EFFECTS OF ETHANOL ON PSYCHOMOTOR PERFORMANCE

Transcription

1 Br. J. Anaesth. (1987), 59, EFFECTS OF ETHANOL ON PSYCHOMOTOR PERFORMANCE D. FAGAN, B. TIPLADY AND D. B. SCOTT Increasingly, psychomotor tests are being used to detect impairment of cerebral function following the administration of drugs used before, during and after anaesthesia. The tests provide a quantitative measure of motor and cognitive function and allow comparison between different drugs or between different doses of the same drug. The seitivity of individual tests, and the implicatio of deviatio from normal following the administration of drugs are not clear. Nevertheless, recommendatio are made that, on the basis of evidence of residual impairment on one or more tests, the patient should not be allowed to drive home or even discharged from hospital. Alcohol is a central nervous system depressant and its effects should be easily quantifiable by modern psychometric testing. As most people have experience of its effects, and legal limits for driving have been set, alcohol provides a convenient yardstick agait which to compare the depressant effects of other drugs. Patients frequently ignore warnings to the contrary and take alcohol together with prescribed drugs. Knowledge of its interaction with such drugs is, therefore, of great importance in assessing safety. It is also important to know the effects of alcohol on its own before deciding whether an interaction is additive or synergistic. The following study was carried out to assess the effects of three different doses of alcohol, using a series of psychomotor tests all of which have been shown to be seitive to commonly used sedative drugs. D. FAGAN, B.SC. (HONS); D. B. SCOTT, M.D., P.R.C.P.E., F.F.A.R.C.S.; Department of Anaesthetics, Royal Infirmary, Lauriston Place, Edinburgh. B. TIPLADY, B.A., PH.D.; Astra Clinical Research Unit, 10 York Place, Edinburgh. Accepted for Publication: December 24, Correspondence to D.F. SUMMARY Three separate doses of alcohol (0.2, 0.4 and 0.8 g kg~ l ) were given to eight volunteers and compared with the effects of a placebo. The order of administration was randomized and the study performed double-blind. A battery of psychometric tests seitive to central nervous system depression was repeatedly performed for 3.5 h. Alcohol, even in the highest dose, had little effect on psychomotor performance. SUBJECTS AND METHODS Eight healthy non-alcoholic males coented to take part in this study, which was approved by the local ethics advisory committee. The subjects were aged between 19 and 39 yr (mean = SD) and weighed between 59 and 86 kg (mean = SD). On each of four sessio they were randomly allocated to receive ethanol 0, 0.2, 0.4 or 0.8 g/kg body weight. The ethanol was given as a solution of 37.5 % Smirnoff vodka made up to 500 ml with water and strong orange juice. Blinding was achieved using 5-mg benzocaine lozenges (Tyrosets) and menthol sweets (cherry menthol Tunes) to mask taste and smell. The drink was coumed over a 10-min period on an empty stomach. Subjects were not allowed to smoke or to drink other alcoholic or caffeine-containing beverages from 6 p.m. the previous night until the end of each test session. Blood samples (5 ml) for the estimation of plasma ethanol concentration were drawn at 0,10, 20, 30, 45, 60, 75, 90, 105, 120 and 180 min after ingestion. Subjective measures of performance were recorded using linear visual analogue scales. The subjects were asked to rate how they felt by marking across 10-cm lines, the ends of which read alert/drowsy, steady/dizzy and bored/interested.

2 962 BRITISH JOURNAL OF ANAESTHESIA Objective assessments of psychomotor performance were made using tests of choice reaction time (CRT), choice reaction latency (CRL), critical flicker frequency (CFF), body sway (BS), continuous attention (CAT), decision making time (DMT) and auditory vigilance (AV). CRT and CRL were measured using a Leeds Psychomotor Tester (Hindmarch and Parrot, 1978) which measured both the delay in respoe and the total respoe time to a visual stimulus. CFF was also measured with the Leeds Tester: the subjects' task was to discriminate the frequency at which flickering lights were just perceived to be "steady" and vice versa. BS was measured in the anterior posterior plane using a Wright Codoc ataxiameter (Wright, 1971) which detected and measured sway in the erect subjects. CAT coisted of brief presentatio of random block patter on a microcomputer screen; the subject had to respond whenever two coecutive patter were the same (Tiplady, 1985). The number of correct and incorrect respoes were computed. DMT was also a computerized task. A series of pictures of animals and objects were presented to the subjects, who were timed in their respoe to the question "Is it an animal?" (Tiplady, 1985). Last, in the AV test a series of short tones was played through headphones at 2-s intervals for 1 h. The subject's task was to identify 90 shorter tones randomly presented within the hour (Wilkion, 1968). Testing was carried out at 0, 30, 60, 120, 150 and 180 min after the ingestion of the alcohol, with the exception of AV which was assessed between 60 and 120 min. Statistical analysis was performed using the Friedman rank sum method (F) followed by Page's L Trend test (L) (Hollander and Wolfe, 1973). RESULTS The mean plasma ethanol concentratio are shown in figure. 1. Every subject reached or surpassed the British legal limit for driving with the high dose, but not with the lower doses. Peak plasma concentratio were measured min after the strongest drink. The data obtained from the psychometric tests and the visual analogue scales are shown in figures 2-4. Baseline values corresponding to 0 h for tests in figures 3 and 4 are shown in table I. There were no significant differences in the baseline scores between sessio. o Time (hi FIG. 1. Plasma concentratio of ethanol in the three active treatment sessio. Figures are mea. O O = 0.2 g kg"'; C = 0.4 g kg" 1 ; = 0.8 g kg" 1 ; = British legal limit for driving. Interested 20i 0 (mm) Bored -50 FIG. 2. Subjective effects of ethanol. Scores were calculated as mean changes from the baseline value (mm). = Placebo; O O = 0.2 g kg" 1 ; = 0.4 g kg" 1 ; #=0.8gkg->. *P<0.05F (at least); \P < 0.05 P (at least). The peak subjective effects occurred at 0.5 h, while the peak psychomotor effects occurred at 2.5 h. All of the analogue scales showed statistically significant effects, subjects showing greater interest (P < 0.05 F, L) and dizziness (P < 0.05 F, P < 0.01 L) 30 min after drinking the greatest dose of ethanol. Increased drowsiness, however, 2.S 2.5

