic-agent toxicity, and VA-ECMO for refractory shock or cardiac arrest — mobilised early, not as a last gasp. The mantra: calcium, insulin, vasopressors, glucagon, lipid, ECMO — and never rely on atropine alone.

^[15] ^[17] ^[1]

SAQ — Severe verapamil overdose

10 minutes · 10 marks

A 28-year-old woman is brought to ED 2 hours after ingesting 9.6 g of modified-release verapamil (60 × 160 mg tablets) in a suicide attempt. She is drowsy (GCS 13), HR 32 with a junctional rhythm, BP 70/40, glucose 12.4 mmol/L, lactate 6 mmol/L, with first-degree AV block and a QRS of 90 ms. Standard ACLS with atropine and an adrenaline infusion at 0.5 µg/kg/min has not improved her haemodynamics.

^[15] ^[16] ^[6] ^[11] ^[5]

SAQ — Beta-blocker overdose with bronchospasm and hypoglycaemia

10 minutes · 10 marks

A 45-year-old man on long-acting propranolol 80 mg daily for migraine presents after ingesting an unknown quantity. He is bradycardic at 28/min, BP 78/45, GCS 11, wheezy with SpO₂ 90%, blood glucose 2.2 mmol/L, and has a history of asthma. An initial 1 mg atropine and a 1 L crystalloid bolus have produced no improvement.

^[9] ^[12] ^[13] ^[4] ^[5] ^[14]

Clinical pearls

High-yight BB/CCB overdose points for the CICM/FFICM exam

CCB overdose is highly lethal — and verapamil/diltiazem are the deadliest. In an Australian series, 4 of 15 CCB-overdose patients died; verapamil or diltiazem doses over 300 mg carry a significant risk of death, and potentially life-threatening arrhythmias occur at lower doses. Amlodipine produces prominent vasodilatory shock (a survivor of 40 to 45 × 10 mg amlodipine needed VA-ECMO).^[18]^[14]
Hyperglycaemia is the bedside discriminator — CCB blocks insulin release. Calcium-channel antagonists inhibit insulin secretion, producing hyperglycaemia and altered myocardial fatty-acid oxidation; beta-blocker poisoning instead impairs lipolysis, glycogenolysis and insulin release via beta-2 blockade. A capillary glucose at presentation separates CCB from BB before any drug history is confirmed.^[17]
HIET — first-line for severe CCB, started early. High-dose insulin euglycaemia therapy at 1 U per kg IV bolus plus 0.5 to 1 U per kg per hour (titrated up to 1 to 10 U per kg per hour) switches the myocardium from fatty-acid to carbohydrate oxidation, restoring calcium fluxes and improving contractility without increasing heart rate. Co-administer dextrose to maintain euglycaemia and monitor potassium. Do not wait for refractory shock — consensus lists it first-line with calcium and vasopressors.^[11]^[6]^[15]
IV calcium — a consensus first-line adjunct. IV calcium (chloride or gluconate, repeated as required) is recommended first-line for CCB poisoning; in one series atropine was effective only after IV calcium had been given, and slow-release verapamil required prolonged treatment with intravenous calcium salts.^[15]^[18]
Glucagon — mainly for beta-blocker overdose. High-dose glucagon infusions provide moderate chronotropic and inotropic benefit in BB poisoning; the BB systematic review found only minor haemodynamic improvements (rise in heart rate). It is less useful in pure CCB toxicity, where HIET is preferred.^[5]^[9]
Vasopressors — expect high doses. Noradrenaline and/or adrenaline are consensus first-line therapies for CCB poisoning alongside calcium and HIET; resistant vasoplegia means high doses are common and expected. Vasopressin and methylene blue are described for refractory vasodilatory shock. Avoid phosphodiesterase inhibitors — their vasodilation can limit blood-pressure improvement.^[15]^[5]
Atropine usually fails. Consensus only suggests atropine for symptomatic bradycardia or conduction disturbance, and in a published series it was effective only after IV calcium. If there is no response, move on to calcium, HIET, vasopressors and pacing.^[15]^[18]
Pacing may fail to capture. Consensus suggests a pacemaker for unstable bradycardia or high-grade AV block only when cardiac inotropism is preserved — in severe poisoning with myocardial dysfunction, escalate pharmacotherapy and have ECMO on standby instead.^[15]
Lipid emulsion — an adjunct for refractory lipophilic-agent toxicity. The evidence-based workgroup suggests NOT using it first-line for CCB or non-lipid-soluble beta-blocker toxicity, recommends it for bupivacaine arrest, and suggests it for other local anaesthetics, amitriptyline and bupropion when other therapies fail; animal verapamil/propranolol models and human verapamil and BB shock cases show benefit. The panel is deliberately neutral on dosing — follow local protocol. Watch for adverse effects and lab interference from lipaemia.^[12]^[13]
ECMO — bridge to clearance, mobilised early. VA-ECMO provides circulatory support while the drug redistributes and is metabolised; consensus suggests it for refractory shock with a cardiogenic component and for cardiac arrest, and the AHA 2023 update provides ECMO recommendations. Survival benefit comes at the cost of limb ischaemia, thrombosis and bleeding; two published interfacility ECMO transfers for BB/CCB overdose survived to discharge.^[15]^[16]^[14]
Decontamination — charcoal early, whole-bowel irrigation for sustained-release. Verapamil and diltiazem are commonly ingested as sustained-release formulations and peak toxicity can be delayed by several hours; early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation may mitigate this.^[5]
The agent matters. Propranolol is lipophilic and non-selective — massive ingestion causes refractory shock and beta-2 effects (bronchospasm, hypoglycaemia risk via impaired insulin release). Sotalol behaves differently: temporary overdrive cardiac pacing was used to prevent arrhythmias in sotalol toxicity. CCBs produce bradycardia, conduction defects (11 of 15 in one series) and vasodilatory shock.^[17]^[9]^[18]
Sustained-release means prolonged toxicity. Peak toxicity can be delayed by several hours after sustained-release ingestion, and slow-release verapamil required prolonged treatment in a published series — deterioration can occur hours after an initially stable presentation.^[5]^[18]
Non-cardiogenic pulmonary oedema occurs in CCB overdose. Two of 15 patients in the Australian CCB series developed non-cardiogenic pulmonary oedema — anticipate it in severe poisoning.^[18]

