Background: Multiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem. Methods: This retrospective study (1993-2010) used a national forensic toxicology database (TOXBASE), and we identified 3943 individuals with two or more arrests for use of illicit drugs and/or impaired driving. These individuals had subsequently died from a fatal drug poisoning or some other cause of death, such as trauma. Results: Of the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p amp;lt; 0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p amp;lt; 0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p amp;lt; 0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p amp;lt; 0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids. Conclusions: This study shows that people arrested multiple times for use of illicit drugs and/or impaired driving are more likely to die by accidentally overdosing with drugs. Lives might be saved if repeat offenders were sentenced to treatment and rehabilitation for their drug abuse problem instead of conventional penalties for drug-related crimes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Background: Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. Methods: This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. Results: The mean age of all victims (N = 895) was 48 +/- 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (+/- SD) 47 +/- 20 years, than alcohol positive cases (35 +/- 14 years) and illicit drug users (34 +/- 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in similar to 7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. Conclusions: The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.
The concentrations of alcohol in blood (BAC) and two successive urine voids (UAC) from 100 drunk drivers were compared with the concentration of ethyl glucuronide (EtG), a minor metabolite of ethanol in urine, and the urinary creatinine content as an indicator of dilution. The subjects consisted of 87 men with mean age 42.2 ▒ 14.2 years (▒standard deviation, S.D.) and 13 women with mean age 42.5 ▒ 14.4 years. Ethanol was measured in blood and urine by headspace gas chromatography (GC) and EtG was determined in urine by liquid chromatography-mass spectrometry (LC-MS). The mean UAC was 2.53 ▒ 1.15g/l for first void compared with 2.35 ▒ 1.17g/l for second void, decreasing by 0.18 ▒ 0.24g/l on average (P < 0.001 in paired t-test). The ratios of UAC/BAC were 1.35 ▒ 0.25 for first void and 1.20 ▒ 0.16 for second void and the difference of 0.15 ▒ 0.27 was statistically significant (P < 0.001). The UAC/BAC ratio was not correlated with creatinine content of the urine specimens, whereas the concentration of urinary EtG was positively correlated with creatinine (r=0.64 for first void and r=0.62 for second void). The UAC was not correlated with urinary EtG directly (r=-0.03 for first void and r=0.08 for second void) but after adjusting for the relative dilution of the specimens (EtG/creatinine ratio) statistically significant positive correlations were obtained (r=0.58 for first void and r=0.57 for second void). The dilution of the urine, as reflected in creatinine content, is important to consider when EtG measurements are interpreted. The excretion of EtG in urine, like glucuronide conjugates of other drugs, is influenced by diuresis. EtG represents a sensitive and specific marker of acute alcohol ingestion with applications in clinical and forensic medicine. ⌐ 2003 Elsevier Science Ireland Ltd. All rights reserved.
The illicit recreational drug of abuse, gamma-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem (R)), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover (R)) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter.-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, gamma-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t1/2 similar to 1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of similar to 100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from administering benzodiazepines.
?-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths.
Concentrations of unconjugated morphine, codeine and 6-acetylmorphine (6-AM), the specific metabolite of heroin, were determined in urine specimens from 339 individuals apprehended for driving under the influence of drugs (DUID) in Sweden. After an initial screening analysis by immunoassay for 5-classes of abused drugs (opiates, cannabinoids, amphetamine analogs, cocaine metabolite and benzodiazepines), all positive specimens were verified by more specific methods. Opiates and other illicit drugs were analyzed by isotope-dilution gas chromatography-mass spectrometry (GC-MS). The limits of quantitation for morphine, codeine and 6-AM in urine were 20 ng/mL Calibration plots included an upper concentration limit of 1000 ng/mL for each opiate. We identified the heroin metabolite 6-AM in 212 urine specimens (62%) at concentrations ranging from 20 ng/mL to > 1000 ng/mL The concentration of 6-AM exceeded 1000 ng/mL in 79 cases (37%) and 31 cases (15%) were between 20 and 99 ng/mL. When 6-AM was present in urine the concentration of morphine was above 1000 ng/mL in 196 cases (92%). The concentrations of codeine in these same urine specimens were more evenly distributed with 35% being above 1000 ng/mL and 21% below 100 ng/mL. These results give a clear picture of the concentrations of unconjugated morphine, codeine and 6-acetylmorphine that can be expected in opiate-positive urine specimens from individuals apprehended for DUID after taking heroin.
