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Low Blood Alcohol Concentrations and Psychomotor Performance in Tolerating and Non-Tolerating Subjects
R Giorgetti, S Zancaner, G Brusini, F Castagna, F Fenato, A Rossi and SD Ferrara
Centre of Behavioural and Forensic Toxicology, Institute of Legal Medicine, University of Padova, Via Falloppio 50, 35121 Padova, Italy
The international literature reveals partial discrepancies regarding experimental and epidemiological evidence on the disabling role of a Blood Alcohol Concentration (BAC) < 50 mg/100 mL, and the uncertainty on the effects is more pronounced in the case of subjects with different metabolic capacities.
In order to achieve an experimental evidence on this subject, the effects of low BACs on driving ability were investigated by means of an experimental trial on 16 alcohol tolerating and non tolerating healthy volunteers, whose mean intake of ethyl alcohol was less than 0.5 (n=8) and more than 1.5 g/Kg (n=8) per week.
The study, random and cross-over, was conducted according to a double blind design, with placebo and verum (lorazepam 0.03 mg/Kg). Alcohol was administered for 15 minutes at doses of 0.5 g/kg.
Neuro-psychomotor functions were examined by correlation of GLC-HS serial dosages of ethyl alcohol in blood/saliva and computerized tests administered 15, 30, 60, 90, 120 and 180 minutes after intake of lorazepam, alcohol or placebo.
The tests explored various functions such as cerebral activation (Critical Flicker Fusion Test), eye-hand coordination (Critical Tracking Task), short-term serial memory (Choice Reaction Time), vigilance (Visual Vigilance Task) and discrimination of deviant stimuli (Response Competition Task).
Results showed: alteration of some neuro-psychomotor functions which are important for driving, in both sample groups; significant functional variations between subjects tolerating and not tolerating ethyl alcohol; and good correlation of blood/saliva levels of ethyl alcohol.
The international literature reveals partial discrepancies in experimental epidemiological evidence regarding the disabling role of BAC values under 80 mg/100 mL (Ferrara et al., 1994).
Experimental studies have shown that, in most subjects, the most marked disabilities regard cognitive functions, information processing and decision-making following attention-distracting stimuli (Hamilton and Copeman, 1970; Moskowitz et al., 1985; Moskowitz, 1973). Only a few subjects, probably in relation to variables of age, sex and tolerance, may show no functional disability.
With the aim of verifying the validity of these assumptions and the possible existence of inter-subject variability determined by different degrees of tolerance to ethyl alcohol, a study was carried out on healthy volunteers with no alcohol intake, occasional alcohol intake, and social drinkers of alcoholic beverages.
MATERIALS AND METHODS
Healthy volunteers were recruited among students and personnel attending the Institute of Forensic Medicine, University of Padova. Exclusion criteria were medical or psychiatric disturbances: pregnancy; body weight more than 15% outside the population mean; abuse of alcohol, drugs and/or psychoactive substances; arterial hypertension; ECG or EEG anomalies; liver-kidney diseases; severe organic disease; mental disturbance. As part of the selection procedure a questionnaire aimed at determining weekly alcohol consumption was administered. Subjects were classified as "non-tolerant" if their average alcohol consumption during the previous three months was less than 60.0 gr per week, and as "tolerant" if their consumption was greater than 120.0 gr per week. The selected sample was composed of 14 men and 2 women, aged between 20 and 42 (mean = 33.8 yrs, sd = 5.9), with a Body Mass Index ranging between 19.1 to 27.5 (mean = 24.0, sd = 2.1). The eight "tolerant" subjects declared an average alcohol consumption of 161.5 gr per week (sd=31.9), and the eight "non-tolerant" subjects 18.8 gr (sd=22.1). All subjects gave their written informed consent to participation in the study. Furthermore, all agreed to refrain from taking any medication during the study, and from taking alcohol or caffeine the day before testing.
Toxicological screening of urine was performed by the immunoassay technique for the following classes of psychoactive substances: amphetamines, antidepressants, barbiturates, benzodiaze-pines, cannabinoids, cocaine, methadone, opiates.
Alcohol and Drug Administration
All treatments were administered according to a double-blind crossover trial design. The three experimental doses were placebo, lorazepam 0.03 mg/Kg, and alcohol 0.5 g/kg. All subjects received each of the three test doses in a counter-balanced order. Pure alcohol at 95% dilution was used for this study. Doses were prepared by mixing drug or alcohol in 200 cc of ginger soft drink. A drop of rum flavour was added in order to vary the taste of the mixture.
