Self-discharge during treatment for acute recreational drug toxicity: an observational study from emergency departments in seven European countries.

BACKGROUND: Self-discharge is a risk factor for readmission and excess mortality. We assess the rate of self-discharge from the emergency department (ED) among presentations for acute recreational drug toxicity and identify factors associated with self-discharge. METHODS: From the Euro-DEN Plus database of presentations to the ED with acute recreational drug toxicity, we extracted data from 11 centres in seven European countries from 2014 to 2017. Self-discharge was defined as taking one's own discharge or escaping from the ED before being medically cleared. We used multiple logistic regression analyses to look for factors associated with self-discharge. RESULTS: Among 15,135 included presentations, 1807 (11.9%) self-discharged. Self-discharge rates varied from 1.7 to 17.1% between centres. Synthetic cannabinoids were associated with self-discharge, adjusted odds ratio 1.44 (95% confidence interval 1.10-1.89), as were heroin, 1.44 (1.26-1.64), agitation, 1.27 (1.10-1.46), and naloxone treatment, 1.27 (1.07-1.51), while sedation protected from self-discharge, 0.38 (0.30-0.48). CONCLUSION: One in eight presentations self-discharged. There was a large variation in self-discharge rates across the participating centres, possibly partly reflecting different discharge procedures and practices. Measures to improve the management of agitation and cautious administration of naloxone to avoid opioid withdrawal symptoms may be approaches worth exploring to reduce self-discharge.

Determinants of Admission to Critical Care Following Acute Recreational Drug Toxicity: A Euro-DEN Plus Study.

This study aimed to characterize patients admitted to critical care following Emergency Department (ED) presentation with acute recreational drug toxicity and to identify determinants of admission to critical care. A retrospective multicenter matched case-control study was conducted by the European Drug Emergency Network Plus (Euro-DEN Plus) over the period 2014-2021. The cases were ED presentations with acute recreational drug toxicity admitted to critical care, the controls consisted of ED presentations with acute recreational drug toxicity medically discharged directly from the ED. The potential determinants of admission to critical care were assessed through multivariable conditional stepwise logistic regression analysis and multiple imputation was used to account for the missing data. From 2014 to 2021, 3448 Euro-DEN Plus presentations involved patients admitted to critical care (76.9% males; mean age 33.2 years; SD 10.9 years). Patient age ≥35 years (as compared to ≤18 years) was a determinant of admission to critical care following acute recreational drug toxicity (adjusted odds ratio, aOR, 1.51, 95% confidence interval, CI, 1.15-1.99), along with polydrug use (aOR 1.39, 95% CI 1.22-1.59), ethanol co-ingestion (aOR 1.44, 95% CI 1.26-1.64), and the use of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL, aOR 3.08, 95% CI 2.66-3.57). Conversely, lower odds of admission to critical care were associated with the use of cocaine (aOR 0.85, 95% CI 0.74-0.99), cannabis (aOR 0.44, 95% CI 0.37-0.52), heroin (aOR 0.80, 95% CI 0.69-0.93), and amphetamine (aOR 0.65, 95% CI 0.54-0.78), as was the arrival to the ED during the night (8 p.m.-8 a.m., aOR 0.88, 95% CI 0.79-0.98). These findings, which deserve confirmation and further investigation, could contribute to a more complete understanding of the decision-making process underlying the admission to critical care of patients with acute recreational drug toxicity.

Severity of emergency department presentations due to acute drug toxicity in Europe: a longitudinal analysis over a 6-year period (2014-2019) stratified by sex.

