Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.

INTRODUCTION: Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020. METHODS: Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of <0.05. RESULTS: Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache. DISCUSSION: Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity. CONCLUSION: This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.

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.

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Background: Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages.Objective: We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO.Methods: We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes.Results: We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient.Conclusion: We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak.

Comparación de las urgencias atendidas por drogas de abuso en dos servicios de urgencias españoles con las atendidas en tres áreas europeas distintas / Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas

Objetivo. Analizar algunas características epidemiológicas, clínicas y asistenciales de los pacientes atendidos por sintomatología directamente derivada del consumo de drogas de abuso en dos servicios de urgencias hospitalarios (SUH) españoles y compararlas con las observadas en otras regiones de Europa. Método. Análisis secundario del Registro Euro-DEN Plus (14 países europeos, 20 SUH) que incluyó todos los pacientes atendidos por sintomatología derivada del consumo de drogas (excepto etanol aislado) durante 39 meses consecutivos (octubre 2013 a diciembre 2016). Se comparan los casos de los 2 centros españoles (Barcelona, Palma) con los de 5 centros de Reino Unido e Irlanda (Islas Británicas -IB-), 6 del Norte de Europa (NE) y 7 de Europa Central (EC). Resultados. Se recogieron 17.104 pacientes: España 1.186, IB 6.653, NE 6.097 y EC 3.168. En España hubo más urgencias por cocaína (48,4%) y menos por opiáceos (12,4%) que en el resto de zonas; los pacientes eran más jóvenes (32,2 años) que en NE y mayores que en IB y EC; menos frecuentemente mujeres (21,9%) que en NE y EC; llegaron menos frecuentemente en ambulancia (70,0%) que en IB y NE; y en el SUH se registró escasamente la temperatura (29,8%) y frecuencia respiratoria (30,3%). Las manifestaciones clínicas difirieron entre zonas por la distinta prevalencia de cada tipo de droga. Naloxona (9,6%) se utilizó menos que en IB y NE, y flumazenilo (5,6%) más que en las otras zonas, y los porcentajes de ingresos (4,6%) y fugas del SUH (6,2%) fueron los menores de todas las regiones analizadas. La mortalidad, en urgencias (0,4%) y global (0,7%), fue significativamente superior que en NE. Conclusiones. Las características de las urgencias generadas por drogas de abuso son diferentes en España respecto a otras zonas europeas, debido a un diferente patrón de consumo. Su manejo en el SUH, en términos de exploraciones realizadas, tratamientos empleados y disposición tras la asistencia también son diferentes

Objectives. To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe. Methods. Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe. Results. A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe. Conclusions. The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition

Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas. / Comparación de las urgencias atendidas por drogas de abuso en dos servicios de urgencias españoles con las atendidas en tres áreas europeas distintas.

OBJECTIVES: To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe. MATERIAL AND METHODS: Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe. RESULTS: A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe. CONCLUSION: The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition.

OBJETIVO: Analizar algunas características epidemiológicas, clínicas y asistenciales de los pacientes atendidos por sintomatología directamente derivada del consumo de drogas de abuso en dos servicios de urgencias hospitalarios (SUH) españoles y compararlas con las observadas en otras regiones de Europa. METODO: Análisis secundario del Registro Euro-DEN Plus (14 países europeos, 20 SUH) que incluyó todos los pacientes atendidos por sintomatología derivada del consumo de drogas (excepto etanol aislado) durante 39 meses consecutivos (octubre 2013 a diciembre 2016). Se comparan los casos de los 2 centros españoles (Barcelona, Palma) con los de 5 centros de Reino Unido e Irlanda (Islas Británicas ­IB­), 6 del Norte de Europa (NE) y 7 de Europa Central (EC). RESULTADOS: Se recogieron 17.104 pacientes: España 1.186, IB 6.653, NE 6.097 y EC 3.168. En España hubo más urgencias por cocaína (48,4%) y menos por opiáceos (12,4%) que en el resto de zonas; los pacientes eran más jóvenes (32,2 años) que en NE y mayores que en IB y EC; menos frecuentemente mujeres (21,9%) que en NE y EC; llegaron menos frecuentemente en ambulancia (70,0%) que en IB y NE; y en el SUH se registró escasamente la temperatura (29,8%) y frecuencia respiratoria (30,3%). Las manifestaciones clínicas difirieron entre zonas por la distinta prevalencia de cada tipo de droga. Naloxona (9,6%) se utilizó menos que en IB y NE, y flumazenilo (5,6%) más que en las otras zonas, y los porcentajes de ingresos (4,6%) y fugas del SUH (6,2%) fueron los menores de todas las regiones analizadas. La mortalidad, en urgencias (0,4%) y global (0,7%), fue significativamente superior que en NE. CONCLUSIONES: Las características de las urgencias generadas por drogas de abuso son diferentes en España respecto a otras zonas europeas, debido a un diferente patrón de consumo. Su manejo en el SUH, en términos de exploraciones realizadas, tratamientos empleados y disposición tras la asistencia también son diferentes.

