Alcohol study on blood concentration estimation: Reliability and applicability of Widmark formula on Chinese male population

Widmark formula suggests estimating blood alcohol concentration level (BAC) on a given amount of alcohol administrated with knowledge of subject’s body weight and sex. The idea has been referenced extensively in forensic science with application in drink driving prosecution. A sample of Chinese subjects was collected in the drinking experiment, and in this study we mainly focus on the verification of the validity of Widmark formula on Chinese male population. A promising result is obtained where the extrapolated BAC measurement is directly proportional to the amount of alcohol administrated, and inversely to the subject’s body weight. The results noted in the general linear model is further supported by the nonlinear regression analysis and a concordant argument reaches by deploying the concept to the BAC level attained at peak.     

Evaluating alleged drinking after driving--the hip-flask defence. Part 1. Double blood samples and urine-to-blood alcohol relationship

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.     

BAK-AAK-Quotient im Konzentrationsbereich von 0,5‰ (0,25 mg/l Ausatemluft) Eine Trinkversuchserie mit dem geeichten Atemalkoholtestgerät Alcotest 7110 MK III A (Österreich-Ausführung)

In this study the analytical performance of the breath alcohol analyser Alcotest MK III A from Dräger was evaluated in the concentration range of 0.25 mg/l to collect data for the determination of the blood alcohol-breath alcohol (BAC-BrAC) quotient. This breath testing device has been approved for use in Austria since 1997 and differs in some technical aspects from the Alcotest 7110 MK III Evidential, which is approved for use in Germany. In 32 controlled experiments the BAC and BrAC of 139 participants were determined simultaneously 30 min after the last consumption of alcohol. The measured BAC and BrAC values ranged between 0.14 and 1.72‰ (g/l), and 0.05 and 0.78 mg/l, respectively. A conversion factor (CF) between BAC and BrAC was determined from these data pairs with a minimum of 1,380 and a maximum 2,720 and a mean value of 2,062. Due to the large variability of the CF, analysis of BAC is preferable to using conversion calculations from a forensic point of view. According to our data, if only BrAC values are available a CF ranging from 1,631 (min) and 2,493 (max) can be used to convert BrAC to BAC with a statisticl significance of 95%.     

The use of an alcometer in clinical forensic practice

Forensic physicians are at times required to provide a professional opinion on a person's degree of intoxication through alcohol, particularly with regard to fitness for interview by the police. Inherent to these assessments is an estimation of the blood alcohol concentration (BAC). Most forensic physicians rely on taking a history regarding recent alcohol consumption and a clinical assessment to estimate the BAC. We report a study in which the BAC of 118 detainees was estimated and compared with the BAC measured by an alcometer. Our estimations were accurate in 66% of cases. Most errors resulted from underestimating the BAC. Additionally, we attempted to determine fitness for interview using a single measurement of the BAC without a clinical assessment. 19% of those who were assessed as unfit for interview had a BAC of less than the UK legal limit for driving (currently 80 mg%) and 37% considered fit, had a BAC above that level. We conclude that the routine use of alcometers would enhance the practice of forensic medicine but could not replace its role in the assessment of levels of alcohol intoxication.     

Comparison of two methods to assess PAEE during six activities in children

PURPOSE: The purpose of this study was to compare the accuracy of physical activity energy expenditure (PAEE)-prediction models using accelerometry alone (ACC) and accelerometry combined with heart rate monitoring (HR+ACC) to estimate PAEE during six common activities in children (lying, sitting, slow and brisk walking, hop-scotch, running). Three PAEE-prediction models derived using the current data, and five previously published prediction models were cross-validated to estimate PAEE in this sample. METHODS: PAEE was assessed using ACC, HR+ACC, and indirect calorimetry during six activities in 145 children (12.4 +/- 0.2 yr). One ACC and two HR+ACC PAEE-prediction models were derived using linear regression on data from the current study. These three new models were cross-validated using a jackknife approach, and a modified Bland-Altman method was used to assess the validity of all eight models. RESULTS: PAEE predictions using the one ACC and two HR+ACC models derived in the current study correlated strongly with measured values (RMSE = 97.3-118.0 J.min.kg). All five previously published models agreed well overall (RMSE = 115.6-245.3 J.min.kg), but systematic error was present for most of these, to a greater extent for ACC. CONCLUSIONS: ACC and HR+ACC can both be used to predict overall PAEE during these six activities in children; however, systematic error was present in all predictions. Although both ACC and HR+ACC provide accurate predictions of overall PAEE, according to the activities in this study, PAEE-prediction models using HR+ACC may be more accurate and widely applicable than those based on accelerometry alone.     

