Hydroxychloroquine overdose: A prospective case series

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. 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. We highlight the use of hypertonic saline and diazepam.

We describe the case of a 37-year-old man who presented to the emergency department after the ingestion of approximately 16 g of HCQ tablets (initial serum concentration 4270 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.

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 because both HCQ toxicity and high-dose diazepam cause profound sedation.

Hydroxychloroquine is a medication used to treat autoimmune conditions. Overdoses of hydroxychloroquine are uncommon, with most recommendations on monitoring drawing from experience with more common overdoses of the related drug chloroquine. We present a case of an adolescent with intentional overdose of approximately 12 g of hydroxychloroquine. The prominent clinical features were hypokalemia and widened QRS and QT intervals on the electrocardiogram. Therapy included epinephrine by intravenous drip and bicarbonate infusions along with supportive care and cardiac monitoring. The patient recovered without sequelae. Urine drug testing showed an absorbance alarm for one of the components of the institution drug of abuse screening panel, an oxycodone screen using an enzyme immunoassay. Analysis of two urine specimens collected during the hospitalization revealed hydroxychloroquine concentrations of greater than 500 mg/L (approximately 7.5 h after ingestion) and 130 mg/L (approximately 14 h after ingestion). Only the urine with greater than 500 mg/L hydroxychloroquine produced absorbance alarms on the drug of abuse testing. We separately analyzed the impact on 24 urine assays of varying concentrations of hydroxychloroquine spiked into de-identified pooled urine samples. For 6 of the assays (buprenorphine, cotinine, oxycodone, and tetrahydrocannabinol qualitative drug screens; microalbumin and urine myoglobin quantitative assays), hydroxychloroquine produced significant bias and/or instrument alarms. Overall, our study demonstrates that urine concentrations of hydroxychloroquine can reach very high concentrations (exceeding 500 mg/L) following overdose, with the potential to interfere with a range of urine assays including drug of abuse screening and microalbumin. Similar to previous reports, hydroxychloroquine overdose can produce hypokalemia and electrocardiographic abnormalities.

A rapid, sensitive and specific method using liquid chromatography coupled to tandem mass spectrometry was developed for the simultaneous quantification of hydroxychloroquine (HCQ) and its three major metabolites in human whole blood. The assay, using a sample volume of 100 μL, was linear in a dynamic 25–2000 ng/mL range (R² > 0.99) for all four compounds and suitable for the determination of elevated HCQ concentrations up to 20,000 ng/mL, after appropriate sample dilution. Inter- and intra-assay precisions were <18.2% and accuracies were between 84% and 113% for any analyte. No matrix effects were observed. The assay was successfully applied to a blood sample obtained from one poisoned patient following a massive HCQ self-ingestion resulting in an estimated concentration of 19,500 ng/mL on hospital admission. In this patient, HCQ metabolites were identified and quantified at 1123, 465 and 91 ng/mL for monodesethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, respectively. Further investigations are still required to assess the usefulness of the simultaneous measurement of blood concentrations of HCQ and its three active metabolites for monitoring HCQ treatment and managing HCQ poisoning.