Intoxication cases in the Emergency Department at a Norwegian University Hospital 2019-20. / Pasienter med forgiftning vurdert ved akuttmottaket på St. Olavs hospital 2019­20.

Background: Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence and prevalence of various toxic substances. The aim of this study was to survey acute intoxications at the emergency department of St Olav's Hospital, Trondheim. Material and method: In this review of patient records, we used data from the emergency department at St Olav's Hospital in Trondheim in the period 1  January 2019-31  December 2020. All cases with 'acute intoxication' as the reason for the emergency department visit were included. Results: In a patient population of 836 unique patients, there were a total of 1423 intoxications, of which 168/836 patients (20.0 %) had more than one intoxication episode in the period. The median age was 31 years (interquartile range 22-47), and 395/836 (47.2 %) of the patients were women. Combined drug intoxication constituted 666/1423 (46.8 %) of the cases, and the most frequent intoxications were from ethanol: 802/1423 (56.4 %); benzodiazepines 314/1423 (24.0 %); and opioids 243/1423 (17.1 %). Altogether, 1146/1423 (80.5 %) incidents resulted in hospital admission. There were no deaths during their hospital stay. Interpretation: Emergency departments must be prepared to manage patients who have taken various poisoning agents. The antidotes must be available, and it must be possible to perform interventions.

Changes in Opioid and Benzodiazepine Poisoning Deaths After Cannabis Legalization in the US: A County-level Analysis, 2002-2020.

BACKGROUND: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

[Epidemiological Characterization of Benzodiazepine and Antidepressant Poisonings in Chile]. / Intoxicaciones por benzodiacepinas y antidepresivos, una realidad preocupante.

INTRODUCTION: Poisonings are a worldwide preventable public health problem that affects the general population. OBJECTIVE: To epidemiologically characterize BZ and AD poisonings registered in Chile between 2002 and 2019. METHODS: An observational retrospective study of poisonings registered in the medical outcome report system of the Chilean Ministry of Health was conducted. The World Health Organization International Classification of Disease codes T42.2, T43.0 and T43.2 were included. RESULTS: 22,807 poisonings associated with BZ or AD were identified, representing 0.08% of all hospitalizations. Poisoning rates distribution were established at regional and national level. There were 9.8% of accidental events, 63.7% of intentional events, and 26.5% of undetermined cases. The highest accidental and intentional poisoning rates were estimated at the ages of 0 to 4 and 15 to 19 years old respectively. Poisoned patients remained hospitalized on average for 3.4 days. 0.3% of cases were related to death of patients. CONCLUSIONS: Poisoning events were characterized according to the studied variables. National poisoning rates decreased over the years with prevalence of those intentional events linked to women. Efforts should be made in creating poisoning prevention campaigns focused on age-based groups in the general population.

Trends in Nonfatal and Fatal Overdoses Involving Benzodiazepines - 38 States and the District of Columbia, 2019-2020.

Nonfatal and fatal drug overdoses increased overall from 2019 to 2020 (1).* Illicit benzodiazepines (e.g., etizolam, flualprazolam, and flubromazolam)† were increasingly detected among postmortem and clinical samples in 2020, often with opioids,§ and might have contributed to overall increases in drug overdoses. Availability of recent multistate trend data on nonfatal benzodiazepine-involved overdoses and involvement of illicit benzodiazepines in overdoses is limited. This data gap was addressed by analyzing annual and quarterly trends in suspected benzodiazepine-involved nonfatal overdoses¶ treated in emergency departments (EDs) (benzodiazepine overdose ED visits) during January 2019-December 2020 (32 states and the District of Columbia [DC]) and benzodiazepine-involved overdose deaths (benzodiazepine deaths), which include both illicit and prescription benzodiazepines, during January 2019-June 2020 (23 states) from CDC's Overdose Data to Action (OD2A) program. From 2019 to 2020, benzodiazepine overdose ED visits per 100,000 ED visits increased (23.7%), both with opioid involvement (34.4%) and without (21.0%). From April-June 2019 to April-June 2020, overall benzodiazepine deaths increased 42.9% (from 1,004 to 1,435), prescription benzodiazepine deaths increased 21.8% (from 921 to 1,122), and illicit benzodiazepine deaths increased 519.6% (from 51 to 316). During January-June 2020, most (92.7%) benzodiazepine deaths also involved opioids, mainly illicitly manufactured fentanyls (IMFs) (66.7%). Improving naloxone availability and enhancing treatment access for persons using benzodiazepines and opioids and calling emergency services for overdoses involving benzodiazepines and opioids, coupled with primary prevention of drug use and misuse, could reduce morbidity and mortality.