Background: Both the illicit drug heroin and the prescription drug codeine are metabolized to morphine, which tends to complicate interpretation of opiate-positive samples. We report here the concentrations of morphine and codeine, the morphine/codeine ratios, and 6-acetylmorphine (6-AM) in blood specimens from individuals arrested for driving under the influence of drugs (DUID) in Sweden. The results were compared with positive findings of 6-AM in urine as evidence of heroin intake. Methods: In 339 DUID suspects, both blood and urine specimens were available for toxicologic analysis. In another 882 cases, only blood was available. All specimens were initially analyzed by immunoassay, and the positive results were verified by isotope-dilution gas chromatography-mass spectrometry. In routine casework, the limits of quantification (LOQs) for unconjugated opiates were 5 ng/g for blood and 20 ╡g/L for urine. Results: The median concentration of morphine in blood was 30 ng/g with 2.5 and 97.5 percentiles of 5 and 230 ng/g, respectively (n = 979). This compares with a median codeine concentration of 20 ng/g and 2.5 and 97.5 percentiles of 5 and 592 ng/g, respectively (n = 784). The specific metabolite of heroin, 6-AM, was identified in only 16 of 675 blood specimens (2.3%). This compares with positive findings of 6-AM in 212 of 339 urine samples (62%) from the same population of DUID suspects. When 6-AM was identified in urine, the morphine/codeine ratio in blood was always greater than unity (median, 6.0, range, 1-66). In 18 instances, 6-AM was present in urine, although morphine and codeine were below the LOQ in blood. The morphine/codeine ratio in blood was greater than unity in 85% of DUID cases when urine was not available (n = 506), and the median morphine and codeine concentrations were 70 ng/g and 10 ng/g, respectively. When morphine/codeine ratios in blood were less than unity (n = 76), the median morphine and codeine concentrations were 10 ng/g and 180 ng/g, respectively. Conclusions: Only 2.3% of opiate-positive DUID suspects were verified as heroin users on the basis of positive findings of 6-AM in blood. A much higher proportion (62%) were verified heroin users from 6-AM identified in urine. When urine was not available for analysis, finding a morphine/codeine concentration ratio in blood above unity suggests heroin use and not medication with codeine. This biomarker indicated that 85% of opiate-positive DUID blood samples were from heroin users. ⌐ 2001 American Association for Clinical Chemistry.
The Evidenzer is a new kind of forensic breath-alcohol analyser, designed for use both at a police station (stationary) and also in a police vehicle (mobile) at the roadside. In this paper we report the accuracy and precision of the Evidenzer, determined under controlled laboratory conditions. The results were compared with a well-established breath-alcohol instrument (Intoxilyzer 5000S) and also with the concentration of alcohol in venous blood. Twenty healthy volunteers (10 men and 10 women) consumed ethanol (0.4 g/kg) in 15 minutes starting two to three hours after their last meal. Venous blood and breath were obtained for determination of ethanol at 15-30 minute intervals for up to four hours post-dosing. There was a good overall agreement between the two breath-alcohol instruments and the mean bias was only 0.003 mg/L (95% limits of agreement of -0.016 to 0.023 mg/L). The standard deviation (SD) of measuring ethanol in breath was about the same for both instruments, being 0.006 mg/L, and this corresponds to a relative precision or coefficient of variation (CV) of 4.7%. When the Evidenzer was used to analyse ethanol vapour (0.50 mg/L) generated from a wet-bath simulator, i.e. in-vitro conditions, the coefficient of variation was 0.7% indicating high analytical precision. The concentration of ethanol in venous blood and breath were highly correlated (r=0.95) although systematic differences existed depending on time after drinking when comparisons were made. Both breath-alcohol instruments gave results higher than venous blood alcohol in tests made at 15 minutes after the end of drinking whereas at all later times the venous blood-alcohol concentration was higher than the breath instrument readings. These observations can be explained by the time necessary for ethanol to equilibrate between arterial blood and tissue water and by the resulting arterial-venous differences. The time-course of alcohol concentration in arterial blood runs closer to the breath-alcohol concentration rather than the venous blood draining the forearm muscle tissue. The new Evidenzer instrument was easy to operate and gave accurate and precise results compared with Intoxilyzer 5000S.
Alkoholutandningsprov används vid polisens trafiknykterhetskontroller men även inom sjukvården och kriminalvården samt allt oftare i arbetslivet.
Dagens utandningsapparater för etanol baseras på antingen halvledarteknik, bränslecell eller infraröd detektion.
Halvledarinstrumenten är billiga men ospecifika för etanol och kan även reagera på andra ämnen som förekommer i utandningsprov.
Mätmetoder med dålig analytisk specificitet innebär alltid en risk för falskt positiva resultat.
Eftersom ett falskt positivt alkoholutandningsprov kan få mycket allvarliga konsekvenser för den enskilde, bör endast användning av säkra instrument baserade på bränslecell eller infraröd detektion accepteras i legala sammanhang.
Acute poisoning involving toxic alcohols other than ethanol is not uncommon. Poisonings from drinking isopropanol are rarely life threatening, whereas methanol and ethylene glycol without prompt treatment cause severe metabolic acidosis, organ damage, and death, mainly due to toxic metabolites. Rapid identification of the type of alcohol responsible for the poisoning requires access to 24/7 toxicological service. The analysis of alcohols is usually done with gas chromatographic (GC) methods, which are not always available at smaller or medium-sized hospitals. As a complement to GC methods, reliable enzymatic oxidation procedures are now available for the analysis of ethanol, methanol, and ethylene glycol. The present study showed good agreement (r2 = 0.996) between the results of methanol analysis with a new enzymatic method (Catachem Inc.) and with GC over the clinically relevant concentration range (1-50 mmol/l). Moreover, high concentrations of ethanol (up to 80 mmol/l), ethylene glycol (to 40 mmol/l), isopropanol (to 100 mmol/l) or acetone (to 20 mmol/l) did not interfere with the analytical results for methanol. Toxicological analysis of the two most dangerous alcohols (methanol and ethylene glycol) can now be done with rapid and specific enzymatic methods, which makes it possible to diagnose and treat poisoned patients at smaller regional hospitals.