A regression model applied to gender-specific ethanol elimination rates from blood and breath measurements in non-alcoholics

As elimination rates for alcohol are suggested to be gender specific, a novel regression model has been applied to estimate these rates for both men and women using experimentally measured data from 81 female and 96 male volunteers described in previous papers. Breath alcohol measurements were done with the Alcotest 7110 Evidential device and were coupled with concomitant sampling of venous blood. Statistical analyses involved use of a mixed linear model for blood alcohol concentration (BAC) and breath alcohol concentration (BrAC), respectively. The model takes regression lines for each test subject into account with an individual starting value (2 h after the end of drinking) and with an individual alcohol elimination rate per hour (coincidental effects). Further, the data was modeled so that an average alcohol elimination rate per hour could be estimated separately for both genders (constant effects). This enables us to methodically correctly estimate the back calculation. The elimination rates β ₆₀, which can be used for minimum and maximum back calculations for the BAC, were 0.115 g/kg/h and 0.260 g/kg/h, respectively, for women and 0.096 g/kg/h and 0.241 g/kg/h, respectively, for men. These figures widely deviate from gender-unspecific values commonly used in Germany (0.1 and 0.2 g/kg/h, respectively). The corresponding values for the BrAC were 0.061 mg/l/h and 0.124 mg/l/h for women and 0.049 mg/l/h and 0.112 mg/l/h for men. The probability of an over- or underestimation of the abovementioned extreme values is 0.3% in each case.     

Pharmacokinetic analyses using absorption kinetics in low-alcohol dose cases of drunken driving

In Japan, low-alcohol dose cases of drunken driving, where drivers drink just before getting behind the wheel, are increasing for expert witnesses since the penalties for drunken driving have become stricter. Widmark’s equation has generally been used for the pharmacokinetic analysis of blood alcohol concentration, which encompasses the one-compartment model with zero-order elimination kinetics but ignores absorption kinetics. We therefore propose that the formula might not be applicable to the analysis of low-alcohol dose cases of drunken driving because the issue is focused on the absorption phase. In this paper, we present two representative low-alcohol dose cases, which were analyzed using the one-compartment model with first-order absorption and zero-order elimination kinetics. This formula is thought to be more suitable and useful for medicolegal practice than Widmark’s formula.     

Computer simulation analysis of blood alcohol

A mathematical model using an iterative algorithm based on the Widmark formula is used to simulate a continuous spectrum of the expected blood alcohol concentration from start of alcohol dosage to time of specific event in numerical and graphic form. Absorption is based on flexible first order rates with provision for an optional good-fit model of the delaying effect of food. Elimination is based initially on selectable zero order rates followed by first order kinetics at low blood alcohol concentrations. A correlation coefficient of 0.94 was obtained in comparisons of projected to observed blood alcohol concentrations. A measurement of the area under the curve is provided. The software program utilizing the algorithm is suitable for forensic and clinical applications.     

Mathematical models for predicting G-duration tolerances

Mathematical models that predict fatigue-based G-duration tolerances for relaxed and straining subjects are developed and validated using published data. These models are based on regression analysis calculations using published G-duration tolerance data of relaxed subjects exposed to 3-5 G and subjects exposed to 6-9 G using an anti-G suit and performing the anti-G straining maneuver. These G-duration models are derived from published G-level tolerance models based on intravascular hydrostatic pressures and physiologic responses to maximum voluntary contractions (MVC%). Included in the validation of these models are the baroreceptor and muscle contraction cardiovascular reflexes that support arterial BP. A basic energy pool that supports a G-duration of 140 s for G exposures > 5 G is theorized. Because of the long duration of sustained G exposures in these models, the physiologic dynamics involved in predicting straining G-duration tolerances, are identified and validated using different time periods, i.e., Phases I and II. These models, based on sustained G exposures to a constant G level are also applicable to exposures of variable G levels known as simulated aerial combat maneuver (SACM) G-profile tolerances. G-duration tolerances > 9 G are predicted using these models for subjects using reclined-seat backs and positive pressure breathing.     

