Tricyclic antidepressant toxicity: Difference between revisions
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*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 | ||
*Coingestants often increase severity of toxicity | *Coingestants that impair metabolism through cytochrome P450 often increase severity of toxicity | ||
**[[Cocaine]]can produce the same sodium blockade effect and exacerbate | **[[Cocaine]] can produce the same sodium blockade effect and exacerbate as TCA overdose | ||
===Ingestion amount=== | ===Ingestion amount=== | ||
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==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 | ||
* | *Antihistamine Effects | ||
**Sedation, coma | **Sedation, [[coma]] | ||
* | *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]] | ||
* | *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 with other serotonergic agents) | **[[Serotonin Syndrome]] (only when used in combination with other serotonergic agents) | ||
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***Abnormal QRS morphology (deep slurred S wave in I and AVL) | ***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 | ***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> | ||
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**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]] | ||
*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== | ==Management== | ||
===GI Decontamination=== | ===GI Decontamination=== | ||
*[[Gastric lavage]] | *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>=== | ||
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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 | **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. | *At 1.5 mg/kg, consider lidocaine for ventricular dysrhythmias if NaHCO<sub>3</sub> alone is ineffective | ||
;NOTE: | *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]]=== | ||
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*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 | *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== |
Revision as of 19:40, 20 January 2020
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
- Na Channel Blockade (2-6 hours post ingestion)
- Negative inotropy, heart block, hypotension, ectopy
- Antihistamine Effects
- Sedation, coma
- Antimuscarinic Effects (early toxicity, within 2 hours)
- Central
- Peripheral
- Mydriasis, decreased secretions, dry skin, ileus, urinary retention
- Tachycardia, hyperthermia, hypertension
- 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
- Medications[1]
- Atropine
- Antihistamines
- Antidepressants
- Antipsychotics
- Muscle relaxants
- Anti-Parkinsonians
- Plants
- Jimson weed (Devil's trumpet)
- Amanita mushroom
Sodium Channel Blockade Toxidrome
- Phenothiazines
- Antihistamines
- Sotalol
- TCAs
- Antipsychotics
- Cocaine
- Anti-spasmodics, cyclobenzaprine
- Chloroquine
- Anti-malarials
- Class Ia and Ic antiarrhythmics
- Local anesthetic systemic toxicity
- Venlafaxine toxicity
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)[2]
- 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%)[3][4]
- 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
- There is no role for Gastric lavage
- Activated charcoal 1gm/kg x1 if <1 hour and patient awake and cooperative without signs of toxicity
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
- Benzodiazepines are 1st line
- Barbituates or propofol are 2nd line
- Phenytoin ineffective as no seizure focus in brain
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
Video
{{#widget:YouTube|id=rMVw4ImwNDo}}
References
- ↑ Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium – theory, evidence and practice. Br J Clin Pharmacol. 2015;81(3):516-24.
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14
- ↑ 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
- ↑ Schneider G. Never Use Physostigmine in a TCA Overdose. Emergency Medicine News: May 2003 - Volume 25 - Issue 5 - p 44.