Objective. After Sweden's zero-tolerance law came into force (1 July 1999), the number of cases of driving under the influence of drugs (DUID) submitted by the police for toxicological analysis increased more than 10-fold. This prompted an in-depth investigation into the kinds of drugs used by DUID offenders, whether licit or illicit, and the frequency of their occurrence. Methods. All blood samples from DUID suspects sent by the police for toxicological analysis over a 4-year period (2001-2004) were investigated (N = 22,777 cases). Specimens of blood or urine were subjected to a broad screening analysis by immunoassay methods aimed at detecting amphetamines, cannabis, opiates, cocaine metabolite, and the major benzodiazepines. All positive results from the screening stage were verified by use of more specific analytical methods (e.g., GC-MS, LC-MS, GC-FID, and GC-NPD). Results. Between 80 and 85% of all the blood samples contained at least one banned substance and many contained two or more therapeutic and/or illicit drugs. About 15% of cases were negative for drugs, although these frequently (30-50%) contained ethanol above the legal limit for driving in Sweden, which is 0.20 mg/g (0.02 g%). Amphetamine was the most prominent illicit drug seen in 55-60% of cases either alone or together with other drugs of abuse. Stimulants like cocaine and/or its metabolite were infrequently encountered (1.2% of cases). The next most prevalent illicit drug was cannabis, with positive results for tetrahydrocannabinol (THC) in blood either alone (4%) or together with other psychoactive substances (20%). Morphine, codeine, and/or 6-acetyl morphine were identified in 2% of all DUID suspects, being indicative of heroin abuse. The major prescription drugs identified in blood were benzodiazepines (10%) as exemplified by diazepam, alprazolam, nitrazepam, and flunitrazepam. Drugs for treating insomnia, zolpidem and zopiclone, were also identified in blood samples from DUID suspects over the study period. Other therapeutic agents were encountered in only 1-2% of all cases. Conclusions. The dramatic increase in DUID after the zero-tolerance law came into force probably reflects enhanced police activity and more enthusiasm to apprehend and charge individuals for this offence. Illicit drugs, particularly amphetamine and cannabis, and poly-drug use were predominant compared with use of scheduled prescription drugs. The typical DUID offender in Sweden abuses central stimulants, particularly amphetamine, and has probably done so over many years. Options for treating offenders for their underlying substance abuse problem should be considered instead of the more conventional penalties for drug-impaired driving.
Background: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood-alcohol concentration (BAC) limit for driving is 0.2 mg/g (∼0.02 g%). Methods: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. Results: We found that 44% of individuals (N = 16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88-93%). The mean age of drunken drivers was ∼40 years compared with ∼35 years for driving under the influence of amphetamine, which was the drug identified in 50-60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5 mg/g (∼0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5 mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1-10 times compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently (∼17%) compared with those taking illicit drugs (68%). Conclusions: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem. © 2007 Elsevier Ltd. All rights reserved.
Specimens of blood and other body fluids were obtained at autopsy from all deaths in Sweden classified as suicide covering a 10-year period (N = 11,441 cases). The mean age (+/- standard deviation, SD) of the victims was 51.3 +/- 18.8 years witha clear predominance of males 71%(mean age 51.3 +/- 18.8 years) compared with 29% females (mean age 51.4 +/- 18.9 years). The concentration of ethanol in blood samples was determined in duplicate by headspace gas chromatography and a mean blood-alcohol concentration (BAC) of 0.1 g/L (10 mg/100 mL) was the cut-off used to identify ethanol positive cases. The suicides were coded (ICD-9) as self-poisonings (N = 2462, 22%), hanging (N = 4474, 39%), asphyxia by gas (N = 509, 4.4%), drowning (N = 803, 7.0%), gun shot (N = 1307, 11.4%), fall from height (N = 632, 5.5%), self-inflicted cuts or sharp-force injury (N = 363, 3.1%) and miscellaneous ways (N = 891, 7.8%). On average 34% of all suicide victims in Sweden had consumed alcohol before death, 36% of the males and 31% of the females had a positive BAC. The mean (median) concentration of alcohol in femoral blood for men was 1.34 g/L (1.3 g/L) compared with 1.25 g/L (1.1 g/L) for women. Many victims were heavily intoxicated and the 90th percentiles of the BAC distributions ranged from 2.3 to 2.8 g/L depending on manner of death. Elevated blood-alcohol was most prevalent in poisoning deaths (45%) and gas asphyxia (51%) and least prevalent in falls from height (19%) and sharp-force injury (18%). Toxicological analysis for presence of drugs other than alcohol showed a predominance of paracetamol, SSRI antidepressants, anti-psychotics, sedative-hypnotics, and centrally acting opioids. A host of psycho-social factors drive a person to commit suicide and one of the catalysts is over-consumption of alcohol and acute alcohol intoxication. Heavy drinking leads to a loss of inhibitions, impulsive behaviour, poor judgment and a tendency to take risks, all of which might increase the propensity of predisposed individuals to take their own lives.
