How do insulin and glucagon help in treating beta blocker (beta-adrenergic blocking agent) overdose?

Insulin and Glucagon in Beta Blocker Overdose Management

High-dose insulin therapy and glucagon are both reasonable and effective treatments for beta blocker overdose with hemodynamic compromise, with insulin showing superior outcomes in severe cases.1

Mechanism of Action

Glucagon

• Counteracts beta blocker effects by activating hepatic adenylate cyclase, promoting glucogenolysis through a pathway that bypasses the blocked beta-adrenergic receptors 2
• Increases heart rate and improves atrioventricular conduction without requiring functional beta receptors 3
• May increase cardiac output but has inconsistent effects on mean arterial pressure 4

High-Dose Insulin

• Works through three main mechanisms: increased inotropy, increased intracellular glucose transport, and vascular dilation 5
• Improves myocardial energy utilization during beta blocker toxicity 1
• Particularly effective in severe beta blocker poisoning with cardiogenic shock 6

Treatment Protocol

Glucagon Administration

• Initial dose: 3-10 mg IV administered slowly over 3-5 minutes 1, 2
• Followed by continuous infusion of 3-5 mg/h (0.05-0.15 mg/kg/h) 1
• Titrate infusion rate to achieve adequate hemodynamic response 1
• Plan for adequate supply as treatment may require >100 mg in 24 hours 1

High-Dose Insulin Administration

• Initial bolus: 1 U/kg regular insulin IV 1, 7
• Accompanied by 0.5 g/kg dextrose bolus 1, 7
• Followed by continuous infusion of 0.5-1 U/kg/h insulin and 0.5 g/kg/h dextrose 1, 7
• Higher doses (up to 10 U/kg/h) may be required in severe cases 5, 6

Monitoring and Precautions

For Glucagon Therapy

• Common side effect: vomiting - protect airway in patients with CNS depression 1
• Monitor for potential interactions with dopamine, isoproterenol, and milrinone which may decrease glucagon effectiveness 1
• Patients taking beta-blockers may experience transient increases in pulse and blood pressure when given glucagon 8

For Insulin Therapy

• Very frequent glucose monitoring (every 15 minutes initially) 1, 7
• Target serum glucose: 100-250 mg/dL (5.5-14 mmol/L) 1, 7
• Monitor potassium levels - insulin causes intracellular potassium shift 1, 7
• Target potassium levels: 2.5-2.8 mEq/L to avoid aggressive repletion 1, 7
• Sustained infusions of concentrated dextrose solutions (>10%) require central venous access 1

Treatment Algorithm for Beta Blocker Overdose

1. Initial Management:

   • Standard resuscitation measures (BLS/ACLS) 1, 2
   • IV fluids for volume resuscitation 5

2. For Symptomatic Bradycardia or Hemodynamic Compromise:

   • Consider calcium (Class IIa, LOE C-LD) - 0.3 mEq/kg of calcium 1
   • Initiate glucagon (Class IIa, LOE C-LD) using protocol above 1, 2

3. For Refractory Cases:

   • Implement high-dose insulin therapy (Class IIa, LOE C-LD) 1, 7
   • Evidence suggests high-dose insulin may be superior to conventional therapies including glucagon in severe cases 5, 6

Important Considerations

• Early initiation of high-dose insulin in the emergency department can be beneficial rather than waiting for conventional therapies to fail 6
• Animal studies and human case reports demonstrate that high-dose insulin is superior in terms of safety and survival compared to conventional therapies 5
• For severe beta blocker overdose with cardiogenic shock, consider escalating to higher insulin doses (up to 10 U/kg/h) if standard doses are ineffective 6