Significant toxicity following an increase in poisonings with designer benzodiazepines in the Netherlands between 2010 and 2020

BACKGROUND: Designer benzodiazepines (DBs) are an emerging class of new psychoactive substances. While structurally derived from pharmaceutical benzodiazepines, their toxicological profile is less clear. We investigated time trends in the rate of DB poisonings and their clinical toxicity. METHODS: A retrospective observational study was performed on the incidence rate of DB poisonings, relative to all recreational drug poisonings reported to the Dutch Poisons Information Center (DPIC) from 2010 to 2020. Time-trend analysis was performed using Poisson regression. A prospective cohort study was performed on toxicity of DBs, including the Poisoning Severity Score, from January 2016-June 2019. Data was collected through telephone interviews. RESULTS: Between 2010 and 2020, the DPIC was consulted on 142 DB exposures. The incidence rate of DB exposures increased from 0.1% to 4.3%, with a year effect estimate of 1.35 (95% CI [1.14;1.54]). Twenty different DBs were reported, mostly etizolam (33%), clonazolam (17%), and flunitrazolam (8%). During consultation (often shortly after exposure), poisoning was graded moderate-severe in 29% of cases (n = 146). In the prospective cohort sample with follow-up (n = 22), 86% of cases (n = 19) showed a moderate-severe poisoning. The severity of poisoning did not differ between mono- and mixed intoxications. Frequently reported symptoms in the prospective cohort sample included drowsiness (86%), confusion (59%), and agitation (55%). Coma was observed in seven cases (32%) and respiratory depression requiring mechanical ventilation in five cases (23%). CONCLUSION: The rate of DB poisonings reported to the DPIC strongly increased from 2010 to 2020, indicating increased (ab)use of DBs. Most DB exposures resulted in moderate-severe toxicity with neurological effects

Evidence of a sudden increase in α-chloralose poisoning in dogs and cats in the Netherlands between 2018 and 2021

BACKGROUND: After changes in European Union biocide legislation, the Dutch Poisons Information Center observed a strong increase in information requests concerning dogs and cats exposed to α-chloralose. To investigate whether α-chloralose-based rodenticides are safe for non-professional use, additional information regarding poisoning scenarios and clinical course was collected. METHODS: Veterinarians reporting α-chloralose exposure over a 2.5-year period were contacted by mail for follow-up information concerning exposure scenario, product formulation, clinical course and treatment, and outcome. In total, information was collected for 96 dogs and 41 cats. RESULTS: Fifty-three of 96 dogs and 17 of 19 cats known to have been exposed to α-chloralose-based rodenticides developed signs of central nervous system (CNS) depression or sensory-induced CNS excitation. Mortality in dogs and cats following exposure was 1% and 18%, respectively. An additional 22 cats presented with clinical signs suggestive of α-chloralose poisoning, with a mortality of 5%. LIMITATIONS: Exposure to α-chloralose was not confirmed by biochemical analyses. CONCLUSION: Dogs and especially cats were at risk of poisoning from α-chloralose. If criteria such as acute toxicity and risk of (secondary) poisoning are applied during the approval of α-chloralose-based rodenticides, similar to anticoagulant-based rodenticides, it can be concluded that α-chloralose is also not safe for non-professional use

High Incidence of Signs of Neuropathy and Self-Reported Substance Use Disorder for Nitrous Oxide in Patients Intoxicated with Nitrous Oxide

Introduction: The number of patients with excessive nitrous oxide (N2O) use and neurological disorders has been rising, indicating an addictive potential of N2O. We studied the incidence of self-reported substance use disorder (SUD)-related symptoms, signs of neuropathy, and the patterns of use in N2O-intoxicated patients. Methods: The Dutch Poisons Information Center (DPIC) provides information by telephone on the management of intoxications to healthcare professionals. Retrospective data on signs of neuropathy and patterns of use were collected for all N2O intoxications reported to the DPIC in 2021 and 2022. Frequent and heavy use were self-reported as "often/frequent/weekly use"and as "use of tanks or >50 balloons/session,"respectively. From this cohort, we included patients with excessive N2O use or signs of neuropathy in a prospective observational cohort study. Online surveys were sent 1 week, 1 month, and 3 months after DPIC consultation. The survey included the drug use disorder questionnaire (validated to measure self-reported substance abuse [SA] and substance dependence [SD] based on Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV-TR criteria) and questions on patterns of use and signs of neuropathy. DSM-IV-TR criteria were translated to DSM-V criteria to score for mild, moderate, or severe SUD, with 2-3, 4-5, or ≥6 symptoms, respectively. Results: We included 101 N2O-intoxicated patients in the retrospective study. Of these, 41% showed signs of neuropathy (N = 41), 53% used N2O tanks to fill balloons (N = 53), 71% used them frequently (N = 72), and 76% used them heavily (N = 77). We included 75 patients in the prospective study and 10 (13%) completed the first survey. All 10 patients fulfilled the criteria for SA and SD (DSM-IV-TR, median number of questions answered "yes"= 10/12), all used N2O tanks to fill balloons, and 90% (N = 9) experienced signs of neuropathy. After 1 and 3 months, 6/7 and 1/1 patients, respectively, continued to fulfill SA and SD criteria. Translating to DSM-V criteria, 1/10 patients fulfilled the criteria for (self-reported) mild SUD, 1/10 patients for moderate SUD, and 8/10 patients for severe SUD, 1 week after consultation. Conclusion: The high proportion of N2O-intoxicated patients reporting frequent and heavy use of N2O indicates an addictive potential of N2O. Although follow-up rate was low, all patients fulfilled self-reported SA, SD (DSM-IV-TR), and SUD (DSM-V) criteria for N2O. Somatic healthcare professionals treating patients with N2O intoxications should be aware of possible addictive behavior in patients. The screening, brief intervention, and referral to treatment approach should be considered to treat patients with self-reported SUD symptoms

