Fatal intoxications in the age group 15-34 years in Denmark in 1984 and 1985. A forensic study with special reference to drug addicts

This survey deals with the Danish part of a study on fatal intoxications conducted in the Nordic countries in 1984 and 1985 with special reference to drug addicts. There were 315 cases of fatal intoxications in people 15-34 years of age. These were examined at the Forensic Institutes in Denmark and described with reference to cause of death, sex, age and drug addiction. Of the deceased, 194 were drug addicts according to a specific definition of this term. Women accounted for 28% of all the fatalities investigated in the study and 24% of those in addicts. More than 90% of the deaths were caused by drugs, with ethanol as a contributory factor in approximately 40% of cases. Deaths caused by heroin/morphine predominated, causing 50% of the deaths among drug addicts, but legal drugs, such as dextropropoxyphene, methadone and ketobemidone were also frequent causes of death in this group. In half the cases the concentration of morphine in blood following injection of heroin/morphine was found to be equal to or less than 0.5 mumol/kg, and in only about one-tenth of cases was the blood concentration above 2.0 mumol/kg.     

Fatal poisonings in young drug addicts in the Nordic countries: a comparison between 1984–1985 and 1991

Fatal poisonings among young drug addicts (15–34 years) in the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden in 1991 were investigated and compared to a similar investigation for 1984–1985 (Sweden for 1984 only). A common definition of ‘drug addict’ has been applied by the participating countries. In both investigations, the greatest number of drug addict deaths was seen in Denmark calculated per 10⁵ inhabitants, followed in descending order by Norway, Sweden, Finland and Iceland. An increased number of deaths was observed from 1984–1985 to 1991 in all five countries. The increase in Denmark and Sweden was small while the number of deaths was more than doubled in Norway and Finland. The increased number of cases in Norway and Sweden in 1991 is mainly due to a greater number of deaths in the age group 25–34 years. In Finland, the increased number was seen mainly in the age group 15–24 years. In the two investigations heroin/morphine caused most of the fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and strong analgesics other than heroin/morphine caused about one third of the deaths. In 1984–1985 it was methadone, propoxyphene and ketobemidone and in 1991 mostly methadone. The number of heroin/morphine related deaths in Finland increased from 1984–1985 to 1991, but other drugs and poisons caused a much higher proportion of the deaths. Pentobarbital caused the only fatal poisoning in Iceland in 1991.     

Fatal poisoning in drug addicts in the Nordic countries in 2007

The frequency of medico-legally examined fatal poisonings in 2007 among drug addicts was investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4.02), Iceland (4.56), and Sweden (3.53) were about half that of Norway and Denmark. Compared with earlier studies, the death rates were unchanged in Denmark and Norway, but increased in Finland, Iceland, and Sweden. In all countries, fewer deaths (29-35%) were recorded in the capital area compared with earlier studies. Females accounted for 11-19% of the fatal poisonings. Iceland deviates with a more equal distribution between men and women (40%). Deaths from methadone overdoses increased in all Nordic countries, and methadone was the main intoxicant in Denmark in 2007, accounting for 51% of the poisonings. In Norway and Sweden, heroin/morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol.     

Deaths among drug addicts in Denmark in 1968-1986

In the period 1968-1986 a total of 1618 fatalities among drug addicts were investigated at the three University Institutes of Forensic Medicine in Denmark. The annual number rose from 5 in 1968 to 163 in 1980, thereafter there has been a gradual fall to 121 in 1986. About 80% were males. The average age has risen from 22/23 years in the early 1970s to 31 years in 1986, and the percentage of addicts with a duration of abuse more than 10 years has increased gradually; both facts indicate a decrease in the recruitment among the quite young. In the whole period morphine was abused, supplemented by various medicines. Amphetamine was abused in the first years and again in 1986. The percentages of addicts with an abuse of alcohol and of addicts dying after a period of abstinence lasting more than 1 year, respectively, have increased. No essential changes were observed regarding distribution of residence or of the cause and manner of death. In the poisoning cases the predominant drug of poisoning was morphine/heroin, in all the years constituting approx. 30-50%. The second most frequent drugs of poisoning in the first half of the period was barbiturate, in the last half dextropropoxyphene and methadone. Only very few cases dying of cocaine poisoning were present and deaths due to so-called designer drugs have not been observed.     

