BIOCHEMICAL MEASUREMENTS AND SCREENING FOR ALCOHOL ABUSE IN DRUNK DRIVERS

Transcription

1 BIOCHEMICAL MEASUREMENTS AND SCREENING FOR ALCOHOL ABUSE IN DRUNK DRIVERS * * * M. S. Devgun, Ph.D. ; J. A. Dunbar, D.M.J. ; * * * * * * * J. Hagart, M.Sc. ; S. Ogston, M.Sc. ; and B. T. Martin, Ph.D. SYNOPSIS Gamma-glutamyl transferase in serum is a better indicator of problem drinking than other liver enzymes or blood alcohol. Moreover, the stability of this enzyme makes it easier to analyze, and the analysis is inexpensive. However, interpretation of the data requires knowledge of previous medical history and drugs prescribed concurrently that may affect the serum levels of gamma-glutamyl transferase. INTRODUCTION Liver enzymes gamma-glutamyl transferase (GGTP) and aspartate transaminase (AST) can be used to identify those individuals who are suspected of having alcohol-related problems. (Other biochemical parameters that can easily be monitored are listed in Table 1.) However, these measurements generally reflect not only drinking problems but also the nutritional status of an individual. Adequate nutritional support in such individuals is usually at the expense of increasing consumption of alcohol although hematological investigation (mean corpuscular volume) can assist in the determination. * Department of Biochemistry, Law Hospital, Carluke, UNITED KINGDOM. ** General Practice, 325 Strathmartine Road, Dundee, UNITED KINGDOM. *** Alcohol Addiction Unit, University of Kent, Canterbury, UNITED KINGDOM. **** Department of Community & Occupational Medicine, Ninewells Hospital, Dundee, UNITED KINGDOM. ***** Area Department of Pathology, Heavitree, Exeter, UNITED KINGDOM. 345

2 In order to screen for alcohol problems by biochemical means the investigator must first establish that measurements are not affected by prolonged delays of samples in transit. Such delays are inevitable because blood is usually taken in a police station (in the United Kingdom), usually out of working hours and inappropriately stored, also, at a some distance from the laboratory performing the tests. The effect of binge drinking must also be investigated. Further, the investigator must bear in mind that many drugs can affect biochemical measurements and, therefore, should be ruled out to increase the sensitivity and specificity, and, therefore, the predictive value of the tests. Finally, the usefulness of blood alcohol (BAC) or breath alcohol measurements as predictors of alcohol related problems must be assessed against against the biochemically measured parameters. Patients and Methods Biochemical estimations were performed on a centrifugal analyser (Rotochem II). Chemical analyses for liver function tests were carried out at 37 C. These function tests included AST, GGTP, and HBD (hydroxybutyrate dehydrogenase). The assessment of quality of sample on biochemical measurements was made by comparing freshly analyzed samples against those samples that had been left standing over-night, using blood samples from the same group of individuals (n=12; age range years with mean age of 24 years). The effect of binge drinking was assessed on 54 healthy volunteers, age range (mean age 33 years). A free supply of drinks was available to all members over a period of 5 hours. Blood samples were taken before drinking session and then at 1.5 hours and at 8 hours after the cessation of drinking. Enzymes and alcohol were measured in the 3 sets of blood samples taken. Results and Discussion The effects of delay on the liver function tests that are usually performed to assess alcohol problems are such that neither AST nor HBD can be reliably measured to predict problem drinkers (Table 2). The increase in the activity of 346

3 these enzymes is related-to their release from the red blood cells. Therefore, if fresh samples cannot be obtained for biochemical measurements, then AST and HBD do not have a role in screening for alcohol-related problems. On the other hand, GGTP is not affected by delays in transit and, therefore, can be used to monitor screening programs. It must be emphasized that such interferences can also arise from the methods for measuring the enzymes. Table 1; Some of the routinely performed biochemical tests useful in screening for alcohol related problems Blood alcohol Breath alcohol Serum osmolality uric acid cholesterol triglycerides bilirubin potassium calcium zinc albumin Table 2: Effect of delay in separation of serum on liver enzymes Test mean + sd, iu/1 % increase over day 1, iu/1 Day 1 Day 2 AST HBD ' GGTP If GGTP is the only enzyme that can be used to screen arrested drunk drivers then drugs taken by the individual must also be taken into account (see Table 3). Moreover, a number of diseases can raise GGTP above the reference range of the population (Table 4). Because of these drugs and diseases many authorities consider GGTP to be of limited predictive value. This problem can only be overcome if an access to patient records is available. 347

4 Table 3: Drugs likely to increase levels of GGTP in serum Analgesic and antipyretic Hypnotic and sedative Anticonvulsant Tranquilliser Central depressent Antibiotic/antifungal Cytotoxic Vasodilator Diagnostic agent Sex hormones Antituberculus Fibrinolytic Antithyroid Antimetabolite/ immunosuppressant Drugs of abuse Anticoagulant acetaminophen, aminopyrine, phenylbutazone, salicylate barbiturates, glutethimide, methaqualone carbamazapine, phenobarbital, phenytoin chlorpromazine, meprobamate ethanol, nikethamide griseofulvin ifosfamide lidoflazine metrizoate oestrogen-progesterone preparations rifampicin streptokinase thiamazole azathioprine cocaine, lysergic acid diethylamide, marihuana warfarin Table 4; Diseases and other conditions in which an increase in the activity of serum GGTP may be observed Hepatitis Pancreatic disorders Obstructive liver disease Infectious mononucleosis Hepatic malignancy Diabetes Cirrhosis Cardiac disease Alcoholic cirrhosis Drug induced hepatitis Renal disease Children, age (1 year) Hepatomegaly Irrespective of the amount of alcohol consumed, the effect on the measurements of the activity of serum GGTP is not significant (Figure 1). The effects are similar at 1.5 and at 8 hours after alcohol consumption. (These intervals were so chosen because they approximate the time intervals when drunk drivers are most likely to be arrested and investigated for blood measurements). When related to grams of alcohol consumed BAC measurements are not good indicators of problem drinking bacause results of these tests are very much time dependent (Figure 2). Also, the delineation of a cut-off point for categorizing probable problem drinkers is not possible at this time. 348

5 In conclusion, we stress that to screen for alcohol-associated problems, especially in drunk drivers, the measurement of AST, HBD, and BAC may not prove useful. The GGTP determinations could be of considerable help only if patient records are available with relevant history of drugs and diseases that can affect this enzyme. Furthermore, measurements of breath alcohol which are thought to reflect BAC levels could also be non-useful for predicting drunk drivers with problems, apart from the fact that many controversies surround the principles and the techniques of analyzing breath samples and the consequent effects on the results. A screening test must be a reliable, inexpensive, and most readily available test that is not affected by the sample quality and has a good predictive value. In these respects GGTP determination is probably the least expensive test and, also, can be performed by almost all hospital laboratories on routine basis, at least in the United Kingdom. As shown, it is reliable and not affected by delays in transit. The predictive value of the test is increased by having patient's medical records available at the time of the assessment. 349

6 NO. SUBJECTS 1 t( ALCOHOL CONSUMPTION, g Figure 1. Alcohol consumption and serum levels of GGTP at 1.5 hours and at 8 hours after cessation of drinks, or at 6.5 hours and at 13 hours from the onset of drinks. NO. SUBJECTS 1 H ALCOHOL CONSUMPTION, fi Figure 2. Alcohol consumption and blood levels of alcohol at 1.5 hours and at 8 hours after cessation of drinks, or at 6.5 hours and at 13 hours from the onset of drinks. 350