What is the likely substance causing bradycardia, hypotension, and central nervous system (CNS) depression in this patient?

Most Likely Substance: Labetalol

This patient most likely overdosed on labetalol, a beta-blocker with combined alpha-blocking properties, based on the constellation of severe bradycardia (HR 35 bpm), profound hypotension (BP 80/30 mmHg), CNS depression (GCS 3), and critically—hypoglycemia (glucose 40 mg/dL).

Clinical Reasoning

Key Distinguishing Features

The hypoglycemia is the critical diagnostic clue that points specifically to beta-blocker toxicity rather than the other options:

• Beta-blockers cause hypoglycemia by blocking the catecholamine-mediated glycogenolysis and gluconeogenesis that normally occurs in response to low blood sugar 1
• The triad of bradycardia, hypotension, and profound CNS depression with hypoglycemia is pathognomonic for beta-blocker overdose 2

Why Not the Other Options?

Clonidine would present with bradycardia, hypotension, and CNS depression, but typically causes miosis (pinpoint pupils) rather than the 5mm minimally reactive pupils seen here, and does not characteristically cause hypoglycemia.

Digitalis overdose presents with bradycardia and various arrhythmias, but typically causes hyperkalemia (not the normal potassium of 4.0 seen here) and gastrointestinal symptoms. The profound hypotension and hypoglycemia are not characteristic 1.

Diltiazem (calcium channel blocker) would cause bradycardia and hypotension, but typically produces hyperglycemia rather than hypoglycemia due to blockade of pancreatic calcium channels and inhibition of insulin release 1.

Labetalol-Specific Toxidrome

The FDA label for labetalol explicitly describes this presentation: "Overdosage with labetalol causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia" 2. The wheezing noted on exam is consistent with bronchospasm, a known complication of beta-blocker overdose 2.

Immediate Management Priorities

First-Line Antidote Therapy

High-dose insulin with glucose is the first-line treatment for beta-blocker overdose with refractory shock according to the American Heart Association (Class 2a, Level C-LD) 1, 3:

• Initial bolus: 1 U/kg regular insulin IV
• Continuous infusion: 1 U/kg/hour, titrated to hemodynamic response
• Mandatory co-administration: 0.5 g/kg dextrose bolus, followed by 0.5 g/kg/hour dextrose infusion 3
• Glucose monitoring: Every 15 minutes initially, targeting 100-250 mg/dL 3

Second-Line Therapies

Glucagon is reasonable for refractory shock (Class 2a, Level C-LD) 1:

• Dosing: 5-10 mg IV bolus rapidly over 30 seconds, followed by continuous infusion of 5 mg/hour 2, 4, 5
• Glucagon bypasses the beta-receptor blockade and increases heart rate and myocardial contractility 4, 5

Calcium salts may be considered (Class 2b, Level C-LD) 1:

• Dosing: 0.3 mEq/kg (0.2 mL/kg of 10% calcium chloride) over 5-10 minutes 3

Vasopressor Support

Norepinephrine is the vasopressor of choice for hypotension in beta-blocker overdose 2. The FDA label specifically states "there is pharmacologic evidence that norepinephrine may be the drug of choice" 2.

Rescue Therapy

VA-ECMO should be considered for shock refractory to all pharmacological interventions (Class 2b, Level C-LD) 1, 3.

Critical Monitoring Requirements

• Frequent glucose checks (every 15 minutes initially) to prevent both hypoglycemia and hyperglycemia during insulin therapy 3
• Serum potassium monitoring with target of 2.5-2.8 mEq/L (moderate hypokalemia is common; aggressive repletion can cause asystole) 3
• Continuous cardiac monitoring for arrhythmias and conduction disturbances 6, 7

Common Pitfalls to Avoid

• Do NOT use lipid emulsion therapy - the American Heart Association explicitly recommends against ILE for beta-blocker poisoning (Class 3: No Benefit) 3
• Avoid dopamine - it is less effective than epinephrine or norepinephrine for hypotension in this setting 3
• Do NOT under-dose insulin - the "high-dose" designation is critical; standard insulin doses will not achieve the desired hemodynamic effect 3, 8
• Treat the hypoglycemia immediately but recognize it as a diagnostic clue rather than an isolated problem 2
• Prepare for bronchospasm management with epinephrine and/or aerosolized beta2-agonists as needed 2