TCA mechanisms of Toxicity

1
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

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 ----gt 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
TCAs and Hypotension

• Dopamine is a precursor to norepinephrine
• Dopamine stimulates the release of stored
  norepinephrine
• Dopamine stimulates adrenergic receptors

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 gt
• Terminal 40 msec right axis

15
TCA toxicity and the ECG

• Tall R in aVR, R/S ratio in aVR gt 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
ECG and Toxicology

• 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

24
Case of the day!

• Vtach

• Management?

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 gt 100 msec (or gt 120 msec)
• New/unexplained RBBB
• R in aVR gt 3mm, R/S ratio gt 0.7, or terminal 40
  msec right axis
• ? Which are goldfranks 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 ------gt what do you say?

31
TCA and lab testing

• Urine TCA screen
• Dip stick screen, immunoassay
• HORRIBLE specificity thus the lab doesnt even do
  it

• Serum TCA levels
• Do NOT correlate with toxicity
• False ves
• Benadryl
• Gravol
• Flexeril
• dfldjf
• fldljfkl

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