Increased risk of fatal intoxication and polypharmacy among psychiatric patients at death

Patients suffering from psychiatric disorders have an excess mortality and a shorter life span expectancy compared to the general population. Furthermore, they are treated with multiple drugs and are known to have an increased risk of drug abuse. In this study, we aimed at investigating the pharmaceutical drug and drug of abuse profiles of the deceased included in the Danish prospective autopsy‐based forensic study on psychiatric patients, SURVIVE. Using the postmortem systematic toxicological analysis results, we identified 129 different consumed compounds in our population (n = 443). Polypharmacy (≥5 compounds) was detected in 39.5% of the deceased. Deceased with a psychiatric diagnosis or who died from a fatal intoxication had significantly more compounds at the time of their death compared to having either no psychiatric diagnosis or another cause of death, respectively. Evidence of drug abuse was present, as 29.8% of our total population had consumed either methadone or illicit drugs of abuse, excluding tetrahydrocannabinol. Of those deceased with a psychiatric diagnosis, 33.6% had either consumed methadone or illicit drugs of abuse, a greater number than those without a psychiatric diagnosis. Fatal intoxication was the most frequent cause of death (40.6%) with methadone as the major intoxicant. Here, we found that those without a psychiatric diagnosis had fewer fatal pharmaceutical drug intoxications compared to the psychiatric diagnosis groups. Our findings add further context to understanding the excess mortality of psychiatric patents, since there is an increased occurrence of fatal intoxication, polypharmacy, and drug abuse in this population.     

Fatal unintentional intoxications with tramadol during 1995-2005

Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 microg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 microg/g (range 1.1-12.0 microg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients.     

Toxicological characteristic of neuroleptics--substituted benzamides

At present in the medical practice the group of neuroleptics, substituted benzamides is widely used. According to literature data they cause acute intoxications under particular conditions. The group of substituted benzamides includes drugs such as amisulpride, tiapride, sulpiride and sultoprid. Substituted benzamides intake causes toxic actions: psychotropic and neurotoxic. The neuroleptic intoxication is an effect of overdosage, abuse and hypersensitization. Severe intoxications with drugs of this group may cause lethal outcome.     

Pesticide intoxications in the Centre of Portugal: three years analysis

Pesticides are used in most countries around the world to protect agricultural and horticultural crops against damage. Poisoning by these toxicant agents occurs as a result of misuse or accidental exposure, and also by oral ingestion (voluntary or not). In Portugal, pesticide intoxications are still a cause of death, found in a considerable number of cases. The authors retrospectively examined the cases of pesticide poisoning in the Centre of Portugal, from autopsies performed in the Forensic Pathology Service of Coimbra's Delegation of the National Institute of Legal Medicine (NILM) and from other autopsies carried out in the Centre of Portugal, as well as some samples taken in hospitals in cases of suspected intoxication. In this study, the positive cases have been especially studied, in order to identify the pesticide used, as well as the etiology. The frequency of intoxications and its distribution by sex and age were also analyzed. Between January 2000 and December 2002, the Forensic Toxicology Laboratory received 639 pesticide analysis requests. In 2000, in a total of 149 analysis requests, 30 cases were positive, 63.3% from male individuals and 36.7% from female. In 2001, the analysis requests increased to 240 as well as the positive cases (43), 74.4% from male individuals and 25.6% from female and in 2002, the total cases analyzed also increased to 250, with 38 positive (73.6% from male individuals and 26.4% from female). Among the pesticides, organophosphorus insecticides still constitute the most important class detected in forensic intoxications, representing 63% of the total positive cases, followed by herbicides, with 33% of the positive results. Quinalphos is the most important organophosphorus insecticide, present in 32 of the 111 positive cases, followed by the herbicide paraquat, detected in 31 cases. The study emphasizes the increasing number of pesticide analyses, particularly relevant for the organophosphorus compounds and herbicides. Intoxication suspicion, accidental or voluntary, seems to be the most common cause of the incidents, for which analyses are requested, but it is also evident that the putative cause is unknown in a large number of cases. Therefore, more stringent legislation and enforcement regarding the sale and distribution of these toxic substances are needed.     

Fatal intoxications in a Swedish forensic autopsy material during 1992-2002

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Link?ping, Sweden, during 1992-2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P <0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).     

Fatal Intoxications in a Forensic Autopsy Material from Epirus,Greece, During the Period 1998‐2010

In this retrospective study, we report the epidemiological characteristics of all poisoning deaths in Epirus, Greece, from 1998 to 2010; we present the toxicological findings and the statistical evaluation of the results. This is the first detailed scientific report on all the officially certified poisoning deaths concerning part of the Greek population. A total of 126 poisoning fatalities were recorded, 67 of them being mono‐intoxications (53.2%). The cause of poisoning was as follows: drugs of abuse (60%); carbon monoxide (19.8%); pesticides (9.5%); corrosives (4.8%); pharmaceuticals (4.8%); and spider bite (0.8%). The most frequently detected poisonous substances were as follows: heroin (65 cases), ethanol (55), benzodiazepines (42), carbon monoxide (25), cocaine (17), cannabinoids (17) and pesticides (12). Increasing tendency in poisoning death rates was recorded, due to an increase in accidental poisoning deaths attributed mainly to drugs of abuse (total, accidental, and drugs‐of‐abuse poisoning death rates per 100,000 inhabitants per year were 1.87, 1.19, and 0.79, respectively, in the period 1998–2002 and 3.97, 3.41, and 2.55, respectively, in the period 2007–2010).     

Increased lung weight in fatal intoxications is not unique to opioid drugs

Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.     

Flunitrazepam: an evaluation of use, abuse and toxicity.

The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Link?ping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.     

Cocaine poisoning

Lethal cocaine intoxications in the Federal republic of Germany are still rather unusual. The present article describes chemical findings in a suicide case after oral/nasal intake. Our experience as well as the results of literature leads to the conclusion that if a cocaine intoxication is suspected, examinations are required which should include parts of the brain, the kidneys and the spleen. The application of RIA or rather the EMIT-Procedure only are not sufficient to clear up an intoxication.     

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.     

Injuries in fatal cases of falls downstairs

Downstairs falls frequently occur within domestic environments and are mainly associated with elderly and intoxicated individuals, often feature multiple injuries on various parts of the body. In most cases it is not possible to determine the cause of the fall and/or death solely by means of external examination. In this retrospective study, which covers a period of 11 years, all cases of death which included a fall downstairs in their case history, were collected from the Forensic Institutes of the Universities of Bonn and Greifswald, Germany. Falls downstairs made up to 2% (166 cases) of all postmortem examinations carried out within this period. Interestingly, almost double of the amount of such falls applied to males as to females. The primary cause of death was cranio-cerebral trauma and the vast majority of skull injuries associated with falls downstairs were found above 'the hat brim line'. Injuries were also often found on several other parts of the body at once. Nineteen of the 116 examined individuals exhibited agonal injuries. In these cases, postmortem examination revealed pre-existing disease or intoxication to be the cause of death and thus, cause of the fall. The injury pattern only allows a tendency towards vital or agonal incident as a conclusion.     

Trends and pattern of drug abuse deaths in Maryland teenagers

The Office of the Chief Medical Examiner of Maryland recorded a total of 149 drug abuse deaths of teenagers aged 13-19 years between 1991 and 2006. Of these deaths, 96 (64.4%) were caused by the use of narcotic drugs only, 29 (19.5%) by both narcotics and cocaine, four (2.7%) by both narcotics and methylenedioxymethamphetamine, six (4.0%) by cocaine only, and 14 (9.4%) by volatile substances (e.g., butane, Freon, nitrous oxide, and propane). The annual death rate from drug abuse for teenagers increased from 1.4 deaths per 100,000 population in 1991 to 2.7 deaths per 100,000 population in 2006 (chi-square test for time trend, p<0.01). The increase in teenager drug abuse deaths occurred in 1999 and since has remained at a higher rate. Further analysis revealed that the increase in drug abuse deaths was attributable to a large degree to narcotic drugs, particularly heroin/morphine and methadone, and was confined to teenagers residing in the suburban and rural areas.     

The problem of determining the manner of death as suicide or accident in borderline cases

The purpose of this study was to check the reliability of the classification of death in cases regarded primarily as accidents or undetermined. The material used for the analysis consisted of the documents of autopsies performed at our department in 1981. There were altogether 283 cases of suicides, accidents or undetermined deaths, accounting for 8.4% of total mortality, and of these 180 cases were of the two last categories. In 125 cases primarily regarded as non-suicides (accidents or undetermined) there were some features of suicide leading to reclassification as probable suicide in 24 cases. Fifteen of these were primarily poisoning "accidents", mainly alcohol intoxications. The result indicates that the suicide rate would be 3.7% instead of 3.0% of the total mortality. It may thus be concluded that the official figure for suicides could be as much as 18.9% smaller than the "actual" figure.     

Post mortem determination of bromureides (author's transl)]

Concentrations of carbromal, carbromide and bromisoval are determined in blood, urine, brain, kidney and muscle taken at autopsy from 41 fatal cases after overdosage of bromureides. In addition values of total bromine in blood are presented. Contents of total bromine can only lead to the deduction that a chronical abuse of bromureides is existent or not. Concentrations of bromureides and carbromide show a wide range according to the different time between taking the drug and death particularly in cases of pure carbromal intoxications which sometimes cause death after several days. In such cases quantitative determination of carbromide, a pharmacologically active metabolite of carbromal, is the only way to prove an acute carbromal intoxication. Especially in cases of additional foreign substances death may occur in early the phase of poisoning. Bromureides decompose post mortem by putrefaction a high degree so that the condition of the cadaver is important. Brain tissue is the most usable material for examination but other organs, particularly muscle and kidney, can be analysed with success. For differential diagnosis fatal cases are presented which were not caused by drug intake.     

Reasons, circumstances and results of repeat forensic medicine autopsy

There are only scant literature data on reasons and circumstances of medico-legal second autopsies. The present study includes 12 second autopsies from the period 1992-1997; the first post-mortem examination took place either in the home country (institutes of pathology) or abroad. 7 of the 12 cases of death investigated happened in Germany (exclusively in hospitals) and 5 of them abroad (Netherlands, Romania, Portugal, Libya). Repeat autopsies were ordered by criminal courts (n = 9), private persons (n = 2) and social insurances (n = 1). The main indication was possible medical malpractice (n = 6); acts of violence (n = 3), insurance questions (n = 2) and accidents (n = 1) followed. The time lapse between death and second autopsy was 2-35 days. It was striking, that German institutes of pathology had partially performed autopsies despite the certification of a non-natural death. Clinical autopsies were stopped twice, when evidence of a possible non-natural death occurred. It could be fundamentally stated, that first autopsies in German institutes of pathology had been carefully performed and sufficiently documented. In these cases the second autopsy presented no or only little additional information, as far as the broader taking of (toxicological) samples is not considered. The final medico-legal expertise was then mainly based on the findings of the clinical first autopsy. However, the concurrence of the forensic expert (instead of the clinical pathologist) is undoubtedly essential for the evaluation of these issues involving frequently questions of malpractice. By contrast, the quality of postmortems performed abroad varies widely. 4 of the 5 first autopsies done abroad were regarded as completely or partly insufficient with superficial or almost absent preparation of organs or contradictions in the medical reports, respectively. A repeat autopsy is absolutely necessary in such cases. On the whole, the initial question could be answered in all second autopsies at least in part. This emphasizes the high value of second autopsies and expertises, especially in non-natural cases of death (10 of 12 deaths were finally judged as non-natural).     