The subjects were first trained for the psychomotor performance tasks until they reached plateau performance level. After the training phase three treatment sessions were scheduled at weekly intervals. Each session lasted approximately 4 hours, from 00:30 pm to 4:30 pm, during which subjects were asked to perform a battery of five psychomotor tests seven times. Baseline was taken at 00:30 pm. Psychomotor testing was then repeatedly assessed after administration of doses at 15, 30, 60, 90, 120 and 180 min. After the last assessment subjects were accompanied home.
Tests were always done in the same order. Since two subjects were simultaneously tested every day, the test order administered to one subject was administered in reverse order to the next. Each test lasted 15 mins. The test battery included the following tasks:
Critical Flicker Fusion (CFF)
Critical fusion frequency was measured using a novel combination of the psychophysical methods of limits and successive approximations, in a computer-controlled system (Olivetti M250 PC), equipped with a dedicated card and software and connected to an Auto-CFF binocular system (Euclid, Maastricht, The Netherlands) (Ramaekers et al., 1992).
Critical Tracking Test(CTT)
The Critical Tracking Test, was developed by Jex and McDonnell (Jex et al., 1966), was carried out on an Olivetti M300 PC, equipped with dedicated software (Institute of Human Psychopharmacology, Maastricht, The Netherlands).
Choice Reaction Time (CRT)
The Choice Reaction Time task (CRT), based on Sternberg's (Sternberg, 1969) memory search paradigm, was carried out on a Macintosh Classic II PC (Ramaekers JG et al. 1992).
Response Competition Task (RCT)
The test, based on Eriksen and Eriksen's (Eriksen BA et Eriksen CW 1974) Response Competition Task, was carried in a Macintosh Classic II personal computer (Apple Inc., Cupertino, CA, USA).
Visual Vigilance Task (VVT)
The Visual Vigilance Task (Nuechterlein et al., 1983, Robbe et al., 1989) is a rapidly paced, visual discrimination task lasting 5 minutes. It was administered using a Macintosh Classic II personal computer (Apple Inc., Cupertino, CA, USA).
As three-factor ANOVA for repeated measures with one grouping factor (tolerance to alcohol assumption) and two repeated factors (treatment and time of testing) was used for analysis. The completed model included group, treatment, and time of testing main effects. Dependent variables were the differences between the test values at 15, 30, 60, 90, 120 and 180 min after administration and baseline performance. Data were subjected to within-subject ANOVA. In case of rejection of some null hypotheses concerning main effects, post-hoc multiple comparisons were performed by means of Duncan's Multiple Range Test. Statistical tests were made at 5% confidence level. The SAS Statistical package was used for all analyses .
Critical Flicker Fusion Test (CFF)
Performance on this task was affected by treatment (F(2, 26)=8.02, p=0.0019), time of testing (F(5, 65)=6.81, p=0.0001), and treatment x time interaction (F(10, 130)=4.92, p=0.0001). Post-hoc comparison indicated that lorazepam reduced the flicker fusion threshold, whereas performances obtained under alcohol and placebo effects were comparable.
Critical Tracking Task (CTT)
Analysis of the lambdac parameter showed the statistical significance of the treatment main effect (F(2, 26)=8.29, p=0.0016), and treatment x time interaction term (F(10, 130)=6.06, p=0.0001) The main effect of drug condition was due to significant slowing of subjects' psychomotor ability due to lorazepam.
Choice Reaction Time (CRT)
Reaction times to Positive answers were only affected by time (F(5, 65)=6.60, p=0.0001). Reaction times to Negative answers and Total number of errors were affected by treatment (F(2, 26)=8.00, p=0.0020 and F(2, 26)=8.27, p=0.0017 respectively). The drug which reduced performance in both cases was lorazepam. The treatment x time interaction effect was borderline in both cases (F(10, 130)=1.86, p=0.0572; and F(10, 130)=1.84, p=0.0599, respectively) although the differential effect on performance of lorazepam with respect to alcohol and placebo appeared quite clear when plotted.
Response Competition Task (RCT)
Reaction times to slightly deviant and highly deviant stimuli and to total number of errors were statistically different among treatments (F(2, 26)=4.20, p=0.0262; F(2, 26)=4.23, p=0.0257; and F(2, 26)=6.55, p=0.0050, respectively). The treatment x time interaction term was statistically significant for all three parameters (F(10, 130)=3.03, p=0.0018; F(10, 130)=2.15, p=0.0248; and F(10, 130)=2.26, p=0.0183, respectively). Reaction times to non-deviant stimuli were only affected by time (F(2, 26)=2.53, p=0.0373). Independently other factors, subject performance improved during the experiment (learning effect still present).
