The interpretation of cocaine and benzoylecgonine concentrations in postmortem cases.

This study examined cocaine and benzoylecgonine concentrations in 100 consecutive deaths where either compound was identified in blood or urine specimens to determine whether any relationship between these concentrations and cause of death can be found. Forty-seven of the 100 cases were deaths attributed to cocaine, narcotic or combined cocaine and narcotic intoxication. There were 13 cases of cocaine intoxication where no psychoactive substance other than ethanol was detected. The mean cocaine concentration in these deaths was 908 ng/ml; three cases had cocaine concentrations greater than 2000 ng/ml, while the other ten cases had cocaine concentrations less than or equal to 700 ng/ml. The mean cocaine concentration in non-cocaine deaths where no psychoactive substance other than ethanol was detected was 146 ng/ml. This difference was not statistically significant. However, the average blood benzoylecgonine concentration in the 13 cocaine deaths was significantly higher than in the 19 non-cocaine deaths. A review of combined cocaine and narcotic deaths suggest that the narcotic is the main causative agent in these deaths.     

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.     

An epidemic of cocaine associated deaths in Utah

This article describes 15 cocaine associated deaths in Utah in a 3 1/2-month period in early 1984, compared to 6 cocaine associated deaths for all of 1983. Brief case histories of the 15 cases are presented along with data on age, sex, county of death, cause of death, association of the cocaine with the death, cocaine analytical methodology, and a summary of cocaine concentrations in blood and urine. In four of the cases, cocaine by injection was the cause of death, whereas the other cases had cocaine or metabolite detected incidentally. The epidemiology of a single, well-defined cocaine source is described and related to this transient, remarkable increase in cocaine associated deaths.     

Cocaine and sudden "natural" death

The cardiovascular effects of cocaine may culminate in clinical episodes of angina pectoris, myocardial infarction, arrhythmias, and intracranial hemorrhage. To clarify whether or not cocaine causes fatalities by these mechanisms, we studied 24 cases of sudden, apparently natural deaths as a result of coronary arteriosclerosis (15 cases), hypertensive cardiovascular disease (4 cases), and intracranial hemorrhage (5 cases) associated with cocaine use. In 11 cases, cocaine was found in the blood (average concentration: 0.57 mg/L, range: 0.05 to 1.45 mg/L), whereas in the remainder, cocaine or its major metabolite was found in the urine or other tissues. In the majority of decedents, autopsy disclosed the existence of severe natural disease which could have been exacerbated by the administration of stimulant drugs, including cocaine. These data, and a review of the current medical literature, indicate that cocaine may precipitate the sudden death of an individual with undiagnosed cardiovascular disease. A contributory role of cocaine should be considered in any apparently natural death occurring in a population where cocaine abuse is prevalent.     

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.     

Post-mortem cases involving amphetamine-based drugs in The Netherlands. Comparison with driving under the influence cases

In this study we reviewed the post-mortem cases in the years 1999-2004 that were presented at the Netherlands Forensic Institute. The concentrations of amphetamine-based drugs in femoral blood from cases of suspected unnatural death were compared with concentrations in whole blood from non-fatal cases of driving under the influence (DUI cases) and with literature. Furthermore, the combinations with other drugs and/or alcohol were investigated. Amphetamine-based drugs were present in 70 post-mortem cases and 467 DUI cases. The most detected amphetamine-based drug was MDMA, followed by amphetamine. The presence of MDA could usually be explained by metabolism of MDMA. Methamphetamine and MDEA were rarely present. Frequently, the amphetamine-based drugs were taken in combination with alcohol and/or other non-amphetamine-based drugs such as cocaine or cannabinoids. The 70 post-mortem cases were divided into 38 amphetamine-based drug caused (i.e. the amphetamine-based drug directly caused or contributed to the death) and 32 amphetamine-based drug related deaths (i.e. death was not directly caused by the amphetamine-based drug). In the latter category, other (poly)drug intoxications and death by violence or drowning were the most frequent causes of death. In 30 cases, MDMA caused death directly. The range in blood concentrations of MDMA in these cases was substantial, i.e. 0.41-84 mg/L with a median concentration of 3.7 mg/L (n=30). MDMA blood concentrations in the MDMA related deaths (n=20) and in the DUI cases (n=360) varied up to 3.7 and 4.0 mg/L, respectively. Seven victims died from the direct effects of amphetamine; the blood concentration of amphetamine ranged from 0.24 to 11.3 mg/L, with a median concentration of 1.7 mg/L (n=7). The median concentrations of amphetamine in the amphetamine related deaths (n=13) and the DUI cases (n=208) were much lower, i.e. 0.28 and 0.22 mg/L, respectively. Amphetamine blood concentrations up to 6.0 and 2.3 mg/L were seen in the drug related deaths and DUI cases, respectively. The most frequently encountered amphetamine-based drugs in the investigated deaths were MDMA and amphetamine. The majority of MDMA- and amphetamine-caused deaths, i.e. 90% of these deaths, occurred with blood concentrations above 1.5 and 0.80 mg/L, respectively. MDMA and amphetamine blood concentrations in drug related deaths and DUI cases, however, overlap the range of fatal concentrations. Therefore, MDMA or amphetamine concentrations should never be used alone to establish the cause of death.     

Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance

We reviewed a series of 66 deaths in Washington State between 1995-2000 in which tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.     

Determining the Toxicological Significance of Pregabalin in Fatalities

Pregabalin has become more widely prescribed and abused in recent years but is still not always included in laboratory analysis. An LC‐MS‐MS method has been developed and applied to measure pregabalin in 93 postmortem cases, including drug‐related deaths, alternative causes of death, and fatalities where pregabalin was likely to have contributed to death. Other drugs or alcohol was detected, and the most common drug types (in decreasing frequency) were antidepressants, opioids, benzodiazepines, opiates, alcohol, antipsychotics, cocaine, cardiac drugs, amphetamines, cannabis, anticonvulsants, and antihistamines. New psychoactive substances (methoxphenidine and synthetic cannabinoids) were only found in two cases. The results provide further data to assist in evaluating the significance of postmortem pregabalin concentrations and a toxicologically significant concentration of 25 mg/L is proposed. Pregabalin, especially with concomitant use of other CNS depressant drugs, presents a significant toxicological risk and existing laboratory protocols should be reviewed for their suitability to detect pregabalin.     

Four deaths due to intravenous injection of cocaine

Cocaine is a potent psychotropic drug that alters mood and behavior by stimulating the central nervous system. Deaths from abuse of cocaine are relatively rare. Most such deaths appear to be related to the intravenous injection of the drug. Acute fatal cocaine intoxication is characterized by headache, cold sweats, rapid pulse, tremors and nausea, followed by convulsions, unconsciousness and death. The prime mode of death appears to be respiratory paralysis, secondary to the effects of cocaine on the medullary portion of the brain. This paper presents four deaths due to acute cocaine intoxication following intravenous injection. Blood concentrations of cocaine were 0.11, 0.37, 0.36 and 0.75 mg/dl.     

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 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.     

Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases

This paper reviews the complex pharmacology of the new class of antidepressant medications exhibiting selective inhibition of serotonin reuptake. The four selective serotonin reuptake inhibitors (SSRIs) considered--fluoxetine, fluvoxamine, sertraline and paroxetine--can result in toxicity and death through contributing to serotonergic excess resulting in serotonin syndrome, inhibiting the metabolism of other centrally acting drugs, leading to accumulation of toxic concentrations, and exerting complex vasoactive effects on the vascular smooth muscle. This latter feature is of particular concern in patients with preexisting heart disease. An analytical method involving isolation of the drugs by liquid/liquid extraction at alkaline pH into n-butyl chloride, and analysis by gas chromatography/mass spectrometry (GC/MS) is described, together with some of its limitations. Toxicologic and cause and manner of death data were examined in 60 deaths involving fluoxetine, 5 involving fluvoxamine, 75 involving sertraline, and 28 involving paroxetine. Deaths involving drug toxicity were generally a result of ingestion of multiple drugs, and in only a small number of the cases was death attributed principally to the SSRI involved. The potential for drug interactions between members of this class of drugs is discussed as well as their metabolites and a variety of other therapeutic and abused drugs which can contribute to their toxicity. In the absence of other risk factors, the lowest concentrations determined to have resulted in death were 0.63 mg/L for fluoxetine, 0.4 mg/L for paroxetine, and 1.5 mg/L for sertraline. We had insufficient data to make even this crude assessment for fluvoxamine. Drug-induced elevation of serotonin concentrations may be a significant risk factor for patients with atherosclerotic cardiovascular disease (ASCVD). Other factors including preexisting disease and the presence of other drugs and their pharmacology need to be carefully considered before determining the appropriate cause and manner of death in these cases.     

One hundred seventy two deaths involving the use of oxycodone in Palm Beach County

Oxycodone is a potent semi-synthetic narcotic prescribed for the management of pain. Previous investigators have reported that the abuse of oxycodone is most frequently seen in conjunction with the abuse of other drugs, although fatalities have been reported with oxycodone alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of oxycodone. A total of 172 consecutive cases were studied, including 18 in which death was attributed to oxycodone toxicity, 117 to combined drug toxicity, 23 to trauma, 9 to natural causes and 5 to another drug or drugs. The postmortem blood concentrations of oxycodone overlapped among the groups. The mean blood oxycodone concentration among the cases of oxycodone toxicity was 0.69 mg/L, combined drug toxicity 0.72 mg/L and trauma 0.62 mg/L. Concentrations were lower in cases of deaths attributed to natural causes and to another drug or drugs (mean each 0.087 mg/L). Benzodiazepines, detected in 96 cases, were the most common co-intoxicants in the cases of combined drug toxicity, followed by cocaine, which was found in 41. The most frequently encountered benzodiazepine was alprazolam. This study confirms that deaths in which oxycodone is a factor are most commonly cases of combined drug toxicity. The high incidence of alprazolam as a co-intoxicant has not been previously recognized.     

Post-mortem cases involving amphetamine-based drugs in the Netherlands: Comparison with driving under the influence cases

In this study we reviewed the post-mortem cases in the years 1999–2004 that were presented at the Netherlands Forensic Institute. The concentrations of amphetamine-based drugs in femoral blood from cases of suspected unnatural death were compared with concentrations in whole blood from non-fatal cases of driving under the influence (DUI cases) and with literature. Furthermore, the combinations with other drugs and/or alcohol were investigated. Amphetamine-based drugs were present in 70 post-mortem cases and 467 DUI cases. The most detected amphetamine-based drug was MDMA, followed by amphetamine. The presence of MDA could usually be explained by metabolism of MDMA. Methamphetamine and MDEA were rarely present. Frequently, the amphetamine-based drugs were taken in combination with alcohol and/or other non-amphetamine-based drugs such as cocaine or cannabinoids. The 70 post-mortem cases were divided into 38 amphetamine-based drug caused (i.e. the amphetamine-based drug directly caused or contributed to the death) and 32 amphetamine-based drug related deaths (i.e. death was not directly caused by the amphetamine-based drug). In the latter category, other (poly)drug intoxications and death by violence or drowning were the most frequent causes of death.In 30 cases, MDMA caused death directly. The range in blood concentrations of MDMA in these cases was substantial, i.e. 0.41–84 mg/L with a median concentration of 3.7 mg/L (n = 30). MDMA blood concentrations in the MDMA related deaths (n = 20) and in the DUI cases (n = 360) varied up to 3.7 and 4.0 mg/L, respectively. Seven victims died from the direct effects of amphetamine; the blood concentration of amphetamine ranged from 0.24 to 11.3 mg/L, with a median concentration of 1.7 mg/L (n = 7). The median concentrations of amphetamine in the amphetamine related deaths (n = 13) and the DUI cases (n = 208) were much lower, i.e. 0.28 and 0.22 mg/L, respectively. Amphetamine blood concentrations up to 6.0 and 2.3 mg/L were seen in the drug related deaths and DUI cases, respectively. The most frequently encountered amphetamine-based drugs in the investigated deaths were MDMA and amphetamine. The majority of MDMA- and amphetamine-caused deaths, i.e. 90% of these deaths, occurred with blood concentrations above 1.5 and 0.80 mg/L, respectively. MDMA and amphetamine blood concentrations in drug related deaths and DUI cases, however, overlap the range of fatal concentrations. Therefore, MDMA or amphetamine concentrations should never be used alone to establish the cause of death.     