Pilots' knowledge of blood alcohol levels and the 0.04% blood alcohol concentration rule

A national sample of licensed pilots was surveyed regarding their knowledge of the Federal Aviation Administration's (FAA) 0.04% blood alcohol concentration (BAC) limit, the relationship between the number of drinks and BAC, and the manner in which BAC decays with time. A majority of the 1039 respondents were unaware of the 1985 0.04% BAC rule change. In addition, many lacked an understanding of the relationship between the amount of alcohol consumed and the resulting BAC, and of the rate at which BAC decays. The number of drinks necessary to raise BAC to specific levels was frequently overestimated, and the amount of time necessary for BAC to decay was frequently underestimated. These errors were more pronounced for moderate and heavy drinkers than for abstainers and infrequent drinkers. These results suggest that pilots could have difficulty if they attempt to use the 0.04% BAC value as a guide to safety in their flying activities.     

Radiobiological dose calculation parameters for cervix cancer brachytherapy: A systematic review

The GEC-ESTRO recommendation in cervical cancer treatment planning, including external beam radiotherapy and brachytherapy boosts, is to use radiobiological dose calculations. Such calculations utilize the linear-quadratic model to estimate the effect of multiple cellular response factors and dose delivery parameters. The radiobiological parameters utilized in these calculations are literature values estimated based on clinical and experimental results. However, the impact of the uncertainties associated with these parameters is often not fully appreciated. This review includes a summary of the radiobiological dose calculation (for both high-dose-rate and pulsed-dose-rate brachytherapy boost treatments) for cervical cancer and a compilation of the reported values of the associated parameters. As discrepancies exist between conventionally recommended and published values, equivalencies between current brachytherapy boosts may be imprecise and could create underappreciated uncertainties in the radiobiological dose calculations. This review highlights these uncertainties by calculating the radiobiological dose delivered by the brachytherapy boost when assuming different radiobiological parameter values (within the range reported by previous research). Furthermore, conventional treatment planning does not consider the effects of proliferation of the tumor over the treatment time, which can significantly decrease its radiobiological dose and can introduce an additional variance of over 7 Gy₁₀. Further investigation of uncertainties in parameter values and modifications of current dose models could improve the accuracy of radiobiological dose calculation.     

Treffsicherheit der Berechnung der Tatzeitblutalkoholkonzentration in Nachtrunkkonstellationen

Background

The calculation of a detectable minimum or maximum blood alcohol concentration (BAC) in the legal sense follows rules based on the basic principle of in dubio pro reo. In traffic law the question of the minimum detectable BAC is often asked in a situation concerning an irrefutable hip flask defence. In this situation the legal principle of in dubio pro reo currently requires the extreme upper and lower values to be included in the calculation, even if this is very problematic from a pharmacokinetic aspect.

Aim

The study aimed to estimate the accuracy of BAC calculations in hip flask defence constellations.

Material and methods

Drinking experiments were carried out with 55 volunteer subjects to simulate a hip flask defence constellation. In group 1 (n?=?32) a large amount of alcohol was drunk before the theoretical offence followed by a small amount of alcohol after the event and in group 2 (n?=?23) a small amount of alcohol was drunk before the theoretical offence followed by a large amount of alcohol after the event. In group 1 there was a time lapse of approximately 60 min between drinking before and after the theoretical event and of 30 min between the two alcohol intake times in group 2. Within this lapse of time, a particular time for the alleged offence was defined shortly before the start of the second alcohol intake. A back calculation to the theoretical time of the offence was performed starting from two fictive points in time of blood sampling of 120 min after the last alcohol intake before the offence occurred. The results of the back calculation were compared with the values measured at the theoretical time of the event.

Results

In most cases the estimated results of the back calculation were approximately 0.05 g alcohol/kg body weight lower than the measured values; however, in three male subjects the back calculation was higher than the analysis values.

Conclusion

The well-established equations for back calculation of the BAC at the time of the event lead to false estimations where resorption is greatly prolonged or where diffusion is drastically affected. However, overestimation can be justified due to a strong resorptive phase and in cases of extreme underestimation this at least does not lead to a disadvantage for the affected individual. The comparatively few miscalculations do not fundamentally cast doubt on the basic principles for estimating the amount of alcohol consumed after an offence. It could be shown that this concerns cases where the amount of alcohol present in the subject’s body, formulated according to current legislation, would have led to a clearly higher blood alcohol concentration irrespective of the alcohol consumed after the offence.     

