2. The clinical impact of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs

Ethanol is frequently used together with recreational / illicit drugs. However, the clinical relevance of this ethanol co-use on acute toxicity presentations is not well described. The aim of this study was to determine the clinical impact of ethanol co-use in patients presenting to the Emergency Department (ED) with acute toxicity involving the use of central nervous system (CNS) depressant drugs (opioids, benzodiazepines, gamma-hydroxybutyrate/gamm-butyrolactone (GHB/GBL), gabapentinoids).

Data were extracted from the Euro-DEN Plus database for all ED presentations with acute recreational drug toxicity from January 2014 to December 2019. We compared epidemiological and clinical characteristics as well as ED and hospital management of cases with toxicity related to lone CNS-depressant use to cases in which co-use of ethanol was reported.

7,644 (17.5%) of the 43,633 presentations, involved only CNS depressants with or without ethanol (median age 35 (IQR 29-43) years; 76.3% men) and ethanol was co-ingested in 3,811 (49.9%) cases. Patients with ethanol co-use more frequently presented with coma (34.1% vs. 22.4%, p<0.001) and were more likely to experience vomiting (8.1% vs. 4.6%, p<0.001), anxiety (12 % vs. 6.4%, p<0.001), agitation/aggression (22% vs. 14.7%, p<0.001), seizures (3.8% vs. 2.4%, p<0.001) and hypotension (7.5% vs. 4.6%, p<0.001) compared to those without ethanol use. They more often required ambulance transport to the ED (85.5% vs. 76.5%, p<0.001), any medical treatment (57.3% vs. 48.0%, p<0.001), treatment with flumazenil (5.4% vs. 2.4%, p<0.001), hospitalization (27.7% vs. 18.9%, p<0.001), and admission to intensive care (12.2% vs. 4.0%, p<0.001). Subgroup analysis showed that severe reduction of consciousness was particularly more common in patients who combined ethanol with opioids (32.5% vs. 20.2%, p<0.001) or with GHB/GBL (56.2% vs. 40.1%, p<0.001).

Co-use of ethanol with CNS-depressant drugs increases the risk of severe adverse effects and is associated with a higher need for medical treatment and intensive care. This is especially the case when ethanol is used with opioids or GHB/GBL. This has important public health implications for the development of prevention and harm reduction and treatment strategies, to address both high-risk drug and alcohol use.