The Prevalence of Paraphernalia Found at the Scene of Drug‐Related Deaths

Many illicit drugs involve the use of paraphernalia, and the presence of paraphernalia found at the scene of death may suggest that the death is drug‐related. Few sources of objective data are available regarding the prevalence of drug paraphernalia found at the scene of drug‐related deaths or the likelihood of a death with drug paraphernalia found at the scene to be drug‐related. This study reviews the deaths which were investigated by the Bexar County Medical Examiner's Office in an attempt to provide objective data. Over 4000 deaths with scene investigations were reviewed, and the presence of paraphernalia was found to be strongly associated with the death being drug‐related, heroin‐related, or cocaine‐related with the relative risk for each being 5.0, 15.4, and 6.6, respectively. This confirms that the presence of drug paraphernalia at the scene of death strongly suggests the death to be drug‐related and in particular heroin‐related.     

Site-dependent postmortem changes in blood cocaine concentrations

When a forensic toxicologist interprets postmortem blood cocaine findings he usually must make assumptions regarding perimortem drug concentrations. In-vitro studies have shown that cocaine rapidly hydrolyzes in unpreserved blood, particularly at elevated temperatures. However, other studies have demonstrated site-dependent postmortem release of some drugs from tissue stores accompanied by increases in drug concentrations in the blood. This study was undertaken to investigate whether blood cocaine concentrations change in the body during the postmortem interval and, if so, to measure the direction and magnitude of the changes. In medical examiner cases in which scene investigation suggested that the decreased was a cocaine user, blood samples were collected as soon after death as possible. At autopsy, a second set of samples was collected. Analysis of paired samples by gas chromatography/mass spectrometry (GC/MS) revealed dramatic differences in the cocaine concentration. The magnitude and direction of the change appears to be site dependent. Usually, but not invariably, cocaine concentration in subclavian vein blood decreases while that in heart, aorta, and femoral vein blood increases during the interval between death and autopsy. The findings emphasize the danger inherent in attempting to estimate the concentration of cocaine in blood at the time of death from postmortem data.     

Cocaine-related deaths in Pima County, Arizona, 1982-1984

A three-year review of toxicology data from medical examiner autopsies in Pima County, Arizona, has demonstrated that cocaine has rapidly become a leading substance of abuse, second only to alcohol in the frequency of drugs detected by toxicologic analysis of all suspicious deaths, motor vehicle accident fatalities, homicides, and suicides. Gastric contents and urine were analyzed by thin-layer chromatography, and nasal swabs, blood, and urine were tested for the combination of cocaine and its metabolite benzoylecgonine by quantitative radioimmunoassay. A total of seventy-two deaths in Pima County from 1982 to 1984 have involved cocaine. Seventy percent of these have occurred in the last fifteen months. Marked variation in the individual response to cocaine compared to the blood concentration of cocaine/metabolite was noted.     

Toxicological findings in victims of traumatic deaths.

The toxicological findings from 6037 analyses of viscera obtained from victims of traumatic death are used to correlate the relative incidence of carbon monoxide, ethyl alcohol, narcotics, hypnotics, analgesics, and tranquilizers-antidepressants in deaths occurring under the following circumstances: fire related, asphyxia by hanging, by use of plastic bags, from physical obstruction of trachae, and by drowning; traumatic injury from impact of moving train, fall from height, and occupational accident; traumatic injury to pedestrian, driver, and passenger from vehicular accidents; and from violent death by shooting, stabbing, strangulation, and beating. The influence of alcohol, narcotic drugs, and tranquilizers on carbon monoxide can be seen in some of these traumatic deaths. Ethanol alone and in combination with other drugs was present in 42.3% and 19.5% of driver and pedestrian victims, respectively, of vehicular accidents in the year 1974. Comparative analysis is presented for the toxicological data obtained on victims of homicide (shooting, stabbing, strangulation, and beating) in New York City and similar data reported for victims of homicide in Detroit. In New York City 45.9% of such victims died while under the influence of alcohol or narcotic drugs, or both, with methadone predominating in the latter category. Tissue concentrations of drugs found in victims of traumatic death are presented. Diphenylhydantoin, diazepam, meperidine, and slow-acting barbiturates were found in normal therapeutic levels. Higher concentrations of amitriptyline, chlorpromazine, propoxyphene, short-acting barbiturates, and methadone were observed. The concentration of methadone in blood and brain (0.13 +/- 0.14 mg/100 ml) and in liver (0.53 +/- 0.42 mg/100 ml) in cases of traumatic death are not different from those observed in deaths classified as due to methadone overdose.