Methadone-related deaths in Hennepin County,Minnesota: 1992-2002

Methadone maintenance therapy (MMT) is the only currently established medical therapy for heroin addiction. However, MMT still remains controversial. In Hennepin County, Minnesota, methadone is one of the top ten drugs reported in medical examiner investigated deaths and one of the most commonly diverted pharmaceuticals. This report reviews the role of methadone in medical examiner deaths over a 10-year period, 1992-2002. We compare cause and manner of death (accidental, natural, suicide) and methadone blood concentrations for decedents who were members of MMT programs with illicit users and those prescribed methadone for chronic pain. Findings reveal that 65% of decedents with measurable blood methadone concentrations were not participating in MMT programs. A total of 96 cases were identified, with the majority white (90.5%) and male (76.8%). MMTP program members were the minority (34.7%) of the methadone positive deaths and 39% were illicit users. Fifteen percent were chronic pain patients with almost half of this group dying from overdose. Methadone concentrations of drug caused/related deaths (0.18-3.99 mg/L) overlapped with those of deaths not attributable to methadone (0.18-3.03 mg/L) with no definable lethal level. Interpretation of methadone blood concentrations must be done in the context of the clinical history for determining cause of death, and may be confounded by postmortem redistribution.     

Methadone-related deaths in Norway

IntroductionThe use of methadone in opioid maintenance treatment (OMT) is potentially associated with a number of adverse effects and the risk of fatal toxicity. Increased methadone availability may lead to an increase in methadone-related deaths. We have investigated methadone-related deaths in Norway over the period 2000–2006.Materials and methodsMethadone-positive samples over the period 2000–2006 were identified from forensic toxicological investigations, and demographic and toxicological data were retrieved. The cases were cross-linked with the Norwegian Cause of Death Registry and regional OMT registers.ResultsA total of 312 individuals had died after taking methadone over the period 2000–2006, predominantly men with a mean age of 36. In 85% of cases (n = 264), the deceased had died of a methadone-related intoxication, most often in combination with other drugs, including benzodiazepines, cannabis and other opioids. Only 22% of the deceased had been in OMT at the time of death. A larger proportion of OMT patients had died of causes other than intoxications compared to those not in OMT (30% vs. 8%, respectively), most commonly related to disease.ConclusionsOne methadone-related death occurred, on average, every week over the time period investigated. Only 22% of the deceased were registered in opioid maintenance treatment (OMT) programs. The findings underline the need to control diversion of medication from OMT programs.     

Temporal clustering of heroin overdoses in Washington, DC

During the 5-day period from 28 Feb. 1985 through 4 March 1985, 24 heroin overdoses occurred in the District of Columbia. Statistical tests for clustering of fatal and nonfatal overdoses during this interval identified 7 heroin-related deaths that occurred on March 1 to 2 as a statistically significant cluster (p = 0.007). An extension of the analysis for clustering to a 15-month period identified 2 additional clusters, 1 of fatal overdoses and 1 of nonfatal ones. When all victims of fatal overdose in cluster intervals were combined and compared with all other heroin-related deaths, no significant differences were noted for levels of morphine or ethanol in blood. However, bile morphine concentrations of cluster decedents were significantly lower than those of noncluster decedents (p = 0.033), suggesting that these decedents were less tolerant to the effects of narcotics than the comparison group. Heroin concentrations in street-level heroin samples collected during clusters did not differ from those collected during comparison intervals. These data conflict with the traditional explanation of overdose clusters, which attributes these events to unusually potent street-level heroin.     

