08. Tricyclic Antidepressant Overdose

Mechanism and Pharmacokinetics

Anticholinergic and antihistamine effects, cardiac fast sodium channel blockade (similar to type IA antiarrhythmics), alpha-1 blockade.

  • Peak effect usually occurs 2-8 hours after ingestion, with half-life of 25-30 hours (prolonged due to high volume of distribution). Anticholinergic effects in overdose may cause delayed GI transit time and delay in absorption/peak effect.
  • Death mostly results from refractory hypotension or arrhythmia and generally occurs in first 24 hours, often within the first 1-2 hours of ingestion. The first 6 hours are the most critical for triage and differentiating non-toxic or mildly toxic ingestions from cases of significant toxicity.

Signs and Symptoms

Anticholinergic toxidrome, cardiac toxicity (hypotension, myocardial depression, arrhythmias [including ST, SVT, VT/VF], conduction delays [QRS prolongation, AV block]), pulmonary edema, AMS, coma, seizures.

Evaluation

  • Laboratory: serum levels are not clinically useful and not readily available. Check FSBG, CHEM10, acetaminophen and salicylate levels.
  • ECG: the single most important test to guide therapy and prognosis. Special attention to QRS, QTc, and PR.
  • QRS prolongation >100 ms, and tall R waves in AVR or AVR R/S >0.7 portends greater risk of arrhythmia and seizures. Bicarbonate should be used if the QRS is >100 ms.

Management

  • Ensure ability to protect airway and intubate if necessary.
  • Triage decision:
  • Admit to ICU if altered mental status, respiratory depression, hypotension, ECG changes, arrhythmias, or seizures.
  • Telemetry alone can be considered for patients who have sinus tachycardia without other ECG changes and normal mental status.
  • Observation for 6 hours with serial ECGs is indicated in patients who are asymptomatic with normal vital signs and no ECG changes.
  • Activated charcoal: 50 g in slurry if within 2 hours of ingestion and normal mental status (able to protect airway).
  • Bicarbonate therapy: goal blood pH 7.50-7.55 (monitor with serial blood gas). The sodium load may increase gradient across cell membranes, reducing effects of sodium channel blockade. A pH-dependent effect also occurs but is poorly understood.
  • Bolus with 1-3 amps (50 mEq) of NaHCO3 IV push for QRS >100 ms or arrhythmias, with continuous 12 lead ECG during bolus to assess response to therapy (QRS narrowing). Watch for pulmonary edema, hypokalemia.
  • Hyperventilation can be used if the patient is intubated to induce alkalemia before bicarb is started, but should not be used concurrently with bicarbonate administration due to risk of severe alkalosis.
  • Ventricular arrhythmias: lidocaine or magnesium if bicarbonate is ineffective. Do not use class IA (quinidine, procainamide) or IC agents, as they can add to toxicity. Amiodarone may worsen QT prolongation.
  • Hypotension: start with IV fluids, then norepinephrine or phenylephrine preferred over dopamine as hypotension related partially to alpha antagonism.
  • Lipid emulsion therapy IV (“intralipid): a strategy to create a “lipid sink” to sequester lipid-soluble TCA in the blood and prevent it from reaching tissues. Used for refractory cases. Consult with Poison Control.
  • CNS complications: prevent seizures by reducing toxicity, treat seizures with benzodiazepines. Flumazenil and physostigmine are contraindicated.

Key Points

  • Most morbidity and mortality from tricyclic overdose are within the first 6 hours as a result of hypotension and cardiac arrhythmias.
  • Serial ECG monitoring can guide when to initiate bicarbonate boluses.
  • Contact Poison Control (800-222-1222) or Medical Toxicology consult (415-443-0122) for assistance.
     

Goldfrank’s Toxicologic Emergencies, 9th ed 2010.

Engels PT, Davidow JS. Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose. Resuscitation 2010; 81(8): 1037-9.

Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: A review. Emerg Med J 2001;18:236-241.