Is secondary chemical exposure of hospital personnel of clinical importance?

INTRODUCTION: There is increasing concern among hospital personnel about potential secondary exposure when treating chemically contaminated patients. OBJECTIVE: To assess which circumstances and chemicals require the use of Level C Personal Protective Equipment (chemical splash suit and air-purifying respirator), to prevent secondary contamination of hospital personnel treating a chemically contaminated patient. METHODS: The US National Library of Medicine PubMed database was searched for the years 1985 to 2020 utilizing combinations of relevant search terms. This yielded 557 papers which were reviewed by title and abstract. After excluding papers on biological or radiological agents, or those not related to hospital personnel, 38 papers on chemicals remained. After a full-text review, 13 papers without an in-depth discussion on the risk for secondary contamination were omitted, leaving 25 papers for review. The references of these papers were searched and this yielded another seven additional citations, bringing the total to 32 papers. INCIDENCE OF SECONDARY TOXICITY: Secondary toxicity in hospital personnel is rare: a large-scale inventory of 120,000 chemical incidents identified only nine cases, an occurrence of 0.0075%. SKIN CONTACT AS A SECONDARY EXPOSURE ROUTE: Skin exposure is rare under normal hygienic working conditions, reflected by the very small number of cases reported in the literature: two cases with corrosive effects due to unprotected contact and one case of presumed skin absorption. INHALATION AS A SECONDARY EXPOSURE ROUTE: Most case reports described secondary toxicity as a result of inhalation. The chemicals involved were irritating solid particles (capsaicin spray/CS), toxic gases formed in the stomach of patients (arsine/hydrazoic acid/phosphine) and vapours from volatile liquids (solvents). FEATURES OF SECONDARY TOXICITY: Reported symptoms after secondary inhalation were generally mild and reversible (mostly irritation of eyes and respiratory tract, nausea, headache, dizziness/light-headedness) and did not require treatment. In many cases, special circumstances increased exposure: treatment/decontamination of multiple patients, regurgitation of the chemical agent from the stomach, or inadequate room ventilation. USE OF MORE THAN STANDARD PERSONAL PROTECTIVE EQUIPMENT: Normal hygienic precautions prevent direct skin contact from exposure to common chemical agents. When solid particle contamination is extensive, a mask and eye protection should be applied. Splash proof outer clothing (splash suit) and eye protection is preferred if (partial) wet decontamination is performed on single patients. Adequate ventilation, careful removal of clothing in case of solid particles contamination and adequate disposal of gastric content reduces exposure. Hospital staff can be rotated if symptoms occur, which can be odour-mediated. The use of more elaborate personal protective equipment with an air-purifying respirator (Level C) is only necessary in exceptional cases of contamination with highly toxic volatile chemicals (e.g., sarin). It should also be considered when decontaminating a large number of patients. CONCLUSIONS: The risk of secondary contamination and subsequent toxicity in hospital personnel decontaminating or treating chemically contaminated patients is small. Normal hygienic precautions (gloves and water-resistant gown) will adequately protect hospital staff when treating the majority of chemically contaminated patients. More extensive protection is only necessary infrequently and there is no reason to delay critical care, even if more elaborate protection is not immediately available

Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans

Background: Recently, the number of new psychoactive substances (NPS) appearing on the illicit drug market has shown a marked increase. Although many users perceive the risk of using NPS as medium or low, these substances can pose a serious health risk and several NPS have been implicated in drug-related deaths. In Europe, frequently detected NPS are 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-fluoroamphetamine (4-FA) and benzofurans (5-(2-aminopropyl)benzofuran (5-APB) or 6-(2-aminopropyl)benzofuran (6-APB)). However, little is known about the health risks of these specific NPS. Methods: In this paper, existing literature on the pharmacokinetics and pharmacodynamics of 2C-B, 4-FA and benzofurans (5-APB/6-APB) was reviewed. Results: Our review showed that the clinical effects of 2C-B, 4-FA and benzofurans (5-APB/6-APB) are comparable with common illicit drugs like amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Therefore, NPS toxicity can be handled by existing treatment guidelines that are based on clinical effects instead of the specific drug involved. Even so, information on the health risks of these substances is limited to a number of case reports that are complicated by confounders such as analytical difficulties, mislabelling of drugs, concomitant exposures and interindividual differences. Conclusion: To aid in early legislation, data on clinical effects from poisons centres and user fora should be combined with (in vitro) screening methods and collaboration on an (inter)national level is essential. As a result, potentially hazardous NPS could be detected more quickly, thereby protecting public health. (C) 2015 Elsevier Ireland Ltd. All rights reserve

Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS) : 2C-B, 4-fluoroamphetamine and benzofurans

BACKGROUND: Recently, the number of new psychoactive substances (NPS) appearing on the illicit drug market has shown a marked increase. Although many users perceive the risk of using NPS as medium or low, these substances can pose a serious health risk and several NPS have been implicated in drug-related deaths. In Europe, frequently detected NPS are 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-fluoroamphetamine (4-FA) and benzofurans (5-(2-aminopropyl)benzofuran (5-APB) or 6-(2-aminopropyl)benzofuran (6-APB)). However, little is known about the health risks of these specific NPS. METHODS: In this paper, existing literature on the pharmacokinetics and pharmacodynamics of 2C-B, 4-FA and benzofurans (5-APB/6-APB) was reviewed. RESULTS: Our review showed that the clinical effects of 2C-B, 4-FA and benzofurans (5-APB/6-APB) are comparable with common illicit drugs like amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Therefore, NPS toxicity can be handled by existing treatment guidelines that are based on clinical effects instead of the specific drug involved. Even so, information on the health risks of these substances is limited to a number of case reports that are complicated by confounders such as analytical difficulties, mislabelling of drugs, concomitant exposures and interindividual differences. CONCLUSION: To aid in early legislation, data on clinical effects from poisons centres and user fora should be combined with (in vitro) screening methods and collaboration on an (inter)national level is essential. As a result, potentially hazardous NPS could be detected more quickly, thereby protecting public health

New psychoactive substances (NPS) in the Netherlands : occurrence in forensic drug samples, consumer drug samples and poisons center exposures between 2013 and 2017

Background and Aims Although European-wide data on the new psychoactive substances (NPS) drug market are available, country-specific data are limited. We studied recent NPS trend data relative to all recreational drugs on the Dutch drugmarket. Design National observational study. Setting The Netherlands. Data sources Three national indicators were used between 2013 and 2017: (1) forensic drug samples offered to the Netherlands Forensic Institute (NFI); (2) drug samples submitted by consumers to the Drugs Information and Monitoring System (DIMS); and (3) exposures in which the Dutch Poisons Information Center (DPIC) was consulted. Measurements Overall NPS incidence rate was the primary outcome. Numbers and specific categories of NPS were also studied. Changes in NPS incidence rates over time were analyzed using Poisson regression analyses [year effect expressed as incidence rate ratios (IRR)]. Findings From 2013 to 2017, NPS were involved in 1892 forensic samples, 6316 consumer samples and 481 poisons center exposures. In 2013, NPS incidence rates were 2.5, 7 and 4% versus 3, 11 and 11% in 2017, respectively, in the NFI, DIMS and DPIC samples/exposures. NPS incidence rates increased significantly in consumer samples between 2013 and 2016 [IRR=1.23; 95% confidence interval (CI) = 1.18, 1.29] and in poisons center exposures between 2013 and 2017 (IRR = 1.19; 95% CI = 1.06, 1.35), while the trend in forensic samples appeared more stable. Phenethylamines were the largest class and were detected in 58, 80 and 63% of NFI, DIMS and DPIC samples/exposures, respectively. Detected phenethylamines mainly involved 4-fluoroamphetamine and 2C-x derivatives. The second largest class were cathinones, which were detected in 21, 11 and 16% of NFI, DIMS and DPIC samples/exposures, respectively. Conclusions Analysis of forensic drug samples, consumer drug samples and exposures reported to poison centers from 2013 to 2017 shows the constant presence of new psychoactive substances on the Dutch drug market and its use by the Dutch population. The two largest classes present in the Netherlands were phenethylamines and cathinones

The Clinical Toxicology of 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): The Severity of Poisoning After Exposure to Low to Moderate and High Doses.