Fatalities associated with fentanyl and co-administered cocaine or opiates

Fatalities associated with fentanyl hydrochloride are increasingly seen in Massachusetts. Between September 2005 and November 2006, 5009 medicolegal investigations associated 107 deaths with licit or illicit fentanyl use, along with a co-detection of an opiate/opioid or cocaine/benzoylecognine, or both. Deaths associated with illicit fentanyl use occur in younger people (39.4 vs. 61.5 years) with higher fentanyl (17.1 ng/mL vs. 4.4 ng/mL) and lower morphine (76.9 ng/mL vs. 284.2 ng/mL) postmortem blood concentrations, and more frequent cocaine co-intoxication (65% vs. 3%), than deaths associated with illicit fentanyl use. A wide range of postmortem blood concentrations of fentanyl was detected (trace-280 ng/mL), with a minimum concentration of 7 ng/mL of fentanyl strongly associated with illicit use of fentanyl in poly-drug cases. The most commonly detected opiates/opioids in illicit fentanyl users were: morphine (29%), oxycodone (14.5%), and methadone (14.5%). Ethanol, cannabinoids, diazepam, citalopram, and diphenhydramine were each detected in greater than 10% of the licit fentanyl cases. Most fentanyl abusers died at their own home and their deaths were most often classified as accidental. Mapping of primary residences of decedents revealed conspicuous clustering of the illicit fentanyl use cases, as opposed to the random pattern in licit use cases. Fentanyl misuse is a public health problem in Massachusetts.     

Forensic medicine experiences with methadone substitution in the Geneva canton

Methadone treatment for heroin addiction has followed three distinct periods in Geneva, Switzerland. The first period (1970-1979) corresponds to the beginning of the heroin addiction epidemic. Treatment was restricted to detoxification and did not succeed in reducing fatal overdoses. During the second period (1980-1989), methadone maintenance program was favoured but access to this program was limited. This period has brought a decrease of illegal heroin consumption and criminality but not of fatal overdoses. Finally, during the third period (since 1990), legislation was changed to allow easier access to methadone maintenance program. As a consequence there was a significant drop in lethal heroin overdoses and in deaths attributed to HIV.     

Heroin Overdose Deaths and Heroin Purity Between 1990 and 2000 in Istanbul,Turkey*

Abstract: Turkey has continuously experienced problems with abuse of, and addiction to, opium derivatives. In this study, we analyzed the relationship between heroin overdose deaths and the characteristics of seized opium derivatives. Data were gathered from the Council of Forensic Medicine of the Ministry of Justice in Istanbul from 1990 to 2000. There were 636 heroin‐related deaths during this period, 595 of which were classified as heroin overdose deaths. Mean crude and weighted heroin purities remained relatively constant and were calculated to be 46% (57–34%) and 51% (39–59%), respectively. The weight of heroin and the number of heroin seizures, but not the heroin purity, were significantly associated with the number of heroin‐related deaths. Prevention strategies are needed to reduce the number of deaths caused by overdoses in countries situated on drug trafficking routes. These strategies should focus on drug trafficking, by providing increased levels of, and support for, law enforcement, stopping the supply of precursor chemicals, and combating corruption among border officials.     

The prevalence of drugs in carbon monoxide-related deaths: a retrospective study, 2000-2003

The objective of this study was to review demographic characteristics and drugs detected in carbon monoxide (CO)-related deaths from cases received by the Office of the Cuyahoga County Coroner in Cleveland, Ohio, from 2000-2003. Postmortem reports were reviewed, and decedents for which CO was listed as the cause of death were included. The data were compiled into 3 groups according to the official coroner's verdict as to the manner of death: accident, suicide, and homicide. Included in this study were 122 cases: 84 (69%) accidental, 31 (25%) suicide, and 7 (6%) homicide. Accident decedents were typically white males, aged 40-59 years, residing in Cleveland. Suicide decedents were also middle-aged, white males but residing in the suburbs. Homicide decedents under the age of 6 were characteristically black (N=2), while decedents over the age of 39 were predominately white (N=3). Carboxyhemoglobin (COHb) levels in suicide cases were higher than concentrations measured in accidental deaths. The highest percentage of suicide decedents (36%) had a COHb level>70% saturation, accident decedents (36%) between 50% and 69% saturation, and homicide decedents (71%) below 50% saturation. Ethanol (N=34) was detected in 28% of deaths, and therapeutic and/or abused drugs (N=50) were detected in 41% of deaths. Illicit drugs were detected in 11% of cases (cocaine/metabolites; THC/metabolites), other drug positives were therapeutic medications. The most common drugs detected were antidepressants and antihistamines in suicides and pain medications and antihistamines in accidents.     

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.     

