A case report on hydroxychloroquine poisoning

History 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)

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

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

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

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

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

Glucose: 6.9

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

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

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%

Chronic neurological deficit Minimal lethal dose in children: 300mg

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.

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

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%

respiratory difficulty -> pulmonary edema + arrest Hypokalemia: 85% Related to severity of intoxication Criterias associated with fatal outcome: 1) > 5gm 2) SBP < 80mmhg 3) Prolongation of QRS interval > 0.12msec 4) Ventricular rhythm disturbance 5) Blood concentration > 5mcg/ml

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

Consequences Decreased contractility Impaired conduction Decreased excitablility Abnormal stimulus to reentry

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

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.

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

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