Prevalence of rhabdomyolysis in drug deaths

Rhabdomyolysis has repeatedly been reported as a possible consequence of illicit drug consumption especially in clinical literature. In order to investigate the prevalence of rhabdomyolysis in cases of drug deaths, immunohistochemical staining of kidney sections with a myoglobin antibody was performed at 103 consecutive fatal drug poisonings. The control group consisted of 107 unselected forensic autopsies. With regard to the presence of intratubular myoglobin, 33% of the study group were categorized as "strongly positive", 17.5% as "slightly positive" and 49.5% as "negative". No single substance showed a particularly high incidence of rhabdomyolysis nor were there correlations to special combinations of substances. In the control group a "strongly positive" result after myoglobin staining was observed in only 10.3% of 107 cases, a "slightly positive" result in 13.1% and a "negative" result in 76.6%. The findings suggest that rhabdomyolysis is a frequent consequence of illicit drug consumption and that it is not promoted by a single factor, but by a combination of several factors.     

Medical negligence in drug associated deaths

According to epidemiological studies adverse drug events are one of the most frequently encountered complications during medical treatment, a leading cause of hospitalisation and frequent cause of death. However, medical malpractice claims due to medication errors seem to be relatively rare. Based on a retrospective multicentre study on medical malpractice cases with lethal outcome (n = 4450), drug related cases (n = 575) were further evaluated. In 50% of cases a causal connection between drug therapy and death could be ruled out already after autopsy. In 232 cases a causal connection between drug therapy and death could be approved (drug allergies, relative overdose, wrong application, mix-up of drugs and sepsis after injection abscess). However, within the legal context only in 70 cases a medication error was approved which was in 42 cases causal for death, in 28 not. Administration of contraindicated drugs, incorrect application and relative overdose in renal insufficiency are the prevalent mistakes. Concerning the frequency of ADE in epidemiological studies medication errors are underreported in all data sources on medical malpractice; this seems to be due to the fact that even doctors and attending physicians rarely recognize an ADE; furthermore approving the connection between drug effect and death is extremely difficult for the expert witness.     

Prevalence of nicotine consumption in drug deaths

One hundred consecutive drug death victims autopsied at the Institute of Forensic Medicine, University of Freiburg, between 1995 and 1997 were studied retrospectively as to whether the drug users had also consumed nicotine. The study included histological examination of the lung tissue for smoker cells and radioimmunological as well as GC-MS assays of the urine for cotinine, the primary metabolite of nicotine. It was found that 98 out of 100 drug victims had consumed nicotine in addition to illicit drugs or replacements. Yellowish-brown discolorations on the middle and index fingers were discernible in 44 drug victims, whereas fresh or scarred burns due to glowing cigarettes were found in six deceased drug consumers. Diseases of the bronchial system typical of heavy smokers were seen in 35 cases. Siderophages could be demonstrated in 17 of the 100 drug 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.     

Four deaths due to carbon monoxide poisoning in car washes.

In a period of 13 months, three separate incidents of lethal carbon monoxide (CO) poisoning in closed car wash bays resulted in the deaths of 4 white men aged 20 to 36 years. Each man appears to have been intoxicated with mind-altering substances, which may impair judgment, perception of outside conditions, and self-awareness. All four died in winter months. For three men, the deaths were ruled accidental, and for the remaining man, the previous deaths appear to have provided a model for suicide. Warning signs may not be effective to prevent future CO deaths in car washes because of the possible role of intoxication. Mechanical or electronic methods to prevent a bay door from closing completely may be preferable.     

Acute ethanol poisoning: a two-year study of deaths in North Carolina

A 24-month study of fatalities in North Carolina with high blood ethanol levels (300 mg/100 ml or over) revealed 502 cases with either acute alcoholism or the effects of this range of blood ethanol concentration having caused or contributed to death. This investigation reassessed the criteria for ethanol poisoning, including its cause and manner of death, and revealed recurrent patterns common to this syndrome. This inquiry also contrasted the frequency of ethanol poisoning in different areas of the country.     

Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism

Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (>0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.     

