Analytically confirmed eutylone (bk-EBDB) exposure in emergency department patients

Abstract

Eutylone [1-(1,3-benzodioxol-5-yl)-2-(ethylamino) butan-1one], also known as bk-EBDB or N-ethylbutylone, is a synthetic cathinone that first appeared in Poland in 2014 [1]. In the US, eutylone was detected in 83 forensic investigations in thirteen states between January 2019 and April 2020 [2]. Although eutylone has been observed in driving-under-theinfluence-of-drug and fatal forensically investigated cases [2], clinical characteristics of eutylone toxicity have not been reported. We describe the clinical presentations of 11 patients who presented to the emergency department (ED) involving eutylone use in Taiwan. In this retrospective chart review study, we collected ED cases with lab-confirmed eutylone exposure from three hospitals between January 2019 and July 2020. The emergency physicians (EP) ordered the toxicology test by liquid chromatography tandem-mass spectrometry (LC-MS/MS) when the EP suspected that the patients’ clinical presentations had resulted from illicit drugs administration. The methodology was used as in a previous report [3]. The compounds detected by this LC-MS/MS assay and their detection cut-offs are provided in the supplementary material. Patients’ clinical characteristics were reviewed by two investigators independently without using a pre-made data extraction form. If the interpretations were different between the investigators, the corresponding author decided the final descriptions. The study was approved by the research ethics committees of the participating hospitals. The 11 patients’ clinical characteristics and the drugs detected in the bio-samples are summarized in Table 1. The average age of patients was 24± 8.01 years (seven were women). Common clinical manifestations were delirium (5 cases) and agitation (5 cases). All patients exhibited tachycardia (pulse rate >100/min) except one who presented with out-of-hospital cardiac arrest (OHCA), four patients developed hyperthermia (body temperature >38 C), and three had hypertension (systolic blood pressure >140mmHg). In non-OHCA patients, five patients developed leukocytosis (white cell counts >11 K/lL) and one patient had rhabdomyolysis (CK > 1,500U/L). All patients reported ingestion of “instant coffee packet” either on hospital arrival or after consciousness recovery except one patient with OHCA. In Taiwan, cathinones are usually sold as “instant coffee packets” [4]. Most patients recovered within 12 h, except one patient with OHCA who expired and two patients who were discharged against medical advice. Although other substances were also found in these patients’ bio-samples, eutylone was the only psychostimulant detected. Patient 1, a 20-year-old man, developed generalized tonicclonic seizures at home after ingestion of an uncertain amount of instant coffee packets according to his mother’s statement. Cardiac arrest occurred in the ambulance, and cardiopulmonary resuscitation (CPR) was performed by paramedics. On arrival to the ED, he exhibited pulseless electrical activity and had a body temperature of 41 C. As CPR continued, ventricular fibrillation developed, and 200 J biphasic defibrillation was given. He regained spontaneous circulation in 4min. Brain computed tomography did not reveal any structural lesions. Despite aggressive external cooling, hydration, and intravenous benzodiazepine therapy, he developed rhabdomyolysis (highest creatine kinase 118,600U/L), anuria, disseminated intravascular coagulopathy, and multiple organ failure, and died 25 h after hospitalization. Eutylone concentrations were 406 and 15,149 ng/mL in his serum and urine, respectively. Our cases of eutylone use, including one fatal case, presented with pronounced sympathomimetic syndromes. Most patients had favourable outcomes. The urine concentrations of eutylone showed large variation (210 to 18,364 ng/ml) and were unrelated to the severity of toxicity in our case series. A previous report also demonstrated a wide blood concentration range of eutylone in post-mortem cases (1.2–4; 4000 ng/ mL) [2]. These results suggest that urine and blood eutylone concentrations do not correlate well with the severity of clinical manifestations. There were some limitations in this case series. The toxicology testing was performed at the discretion of the treating clinicians. Eutylone-exposed patients without overt sympathomimetic symptoms might not be detected from our analysis because testing was not ordered. Eutylone use is highly prevalent in recent years. Although most patients had good outcomes, severe toxicity may occur after eutylone use. Users should be warned of the possible catastrophic health consequences.