Tca mechanisms of toxicity
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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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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

Anticholinergic Toxidrome

  • Agitation/altered LOC

  • Red, hot, dry skin

  • Tachycardia

  • Dilated pupils

  • No bowel sounds

  • Urinary retension

  • Mild hyperthermia

  • Mild hyperreflexia


Case of the day

Case of the day!

  • After you intubate, patient has a generalized seizure

  • Why?

    • Anticholinergic effect

    • Gaba antagonism

    • Hypotension

  • Why are seizures so bad?

  • Management?


Tca overdoses and seizures

TCA overdoses and seizures

Acidosis

Seizure

Cardiac toxicity

DEATH

Shock


Tca toxicity and seizures

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


Flumazenil

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


Case of the day1

Case of the day!

  • HR 120, BP 80/50

  • What is your management?

  • Why?


Tcas and hypotension

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?


Tcas and hypotension1

Dopamine is a precursor to norepinephrine

Dopamine stimulates the release of stored norepinephrine

Dopamine stimulates adrenergic receptors

TCAs and Hypotension


Tcas and hypotension2

TCAs and Hypotension


Tcas and hypotension3

TCAs and Hypotension


Tcas and hypotension4

TCAs and Hypotension

  • Extreme options!

    • ECMO

    • Cardiac bypass

    • IABP


Case of the day interpretation will she have a bad outcome

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


Tca toxicity and the ecg

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


Tca toxicity and the ecg1

TCA toxicity and the ECG

  • Tall R in aVR, R/S ratio in aVR > 0.7


Tca toxicity and the ecg2

TCA toxicity and the ECG

  • Terminal 40 msec right axis


Tca toxicity and the ecg3

TCA toxicity and the ECG

  • Terminal 40 msec right axis


Tca toxicity and the ecg4

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?


Qrs width

QRS width


Avr tall r wave and r s ratio

aVR: tall R wave and R/S ratio


Terminal 40 msec right axis

Terminal 40 msec right axis


What is the differential dx of wide qrs in the overdose setting

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


Ecg and toxicology

Wide QRS (Na+ channel blockade)

TCAs

Gravol, bendadryl

Cocaine and other sympathomimetics

Haldol and other neuroleptics

Celexa

Carbemezepine?

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Prolonged QTc

TCA

Haldol etc

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Ic

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ECG and Toxicology


Case of the day2

Vtach

Management?

Case of the day!


Tca and sodium bicarbonate

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


Tca and sodium bicarbonate how does it work

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


Tca and sodium bicarbonate what are the indications

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


Tca and sodium bicarbonate bolus versus infusion

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


Could fab fragments be the cure for the tca overdose

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


Case of the day3

Case of the day!

  • ICU resident order serum TCA level and urine TCA screen ------> what do you say?


Tca and lab testing

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

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TCA and lab testing


Tca overdose and disposition

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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