Tricyclic antidepressant toxicity: Difference between revisions
 
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==Background==
==Background==
#Serious toxicity is almost always seen within 6hr of ingestion
*Abbreviation: TCA
#Ingestion amount:
*Used in depression and neuropathic pain
##<1mg/kg: Nontoxic
*Serious toxicity is almost always seen within 6hr of ingestion
##>10mg/kg: Life-threatening
*Coingestants that impair metabolism through cytochrome P450 often increase severity of toxicity
##>1gm: Commonly fatal
**[[Cocaine]] can produce the same sodium blockade effect and exacerbate as TCA overdose
#Coingestants often increase severity of toxicity
 
===Ingestion amount===
*<1mg/kg: Nontoxic
*>10mg/kg: Life-threatening
*>1gm: Commonly fatal


==Clinical Features==
==Clinical Features==
#Na Channel Blockade
*Na Channel Blockade (2-6 hours post ingestion)
##Negative inotropy, heart block, hypotension, ectopy
**Negative inotropy, [[heart block]], [[hypotension]], ectopy
#Anti-Histamine Effects
*Antihistamine Effects
##Sedation, coma
**Sedation, [[coma]]
#Anti-Muscarinic Effects
*Antimuscarinic Effects (early toxicity, within 2 hours)
##Central
**Central
###Agitation, delirium, confusion, [[hallucinations]]
***[[Agitation]], [[delirium]], [[confusion]], [[hallucinations]]
###Slurred speech, ataxia
***Slurred speech, [[ataxia]]
###Sedation, coma
***Sedation, [[coma]]
###[[Seizures]]
***[[Seizures]]
##Peripheral
**Peripheral
###Mydriasis, decreased secretions, dry skin, ileus, urinary retention
***Mydriasis, decreased secretions, dry skin, [[ileus]], [[urinary retention]]
###Tachycardia, hyperthermia
***[[Tachycardia]], [[hyperthermia]], [[hypertension]]
#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
##Sympathomimetic effects
**[[Sympathomimetic]] effects
##Myoclonus, hyperreflexia
**Myoclonus, hyperreflexia
##[[Serotonin Syndrome]] (only when used in combination w/ other serotonergic agents)
**[[Serotonin Syndrome]] (only when used in combination with other serotonergic agents)
*Antagonism at GABA A receptors
**[[Seizures]]


==Diagnosis==
==Differential Diagnosis==
#Serious toxicity
{{Anticholinergic types}}
##Conduction delays, [[SVT]], [[V-tach]], [[hypotension]]
{{Sodium channel blocking toxidromes}}
##Respiratory depression
##[[Seizures]]
##[[Pulmonary Edema]]
#[[ECG]]
##[[Sinus Tachycardia]] (most frequent dysrhythmia)
##PR, QRS, [[QT Prolongation]]
##Right axis deviation (of terminal 40ms)
###Terminal R wave in aVR, S wave in I/aVL<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>
##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]]


==Treatment==
==Evaluation==
*Serious toxicity
**Conduction delays, [[SVT]], [[V-tach]], [[hypotension]]
**Respiratory depression
**[[Seizures]]
**[[Pulmonary Edema]]
*[[ECG]]
**[[Sinus Tachycardia]] (most frequent dysrhythmia)
**PR, QRS, [[QT Prolongation]]
***Abnormal QRS morphology (deep slurred S wave in I and AVL)
***Threshold of QRS>100 for seizures
***Threshold of QRS>160 for ventricular dysrhythmias
**[[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>
***Terminal R wave in aVR, S wave in I/aVL
***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>
[[File:TCA_Toxicity.jpg|thumb|ECG in TCA toxicity]]
*An urine positive test result suggests only use of a TCA or another drug that cross-reacts with the screen (antimuscarinic, antipsychotic, carbamazepine, etc.)
*Quantitative serum level does not correlate with severity of illness
 
==Management==
===GI Decontamination===
===GI Decontamination===
#Gastric lavage if <1hr after ingestion
*There is no role for [[Gastric lavage]]
#Activated charcoal 1gm/kg x1
*[[Activated charcoal]] 1gm/kg x1 if <1 hour and patient awake and cooperative without signs of toxicity
 
===Cardiac Toxicity<ref>Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14</ref>===
===Cardiac Toxicity<ref>Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14</ref>===
====Sodium Bicarbonate====
====[[Sodium Bicarbonate]]====
#Indications:
*Indications:
##QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
**QRS >100ms, terminal RAD >120 deg, Brugada pattern, ventricular dysrhythmias
#Initial Dosing:
*Initial Dosing:
#Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.55)
**Give 1-2 mEq/kg as rapid IVP; may repeat as necessary (stop if pH > 7.50-7.55)
#May give as 2-3 vials or prefilled syringes (50mL each) of 8.4% NaHCO3
**May give as 3 ampules of 8.4% NaHCO3 (150 mEq) or 7.5% NaHCO3 (134 mEq)
#Infusion Dosing
*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
#Treatment Goal:
*Treatment Goal:
#QRS <100ms
**QRS <100ms
#pH 7.50-7.55
**pH 7.50-7.55
#Treatment Monitoring
**May continue for 12-24hrs due to the drugs redistribution from tissue
##Monitor for volume overload, hypokalemia, hypernatremia, metabolic alkalosis
*Treatment Monitoring
**Monitor for volume overload, hypocalcemia, hypokalemia, hypernatremia, metabolic alkalosis
**Aggressively replace serum electrolytes


====Hyperventilation====
====Hyperventilation====
*Consider in patients unable to tolerate NaHCO<sub>3</sub> (renal failure, pulm/cerebral edema)  
*Consider in patients unable to tolerate NaHCO<sub>3</sub> (renal failure, pulm/cerebral edema)
*Hyperventilate to pH of 7.50 - 7.55 (same as bicarb administration)


====Lidocaine====
====[[Lidocaine]]====
*Consider 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]]====
*Consider for ventricular dysrhythmias resistant to NaHCO<sub>3</sub> and lidocaine
*Consider for ventricular dysrhythmias resistant to NaHCO<sub>3</sub> and lidocaine


====Synchronized cardioversion====
====Synchronized cardioversion====
*Appropriate in pts w/ 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]] 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 200 ml of [[hypertonic saline|hypertonic 3% saline]] for refractory hypotension and ventricular dysrhythmias despite maximal alkalinization (pH > 7.55)


===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 over 2-3 minutes if life-threatening toxicity refractory to bicarbonate administration
*May be repeated once in 5 minutes if no improvement, followed by an infusion of 0.25 ml/kg/min for 15-30 minutes


==Disposition==
==Disposition==
*Consider discharge for pts who remain asymptomatic after 6hr of observation
*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==
==See Also==
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*[[Beta-Blocker Toxicity]]
*[[Beta-Blocker Toxicity]]
*[[Antipsychotic Toxicity]]
*[[Antipsychotic Toxicity]]
*[[Antidotes]]


==Source==
==References==
*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
 
<references/>
<references/>
[[Category:Tox]]
[[Category:Toxicology]]

Latest revision as of 20:10, 17 April 2024

Background

  • Abbreviation: TCA
  • Used in depression and neuropathic pain
  • Serious toxicity is almost always seen within 6hr of ingestion
  • Coingestants that impair metabolism through cytochrome P450 often increase severity of toxicity
    • Cocaine can produce the same sodium blockade effect and exacerbate as TCA overdose

Ingestion amount

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

Clinical Features

Differential Diagnosis

Anticholinergic toxicity Causes

Sodium Channel Blockade Toxidrome

Evaluation

ECG in TCA toxicity
  • An urine positive test result suggests only use of a TCA or another drug that cross-reacts with the screen (antimuscarinic, antipsychotic, carbamazepine, etc.)
  • Quantitative serum level does not correlate with severity of illness

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 200 ml of hypertonic 3% saline for refractory hypotension and ventricular dysrhythmias despite maximal alkalinization (pH > 7.55)

Dialysis

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

Intralipid

  • 1.5 mL/kg bolus over 2-3 minutes if life-threatening toxicity refractory to bicarbonate administration
  • May be repeated once in 5 minutes if no improvement, followed by an infusion of 0.25 ml/kg/min for 15-30 minutes

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

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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