Fatal poisoning in drug addicts in the Nordic countries.

The study includes medicolegally examined fatal poisonings among drug addicts in 1997 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden, and the results are compared to a similar investigation from 1991. A common definition of "drug addict" was applied by the participating countries.The highest death rate by poisoning in drug addicts was observed in Denmark, where it was 6.54 per 10(5)inhabitants, followed by Norway with 6.35, Sweden with 2.21, Finland with 1.63 and Iceland with 1.20 per 10(5)inhabitants. All countries showed a higher death rate in 1997 than in 1991. For all countries the distribution of deaths according to geographical regions showed a decreasing number of drug deaths in the metropolitan area and an increasing number in other cities. Heroin/morphine dominated as the cause of death and was responsible for about 90% of the cases in Norway. In Sweden and Denmark, however, heroin/morphine caused only about 70% of the fatal poisonings. About 30% of the fatal poisonings in Denmark and Sweden were caused by other group I drugs, in Denmark mainly methadone and in Sweden mainly propoxyphene. Apart from two cases in Sweden methadone deaths were not seen in the other Nordic countries. In Finland heroin/morphine deaths have increased from about 10% in 1991 to about 40% in 1997. Forty-four percent of the fatal poisonings in Finland were caused by other group I drugs, mainly codeine and propoxyphene. The two fatal poisonings in Iceland were caused by carbon monoxide. Only few deaths in this investigation were caused by amphetamine and cocaine. A widespread use of alcohol, cannabis and benzodiazepines, especially diazepam, was seen in all the countries.     

Some observations concerning blood morphine concentrations in narcotic addicts

Blood samples from deceased narcotic addicts were analyzed for morphine, and the results form persons who died from narcotic addiction were compared with those from homicide victims. In most instances morphine was detectable in both types of death, and usually the values obtained were less than 30 microgram/dl. Narcotic addiction deaths involving only morphine, or morphine plus a combination of ethanol, quinine, or diazepam (Valium), were also evaluated. In some cases high quantities of ethanol were present, and death could be attributed to the combined CNS depressant effects of morphine and ethanol. The quinine levels would not normally be considered toxic, however, and it could not be ascertained that the quantity of this drug present contributed to death. Diazepam was present in elevated concentrations, and its depressant effect may have been a factor in some narcotic addiction deaths.     

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.     

Fatal intoxications in the Nordic countries. A forensic toxicological study with special reference to young drug addicts

Fatal intoxications in the 15-34 age group in the five Nordic countries during the years 1984 and 1985 (Sweden only in 1984) were investigated. The known drug addicts were studied separately. The highest incidence of intoxications, calculated per 10(5) population, was found in Finland (11.3), followed by Denmark (10.3), Sweden (8.5), Iceland (7.2) and Norway (6.6). The percentage of intoxications caused by drugs was 92 in Denmark, 71 in Norway, 66 in Sweden, 50 in Finland and 17 in Iceland. Ethanol intoxications were seen 5-7 and 2-3 times as frequently in Finland and in Iceland, respectively, than in the other three countries. Carbon monoxide intoxications accounted for two-thirds of all fatal intoxications in Iceland. Drug addicts accounted for 62% of all fatal intoxications in the Danish material. The corresponding figures were 33% in the Norwegian, 16% in the Swedish and 5% in the Finnish material. No deaths in drug addicts were found in Iceland. Most drug addicts in Denmark, Norway and Sweden died of hard drugs and most in Norway and Sweden, from heroin or morphine, whereas in Denmark other strong analgesics, such as methadone, dextropropoxyphene and ketobemidone, accounted for 40% of all hard-drug-related fatal intoxications. To a certain extent the results reflect differences in the legal autopsy routines in the various Nordic countries. However, the ascertainment of drug addicts is assumed to be near-complete in each country.     

