key: cord-0043289-lg5isnb7
authors: McKeever, Rita
title: Chloroquine/Hydroxychloroquine Overdose
date: 2020-05-11
journal: Vis J Emerg Med
DOI: 10.1016/j.visj.2020.100777
sha: 204f95d056a9f9bcfc51009a713a36c278bce108
doc_id: 43289
cord_uid: lg5isnb7

nan

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. 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.

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

 Block the synthesis of DNA and RNA and have some quinidine like cardiotoxicity o Chloroquine is 2-3 times more toxic than hydroxychloroquine o Sodium and potassium channel blockade are proposed mechanisms of cardiovascular collapse Toxic Dose:

 Therapeutic dose of chloroquine o Prophylaxis for malaria: 500mg/week for prophylaxis o Treatment of malaria 2.5gm over 2 days  Reports of deaths in children after ingestion of 1-2 tabs.  Lethal dose in adult ~30-50mg/kg Clinical Presentation:

 Symptom onset is rapid usually within 30min, death within 1-3 hours usually from cardiac arrest o 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 o Severe  Convulsions, coma, shock, respiratory/cardiac arrest  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 o Clinical criteria associated with fatal outcome  Ingestion of greater than 5gm  Systolic BP <80mm/Hg  Prolongation of QRS longer than 120 msec  Ventricular rhythm disturbances  Blood concentrations >8mcg/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 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 o Hypokalemia correlates with severity of ingestion and occurs within a few hours of ingestion  Vasopressor support for hypotension not responsive to fluids o Hypotension multifactorial  distributive from hydroxychloroquine/chloroquine induced vasodilation,  bradycardia from negative ionotropic effect  cardiogenic effects from direct cardiotoxicity o Studies done with use of epinephrine (first line treatment)-0.25mcg/kg/min and increase by 0.25mcg/kg/min until adequate BP (~100mmhg)-again monitor potassium as this can further cause intracellular shift o High dose benzos-studies done with diazepam 2mg/kg IV over 30 min after intubation then 1-2mg/kg/day  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

Treatment of severe chloroquine poisoning

Protective cardiovascular effects of diazepam in experimental acute chloroquine poisoning

Treatment of hydroxychloroquine overdose

Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication