The rise of suicides using a deadly dose of barbiturates in Amsterdam and Rotterdam, the Netherlands, between 2006 and 2017.

INTRODUCTION: The three 'advised' suicide methods are helium asphyxiation, voluntarily stop eating and drinking and the use of a deadly dose of medication such as barbiturates. The aim of this study was to analyse the number of suicides resulting from barbiturate overdose and examine the influence of publications and internet on this suicide method in the two larger cities of the Netherlands. METHODS: Data of suicides by medication and drugs overdose were extracted from the electronic registration systems of the forensic physicians of the district of Amsterdam and Rotterdam over the period 1 January 2006-31 December 2017. We analysed whether or not the number of suicides using barbiturate overdose has significantly risen since 2013. This was the year 'right-to-die-organisations' informed individuals about this method and a book was published describing this as a humane death. In addition, a regression analysis was used to examine which factors predict a suicide resulting from barbiturate overdose. RESULTS: A total of 553 overdose suicides were identified and 91 suicides resulting from barbiturate overdose were included for further evaluation. During 2013-2017 there were significantly (p < 0.00) more suicides resulting from barbiturate overdose compared to 2007-2012. Individuals using barbiturate overdose to die by suicide were significantly (p < 0.00) older than those using other medication and drugs (65 years compared to 55 years respectively). 48% of these cases were male. In barbiturate suicides, information sources (books or information on the internet, p < 0.01) and the presence of family during suicide (p < 0.00) occurred significantly more often than in suicides resulting from other medication and/or drugs overdose. The odds for barbiturate suicides were 4.8 higher (CI 2.6-9.2) after 2013 compared to before 2013 after correction for age, sex, city and postmortem toxicology results. DISCUSSION: Our data showed a rise in suicides resulting from barbiturate overdose whereas the total number of inhabitants and suicides resulting from medication overdose has remained more or less constant. Easy access of information or medication through the internet and 'right-to-die-organisations' may have directly impacted the rise in suicides resulting from an overdose of barbiturates. To our knowledge this is the first study analysing the rise of barbiturate suicides and the influence of media in published literature.

[Peculiarities of barbituric acid derivatives acute poisoning clinical picture in patients of elderly and senile age and their therapy.]

In this article materials obtained during treatment of 61 patients with acute poisoning with phenobarbital, which is part of Corvalol and Valocordin, are presented. It has already been established that phenobarbital acute poisoning in elderly and senile patients is accompanied by more frequent development of central nervous system, respiratory system (pneumonia) and cardiovascular system complications, which cause more severe clinical course and risk of an adverse outcome of acute poisoning. This research has shown that for hypoxia correction during phenobarbital acute poisoning in elderly and senile patients it is advisable to include Reamberin in the treatment regimen, which has no adverse effects on central haemodynamic parameters and effectively reduces severity of metabolic disorders.

Extracorporeal elimination of butalbital in acute aspirin-butalbital-caffeine-codeine (Fiorinal with Codeine) poisoning.

BACKGROUND: Butalbital is a small molecule (approximately 220 Da), with 26% protein binding, a 0.8 L/kg volume of distribution, and is eliminated nearly 80% unchanged in the urine. Although hemodialysis has been used to treat overdoses of other barbiturates, the extracorporeal clearance of butalbital is unknown. The objective of this case is to describe the use of extracorporeal therapy to augment elimination of butalbital after an overdose of aspirin 325 mg-butalbital 50 mg-caffeine 40 mg with codeine 30 mg (Fiorinal with Codeine). METHODS: This is a case report of a single patient. RESULTS: A 67-year-old female was admitted to the medical intensive care unit approximately 3 h after ingestion of 40 tablets of Fiorinal with Codeine. Her presentation was notable for a decline in mental status, preserved renal function and a relatively low peak salicylate concentration at 46.4 mg/dL (3.4 mmol/L). Approximately 8 h after ingestion of 2000 mg of butalbital, our patient's serum concentration was 26.9 mg/L (normal <10 mg/L). At the end of a four-hour hemodialysis session, the total body elimination of butalbital was approximately 60% which corresponded to an intradialytic clearance of 233-300 mL/min. CONCLUSIONS: The extracorporeal clearance of butalbital observed in this case demonstrates the utility of dialysis to augment drug elimination in a Fiorinal with Codeine overdose.