Morphologic studies in criminal justice--requirements and reality

A critical analysis is given of the investigation and examination of fatalities for the public prosecution office and for the courts. Rationalistic simplifications in legal quarters, changes in legal procedures and bureaucracy have had negative effects on the field of forensic medicine. It is questionable whether forensic science today can fulfil the scientific demands with regard to a complete and thorough explanation of the cause of death. The reduced interest in expert opinions concerning the pattern of injuries that can help in the reconstruction of the act or in judging the intention and guilt of the perpetrator is a striking and alarming development in criminal justice. Medical examinations in the somatic field are no longer used enough in forensic cases; with regard to the administration of justice, the role of the forensic expert is limited to the postmortem findings and the cause of death. On the other hand, there is increased interest in the expert opinion of psychologists, psychiatrists and specialists in the field of drugs and alcohol. The fact that the number of autopsies and histological as well as toxicological examinations ordered by the public prosecutor is rather small has serious and negative implications for establishing the truth. Such orders are merely dependent on the circumstance of death and the situation in which the body was found. However, the external circumstances can be misleading or they can be manipulated. That is why some crimes are not revealed. In the Federal Republic of Germany, if there is no suspicion of external violence permission is granted for corpses to be buried without the cause of death being clarified by autopsy. However, the fact that the opinions of forensic specialists differ regarding this development in the administration of justice must also be criticized. There is an increasing tendency for investigations to be carried out only if they are ordered by the prosecutor and for questions to be answered only if they are asked officially. Even our colleagues are influenced too much by external circumstances and consider an autopsy unnecessary if the cause of death seems to be clear (for instance in cases of hanging, drowning or bleeding to death). Second autopsies have shown that the thoroughness and the quality of the first autopsy often leave much to be desired. It is, for instance, unforgivable if organs are described without being examined. Special interest is afforded to the necessity for the significance of histological examinations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ecstasy (MDMA) deaths in New York City: a case series and review of the literature

MDMA ("ecstasy") has gained renewed popularity as a drug of abuse. To access the epidemiology and causes of death of MDMA-positive fatalities, all deaths investigated by the OCME that tested positive for MDMA (22 deaths) between January 1997 and June 2000 were reviewed. There were three deaths in each 1997 and 1998, eleven in 1999, and five in the first part of 2000. Of these 22 deaths, 13 were due to acute drug intoxications, 7 due to mechanical injury (blunt trauma, gunshot wounds), and 2 due to a combination of natural disease and acute drug intoxication. Evidence of recent opiate and/or cocaine use was found in 7 of the acute intoxication deaths and in none of the traumatic or combination natural/intoxication deaths. The race of all decedents was White between the ages of 17-41 years, and 18 of 22 were men.     

Histomorphometric indices of the pancreas in intoxication with alcohol and narcotics

The results of histomorphometric examinations of the pancreas in drug- and alcohol-addiction as well as in acute intoxications are described. They show that, in chronic alcoholic intoxication as compared with opiomania, there are more pronounced interlobular sclerosis and lipomatosis, which is manifested by an enlarged middle lobe of the stroma (containing fat and connective tissue fibers), by a higher density of islands of Langerhans and by their higher sectional area. Autolysis and edema of the stroma are more severe in an acute intoxication with drugs than in other cases of fatal outcome. A possibility is demonstrated to differentiate between various types of the so-called long-term exogenous intoxication and to discriminate between different types of thanatogenesis typical of various cases of acute intoxications. Data are presented that demonstrate the advantage of the quantitative analysis of histological preparations over the qualitative one.     

Subdural Hemorrhage,a Retrospective Review with Emphasis on a Cohort of Alcoholics

Subdural hemorrhage (SDH) is a common cause of death. As external evidence of injury may be absent, an autopsy is frequently needed to detect it. We conducted a 3‐year review of SDH from the New York City Office of Chief Medical Examiner, with emphasis on a cohort of alcoholics. Our study population of 1942 included 1588 alcoholics. Of the alcoholics, c. 8% had SDH (26% of the total number of SDH). Of the alcoholics with SDH, 57% had associated brain injuries. As alcohol intoxication is frequently associated with aggressive and violent behavior, we are concerned that 6% of alcoholics in our review had no autopsy or imaging studies. It is possible that a portion of these may have had a SDH due to an unrecognized inflicted injury. We recommend that autopsies be performed on all alcoholics without a clear cause or mechanism of death.