Methadone (MTD) is widely used for detoxification of heroin addicts and also in pain management programs. Information about the distribution of methadone between blood, plasma, and alternative specimens, such as oral fluid (OF), is needed in clinical, forensic, and traffic medicine when analytical results are interpreted. We determined MTD and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in blood, plasma, blood cells, and OF by gas chromatography-mass spectrometry (GC-MS) after adding deuterium-labeled internal standards. The analytical limits of quantitation for MTD and EDDP by this method were 20 and 3 ng/mL, respectively. The amounts of MTD and EDDP were higher in plasma (80.4 % and 76.5 %) compared with blood cells (19.6 % and 23.5 %) and we found that repeated washing of blood cells with phosphate-buffered saline increased the amounts in plasma (93.6 % and 88.6 %). Mean plasma/blood concentration ratios of MTD and EDDP in spiked samples (N = 5) were 1.27 and 1.21, respectively. In clinical samples from patients (N = 46), the concentrations of MTD in plasma and whole blood were highly correlated (r = 0.92, p andlt; 0.001) and mean (median) plasma/blood distribution ratios were 1.43 (1.41). The correlations between MTD in OF and plasma (r = 0.46) and OF and blood (r = 0.52) were also statistically significant (p andlt; 0.001) and the mean OF/plasma and OF/blood distribution ratios were 0.55 and 0.77, respectively. The MTD concentration in OF decreased as salivary pH increased (more basic). These results will prove useful in clinical and forensic medicine when MTD concentrations in alternative specimens are compared and contrasted.
This two-part article examines the strengths and weaknesses of various ways of investigating claims of drinking alcohol after driving, commonly known as the hip-flask or glove-compartment defence. In many countries the onus of proof in hip-flask cases rests on the prosecution. With good co-operation from the police and timely sampling of body fluids, such as blood and urine for forensic analysis of ethanol, useful evidence can be mustered to support or challenge the truthfulness of alleged drinking after driving. The person's blood-alcohol concentration (BAC) can be compared with values expected on the basis of the amount of alcohol consumed after driving, according to theoretical Widmark calculations. The actual BAC measured is then adjusted for the additional amount of alcohol consumed in the after-drink. Double blood samples, that is, taking two specimens of venous blood about 30-60 minutes apart and looking at the magnitude and direction of change in BAC provides little or no more information than a single blood specimen. However, the relationship between alcohol in blood and urine is very useful in hip-flask cases whereby the concentration expected in the primary urine is compared with the concentration in the bladder urine voided. The concentration of alcohol determined in a second urine sample collected 30-60 min later gives supporting evidence in hip-flask cases. A graphical method, which entails plotting ethanol concentrations in blood and urine as a function of time provides a robust and practical way to investigate hip-flask defences. In the second part of the review, congener analysis is presented, which entails comparing the concentrations of n-propanol, isobutanol and occasionally other congeners in the alcoholic beverage allegedly consumed after driving with the volatiles present in the suspect's blood and urine determined by headspace gas chromatography.
The second part of this review describes the principles and practice of forensic congener analysis as an alternative way to evaluate claims of drinking alcohol after driving. Congener analysis was developed, perfected and practised in Germany as a way to evaluate hip-flask defences. This kind of defence challenge arises frequently when the drunk driving suspect is not apprehended at the wheel and especially after hit-and-run incidents. Besides ethanol and water, alcoholic beverages contain trace amounts of many other low-molecular substances, known collectively as the congeners, which impart the characteristic smell and taste to the drink. Importantly, the congener profile can be used to identify a particular kind of alcoholic beverage. Forensic congener analysis entails making a qualitative and quantitative analysis of ethanol, methanol, n-propanol and the isomers of butanol in blood and urine from the apprehended driver and comparing the results with the known congener profile of the alcoholic beverage allegedly consumed after driving. Interpreting the results of congener analysis requires knowledge about the absorption, distribution and elimination pattern of the congener alcohols, including their oxidation and conjugation reactions, and any metabolic interactions with ethanol. Complications arise if drinks with widely different congener profiles are consumed or if the same beverage was ingested both before and after driving. Despite these limitations, congener analysis can furnish compelling evidence to challenge or support claims of drinking alcohol after driving.