Combination Clearance Therapy and Barbiturate Coma for Severe Carbamazepine Overdose.

A 15-year-old female subject presented comatose, in respiratory failure and shock, after the intentional ingestion of ∼280 extended-release 200-mg carbamazepine tablets with a peak serum concentration of 138 µg/mL (583.74 µmol/L). The patient developed clinical seizures and an EEG pattern of stimulus-induced rhythmic, periodic, or ictal discharges, suggestive of significant cortical dysfunction. Due to the extremely high drug serum concentration and clinical instability, a combination of therapies was used, including lipid emulsion therapy, plasmapheresis, hemodialysis, continuous venovenous hemodiafiltration, and endoscopic intestinal decontamination. The patient's elevated serum lactate level with a high mixed venous saturation suggested possible mitochondrial dysfunction, prompting treatment with barbiturate coma to reduce cerebral metabolic demand. The serum carbamazepine concentration declined steadily, with resolution of lactic acidosis, no long-term end-organ damage, and return to baseline neurologic function. The patient was eventually discharged in her usual state of health. In the laboratory, we demonstrated in vitro that the active metabolite of carbamazepine hyperpolarized the mitochondrial membrane potential, supporting the hypothesis that the drug caused mitochondrial dysfunction. We thus successfully treated a life-threatening carbamazepine overdose with a combination of modalities. Future studies are required to validate this aggressive approach. The occurrence of mitochondrial dysfunction must be confirmed in patients with carbamazepine toxicity and the need to treat it validated.

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.

[Attempted suicide with barbiturates purchased online]. / Tentamen suicidii met barbituraten van internet.

BACKGROUND: Barbiturate intoxication is potentially lethal. With the availability of the newer anticonvulsants the use of barbiturates in treating epilepsy has decreased significantly, with a concurrent decrease in the incidence of overdose with these medications. There have, however, been recent alarm signals from governmental sources concerning the increase in the Internet purchase of illegal medications, including barbiturates, for use in attempted suicide. CASE DESCRIPTION: Here we describe two patient cases involving barbiturate intoxication with amobarbital and thiopental, respectively. They had both obtained the barbiturates via the Internet. Both patients were comatose and showed signs of respiratory depression; one of them was also haemodynamically unstable. Both patients recovered fully following intensive supportive therapy. CONCLUSION: In patients with coma, respiratory depression, absence of brainstem reflexes and shock with no evident cause one should be aware of the possibility of barbiturate intoxication, even when there is no indication that these have been prescribed or that the patient has direct or indirect access to barbiturates. Prompt, optimal supportive therapy will give a good chance of full somatic recovery.

Pioneering early Intensive Care Medicine by the 'Scandinavian Method' of treatment for severe acute barbiturate poisoning.

