Non-fatal overdose following ingestion of encapsulated pure bromazolam powder: A case report

PAROXETINE OVERDOSE LEADING TO SEROTONIN SYNDROME

1. There is little hypothesis-testing clinical research performed in toxicology. Randomized clinical trials are rare and most observational studies are performed on highly selected patients and are subject to marked bias. Thus, for many poisonings, our approach has been based almost entirely on deduction from known pharmacological/toxicological effects, generalizations from drugs within the same therapeutic class, animal data and case reports. This is also far from satisfactory, as many toxicological mechanisms are poorly understood and not related to the therapeutic class. 2. Although we need much better data to address the clinical and public health aspects of poisoning, there are many practical and ethical reasons why randomized clinical trials are difficult in this field. However, the scope for observational research, in particular population-based clinical epidemiology, is almost unlimited. The collection of data on human poisoning is facilitated because most non-fatal overdoses are admitted to hospital and by legal requirements to report to the coroner deaths that are due to poisoning. In the present article I argue that 'toxicoepidemiology', meaning the application of epidemiological methods to the problem of acute poisoning, is the best means we have of addressing deficiencies in our knowledge of poisoning. 3. Examples are given of a variety of observational research strategies, ranging from audit to meta-analysis, that may be applied to clinical toxicology. From coronial and clinical data obtained from reasonably well-defined populations, it has been possible to identify a number of previously unrecognized differences in the severity and spectrum of toxicity between and within drug classes. Also, the demographic risk factors for poisoning and the reproducibility, validity and optimal use of diagnostic and therapeutic interventions can be assessed. 4. The major limitations to the range of associations and interventions that may be studied are the need to achieve adequate power to study uncommon outcomes or poisonings and the ability to replicate findings at other centres using similar methodology. The expansion of data collection to other centres has the potential largely to overcome these obstacles.

Incidence of opioid-related overdoses in the United States has increased dramatically over the past two decades. Despite public emphasis on overdose fatalities, most overdose cases are not fatal. Although there are case reports of amnestic syndromes and acute injury to the hippocampus following non-fatal opioid overdose, the effects of such overdoses on brain structure are poorly understood. Here, we investigated the neuroanatomical correlates of non-fatal opioid overdoses by comparing hippocampal volume in opioid use disorder (OUD) patients who had experienced an opioid overdose (OD; N= 17) with those who had not (NOD; N= 32). Voxel-based morphometry showed lower hippocampal volume in the OD group than in the NOD group, which on post hoc analysis was evident in the left but not the right hippocampus. These findings strengthen the evidence that hippocampal injury is associated with non-fatal opioid overdose, which is hypothesized to underlie overdose-related amnestic syndrome.

Introduction Heroin overdose is a leading cause of mortality among drug users. This paper aims to identify individual and contextual factors associated with lethal and non-lethal heroin-related overdoses on the basis of case reports and semi-structured proxy interviews. Typical patterns within these cases are determined by means of cluster analysis. Methods Within the CaRe (Case Reports of heroin-related overdoses) study, case reports (100 proxy reports of overdose events from 36 different facilities) were gathered and evaluated as part of a nationwide survey of experts conducted in Germany in 2019. Following initial descriptive analyses a two-step cluster analysis with the four binary variables of gender, age, time and place was conducted to identify patterns within the reported cases. Results The case reports grouped into five clusters: 1) Younger male drug users, found in a public space during the daytime; 2) Female drug users; 3) Older male drug users, found in a public space during the daytime; 4) Drug users found at home at night; 5) Drug users found outside at night. Overdoses by female drug users and those which occurred at home and/or at night were significantly more likely to have a fatal outcome. Conclusion Future prevention and intervention measures should aim to consider the context, i.e. typical constellations of risk, and attempt to inhibit this through appropriate counter measures.

Paliperidone as an Alternative for Risperidone in a Case of Schizophrenia With Retrograde Ejaculation

Olanzapine is a widely used second generation antipsychotic drug. Case reports of intoxications have been published, but reports in the literature of non-fatal intoxications of olanzapine containing repeated measurements of serum levels are scarce. Therefore, this case of non-fatal olanzapine intoxication is presented, in which 19 blood samples were drawn during 2 weeks. The highest (initial) measured value was estimated at 800 pg/L. This patient ingested 550 mg of olanzapine resulting in clinical signs of intoxication, including seizures. Because the patient was found the day after the intoxication, the initial concentration had probably been higher. The pharmacokinetics of olanzapine has been described as linear and dose-proportional throughout the therapeutic dosing range. Large overdoses, however, have been described to show non-linear pharmacokinetics. In this study's series of serum concentrations, a two-phase elimination was seen, with an initial elimination half-life of about 24 h during the first 3 days, followed by a second phase with a half-life of about 2.5 days. The patient in this case recovered completely. Because the elimination time after intoxication can be considerably longer than expected, it is recommended that the patient's serum concentrations after intoxication be monitored.

