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TCA mechanisms of Toxicity

Anti-cholinergic Na+ channel blockade K+ channel blockade Alpha 1 antagonism Serotonin reuptake inhibition GABA antagonism. Anticholinergic toxidrome Wide QRS Prolonged QT Hypotension Seritonin syndrome Seizures. TCA mechanisms of Toxicity. Anticholinergic Toxidrome.

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TCA mechanisms of Toxicity

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  1. Anti-cholinergic Na+ channel blockade K+ channel blockade Alpha 1 antagonism Serotonin reuptake inhibition GABA antagonism Anticholinergic toxidrome Wide QRS Prolonged QT Hypotension Seritonin syndrome Seizures TCA mechanisms of Toxicity

  2. Anticholinergic Toxidrome • Agitation/altered LOC • Red, hot, dry skin • Tachycardia • Dilated pupils • No bowel sounds • Urinary retension • Mild hyperthermia • Mild hyperreflexia

  3. Case of the day! • After you intubate, patient has a generalized seizure • Why? • Anticholinergic effect • Gaba antagonism • Hypotension • Why are seizures so bad? • Management?

  4. TCA overdoses and seizures Acidosis Seizure Cardiac toxicity DEATH Shock

  5. TCA toxicity and Seizures • Management • First line: benzodiazepines • Second line: phenobarbital • Third line agents: propofol • Avoid dilantin (Na+ channel blockade) • Should you give bicarb? Yes

  6. Flumazenil • Why is flumazenil contraindicated in a patient with BZD + TCA overdose? • Will precipitate seizures ----> acidosis, cardiac toxicity, death, call CMPA • Flumazenil is generally not indicated in the overdose setting for this reason • One exception may be a pediatric ingestion of BZD with absolutely no suspicion of coingestant

  7. Case of the day! • HR 120, BP 80/50 • What is your management? • Why?

  8. TCAs and Hypotension • Fluids, go early to pressors • Norepinephrine is the pressor of choice • If you are going to use dopamine, titrate up to alpha range (15 - 20 ug/kg/min) • Why is norepinephrine better than dopamine?

  9. Dopamine is a precursor to norepinephrine Dopamine stimulates the release of stored norepinephrine Dopamine stimulates adrenergic receptors TCAs and Hypotension

  10. TCAs and Hypotension

  11. TCAs and Hypotension

  12. TCAs and Hypotension • Extreme options! • ECMO • Cardiac bypass • IABP

  13. Case of the day!Interpretation?Will she have a bad outcome?

  14. TCA toxicity and the ECG • Sinus tachycardia • Prolonged QT • Wide QRS • Wide complex tachycardia: SVT with aberrancy or Vtach • Right BBB • Tall R wave in aVR • R/S ration in aVR > • Terminal 40 msec right axis

  15. TCA toxicity and the ECG • Tall R in aVR, R/S ratio in aVR > 0.7

  16. TCA toxicity and the ECG • Terminal 40 msec right axis

  17. TCA toxicity and the ECG • Terminal 40 msec right axis

  18. TCA toxicity and the ECG • What ECG features are predictive of TCA toxicity? • QRS width • Tall R in aVR • R/S ratio in aVR • Terminal 40 msec right axis • Which are the most sensitive/specific for TCA toxicity?

  19. QRS width

  20. aVR: tall R wave and R/S ratio

  21. Terminal 40 msec right axis

  22. What is the differential dx of wide QRS in the overdose setting?

  23. Wide QRS (Na+ channel blockade) TCAs Gravol, bendadryl Cocaine and other sympathomimetics Haldol and other neuroleptics Celexa Carbemezepine? kdjflfjljletc Prolonged QTc TCA Haldol etc Ia Ic dfjkl ECG and Toxicology

  24. Vtach Management? Case of the day!

  25. TCA and Sodium Bicarbonate • Sodium Bicarbonate is the treatment of choice for cardiac toxicity • Dose = 1-2 mEq/kg iv bolus q10 min prn • End points = no indication, pH 7.50 - 7.55 • Monitor response with repeat ECGs

  26. TCA and Sodium Bicarbonate: How does it work? • Increases protein binding • TCAs are albumin bound which is pH sensitive; minor role b/c large Vd and lipophilic thus most TCA is in tissue not serum • Alkalosis • the TCA to Elevated pH decreases the binding of the voltage gated sodium channel • Sodium loading • Na load with bicarb creates a larger gradient across the Na+ channel

  27. TCA and Sodium Bicarbonate: What are the indications? • Hypotension • Wide complex tachycardia • Conduction blocks • QRS > 100 msec (or > 120 msec) • New/unexplained RBBB • R in aVR > 3mm, R/S ratio > 0.7, or terminal 40 msec right axis • ? Which are goldfrank’s recommendations • ? seizures

  28. TCA and Sodium Bicarbonate: Bolus versus infusion? • Boluses are preferred for initial indications: Why? • All studies showing effect of bicarb have used a bolus • Probably better b/c big Na load with bolus overcomes Na blockade; Na load likely more important than pH change • Repeat boluses vs infusion never directly studied • Bicarb infusion resonable for patient requiring repeat boluses

  29. Could Fab fragments be the cure for the TCA overdose??

  30. Case of the day! • ICU resident order serum TCA level and urine TCA screen ------> what do you say?

  31. Urine TCA screen Dip stick screen, immunoassay HORRIBLE specificity thus the lab doesn’t even do it Serum TCA levels Do NOT correlate with toxicity False +ves Benadryl Gravol Flexeril dfldjf fldljfkl TCA and lab testing

  32. TCA overdose and disposition • Toxicity develops within 6 hrs • Monitored for 6hrs: NO seizures, hypotension, arrythmias, no bicarb Rx • Can d/c home or to psych • ICU for seizures, hypotension, arrythmias, decreased LOC • Telemetry for prolonged QTc • Duration of cardiac monitoring • 24hrs after normalization of BP, off alkalinization/antidysrhythmics/pressors

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