COVID-19 pandemic has brought two old medications – chloroquine and Hydroxychloroquine – back from the past. 

A couple in Arizona self-medicated with chloroquine this week and experienced chloroquine toxicity; the man died and his wife was admitted to the ICU.

https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html

Chloroquine and hydroxychloroquine overdose result in cardiotoxicity by Na and K channel blockade (similar to other membrane stabilizing agents such as TCAs, loperamide, etc.). Onset of toxicity is usually within 1 – 3 hours after ingestion.

Other symptoms of toxicity include: nausea/vomiting, respiratory depression/apnea, altered mental status and seizure. Hypokalemia is often encountered.

Use of sodium bicarbonate is controversial due to worsening of hypokalemia. Instead, administration of high dose diazepam and epinephrine (EPI) infusion has shown to decrease mortality (see below).

Riou B et al. NEJM 1988 DOI: 10.1056/NEJM198801073180101

• A retrospective control (n=11) vs. prospective diazepam (2 gm/kg daily) and EPI (0.25 microgm/kg/min with titrate to SBP >= 100 mmHg) group (n=11) involving large chloroquine ingestion (> 5 mg)

Survival:

• Combination treatment group: 91%
• Control: 9%

 

Clemessy JL et al. Crit Care Med 1996. DOI:10.1097/00003246-199607000-00021

• 5 year retrospective study (n=167)
• Mean chloroquine ingestion: 4.5 gm +/- 2.8 gm
• >5 gm ingestion: 43 (26%)

Treatment: 87% received at least one of the interventions below.

• 79/167 (48%) received EPI infusion
• 142/167 (85%) received diazepam
• Mechanical ventilation: 123/167 (74%)

Mortality

• Overall: 8.4%
• >5 gm ingestion: 9.3%

Bottom line

• Chloroquine and hydroxychloroquine toxicity may increase due to COVID19 pandemic
• Limited studies show that combined therapy of high dose diazepam and epinephrine infusion may decrease mortality associated with chloroquine and hydroxychloroquine toxicity.