Tricyclic antidepressant toxicity: Difference between revisions

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==Background==
==Background==
# Used in depression and neuropathic pain
* Used in depression and neuropathic pain
#Serious toxicity is almost always seen within 6hr of ingestion
*Serious toxicity is almost always seen within 6hr of ingestion
#Ingestion amount:
*Ingestion amount:
##<1mg/kg: Nontoxic
**<1mg/kg: Nontoxic
##>10mg/kg: Life-threatening
**>10mg/kg: Life-threatening
##>1gm: Commonly fatal
**>1gm: Commonly fatal
#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


==Clinical Features==
==Clinical Features==
#Na Channel Blockade
*Na Channel Blockade
##Negative inotropy, heart block, hypotension, ectopy
**Negative inotropy, heart block, hypotension, ectopy
#Anti-Histamine Effects
*Anti-Histamine Effects
##Sedation, coma
**Sedation, coma
#Anti-Muscarinic Effects
*Anti-Muscarinic Effects
##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
#Alpha1 Receptor Blockade
*Alpha1 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 w/ other serotonergic agents)


==Diagnosis==
==Diagnosis==
#Serious toxicity
*Serious toxicity
##Conduction delays, [[SVT]], [[V-tach]], [[hypotension]]
**Conduction delays, [[SVT]], [[V-tach]], [[hypotension]]
##Respiratory depression
**Respiratory depression
##[[Seizures]]
**[[Seizures]]
##[[Pulmonary Edema]]
**[[Pulmonary Edema]]
#[[ECG]]
*[[ECG]]
##[[Sinus Tachycardia]] (most frequent dysrhythmia)
**[[Sinus Tachycardia]] (most frequent dysrhythmia)
##PR, QRS, [[QT Prolongation]]
**PR, QRS, [[QT Prolongation]]
###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 dysrhymthmias  
##Right axis deviation (of terminal 40ms)
**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>
***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>
**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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==Treatment==
==Treatment==
===GI Decontamination===
===GI Decontamination===
#Gastric lavage if <1hr after ingestion
*Gastric lavage if <1hr after ingestion
#Activated charcoal 1gm/kg x1
*Activated charcoal 1gm/kg x1
===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 > 7.50-7.55)
**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 3ampules (132 mEq) of 8.4% NaHCO3
#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
#Treatment Goal:
*Treatment Goal:
##QRS <100ms
**QRS <100ms
##pH 7.50-7.55
**pH 7.50-7.55
##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, hypokalemia, hypernatremia, metabolic alkalosis


====Hyperventilation====
====Hyperventilation====
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===Seizures===
===Seizures===
#Benzodiazapines are 1st line
*Benzodiazapines are 1st line
#Barbituates or Propofol are 2nd line
*Barbituates or Propofol are 2nd line


===Hypotension===
===Hypotension===
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==Video==
==Video==
{{#widget:YouTube|id=rMVw4ImwNDo}}
{{*widget:YouTube|id=rMVw4ImwNDo}}


==References==
==References==
<references/>
<references/>
[[Category:Toxicology]]
[[Category:Toxicology]]

Revision as of 22:44, 24 May 2016

Background

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

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
  • Alpha1 Receptor Blockade
    • Sedation, orthostatic hypotension, miosis
  • Inhibition of amine reuptake
    • Sympathomimetic effects
    • Myoclonus, hyperreflexia
    • Serotonin Syndrome (only when used in combination w/ other serotonergic agents)

Diagnosis

ECG in TCA toxicity

Differential Diagnosis

Anticholinergic toxicity Causes

Treatment

GI Decontamination

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

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 3ampules (132 mEq) of 8.4% NaHCO3
  • 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, hypokalemia, hypernatremia, metabolic alkalosis

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
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

  • Benzodiazapines are 1st line
  • 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

Video

Template:*widget:YouTube

References

  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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