Morphine in lymph nodes of heroin users

During the autopsy of heroin users, the most consistent morphologic finding is the enlargement of hepatic lymph nodes. Nodes from seven heroin addicts were analyzed for morphine and a concentration range of 0.02 to 0.87 mg/100 g was found. Morphine was detected in all of the nodes examined and the concentration was generally higher than that in the blood.     

Methadone toxicity causing death in ten subjects starting on a methadone maintenance program.

Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates.     

Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/mass spectrometry

Hair of young subjects (N = 36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography/mass spectrometry (GC/MS). For amphetamine, methamphetamine, MDA, MDMA, and MDEA analysis, hair samples were incubated in 1M sodium hydroxide, extracted with ethyl acetate, derivatised with heptafluorobutyric acid anhydride (HFBA), and assayed by GC/MS. The methods were reproducible (R.S.D. = 5.0-16.1%), accurate (85.1-100.6%), and sensitive (LoD = 0.05-0.30ng/mg). The applied methods confirmed consumption of heroin in 18 subjects based on positive 6-acetylmorphine. Among these 18 heroin consumers, methadone was found in four, MDMA in two, and cocaine in two subjects. Cocaine only was present in two, methadone only in two, methamphetamine only in two, and MDMA only in seven of the 36 subjects. In two out of nine coloured and bleached hair samples, no drug was found. Despite the small number of subjects, this study has been able to indicate the trend in drug abuse among young people in Croatia.     

The detection of acetylcodeine and 6-acetylmorphine in opiate positive urines

Acetylcodeine (AC), an impurity of illicit heroin synthesis, was investigated as a urinary biomarker for detection of illicit heroin use. One hundred criminal justice urine specimens that had been confirmed positive by GC/MS for morphine at concentrations >5000 ng/ml were analyzed for AC, 6-acetylmorphine (6AM), codeine, norcodeine and morphine. The GC/MS analysis was performed by solid phase extraction and derivatization with propionic anhydride. Total codeine and morphine concentrations were determined by acid hydrolysis and liquid/liquid extraction. AC was detected in 37 samples at concentrations ranging from 2 to 290 ng/ml (median, 11 ng/ml). 6AM was also present in these samples at concentrations ranging from 49 to 12 600 ng/ml (median, 740 ng/ml). Of the 63 specimens negative for AC, 36 were positive for 6AM at concentrations ranging from 12 to 4600 ng/ml (median, 124 ng/ml). When detected, the AC concentrations were an average of 2.2% (0.25 to 10.2%) of the 6AM concentrations. There was a positive relationship between AC concentrations and 6AM concentrations (r=0.878). Due to its very low concentration in urine, AC was found to be a much less reliable biomarker for illicit heroin use than 6AM in workplace or criminal justice urine screening programs. However, AC detection could play an important role in determining if addicts in heroin maintenance programs are supplementing their supervised diacetylmorphine doses with illicit heroin.     

Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis

In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.     

Comparative Toxicology of Intentional and Accidental Heroin Overdose*

Abstract: The demographic and toxicological characteristics of deliberate (SUI, n = 50) and accidental (ACC, n = 927) fatal heroin overdose cases were examined. SUI cases were more likely to be female, had lower body mass indices, were more likely to be enrolled in treatment and less likely to have hepatic pathology. The median blood morphine concentration of SUI cases was significantly higher than that of ACC cases (0.70 vs. 0.40 mg/L, p < 0.001). Blood morphine concentrations of >1 mg/L were seen among 38.0% of SUI cases compared to 13.9% of ACC cases. Being a member of the SUI group remained a significant independent predictor of higher morphine concentrations after controlling for the effects of potential confounders (p < 0.001), other significant predictors being the absence of alcohol (p < 0.001), the presence of methadone (p < 0.05), and the presence of cocaine (p < 0.05). The current data are consistent with the view that suicide forms a small, but distinct, category of heroin overdose cases, rather than overdose being a parasuicidal phenomenon per se.     

