This is a case of TCA poisoning in NT West Cluster of HA in Hong Kong. For education purpose in Certificate course in Clinical Toxicology 2013-2014.

1. A fainting case in a FM clinic
Dr Aaron LEE Fook Kay
NTWC Resident
Family Medicine & Primary Care Unit

2. A 20 year old lady with major depressive
disorder
 Regular FU in FM Clinic
 Accompanied by her mother who stated that her
daughter had taken 25 of the patient’s
antidepressant tablets 2 hours earlier
 The patient was alert and feel fainting with only slight
abnormalities in vital signs
 These include pulse of 125 bpm, and RR at 28 per
minute. Bowel sounds are hypoactive

3. ECG changes
 ECG showed a sinus tachycardia and QRS duration
of 0.10 seconds
 Ipecac was given by mouth and emesis contained
some pill fragments
 The patient was closely observed for the next 2
hours in the FMC and sent to AED by ambulance
because of semi-consciousness

4. At AED
 BP 90/ 60 mmHg
 P= 120 bpm
 GCS- 12/ 15
 The patient was closely observed for the next 4
hours in the Emergency Department
 During this time, she slowly improved and was
awake, alert and able to walk unassisted to the
washroom

5. In Medical ward
 She was then (3:30 am) transferred to the medical
ward for further evaluation
 All vital signs were now approximately normal
 At 5 am, a MO examined her and noted that her
speech was slurred, her gait unsteady and she was
fearful, agitated and hallucinating
 Another ECG was performed

7. ECG now…
 Wide complex tachycardia (WCT), Right Axis
Deviation (RAD), hidden p wave in ST/ T complex
(best seen II, aVF);
 terminal R wave in aVR> 3mm. R/S ratio in aVR. 0.7;
 atypical RBBB in V1-2 (Bizzare morphology with
taller L rabbit ear)

9. What is the diagnosis?
 Tachycardia, wide QRS
 Terminal 40 ms, RAD presenting as a R wave in lead
aVR; R wave typically > 3 mm in this particular drug
overdose

10. Final outcome
 During the following 2 hours, her vital signs
collapsed with respirations becoming labored, blood
pressure dropping precipitously, and pulse become
irregular
 Despite efforts at cardiopulmonary resuscitation, she
was certified dead at 6 am, 11 hours after ingestion
of the drug

11. What was the drug which caused this
woman’s death?
 a) Amitriptyline
 b) Acetaminophen
 c) Fluoxetine (Prozac)
 d) Digoxin

12. Answer is (a)
 This is a diagnostic dilemma because the patient’s
presentation is very unusual. An important point is
that the drug was identified by the mother was an
anti-depressant. This allows us to rule out digoxin
and acetaminophen as possible causes
 Of the remaining 2, the former is relatively benign &
would be under less suspicion than amitriptyline, a
drug that causes many deaths

13.  There are a number of case reports that patients
who have improved significantly after a TCA
poisoning & then abruptly reversed course with
marked increase in symptom severity

14. What is the expected lethal plasma level of
TCA?
 a) > 15 ng/ mL
 b) >100 ng/ mL
 c) > 1000 ng/ mL
 d) > 10,000 ng/ mL

15. Answer is (c)
 Case reports show that plasma level greater than
1000 ng/ mL have been correlated with seizure,
coma, arrhythmias, cardiac arrest, and death

16. Specific levels
 Plasma level of some of the TCA can be measured
by clinical laboratories
 Therapeutic concentration are usually less than 0.3
mg/L (300 ng/ mL)
 Total concentrations of parent drug plus metabolite
of 1 mg/ L (1000 ng/ mL) or greater are usually
associated with serious poisoning
 In general, QRS interval & clinical manifestations are
reliable indicators of toxicity

17. Why was there a fluctuating course for this
patient’s clinical presentation?
 a) TCA is known to be absorbed very slowly
 b) TCA takes days to become effective
 c) In overdose the anticholinergic effects of TCA slow
absorption from the gut
 d) none of the above

18. Answer is (c)
 Among the toxic effects of TCA , anticholinergic
activity is one of the earliest to occur
 This inhibition of nerve transmission across
cholinergic synapses include GI peristalsis
 Therefore, it makes sense that the presence of TCA
would slow its own absorption

19. How can we rule out a second dose of TCA
while the patient was in hospital?
 a) Drug unavailable to the patient
 b) She was under constant observation
 c) This drug is known to display this kind of
behaviour
 d) All of the above

20. Answer is (d)
 In view of the dramatic change in this patient’s
disease course, which occurred after she appeared
to be improving, it is logical to suspect that she took
a second dose of TCA
 This was doubted in this case as the patient was
closely watched & was dressed in a hospital gown in
which she could not hide any drugs
 It is, therefore, reasonable to assume that all of her
symptoms were related to the original dose

21. Which are common signs of TCA overdose?
 a) Tachycardia
 b) Agitation
 c) Seizures and coma
 d) All of the above
 e) none of the above

22. Answer is (d)
 The major problem with TCA is that they are not
sufficiently specific
 They interfere with many different neurotransmitters
 Thus,3 major organ systems are affected: the
Autonomic Nervous System, the Central Nervous
System and cholinergic neurons

23. TCA poisoning
 TCA exerts its major toxicity via Na channel
blockade and anti-cholinergic effect
 Toxicity is expected within 6 hours after ingestion,
usually within 1-2 hours in significant poisoning,
including cardiac toxicity, CNS toxicity and anti-
cholinergic toxidrome
 Cardiac toxicity, in form of hypotension and
tachyarrhythmia, is the major concern
 QRS duration in ECG predicts the probability of
seizure(1/3 > 100ms) and ventricular arrhythmia (1/2
> 160ms)
 Clinical worsening can be rapid and lethal

24. TCA poisoning
 Anti-cholinergic toxidrome (- atropine effect)
 -Blind as a bat (pupil dilatation)
 -Red as a beet (flushed skin)
 -Hot as a hare (hyperthermia secondary to lack of
sweat)
 Dry as a bone (dry mucous membrane)

25. Mx of TCA poisoning
 Ensure ABC intensive monitoring; consider early
intubation and hyperventilation
 GI decontamination with gastric lavage and activated
charcoal 1 g/ kg within 1-2 hr post-ingestion
 1st-line treatment of arrhythmia: NaHCO3
 Avoid Ia (Procainamide) & Ic (Flecanide)
antiarrhythmics, B-blockers & Amiodarone as may
worsen hypotension & conduction abnormalities

26. Endpoint of Tx
 Early serum alkalization by NaHCO3 using width of
QRS as guide for therapeutic endpoint
 Endpoint of serum alkalization: QRS < 100 ms, pH –
7.55 and Na <150 mmol/l
 Treat hypotension with crystalloid & inotropic infusion;
treat seizure with benzodiazepine

27. Q&A

28. The End