STUDY OBJECTIVE: We studied the severity of poisoning after exposure to low to moderate and high doses of 4-bromo-2,5-dimethoxyphenethylamine (2C-B). METHODS: Patients for whom the Dutch Poisons Information Centre was consulted for 2C-B exposure from 2016 to 2018 were included in a prospective cohort study. Data were collected through telephone interviews with the physician or patient. Patients were categorized according to the reported 2C-B dose: low to moderate (up to 20 mg), high (greater than 20 mg), or unknown. Presence of 2C-B was analyzed in leftover drug and biological samples with liquid/gas chromatography-mass spectrometry. The severity of poisoning was graded with the Poisoning Severity Score. RESULTS: We included 59 patients, of whom 32 could be followed up. Low to moderate 2C-B doses were reported by 9 patients (28%), high doses by 17 (53%), and unknown doses by 6 (19%). Poisoning was moderate in the majority of patients in both the low- to moderate-dose and high-dose groups. Frequently reported symptoms included mydriasis, agitation or aggression, hallucinations, confusion, anxiety, hypertension, and tachycardia. The presence of 2C-B was confirmed in 5 patients in urine (n=3) or drug samples (n=4). CONCLUSION: In this study, most 2C-B poisonings resulted in moderate toxicity even at high reported doses up to 192 mg. No severe cases were observed. The clinical course was usually short-lived (up to 24 hours) and typically involved hallucinations in addition to mild somatic effects

New psychoactive substances (NPS) in the Netherlands: occurrence in forensic drug samples, consumer drug samples and poisons center exposures between 2013 and 2017

Background and Aims Although European-wide data on the new psychoactive substances (NPS) drug market are available, country-specific data are limited. We studied recent NPS trend data relative to all recreational drugs on the Dutch drugmarket. Design National observational study. Setting The Netherlands. Data sources Three national indicators were used between 2013 and 2017: (1) forensic drug samples offered to the Netherlands Forensic Institute (NFI); (2) drug samples submitted by consumers to the Drugs Information and Monitoring System (DIMS); and (3) exposures in which the Dutch Poisons Information Center (DPIC) was consulted. Measurements Overall NPS incidence rate was the primary outcome. Numbers and specific categories of NPS were also studied. Changes in NPS incidence rates over time were analyzed using Poisson regression analyses [year effect expressed as incidence rate ratios (IRR)]. Findings From 2013 to 2017, NPS were involved in 1892 forensic samples, 6316 consumer samples and 481 poisons center exposures. In 2013, NPS incidence rates were 2.5, 7 and 4% versus 3, 11 and 11% in 2017, respectively, in the NFI, DIMS and DPIC samples/exposures. NPS incidence rates increased significantly in consumer samples between 2013 and 2016 [IRR=1.23; 95% confidence interval (CI) = 1.18, 1.29] and in poisons center exposures between 2013 and 2017 (IRR = 1.19; 95% CI = 1.06, 1.35), while the trend in forensic samples appeared more stable. Phenethylamines were the largest class and were detected in 58, 80 and 63% of NFI, DIMS and DPIC samples/exposures, respectively. Detected phenethylamines mainly involved 4-fluoroamphetamine and 2C-x derivatives. The second largest class were cathinones, which were detected in 21, 11 and 16% of NFI, DIMS and DPIC samples/exposures, respectively. Conclusions Analysis of forensic drug samples, consumer drug samples and exposures reported to poison centers from 2013 to 2017 shows the constant presence of new psychoactive substances on the Dutch drug market and its use by the Dutch population. The two largest classes present in the Netherlands were phenethylamines and cathinones

Evidence of a sudden increase in α-chloralose poisoning in dogs and cats in the Netherlands between 2018 and 2021

BACKGROUND: After changes in European Union biocide legislation, the Dutch Poisons Information Center observed a strong increase in information requests concerning dogs and cats exposed to α-chloralose. To investigate whether α-chloralose-based rodenticides are safe for non-professional use, additional information regarding poisoning scenarios and clinical course was collected. METHODS: Veterinarians reporting α-chloralose exposure over a 2.5-year period were contacted by mail for follow-up information concerning exposure scenario, product formulation, clinical course and treatment, and outcome. In total, information was collected for 96 dogs and 41 cats. RESULTS: Fifty-three of 96 dogs and 17 of 19 cats known to have been exposed to α-chloralose-based rodenticides developed signs of central nervous system (CNS) depression or sensory-induced CNS excitation. Mortality in dogs and cats following exposure was 1% and 18%, respectively. An additional 22 cats presented with clinical signs suggestive of α-chloralose poisoning, with a mortality of 5%. LIMITATIONS: Exposure to α-chloralose was not confirmed by biochemical analyses. CONCLUSION: Dogs and especially cats were at risk of poisoning from α-chloralose. If criteria such as acute toxicity and risk of (secondary) poisoning are applied during the approval of α-chloralose-based rodenticides, similar to anticoagulant-based rodenticides, it can be concluded that α-chloralose is also not safe for non-professional use