Methadone in maintenance treatment of narcotic addicts; joint revision of conditions for use; interim maintenance treatment; human immunodeficiency virus disease counseling--FDA and SAMHSA. Final rule

The Food and Drug Administration (FDA) and the Substance Abuse and Mental Health Services Administration (SAMHSA) formerly the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) are revising the conditions for the use of methadone in the maintenance treatment of narcotic addicts. The final rule allows, contingent on FDA and State approval, public and nonprofit private narcotic treatment programs to provide interim maintenance treatment to patients awaiting placement in comprehensive maintenance treatment and to require all narcotic treatment programs to provide counseling on preventing exposure to, and the transmission of, human immunodeficiency virus (HIV) disease.     

Nutritional status of deceased illicit drug addicts in Stockholm, Sweden--a longitudinal medicolegal study

Autopsy investigations, toxicological analyses, and calculation of body mass index were performed in 1180 deceased illicit drug addicts (IDAs) in Stockholm. Sweden during 1988-2000, i.e., during a period of time when the general population in numerous countries showed a dramatic increase in the prevalence of overweight. Nutritional deficit in IDAs has been pointed out as a threat to their health as well as to their quality of life. The prevalence of overweight in deceased IDAs increased from 27.4% in 1988 to 45.5% in 2000. The prevalence of overweight among all heroin users, heroin injectors, methadone, cocaine, and amphetamine users was 36.0, 38.4, 43.1, 45.0 and 50.9%, respectively, the lowest prevalence being among users of cannabis alone and HIV-positive IDAs (22.0 and 16.1%, respectively). In conclusion, Stockholm's IDAs are affected by the past decade's dramatically increased prevalence of overweight, at least to the same degree as the general population. The increased body weight seems not to influence the danger of dying upon heroin administration.     

血液和尿液样品中海洛因代谢物稳定性研究

目的对尿液和血液中海洛因代谢物3-β-D-葡萄糖醛酸吗啡（M3G）,吗啡,O6-单乙酰吗啡（O6）在180d内的稳定性进行研究。方法准备空白添加血液、尿液、染毒动物（大白兔）血液、尿液和吸食海洛因者血液、尿液样本,分别置于20℃、4℃、-20℃下,分别于0、1、2、4、7、14、28、56、112、156、180d时间点测定样品中M3G、吗啡,O6相对含量。结果在3种不同温度下,随保存时间的延长,血液、尿液中的O6含量均逐渐下降至零;血液中吗啡含量升高（空白血液添加组）或下降（染毒动物组）,在尿液则均升高;血液样中M3G含量均升高,尿样中则略有下降。下降和升高的幅度均随保存温度的下降而缩小。结论海洛因代谢物在-20℃时保存稳定性最佳。     

Role of alcohol in heroin overdose

The relationship between ethanol and risk of heroin overdosage was studied. Statistical processing of the results of forensic chemical analysis (460 expert evaluations) carried out in Chelyabinsk Regional Bureau of Forensic Medical Expert Evaluations in 2000 was carried out. The results of morphine and ethanol measurements in the blood and urine from corpses where deaths ensued from narcotic or ethanol poisoning, were analyzed. The concentrations of morphine in the blood and urine were measured on a gaseous chromatographer with mass-selective detector (Hewlett Packard HP 6890/HP-5972). Methods for measuring urinary and blood morphine are described. The results of statistical analysis demonstrated relationships between the age and ethanol concentrations in the blood and urine; blood ethanol and total urinary and blood morphine concentrations; blood concentration of free morphine and presence of 6-monoacetylmorphine in the blood. The authors conclude that the presence of ethanol in the blood together with morphine drastically augments the risk of rapid death from respiration arrest. It can also lead to a relatively high risk of overdosage in experienced narcomaniacs using heroin and ethanol.