Epidemiology of acute poisoning by substances of abuse in the Emergency Department. Descriptive study in District IV of Asturias. / Epidemiología de las intoxicaciones agudas por sustancias de abuso en Urgencias. Estudio descriptivo en el área IV de Asturias.

The incidence of acute poisonings has increased in recent years and constitutes approximately 2% of the services provided by the Emergency Department currently. The objective of this study is to describe the frequency and characteristics of the intoxications treated at the Central University Hospital of Asturias during 2015 from biochemical-analytical, epidemiological and medical-legal perspectives. We conducted a retrospective study and a descriptive analysis of the clinical and sociodemographic variables included in the acute intoxication (AI) protocol at the national level. This hospital treated 2,478 cases of acute poisoning, representing 2.3% of the emergencies treated and corresponding to an incidence of 764 cases/100,000 inhabitants/year with an age ranging from under 1 year to over 80 years. The average age of the patients was 43.6 (SD = 16.6) years. Of these patients, 59.4% were males with an average age of 44 (SD = 16.8) years, and women represented 43.1% with an average age of 42.8 (SD = 16.5) years. These intoxications have a frequency of 47.2% during the weekend, while 37.4% occur between June and September. Acute voluntary intoxication is the most frequent intentionality, corresponding to 83.2% of the cases. We must point out that the medical records register 16.8% of the cases as suicide attempts. Ethanol and benzodiazepines are the most commonly-used toxics. These intoxications are treated in the Emergency Department without requiring hospitalization and have a very low mortality rate.

La incidencia de las intoxicaciones agudas ha aumentado en los últimos años, y actualmente constituye aproximadamente el 2% de las atenciones sanitarias llevadas a cabo por los Servicios de Urgencias. El objetivo de este estudio es describir la frecuencia y características de las intoxicaciones atendidas en el Hospital Universitario Central de Asturias durante el año 2015 desde la perspectiva bioquímica-analítica, epidemiológica y médico-legal. Se realizó un estudio retrospectivo y un análisis descriptivo de las variables clínicas y sociodemográficas incluidas en el protocolo de intoxicación aguda a nivel nacional. Este hospital atendió 2478 casos de intoxicaciones agudas representando el 2,3% de las urgencias atendidas y que corresponde a una incidencia de 764 casos/100000 habitantes/año con un rango de edad de menores de 1 año a mayores de 80 años. La edad media de los pacientes atendidos fue de 43,6 (DE = 16,6) años. El 59,4% de los pacientes eran varones con una edad media de 44 (DE = 16,8) años, las mujeres representaban el 43,1% y su edad media era de 42,8 (DE = 16,5) años. El 47,2% de estas intoxicaciones ocurren durante el fin de semana y el 37,4% se dan entre junio y septiembre. La intencionalidad más frecuente es la intoxicación aguda voluntaria correspondiente al 83,2% de los casos. Cabe destacar que el 16,8% de los casos están referenciados en su historia clínica como intentos de suicidio. Los tóxicos más empleados son el etanol y las benzodiacepinas. Estas intoxicaciones son resueltas en el Servicio de Urgencias sin requerir ingreso hospitalario y poseen una tasa de mortalidad muy baja.

