What is the emergency management of a suspected tricyclic antidepressant overdose with possible concomitant benzodiazepine ingestion?

Emergency Management of Tricyclic Antidepressant Overdose with Concomitant Benzodiazepine Ingestion

Never administer flumazenil in this scenario—it is absolutely contraindicated in tricyclic antidepressant (TCA) overdose and carries a Class III (Harm) recommendation from the American Heart Association, as it precipitates life-threatening seizures and ventricular arrhythmias. 1, 2, 3

Immediate Stabilization and Airway Management

• Establish an open airway immediately and provide bag-mask ventilation if respiratory depression occurs; maintain oxygen saturation ≥95% on room air. 2, 3
• Proceed to endotracheal intubation when the patient cannot protect the airway or shows progressive CNS depression. 1, 3
• Contact your regional poison control center (1-800-222-1222 in the United States) as soon as the patient presents for expert guidance. 1, 2
• Initiate continuous cardiac monitoring immediately to detect QRS prolongation, ventricular dysrhythmias, heart block, bradyarrhythmias, or asystole. 3, 4

Critical ECG Assessment and Sodium Bicarbonate Therapy

• Obtain an ECG or rhythm strip during initial assessment—a QRS duration >100 ms indicates severe TCA toxicity requiring immediate intervention. 3, 4
• Administer sodium bicarbonate 1–2 mEq/kg IV bolus immediately if QRS duration >100 ms is observed, repeating every 5–10 minutes as needed. 3, 4
• Target arterial pH of 7.45–7.55 and serum sodium <150–155 mEq/L to avoid iatrogenic harm during bicarbonate therapy. 3
• Avoid respiratory acidosis during mechanical ventilation—maintain mild hyperventilation to support alkalemia, as acidosis potentiates cardiotoxicity. 3

Common Pitfall: Flumazenil Use

Even though benzodiazepine co-ingestion is present, flumazenil must never be used because:

• It removes benzodiazepine-mediated suppression of sympathetic tone and precipitates dysrhythmias (supraventricular tachycardia, ventricular dysrhythmias, asystole) in the presence of TCAs. 1
• It provokes refractory withdrawal seizures in benzodiazepine-dependent patients. 1, 2
• The American Heart Association assigns a Class III (Harm) recommendation specifically for this scenario. 1, 2

Management of Hypotension

• Administer IV fluid boluses (10 mL/kg) of normal saline for initial management of hypotension. 3
• Continue sodium bicarbonate therapy for persistent hypotension despite fluid resuscitation, as it improves cardiac contractility. 3
• Consider vasopressors if hypotension remains refractory to fluids and bicarbonate. 3

Escalation for Refractory Cardiac Toxicity

If QRS duration remains ≥120 ms despite optimized bicarbonate therapy, proceed sequentially:

Second-Line: Lidocaine

• Administer lidocaine 1–1.5 mg/kg IV bolus slowly for persistent wide-complex tachycardia (Class IIb recommendation). 3
• Lidocaine is a Class Ib antiarrhythmic that may narrow the QRS complex and improve hemodynamics. 3
• Avoid Class Ia (quinidine, procainamide), Class Ic (flecainide), and Class III (amiodarone) antiarrhythmics—they exacerbate sodium-channel blockade and worsen toxicity. 3

Third-Line: Intravenous Lipid Emulsion (ILE)

• Administer 20% lipid emulsion 1.5 mL/kg bolus over 1 minute, followed by continuous infusion at 0.25 mL/kg/min for life-threatening toxicity refractory to bicarbonate and lidocaine (Class IIb recommendation). 3
• The "lipid sink" effect sequesters lipophilic TCAs, reducing free plasma concentration. 3

Fourth-Line: VA-ECMO

• Consider veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac arrest or refractory cardiogenic shock unresponsive to high-dose vasopressors, bicarbonate, lidocaine, and ILE (Class IIa recommendation). 3
• Early ECMO consultation improves outcomes, especially when initiated before prolonged cardiac arrest. 3

Management of Benzodiazepine-Related Respiratory Depression

• Provide standard supportive care with bag-mask ventilation and intubation as needed—this is the cornerstone of benzodiazepine overdose management. 1, 2
• Do not withhold naloxone if opioid co-ingestion is suspected, as opioid-adulterated illicit drugs are common and naloxone does not worsen TCA toxicity. 1

Seizure Management

• Administer benzodiazepines (e.g., lorazepam 2–4 mg IV or diazepam 5–10 mg IV) for TCA-associated seizures. 4
• Never use physostigmine for anticholinergic symptoms, as it worsens cardiac toxicity. 3

Gastrointestinal Decontamination

• Administer activated charcoal 1 g/kg orally only if the patient presents within 1–4 hours of ingestion and has a protected airway. 2, 5
• Do not induce emesis—it increases aspiration risk and delays definitive care. 4

Monitoring and Temperature Management

• Maintain normothermia—hyperthermia aggravates TCA toxicity. 3
• Monitor serum potassium levels, as hypokalemia may develop during sodium bicarbonate therapy. 3
• Observe for a minimum of 24–48 hours because benzodiazepines have long half-lives (e.g., clonazepam 22–32 hours) and delayed resedation can occur. 2, 6
• Continue cardiac monitoring throughout the observation period even after clinical improvement, as late-onset arrhythmias can occur. 3, 4

Disposition

• Never discharge based solely on early clinical improvement—the full 24–48-hour observation must be completed. 2
• Obtain formal psychiatric evaluation before discharge in intentional overdose cases; discharge without psychiatric clearance is unsafe. 2