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.

Digoxin-specific antibodies: a novel dosing strategy.

Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These antibodies are not registered for use in Europe; therefore Dutch hospital pharmacies are not allowed to keep them in stock. In the Netherlands, digoxin-Fabs are stored in a national calamity stock of emergency medicines at the National Institute for Public Health and the Environment. In the case of a medical emergency, digoxin-Fabs are available after contact with the Dutch Poisons Information Centre. Recent studies have shown that the dose of digoxin-Fabs required to effectively treat digoxin toxicity is lower than previously thought. In this article, we present the adjusted digoxin-Fab dosing strategy currently recommended by the Dutch Poisons Information Centre ( www.vergiftigingen.info ). This new dose titration strategy is safe and effective and has a cost-saving side-effect.

[Needle spiking, injecting people with a substance without their knowledge or consent]. / Needle spiking, het drogeren met een injectienaald.

BACKGROUND: In the Netherlands therewereseveralreports on needlespiking: people have found themselvessubjectedtosurreptitiousinjections. CASE DESCRIPTION: A 23-year-old female was seenafterbeingsurroundedby a group of men andfeltwhatshethought was a jab. She was abletoevadethegroup. Several minutes later sheexperienceddizziness, nausea andvomiting. On physical examination, a bleedingpuncturewound was seen on her upper arm withaccompanying erythema. Toxicology on bloodand urine didnot show evidenceforintoxicationotherthan alcohol which was higherthanwouldbesuspectedbythenumber of drinks thevictimreported. CONCLUSION: There is evidencethatpeople are puncturedwithneedles in busy surroundings like thenightlife. Possiblealso drugs are injected. Experiencedsymptomsbyvictims (n=19) wereheterogeneousandnotlikelyattributedtooneandthesamecausal drug. Toxicologydidnotrevealanysubstanceuntilnow.

Recreational drug use among young, hospitalized patients with acute coronary syndrome: A retrospective study.

Background: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS. Objective: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients. Methods: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up. Results: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007). Conclusion: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users.

4-Fluoroamphetamine (4-FA) intoxication results in exaggerated blood pressure effects compared to MDMA and amphetamine: A retrospective analysis.

Objective: 4-Fluoroamphetamine (4-FA) is an amphetamine-type stimulant, with effects comparable to amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Severe 4-FA-related complications, such as cardiomyopathy, myocardial infarction, and cerebral hemorrhage, have been described. The aim of this study was to explore the cardiovascular symptoms and complications in 4-FA and compare them to MDMA and amphetamine in intoxicated patients who presented to the emergency department (ED). Methods: Between November 2015 and March 2020, all self-reported 4-FA, MDMA, and amphetamine-intoxicated adult patients that presented at the ED of an inner-city hospital in Amsterdam, were retrospectively analyzed for cardiovascular symptoms, vital parameters, cardiovascular complications, interventions, admission rate, and Poisoning Severity Score (PSS). Results: A total of 582 patients were included, of which 31 (5.3%) with 4-FA intoxication (10/31 mono-intoxications, 32.3%), 406 (69.8%) with MDMA (59/406 mono-intoxications, 14.5%), 100 (17.2%) with amphetamine (10/100 mono-intoxications, 10.0%), and 45 (7.7%) with a cross intoxication of these drugs. 4-FA mono-intoxicated patients experienced more headache (n = 8; 80.0%) compared to MDMA (n = 2; 3.3%; P < 0.001) and amphetamine mono-intoxicated patients (n = 0; 0.0%; P < 0.001) and their systolic blood pressure was higher (164 mm Hg ± 31 vs 139 mm Hg ± 19; P = 0.031 vs 135 mm Hg ± 22; P = 0.033, respectively). Severe 4-FA-related cardiovascular complications included Takotsubo cardiomyopathy (n = 1; 3.2%), subarachnoid hemorrhage (n = 1; 3.2%), and hypertensive urgency (n = 2; 6.5%). Conclusions: 4-FA intoxication-related ED symptoms resemble MDMA and amphetamine complications, although patients presented more often with headache and hypertension. Severe 4-FA-related cardiovascular complications occurred in 40% of mono-intoxications.

[Impact of the COVID-19 pandemic on recreational drug intoxications]. / Invloed van covid-19-pandemie op drugsintoxicaties.

