Tricyclic antidepressant toxicity: Difference between revisions
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*Serious toxicity is almost always seen within 6hr of ingestion
*Serious toxicity is almost always seen within 6hr of ingestion
*Coingestants often increase severity of toxicity
*Coingestants often increase severity of toxicity
**Cocaine can produce the same sodium blockade effect and exacerbate a TCA overdose
**[[Cocaine]] can produce the same sodium blockade effect and exacerbate a TCA overdose


===Ingestion amount===
===Ingestion amount===
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***Mydriasis, decreased secretions, dry skin, ileus, urinary retention
***Mydriasis, decreased secretions, dry skin, ileus, urinary retention
***Tachycardia, hyperthermia
***Tachycardia, hyperthermia
*Alpha1 Receptor Blockade
*α<sub>1</sub> Receptor Blockade
**Sedation, orthostatic hypotension, miosis
**Sedation, orthostatic hypotension, miosis
*Inhibition of amine reuptake
*Inhibition of amine reuptake
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**[[Sinus Tachycardia]] (most frequent dysrhythmia)
**[[Sinus Tachycardia]] (most frequent dysrhythmia)
**PR, QRS, [[QT Prolongation]]
**PR, QRS, [[QT Prolongation]]
***Abnormal QRS morphology (deep slurred S wave in I and AVL)
***Threshold of QRS>100 for seizures
***Threshold of QRS>100 for seizures
***Threshold of QRS>160 for ventricular dysrhymthmias
***Threshold of QRS>160 for ventricular dysrhythmias
**[[RBBB]]
**[[RBBB]]
**[[Right axis deviation]] (of terminal 40ms)<ref>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</ref>
**[[Right axis deviation]] (of terminal 40ms)<ref>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</ref>
***Terminal R wave in aVR, S wave in I/aVL
***Terminal R wave in aVR, S wave in I/aVL
***R/S > 0.7
***R/S > 0.7
***Otherwise, more simply put, tall R wave in aVR
**Brugada pattern (15%)<ref>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</ref><ref>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</ref>
**Brugada pattern (15%)<ref>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</ref><ref>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</ref>
[[File:TCA_Toxicity.jpg|thumb|ECG in TCA toxicity]]
[[File:TCA_Toxicity.jpg|thumb|ECG in TCA toxicity]]
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*Initial Dosing:
*Initial Dosing:
**Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
**Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
**May give as 3ampules (132 mEq) of 8.4% NaHCO3
**May give as 3 ampules of 8.4% NaHCO3 (150 mEq) or 7.5% NaHCO3 (134 mEq)
*Infusion Dosing<ref>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</ref>
*Infusion Dosing<ref>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</ref>
**Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
**Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
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**May continue for 12-24hrs due to the drugs redistribution from tissue
**May continue for 12-24hrs due to the drugs redistribution from tissue
*Treatment Monitoring
*Treatment Monitoring
**Monitor for volume overload, hypokalemia, hypernatremia, metabolic alkalosis
**Monitor for volume overload, hypocalcemia, hypokalemia, hypernatremia, metabolic alkalosis
**Aggressively replace serum electrolytes


====Hyperventilation====
====Hyperventilation====
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====[[Lidocaine]]====
====[[Lidocaine]]====
*At 1.5mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO<sub>3</sub> alone is ineffective
*At 1.5 mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO<sub>3</sub> alone is ineffective
;NOTE: avoid IA, IB, IC antiarrhythmics, Beta-Blockers, and Calcium Channel Blockers
*Competitively inhibits sodium channel blockade effects of TCAs
;NOTE: Avoid IA, IC antiarrhythmics, Beta-Blockers, Calcium Channel Blockers, and amiodarone


====[[Phenytoin]]====
====[[Phenytoin]]====
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====Synchronized cardioversion====
====Synchronized cardioversion====
*Appropriate in patients with persistent unstable tachydysrhythmias
*Appropriate in patients with persistent unstable tachydysrhythmias
====NEVER Use [[Physostigmine]]====
*'''''NEVER''''' use [[physostigmine]] in TCA overdose as the combination leads to lethal bradyarrhythmias<ref>Schneider G. Never Use Physostigmine in a TCA Overdose. Emergency Medicine News: May 2003 - Volume 25 - Issue 5 - p 44.</ref>
**Due to dose dependent AV blockade by physostigmine
**TCA toxicity and physostigmine interact synergistically to cause AV conduction delays


