THRESHOLD CONCENTRATION OF NITROUS OXIDE AFFECTING PSYCHOMOTOR PERFORMANCE

Br.J. Anaesth. (1979), 51, 177

THRESHOLD CONCENTRATION OF NITROUS OXIDE AFFECTING PSYCHOMOTOR PERFORMANCE R. H. ALLISON, A. W. SHIRLEY AND G. SMITH SUMMARY

Amongst the effects which have been attributed to contamination of the operating theatre with waste anaesthetic gases is impairment of the psychomotor and psychological performance of theatre staff. It is obvious that high subhypnotic concentrations of anaesthetics impair many aspects of performance, but it is important to determine if concentrations reached in both the unscavenged and scavenged operating theatre also cause a decrement in performance. Previous studies from this department (Smith and Shirley, 1977) failed to confirm studies from Chicago indicating that concentrations of nitrous oxide of 500 p.p.m. with or without halothane 15 p.p.m. (Bruce, Bach and Arbit, 1974) affected psychomotor performance. Subsequently, the Chicago workers demonstrated a threshold concentration for nitrous oxide of between 25 and 50 p.p.m. (Bruce and Bach, 1976). A recent review (Smith and Shirley, 1978) of this subject stated that the balance of evidence indicated that much higher concentrations of nitrous oxide were required to affect psychomotor performance. We present additional evidence supporting this conclusion and also attempt to establish a threshold concentration.

were anaesthetists or technicians and none was receiving any drug therapy at the time of this study. Each was requested to forgo tea or coffee during breakfast on the day of study and each was tested on two occasions at identical times of the same day of the week. After two practices with the audiovisual reaction-time equipment, the subject donned an Air Force type of mask and breathed air and measurements of reaction times were obtained. The gas was then changed to 1, 2, 4 or 8% nitrous oxide in air and after 1.5 h, reaction time measurements were again obtained. Subsequently, the inspired gas was changed to a different concentration of nitrous oxide and after 1.5 h, the measurements were repeated. On the second occasion, this procedure was repeated with the two concentrations of nitrous oxide not tested. The order of administration of the different concentrations of nitrous oxide was randomized and was not known to the subject. There were no significant differences between any of the measurements, but this pilot study suggested that an effect might be detectable with a concentration slightly greater than 8% and so this was tested. Part 1 •

METHODS

Twelve healthy subjects, age range 25-35 yr, gave informed consent to enter this study of the effect of four different concentrations of nitrous oxide on performance (1, 2, 4 and 8% nitrous oxide in air). All R. H. ALLISON, F.F.A.R.C.S., Division of Anaesthesia, Western Infirmary, Glasgow G i l 6NT. A. W. SHIRLEY, M.ED., PH.D.,

Department

of Psychology, University of Glasgow,

Glasgow G12. G. SMITH, B.SC, M.D., F.F.A.R.C.S., University

Department of Anaesthesia, Western Infirmary, Glasgow G116NT. 0007-0912/79/030177-04 $01.00

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Using audiovisual reaction times, no effects were found in 12 subjects exposed to 1, 2, 4, or 8% nitrous oxide. In subsequent studies on 30 subjects, a positive effect on performance was found at a concentration of between 8 and 12% nitrous oxide. In addition, there was no difference in mean reaction time in 12 subjects exposed to air or 8% nitrous oxide. It is concluded that the threshold concentration of nitrous oxide for an effect on psychomotor performance as assessed by choice reaction times probably lies between 8 and 12%.

Thirty healthy subjects age 19-36 yr not receiving medication gave informed consent to enter this study. Apart from three technicians, all were junior anaesthetists in this department and there were three females. Each subject was tested on one occasion, but never on a day following a night of emergency duty. Each subject was allowed to sit comfortably and read magazines or journals during the course of the study. Following two practice runs on the reaction time equipment, each subject donned an Air Force mask and breathed air. Reaction times were then obtained © Macmillan Journals Ltd 1979

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and the gas was changed to either 8 or 12% nitrous oxide, the order being randomized. After 1.5 h, audiovisual reaction times were measured. The gas was then changed to the concentration of nitrous oxide not tested initially and, after 1.5 h, the measurements were repeated.

RESULTS

Parti A "repeated" trial analysis of variance for the mean reaction times for the 30 subjects is shown in table I. Subsequent t tests on the treatment means using the error variance as the best estimate of the "population" variance from which to calculate the standard error of the difference between means showed that the only significant differences were those between the two pairs containing nitrous oxide (P< 0.001) (table II).

Sum of squares D.f.

Source Total Subjects Gas condition Error

Mean of squares F ratio

10.4502 8.2753 0.3226

89 29 2

0.2854 0.1613

1.8523

58

0.0319

8.947 5.0508

P < 0.00001 < 0.001

TABLE II. Mean reaction times for 30 subjects exposed to air, 8 and 12% nitrous oxide (SEM is standard error derived from error variance of the analysis of variance)

Reaction time SEM

Air

8% N 2 O

1.2517 0.0374

1.2787 0.0374 n.s.

