گروه طب اورژانس دانشگاه علوم پزشکی اصفهان
Woman 34 years old
Hx = negative
Finding= confused, agitated, dry skin, pupil dilatated,
Man, 42 years old
Agitated with no problem
Hx of suicide
Is the most common cause of
death due to drug overdose
High Mortality Rate
Anxiolytic & Antidepressive
T.C.A Poisoning is common
Poisoning is usually suicidal
Toxic effects are typically moderate
Severe toxicity or death may occur in
large ingestion or co-ingestion
THE CAUSES OF THE
HIGH MORTALITY RATE
USE BY DEPRESSIVE PATIENTS
SEVERE CARDIOVASCULAR TOXICITY
SEVERE C.N.S TOXICITY
Serum peak 2-8 h
First pass hepatic metabolism: 20-70%
High v/d 10-20 l/kg
High Tissue Concentration: 100 times
T.C.A s Inhibit Reuptake of Neurotransmitters:
AT TERAPEUTIC DOSE :
Have Different Anticholinergic &
AT TOXIC DOSE :
Most Have Similar Effects
Lofepramin : Minimum Toxicity
Amoxapin : Max. Incidence of Seizure &
Min. Cardiovascular Toxicity
Maprotiline : High Cardiovas. Toxicity
AFTRE OVERDOSE :
Onset of Toxicity is typically rapid
Gastric emptying become slow & absorption
Most death occur within first 24 hrs
Tissues distribution is very rapid
Rapidly progression from no symptom to life-
threatening cardiotoxicity or seizure occur in less
than 1 hr
HEART :Myocardial Depression, Dysrhythmia
, Conduction abnormality
VASCULAR : Hypotention
C.N.S : seizure, myoclonus, coma
OTHERS : G.I.T ,Urinary System, Hyperthermia ,
Metabolic Acidosis , Mydriasis , Dry Skin , . . .
Conduction Delay ( QRS Prolongation )
ventricular bigeminy , right axis deviation , wide QRS complex
, long Q-T interval , and right deviation of terminal 40-msec
QRS vector in limb leads , with prominent R wave in aVR
Loss of consciousness :
Lethargy & Coma
Dellirium: Agitation, Disorientation,
Seizure & Myoclonus
MECHANISM OF C.N.S TOXICITY
Block of cholinergic Receptors
Block of GABA Receptors in Brain
Inhibition of Fast Na Channel in
Seizure & Coma
* Alpha Blockade Vasodilation &
Excessive heat generation
A.R.F (Rhabdomyolysis , Hypotension)
As low as 100 mg in children
Ingestion of 2-3 times the daily dose in adult
Ingestion of more than 1 gr is lifethreatening
Ingestion of 300-1000 mg Mild toxicity
1-2 g Moderate
2-3 g Severe ( lethal)
Seizure , Loss of consciousness
Agitation , increased DTR , myoclonus
ECG findings QRS Widening
B.L.S & A.L.S
Air way Management
Treatment of Shock & Hypotension
Fluid & Electrolyte Correction
Acid - Base disturbances
Focused on aggressive airway management:
Endotracheal intubation should be performed
if the patient is exhibiting a markedly decreased level of
if the level of consciousness is rapidly deteriorating.
Gasteric Lavage ( O.G.T, Char. - Lav. - Char )
Activated Charcoal ( M.D.A.C )
EMESIS is contraindicated
Dialysis is not effective
Flumazenil should not be used
Physostigmine is contraindicated in CA overdose.
Seizures, cardiac arrest, and death have occurred
when physostigmine has been used in CA overdose."
Hypertension is usually mild and transient and requires no
begins with isotonic crystalloids, 10 cc/kg
Second line : sodium bicarbonate
If hypotension does not resolve, third line : norepinephrine or dopamine is
High-dose dopamine (20 to 30 mic g/kg/min)
norepinephrine (2 to 20 mic g/min) may be necessary for the direct α,- agonist effect.