===[[Seizures]]===
===[[Seizures]]===
*[[Benzodiazapines]] are 1st line
*[[Benzodiazepines]] are 1st line
*[[Barbituates]] or [[propofol]] are 2nd line
*[[Barbituates]] or [[propofol]] are 2nd line
*[[Phenytoin]] infefective as no seizure focus in brain
*[[Phenytoin]] ineffective as no seizure focus in brain


===Hypotension===
===Hypotension===
*After repeat fluid boluses and with sodium load from NaHCO<sub>3</sub> norepinepherine should be the first line vasopressor
*After repeat fluid boluses and with sodium load from NaHCO<sub>3</sub> norepinepherine should be the first line vasopressor
*ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed
*ECMO is a successful adjunct for refractory hypotension after maximal therapy has failed
*May also consider [[hypertonic saline|hypertonic 3% saline]] for refractory hypotension


===Dialysis===
===Dialysis===
Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility
*Not useful for enhancing elimination due to the large volume of distribution and high lipid solubility
 
===[[Intralipid]]===
1.5 mL/kg bolus


==Disposition==
==Disposition==

Revision as of 17:24, 5 May 2019

Background

  • Abbreviation: TCA
  • Used in depression and neuropathic pain
  • Serious toxicity is almost always seen within 6hr of ingestion
  • Coingestants often increase severity of toxicity
    • Cocaine can produce the same sodium blockade effect and exacerbate a TCA overdose

Ingestion amount

  • <1mg/kg: Nontoxic
  • >10mg/kg: Life-threatening
  • >1gm: Commonly fatal

Clinical Features

  • Na Channel Blockade
    • Negative inotropy, heart block, hypotension, ectopy
  • Anti-Histamine Effects
    • Sedation, coma
  • Anti-Muscarinic Effects
    • Central
    • Peripheral
      • Mydriasis, decreased secretions, dry skin, ileus, urinary retention
      • Tachycardia, hyperthermia
  • α1 Receptor Blockade
    • Sedation, orthostatic hypotension, miosis
  • Inhibition of amine reuptake
    • Sympathomimetic effects
    • Myoclonus, hyperreflexia
    • Serotonin Syndrome (only when used in combination with other serotonergic agents)

Differential Diagnosis

Anticholinergic toxicity Causes

Sodium Channel Blockade Toxidrome

Evaluation

ECG in TCA toxicity

Management

GI Decontamination

Cardiac Toxicity[5]

Sodium Bicarbonate

  • Indications:
    • QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
  • Initial Dosing:
    • Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
    • May give as 3 ampules of 8.4% NaHCO3 (150 mEq) or 7.5% NaHCO3 (134 mEq)
  • Infusion Dosing[6]
    • Mix 125-150 mEq of NaHCO3 in 1L of D5W; infuse at 250 mL/hr
  • Treatment Goal:
    • QRS <100ms
    • pH 7.50-7.55
    • May continue for 12-24hrs due to the drugs redistribution from tissue
  • Treatment Monitoring
    • Monitor for volume overload, hypocalcemia, hypokalemia, hypernatremia, metabolic alkalosis
    • Aggressively replace serum electrolytes

Hyperventilation

  • Consider in patients unable to tolerate NaHCO3 (renal failure, pulm/cerebral edema)
  • Hyperventilate to pH of 7.50 - 7.55 (same as bicarb administration)

Lidocaine

  • At 1.5 mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO3 alone is ineffective
  • Competitively inhibits sodium channel blockade effects of TCAs
NOTE
Avoid IA, IC antiarrhythmics, Beta-Blockers, Calcium Channel Blockers, and amiodarone

Phenytoin

  • Consider for ventricular dysrhythmias resistant to NaHCO3 and lidocaine

Synchronized cardioversion

  • Appropriate in patients with persistent unstable tachydysrhythmias

NEVER Use Physostigmine

  • NEVER use physostigmine in TCA overdose as the combination leads to lethal bradyarrhythmias[7]
    • Due to dose dependent AV blockade by physostigmine
    • TCA toxicity and physostigmine interact synergistically to cause AV conduction delays

Seizures

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
  • May also consider hypertonic 3% saline for refractory hypotension

Dialysis

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

Intralipid

1.5 mL/kg bolus

Disposition

  • Consider discharging patients who remain asymptomatic after 6hr of observation
  • Patients with decreased level of consciousness or seizures should be admitted to ICU

See Also

Video

{{#widget:YouTube|id=rMVw4ImwNDo}}

References

  1. ↑ Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium – theory, evidence and practice. Br J Clin Pharmacol. 2015;81(3):516-24.
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  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
  7. ↑ Schneider G. Never Use Physostigmine in a TCA Overdose. Emergency Medicine News: May 2003 - Volume 25 - Issue 5 - p 44.
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