Wednesday, September 26, 2007

BAC - If overweight or obese, Widmark rho factors inappropriate

California DUI criminal defense attorney news:

Blood alcohol calculations: the usually Widmark rho factors are not appropriate for people who are overweight and certainly for those that are obese.


Journal of Analytical Toxicology, Vol. 31, April 2007 177

To the Editor:
Alcohol tops the list of psychoactive substances encountered in police investigations of crimes such as mugging, murder,
sexual assault, and especially impaired driving (1). 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 (2). 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 (3).
Two pharmacokinetic parameters of ethanol are important in forensic science and legal medicine when expert witnesses
and others engage in making various blood-alcohol calculations, such as retrograde extrapolation or relating a person’s BAC to
the number of drinks consumed (4). These parameters are the disappearance rate of ethanol from the bloodstream and the
volume of distribution of alcohol (Vd). This latter parameter expresses the ratio between the concentration of alcohol in the body
as a whole and the prevailing BAC and is an important concept introduced in the 1930s. The lean body mass (LBM) of the
average person has changed considerably since the distribution volume of ethanol was first determined.
Ethanol distributes into the total body water (TBW) compartment without binding to plasma proteins and solubility in fat
and bone is negligible (1). The Vd for ethanol depends on the person’s age, gender, and body composition, especially the
proportions of fat to LBM (4,7). Indeed, total body water (TBW) can be determined fairly reliably using ethanol as a biomarker,
and the results of such experiments show good agreement with values determined by isotope dilution (3H2O and 2H2O)
methods (8).
Many equations commonly used for blood-alcohol calculations assume population average values for Vd such as 0.7 L/kg for
men and 0.6 L/kg for women (2,3). Sex-related differences in Vd stem from differences in body composition between men and
women especially degree of adiposity (4). Instead of using population averages, a better approach would be to estimate TBW
using anthropometric data, such as age, height, and weight (9). From the percentage of TBW a more appropriate value of Vd for
ethanol can be derived from knowledge about the blood-water content, which is close to 80% w/w (~85% w/v) on average
(1 mL blood = 1.06 g). Others have devised nomograms incorporating the person’s body mass index (BMI) as an indirect way to
estimate Vd, although empirical studies
demonstrating the strength of this relationship have
not been published (10).
During experiments on the clinical
pharmacokinetic of ethanol (7,11), two of the
volunteers had widely different BMI and
correspondingly large differences in Vd for ethanol. The
intravenous route of administration was used to avoid
problems caused by first-pass metabolism and to
guarantee 100% bioavailability of the dose (11). Figure
1 shows the resulting concentration-time profiles of
ethanol in a male (BMI = 19.1) and female subject
(BMI = 31.6) who received 0.40 g ethanol/kg body
weight by constant rate intravenous infusion (10% w/v
in glucose) over 30 min. Specimens of venous blood
were taken at 5-min intervals from indwelling
catheters and the concentrations of ethanol were
determined by headspace gas chromatography, a
method with high analytical precision and a coefficient
of variation of about 1% (12).
Letter to the Editor
Body Mass Index and Blood-Alcohol Calculations*
Reproduction (photocopying) of editorial content of this journal is prohibited without publisher‘s permission.
* Supported by the Swedish National Board of Forensic Medicine (Rättsmedicinalverket).
Figure 1. Concentration-time profiles pf ethanol in a healthy male (BMI = 19.1 kg/m2)
and female (BMI = 31.6 kg/m2) after intravenous administration of ethanol (0.4 g per
Journal of Analytical Toxicology, Vol. 31, April 2007
178
The dashed diagonal lines in Figure 1 were obtained by least-squares linear regression using selected concentration-time
points on the post-absorptive phase. The Vd for ethanol was then derived as ratio of dose (g/kg) to C0 (g/L), where C0 represents
the BAC expected if absorption and distribution of the entire dose had occurred instantaneously without any metabolism taking