Background Caffeine poisoning may cause life-threatening arrhythmias and hemodynamic failure. We aimed to investigate the toxicokinetics (TK), toxicodynamics (TD) and TK/TD relationships of caffeine in a case of poisoning. Case report A 47-year-old male ingested pure anhydrous caffeine powder (70 g) in a suicide attempt. He developed agitation, tachycardia, and two episodes of ventricular fibrillation treated with defibrillation and tracheal intubation. He was successfully managed using intravenous infusions of esmolol and norepinephrine. Methods We modelled the time-course of plasma caffeine concentration (TK study using online liquid chromatography-tandem mass spectrometry), the time-course of blood lactate concentration and infusion rates of esmolol and norepinephrine (TD studies) and the TK/TD relationships. Results Caffeine TK was of first-order peaking at 258 mg/L with an elimination half-life of 46.2 h and clearance of 2.2 L/h. Caffeine-related effects on blood lactate (peak, 10 mmol/L at 1.25 h postingestion) were described by a Bateman-type equation (formation rate, 0.05 mmol/mg.h; elimination rate, 0.9 mmol/mg.h). Esmolol and norepinephrine infusion rates to reverse caffeine-related cardiovascular effects (peaks at 51-h postingestion) fitted well with a sigmoidal Emax model (EC50, 180.0 and 225.9 mg/L, respectively; Hill coefficient, 10.0). Conclusion Massive caffeine ingestion is characterized by prolonged caffeine elimination. TK/TD relationships are helpful to quantify caffeine-related catecholaminergic effects.

To review the literature regarding neurologic, cognitive, and behavioral disorders resulting from non-fatal opioid overdose. Although there is extensive literature regarding hypoxic-ischemic brain injury resulting from cardiac arrest, studies specifically examining opioid-induced brain injury are limited, derived mainly from patient case reports or animal models. Medical management of this population requires careful consideration of acute and long-term complications, as well as careful treatment planning in coordination with neurology, neuropsychology, psychiatry, and addiction medicine. In addition to interventions to prevent fatal opioid overdose, further studies are needed on the neurologic, cognitive, and behavioral sequelae of opioid overdose in order to develop an effective long-term treatment strategy to manage the healthcare needs of this population.

Annals for Educators - January 2022.

The emergence of new psychoactive substances (NPS) and the number of new chemically diverse substances in the global illicit drug market have significantly increased over the last few years. Designer benzodiazepines are some of the most misused NPS worldwide, contributing to both nonfatal and fatal drug overdose cases. The use of desalkylgidazepam and bromazolam has recently emerged, and their prevalence has been internationally reported. In this study, we quantified desalkylgidazepam and bromazolam using gas chromatography coupled with mass spectrometry (GC-MS) in the postmortem specimens of a subject found deceased due to suspected drug overdose. A 24-year-old white male with a history of drug use was found unresponsive and not breathing in his home with drug paraphernalia nearby. A yellow powdery substance and prescription tablets were also found at the scene. The GC-MS analysis of the postmortem blood and urine samples confirmed the presence of fentanyl, desalkylgidazepam, and bromazolam. The desalkylgidazepam concentration was 1100 ng/mL in the blood, which was higher than previous reports in the literature, and estimated to be 89 ng/mL in the urine. The bromazolam concentration was 352 ng/mL in the blood and estimated to be 398 ng/mL in the urine. Additionally, fentanyl was detected in the blood (11 ng/mL), and fentanyl, norfentanyl, and gabapentin were detected in the urine. The present study aims to provide the toxicological community with information regarding a fit-for-purpose analysis of two NPS benzodiazepines.

A successful experience using labetalol and hemodialysis to treat near-fatal caffeine poisoning: A case report with toxicodynamics

Baclofen overdose following recreational use in adolescents and young adults: A case report and review of the literature

4-Fluoroethylphenidate (4F-EPH) is a psychoactive substance, sold primarily over the Internet as a `research chemical'. Recreational and `functional' use of this drug has been reported by online user fora. Scientifically-based data on the pharmacological, physiological, psychopharmacological, toxicological, and epidemiological characteristics of this molecule is non-existent. The aim of this paper is to remedy this situation. Recent literature (including 'grey') was searched to update what is known about 4F-EPH, especially its toxicity. This was supplemented by netnographic examinations of internet sites. The resultant information is presented, including details of the first reported death involving 4F-EPH use in 2016. There are no international controls imposed on 4F-EPH. However, it has been made a controlled drug in several European countries, including the United Kingdom since 31 May 2017, as well as Canada. It is vital that any other cases, including non-fatal overdoses, are documented so that a firmer scientific evidence-base can be established for this molecule. This will then help inform clinical practice.

Successful Treatment of Potentially Fatal Heavy Metal Poisonings

Combined intoxication with methylone and 5-MeO-MIPT