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

Essink, Sharon; Lonkhuyzen, Johanna J. Nugteren–van; Riel, Antoinette van; Dekker, D.; Hondebrink, Laura

doi:10.1016/j.drugalcdep.2021.109244

Cited by 8 publications

(6 citation statements)

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“…Although poison center data have their limitations, our study on health problems related to N 2 O (ab)use is not the first example to show that toxicovigilance by poison centers is usually one of the first sources to identify a substance-related public health threat [1,[42][43][44][45]. This monitoring role of poison control centers is further corroborated in the report on N 2 O by the EMCDDA [26].…”

Section: Substance Use Disorder For Nitrous Oxide In Intoxicated Pati...supporting

confidence: 60%

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

et al. 2023

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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.

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Section: Substance Use Disorder For Nitrous Oxide In Intoxicated Pati...supporting

confidence: 60%

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

et al. 2023

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“…Just as our study demonstrated, elderly-aged patients with substance abuse have higher mortality as described in the previous study [ 14 ]. Another retrospective study from the five Nordic countries: Denmark, Finland, Iceland, Norway, and Sweden, also showed many deaths numbers of addicts more than 45 years old [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…These kinds of patients are prone to be intubated for airway protection. Sharon Essink et al reported NPS intoxication symptoms in a prospective cohort that included patients with coma in seven cases (32%) and respiratory depression requiring mechanical ventilation in five cases (23%) [ 15 ]. Thus, when illicit drug users are in a deep coma, never hesitate to intubate the patients to have good supportive care.…”

Section: Discussionmentioning

confidence: 99%

Clinical Presentations and Predictors of In-Hospital Mortality in Illicit Drug Users in the New Psychoactive Substances (NPS) Endemic Era in Taiwan

Yeh

Chen

Liu

et al. 2022

Toxics

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Predictors of mortality in illicit drug users involving Novel Psychoactive Substances (NPS) and multiple substances have not been elucidated. We aimed to define predictors of mortality in the NPS endemic era’s illicit drug users to strengthen patient care in emergency treatment. This was a retrospective study. LC-MS/MS-confirmed positive illicit drug users who visited the emergency departments (ED) of six medical systems were enrolled. Demographic information, physical examinations, and laboratory data were abstracted for mortality analysis. There were 16 fatalities in 355 enrolled patients. The most frequently used illicit drugs were amphetamines, followed by opioids, cathinones, and ketamine. The most frequently detected cathinones among the 16 synthetic cathinones were eutylone, followed by mephedrone. The combined use of cathinones and ketamine was most commonly observed in our results. Univariate analysis revealed that the mortality patients were older, with deep coma, faster heart rate and respiratory rate, lower blood pressures and O2 room air saturation, more seizures, abnormal breath sounds, and had urine incontinence compared to the survivor patients. The mortality patients also had acute kidney injury, higher potassium, blood sugar, liver function test, and lactate level. The results of multiple logistic regression demonstrated that SBP < 90 mmHg, dyspnea, blood sugar > 140 mg/dl, and HCO3 < 20.6 mmHg were independent predictors of in-hospital mortality. Regardless of the pattern of the use of illicit drugs, the predictors allow for risk stratification and determining the optimal treatment.

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“…33 In the Netherlands, the rate of reported DBZD poisoning significantly increased from 2010 to 2020, indicating increased (ab)use of DBZDs. 34 By 2021, this class of substances had reached markets in South America, with Brazil already classifying etizolam and flualprazolam as controlled psychotropic substances, as recommended by the World Health Organization. 35 The reasons for the increasing availability, number of molecules, and prevalence of consumption are not entirely clear or documented.…”

Section: Background Of a Success Story!mentioning

confidence: 99%

“…Coma was observed in 7 cases, and respiratory depression requiring mechanical ventilation in 5 cases. 34 Overall, 20 DBZDs were found to have been abused. The most severe poisonings were caused by etizolam, flubromazolam, flunitrazolam, and phenazepam.…”

Section: Toxicitymentioning

confidence: 99%

Designer Benzodiazepines: Effects, Toxicity, and Interactions

Balkhi

Abbara

2023

Therapeutic Drug Monitoring

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Purpose: Although designer benzodiazepines (DBZDs) constitute a minor part of new psychoactive substances, they deserve the greatest attention because of their popularity among drug users and increasing number and availability. This review covers the effects of different DBZDs, available pharmacological evaluation tools, and their reported toxicity and potential pharmacodynamic and pharmacokinetic interactions with other drugs commonly co-abused with DBZDs.Methods: For this narrative review, a nonsystematic search was performed on PubMed, EMBASE, Google Scholar, and PubMed Central databases between June and July 2021. Results:The current consensus hypothesis suggests that DBZDs mediate their effects through interactions with the GABA A receptor, producing similar effects to benzodiazepines used in therapy, including sedation, hypnosis, anxiolysis, muscle relaxation, euphoria, amnesia, and addiction. Owing to the complexity of their action mechanism and the numerous GABA A subtype receptors, the pharmacodynamic metrics of DBZDs are very difficult to establish. The pharmacological effects of DBZD are related to their structure, influencing their binding to GABA A receptor subunits. Quantitative structure-activity relationship studies successfully predicted the biological activity and relative potency of DBZD but could not predict the main pharmacological effect of a given DBZD. Exploring the effects by netnographic studies is one of the available alternatives, despite its limitations. DBZDs are usually identified in the context of polysubstance use. Pharmacodynamic interactions between DBZDS and other CNS depressants, such as opioids, have been extensively reported. However, pharmacokinetic interactions between DBZDs and opioids are considered less important, and contradictory conclusions about their clinical significance have been reported. Conclusions:Understanding the mechanism of action and other pharmacological metrics is highly important in the clinical management of DBZDs.

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

Cited by 8 publications

References 15 publications

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

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

Clinical Presentations and Predictors of In-Hospital Mortality in Illicit Drug Users in the New Psychoactive Substances (NPS) Endemic Era in Taiwan

Designer Benzodiazepines: Effects, Toxicity, and Interactions

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