Utility of Hypertonic Saline and Diazepam in COVID-19–Related Hydroxychloroquine Toxicity

Abstract

Background Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use. 1 Hence, HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion. 2–5 Here, we highlight the use of hypertonic saline and diazepam. Case Report We describe the case of a 37-year-old man who presented to the emergency department (ED) after the ingestion of approximately 16 grams of HCQ tablets (initial serum concentration 4,270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up. Why should an emergency physician be aware of this? For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients as both HCQ toxicity and high-dose diazepam cause profound sedation.

Nearly Fatal Hydroxychloroquine Overdose Successfully Treated with Midazolam, Propofol, Sodium Bicarbonate, Norepinephrine, and Intravenous Lipid Emulsion

“…However, caution is advised because of its alkalinizing effects, which can worsen the intracellular potassium shift [21]. As an alternative, administration of hypertonic saline can be considered when serum potassium is either not yet known or still low [8,25]. In our case, we immediately opted for a continuous infusion of sodium bicarbonate and did not encounter a worsening hypokalemia.…”

“…In our case, we immediately opted for a continuous infusion of sodium bicarbonate and did not encounter a worsening hypokalemia. When the QRS drops under 100 ms, the sodium bicarbonate infusion can be weaned off [25].…”

“…In a protocol together with highdose diazepam and early mechanical ventilation, epinephrine was proven to improve outcome in severe chloroquine toxicity [7]. Although formal evidence of the benefit of epinephrine in hydroxychloroquine toxicity is lacking, its use is mentioned in several case reports with good outcomes [1,[20][21][22][25][26][27]. In the case presented above, norepinephrine was used with success.…”

“…However, since we found very few reports using norepinephrine in this context, we advise using epinephrine until more data is available [22,28,29]. In order to avoid R-on-T phenomenon in case of QT prolongation, it is recommended to target the heart rate above 90 beats per minute [25,30].…”

Acute Hydroxychloroquine Overdose

“…2,10,50 Information from adult cases suggests that use of hypertonic saline (3% NaCl), or alternatively sodium acetate, may also be considered to overcome sodium channel blockade and avoid worsening of hypokalemia. 11,51 Arrhythmias resulting from electrolyte derangements including potassium should be rapidly but carefully corrected. 11 Magnesium sulfate may be used for torsade de pointes treatment.…”