References19Show

[1]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circulation, 2023.PMID 37721023
[2]St-Onge M. Cardiovascular Drug Toxicity Crit Care Clin, 2021.PMID 34053706
[3]Wong A, Hoffman RS, Walsh SJ, Roberts DM, Gosselin S, et al. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup Clin Toxicol (Phila), 2021.PMID 33555964
[4]Bouchard J, Shepherd G, Hoffman RS, Gosselin S, Roberts DM, et al. Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup Crit Care, 2021.PMID 34112223
[5]Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies Br J Clin Pharmacol, 2016.PMID 26344579
[6]Engebretsen KM, Kaczmarek KM, Morgan J, Holger JS. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning Clin Toxicol (Phila), 2011.PMID 21563902
[7]Holger JS, Stellpflug SJ, Cole JB, Harris CR, Engebretsen KM. High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock Clin Toxicol (Phila), 2011.PMID 21819291
[8]Lheureux PE, Zahir S, Gris M, Derrey AS, Penaloza A. Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers Crit Care, 2006.PMID 16732893
[9]Rotella JA, Greene SL, Koutsogiannis Z, Graudins A, et al. Treatment for beta-blocker poisoning: a systematic review Clin Toxicol (Phila), 2020.PMID 32310006
[10]Schult RF, Nacca N, Grannell TL, Jorgensen RM, Acquisto NM. Evaluation of high-dose insulin/euglycemia therapy for suspected β-blocker or calcium channel blocker overdose following guideline implementation Am J Health Syst Pharm, 2022.PMID 34957477
[11]Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose Pharmacotherapy, 2018.PMID 30141827
[12]Gosselin S, Hoegberg LC, Hoffman RS, Graudins A, et al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning() Clin Toxicol (Phila), 2016.PMID 27608281
[13]Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review Acad Emerg Med, 2009.PMID 19845549
[14]Fisher R, Minaya SB, Brunette H, Nogar J, Sud P. Interfacility Transfer for VA-ECMO in Beta Blocker and Calcium Channel Blocker Overdoses: A Report of Two Cases Clin Pract Cases Emerg Med, 2025.PMID 39903613
[15]St-Onge M, Anseeuw K, Cantrell FL, Gilchrist IC, Hantson P, Bailey B, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults Crit Care Med, 2017.PMID 27749343
[16]St-Onge M, Dubé PA, Gosselin S, et al. Treatment for calcium channel blocker poisoning: a systematic review Clin Toxicol (Phila), 2014.PMID 25283255
[17]Mégarbane B, Karyo S, Baud FJ The role of insulin and glucose (hyperinsulinaemia/euglycaemia) therapy in acute calcium channel antagonist and beta-blocker poisoning Toxicol Rev, 2004.PMID 15898827
[18]Howarth DM, Dawson AH, Smith AJ, Buckley N, Whyte IM. Calcium channel blocking drug overdose: an Australian series Hum Exp Toxicol, 1994.PMID 7909677
[19]Jang DH, Spyres MB, Fox L, Manini AF. Toxin-induced cardiovascular failure Emerg Med Clin North Am, 2014.PMID 24275170