3 ETHANOL AND PSYCHOMOTOR PERFORMANCE 963 Choice Reaction Time (ms) Continuous Attention o (Errors) -3 (ms) FIG. 3. Effects of ethanol on psychomotor performance. Choice reaction time, latency and decision making times were the mea of 30 measurements. Scores were calculated as mean changes from the baseline value. = Placebo; O O = 0.2 g kg"' j C C = 0.4 g kg" 1 ; = 0.8 g kg-i. *P < 0.05 F (at least); jp < 0.05 P (at least). was not apparent until the 2.5-h test period (P < 0.05 F). There were few statistically significant objective effects of ethanol, and those which were in evidence occurred late. CRT and CRL were not significantly prolonged until 2.5 h after the 0.8-g kg" 1 dose, while sway was only significantly increased at 2.5 and 3 h (all P < 0.05 F, L) despite the trend appearing earlier. The total number of errors (omission plus commission) increased at 3 h for the CAT test (P < F, P < 0.01 L), although there was a tendency for scoring to (20'ofarc) Time(h) FIG. 4. Effects of ethanol on psychomotor performance. The false positive and false negative scores were summed to give an overall score for continuous attention. The maximum possible error score for CAT was 120. For criticalflickerfrequency the mean of 6 ascending and 6 descending values was taken. Two 1-min determinatio of sway were made. All scores were calculated as mean changes from the baseline value. = Placebo; O O = ethanol 0.2 g kg" 1 ; C = 0.4 gkg-'; =0.8gkg-». *P<0.05F (at least); fp < 0.05 P (at least). improve with the 0.2-g kg" 1 dose (not significant). CFF tended to be decreased by the ethanol, and DMT prolonged (not significant). The scores for AV and the errors of commission are shown in table II. The number of correct respoes for AV was inclined to decrease at the higher doses, while the AV error scores tended to increase with the highest dose only (not significant). Ethanol had no significant effect on the DMT errors. TABLE I. Baseline (pre-drug) values {mean (SD)) for psychomoter tests. CRT = choice reaction time; CRL = choice reaction latency; DMT = decision making time; CAT = continuous attention task; CFF = criticalflickerfrequency ; BS = body sway Ethanol Test Placebo 0.2 g kg~ 0.4 g kg" 0.8 g kg"' CRT(ms) 485 (71) 481 (44) 489 (64) 478 (64) CRL(ms) 313 (45) 312 (38) 309 (59) 311 (44) DMT(ms) 502 (86) 495 (77) 542 (122) 505 (106) CAT (correct) 18 (1) 17 (3) 17 (2) 18 (2) CFF (Hz) 33.2 (3.5) 32.9 (4.4) 33.1 (4.4) 32.8 (4.2) BS(20'arc) 10 (4) 11 (6) 12 (4) 10 (5)

