Alison M. Dines

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

Context. Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe. Objective. To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap. Methods. Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013–September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting. Results. Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1–2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The ‘top five’ drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24–39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13. Conclusion. The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build a fuller picture of the public health implications of drug use in Europe.

The European Drug Emergencies Network (Euro-DEN)

1Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, UK 2King’s College London, London, UK 3Department of Acute Medicine, The National NBC Centre, Oslo University Hospital, Ullevaal, Oslo, Norway 4Emergency Department and Clinical Toxicology Unit, Hospital Universitari Son Espases, Palma de Mallorca, Spain 5Action on New Drugs and Epidemiology Units, European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal

Current European data collection on emergency department presentations with acute recreational drug toxicity: Gaps and national variations

Abstract Background. The number of new (novel) psychoactive substances (NPS) available in the illegal market is increasing; however, current monitoring of the drug situation in Europe focuses mainly on classical drugs of abuse, with limited emphasis on clinical presentation in the emergency department (ED). The European Drug Emergencies Network (Euro-DEN) is a European Commission-funded project that aims to improve the knowledge of acute drug toxicity of both classical recreational drugs and NPS. As a baseline for this project, we performed a study to establish which data are currently being collected and reported in Europe on ED presentations with acute toxicity related to NPS and classical drugs of abuse. Methods. We used a three-pronged approach to identify any systematic collection of data on NPS toxicity in Europe by i) performing a literature search, ii) utilising an online survey of the European Monitoring Centre for Drugs and Drug Addiction Re seau Europe en d’Information sur les Drogues et les Toxicomanies national focal points and iii) exploiting the knowledge and resources of the Euro-DEN network members. Results. The literature search revealed 21 papers appropriate for assessment, but only one described a systematic collection of clinical data on NPS. Twenty-seven of thirty countries responded to the online survey. More than half of all the countries (52%) did not perform any registration at all of such data, 37% collected systematic clinical data on NPS at a national level, while 44% collected data on classical drugs. A few examples for good practice of systematic collection of clinical data on ED presentations due to acute toxicity were identified. Conclusion. The systematic collection of data on ED presentation of toxicity related to NPS and classical drugs in Europe is scarce; the existing collection is limited to single centres, single countries, groups of patients or not focused on novel drugs; the collection of data is highly variable between the different countries. Euro-DEN, a European Commission funded project, aims at closing some of these gaps.

Nopaine no gain: recreational ethylphenidate toxicity.

To the Editor: Availability of novel psychoactive substances (NPS), or ‘legal highs’, has increased markedly over recent years, with an average of 1–2 new NPSs reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) every week in 2013/2014. 1 Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2-yl)acetate) is a psychostimulant NPS that inhibits reuptake of both dopamine and noradrenaline. 2 It is an analogue of methylphenidate that was first reported to the EMCDDA in 2011 from the UK. 3 It is often sold under the street name ‘Nopaine’. We present a series of three cases of acute ethylphenidate toxicity, including one with analytical confirmation. The first case was a previously well 21-year-old male brought to the Emergency Department (ED) by ambulance with anxiety, paranoia, agitation and visual disturbances. He also described leftsided, retrosternal chest pain lasting for ‘seconds’ associated with palpitations and ‘tingling’ in both hands. He reported using 500 mg of ethylphenidate in incremental doses over several hours on the evening of presentation, predominantly by nasal insufflation but also by smoking, and had also consumed seven cans of beer; he had purchased the ethylphenidate from a UK-based internet supplier. His symptoms developed 3 h after using ethylphenidate, for which he had self-medicated with 3 mg of etizolam, purchased from the same internet supplier. On arrival to the ED 17 h after the first ethylphenidate use, he was restless with tachycardia (heart rate: 114 bpm), hypertension (blood pressure: 184/98 mmHg) and dilated (4 mm) pupils; there was no hypertonia or clonus and he was afebrile (37.1°C). Electrocardiogram demonstrated sinus tachycardia with normal corrected QT interval. Venous blood gas, full blood count and renal profile were normal; creatine kinase was 290 I U/L (normal range: 0–229 IU/L). He was treated with 15 mg of oral diazepam in divided doses and admitted for observation; his symptoms resolved and he was discharged 10 h after presentation to the ED. Paired serum and urine samples were collected with informed consent 20 h after ethylphenidate and etizolam use. Analysis by highresolution liquid chromatography–mass spectrometry (LC–MS) identified ethylphenidate (0.24 microg/mL in blood and 0.98 microg/ mL in urine). Methylphenidate and ritalinic acid were not detected in blood; low concentrations of methylphenidate (0.059 microg/mL) and ritalinic acid (0.098 microg/mL) were detected in urine, consistent with in vivo de-ethylation of ethylphenidate to methylphenidate and its subsequent metabolism to ritalinic acid. Diazepam and etizolam were the only other substances detected, in trace amounts. The second case was a 37-year-old female brought to the ED by ambulance following intravenous injection of 1 g of ethylphenidate. She was feeling drowsy, had palpitations and felt feverish. Assessment in the ED demonstrated tachycardia (heart rate: 143 bpm), hypertension (blood pressure: 186/96 mmHg) and fever

Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse

OBJECTIVE To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. METHOD We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes. RESULTS We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01). CONCLUSIONS The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse.