Hospital-treated deliberate self-poisoning in the older adult: Identifying specific clinical assessment needs.

BACKGROUND: Hospital-treated deliberate self-poisoning is common, with a median patient age of around 33 years. Clinicians are less familiar with assessing older adults with self-poisoning and little is known about their specific clinical requirements. OBJECTIVE: To identify clinically important factors in the older-age population by comparing older adults (65+ years) with middle-aged adults (45-64 years) during an index episode of hospital-treated deliberate self-poisoning. METHODS: A prospective, longitudinal, cohort study of people presenting to a regional referral centre for deliberate self-poisoning (Calvary Mater Newcastle, Australia) over a 10-year period (2003-2013). We compared older-aged adults with middle-aged adults on demographic, toxicological and psychiatric variables and modelled independent predictors of referral for psychiatric hospitalisation on discharge with logistic regression. RESULTS: There were (n = 157) older-aged and (n = 925) middle-aged adults. The older-aged group was similar to the middle-aged group in several ways: proportion living alone, reporting suicidal ideation/planning, prescribed antidepressant and antipsychotic drugs, and with a psychiatric diagnosis. However, the older-aged group were also different in several ways: greater proportion with cognitive impairment, higher medical morbidity, longer length of stay, and greater prescription and ingestion of benzodiazepines in the deliberate self-poisoning event. Older age was not a predictor of referral for psychiatric hospitalisation in the multivariate model. CONCLUSION: Older-aged patients treated for deliberate self-poisoning have a range of clinical needs including ones that are both similar to and different from middle-aged patients. Individual clinical assessment to identify these needs should be followed by targeted interventions, including reduced exposure to benzodiazepines.

Little Helpers No More: A Framework for Collaborative Deprescribing of Benzodiazepines in Older Adults.

Benzodiazepines are a class of medications that tend to fly "under the radar" within the general population but nonetheless post a significant risk to older adults when not used appropriately. The current article aims to shine a spotlight on this medication class along with a framework for a team-based approach to successfully de-escalate use when clinically appropriate. [Journal of Psychosocial Nursing and Mental Health Services, 58(1), 23-28.].

Benzodiazepine ingestion as a way to die by suicide and related safety: the case of an elderly patient.

Benzodiazepines (BDZs) are widespread psychotropic compounds, often prescribed as first-line symptomatic option by general practitioners in patients with different psychiatric disorders. Sometimes, however, they contribute to delay the administration of the first appropriate psychopharmacological treatment, thus leading to a longer duration of untreated illness in patients with depressive and anxiety disorders. The well-established pros of BDZs use in clinical practice include efficacy, rapidity of action, versatility, and safety. Among the cons, BDZs can provoke cognitive side-effects, asthenia, and misuse/abuse. Although their overall safety has been traditionally viewed as one of their greatest strengths, BDZs massive ingestion for suicidal purposes may pose, in some cases, serious life-threatening conditions, as described in the present case report. Hence, particular attention needs to be paid in prescribing these compounds to special populations, such as elderly patients. Among these, their prescription should be limited to the short-term and particularly monitored in case of risk factors, as they may be unsafe in case of overdose.

Nurse suicide in the United States: Analysis of the Center for Disease Control 2014 National Violent Death Reporting System dataset.

OBJECTIVE: This study explored nurse suicide in the United States. METHODS: Characteristics were compared between occupations using 2014 National Violent Death Reporting System data. RESULTS: Female nurse suicides were significantly higher (11.97/100,000) than in the female population (7.58/100,000) (p < 0.001); similarly male nurses (39.8/100,000) compared to the male population (28.2/100,000) (p < 0.001). Benzodiazepines and opioids were the most commonly used substances used in clinician suicide. CONCLUSION: These results suggest a public health imperative for future research and development of effective preventative strategies for nurses; a largely understudied population.

First aid interventions by laypeople for acute oral poisoning.

