• Energy Research
• SE close
• Forensic Science International close

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 suspect's 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 2-10mg/100mL. 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>20mg/100mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15 mg/100mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20mg/100mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35 mg/100mL/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/100mL/h. In moderate drinkers 15 mg/100mL/h remains a good average value for the population, whereas in apprehended drivers 19 mg/100mL/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.

Hand-held electronic breath-alcohol analyzers are widely used by police authorities in their efforts to detect drunken drivers and to improve road-traffic safety. Over a three month period, the results of roadside breath-alcohol tests of drivers apprehended in Finland were compared with venous blood alcohol concentration (BAC). The mean (median) time between sampling blood and breath was 0.71h (0.58h) with a range from 0 to 6h. Some hand-held instruments gave results as the concentration of alcohol in breath and were converted into BAC assuming a blood-breath alcohol ratio (BBR) of 2260. The mean venous BAC (1.82g/kg) in traffic offenders was higher than the result predicted by the hand-held breath analyzers (1.72g/kg). In 1875 roadside tests, the relationship between venous BAC (x) and BrAC (y) was defined by the regression equation y=0.18+0.85x. The coefficients show both a constant bias (y-intercept 0.18g/kg) and a proportional bias (slope=0.85). The residual standard deviation (SD), an indicator of random variation, was ±0.40g/kg. After BAC results were corrected for the time elapsed between sampling blood and breath, the y-intercept decreased to 0.10g/kg and 0.004g/kg, respectively, when low (0.1g/kg/h) and high (0.25g/kg/h) rates of alcohol elimination were used. The proportional bias of 0.85 shows that the breath-alcohol test result reads lower than the actual BAC by 15% on average. This suggests that the BBR of 2260 used for calibration should be increased by about 15% to give closer agreement between BAC and BrAC. Because of the large random variation (SD±0.40g/kg), there is considerable uncertainty if and when results from the roadside screening test are used to estimate venous BAC. The roadside breath-alcohol screening instruments worked well for the purpose of selecting drivers above the statutory limit of 0.50g/kg.

In Sweden, ca. 25% of unnatural deaths ascribed to self-inflicted injury are finally recorded as 'undetermined suicide' (abbreviated UMSA), i.e. the forensic pathologist has not been able to establish whether the fatality was an accident or a suicide. In the present study, a series of UMSA cases was investigated with the aims to study the impact of immigrant status, and alcohol abuse on the occurrence of this forensic diagnosis on the mode of death. The alcohol issue was addressed by focusing on blood alcohol concentrations at autopsy (BAC) and post mortem signs of alcohol-related organ pathology. The results can be summarised as follows: Positive BAC occurred at an equal rate in the UMSA group and in definite suicides, i.e. about 45%. Among non-Swedish UMSA victims positive BAC was more common (50%) than among the Swedish (41%), whereas no difference was found in the definite suicide group. The level of BAC at autopsy was significantly higher in Finnish immigrants than in other ethnic groups. Organic signs of chronic alcohol abuse were found in 13 of 40 cases testing positive for BAC; thus, presence of alcohol at autopsy may reflect incidental intake rather than habitual overconsumption.

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (i.v.) infusion over 45 min. After removing a mean fluid volume of 2.46 +/- 0.48 liters (+/- SD), span 1.76-3.43 liters by hemodialysis, the same subjects received a second i.v. infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05-1.10). The rate of ethanol disappearance from blood (beta-slope) was faster (0.185 +/- 0.013 versus 0.157 +/- 0.022 g/l/h), the Co value was higher (0.79 +/- 0.08 versus 0.73 +/- 0.10 g/l) and the apparent volume of distribution (Vd) of ethanol was lower (0.507 +/- 0.049 versus 0.558 +/- 0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P < 0.001) before dialysis (88.6 +/- 1.97 g/100 ml) compared with after dialysis (87.4 +/- 2.01 g/100 ml). The higher Vd for ethanol and lower Co as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (beta-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.

We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case.

Reference concentrations of drugs in post-mortem femoral blood furnishes useful information when poisoning (intoxication) deaths are investigated. However, few publications compare the concentrations of drugs in single-drug fatalities with multi-drug intoxications. This article attempts to fill this gap in knowledge.We searched a national forensic toxicology database (TOXBASE) and found N=13,963 deaths attributed by pathologists to intoxication by drugs (poisoning). The manner of death, whether accidental, suicidal or undetermined intent, was also available. To compare drug concentrations in living and deceased persons, we used information from people arrested for driving under the influence of drugs (DUID).The percentage of drug intoxication deaths classified as undetermined intent decreased and accidental overdose deaths increased during the study period. In 2010 manner of death was considered accidental, suicidal or undetermined, in 41%, 30% and 28% of victims, respectively. Most of the deceased had taken multiple drugs (mean three drugs/case) and four or more drugs were identified in 35% of deaths. In single-drug fatalities ethanol (1585), morphine (114), citalopram (28), propoxyphene (51), flunitrazepam (70), propiomazine (46), tramadol (20) and zopiclone (15) were most prevalent. Alprazolam and diazepam were common findings in multi-drug deaths, although these benzodiazepines were rarely encountered in mono-drug intoxication deaths. Median blood concentrations were appreciably higher (2-10 fold) in single-drug fatalities compared with multi-drug deaths. The blood concentrations in DUID suspects were mostly lower than in the multi-drug poisoning deaths.This compilation of femoral blood concentrations of drugs in poisoning deaths provides a useful reference material, because we have distinguished between mono-drug intoxication deaths and poisoning with multiple-drugs.