Review of European-Drug Emergencies Network (Euro-DEN) training package for non-specialist workers to assess acute recreational drug and new psychoactive substance toxicity in night-time economy environments

Abstract Aims: The initial management of acute recreational drug and new psychoactive substance (NPS) toxicity is often by non-specialists working in the night-time economy. The aim was as part of the European Drug Emergencies Network (Euro-DEN) project to pilot training of these workers in multiple European countries. Methods: Following evaluation of training needs, guidelines and training package were developed. Night-time economy workers in London, UK; Pärnu/Tallinn, Estonia; and Oslo, Norway participated in a 1- to 2-h interactive case-based training session. Participants completed a questionnaire pre-/post-training to assess confidence in managing acute recreational drug/NPS toxicity and evaluate the training package/guidelines. Findings: 98 (London: 42; Oslo: 39; Pärnu/Tallinn: 17) completed both pre-/post-training questionnaires. Participants felt significantly more confident in managing someone unwell following classical recreational drug use compared to NPS (5.6 ± 2.9 vs. 4.3 ± 2.7, p < 0.001); this difference persisted after the training (7.6 ± 1.9 vs. 6.9 ± 2.0, p < 0.001). 147 (London: 42; Oslo: 88; Pärnu/Tallinn: 17) completed the post-training evaluation; the training session and the guidelines were rated 8.2 ± 1.4 and 8.7 ± 1.7, respectively (out of 10). Conclusions: The guidelines and training were well received by night-time economy workers in three European countries and improved confidence in managing acute recreational drug/NPS toxicity. Appropriate national and European bodies need to look at wider dissemination of this work.

Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series

Abstract The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity. We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project. Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively. In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives.

Concurrent Use of Benzodiazepine by Heroin Users—What Are the Prevalence and the Risks Associated with This Pattern of Use?

IntroductionPolydrug use involving heroin and benzodiazepines is common. The potential risk of additive pharmacological effects may be associated with poorer outcomes in patients who use benzodiazepines together with heroin. The aim of this study was to determine the clinical picture of patients presenting to the emergency department following acute drug toxicity involving heroin and benzodiazepines.MethodsExposure information, clinical data and outcome of acute drug toxicity presentations were collected between 1 October 2013 and 30 September 2014 as part of the European Drug Emergencies Network (Euro-DEN) project. The database was interrogated to identify patients who had taken heroin with or without benzodiazepine(s).ResultsA total of 1345 presentations involving acute heroin toxicity were identified: 492 had used one or more non-heroin/benzodiazepine drug and were not further considered in this study; 662 were lone heroin users and 191 had co-used heroin with one or more benzodiazepines. Co-users were more likely than lone heroin users to have reduced respiratory rate at presentation 12.7 ± 4.9 vs 13.6 ± 4.4 (p = 0.02) and require admission to hospital 18.3 vs 9.8% (p < 0.01). There were no differences in critical care admission rates 3.1 vs 3.9% (p = 0.83) or length of stay 4 h 59 min vs 5 h 32 min (p = 0.23). The 3 most common benzodiazepines were clonazepam, diazepam, and alprazolam. No differences were observed for clinical features between the three benzodiazepines.ConclusionThis study shows that co-use of heroin and benzodiazepines is common, although the overall outcomes between co-users of heroin and benzodiazepines and heroin-only users were similar.

Change in the new psychoactive substances associated with Emergency Department acute toxicity presentations associated with the introduction of the UK 2016 Psychoactive Substances Act

Abstract Objectives: In May 2016, the Psychoactive Substances Act (PSA) came into effect in UK making it an offence to produce or supply new psychoactive substances (NPS). The aim of this study was to determine whether this was associated with a change in Emergency Department (ED) presentations with acute NPS toxicity. Method: ED presentations to our inner-city hospital in London, UK, with acute NPS toxicity in the 12 months before and after the PSA introduction [June 2015–May 2016 (2015/2016) and June 2016–May 2017 (2016/2017)] were obtained from our database. The following data were extracted: (i) demographics; (ii) NPS(s) self-reported [categorized as synthetic cannabinoids (SC), cathinones, and “other NPS”)]; and (iii) month of presentation. Results: There were 1884 presentations with recreational drug toxicity, 447 (23.7%) involved NPS. There was no difference in the overall proportion of presentations involving an NPS in 2015/2016 [n = 196 (22.3%)] and 2016/2017 [251 (24.9%); (p = .48)]. There were a mean ± SD of 16.3 ± 3.7 NPS-related presentations per month in 2015/2016 and 20.9 ± 9.2 in 2016/2017; there was no significant change in overall monthly NPS-related presentations between these periods (p = .15). However, mean ± SD monthly SC-related presentations increased from 2015/2016 (5.9 ± 2.5) to 2016/2017 (17 ± 9.8); p = .004. Mean monthly cathinone-related presentations decreased from 2015/2016 (8.8 ± 4.2) to 2016/2017 (3.8 ± 2.7); p = .001. There was no significant change in monthly mean “other NPS” presentations from 2015/2016 (1.8 ± 2.2) to 2016/2017 (0.5 ± 0.8); p = .062. Between 2015/2016 and 2016/2017, SCs as a proportion of NPS-related presentations increased (r = .90) whilst cathinones decreased (r = −0.82). Conclusion: NPS present front-line health services with unique challenges, and the PSA 2016 represents a major legislative effort in UK to limit their availability and supply. The burden of NPS use on this inner-city  ED remains large 12 months after this legislation has come into force, with evolving patterns of NPS use.