Why is insulin administered in beta blocker (beta-adrenergic blocking agent) poisoning?

Why Insulin is Given in Beta-Blocker Poisoning

High-dose insulin therapy is administered in beta-blocker poisoning because it directly improves myocardial contractility, optimizes cardiac energy utilization by shifting metabolism from fatty acids to carbohydrates, and has been shown to improve hemodynamic parameters and survival better than conventional therapies like glucagon or catecholamines alone. 1, 2

Pathophysiologic Rationale

Beta-blocker toxicity causes severe cardiovascular collapse through multiple mechanisms that insulin specifically counteracts:

• Metabolic dysfunction: Beta-blocker poisoning impairs insulin secretion, lipolysis, and glycogenolysis, leading to altered myocardial fatty acid oxidation and decreased cardiac energy availability 3
• Direct inotropic effect: Insulin has intrinsic positive inotropic properties independent of its metabolic effects, directly improving cardiac contractility 2, 3
• Substrate switching: Insulin shifts myocardial metabolism from fatty acids to carbohydrates (glucose), which is more oxygen-efficient and improves cardiac performance in the setting of toxin-induced shock 3, 4
• Calcium flux restoration: Insulin restores intracellular calcium fluxes that are disrupted by beta-blocker toxicity, further enhancing contractility 3

Evidence Base for Superiority

The ACC/AHA/HRS guidelines give high-dose insulin a Class IIa recommendation (reasonable to use) for symptomatic bradycardia or hemodynamic compromise from beta-blocker overdose 1:

• Animal studies demonstrate superiority: High-dose insulin outperformed calcium salts, glucagon, epinephrine, and vasopressin in terms of survival in animal models of beta-blocker toxicity 2, 3
• Human case series show benefit: Multiple case series document improved hemodynamic parameters, reduced vasopressor requirements, and improved survival with high-dose insulin therapy 1, 2, 5
• Sustained hemodynamic improvement: Unlike catecholamines that increase systemic vascular resistance and myocardial oxygen demand, insulin improves cardiac output without these deleterious effects 2, 4

Treatment Protocol

Initial Dosing

• Bolus: 1 U/kg regular insulin IV 1, 6
• Concurrent dextrose bolus: 0.5 g/kg (typically 25-50 grams) 6, 2
• Continuous infusion: 0.5-1 U/kg/hour insulin, titrated up to 10 U/kg/hour based on hemodynamic response 1, 2, 5
• Dextrose infusion: 0.5 g/kg/hour, adjusted to maintain euglycemia 6, 2

Monitoring Requirements

• Glucose: Every 15 minutes initially, then every 30-60 minutes once stable; target 100-250 mg/dL (5.5-14 mmol/L) 6, 2
• Potassium: Frequent monitoring as insulin causes intracellular potassium shift; target 2.5-2.8 mEq/L to avoid aggressive repletion 1, 6, 2
• Hemodynamics: Continuous cardiac monitoring, blood pressure, and assessment of perfusion 5

Treatment Algorithm for Beta-Blocker Poisoning

First-Line Interventions (initiate simultaneously)

1. Fluid resuscitation: Essential to correct low cardiac filling pressures 2, 5
2. Atropine: 0.02 mg/kg (minimum 0.1 mg, maximum 0.5 mg) if bradycardia present 1, 5
3. Catecholamines/vasopressors: Based on type of shock (epinephrine for inotropy, norepinephrine for blood pressure) 1, 5

Second-Line: High-Dose Insulin

• Indication: Hemodynamic instability refractory to first-line therapies, or documented myocardial dysfunction 1
• Initiate protocol as described above 6, 2
• Titrate insulin infusion incrementally (up to 10 U/kg/hour) based on hemodynamic response 2, 5

Adjunctive Therapies

• Glucagon: 3-10 mg IV bolus over 3-5 minutes, then 3-5 mg/hour infusion (less effective than insulin but can be used concurrently) 1, 6
• Calcium salts: More effective for calcium channel blocker toxicity, but can be tried in beta-blocker poisoning 1, 5

Rescue Therapies for Refractory Cases

• Lipid emulsion therapy: Variable response but reasonable to attempt 5, 7
• VA-ECMO: For severe cardiogenic shock or cardiac arrest unresponsive to all pharmacologic interventions 1, 5
• Temporary pacing: Primarily for sotalol toxicity with arrhythmias 5

Critical Pitfalls and Adverse Effects

Hypoglycemia

• Most common adverse effect: Requires aggressive glucose supplementation throughout therapy and for up to 24 hours after discontinuation 2, 4
• Prevention: Start dextrose infusion simultaneously with insulin bolus, never delay dextrose 6, 2

Hypokalemia

• Mechanism: Intracellular potassium shift, not total body depletion 1, 2
• Management: Target lower potassium levels (2.5-2.8 mEq/L) to avoid excessive repletion that will reverse once insulin is stopped 6, 2

Common Mistake

Do not wait for conventional therapies to definitively fail before initiating high-dose insulin in severe poisoning—early initiation (within the first-line treatment phase) may prevent progression to refractory shock 2, 4

Quality of Evidence Caveat

The evidence base consists primarily of animal studies, case reports, and case series with no randomized controlled trials in humans 1, 2. However, the consistent demonstration of hemodynamic improvement and survival benefit across multiple studies, combined with the relatively low risk profile when properly monitored, supports its use as a Class IIa recommendation 1, 5.