Background: New legislation aimed at combating driving under the influence of drugs (DUID) in Sweden stipulated zero-concentrations in blood for scheduled substances. DUID suspects (n = 300), with amphetamine as the only psychoactive drug identified in blood, were investigated in relation to age and gender. In a smaller retrospective sample (n = 70) the relationship between clinical tests of impairment were compared with the concentration of amphetamine in blood. Measurements: All forensic blood samples were subjected to a broad toxicological screening analysis by immunoassay methods [enzyme multiplied immunoassay technique/cloned enzyme donor immunoassay (EMIT/CEDIA)] and positive results were verified by gas chromatography-mass spectrometry (GC-MS). The limit of quantitation (LOQ) for determination of amphetamine in blood was 0.03 mg/l. People suspected of being under the influence of drugs were examined by a physician who asked various questions about state of health and use of drugs and also administered simple psychomotor and cognitive tests of impairment. After conducting these tests the physician concluded whether the suspects were not impaired, slightly, moderately or highly impaired by drugs other than alcohol. Findings: Among 300 DUID suspects with amphetamine in blood there were 246 men (82%) and 54 women (18%). Mean age (± SD) of the men was 37.1 ± 8.7 years compared with 35.5 ± 7.1 years for the women (P > 0.05). The frequency distribution of blood amphetamine concentration was positively skewed with mean, median and highest values of 1.0 mg/l, 0.9 mg/l and 7.1 mg/l, respectively. The mean concentrations were slightly higher in the women 1.11 mg/l (median 1.0 mg/l) compared with 0.97 mg/l (median 0.8 mg/l) in the men (P > 0.05). There was a weak but statistically significant correlation between the person's age and the concentration of amphetamine in blood (r = 0.18, P < 0.05). The results of clinical tests of impairment showed no relationship with the concentration of amphetamine in blood according to analysis of variance (P > 0.05). Conclusions: The lack of association between degree of drug influence and the concentration of amphetamine in blood speaks against the notion of introducing concentration per se limits or graded penalties depending on the blood-concentration of this stimulant. Zero-concentration limits or LOQ-limits are a much more pragmatic way to enforce DUID legislation. © 2007 The Author.
Background: Knowledge about the stability of drugs and metabolites in biological fluids is important information when the analytical results are evaluated and interpreted. This study examines changes in blood-ethanol concentration (BEC) during the storage of specimens for up to 12 months at 4°C. Methods: Venous blood samples were taken from drunk drivers in evacuated glass tubes containing sodium fluoride and potassium oxalate as chemical preservatives. The concentrations of ethanol in blood were determined in duplicate by headspace gas chromatography on arrival at the laboratory and again after storage in a refrigerator at 4°C for up to 12 months. Results: The relationship between the standard deviation (SD) of analysis of ethanol at concentration intervals of 0.2 mg/g (BEC) was defined by the linear regression equation SD=0.00243+0.0104 BEC (r=0.99). At a mean BEC of 1.64 mg/g, the SD was 0.019 mg/g which corresponds to a coefficient of variation of 1.1%. The mean decrease in BEC (±SD) between first and second analysis was 0.105± 0.0686 mg/g (t=19.3, d.f.=158, p
[No abstract available]
n/a
This case report describes the police investigation of a road-traffic accident involving a collision at night (01.00 am) between a car and a truck in which a passenger in the car was killed. The driver of the truck was found responsible for the crash although a roadside breath-alcohol test was negative (less than0.1 mg/L breath or 20 mg/100 mL blood). Because of injuries sustained in the crash, the female driver of the car was not breath-tested at the time but was transported to a local hospital for emergency treatment. After swabbing the skin with isopropanol an indwelling catheter was inserted at 01.40 am. A blood sample was taken at 02.10 am and the plasma portion contained 8 mmol/L ethanol according to analysis at the hospital clinical laboratory using a gas chromatographic method. Another blood sample was taken at 05.45 am for analysis of ethanol at a forensic toxicology laboratory, although the result was negative (less than10 mg/100 mL). The police authorities wanted an explanation for the discrepancy between the clinical and forensic laboratory results and inquired whether the driver of the car was above the legal alcohol limit (greater than20 mg/100 mL) at the time of the crash. The scientific basis for converting a plasma-ethanol concentration into a blood-ethanol concentration and back extrapolation of the drivers blood-alcohol concentration (BAC) is explained. The risk of contaminating a blood sample by swabbing the skin with isopropanol is discussed along with the use of alcohol biomarkers (ethyl glucuronide and ethyl sulphate) as evidence of recent drinking.
Methanol has a very simple chemical structure (CH3OH) considering its potential health hazard, including the many poisoning deaths after ingestion. In countries where authentic alcoholic beverages are expensive, restricted, or banned for religious or other reasons, some people resort to purchasing alcoholic drinks made illegally. These clandestine sources of "booze" often contain high concentrations of methanol, added by the perpetrators to enhance potency and increase profits. Although an effective medical treatment for methanol poisoning exists, because most such incidents occur in socially deprived parts of the world, the hospital emergency facilities are scarce and/or inadequate. Trace amounts of methanol (median ~1.0 mg/L) are produced endogenously via certain enzymatic processes, such as one-carbon metabolism. Methanol and methyl esters are also contained in fresh fruits and vegetables as well as in alcoholic beverages. During a period of heavy drinking the blood-methanol concentration (BMC) increases and might surpass 10 mg/L, which is considered a biomarker for alcohol abuse and alcoholism. Methanol itself has a low intrinsic toxicity, but is converted in the body into two highly toxic metabolites, formaldehyde and formic acid. This metabolism is delayed by co-ingestion of ethanol, which creates a latent period of 12-24 h before toxic symptoms develop. Accordingly, when patients are admitted to hospital for diagnosis and treatment, a life-threatening metabolic acidosis has already developed and is irreversible. Symptoms of methanol poisoning include blurred vision, breathlessness, nausea, gastric pains, and acid-base disturbances and deficiency of oxygen in arterial blood. The visual disturbances might even develop into permanent blindness, owing to an interaction of toxic metabolites with the optic nerve. The minimum lethal dose of ethanol in humans is not easy to specify, because most poisonings involve co-ingestion of ethanol, which to some extent protects the patient from toxic sequelae. Effective antidotes for treatment of methanol poisoning are administration of ethanol or the therapeutic drug fomepizole (Antizol®), which is 4-methyl pyrazole (4-MP). Both treatments work by blocking the metabolism of methanol by liver alcohol dehydrogenase (ADH). The metabolic acidosis caused by the accumulation of formic acid in the body is treated with sodium bicarbonate, which helps to normalize pH in the bloodstream. Thereafter, methanol and its metabolites in the blood are removed by hemodialysis. However, the long-term prognosis for survivors of methanol poisoning is not good, because many are elderly males who are in poor health and often suffer from an alcohol-use disorder.
