This presentation includes overview of Sri cyclic antidepressants, its toxicokinetics, toxic mechanism and clinical features. The management is explained in detailed according Resus- RSI- DEAD steps. Main steps includes resuscitation, risk assessment, investigations, supportive therapy, decontamination, antidote- sodium bicarbonate, lipid emulsion and elimination methods.

1. TRI CYCLIC
ANTIDEPRESSANT
POISONING
Dr KTD Priyadarshani
Registrar in Emergency Medicine
Teaching Hospital Peradeniya
2023/03/31

2. SCOPE
• OVERVIEW
• TOXIC MECHANISM
• CLINICAL FEATURES
• MANAGEMENT
• DISPOSITION

3. OVERVIEW
• Amitriptyline, Clomipramine,
Imipramine
• Narrow therapeutic index
• Toxicity can occur at therapeutic
dosages
• Potentially life threatening
• Rapid onset on anticholinergic,
CNS & CVS toxicity

4. TOXICOKINETIC
• Overdose >10-20mg/kg result in severe, life threatening poisoning
• Rapid absorption- peak levels 2-6 hrs (Severe toxicity usually
manifests within 2 hours but any overdose requires close cardiac
monitoring for 6 hours post ingestion)
• Lipophilic- readily cross BBB
• Highly protein bound and the amount of unbound TCA increases in
acidosis
• Metabolized by the liver CYP450 to active metabolites
• Excreted by the kidney elimination t1/2 10-80 hours

5. TOXIC MECHANISM
• NE & 5HT reuptake inhibitors, GABA A Blockers & use dependent fast
Sodium channel blockers. Also block M1,H1, peripheral alpha 1, inhibit K
channel & direct myocardial depression
• C/F is a combination of
• anticholinergic effects at autonomic nerve ending and in the brain
• blockade of cardiac sodium channels
• blockade of alpha1 adrenergic receptors

6. CLINICAL FEATURES
Anticholinergic Cardiovascular CNS Serotonin
syndrome
Secondary
complications
Dry mouth
Hot dry skin
Urinary retention
Ileus
Dilated pupils
Pyrexia
Confusion
Convulsions
Hypotension
Sinus tachycardia
Prolonged PR, QRS
& QT
AV Block
Broad complexes
bradycardias
Drowsiness
Ataxia
Divergent squint
Hyperreflexia
Hypertonia
Extensor plantar
Seizures
Coma
Respi depression
CNS effects
NM hyperactivity
Autonomic
instability
Aspiration
pneumonia
Pulmonary edema
Anoxic
encephalopathy
Hyperthermia
Rhabdomyolysis
Seizures

7. MANAGEMENT- RESUSCITATION
• A- Oxygen, intubation
• Coma, respiratory acidosis, seizures
• B- hyperventilate to max pCO2 >30mmHg
• C- Hypotension, cardiac arrhythmias/ arrest
• Serial ECGs
• Fluid up to 30ml/kg
• IV bicarbonate (pH 7.5- 7.55)
• Lignocaine 1.5mg/kg
• If refractory- glucagon (IV 1mg bolus), adrenaline or
noradrenaline infusions
• Cardiac monitor
• D- seizures
• BDZ
• Phenobarbitone 10-15 mg/kg
• Continuous infusion of midazolam or Propofol
• Urine catheter, NG tube

8. MANAGEMENT- RISK ASSESSMENT
Dose Effect
< 5 mg/kg Minimal symptoms
5-10 mg/kg Minor toxicity: Drowsiness & some anticholinergic symptoms
>10 mg/kg Significant toxicity expected within 2-4 hr. anticholinergic
effects may be masked by coma
>15 mg/kg Potentially life threatening. Seizures & myoclonus
>30 mg/kg Severe toxicity with pH dependent cardiotoxicity & coma
expected to last >24 hr
Concurrent administration with
• CYP2D6 inhibitors may enhance toxicity
• Benztropine or diphenhydramine may cause additive anticholinergic or antihistamine effects
• Antihypertensive

9. MANAGEMENT- INVESTIGATIONS
Bedside
• ECG- serial monitoring
• Blood sugar
• ABG- hypoxia, hypercapnia, metabolic acidosis
Laboratory
• RFT

10. ECG
• Widening of the QRS
• >100 mS- predictive of
seizures
• >160 mS- predictive of VT
• Large terminal R wavein
aVR
• increased R/S ratio (>0.7)
in aVR
• QT prolongation

11. MANAGEMENT- SUPPORTIVE THERAPY
• Hypokalemia
• Replace potassium as needed
• Altered level of consciousness
• Reassurance
• Decreased environmental stimulation
• BDZ
• Avoid physostigmine, flumazenil or phenytoin

12. MANAGEMENT- SUPPORTIVE THERAPY
• Torsade pointes & refractory dysrhythmias
• Cardioversion is unlikely to be successful
• Repeat dose of Sodium bicarbonate (2mmol/kg) every 1-2 min max 6mmol/kg
or until perfusing rhythm is restored
• 3% NS 1-3 ml/kg over 10 min
• Lignocaine 1.5mg/kg IV when pH of >7.5
• Mg SO4 2g IV
• Overdrive pacing
• Lipid emulsion
• Avoid class I antiarrhythmics (procainamide, lidocaine, phenytoin,
flrcainide), beta blockers, calcium channel blockers or class III
antiarrhythmics (amiodarone, sotalol, ibutilide)

13. MANAGEMNT- DECONTAMINATION
• Activated charcoal >1g/kg PO
• With in 1hr of ingestion as long as airway is stable & patient is awake
• Multi dose charcoal- AVOID
• Whole bowel irrigation - AVOID

14. MANAGEMENT- ANTIDOTE
• Na Bicarbonate & hyperventilation
• Ventricular dysrhythmia
• Hypotension refractory to IV fluid
• Seizure
• QRS >100ms
• IV Lipid emulsion

15. SODIUM BICARBONATE
• Initial bolus- 1-2 mEq/kg
• Repeat until patient improvement is noted or until blood pH is between
7.5-7.55
• Or continuous infusions of sodium bicarbonate 150 mEq added to 1L of
5% dextrose in water IV in 2-3 ml/kg/hr

16. • 3 end goals of sodium loading – perform 30 min repeat ABG
• Narrowing the QRS to normal for the patient or less than 140 mS (<100mS)
• Max Na 155 mmol/L
• pH 7.5-7.55
• Excess sodium bicarbonate can kill
• Severe alkalemia
• Hypernatremia
• Hypokalemia
• Maximum dose 6mmol/kg

17. LIPID EMULSION
• Highly lipid soluble- lipid sink
• No convincing evidence
• Refractory Cardiotoxicity- 20% lipid emulsion
• 100ml IV bolus (1.5 ml/kg) over 2-3 min
• Infusion 18 ml( 0.25 mk/kg) per/min to a total dose of 10ml/kg
•

18. MANAGEMENT- ELIMINATION
• Hemodialysis, hemofiltration , peritoneal dialysis, forced diuresis – is
ineffective as only 1-2% of total TCA burden is found in blood.

19. DISPOSITION
• Asymptomatic after 6hrs
• Can discharge
• Symptomatic patients
• Admit & observe
• Severe toxicity
• ICU

20. REFERNCES
• Tintinali’s Emergency Medicine- 9th edition
• https://litfl.com/tricyclic-overdose-sodium-channel-blocker-toxicity/
• https://emcrit.org/ibcc/nacb/
• https://emedicine.medscape.com/article/819204-overview
• https://geekymedics.com/tricyclic-antidepressant-overdose/