For inotropic support alone, dobutamine is controversial
Antidote Therapy : Sodium Bicarbonate
Wide QRS > 100 ms
R terminal > 3 mm in AVR
Antidote Therapy : Sodium Bicarbonate
Serum alkalinization is clinically effective in decreasing CA-induced
intraventricular conduction delays.
The major effect of increasing pH seems to be increased sodium
conductance through myocardial sodium channels rather than the
increase in plasma protein binding.·
NaHC03 is administered by intra- venous boluses of 1 to 2 mEq/kg until
hypotension improves and the QRS narrows to 100 msec, or until serum
pH increases to a maximum of 7.50 to 7.55.
Speed of infusion : 2-3 cc/kg/min
After obtaining the desired endpoint with intravenous NaHC0
boluses initiating continuous isotonic intravenous infusion by
adding three ampules of 8.4% NaHC03 (50 mEq/ampule, 100
mOsm/ampule) to 1 L of 5% dextrose in water.
Repeat boluses and continuous intravenous infusion should be guided by serial
measurements of arterial pH and QRS duration.
Sinus tachycardia is usually well tolerated and does not require specific therapy.
β-Receptor antagonists and physostigmine are contraindicated.
Determining the specific type of wide-complex rhythm is unnecessary
because treatment in either case is intravenous NaHC03
Lidocaine has not been consistently effective.
Phenytoin has been shown to increase the frequency and duration of
episodes of ventricular tachycardia and is not recommended as an
anti dysrhythmic agent
Type IA antidysrhythmics (quinidine, disopyramide, procainamide)
and type IC antidysrhythmics (flecainide, moricizine, propafenone)
are contraindicated because they also inhibit fast sodium channels.
A transvenous pacemaker and over- drive pacing can be used for
associated polymorphic ventricular tachycardia (torsades de pointes) not
responsive to magnesium.
Bradydysrhythmias are rare and late .
Q-T prolongation, PR prolongation, do not mandate specific therapy
Treatment with NaHC03 , hypertonic sodium chloride, and
hyperventilation does not resolve completely Q-T prolongation, which
involves not only sodium channel blockade, but also protracted
depolarization from potassium efflux blockade.
Benzodiazepines should be used for agitation
seizures usually respond to intravenous lorazepam or diazepam. '
Seizures refractory to other benzodiazepines have terminated with intravenous
midazolam boluses of 2.5 to 10 mg and continuous intravenous infusions."
If benzodiazepines fail to terminate prolonged o repetitive seizures, phenobarbital
may be administered in a loading dose of 20 mg/kg, given at a rate of up to 50
mg/min in adults or up to 1 mg/kg/min in children.
Propofol also has been used to treat refractory seizures successfully. A loading dose
of 2.5 mg/kg is followed by continuous infusion of 25 to 200 µg/kg/min.
Phenytoin may cause more and longer episodes of ventricular tachycardia.
If maximal doses of benzodiazepines, phenobarbital, or propofol are ineffective,
neuromuscular blockade and general anesthesia with continuous
electroencephalogram monitoring are recommended to prevent rhabdomyolysis
and hyperthermia caused by excessive muscle activity .
Life-threatening hyperthermia (rectal temperature >40° C) is best treated
with control of seizures and neumuscular blockade.
A nondepolarizing neuromuscular blocker (e.g., rocuronium) is
recommended if rabdomyolysis and hyperkalemia with ECG changes
Evaporative cooling should be used until core temperature reaches 38.5° C.,
Treatment of Neurologic Complications
of Antidepressant Poisoning
Patients with known or suspected CA overdoses require 6 hours of observation
with continuous cardiac monitoring and pulse oximetry.
After 6 hours of obser vation, patients may be discharged for psychiatric
evaluation if they do not develop :
(1) ventilatory insufficiency,
(2) desaturation on pulse oximetry,
(3) QRS greater than 100 msec,
(4) sinus tachycardia greater than 120 beats/min,
(7) decreased level of consciousness,
(9) abnormal or inactive bowel sounds.
Patients who exhibit any of these findings should
be admitted to an lCU