Determination of phosphatidyl ethanol (PEth) 16:0/18:1 in dried blood samples of drivers involved in traffic accidents: A pilot study

In routine forensic toxicology practices, blood alcohol concentration (BAC) levels are measured in traffic accidents that ended up in emergency departments. Nevertheless, since the elimination of ethanol from the blood is fast and the detection time is short, BAC cannot indicate the occurrence of chronic excessive alcohol consumption. Phosphatidylethanol (PEth) is a unique ethanol direct biomarker that occurs only in the presence of phospholipase D enzyme in erythrocyte membranes during alcohol intake, and it indicates alcohol intake.In this study, both whole blood and dried blood samples were collected from 50 patients who were admitted to Cukurova University Hospital Emergency Department due to a traffic accident. While studying BAC in whole blood samples, PEth 16:0/18:1 analysis was performed on dried blood samples by LC-MS/MS.According to the BAC (50 mg/dL) value, the legal limit in Turkey, the optimal threshold PEth 16:0/18:1 value was set as 160 ng/mL and over. This study determined that 15 people with above PEth 16:0/18:1 concentrations above 160 ng/mL were classified as excessive alcohol consumption.The data obtained in this study showed a positive correlation between BAC and PEth concentration when driving under the influence of ethanol.     

The blood alcohol concentration at post-mortem in 175 fatal cases of alcohol intoxication

The mean blood alcohol concentration (BAC) in 175 fatal cases of acute alcohol intoxication was found to be 355 mg/100 ml. This figure is less than that quoted in many standard textbooks on forensic medicine. The BAC in fatal cases of acute alcohol intoxication complicated by aspiration was lower than in those cases where there was no evidence of aspiration at autopsy. In those individuals with a previous history of alcohol abuse the BAC causing death was found to be significantly higher than in those without a history of prolonged heavy alcohol consumption suggesting that a degree of tolerance to the effects of alcohol may be induced.     

COMKAT: compartment model kinetic analysis tool.

Compartment models are the basis for most physiologically based quantification of nuclear medicine data. Although some software packages are available for this purpose, many are expensive, run on relatively few types of computers or are of limited capability, and cannot be extended because of the unavailability of source code. Consequently, institutions with modeling expertise often develop software for themselves, which has the disadvantages of lack of standardization and possible replication of effort. Therefore, general-purpose compartment-modeling software distributed with source code would be a welcome resource for the nuclear medicine community. METHODS: We formulated a mathematic framework within which compartment models containing unimolecular and bimolecular (receptor saturation) kinetics can be described. We implemented this framework within MATLAB and call the resultant software COMKAT (Compartment Model Kinetic Analysis Tool). RESULTS: COMKAT simplifies the process of defining and solving standard blood flow, 18F-FDG, and receptor models as well as models of a user's own design. In particular, COMKAT automatically defines and implements state, analytic sensitivity, and Jacobian equations. Given these, COMKAT can perform simulations in which model outputs are solved for specified parameter values, thereby allowing the user to predict how sensitive data are to these parameters. In addition, COMKAT can be used to estimate values for the parameters by fitting model output to experimental data. COMKAT is equipped with command-line and graphic user interfaces from which the user can access these features. Examples of these applications are presented along with validation and performance summaries. CONCLUSION: COMKAT is a useful software tool and is available without cost to researchers, at www.nuclear.uhrad.com/comkat.     

Ultra-rapid rate of ethanol elimination from blood in drunken drivers with extremely high blood-alcohol concentrations