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.

Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

BACKGROUND: Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. METHODS: We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). CONCLUSIONS: The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis.

Retrospective case series analysis of characteristics and trends in unintentional pharmaceutical drug poisoning by methadone, opioid analgesics, antidepressants and benzodiazepines in Clark County, NV 2009-13.

Background: Poisoning has become the leading cause of injury death in the USA-with opioid analgesic involved in more fatal poisonings than any other drug, including cocaine and heroin. The epidemic of prescription drug poisonings is a public health concern. This study aimed to define potential high-risk groups for unintentional prescription drug poisoning by methadone, opioid analgesics, antidepressants or benzodiazepines. Methods: A hospital-based retrospective case series analysis of admissions related to prescription drug poisonings associated with methadone, opioid analgesics, antidepressants or benzodiazepines for hospitals in Clark County, Nevada between 2009 and 2013 was employed. Results: There were 7414 admissions with a primary diagnosis of an unintentional poisoning due to methadone, opioid analgesics, antidepressants or benzodiazepines. Women had the highest rate of admissions particularly in the 45-54 age group. Higher rates of admissions were also found among non-Hispanic whites, single and uninsured populations. There were concerning increases in admissions among 65+ and Native American/Alaskan Native subgroups in 2013. Benzodiazepines and opioid analgesics were the most prevalent drug categories for prescription drug poisoning admissions. Conclusion: Public health professionals can utilize hospital data to identify populations at risk and in need of targeted interventions.

Body pushing, prescription drugs and hospital admission.

A 39-year-old man died of multi-organ failure complicating mixed drug toxicity that included methadone, oxazepam, oxycodone and nitrazepam. His past medical history involved alcohol and poly-substance abuse with chronic self-harm and suicidal ideation. There had been multiple hospital admissions for drug overdoses. At autopsy the most unusual finding was of two packages of 10 tablets each, wrapped in thin plastic film within the rectum. The insertion of drugs into body orifices and cavities has been termed body pushing to distinguish it from body packing where illicit drugs are wrapped and swallowed for transport and smuggling, and body stuffing where small amounts of loosely wrapped or unwrapped drugs are swallowed to conceal evidence from police. This case demonstrates that body pushing may not always involve illicit drugs or attempted concealment from police or customs officials. It appears that the drugs had been hidden to ensure an additional supply during the time of residence in hospital. The extent to which body pushing is currently being used by patients to smuggle drugs into secure medical facilities is yet to be determined.

An autopsy case of death by combined use of benzodiazepines and diphenidine.

We present an autopsy case involving benzodiazepines and diphenidine. Quantitative toxicological analysis showed concentrations of 7-aminoflunitrazepam (a flunitrazepam metabolite), 7-aminonimetazepam (a nimetazepam metabolite), chlorpheniramine and diphenidine in femoral blood of 0.086 µg/ml, 0.027 µg/ml, 0.066 µg/ml, and 0.073 µg/ml, respectively. Death was attributed to combined toxicity due to the influence of multiple drug interactions.

Flumazenil, naloxone and the 'coma cocktail'.

Flumazenil and naloxone are considered to be pharmacologically ideal antidotes. By competitive binding at the molecular target receptors, they are highly specific antagonists of two important drug classes, the benzodiazepines and opioids, respectively. Both antidotes enjoy rapid onset and short duration after parenteral administration, are easily titrated and are essentially devoid of agonist effects. Yet only naloxone is widely used as a component of the 'coma cocktail', a sequence of empirical treatments to correct altered mental status, while experts discourage the use of flumazenil for such patients. This review contrasts the history, indications, published evidence and novel applications for each antidote in order to explain this disparity in the clinical use of these 'ideal' antidotes.

Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. RESULTS: Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. CONCLUSIONS: Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection.

Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature.