The importance and prestige of a scientific journal is increasingly being judged by the number of times the articles it publishes are cited or referenced in articles published in other scientific journals. Citation counting is also used to assess the merits of individual scientists when academic promotion and tenure are decided. With the help of Thomson, Institute for Scientific Information (Thomson ISI) a citation database was created for six leading forensic science and legal medicine journals. This database was used to determine the most highly cited articles, authors, journals and the most prolific authors of articles in the forensic sciences. The forensic science and legal medicine journals evaluated were: Journal of Forensic Sciences (JFS), Forensic Science International (FSI), International Journal of Legal Medicine (IJLM), Medicine, Science and the Law (MSL), American Journal of Forensic Medicine and Pathology (AJFMP), and Science and Justice (S&J). The resulting forensics database contained 14,210 papers published between 1981 and 2003. This in-depth bibliometric analysis has identified the crème de la crème in forensic science and legal medicine in a quantitative and objective way by citation analysis with focus on articles, authors and journals. © Springer-Verlag 2005.
This article describes a case of driving under the influence of the sedative-hypnotic-anticonvulsant drug chlormethiazole. The suspect, who was a physician, was driving dangerously on a busy highway and caused a traffic collision. When apprehended by the police, the man had bloodshot and glazed eyes and pupil size was enlarged. He could not answer the questions properly and his gait was unsteady. A roadside breath-alcohol screening test was positive but an evidential breath-alcohol test conducted about one hour later was below the legal limit for driving of 0.10 mg/L (10 μg/100 mL or 0.021 g/210 L). Because of the special circumstances of the traffic crash and the man's appearance and behaviour, the police suspected that drugs other than alcohol were involved and obtained a venous blood sample for toxicological analysis. The blood contained 0.23 mg/g alcohol, which is above the legal limit for driving in Sweden 0.20 mg/g (20 mg/100 mL or 0.020 g/100 mL), and codeine was also present at a therapeutic concentration of 0.02 mg/L. The conflict between the clinical signs of impairment and the toxicology report prompted a reanalysis of the blood sample with major focus on sedative-hypnotic drugs. Analysis by capillary GC-NPD identified chlormethiazole at a concentration of 5 mg/L, the highest so far encountered in traffic cases in Sweden. In 13 other impaired driving cases over 10 years the mean (median) and range of concentrations of chlormethiazole were 1.6 mg/L (1.6 mg/L) and 0.3-3.3 mg/L. This case report underscores the need to consider clinical observations and the person's behaviour in relation to the toxicology report when interpreting and testifying in drug-impaired driving cases. © 2005 Elsevier Ireland Ltd. All rights reserved.
Objective. This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. Methods. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Results. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified. Most DUID suspects in Sweden were men (85%) who were poly-drug users combining illicit substances, like amphetamine and/or cannabis, with a prescription medication such as various benzodiazepines. Conclusions. Sweden's zero-concentration limit has done nothing to reduce DUID or deter the typical offender because recidivism is high in this population of individuals (40-50%). Indeed, many traffic delinquents in Sweden are criminal elements in society with previous convictions for drunk and/or drugged driving as well as other offenses. The spectrum of drugs identified in blood samples from DUID suspects has not changed much since the zero-limit law was introduced. Copyright © 2005 Taylor & Francis Inc.
Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century natures pharmaceuticals were all that were available to relieve mans pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal ( coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin., the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history.
Two instances of finding abnormally high concentrations of acetone in urine (0.10 g/dL and 0.052 g/dL) without any measurable amounts of ethanol (< 0.005 g/dL) or isopropanol (< 0.005 g/dL) prompted a survey of the elimination kinetics of isopropanol and its metabolite acetone in humans. In a hospital patient who had ingested denatured alcohol, the elimination half- life (t( 1/2 )) of acetone during detoxification was 27 h and not 3-5 h as reported by other workers. Several other literature reports of individuals who had ingested isopropanol as well as controlled studies after administration of moderate amounts of acetone and/or isopropanol support the notion of a long elimination half-life of 17-27 h for acetone compared with a t( 1/2 ) of 1-3 h for isopropanol.