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.

Correction: The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.

[This corrects the article DOI: 10.1371/journal.pone.0152676.].

The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.

BACKGROUND: Outbreaks of methanol poisoning occur frequently on a global basis, affecting poor and vulnerable populations. Knowledge regarding methanol is limited, likely many cases and even outbreaks go unnoticed, with patients dying unnecessarily. We describe findings from the first three large outbreaks of methanol poisoning where Médecins Sans Frontières (MSF) responded, and evaluate the benefits of a possible future collaboration between local health authorities, a Non-Governmental Organisation and international expertise. METHODS: Retrospective study of three major methanol outbreaks in Libya (2013) and Kenya (May and July 2014). Data were collected from MSF field personnel, local health personnel, hospital files, and media reports. FINDINGS: In Tripoli, Libya, over 1,000 patients were poisoned with a reported case fatality rate of 10% (101/1,066). In Kenya, two outbreaks resulted in approximately 341 and 126 patients, with case fatality rates of 29% (100/341) and 21% (26/126), respectively. MSF launched an emergency team with international experts, medications and equipment, however, the outbreaks were resolving by the time of arrival. INTERPRETATION: Recognition of an outbreak of methanol poisoning and diagnosis seem to be the most challenging tasks, with significant delay from time of first presentations to public health warnings being issued. In spite of the rapid response from an emergency team, the outbreaks were nearly concluded by the time of arrival. A major impact on the outcome was not seen, but large educational trainings were conducted to increase awareness and knowledge about methanol poisoning. Based on this training, MSF was able to send a local emergency team during the second outbreak, supporting that such an approach could improve outcomes. Basic training, simplified treatment protocols, point-of-care diagnostic tools, and early support when needed, are likely the most important components to impact the consequences of methanol poisoning outbreaks in these challenging contexts.

Risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes--a multicenter study.

INTRODUCTION. Thorough prognostic and metabolic studies of methanol poisonings are scarce. Our aims were to evaluate the factors associated with sequelae and death from methanol poisoning, to develop a simple risk-assessment chart to evaluate factors associated with sequelae and death from methanol poisoning, and to compare the antidotes ethanol and fomepizole. PATIENTS AND METHODS. We present a retrospective observational case series of methanol-poisoned patients from Norway (1979 and 2002-2005), Estonia (2001) and Tunisia (2003/2004), and patients from two different centers in Iran (Teheran 2004-2009 and Mashhad 2009-2010) who were identified by a positive serum methanol and had a blood acid-base status drawn on admission. The patients were divided into different groups according to their outcome: Survived, survived with sequelae, and died. RESULTS. A total of 320 patients were identified and 117 were excluded. Of the remaining 203 patients, 48 died, and 34 were discharged with neurological sequelae. A pH < 7.00 was found to be the strongest risk factor for poor outcome, along with coma (Glasgow Coma Scale (GCS) < 8) and a pCO(2) ≥ 3.1 kPa in spite of a pH < 7.00. More patients died despite hyperventilation (low pCO(2)) in the ethanol group. CONCLUSIONS. Low pH (pH < 7.00), coma (GCS < 8), and inadequate hyperventilation (pCO(2) ≥ 3.1 kPa in spite of a pH < 7.00) on admission were the strongest predictors of poor outcome after methanol poisoning. A simple flow-chart may help identify the patients associated with a poor outcome.

Methanol poisoning and long term sequelae - a six years follow-up after a large methanol outbreak.

BACKGROUND: Mass poisonings with methanol are rare but occur regularly both in developed and in developing countries. Data from the poisoning episodes are often published, but follow-up-data is scarce. We therefore conducted a six year follow-up study after the large methanol outbreak in Estonia in September 2001. METHODS: Surviving victims from the outbreak were contacted and invited to an interview and a clinical evaluation by an ophthalmologist and a physician. The patients that failed to respond were searched for in the Estonian Register of Population and through their General Practitioner. RESULTS: During the outbreak in 2001, 86/111 hospitalized patients survived: 66 without sequelae (Group I) and 20 with sequelae (Group II). Six years later, 26/86 were dead, 33/86 could not be tracked down, and so only 27/86 of these were followed up and examined: 22/66 of the patients in Group I, and 5/20 in Group II were found and examined. From Group I, 8/22 were identified with new neurological impairment and 8/22 with new visual disturbances after discharge. From Group II, visual disturbances (n = 4) and neurological impairment (n = 3) were still present in all patients. Among the 26 dead, 19 were from Group I, and seven were from Group II. Alcohol intoxication was the most frequent cause of death (7/26). CONCLUSION: All sequelae were still present six years after the initial poisoning suggesting that these were irreversible damages. On follow-up, apparently new neurological and visual complications were identified in 36% and 36%, respectively. 35% of the patients initially discharged with sequelae and 29% discharged without were dead six years later; 27% of them from alcohol intoxication.