OBJECTIVE: To investigate whether the severity of acute recreation drug toxicity presentations to emergency departments (EDs) in Europe has changed in recent years and to uncover potential sex differences. DESIGN: We analysed presentations to 36 EDs in 24 European countries relating to acute recreational drug toxicity, with separate analysis for presentations involving lone use of cannabis, cocaine, and heroin. As severity markers, we calculated rates of hospitalization, admission to ICU, intubation, and death by annual quarters between 2014 and 2019. Trends on severity over time were estimated by logistic regression. Differences between men and women were assessed by interaction. Sensitivity analysis was performed including only EDs that provided data for all 24 quarters. Analyses of intoxications taken altogether were adjusted by age and sex, while of lone intoxications being also adjusted by ethanol co-ingestion. RESULTS: There were 43 633 presentations (median age = 31 years, interquartile range = 25-40 years, men = 76.5%) resulting in 10 344 hospitalizations (23.9%), 2568 ICU admissions (5.9%), 1391 intubations (3.2%), and 171 deaths (0.39%). Hospitalization, ICU admission and death did not differ by sex, but intubation was more frequent in men (3.4% vs. 2.3%, P < 0.001). No significant changes in the severity of drug intoxications over time were found when considered altogether, neither for lone cannabis (n = 4264) nor cocaine (n = 3562). Conversely, significant increases in hospitalization [odds ratios (OR) = 1.023, 95% confidence interval (CI) = 1.004-1.041], ICU admission (OR = 1.080, 95% CI = 1.042-1.118) and in intubation (OR = 1.049, 95% CI = 1.001-1.099) were detected for lone heroin presentations (n = 1997). Sensitivity analysis (32 245 presentations, 14 EDs, 9 countries) confirmed the overall absence of changes in severity markers (except for death rate, which significantly decreased by quarter: OR = 0.968, 95% CI = 0.943-0.994). Additionally, it suggested an increased risk over time of intubation for cocaine (OR = 1.068, 95% CI = 1.009-1.130) and confirmed the increased risk of ICU admission for heroin (OR = 1.058, 95% CI = 1.013-1.105). Changes in severity over time did not differ according to sex in the main analysis of the whole cohort, while a significantly higher decrease in risk of death in men was found in the sensitivity analysis (OR = 0.894, 95% CI = 0.825-969 vs. OR = 0.949, 95% CI = 0.860-1.048; P interaction = 0.042). CONCLUSIONS: The severity of presentations to European EDs remained mainly unchanged during 2014-2019, but the risk of death may have decreased. Conversely, intubation in lone cocaine and ICU admission in lone heroin intoxications have increased. Although men and women exhibited a similar pattern over the period for the majority of comparisons, our data suggest that women exhibited a smaller decrease of the overall risk of death.

Novel psychoactive substances-related presentations to the emergency departments of the European drug emergencies network plus (Euro-DEN plus) over the six-year period 2014-2019.

INTRODUCTION: Novel psychoactive substances (NPS) have been increasingly reported in the last 15-20 years. We aimed to describe presentations to the emergency department (ED) with acute recreational drug toxicity involving NPS. METHODS: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all presentations to ED (36 EDs in 24 European countries) with acute toxicity between January 2014 and December 2019. Patient demographics, agents involved, and clinical outcomes were described and the subgroup of presentations involving NPS was compared with the rest of the cohort. RESULTS: Out of 43,633 Euro-DEN Plus presentations, 3304 (7.6%) involved at least one NPS. Agents were identified mainly based on self-report or clinical presentation, with analytical confirmation being performed only in 17.9% of NPS presentations. The proportion of NPS presentations varied by centre (0-48.8%). For centres where data were available for all 6 years, NPS-related presentations peaked in 2015 (11.9%). In 2014, 78.4% of NPS agents reported were cathinones, while only 3.4% were synthetic cannabinoids (SCs); conversely, in 2019 only 11.6% of NPS agents reported were cathinones, while 72.2% were SCs. NPS-related presentations involved younger patients (median 30 (23-37) vs. 32 (25-40) years, p < 0.001) and more males (84.8 vs. 75.8%, p < 0.001) compared with the rest of the cohort. Patients presenting to ED after using NPS were more likely to self-discharge (22.8 vs. 15.1%), less likely to be admitted to critical care (3.6 vs. 6.1%) but had a longer length of stay in hospital (median 5.1 (2.7-18.7) vs. 4.7 (2.5-9.2) h, p < 0.001). Death occurred in 0.5% of all presentations involving NPS and in 0.4% of non-NPS presentations. CONCLUSIONS: This large multicentre series of NPS presentations to European EDs showed marked geographical variation and changes over time in the proportion of presentations to ED involving NPS, as well as the proportion of NPS subgroups.

Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex.

OBJECTIVE: To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex. METHODS: We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20-29, 30-39, 40-49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion. RESULTS: 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20-34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299-3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432-2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390-2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065-3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677-0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561-0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350-0.671). CONCLUSIONS: The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups.

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

BACKGROUND AND IMPORTANCE: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described. OBJECTIVE: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019. OUTCOMES MEASURE AND ANALYSIS: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use. MAIN RESULTS: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P < 0.001), 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). They more often required ambulance transport (85.5% vs. 76.5%; P < 0.001), medical treatment (57.3% vs. 48.0%; 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 GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL). CONCLUSION: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.