Aspects of human metabolism of ethanol are reviewed with the main focus on the rate of ethanol clearance from blood in patients suffering from liver cirrhosis. Studies in humans and experimental animals do not support the notion of a slower rate of ethanol metabolism in patients with liver cirrhosis compared with those with normal liver function. The rate of ethanol disappearance from blood in healthy non-alcoholic subjects falls within the range 9-20 mg/dL/h and there is no compelling evidence to suggest that this should be much different in cirrhotic patients.
Reliable information about the elimination rate of alcohol (ethanol) from blood is often needed in forensic science and legal medicine when alcohol-related crimes, such as drunken driving or drug-related sexual assault are investigated. A blood sample for forensic analysis might not be taken until several hours after an offence was committed. The courts usually want to know the suspects blood-alcohol concentration (BAC) at some earlier time, such as the time of driving. Making these back calculations or retrograde extrapolations of BAC in criminal cases has many proponents and critics. Ethanol is eliminated from the body mainly by oxidative metabolism in the liver by Class I isoenzymes of alcohol dehydrogenase (ADH). Ethanol is an example of a drug for which the Michaelis-Menten pharmacokinetic model applies and the Michaelis constant (k(m)) for Class I ADH is at a BAC of 2-10 mg/100 mL. This means that the enzyme is saturated with substrate after the first few drinks and that zero-order kinetics is adequate to describe the declining phase of the BAC profile in most forensic situations (BAC greater than 20 mg/100 mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15 mg/100 mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20 mg/100 mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35 mg/100 mL/h. The slope of the BAC declining phase is slightly steeper in women compared with men, which seems to be related to gender differences in liver weight in relation to lean body mass. The present evidence-based review suggests that the physiological range of ethanol elimination rates from blood is from 10 to 35 mg/100 mL/h. In moderate drinkers 15 mg/100 mL/h remains a good average value for the population, whereas in apprehended drivers 19 mg/100 mL/h is more appropriate, since many of these individuals are binge drinkers or alcoholics. In preparing this article, a large number of peer-reviewed publications were scrutinized. Only those meeting certain standards in experimental design, dose of alcohol and blood-sampling protocol were used. The results presented can hopefully serve as best-practice guidelines when questions arise in criminal and civil litigation about the elimination rate of ethanol from blood in humans.
This article is intended as a brief review or primer about cocaethylene (CE), a pharmacologically active substance formed in the body when a person co-ingests ethanol and cocaine. Reference books widely used in forensic toxicology contain scant information about CE, even though this cocaine metabolite is commonly encountered in routine casework. CE and cocaine are equi-effective at blocking the reuptake of dopamine at receptor sites, thus reinforcing the stimulant effects of the neurotransmitter. In some animal species, the LD50 of CE was lower than for cocaine. CE is also considered more toxic to the heart and liver compared with the parent drug cocaine. The plasma elimination half-life of CE is similar to 2 h compared with similar to 1 h for cocaine. The concentrations of CE in blood after drinking alcohol and taking cocaine are difficult to predict and will depend on the timing of administration and the amounts of the two precursor drugs ingested. After an acute single dose of cocaine and ethanol, the concentration-time profile of CE runs on a lower level to that of cocaine, although CE is detectable in blood for several hours longer. A strong case can be made for adding together the concentrations of cocaine and CE in forensic blood samples when toxicological results are interpreted in relation to acute intoxication and the risk of an overdose death.
This article reviews how the Nordic countries of Denmark, Finland, Norway, and Sweden enforce their legislation pertaining to driving under the influence of alcohol and/or other impairing drugs. The evidence necessary for a successful prosecution of traffic offenders has undergone radical changes over the past 50 years. The once widely used clinical tests of impairment are no longer a major element of the prosecution case and a physician is more seldom required to examine apprehended drivers and document any clinical signs and symptoms of alcohol and/or drug influence. These clinical tests have been superseded by results derived from a comprehensive toxicological analysis of psychoactive substances in samples of the driver's blood. The current statutory limits of blood-alcohol concentration (BAC) are among the lowest in the world: Norway and Sweden (0.20 g/kg) and Denmark and Finland (0.50 g/kg). Results from using evidential quality breath-alcohol instruments are accepted as evidence in drunk-driving cases and this has necessitated setting statutory breath-alcohol concentration (BrAC) limits. Laws dealing with driving under the influence of drugs (DUID) other than alcohol have also been updated and made more pragmatic for prosecution of traffic offenders. In Finland and Sweden zero-tolerance laws exist, making it illegal to drive with any quantifiable amount of a scheduled drug in the driver's blood. Prescription drugs are exempt from this zero-tolerance mandate provided the medication was used in accordance with a physician's ordination. Lacking a valid prescription or if there is a supratherapeutic concentration of the drug in blood, this will lead to a prosecution for DUID. In Denmark and Norway threshold concentration limits have been established for many psychoactive drugs, both licit and illicit. After these stricter laws for DUID were introduced, the number of suspects apprehended by the police per year increased by as much as tenfold in some Nordic countries. There is increasing evidence that many traffic delinquents in the Nordic countries suffer from a substance-use disorder, because repeat-offending is a common occurrence. This suggests that some type of treatment and rehabilitation program might be more beneficial compared with conventional penalties for people arrested for DUI and/or DUID.