Between the 1920s and the mid-1950s, barbiturates were the sedative-hypnotic agents most used in clinical practice. Their ready availability and narrow therapeutic margin accounted for disturbingly high rates of acute poisoning, whether suicidal or accidental. Until the late 1940s, medical treatment was relatively ineffective, with mortality subsequently high - not only from the effects of coma, respiratory depression and cardiovascular shock with renal impairment, but also from complications of the heavy use in the 1930s and 1940s of analeptic stimulating agents. Incidence of barbiturate intoxication increased substantially following World War II and this paper details development of what became known as the 'Scandinavian Method' of treatment, which contributed substantially to the earliest establishment of intensive care units and to the practice and methods of intensive care medicine. Three names stand out for the pioneering of this treatment. Successively, psychiatrist, Aage Kirkegaard, for introducing effective anti-shock fluid therapy; anaesthetist, Eric Nilsson, for introducing anaesthesiologic principles, including manual intermittent positive pressure ventilation into management; and, psychiatrist, Carl Clemmesen, for introducing centralisation of seriously poisoned patients in a dedicated unit. Clemmesen's Intoxication Unit opened at the Bispebjerg Hospital, Copenhagen, on 1 October 1949. ICU pioneer Bjørn Ibsen suggested it was the initial ICU, while noting that it supplied Intensive Therapy for one type of disorder only (as had HCA Lassen's Blegdam Hospital unit for Denmark's 1952 to 1953 polio epidemic). Treatment for barbiturate poisoning during the 1950s in some other Scandinavian hospitals will also be considered briefly.

[On the history of barbiturates]. / Pionerer bag barbituraterne.

Throughout the history of humanity, numerous therapeutic agents have been employed for their sedative and hypnotic properties such as opium, henbane (Hyoscyamus niger) and deadly nightshade (Atropa belladonna), but also alcohol and wine. In the 19th century potassium bromide was introduced as a sedative - and antiepileptic drug and chloral hydrate as sedative-hypnotics. A new era was reached by the introduction of barbiturates. The story started with the chemist Adolf von Baeyer. His breakthrough in the synthesis of new agents as barbituric acid and indigo and his education of young chemists was of great importance for the science of organic chemistry and the development of the dye and medicine industry in the late 19th century. The next important step was the development of barbiturates. The pioneers were Josef von Mering and Emil Fischer. Using the Grimaux-method they synthesized various barbiturates. It was von Mering who got the idea of introducing ethyl groups in the inactive barbituric acid to obtain sedatives, but the synthesis was succeeded by the chemist Emil Fischer. Experiments with dogs clearly showed sedative and hypnotic effect of the barbiturates and the oral administration of barbital (Veronal) confirmed the effect in humans. Barbital was commercialized in 1903 and in 1911 phenobarbital (Luminal) was introduced in the clinic, and this drug showed hypnotic and antiepileptic effects. Thereafter a lot of new barbiturates appeared. Dangerous properties of the drugs were recognized as abuse, addiction, and poisoning. An optimum treatment of acute barbiturate intoxication was obtained by the "Scandinavian method", which was developed in the Poison Centre of the Bispebjerg Hospital in Copenhagen. The centre was established by Carl Clemmesen in 1949 and the intensive care treatment reduced the mortality of the admitted persons from 20% to less than 2%. To-day only a few barbiturates are used in connection with anaesthesia and for the treatment of epilepsy, and chemists are focusing on drugs with more selective effects.

Extracorporeal treatment for barbiturate poisoning: recommendations from the EXTRIP Workgroup.

The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR is indicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present.

Enhanced elimination in acute barbiturate poisoning - a systematic review.

