Tricyclic Antidepressant Overdose.

CLINICAL COURSE

The patient is orally intubated without complications. The patient's wide complex tachycardia resolves with hyperventillation and 5 ampules of sodium bicarbonate. The family returns with 2 empty pill bottles, which used to contain amitryptyline. Patient had 2 tonic-clonic seizures which respond to IV. Valium (10mg) Patient lavaged with no pill fragment return, and given activated charcoal. The patient is admitted to the ICU, and was extubated and medically cleared within 72 hours. After psychiatry treatment as an inpatient for one week, the patient is discharged to home.

QUESTIONS AND CONTROVERSIAL ISSUES

1) What are the mechanisms of action of tricyclic antidepresants?

• Anticholinergic effects
• Norepinephrine reuptake blockade
• Quinidine-like effect
• Soddium channel blocker
• peripheral alpha blocade

2)How may TCA-induced cardiotoxicity be demonstrated on an ECG?

• Sinus tachycardia
• QRS complex prolongation >100msec
• Right Bundle Branch Block
• V-Tach
• V-Fib
• QT Prolongation (Can Progress to Torsade de Pointes)
• Rightward Terminal 40msec of QRS
• - R in AVR
• - S in Lead I and AVL

3) What is the role of sodium bicarbonate in TCA toxicity?

• Alkalinization promotes protein binding of drug (Less free drug in circulation)
• Improves conduction through sodium channels (?Role for hypertonic saline)
• Decreases ventricular dysrhythmias
• Treats acidosis created by seizure activity
• Goal of pH is 7.45-7.55
• Bolus dose preferred over IVPB administration.

4)How should TCA-induced hypotension be managed?

• Trendelenberg position
• IV. Fluids Saline or Lactated Ringer's Solution.
• Pressor agents
• Norepinephrine- Best for treating alpha blockade induced hypotension
• Dopamine- Intermediate doses stimulate Beta-1 reccepters and may increase cardiac output. Higher doses will stimulate alpha receptors.
• Cardiopulmonary Bypass: Under investigation.

5) How should TCA-associated seizures be treated?

• Aggressively! Resultant acidosis exacerbates cardiotoxicity
• Benzodiazepines
• Phenobarbitol
• Phenytoin
• - Not very efficacious with toxic seizures in general
• - Anecdotal reports of controlling TCA-Induced seizure activity
• - Debate over cardiovascular effects; potentially helpful? (Phenytoin is a type 1B antiarrhythmic agent which may counteract the type 1A effects of TCA's)
• Paralyze and intubate (Avoid long-acting agents)

6)While stabilizing the patient, is there a role for gastric decontamination?

• Ipecac: contraindicated in a comatose patient with seizures
• Gastric lavage: Latest literature supports lavage if patient presents within one hour following a potentially life threatening ingestion. (In this case, time of ingestion was unknown)
• TCA's have anticholinergic properties which slow gastric emptying time (?Role for delayed lavage?)
• Activated charcoal: First dose indicated, multiple dose controversial.

7) Is there an indication for physostigmine in a hemodynamically unstable TCA overdose?

• Not a first line drug. May be contraindicated.
• Consider only if severe, lifethreatening anticholinergic effects. (last resort)
• Danger of asystole has been described in case reports.

8) Should all TCA overdoses be admitted to the intensive care unit?

• After six hours of monitoring, if no signs of CNS toxicity, anticholinergic signs, and QRS is less than 100msec, consider it safe to discharge or transfer to psychiatry.
• If any CNS or cardiac toxicity, 24 hour admission to a monitored setting is recommended.

9) What is the toxicity of the newer antidepressant agents?

• Trazadone (Desaryl)- Hypotension from alpha blockade
• Amoxapine (Ascendid) -Seizures
• Maprotiline (Ludiomil) Seizures
• Fluoxetine (Prozac)/Sertraline (Zoloft)
• Mild toxicity (Agitation, insomnia)
• Large doses can lead to CNS depression, seizures
• With mixed ingestions (MAOI's, TCA's) can lead to the serotonin syndrome: Mild form of Neuroleptic Malignant Syndrome.