This article presents review and opinion about the use and abuse of journal impact factors for judging the importance and prestige of scientific journals in the field of forensic science and toxicology. The application of impact factors for evaluating the published work of individual scientists is also discussed. The impact factor of a particular journal is calculated by dividing the number of current year citations to a journal's articles that were published in the previous 2 years by the total number of citable items (articles and reviews) published in the same 2-year period. Journal impact factors differ from discipline to discipline and range from 0 for a journal whose articles are not cited in the previous 2 years to 46 for a journal where the average recent article is cited 46 times per year. The impact factor reflects the citation rate of the average article in a journal and not a specific article. Many parameters influence the citation rate of a particular journal's articles and, therefore, its impact factor. These include the visibility and size of the circulation of the journal including availability of electronic formats and options for on-line search and retrieval. Other things to consider are editorial standards especially rapid and effective peer-reviewing and a short time lag between acceptance and appearance in print. The number of self-citations and citation density (the ratio of references to articles) and also the inclusion of many review articles containing hundreds of references to recently published articles will boost the impact factor. Judging the importance of a scientist's work based on the average or median impact factor of the journals used to publish articles is not recommended. Instead an article-by-article citation count should be done, but this involves much more time and effort. Moreover, some weighting factor is necessary to allow for the number of co-authors on each article and the relative positioning of the individual names should also be considered. Authors should submit their research results and manuscripts to journals that are easily available and are read by their peers (the most interested audience) and pay less attention to journal impact factors. To assess the true usefulness of a person's contributions to forensic science and toxicology one needs to look beyond impact factor and citation counts. For example, one might consider whether the articles contained new ideas or innovations that proved useful in routine forensic casework or are widely relied upon in courts of law as proof source. ⌐ 2003 Elsevier Science Ireland Ltd. All rights reserved.
The Journal of Analytical Toxicology (JAT) recently celebrated its 25th anniversary as an international periodical devoted to publishing scholarly articles in the field of analytical and forensic toxicology. Over the years many important papers spanning the entire field of chemical toxicology have appeared in JAT. One way to assess the usefulness of these papers is by looking at the number of times they subsequently become cited in the reference lists of papers published in other peer-reviewed journals including JAT itself (self-citations). The Thomson Institute for Scientific Information (ISI), headquartered in Philadelphia, PA, has produced a citation database containing all JAT articles published between 1981 through 2003 (N = 2254). This database was used to gather information about the most prolific authors of articles appearing in JAT, the most highly cited articles, the inter-relationships between co-authors, and the countries where the work originated. The person listed most frequently as an author was E.J. Cone, who authored or co-authored 69 papers that attracted a total of 1432 citations, giving a citation impact of 20.76. However, the most highly cited article in JAT was a solo-author work from 1981 by M.E. Jolley describing a fluorescence polarization immunoassay for the analysis of therapeutic drugs in plasma, which was cited 184 times. Working and writing in teams can boost the output of scientific articles as exemplified by the Institut de Médecine Légale in Strasbourg with P. Kintz as the driving force. Kintz and his associates produced the most collaborative work published in JAT. Citation analysis is being increasingly used to evaluate the importance of scientific articles and the journals where these works are published (e.g., impact factors). This article has identified JAT's scientific elite as evidenced by the most prolific authors and the most highly cited papers.
Alcohol tops the list of psychoactive substances encountered in police investigations of crimes such as mugging, murder, sexual assault, and especially impaired driving. Accordingly, the need often arises to interpret a person`s blood-alcohol concentration (BAC) in relation to the degree of alcohol influence and the amount of alcohol consumed. Such calculations are usually done with the aid of so-called “know your limit” or blood-alcohol charts, and more recently, several computer programs have been developed for this purpose.
This article presents a review of medicolegal investigations of drug-related deaths among various Hollywood celebrities and popular music icons. The movie stars included: Marilyn Monroe, River Phoenix, John Belushi, Chris Penn, Heath Ledger and Philip Seymour Hoffman. The musicians are exemplified by Elvis Presley, Janis Joplin, Jimi Hendrix, Keith Moon, Sid Vicious, Kurt Cobain, Amy Winehouse, Michael Jackson, Whitney Houston and Prince. The tragic drug-related death of Anna Nicole Smith, a sex-symbol and Playboy model, is also included. The illicit drugs mainly responsible for the fatalities were heroin and/or cocaine or a mixture of the two narcotics. Some of the celebrity deaths were caused by inappropriate use of prescription medications, mostly combined influences of one or more benzodiazepine together with an opiate or opioid pain medication. Polypharmacy increases the risk of adverse drug events and this sometimes causes a sudden and unexpected death. As tolerance to the pharmacological effects of drugs develop, the amounts taken (the dose) are increased, which enhances the risk of a fatal drug-drug interaction. Ethanol was implicated in some of the celebrity deaths, which underscores the dangers of excessive drinking when taking centrally acting drugs. In the case of Amy Winehouse, a talented jazz singer, she died from acute alcohol poisoning, because ethanol was the only psychoactive drug identified in postmortem blood. © 2017 Société Française de Toxicologie Analytique