What is the first specific antidote and its dosing for a patient who has overdosed on calcium‑channel blockers such as amlodipine, verapamil, diltiazem, or nifedipine?

Calcium Gluconate for Calcium Channel Blocker Overdose

Intravenous calcium is reasonable as a first-line antidote for calcium channel blocker overdose, but it should be administered alongside high-dose insulin euglycemia therapy (HIET) and vasopressors—not as monotherapy—because calcium alone is insufficient for most patients with hemodynamic compromise. 1

First-Line Antidotal Therapy

The 2023 American Heart Association guidelines recommend a multimodal approach prioritizing three interventions simultaneously for CCB overdose with hypotension: 1

• Intravenous calcium (Class 2a recommendation, C-LD evidence) 1
• High-dose insulin euglycemia therapy (HIET) (Class 1 recommendation, B-NR evidence) 1
• Vasopressors (norepinephrine and/or epinephrine) (Class 1 recommendation, B-NR evidence) 1

Calcium Dosing and Administration

Initial bolus: Administer 0.3 mEq/kg (equivalent to 0.6 mL/kg of 10% calcium gluconate OR 0.2 mL/kg of 10% calcium chloride) IV over 5-10 minutes. 2

Continuous infusion: Follow with 0.3 mEq/kg per hour, titrated to hemodynamic response. 2

Target levels: Aim for ionized calcium levels up to twice the normal range, but avoid severe hypercalcemia exceeding 2× the upper limit of normal. 1, 2

The 2017 Critical Care Medicine expert consensus similarly recommends IV calcium as first-line therapy alongside HIET and vasopressors. 1 Calcium was helpful in only 5 of 14 patients who received it in one retrospective series, underscoring that it is rarely sufficient as monotherapy. 3

High-Dose Insulin Euglycemia Therapy (HIET)

HIET is a Class 1 recommendation with stronger evidence (B-NR) than calcium for CCB-induced hypotension. 1 It enhances myocardial inotropy and carbohydrate utilization, with lower rates of vasoconstrictive complications compared to vasopressor-only regimens. 1

Initial dosing: 2

• Insulin bolus: 1 U/kg regular insulin IV
• Dextrose bolus: 0.5 g/kg IV simultaneously

Continuous infusion: 2

• Insulin: 0.5-1 U/kg/hr initially, titrated incrementally up to 10 U/kg/hr based on clinical response 1, 2
• Dextrose: 0.5 g/kg/hr, adjusted to maintain glucose 100-250 mg/dL 2

Monitoring: Check glucose every 15 minutes during titration, then hourly once stable; monitor potassium every 1-2 hours to detect hypokalemia. 2

Begin HIET early, preferably before marked hemodynamic collapse, and escalate doses if myocardial dysfunction persists. 1, 2

Vasopressor Support

Norepinephrine and/or epinephrine are Class 1 recommendations for CCB-induced hypotension because they are readily available and act quickly. 1 One large retrospective series demonstrated excellent survival with norepinephrine doses up to 100 μg/min in adults, with low rates of ischemic complications. 1

• Norepinephrine: First-line for vasoplegic shock 2
• Epinephrine: Increases contractility and heart rate; useful when cardiogenic shock predominates 1, 2
• Dobutamine: Add when confirmed myocardial dysfunction is present 1, 2

Critical Pitfall: Calcium Monotherapy is Inadequate

Do not rely on calcium alone. 1, 2 The 2023 AHA guidelines explicitly state that calcium is insufficient for most patients and must be combined with HIET and vasopressors. 1 The FDA label for verapamil notes that "parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively," but emphasizes that "continued treatment with large doses of calcium may produce a response" only in refractory cases—implying repeated or high-dose calcium is needed, not a single bolus. 4

Adjunctive and Rescue Therapies

Atropine

Class 2a recommendation (C-LD) for hemodynamically significant bradycardia, though efficacy is limited. 1, 2

Glucagon

The usefulness of glucagon is uncertain (Class 2b, C-LD). 1 Clinical response is inconsistent, with frequent vomiting and rapid tachyphylaxis. 1 The 2017 consensus suggests it may be reasonable for refractory cases, but it is not prioritized. 1

Intravenous Lipid Emulsion (ILE)

The 2023 AHA guidelines recommend against routine use of ILE (Class 3: No Benefit, C-LD). 1 Evidence suggests ILE may increase gastrointestinal absorption of oral CCBs, potentially worsening toxicity. 1, 2 Reserve ILE only for refractory shock or periarrest states unresponsive to all other therapies. 1, 2

If employed: 1.5 mL/kg of 20% lipid emulsion bolus (repeat up to twice), followed by 0.25 mL/kg/min infusion for 30-60 minutes; maximum cumulative dose 12.5 mL/kg/24 hours. 2

Temporary Cardiac Pacing

Class 2b recommendation (C-LD) for refractory bradycardia. 1 Consider pacing only when myocardial function is preserved and unstable bradycardia or high-grade AV block is present. 1, 2 Pacing is often ineffective in complete AV nodal blockade or vasodilatory shock. 1, 2

Extracorporeal Life Support (VA-ECMO)

Class 2a recommendation (C-LD) for refractory cardiogenic shock unresponsive to maximal pharmacologic therapy. 1, 2 Case series report survival rates up to 77% in CCB overdose patients treated with VA-ECMO. 1 VA-ECMO is especially beneficial when pump failure (cardiogenic component) predominates. 1, 2

Cardiac Arrest Management

During ACLS for CCB-related cardiac arrest: 1, 2

• Administer IV calcium bolus in addition to standard resuscitation measures
• Consider IV lipid emulsion therapy concurrently with ACLS
• Deploy VA-ECMO if available for refractory arrest

Monitoring Parameters

• Continuous cardiac telemetry for rhythm and conduction abnormalities 2
• Arterial line preferred for shock states 2
• Serum glucose: Every 15 minutes initially, then hourly once stable 2
• Serum potassium: Every 1-2 hours during HIET 2
• Ionized calcium levels: During calcium infusions 2

Key Pitfalls to Avoid

• Do not use calcium as monotherapy—most patients require combined modalities. 1, 2
• Do not use ILE routinely—reserve for refractory cases to avoid increasing oral CCB absorption. 1, 2
• Avoid electrical pacing in patients with significant myocardial dysfunction, as it is likely ineffective. 1, 2
• Monitor for hypokalemia and volume overload during HIET and correct promptly. 1
• Observe for at least 48 hours, especially with sustained-release formulations, as delayed pharmacodynamic consequences may occur. 4