Tricyclic antidepressant toxicity
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)
- Antagonism at GABA A receptors
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
- Toxicology (Main)
- Calcium Channel Blocker Toxicity
- Beta-Blocker Toxicity
- Antipsychotic Toxicity
- Antidotes
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.