4 964 BRITISH JOURNAL OF ANAESTHESIA TABLE II. Effects of ethanol on correct and error scoring for auditory vigilance, and on error scoring for decision making. The maximum possible number of correct scores for auditory vigilance was 90, and the maximum number of false positive errors As so few errors for decision making were made, these were expressed as errors/day after ingestion. The maximum possible number of errors/day for decision making was 150 Test Placebo 0.2 g kg" 1 Ethanol 0.4 g kg" g kg" 1 Friedman ANOVA Page's L-trend AV AV errors DMT errors 46.3(11.9) 12.7(11.9) 2.8 (4.5) 47.0 (5.6) 14.0 (12.9) 4.3 (3.5) 33.2(11.6) 10.3 (8.7) 2.0 (2.8) 40.8 (10.8) 22.3 (10.9) 3.8 (5.6) DISCUSSION The most notable result of this study was how little effect quite high doses of alcohol had on the psychomotor tests used. This cannot be attributed to a general lack of seitivity of the tests, since previous studies have shown that they are easily capable of detecting the effects of moderate doses of other central depressant drugs (Hindmarch, 1979; Scott, Fagan and Tiplady, 1982; Fagan, Scott and Tiplady, 1984; Swift, 1984). Figure 5 shows a composite graph of results of body sway, measured in our laboratory, after the highest ethanol dose compared with results associated FIG. 5. Composite graph of the acute effect of central depressants on sway in healthy volunteers. The scores are presented as post-drug :pre-drug ratios for each drug. = Ethanol 0.8 g kg" 1 ; = amitriptyline 75 mg; x x = chlormethiazole 452 mg; = temazepam 20 mg; = zimelidine 200 mg. with normal clinical doses of amitriptyline, temazepam, chlormethiazole and zimelidine. At the highest dose, our volunteers were taking one-quarter to one-third of a bottle of vodka, yet the reaction times and sway scores of most were only affected minimally when the plasma concentratio reached their peak. Indeed, the statistically significant results of the objective tests only appeared in the "hangover" period, some hours later, by which time the plasma concentratio were lower and the subjects felt drowsy. Several other authors have reported a lack of strong deleterious effect on many psychomotor skills using similar doses of alcohol (Palva et al., 1979; McManus et al., 1983). Very high doses of alcohol have to be taken before marked impairment of psychomotor function is seen coistently, especially in younger male subjects. Palva and co-workers (1979) found that their subjects' performance on a reaction time task actually improved with doses of ethanol up to 0.8 g kg" 1, and was still not significantly impaired even after 1.2 g kg" 1 taken acutely. Changes in respoes on an attention task were, however, detected at lower doses. Interestingly, the subjective tests seemed to be more seitive at picking up the central nervous system effects during the acute phase after alcohol. We do not infer from our results that it is safe to drink and drive or that the legal limit is too low. The well-known propeity for individuals to behave inappropriately while driving with quite low plasma ethanol concentratio would obviate that opinion. Our concern is that other depressant drugs in normal therapeutic doses cause much greater impairment than large amounts of alcohol, but warnings are much less strident and are frequently ignored. Moreover, since small amounts of alcohol can potentiate the effects of many of these drugs (Ferrara, Pikkarainen and Mattila,

5 ETHANOL AND PSYCHOMOTOR PERFORMANCE ), the resulting hazard to patients is likely to be coiderable. Using alcohol as a yardstick, measurable abnormalities in the tests used in this study would indicate significant depression, with inability to perform complicated tasks such as driving or operating machinery. REFERENCES Fagan, D., Scon, D. B., and Tiplady, B. (1984). A study of the effects of zimelidine on the pharmacokinetics and pharmacodynamics of temazepam in healthy volunteers. Psychopharmacology, 82, 252. Ferrara, S. D., Pikkarainen, J., and Manila, M. (1982). Psychotropic drugs in traffic accidents; in Public Health Problems and Psychotropic Substances (eds J. Idanpaan- Heikkila and I. Khan). Helsinki: The Government of Finland. Hindmarch, I. (1979). Effects of hypnotics and sleep inducing drugs on objective assessments of human psychomotor performance and subjective appraisals of sleep and early morning behaviour. Br. J. Clin. Pharmacol., 8, 43S. Parrot, A. C. (1978). The effects of a subchronic administration of three dose levels of a 1,5-benzodiazepine derivative, clobazam, on subjective assessments of sleep and aspects of psychomotor performance the morning following night time medication. Arzneim-Forsch. (Drug Res., 28, Hollander, M., and Wolfe, D. A. (1973). Nonparametric Statistical Methods, pp. 138, 147. New York: Wiley. McManus, I. C, Ankiers, I., Norfolk, J., Phillips, M., and Priest, R. G. (1983). Effects on psychological performance of the benzodiazepine loprazolam alone and with alcohol. Br.J. Clin. Pharmacol., 16, 291. Palva, E. S., Linnoila, M., Saario, I., and Manila, M. J. (1979). Acute and subacute effects of diazepam on psychomotor skills: interaction with alcohol. Acta Pharmacol. Toxicol. (Copenh.), 45, 257. Scon, D. B., Fagan, D., and Tiplady, B. (1982). Effects of amitriptyline and zimelidine in combination with ethanol. Psychopharmacology, 76, 209. Swift, C. G. (1984). Postural itability as a measure of sedative drug respoe. Br. J. Clin. Pharmacol., 18, 87S. Tiplady, B. (1985). (Abstract.) Br. J. Clin. Pharmacol, (In press). Wilkion, R. T. (1968). Sleep deprivation: performance tests for partial and complete deprivation; in Progress in Clinical Psychology, Vol. 8 (eds B. F. Reiss and L. A. Abt), p. 28. New York: Grune and Stratton. Wright, B. M. (1971). A simple mechanical ataxiameter. J. Physiol. (Lond.), 218, 27P.