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A case report on hydroxychloroquine poisoning

A case report on hydroxychloroquine poisoning. A 40 year old man Suffered from depression + dermatomyositis Followed up in PWH On 24th March, 2003, quarreled with wife Took 40 tablets of hydroxychloroquine after drunk Accompanied by wife to hospital (AHNH). History.

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A case report on hydroxychloroquine poisoning

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  1. A case report on hydroxychloroquine poisoning

  2. A 40 year old man Suffered from depression + dermatomyositis Followed up in PWH On 24th March, 2003, quarreled with wife Took 40 tablets of hydroxychloroquine after drunk Accompanied by wife to hospital (AHNH) History

  3. No other medication was taken • On presentation to ED, • Generalised weakness, nausea, vomiting. • Drowsy and responded slowly • No abdominal pain • No chest pain or palpitation

  4. Physical examination • Obese, sleepy • GCS E3M5V3 • Hypotensive (BP 100/53) • Pulse: 70/min, regular • Heart sound : dual, no murmur • Respiratory and abdominal examination: unremarkable • H’stix: 5.1

  5. Condition detriorates • During physical examination, blood pressure dropped to 80/40, pulse: 52/min • GCS 3/15 • Nasopharyngeal airway was put in • 500mlNS given in bolus • BP 90/50, no tachycardia • ECG: SR, prolonged QTC interval • Adrenaline infusion started 2mg /hr

  6. ICU admission Patient remained comatose ICU contacted Beds full Tranferred to another hospital’s ICU

  7. Investigation results • Blood investigation: • Na: 134; K :3.6 • U: 5.6; creatinine: 100 • LFT: normal • Phosphate : 0.75; adjusted Ca:2.02 • WBC: 21.6 • Hb & platelet: normal

  8. Glucose: 6.9

  9. Discussion • Hydroxychloroquine : 4-aminoquinoline derivative of chloroquine • Indications: malaria, rheumatoid arthritis, dermatomyositis and lupus erythematosus • Plaquenil • 1 tablet: 200mg of hydroxychloroquine phosphate • Each contain 155 mg of hydroxychloroquine

  10. Rarely used for drug overdose • Life threatening symptoms : within an hour of ingestion • Treatment recommendation: controversial

  11. Chloroquine poisoing • Chloroquine poisoning is more common • Used an analogy for study of hydroxycholorquine poisoning • Mortality rate in adults: 10-30% • Therapeutic dose: 10mg/kg • Toxic dose: 20mg/kg • Lethal dose: 30mg/kg • Fatality rate in children : 80%

  12. Chronic neurological deficit • Minimal lethal dose in children: 300mg

  13. Pharmacokinetics • Readily absorbed from the GIT • Large volume of distribution (61 L/kg) • Protein binding 50-65%; highly bound to tissues particularly kidney, liver and lung. • Main metabolite is monodesethylchloroquine • Mainly eliminated in urine.

  14. Pathophysiology • Cardiotoxicity is related to quinidine-like effects • Hypokalemia is due to direct chloroquine-induced intracellular shifts and will exacerbated by epinephrine therapy.

  15. Clinical manifestations • Serious and rapid clinical consequence • Onset of symptoms: 30 minutes • Death: 1-3 hr • Drowsiness, dizziness, visual disturbance • Seizures, apnea, dysrythmias and hypotension • Cardiotoxicity: > 50%

  16. respiratory difficulty -> pulmonary edema + arrest • Hypokalemia: 85% • Related to severity of intoxication • Criterias associated with fatal outcome: • > 5gm • SBP < 80mmhg • Prolongation of QRS interval > 0.12msec • Ventricular rhythm disturbance • Blood concentration > 5mcg/ml

  17. Cardiotoxicity of chloroquine • Cardiotoxicity – quinidine like action • Negative inotropic • Inhibits spontaneous diastolic depolarization • Slow conduction • Lengthen effective refractory period • Raised electrical threshold

  18. Consequences • Decreased contractility • Impaired conduction • Decreased excitablility • Abnormal stimulus to reentry

  19. Treatment model for HCQ poisoning • Early intubation + mechanical ventilation • Cardiovascular monitoring • Epinephrine : hypotension, dysrhythmia, QRS widening, circulatory collapse • Diazepam : seizure, sedation • Alkalinization: NaHCO3 for widen QRS, hypotension • Activated Charcoal (AC) for GI decontamination, but multiple dose AC had no effect on the rate of elimination

  20. Gastric lavage • Treat hypokalemia • Avoid drugs with Na channels blocking activities • Hemodialysis, hemoperfusion, peritoneal dialysis, plasmaphersis and diuresis are of little value in removing drug from the body because cholorquine has large volume of distribution.

  21. Back to the patient • Characteristic rapid onset of symptoms • Drowsiness progressive rapidly to coma • Hypotension • Widen QRS complex • No hypokalemia • Absence of seizure, early recovery and short hospital stay • IV inotrope was given with BP maintained

  22. Conclusion • HCQ overdose is rare but serious • Early treatment required • Current treatment model is based on chloroquine overdose • Treatment modality need modification as experience accumulates

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