Lethal poisoning by zipeprol in drug addicts

Two cases of lethal intoxication involving or due to oral ingestion of zipeprol are described. The two cases concerned abusers of the substance for nonmedical purposes. Data regarding the distribution of the unmodified drug in biological fluids and tissues are presented.     

Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning

A suicide caused by ingestion of multiple psychoactive drugs is reported. A 42-year-old man with a history of psychosis was found dead in a blood pool in his room. The forensic autopsy revealed two stab wounds on his chest. However, these wounds could not explain the cause of death. Eighty-six tablets were found in his stomach. Four psychoactive drugs; clocapramine (CC), chlorpromazine (CP), promethazine (PM) and clotiazepam (CT) were detected in blood and tissues. The concentrations of CC, CP, PM and CT in the femoral vein (FV) blood were 0.39, 0.61, 1.23 and 0.09 microg/ml, respectively. The cause and manner of death were attributed to suicidal multiple psychoactive drug poisoning.Postmortem drug redistribution showed great site-dependent variations with the lowest level in the FV blood. Remarkable variations were observed in CC, CP and PM, but not in CT compared to other three drugs. The variations were dependent on the volume of distribution (Vd) of the drugs. Our human case has demonstrated drugs with higher Vd values showed higher degree of postmortem redistribution of the drug and vice versa.     

The significance of ethanolemia for the diagnosis of death from acute ethanol poisoning

Foci of myolysis of cardiac muscle fibers are suggested to be used for evaluation of thanatogenetic significance of ethanol concentration in cadaveric blood. This sign of acute ethanol poisoning is absent in case of other cause of death in a state of ethanol intoxication, even in the presence of high ethanolemia. Therefore, foci of myolysis are a sign of ethanol tolerance.     

Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism

The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean+/-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18+/-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N=457) the mean+/-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30+/-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47 g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41 g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.     

Detection of injuries in traumatic deaths. The significance of medico-legal autopsy

A material of 218 medico-legal autopsies on persons with traumatic injuries was analysed. All these persons had been admitted to hospital. In 75 (34%) injuries had been missed in hospital. In 11 (5%) the overlooked injuries were the sole cause of death, while in 51 (23%) they were contributory. The missed injuries were found in all regions: 27% were moderate (AIS 2), 28% serious (AIS 3), 40% severe (AIS 4), and 5% critical (AIS 5). It is concluded that medico-legal autopsies are necessary for an exhaustive evaluation of traumatic deaths. They are of significance not only to legal security, but also to the social need for analysing injury mechanisms and the consequent possibility of preventive efforts.     

8例利多卡因过敏性休克死的血药浓度分析

目的研究利多卡因过敏性休克死者利多卡因血药浓度及其与死因的关系。方法采用高效液相色谱法(HPLC),分别对使用利多卡因麻醉术中各项指标均正常的8例术中因利多卡因过敏性休克死者的血液和11例顺利完成手术患者的血液进行利多卡因浓度的检测,对比分析两者结果。结果 8例死者利多卡因血药浓度(1．61mg± 0．45mg／L)低于11例正常患者利多卡因血药浓度(2．44mg±0．47mg／L)。结论利多卡因过敏性休克死者血药浓度在正常值范围内,与发生过敏性休克致死无关。     

Bromadiolone poisoning: LC-MS method and pharmacokinetic data

Abstract:  Poisoning with superwarfarins, like bromadiolone, is a growing public health problem, and the mortality is high. Pharmacokinetic data on bromadiolone in humans are however scarce, and there are no reports following repeated exposures to bromadiolone. We have developed a method for quantification of bromadiolone in whole blood, using liquid chromatography–mass spectrometry (LC-MS). The analytical method is reported. Limit of detection was 0.005 mg/L and limit of quantification was 0.01 mg/L. The concentrations of bromadiolone in whole blood and plasma in serial samples from a 62-year-old woman were measured. The half-life of bromadiolone in blood was estimated to be about 6 days in the initial phase of elimination and about 10–13 days in the terminal phase. The mean plasma/blood ratio of bromadiolone was 1.7 ± 0.6. Stability testing of bromadiolone in whole blood samples after two cycles of freeze and thaw revealed that bromadiolone concentrations decreased.