BACKGROUND: Among the rare neurological complications of substances of abuse is the selective cerebral white matter injury (leukoencephalopathy). Of which, the syndrome of delayed post hypoxic encephalopathy (DPHL) that follows an acute drug overdose, in addition to "chasing the dragon" toxicity which results from chronic heroin vapor inhalation remain the most commonly described syndromes of toxic leukoencephalopathy. These syndromes are reported in association with opioid use. There are very few cases in the literature that described leukoencephalopathy following benzodiazepines, especially with an acute and progressive course. In this paper, we present a patient who developed an acute severe fatal leukoencephalopathy following hypoxic coma and systemic shock induced by benzodiazepine overdose. CASE PRESENTATION: A 19-year-old male was found comatose at home and brought to hospital in a deep coma, shock, hypoxia, and acidosis. Brain magnetic resonant imaging (MRI) revealed a strikingly selective white matter injury early in the course of the disease. The patient remained in a comatose state with no signs of neurologic recovery until he died few weeks later following an increase in the brain edema and herniation. CONCLUSION: Toxic leukoencephalopathy can occur acutely following an overdose of benzodiazepine and respiratory failure. This is unlike the usual cases of toxic leukoencephalopathy where there is a period of lucidity between the overdose and the development of white matter disease. Unfortunately, this syndrome remains of an unclear pathophysiology and with no successful treatment.

Lack of adverse effects from flumazenil administration: an ED observational study.

BACKGROUND: Flumazenil is an effective benzodiazepine (BZD) antagonist. Empiric use of flumazenil in the emergency department (ED) is not widely recommended due to concerns of seizures, which are commonly associated with coingestants and BZD withdrawal. OBJECTIVE: The objective of the study is to assess adverse events and clinical outcomes of flumazenil administration in known and suspected BZD overdose in an ED at a tertiary academic medical center. METHODS: This is a retrospective observational study of adult patients administered flumazenil for known or suspected BZD overdose in the ED over 7 years. Outcomes included mental status improvement, the incidence of seizures, and intubation of the trachea after flumazenil administration. RESULTS: Twenty-three patients were included in the analysis, of which 15 (65%) of patients experienced some type of clinically significant mental status improvement. No seizures were identified despite 7 (35%) reported proconvulsant coingestants. One patient required intubation of the trachea but was subsequently extubated in the ED. CONCLUSIONS: A majority of patients had improved mental status after the administration of flumazenil. No patient experienced seizures. Additional studies that clarify the role of flumazenil for ED patients with suspected BZD toxicity are warranted.

Abnormal olanzapine toxicokinetic profiles--population pharmacokinetic analysis.

CONTEXT: Olanzapine is widely used in the treatment of schizophrenia and it is becoming more frequently responsible for overdoses. Standard pharmacokinetic models do not fit to the toxic concentration data. OBJECTIVE: The aim of present study is to investigate the reasons for an abnormal olanzapine plasma concentration time curve in the range of toxic concentrations. Two hypotheses were verified: entering the enterohepatic cycle, and drug deposition and its desorption from activated charcoal used for gastrointestinal decontamination. MATERIALS AND METHODS: One-hundred thirty-five plasma concentration data from 21 patients hospitalized for acute olanzapine poisoning were analyzed with the use of the population pharmacokinetic approach. A non-linear mixed-effects modeling approach with Monolix 4.3.1 was employed. RESULTS: A model assuming gallbladder emptying at irregular intervals was developed. Also, a model that describes desorption of olanzapine from the charcoal surface, in which the dose is divided into two absorbed fractions, was constructed. The analysis has found gastrointestinal decontamination and previous olanzapine treatment, as the significant covariates for toxicokinetic parameters of olanzapine. CONCLUSION: Our study provides interesting models for investigation of toxic concentration of olanzapine, which may also be used as the basis for further model development for other drugs as well. The investigated population was not large enough to reliably confirm any of the proposed models. It would be well worth continuing this study with more substantial data. Also, any additional information about olanzapine metabolite concentration could be vital.