Increasing emergency department attendances in central London with methamphetamine toxicity and associated harms.

BACKGROUND: Methamphetamine is a stimulant drug of abuse with increasing prevalence of use worldwide leading to public health concern. While previous research by our group a decade ago found no evidence of increasing harms associated with methamphetamine use in the UK, there are conflicting data on whether or not this is still the case. This paper aims to identify trends in methamphetamine-related harms and characterise the clinical features of ED presentations involving methamphetamine with gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL). METHODS: We retrospectively interrogated a database of all toxicology-related presentations to two central London EDs, extracting data on drugs involved for presentations relating to methamphetamine between 2005 and 2018 to enable analysis of trends. Further clinical data were extracted for presentations between 2014 and 2018 to give a 4-year case series. RESULTS: A total of 1244 presentations involving the use of methamphetamine were identified. The number of presentations rose from 4 in 2005 (1.9% of all recreational drug presentations) to 294 (16.2%) in 2018. A total of 850 cases were identified for the 2014-2018 case series, 94.9% were male with a median (range) age of 35.1 (16-67) years. The most common clinical features in the methamphetamine presentations were neuropsychiatric: agitation (41.5%), anxiety (35.2%), hallucinations (16.5%) and psychosis (14.8%). GHB/GBL was co-used in 54.2% of presentations and appeared to attenuate the neuropsychiatric features seen. Use of GHB/GBL was associated with a higher Poisoning Severity Score and requirement for level 2/3 (high dependency unit/intensive care unit (ICU)) care. CONCLUSION: ED attendances in central London relating to methamphetamine use have risen over the last decade. Combining methamphetamine with GHB/GBL is common and is associated with a higher Poisoning Severity Score and need for ICU level care. Further work is required to establish whether further resources need to be directed at this clinical and public health problem.

Paracetamol toxicity in mild overdose in combination with opioids: A retrospective observational study.

AIMS: Toxicity in paracetamol overdose with opioid co-ingestion is poorly understood. We compared outcomes in both paracetamol-only and paracetamol-opioid overdoses to determine whether toxicity differed significantly between the groups, and to assess the utility of the ratio of measured plasma paracetamol concentration relative to the 4-hour nomogram-adjusted level (APAPpl /APAPt ). METHODS: We conducted a retrospective observational study of all patients (n = 1159) presenting to 2 large UK hospitals between 2005 and 2013 with acute single-dose ingestion paracetamol overdose, with (n = 221) or without (n = 938) opioid co-ingestion. Adverse outcomes included biomarkers of hepatotoxicity and the need for extended treatment. Several outcomes were assessed in relation to the APAPpl /APAPt ratio. RESULTS: Median ingested dose of paracetamol was low in both groups (10 g). Statistical comparison of the median APAPpl /APAPt ratios showed a significant difference (0.65 vs. 0.56 for the paracetamol-only and paracetamol-opioid groups respectively, P = .0329). Although there was a trend towards a lower risk of predefined toxic outcomes with opioid co-ingestion, statistical analysis did not show a significant difference, with outcomes for the paracetamol-only and paracetamol-opioid groups including the following: alanine transaminase >2× upper limit of normal, 7.7 vs. 5.7% (P = .6480); alanine transaminase >1000 IU/L, 2.4 vs. 0% (P = .2145); international normalised ratio > 1.3, 8.6 vs. 4.4% (P = .2774); and transfer to tertiary liver unit, 0.2 vs. 0% (P nonsignificant). CONCLUSION: Our study does not support a change in current clinical practise beyond standard testing at 4 hours or longer post ingestion for mixed low dose paracetamol-opioid overdose.

Rhabdomyolysis related to acute recreational drug toxicity-A Euro-DEN study.