place. The female subject had a Vd of 0.45 L/kg, compared with the man’s Vd of 0.70 L/kg, and the corresponding rates of alcohol
elimination from blood (slopes of the diagonal lines) were 0.15 g/L/h for the woman and 0.11 g/L/h for the man.
The woman’s BMI was 31.6 kg/m2, which is in the range for clinical obesity class I, and the Vd for ethanol was abnormally
low (0.45 L/kg), being 25% less than the value of 0.6 L/kg used in many blood-alcohol charts and computer programs (2,3).
Using a Vd of 0.6 L/kg in blood-alcohol calculations instead of the correct value of 0.45 L/kg obviously impacts on the reliability
of the results if and when a person’s BAC is compared with information about the number of drinks consumed. The man’s Vd
was 0.7 L/kg (BMI = 19.1 kg/m2), which is in good agreement with the population average value for men incorporated into many
blood-alcohol charts.
This preliminary report confirms that Vd for ethanol is likely to be abnormally low for people who are clinically obese,
which calls for caution when making blood-alcohol calculations for teaching, research, or legal purposes. It would be much
more acceptable to use subject-specific values for Vd based on information about TBW, BMI, or LBM for the individual
concerned. Use of inappropriate values of Vd will have consequences in litigation concerning driving under the influence of
alcohol, for example when a person’s BAC is compared with information about prior consumption of alcohol.
Obesity has become a major public health concern along with binge drinking and drunkenness (13,14). Besides the
importance of BMI in blood-alcohol calculations, obesity is also a concern in connection with the pharmacokinetics and
pharmacodynamics of therapeutic drugs (15). The relationship between BMI and Vd for ethanol needs to be investigated in many
more individuals of different ages, ethnicity, and body composition, including those underweight for height, emaciated, and
morbidly obese.
A.W. Jones
Department of Forensic Chemistry
Artillerigatan 12
581 33 Linköping
Sweden
References
1. M.D. Slater, M. Long, and V.L. Ford. Alcohol, illegal drugs, violent crime, and traffic-related and other unintentional injuries in U.S. local and
national news. J. Stud. Alcohol 67: 904–910 (2006).
2. J. Brick. Standardization of alcohol calculations in research. Alcohol. Clin. Exp. Res. 30: 1276–1287 (2006).
3. B.T. Davis and C.K. Bowen. Peak blood alcohol prediction: an empirical test of two computer models. J. Stud. Alcohol 61: 187–191
(2000).
4. A.W. Jones. Disposition and fate of ethanol in the body. In Medical and Legal Aspects of Alcohol, 4th ed., J.C. Garriott, Ed. Lawyers and
Judges, Tucson, AZ, 2003, pp 47–112.
5. E.M.P. Widmark. Die theoretischen Grundlagen und die praktische Verwendbarkeit der gerichtlich-medizinischen Alkoholbestimmung.
Urban & Schwarzenberg, Berlin, Germany, 1932, p 140.
6. R. Andreassson and A.W. Jones. The life and work of Erik MP Widmark. Am. J. Forensic Med. Pathol. 17: 177–190 (1996).
7. A. Norberg, A.W. Jones, R. Hahn, and J. Gabrielsson. Role of variability in explaining ethanol kinetics—research and forensic applications.
Clin. Pharmacokinet. 42: 1–31 (2003).
8. H.G. Endres and O. Gruner. Comparison of D2O and ethanol in total body water measurements in humans. Clin. Investig. 72: 830–837 (1994).
9. P.E. Watson, I.D. Watson, and R.D. Batt. Prediction of blood alcohol concentrations in human subjects; updating the Widmark equation.
J. Stud. Alcohol 42: 547–556 (1981).
10. A.R.W. Forrest. The estimation of Widmark’s factor. J. Forensic Sci. Soc. 26: 249–252 (1986).
11. A. Norberg, J. Gabrielsson, A.W. Jones, and R.G. Hahn. Within- and between-subject variations in pharmacokinetic parameters of ethanol by
analysis of breath, venous blood, and urine. Br. J. Clin. Pharmacol. 49: 399–408 (2000).
12. A.W. Jones and J. Schuberth. Computer-aided headspace gas chromatography applied to blood-alcohol analysis; importance of on-line process
control. J. Forensic Sci. 34: 1116–1127 (1989).
13. D.W. Haslam and W.P.T. Jones. Obesity. Lancet 366: 1197–1209 (2005).
14. R. Room, T. Babor, and J. Rehm. Alcohol and public health. Lancet 365: 519–530 (2005).
15. G. Cheymol. Effects of obesity on pharmacokinetics: implications for drug therapy. Clin. Pharmacokinet. 39: 215–231 (2000).

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