The rate of alcohol elimination from blood was determined in drunken drivers by taking two blood samples about 1 h apart. These cases were selected because the individuals concerned had reached an extremely high blood-alcohol concentration (BAC) when they were apprehended. This suggests a period of continuous heavy drinking leading to the development of metabolic tolerance. Use of double blood samples to calculate the elimination rate of alcohol from blood is valid provided that drunken drivers are in the post-absorptive phase of the BAC curve, the time between sampling is not too short, and that zero-order elimination kinetics operates. Evidence in support of this came from other drunken drivers in which three consecutive blood samples were obtained at hourly intervals. The mean BAC (N = 21) was 4.05 g/l (range, 2.71–5.18 g/l), and the average rate of alcohol elimination from blood was 0.33 g l⁻¹ h⁻¹ with a range of 0.20–0.62 g l⁻¹ h⁻¹. The possibility of ultra-rapid rates of ethanol elimination from blood in drunken drivers having extremely high BAC deserves to be considered in forensic casework, e.g., when retrograde extrapolations and other blood-alcohol calculations are made. The mechanism accounting for more rapid metabolism is probably related to induction of the microsomal enzyme (CYP2E1) pathway for ethanol oxidation, as one consequence of continuous heavy drinking. However, the dose of alcohol and the duration of drinking necessary to boost the activity of CYP2E1 enzymes in humans have not been established.     

The influence of alcohol and aging on radio communication during flight

This study finds that alcohol and pilot age impair radio communication during simulated flight. Young (mean age 25 years) and older (mean age 42 years) pilots flew in a light aircraft simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and flew after reaching 0.04% BAC, after reaching 0.10% BAC, and then 2, 4, 8, 24, and 48 h after they stopped drinking at 0.10% BAC. They flew at the same times in the placebo condition. Alcohol and age impaired communication-based and overall flying performance during and immediately after drinking. Most important, alcohol and age cumulatively impaired performance, since older pilots were more impaired by alcohol. Notably, performance was as impaired 2 h after reaching 0.10% BAC as it was at 0.10% BAC. Moreover, overall performance was impaired for 8 h after reaching 0.10% BAC.     

Pilot alcohol violations reported in U.S. newspapers, 1990-2006

INTRODUCTION: Alcohol violations by airline pilots are rare yet remain a public concern. Such incidents often generate widespread news coverage. This study examines the frequency and characteristics of alcohol violation incidents involving airline pilots reported in U.S. newspapers. METHODS: The database of Lexis-Nexis, which contains full-text articles for over 350 newspapers, was searched to identify alcohol violation incidents involving airline pilots in the U.S. between January 1990 and June 2006. Information pertaining to the pilot, flight, blood alcohol concentration (BAC), and consequence was ascertained for each incident based on the newspaper coverage. RESULTS: During the study period, newspapers reported on a total of 13 incidents of alcohol violations involving 17 pilots. All but two of the incidents occurred during January 2002 through June 2006. The majority (85%) of the incidents were first identified by airport personnel, such as security screeners, based on suspicion of alcohol use by the pilot. Subsequent alcohol testing revealed a mean BAC of 90 mg/dL (ranging from 10 mg x dL(-1) to 182 mg x dL(-1)). Of the 17 pilots, 6 were known to be prosecuted criminally, including 5 who were sentenced to jail terms. DISCUSSION: Incidents of alcohol violations by airline pilots reported in U.S. newspapers have increased in recent years. This increase is likely due in part to increased detection resulting from enhanced aviation security and enforcement following the September 2001 terrorist attacks.     

On determining the relationship between blood alcohol concentration and smooth pursuit eye movements

Residual impairment after alcohol consumption implies that the relationship between blood alcohol concentration (BAC) and deficits in performance of some task is not the same when becoming intoxicated as it is when returning to sobriety. A pilot study was performed to determine the feasibility of and the appropriate methodology for studies on residual impairment of smooth pursuit performance. Four subjects consumed alcohol for 2 h. Measurements of BAC and smooth pursuit eye movements were made every 30 min during drinking and for 4 h after drinking. Pursuits were elicited by having subjects track a sinusoidal target (0.40 Hz and 0.60 Hz) for 10 s. Impairment of smooth pursuit was quantified with frequency analysis scores. Frequency analysis scores declined as BAC increased. As BAC decreased, frequency analysis scores tended to increase toward pre-drink levels. The relationship between BAC and frequency analysis score was not significantly different on the ascending and descending limbs of the blood alcohol curve. However, the idea that residual impairment does not occur could not be conclusively demonstrated for several reasons. First, as BAC returned to pre-drink levels, frequency analysis scores were inconsistent for each subject perhaps because of boredom and fatigue. Second, the relationship between BAC and frequency analysis score varied between subjects. Finally, because the recording periods were short, the effect of alcohol on sustained attention could not be assessed. In this paper, potential artifacts in studies of residual impairment of pursuits are discussed and potential solutions to the methodological problems encountered in the pilot study are provided.