Chloroquine/hydroxychloroquine overdose.

During the COVID-19 pandemic, there have been many proposed medications that may be used to help treat this virus. One such medication is chloroquine/hydroxychloroquine Fig. 1 . Numerous institutions are currently studying these drugs to see their efficacy in the treatment of COVID-19. These notes are to help in guiding the diagnosis/management of overdoses of this medication.

Fig. 1

Representative bottle of hydroxychloroquine tablets.

These are antimalarial drugs that are also used for autoimmune diseases such as rheumatoid arthritis and lupus1, 2.

Mechanism of action

Block the synthesis of DNA and RNA and have some quinidine like cardiotoxicity

Chloroquine is 2-3 times more toxic than hydroxychloroquine

Sodium and potassium channel blockade are proposed mechanisms of cardiovascular collapse

Toxic dose

Therapeutic dose of chloroquine

Prophylaxis for malaria- 500 mg/week for prophylaxis

Treatment of malaria 2.5 gm over 2 days

Reports of deaths in children after ingestion of 1-2 tabs.

Lethal dose in adult ~30–50 mg/kg

Clinical Presentation

Symptom onset is rapid usually within 30 min, death within 1–3 hours usually from cardiac arrest1, 2 .

Mild to moderate

Dizziness, nausea/vomiting, abdominal pain, headache, visual/retinal disturbances, auditory disturbances, agitation, neuromuscular excitability.

Can cause hemolysis in G6PD deficiency, rarely causes retinal damage, sensorineural deafness, hypoglycemia.

Severe

Convulsions, coma, shock, respiratory/cardiac arrest1, 2.

Quinidine-like cardiotoxicity- Sino-atrial node arrest, depressed myocardial contractility, QRS and/or QTc prolongation, heart block, ventricular arrythmias, ST and T wave depression, u waves. Hypokalemia can occur and contribute to dysrhythmias.

Clinical criteria associated with fatal outcome

Ingestion of greater than 5 gm.

Systolic BP <80 mm/Hg.

Prolongation of QRS longer than 120 msec.

Ventricular rhythm disturbances.

Blood concentrations >8 mcg/ml.

Diagnosis/Treatment

Early intubation/mechanical ventilation for significant ingestions/symptoms due to seizure risk/airway protection.

Electrolytes, glucose, BUN, creatinine, EKG and tele-monitoring.

Treatment of QRS prolongation with sodium bicarbonate is controversial. Be mindful that alkalinization can further exacerbate hypokalemia—before using sodium bicarbonate assess the full clinical picture specifically cardiac toxicity and degree of hypokalemia.

K repletion for severe hypokalemia (usually due to intracellular shift not overall potassium deficit)—dose with caution and frequent potassium checks as redistribution of potassium may cause a rebound hyperkalemia and may worsen cardiotoxicity.

Hypokalemia correlates with severity of ingestion and occurs within a few hours of ingestion.

Vasopressor support for hypotension not responsive to fluids.

Hypotension is multifactorial→

distributive from hydroxychloroquine/chloroquine induced vasodilation,

bradycardia from negative ionotropic effect

cardiogenic effects from direct cardiotoxicity

Studies done with use of epinephrine (first line treatment)—0.25 mcg/kg/min and increase by 0.25 mcg/kg/min until adequate BP (~100 mmhg)—again monitor potassium as this can further cause intracellular shift1, 2.

High dose benzos—studies done with diazepam 2mg/kg IV over 30 min after intubation then 1-2 mg/kg/day1, 2.

Avoid type 1A anti-arrhythmics.

Extracorporeal removal methods have not been shown to be useful—as hydroxychloroquine/chloroquine have large volume of distribution and significant protein binding.

Questionable benefit from lipid emulsion therapy—there are a few case reports that have demonstrated improvement in patients that have overdosed on these medications.