CONTEXT: Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings often require prolonged admission to an intensive care unit, so enhanced elimination might be useful to hasten recovery. Information regarding the efficacy of these techniques for individual barbiturates is not available in standard textbooks. OBJECTIVE: To determine the evidence supporting the effect of enhanced elimination and its role in the management of acute barbiturate poisoning. METHODS: A systematic review was conducted using broad search criteria in three databases. All potentially relevant articles were obtained, and reference lists were manually reviewed. Ninety-four publications fulfilling inclusion criteria were located. Studies were classified as controlled or uncontrolled, and clinical and pharmacokinetic end points were manually extracted. If not directly stated, standard pharmacokinetic methods were used to calculate the clearance and efficiency of enhanced elimination techniques for each barbiturate and tabulated for direct comparison. PROSPECTIVE CONTROLLED CLINICAL TRIALS: Two of the 94 publications were prospective controlled studies (only one stated that allocation was via blinded randomisation), and both assessed the effect of multiple-dose activated charcoal for acute phenobarbital poisoning. These studies demonstrated enhanced elimination with a decrease in elimination of half-life from approximately 80 to 40?h, but only one study reported clinical benefits. UNCONTROLLED SERIES AND SINGLE CASE REPORTS: Sufficient data to determine the clearance due to enhanced elimination were available in only 52 of these papers. Barbiturate clearances by enhanced elimination varied markedly among studies. While extracorporeal modalities appeared to increase the direct clearance of many barbiturates, there was insufficient information to confirm a clinical benefit. CONCLUSIONS: There is limited evidence to support the use of enhanced elimination in the treatment of poisoning with most barbiturates. There is no role for urine alkalinisation, while multiple-dose activated charcoal may be useful for most phenobarbital and possibly primidone poisonings. Extracorporeal techniques appear to enhance elimination, but the clinical benefits, relative to the potential complications and cost, are poorly defined. Extracorporeal techniques such as haemodialysis and haemoperfusion can be considered for patients with life-threatening barbiturate toxicity such as refractory hypotension.

Euthanasia in patients dying at home in Belgium: interview study on adherence to legal safeguards.

BACKGROUND: Euthanasia became legal in Belgium in 2002. Physicians must adhere to legal due care requirements when performing euthanasia; for example, consulting a second physician and reporting each euthanasia case to the Federal Review Committee. AIM: To study the adherence and non-adherence of GPs to legal due care requirements for euthanasia among patients dying at home in Belgium and to explore possible reasons for non-adherence. DESIGN OF STUDY: Large scale, retrospective study. SETTING: General practice in Belgium. METHOD: A retrospective mortality study was performed in 2005-2006 using the nationwide Belgian Sentinel Network of General Practitioners. Each week GPs reported medical end-of-life decisions taken in all non-sudden deaths of patients in their practice. GP interviews were conducted for each euthanasia case occurring at home. RESULTS: Interviews were conducted for nine of the 11 identified euthanasia cases. Requirements concerning the patient's medical condition were met in all cases. Procedural requirements such as consultation of a second physician were sometimes ignored. Euthanasia cases were least often reported (n = 4) when the physician did not regard the decision as euthanasia, when only opioids were used to perform euthanasia, or when no second physician was consulted. Factors that may contribute to explaining non-adherence to the euthanasia law included: being unaware of which practices are considered to be euthanasia; insufficient knowledge of the euthanasia law; and the fact that certain procedures are deemed burdensome. CONCLUSION: Substantive legal due care requirements for euthanasia concerning the patient's request for euthanasia and medical situation were almost always met by GPs in euthanasia cases. Procedural consultation and reporting requirements were not always met.

Out-of-hospital cardiac arrest caused by acute intoxication.

We experienced 20 cases of out-of-hospital cardiac arrest (OHCA) caused by acute intoxication between April 1999 and March 2008. The causative agents were organophosphates in 8 cases, carbon monoxide in 5 cases, and barbiturates in 3 cases. Other agents were paraquat, tricyclic anti-depressants, lime sulfur, and amphetamine. Cardiac arrest was witnessed by bystanders while waiting for the ambulance arrival in 3 cases, and by emergency medical personnel during transfer to our hospital in 4 cases. In these 7 witnessed cases, prehospital resuscitation was provided in 6 cases. No case demonstrated ventricular arrhythmia at the prehospital scene. The restoration of spontaneous circulation was achieved in 8 cases, and 4 cases were discharged alive with overall performance category 1. All the survivors were victims of organophosphate or barbiturate intoxication. It is assumed that these agents caused myocardial depression or respiratory insufficiency following cardiac arrest. From the review of the OHCA caused by organophosphate or barbiturate intoxication, cardiopulmonary resuscitation alone seemed to be effective for restoration of spontaneous circulation and should be emphasized in the prehospital care setting as well as in cardiogenic OHCA.