Results of toxicological analysis of blood and urine specimens from 1806 female victims of alleged non-consensual sexual activity are reported. After making contact with the police authorities, the victims were examined by a physician for injuries and biological specimens were taken for forensic toxicology and other purposes (e.g. DNA). Urine if available or otherwise on an aliquot of blood after protein precipitation was screened for the presence of drugs by enzyme immunoassay methods (EMIT/CEDIA). All positive results from screening were verified by more specific methods, involving isotope dilution gas chromatography-mass spectrometry (GC-MS) for illicit drugs. A large number of prescription drugs were analyzed in blood by capillary column gas chromatography with a nitrogen-phosphorous (N-P) detector. Ethanol was determined in blood and urine by headspace gas chromatography and concentrations less than 0.1g/L were reported as negative. The number of reported cases of alleged sexual assault was highest during the warmer summer months and the mean age of victims was 24 years (median 20 years), with approximately 60% being between 15 and 25 years. In 559 cases (31%) ethanol and drugs were negative. In 772 cases (43% of total) ethanol was the only drug identified in blood or urine. In 215 cases (12%) ethanol occurred together with at least one other drug. The mean, median and highest concentrations of ethanol in blood (N=806) were 1.24 g/L, 1.19 g/L and 3.7 g/L, respectively. The age of victims and their blood-alcohol concentration (BAC) were positively correlated (r=0.365, p<0.001). Because BAC decreases at a rate of 0.10-0.25 g/(Lh), owing to metabolism the concentration in blood at time of sampling is often appreciably less than when the crime was committed several hours earlier. Licit or illicit drugs were identified in blood or urine in N=262 cases (15%). Amphetamine and tetrahydrocannabinol were the most common illicit drugs at mean (median) concentrations in blood of 0.22 mg/L (0.1mg/L) and 0.0012 mg/L (0.0006 mg/L), respectively. Among prescription drugs, sedative-hypnotics such as diazepam and zopiclone were common findings along with SSRI antidepressants and various opiate analgesics. Interpreting the analytical results in terms of voluntary vs. surreptitious administration of drugs and the degree of incapacitation in the victim as well as ability to give informed consent for sexual activity is fraught with difficulties.

The prevalence of dextroproxyphene (DXP) in the total medico-legal autopsy material in Sweden during 1992 to 1996 was examined. Simultaneous findings of paracetamol and alcohol in the blood were considered in the analyses. DXP in peripheral blood was found in 1782 (7.5%) of the 23,691 cases analysed during 1992-1996. The autopsy prevalence of DXP increased by 25% from 1992 to 1996. The mean blood DXP concentration was 1.62 micrograms/g (the blood level of DXP after a therapeutic dose is 0.05-0.75 microgram/g). The blood DXP level was or = 0.75 microgram/g in 835 cases. The cases or = 50 years (1.04 micrograms/g). Paracetamol in the blood was found in 53% of the DXP cases (mean 75.0 micrograms/g; therapeutic level 2.5-25 micrograms/g) and alcohol in 43% (mean level 0.14%). According to the death certificates 54% (956) died from fatal poisoning. Among these, 74% (707) showed a blood DXP concentration > or = 0.75 microgram/g. Other Scandinavian countries, Denmark and Norway have reduced the rate of fatal DXP poisonings through government regulations for prescription. As the defined daily dose/1000 inhabitants during a 12-month period (DDD) of DXP preparations in Sweden (14.4 in 1996) is six times as high as in Denmark and nine times as high as in Norway, introduction of similar regulations in Sweden should be considered.

Determinations of blood cyanide and carboxyhemoglobin concentrations were performed in 18 victims found dead in buildings after fires during a 2-year period. The results indicated that 50% of the victims had been exposed to toxic levels of hydrogen cyanide and 90% to toxic levels of carbon monoxide. Lethal concentrations of carbon monoxide were found in 83% of the victims. In one case a lethal blood cyanide but a non-toxic blood carboxyhemoglobin value was found. It is concluded that carbon monoxide appears to be more important than hydrogen cyanide as a toxic agent in the fire atmosphere, but cyanide poisoning without carbon monoxide poisoning may, under certain circumstances, be the cause of death in fire victims.