Transcript TCA mechanisms of Toxicity

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
Anticholinergic Toxidrome
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Agitation/altered LOC
Red, hot, dry skin
Tachycardia
Dilated pupils
No bowel sounds
Urinary retension
Mild hyperthermia
Mild hyperreflexia
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
Acidosis
Seizure
DEATH
Shock
Cardiac
toxicity
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
• 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 day!
• HR 120, BP 80/50
• What is your management?
• Why?
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 Hypotension
• Dopamine is a
precursor to
norepinephrine
• Dopamine stimulates
the release of stored
norepinephrine
• Dopamine stimulates
adrenergic receptors
TCAs and Hypotension
TCAs and Hypotension
TCAs and Hypotension
• Extreme options!
– ECMO
– Cardiac bypass
– IABP
Case of the day!
Interpretation?
Will she have a bad outcome?
TCA toxicity and the ECG
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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 ECG
• Tall R in aVR, R/S ratio in aVR > 0.7
TCA toxicity and the ECG
• Terminal 40 msec right axis
TCA toxicity and the ECG
• Terminal 40 msec right axis
TCA toxicity and the ECG
• What ECG features are predictive of TCA
toxicity?
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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
aVR: tall R wave and R/S ratio
Terminal 40 msec right axis
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
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TCA
Haldol etc
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Case of the day!
• Vtach
• Management?
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?
• 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?
• 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?
• 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??
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
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Benadryl
Gravol
Flexeril
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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