OBJECTIVE: To investigated the impact of the lockdown during the COVID-19 pandemic, since March 2020, on the occurrence and characteristics of recreational drug intoxications in the Emergency Department (ED), compared to previous years. DESIGN: Retrospective cohort study METHOD: Patients ≥ 18 years old who presented to the ED of OLVG hospital in Amsterdam with recreational drug intoxication(s), with or without alcohol, were divided into the pre-COVID-19-period (January 2017 to February 2020), and the COVID-19-period (March to December 2020). An intoxication was registered by the treating physician, or retrospectively by researchers. Subgroup analysis was performed for foreign tourists, Dutch tourists and Amsterdam residents, as for the four most common drugs used. RESULTS: A total of 3,881 patients (73.6% male, aged 32 (±12) years) were included, of whom 49.0% were tourists. During the COVID-19-period, a 53% decrease of intoxications was observed (1090.1 vs. 514.8 patients/year), with an 83% decrease of tourists (574 vs. 98.4 patients/year), 20% decrease in Dutch residents (516 vs. 416 patients/year) and 4,5% decrease in Amsterdam residents (354 vs.338 patients/year). Among Dutch patients, a significant decrease in cocaine (85.6 vs. 75.6 patients/years), MDMA (25.1 vs. 27.6 patients/year), and THC (108.6 vs. 76.8 patients/year) intoxications were observed. However, the amount of GHB/GBL related intoxications was comparable between groups (100.7 vs. 105.6 patients/year). CONCLUSION: During the COVID-19-period, drug-related intoxications decreased by 53%. Among Dutch residents this decrease was 20%, with a significant decrease in cocaine, MDMA and THC intoxications. However, the amount of GHB/GBL related intoxications was comparable with the pre-COVID-19 period.

Clinical toxicology of exposures to chemicals from clandestine drug laboratories: a literature review.

INTRODUCTION: The synthesis of clandestine drugs is a widespread worldwide phenomenon, with clandestine drug laboratories occurring both in rural and urban areas. There is considerable unfamiliarity among medical professionals about the health risks that are associated with chemicals used in clandestine drug laboratories. OBJECTIVE: To evaluate the adverse health effects resulting from exposure to chemicals involved in the production of clandestine drugs. METHODS: The US National Library of Medicine PubMed database and the Excerpta Medica database (EMBASE) were searched from their date of inception to October 26, 2021 using combinations of relevant search terms. This yielded 1,558 unique articles, which were subjected to two eligibility criteria: (i) exposure to clandestine drug laboratory chemicals resulting in adverse health effects; (ii) subjects were human. A total of 22 unique articles were retrieved, consisting of 10 reviews, eight case reports/series and four retrospective studies. Further searches among the references cited in these publications yielded another seven case reports/series and six retrospective studies. RESULTS: Inhalation: Surveillance studies reported respiratory symptoms (including cough, throat irritation, nasal irritation, and dyspnea) in 59% (n = 1,657 of 2,803) of those exposed. The case reports/series described respiratory symptoms in 43% of the cases (n = 36 of 84). Lung edema was reported occasionally (n = 2). Eye exposure: Surveillance studies reported eye irritation and burns in 23% (n = 647 of 2,803) of those exposed. The case reports/series described ocular adverse events in 36% of the cases (n = 30 of 84). More severe ocular effects, such as corneal damage and conjunctival necrosis, were reported after direct eye contact with caustic fluids. Skin exposure: Surveillance studies reported dermal effects, ranging from skin irritation to severe burns, in 6% of those exposed (n = 174 of 2,803). The case reports/series described dermal effects in 30% of the cases (n = 25 of 84). Ingestion: Gastrointestinal burns were observed after ingestion of caustic substances in 5% of the patients reported in the case reports/series (n = 4 of 84). Systemic effects: Surveillance studies reported headache and dizziness in 31% (n = 882 of 2,803) and 7% (n = 187 of 2,803) of those exposed, respectively. The case reports/series described sympathomimetic effects, including mydriasis, hypertension, tachycardia, in 4% of the cases (n = 3 of 84). Fatalities: Surveillance studies reported death in 1% of those exposed (n = 29 of 2803). Ten percent of the people reported in the cases report/series died (n = 8 of 84). Death was reported after inhalation of phosphine (n = 5), hydrogen sulfide (n = 1), methanol (n = 1), and after ingestion of sulfuric acid (n = 1). CONCLUSIONS: Exposure to chemicals involved in the production of clandestine drugs mostly resulted in mild to moderate respiratory, ocular or dermal effects, usually caused by caustic chemicals or solvents. Systemic effects were generally mild, but severe symptoms and eight deaths were reported after exposure to phosphine, hydrogen sulfide, methanol and sulfuric acid.

[Complications of contaminated drugs: how to reduce the number of future victims?] / Complicaties van vervuilde drugs.

Serious complications of drug abuse are frequently seen in acute care. When the clinical signs and symptoms of drug use are discordant with the expected clinical features of the intended substance used, it may involve misleading, contaminated and therefore dangerous illicit drugs. In 2014 and 2015, multiple young patients presented to several Dutch emergency departments in Amsterdam with an opioid toxidrome after supposed use of cocaine. However, it required months and multiple patient presentations, including fatalities, to discover that heroin was sold as cocaine, resulting in serious opioid toxidrome complications. The improvement and formalization of local collaboration and the instatement of an accessible central coordinating party enables early pattern recognition, treatment, sample testing and prevention of future cases of serious drug complications. This was demonstrated in a case of accidental fentanyl intoxication after alleged cocaine use in 2018. Extension of such collaborative networks to create a national coverage is desirable.

The current practice for cocaine-associated chest pain in the Netherlands.

