Tricyclic antidepressant toxicity

Background

  1. Used in depression (less), neuropathic pain
  2. Serious toxicity is almost always seen within 6hr of ingestion
  3. Ingestion amount:
    1. <1mg/kg: Nontoxic
    2. >10mg/kg: Life-threatening
    3. >1gm: Commonly fatal
  4. Coingestants often increase severity of toxicity
    • Cocaine can produce the same sodium blockade effect and exacerbate a TCA overdose

Clinical Features

  1. Na Channel Blockade
    1. Negative inotropy, heart block, hypotension, ectopy
  2. Anti-Histamine Effects
    1. Sedation, coma
  3. Anti-Muscarinic Effects
    1. Central
      1. Agitation, delirium, confusion, hallucinations
      2. Slurred speech, ataxia
      3. Sedation, coma
      4. Seizures
    2. Peripheral
      1. Mydriasis, decreased secretions, dry skin, ileus, urinary retention
      2. Tachycardia, hyperthermia
  4. Alpha1 Receptor Blockade
    1. Sedation, orthostatic hypotension, miosis
  5. Inhibition of amine reuptake
    1. Sympathomimetic effects
    2. Myoclonus, hyperreflexia
    3. Serotonin Syndrome (only when used in combination w/ other serotonergic agents)

Diagnosis

  1. Serious toxicity
    1. Conduction delays, SVT, V-tach, hypotension
    2. Respiratory depression
    3. Seizures
    4. Pulmonary Edema
  2. ECG
    1. Sinus Tachycardia (most frequent dysrhythmia)
    2. PR, QRS, QT Prolongation
    3. Right axis deviation (of terminal 40ms)
      1. Terminal R wave in aVR, S wave in I/aVL[1]
    4. Brugada pattern (15%)[2][3]
ECG in TCA toxicity

Differential Diagnosis

Anticholinergic toxicity Causes

Treatment

GI Decontamination

  1. Gastric lavage if <1hr after ingestion
  2. Activated charcoal 1gm/kg x1

Cardiac Toxicity[5]

Sodium Bicarbonate

  1. Indications:
    1. QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
  2. Initial Dosing:
    1. Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
    2. May give as 3ampules (132 mEq) of 8.4% NaHCO3
  3. Infusion Dosing[6]
    1. Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
  4. Treatment Goal:
    1. QRS <100ms
    2. pH 7.50-7.55
    3. May continue for 12-24hrs due to the drugs redistribution from tissue
  5. Treatment Monitoring
    1. Monitor for volume overload, hypokalemia, hypernatremia, metabolic alkalosis

Hyperventilation

  • Consider in patients unable to tolerate NaHCO3 (renal failure, pulm/cerebral edema)

Lidocaine

  • Consider for ventricular dysrhythmias if NaHCO3 alone is ineffective
NOTE
avoid IA, IB, IC antiarrhythmics, Beta-Blockers, and Calcium Channel Blockers

Phenytoin

  • Consider for ventricular dysrhythmias resistant to NaHCO3 and lidocaine

Synchronized cardioversion

  • Appropriate in pts w/ persistent unstable tachydysrhythmias

Seizures

  1. Benzodiazapines are 1st line
  2. Barbituates or Propofol are 2nd line

Hypotension

  • After repeat fluid boluses and with sodium load from NaHCO3 norepinepherine should be the first line vasopressor
  • ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed

Dialysis

Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility

Disposition

  • Consider discharge for pts who remain asymptomatic after 6hr of observation

See Also

Source

  • Goldfrank's Manual of Toxicology - Cyclic Antidepressants
  • Frommer DA, Kulig KW, Marx JA, Rumack B. Tricyclic antidepressant overdose. A review. JAMA. Jan 23-30 1987;257(4):521-6
  1. ↑ Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med. Aug 1995;26(2):195-201
  2. ↑ Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med. May 16 2002;346(20):1591-2
  3. ↑ Monteban-Kooistra WE, van den Berg MP, Tulleken JE. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. Feb 2006;32(2):281-5
  4. ↑ Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium – theory, evidence and practice. Br J Clin Pharmacol. 2015;81(3):516-24.
  5. ↑ Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14
  6. ↑ Seger DL, Hantsch C, Zavoral T, Wrenn K. Variability of recommendations for serum alkalinization in tricyclic antidepressant overdose: a survey of U.S. Poison Center medical directors. J Toxicol Clin Toxicol. 2003;41(4):331-8
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