Analysis of cocaine-positive fatalities

A review of all autopsy and toxicology reports for persons dying in New York City in an 11-month period found 935 persons dying with cocaine in their bodies. Cocaine-positive fatalities were more likely in the young black and Hispanic and male population. In addition to cocaine and its metabolites, heroin and other opiates were found in 39% of persons and ethanol in 33% and barbiturates and minor tranquilizers in only 2% of the deceased. Cocaine overdose was responsible for 4% of the deaths and overdose with heroin and cocaine for 12% of the deaths. Violence was often the cause of death. Thirty-eight percent died of homicide, seven percent of suicide, and eight percent from accidents. Of particular interest were 6 persons who died of acute cardiac events directly related to cocaine as well as 4 cases of ruptured dissections of the ascending aorta, and 9 cases of cerebral hemorrhage. Autopsy findings for these individuals are described, and possible mechanisms of death are discussed.     

Fatal intoxication as a consequence of intranasal administration (snorting) or pulmonary inhalation (smoking) of heroin

In recent years we have noticed an increasing proportion of mortalities resulting from an overdose of heroin that involve routes of administration other than injection. Of 239 cases of fatal heroin intoxication examined at our department during the period 1997-2000, 18 deaths were associated with non-parental administration. Seven of these fatalities were experienced heroin users who had begun to use more sporadically, seven were recreational "party-users", while the remaining four persons had relapsed into heroin use following long periods of abstinence. The median blood morphine concentration of these non-injectors was 0.095 microg/g (range: 0.02-0.67 microg/g), significantly lower than that of the injectors. Concurrent use of alcohol, other illicit drugs and/or pharmaceutical preparations was observed in 17 of the 18 cases. However, there were no statistically significant differences between the victims of heroin intoxication by injection or by other routes with respect to the proportion who had simultaneously consumed alcohol or benzodiazepines. Pathological alterations like lung fibrosis, liver cirrhosis, endocarditis, etc. were not found to play a significant role in any of the 18 mortalities. We conclude that snorting or smoking heroin probably involves a reduced risk of obtaining high blood concentrations of morphine but still constitutes a considerable risk of lethal outcome due to high variability in blood concentrations. Furthermore, decreased tolerance resulting from periods of reduced or sporadic use appears to be an important risk factor in connection with heroin overdosing by snorting or smoking, which indicate that some heroin addicts may inaccurately assume that these routes of administration are safe when resuming their use of heroin after a period of abstinence.     

Evaluation of Non‐Natural Deaths among Veterans: New Mexico Medical Examiner‐Investigated Deaths, 2002–2011

While it is recognized that veterans have increased rates of depression, post‐traumatic stress disorder (PTSD), suicide, and substance use disorders, rates of homicide and unintentional injury deaths in veterans have been minimally investigated. We evaluated all non‐natural deaths in New Mexico veterans between 2002 and 2011 in comparison with non‐natural deaths among non‐veterans. We reviewed all decedents in New Mexico with a history of military service and investigated by the medical examiner, excluding natural deaths and deaths due to fall from standing height. The most common manner of death was unintentional injury (62%), most of these deaths due to motor vehicle accidents (29%) followed by unintentional overdose (26%). Suicide rates among veterans were consistently higher than the general population. The most common mechanism of suicide in men was gunshot wound (72%), and intentional overdose in women (49%). Services are needed for veterans that are tailored to all ages and both sexes.     

Death caused by drug addiction: a review of the experiences in Hamburg and the situation in the Federal Republic of Germany in comparison with the literature

Based on criminological experiences and pathomorphological, serological and toxicological studies of more than 300 fatalities, an overview is given of drugs, their intravenous abuse and drug deaths in Hamburg and the Federal Republic of Germany. The number of drug deaths has increased dramatically in Hamburg, where there were more than 50 cases each year in 1987 and 1988. In the F.R.G. approximately 400 cases are registered per annum. The percentage of female intravenous drug abusers is growing and the age of the decedents is increasing. The mean was formerly 25 years, but is now 30 years. Among the histopathological findings, foreign-body granulomas are of special value; infectious diseases, especially hepatitis B and HIV-infection, have to be investigated serologically and morphologically. The prevalence of HIV-1 antibodies among drug deaths in Hamburg is approximately 15%, in comparison with approximately 50% in Berlin. The "supply" of heroin has apparently become so copious that nearly all deaths are caused by overdosage with this substance. An international agreement about a definition of a drug death is a prerequisite for nationwide analyses.     

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.     

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.