BACKGROUND: This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested. METHODS: All presentations to the 16 sentinel Euro-DEN centres in 10 European countries with acute recreational drug toxicity during the first year of the Euro-DEN study (October 2013 to September 2014) were considered. Cases that had abnormal CK activity recorded as part of routine clinical care were divided into 3 cohorts depending on peak CK activity. Cases with normal CK activity were included as a control group (4th cohort). RESULTS: Only 1,015 (18.4%) of the 5,529 Euro-DEN presentations had CK activity concentration recorded. Of this group 353 (34.8%) had also creatinine concentration measured. There were 375 (36.9%) with minor rhabdomyolysis, 69 (6.8%) with moderate rhabdomyolysis, and 24 (2.4%) with severe rhabdomyolysis; 547 (53.9%) were included in the control group. There was a positive correlation between CK activity and creatinine concentration (correlation coefficient r = 0.71, p<0.0001). There was no correlation between CK activity and body temperature at the time of presentation to the ED (correlation coefficient r = 0.07, p = 0.03). There was a positive correlation between CK activity and length of stay in the hospital (r = 0.31, p<0.001). There was no association between CK activity and the presence of seizures (p = 0.33) or agitation/aggression (p = 0.45), patients age (p = 0.4) or sex (p = 0.25). The 5 most common agents amongst patients presenting with rhabdomyolysis were: cocaine (n = 107; 22.9% presentations), amphetamine (76; 16.2%), cannabis (74; 15.8%), GHB/GBL (72; 15.4%) and heroin (67; 14.3%). The distribution of rhabdomyolysis in 5 most common drugs was (drug; patients with rhabdomyolysis, patients without rhabdomyolysis): cocaine (107, 122), cannabis (74, 117), GHB/GBL (72, 81), amphetamine (76, 66), heroin (67, 70). CONCLUSIONS: Abnormal values of CK activity occurred in almost half (46.1%) of presentations to the Emergency Department with acute recreational drug toxicity in whom CK activity was measured; however, severe rhabdomyolysis is seen in only a small minority (2.4%). Those with rhabdomyolysis are at significantly higher risk of kidney injury and have a longer length of hospital stay.

Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

OBJECTIVE: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata. METHODS: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families. RESULTS: Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years; p < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years; p = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males. CONCLUSION: Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.

Acute toxicity related to misuse (nonmedical use) of tramadol: Experience of the European Drug Emergencies Network Plus.

Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate <12 breaths/min. These presentations potentially pose a significant burden on emergency departments with a large proportion requiring admission to hospital for ongoing care.

MDMA-related presentations to the emergency departments of the European Drug Emergencies Network plus (Euro-DEN Plus) over the four-year period 2014-2017.

CONTEXT: 3,4-Methylenedioxymethamphetamine (MDMA) remains one of the most commonly used recreational drugs in Europe. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with MDMA is important to determine trends in MDMA use and harms. METHODS: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all ED presentations with acute toxicity involving MDMA use, alone or in combination with other substances, between 1 January 2014 and 31 December 2017. Geographical distribution, time trends, patient demographics, clinical features, management and outcome were analysed. RESULTS: Out of 23,947 presentations, 2013 (8.4%) involved MDMA, used alone (88, 4.4%) or with other substances (1925, 95.6%). The proportion of MDMA presentations varied by country, from over 15% in France to less than 5% in Norway. For the 15 sentinel centres where data were available for all four years, MDMA-related presentations peaked in 2016 (10.4% versus 8.1% in 2015, p < 0.0001), thereafter decreasing in 2017 (8.2%, p = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20-27 years, versus median 25 years, IQR 21-30 years, p < 0.0001). Compared to presentations of acute toxicity with lone-use cocaine, presentations with lone-use MDMA occurred more frequently during the weekend (58.0% versus 43.9%, p = 0.02), were more frequently medically discharged directly from the ED (74.7% versus 62.4%, p = 0.03), and less frequently received sedation (43.5% versus 66.5%, p = 0.003). CONCLUSIONS: This large multicentre series of MDMA presentations to EDs showed geographical variation and changes in time trends and in patient demographics. Triangulation with data from complementary sources including seizures, prevalence of use and wastewater analysis, will enable a greater understanding of the public health implications of MDMA use in Europe.

Cold water extraction of codeine/paracetamol combination products: a case series and literature review.

Introduction: Tampering with opioid containing medications for use other than their prescribed indication is well documented; however, the published literature has concentrated on stronger, prescription opioids. Less potent opioids, such as codeine, are available without prescription in many European countries in the form of combination analgesic products and these can also be altered, with reports in particular of "cold-water extraction" being a tampering method achievable using household kitchen equipment.Methods: We searched a database of patients attending two South London emergency departments for cases of self-reported ingestion of the products of cold-water extraction, with subsequent review of their case notes. We searched the scientific and grey literature to identify current knowledge of this technique.Results: We identified seven presentations in six patients, none of whom developed paracetamol toxicity or had concentrations suggesting ingestion of a significant dose of paracetamol. A review of the scientific literature on the method also demonstrated that the technique reduces recovered paracetamol in experimental laboratory settings. Additionally, the established literature characterizes the use of codeine in a recreational setting and reports one fatality associated with the method. Review of grey literature user-forums further describes recreational codeine use in relation to the method and frequent adverse events including hospital admission for paracetamol toxicity.Discussion: Whilst the method appears capable of providing a recreational dose of codeine with reduction in the recovered paracetamol, it cannot be considered safe. Pharmaceutical production methods have been successfully developed to prevent tampering through other means but none thus far have been directed at the cold water extraction technique.Conclusions: Clinicians should be aware of the potential toxicity from tampered nonprescription analgesics. There is also the need for public health education regarding the potential risks associated with these methods.