Visual Vigilance Test (VVT)
In the analysis of the A't index (non-parametric perceptual sensitivity index), the treatment main effect was statistically significant (F(2, 26)=6.94, p=0.0039) as well as the group x treatment interaction term (F(2, 26)=3.48, p=0.0457). Analysis of total number of errors showed performances which were statistically different only among treatments (F(2, 26)=8.67, p=0.0013). For both parameters, post-hoc multiple comparisons revealed that lorazepam was the treatment condition reducing performance. Performances under alcohol and placebo conditions were comparable. Table 1 shows full statistical results.
Treatment effect was always statistically significant in the analysis of experimental responses, except for performances for CRT-Positive answers and RCT-Response to non-deviant stimuli. Post-hoc comparisons showed that lorazepam was the treatment condition in which performance was reduced with respect to placebo. Subjects performed comparably in alcohol and placebo conditions. Alcohol tolerance never influenced subjects' performance. Two spurious borderline results appear in the analyses: group x treatment interaction in the VVT test, and group x treatment x time interaction in the RCT test. The time effect rarely showed a statistical influence on performance; more often interaction treatment x time was significant.
Performance with alcohol was comparable to that with placebo except for a few minutes after drug administration, when it was comparable to performance with lorazepam.
Results thus indicate that:
Confirmation of this may derive from a similar forthcoming study which, however, uses objective procedures for subject selection such as study of transferrin metabolism or checking of average alcohol intake during the month preceding the test by means of continuous monitoring associated with laboratory tests.
In the present study, the tests which turned out not to be influenced by alcohol intake explore functions which are simple although still related to driving ability. The behaviour of subjects with different tolerances on complex and real driving tests must be verified before we can exclude the negative influence of alcohol on driving ability at BACs under 50 mg%.
The results of this study which indicate no impairment after an alcohol intake producing a BAC of less than 50 mg%mL, confirm similar results by many othe authors (Pickworth et al. 1992, Richter and Hobi 1979, Maylor et al. 1987, Mongrain and Standing 1989). These observations also justify the lack of significant differences between the tolerant and non-tolerant groups. Lastly, the negative influence of alcohol on driving ability at BACs under 50 mg% can only be excluded after assessment of experimental results from tests involving combined laboratory tests, driving simulator and real driving tests.
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Ferrara SD, Zancaner S, Giorgetti R (1994). Low blood alcohol concentrations and driving impairment, Int J Leg Med 106, 169-177.
Hamilton P, Copeman A (1970). The effect of alcohol and noise on components of a tracking and monitoring task. Br J Psychol 61, 149-156.
Jex HR, McDonnell JD (1966). Critical tracking task for manual control research. IEEE Trans Hum Factors 7, 138-145.
Maylor EA, Rabbitt PMA, Sahgal A, Wright C (1987). Effects of alcohol on speed and accuracy in choice reaction time and visual search. Acta Psychol 65, 147-163.
Mongrain S, Standing L (1989). Impairment of cognition, risk taking, and self-perception by alcohol. Percept Mot Skills 69, 199-210.
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Moskowitz H, Burns MM, Williams AF (1985). Skills performance at low blood alcohol levels. J Stud Alcohol 46, 482-485.
Nuechterlein KH, Parasuraman R, Jiang Q, (1983). Visual sustained attention: image degradation produces rapid sensitivity decrement over time. Science 220, 327.
Pickworth WB, Klein SA, George FR, Henningfield JE (1992) Acetaminophen fails to inhibit ethanol-induced subjective effects in human volunteers. Pharmacol Biochem Behav 41, 184-194.
Ramaekers JG, Swijgman HF, O'Hanlon JF (1992). Effects of moclobemide and mianserin on highway driving, psychometric performance and subjective parameters, relative to placebo. Psychopharmacology 106, S62-S67.
Richter R, Hobi V (1979). Der Einfluß niedriger Alkoholmengen auf Psychomotorik und Aufmerksamkeit. Blutalkohol 16, 384-394.
Robbe HWJ, Schoenmakers EAMJ, O'Hanlon JF, (1989). Paroxetine and Amitriptyline. Acute and subchronic effects on psychomotor and actual driving performance. Maastricht: Institute for Drugs, Safety and Behavior, IGVG pp. 18-19.
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