INTRODUCTION: Cocaine is considered a cardiovascular risk factor, yet it is not included in the frequently used risk stratification scores. Moreover, many guidelines provide limited advice on how to diagnose and treat cocaine-associated chest pain (CACP). This study aimed to determine the current practice for CACP patients in emergency departments and coronary care units throughout the Netherlands. METHODS: An anonymous online questionnaire-based survey was conducted among Dutch emergency physicians and cardiologists between July 2015 and February 2016. The questionnaire was based on the American Heart Association CACP treatment algorithm. RESULTS: A total of 214 subjects were enrolled and completed the questionnaire. All responders considered cocaine use a risk factor for developing acute coronary syndrome (ACS), nevertheless 74.4 % of emergency physicians and 81.1 % of cardiologists do not always question chest pain patients about drug use. Of all responders, 73.6 % never perform toxicology screening. Most responders (60 %) observe patients with CACP according to the European Society of Cardiology ACS guideline, and 24.3 % give these patients ß-blockers. CONCLUSION: The current practice for CACP patients in most emergency departments and coronary care units in the Netherlands is not in line with the AHA scientific statement. Emergency physicians and cardiologists should be advised to routinely question all chest pain patients on drug history and be aware that the risk stratifications scores are not validated for CACP. Despite the AHA scientific statement of 2008, many respondents utilize ß-blockers for CACP patients, which is supported by published evidence since the statement appeared.

Prospective Investigation of the Performance of 2 Gamma-Hydroxybutyric Acid Tests: DrugCheck GHB Single Test and Viva-E GHB Immunoassay.

BACKGROUND: Gamma-hydroxybutyric acid (GHB) is a recreational drug with central nervous system depressing effects that is often abused. A urine GHB point-of-care test can be of great diagnostic value. The objective of this prospective study was to determine the performance of the new DrugCheck GHB Single Test and the Viva-E GHB immunoassay for urine samples in emergency department patients. METHODS: Patients presented to the emergency department of the OLVG hospital in Amsterdam with a Glasgow Coma Scale score <15 and potential drug of abuse intoxication were included in the study. Between June 2016 and October 2017, 375 patients were included. Using the DrugCheck GHB Single Test (Express Diagnostics Int'l, Blue Earth, MN) and the Viva-E GHB immunoassay (Siemens Healthineers, The Hague, the Netherlands), patients' urine samples were tested for GHB (cutoff for a positive result, 10 or 50 mcg/mL GHB). To ensure quality, the results obtained were compared with those generated using a validated gas chromatography method. The tests were considered reliable if specificity and sensitivity were both >90%. Possible cross-reactivity with ethanol was investigated by analyzing ethanol concentrations in patients' samples. RESULTS: Seventy percentage of the included patients was men, and the median age was 34 years old. The DrugCheck GHB Single Test's specificity and sensitivity were 90.0% and 72.9%, respectively, and using 50 mcg/mL as a cutoff value, its specificity and sensitivity improved to 96.7% and 75.0%, respectively. Serum and urine ethanol levels in the false-positive group were significantly higher compared with those in the true-negative group. The specificity and sensitivity of the Viva-E GHB immunoassay (cutoff value of 50 mcg/mL and excluding samples with ethanol levels ≥2.0 g/L) were 99.4% and 93.5%, respectively. CONCLUSIONS: The DrugCheck GHB Single Test's specificity was sufficient, whereas its sensitivity was poor, making it unsuitable for use at point-of-care. Contrarily, using 50 mcg/mL as the cutoff value and excluding samples with ethanol levels ≥2.0 g/L, the Viva-E GHB immunoassay showed acceptable results to detect clinically relevant GHB intoxications.

Safety of withholding intubation in gamma-hydroxybutyrate- and gamma-butyrolactone-intoxicated coma patients in the emergency department.

OBJECTIVE: The objective of this study was to determine if supportive care without endotracheal intubation in the emergency department (ED) was safe in the absence of complications in gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) intoxicated patients with a decreased Glasgow Coma Scale (GCS) score. METHODS: This was a retrospective chart review of patients presenting to a Dutch tertiary urban ED with a reduced level of consciousness related to alleged GHB/GBL intoxication between April 2011-December 2014. Primary endpoint was major adverse events, defined by: upper airway obstruction not resolved with mayo tube or nasopharyngeal airway, hypoxia not resolved with 15 l of oxygen delivered via non-rebreathing mask, bradypnea not resolved after stimulation, intubation, bradycardia not resolved after intravenous atropine bolus, hypotension for which inotropes were started. RESULTS: Data of 209 patients were retrieved. Major adverse events were reported in five patients (2.4%; 95% CI: 0.8-5.5). Intubation with subsequent ICU admission was required for 1.4% of patients (95% CI: 0.3-4.1). The most frequently seen minor adverse events (N = 209) were: airway obstruction (22%), hypothermia (14.8%), hypoxia (12.9%), bradycardia (8.1%), hypotension (6.7%), bradypnea (5.7%), vomiting (5.3%). There were no deaths. None of the patients had signs of aspiration pneumonia or returned to our ED due to complications. CONCLUSION: Our study suggests that conservative airway management for patients with a decreased GCS due to suspected GHB intoxication may be safe. Major adverse events were present in 2.4% of patients, only 1.4% of patients required intubation. All minor adverse events were managed effectively with conservative treatment.