Clinical relevance of ethanol coingestion in patients with GHB/GBL intoxication.

OBJECTIVE: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use. METHOD: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs. RESULTS: A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003). CONCLUSIONS: Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay.

Seizures as a complication of recreational drug use: Analysis of the Euro-DEN Plus data-set.

Seizures are a recognized and potentially serious complication of recreational drug use. This study examined a large international data set of presentations to Emergency Departments with acute recreational drug toxicity, the European Drug Emergencies Plus (Euro-DEN Plus) Network, to compare presentations with and without seizures and estimate incidence and associated drugs. Amongst 23,947 presentations between January 2014 and December 2017, there were 1013 (4.2%) with reported seizures. Clinical and demographic features were similar between individuals who had a seizure and those who did not, although rates of coma, cardiac arrest, intubation, intensive care admission, and death were significantly higher in those with seizures. There was a significant association between specific drugs and a higher seizure incidence, including fentanyl (odds ratio 2.63, 95% confidence interval 1.20-5.80), and synthetic cannabinoids (OR 2.90, 95% CI 2.19-3.84). Other drugs were associated with a lower seizure incidence, including heroin (OR 0.46, 95% CI 0.35-0.61), clonazepam (OR 0.22, 95% CI 0.06-0.91), and cannabis (OR 0.65, 95% CI 0.50-0.86). This substantiates observations that the synthetic cannabinoids as a group of novel psychoactive substances are clinically different in consequence of intoxication than cannabis, and that individuals who suffer a seizure in the context of recreational drug intoxication are likely to have worse outcomes overall. Utilising this information of what substances have a greater risk of seizures, could provide tailored harm reduction and education strategies to users to reduce the risk of seizures and their associated complications.

Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: comparison between powder cocaine and crack cocaine cases.

Objective: To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C1 group) and crack (C2 group) consumers. Methods: Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C1 and C2 patients were performed adjusting for alcohol and other drug co-ingestion. Results: We included 3002 cases (C1: 2600; C2: 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C1>C2) and other drugs (56.8%, C2>C1), the most frequent amphetamine (19.4%, C1>C2) and opioids (18.9%, C2>C1). C2 patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% (n = 12) died. Conclusion: Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.

Poor Identification of Emergency Department Acute Recreational Drug Toxicity Presentations Using Routine Hospital Coding Systems: the Experience in Denmark, Switzerland and the UK.

BACKGROUND: Understanding emergency department and healthcare utilisation related to acute recreational drug toxicity (ARDT) generally relies on nationally collated data based on ICD-10 coding. Previous UK studies have shown this poorly captures the true ARDT burden. The aim of this study was to investigate whether this is also the case elsewhere in Europe. METHODS: The Euro-DEN Plus database was interrogated for all presentations 1st July to 31st December 2015 to the EDs in (i) St Thomas' Hospital, London, UK; (ii) Universitätsspital Basel, Basel, Switzerland; and (iii) Zealand University Hospital, Roskilde, Denmark. Comparison of the drug(s) involved in the presentation with the ICD-10 codes applied to those presentations was undertaken to determine the proportion of cases where the primary/subsequent ICD-10 code(s) were ARDT related. RESULTS: There were 619 presentations over the 6-month period. Two hundred thirteen (34.4%) of those presentations were coded; 89.7% had a primary/subsequent ARDT-related ICD-10 code. One hundred percent of presentations to Roskilde had a primary ARDT ICD-10 code compared to 9.6% and 18.9% in Basel and London respectively. Overall, only 8.5% of the coded presentations had codes that captured all of the drugs that were involved in that presentation. CONCLUSIONS: While the majority of primary and secondary codes applied related to ARDT, often they did not identify the actual drug(s) involved. This was due to both inconsistencies in the ICD-10 codes applied and lack of ICD-10 codes for the drugs/NPS. Further work and education is needed to improve consistency of use of current ICD-10 and future potential ICD-11 coding systems.

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

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.