Beta-blocker and calcium channel blocker overdose

Also known as Beta-blocker poisoning · Calcium channel blocker poisoning · CCB overdose · High-dose insulin euglycaemia therapy (HIET)

low19 referencesUpdated 26 July 202623 min readVerification in progress

Clinical pearls

References19Show

[1]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circulation, 2023.PMID 37721023
[2]St-Onge M. Cardiovascular Drug Toxicity Crit Care Clin, 2021.PMID 34053706
[3]Wong A, Hoffman RS, Walsh SJ, Roberts DM, Gosselin S, et al. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup Clin Toxicol (Phila), 2021.PMID 33555964
[4]Bouchard J, Shepherd G, Hoffman RS, Gosselin S, Roberts DM, et al. Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup Crit Care, 2021.PMID 34112223
[5]Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies Br J Clin Pharmacol, 2016.PMID 26344579
[6]Engebretsen KM, Kaczmarek KM, Morgan J, Holger JS. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning Clin Toxicol (Phila), 2011.PMID 21563902
[7]Holger JS, Stellpflug SJ, Cole JB, Harris CR, Engebretsen KM. High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock Clin Toxicol (Phila), 2011.PMID 21819291
[8]Lheureux PE, Zahir S, Gris M, Derrey AS, Penaloza A. Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers Crit Care, 2006.PMID 16732893
[9]Rotella JA, Greene SL, Koutsogiannis Z, Graudins A, et al. Treatment for beta-blocker poisoning: a systematic review Clin Toxicol (Phila), 2020.PMID 32310006
[10]Schult RF, Nacca N, Grannell TL, Jorgensen RM, Acquisto NM. Evaluation of high-dose insulin/euglycemia therapy for suspected β-blocker or calcium channel blocker overdose following guideline implementation Am J Health Syst Pharm, 2022.PMID 34957477
[11]Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose Pharmacotherapy, 2018.PMID 30141827
[12]Gosselin S, Hoegberg LC, Hoffman RS, Graudins A, et al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning() Clin Toxicol (Phila), 2016.PMID 27608281
[13]Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review Acad Emerg Med, 2009.PMID 19845549
[14]Fisher R, Minaya SB, Brunette H, Nogar J, Sud P. Interfacility Transfer for VA-ECMO in Beta Blocker and Calcium Channel Blocker Overdoses: A Report of Two Cases Clin Pract Cases Emerg Med, 2025.PMID 39903613
[15]St-Onge M, Anseeuw K, Cantrell FL, Gilchrist IC, Hantson P, Bailey B, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults Crit Care Med, 2017.PMID 27749343
[16]St-Onge M, Dubé PA, Gosselin S, et al. Treatment for calcium channel blocker poisoning: a systematic review Clin Toxicol (Phila), 2014.PMID 25283255
[17]Mégarbane B, Karyo S, Baud FJ The role of insulin and glucose (hyperinsulinaemia/euglycaemia) therapy in acute calcium channel antagonist and beta-blocker poisoning Toxicol Rev, 2004.PMID 15898827
[18]Howarth DM, Dawson AH, Smith AJ, Buckley N, Whyte IM. Calcium channel blocking drug overdose: an Australian series Hum Exp Toxicol, 1994.PMID 7909677
[19]Jang DH, Spyres MB, Fox L, Manini AF. Toxin-induced cardiovascular failure Emerg Med Clin North Am, 2014.PMID 24275170