12% N 2 O

1.3900 0.0374 P< 0.001

As in our previous studies, the analysis also showed significant differences between subjects. Part II There was no significant difference in the mean reaction time for the 12 subjects during exposure to air or 8% nitrous oxide, as assessed by a paired Student's t test (table III). TABLE III. Mean reaction times for 12 subjects exposed to air or 8% nitrous oxide Air

Mean SEM t

0.9520 0.077

8% nitrous oxide 0.9439 0.070 0.3475

DISCUSSION

Although previous studies from Chicago (Bruce, Bach and Arbit, 1974; Bruce and Bach, 1975, 1976) suggested that psychomotor performance was affected by concentrations of nitrous oxide as small as 25-50 p.p.m., three independent groups of workers failed to detect any measureable effects with 500 p.p.m. of nitrous oxide, using the same tests of performance (Smith and Shirley, 1977; Cook et al., 1978a; Frankhuizen et al., 1978). There must, inevitably, be small differences in the design of experiments in four different laboratories, but one important difference in a previous study from our laboratory (Smith and Shirley, 1977) was that subjects were allowed to ingest caffeine during the

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Part II As it was not possible to exclude a practice effect in the comparison of nitrous oxide and air in Part I, 8% nitrous oxide and air were tested in 12 subjects (aged 20-35 yr), all of whom were anaesthetists. The test sequence was similar to that of Part I in that subjects practised on the reaction-time equipment, donned the mask and breathed either air or 8% nitrous oxide for 1.5 h. Reaction time was then measured and the inspired gas changed to either 8% nitrous oxide or air, the order being randomized so that six subjects were exposed to air first and six to nitrous oxide first. At no time during the experiments described in Part I or Part II was the mask removed or caffeine ingested. None of the subjects fell asleep during the course of the experiment and none was aware of the concentration of nitrous oxide in the gas delivered. The audiovisual reaction-time test has been described fully in a previous communication (Smith and Shirley, 1977). The only difference in the reactiontime equipment as used in the present experiments was that the reaction times were counted electronically and recorded on an automatic printer, whereas previously reaction times were calculated manually from paper recordings. Nitrous oxide concentrations were obtained by dilution of Entonox with air (Smith and Shirley, 1977) and the concentrations delivered to the mask were monitored intermittently using a mass spectrometer (MGA 200). The concentrations were not found to vary outside the range of ± 5 % of the stated values. The means of about 90 measurements of correct reaction-time responses in each subject in each condition were used as the best estimate of the subject's reaction time in those conditions.

TABLE I. Analysis of variance

N 2 0 THRESHOLD FOR PSYCHOMOTOR PERFORMANCE

A

^

1

t

*

' i

and Shirley, 1978) that the balance of existing evidence (Smith and Shirley, 1977; Cooket al., 1978a, b ; Frankhuizen et al., 1978) suggests that the concentrations of anaesthetic agents present in the atmosphere of unscavenged operating theatres do not affect psychomotor performance as assessed by the tests used in these studies. ACKNOWLEDGEMENTS

We are grateful to the Association of Anaesthetists of Great Britain and Ireland for a grant for the purchase of equipment used in this study and to Messrs W. O. M. Davis, T. Hutchison, D. Brown and M. Terrace for invaluable technical assistance. REFERENCES

Bruce, D. L., and Bach, M. J. (1975). Psychological studies of human performance as affected by traces of enflurane and nitrous oxide. Anesthesiology, 42, 194. (1976). Effects of trace anaesthetic gases on behavioural performance of volunteers. Br. J. Anaesth.. 48, 871. Arbit, J. (1974). Trace anesthetic effects on perceptual, cognitive and motor skills. Anesthesiology, 40, 453. Cook, T. L., Smith, M., Starkweather, J. A., Winter, P. M., and Eger, E. I. (1978a). Behavioral effects of trace and subanesthetic halothane and nitrous oxide in man. Anesthesiology (in press). Winter, P. M., Starkweather, J., and Eger, E. I. (1978b). Effect of subanesthetic concentrations of enflurane and halothane on human behavior. Anesth. Analg. (Cleve)., 57, 434. Frankhuizen, J. L., Vlek, C. A. J., Burm, A. G. L., and Rejger, V. (1978). Failure to replicate negative effects of trace anaesthetics on mental performance. Br.J. Anaesth., 50, 229. Smith, G., and Shirley, A. W. (1977). Failure to demonstrate effect of trace concentrations of nitrous oxide and halothane on psychomotor performance. Br. J. Anaesth., 49, 65. (1978). A review of the effects of trace concentrations of anaesthetics on performance. Br. J. Anaesth., 50, 701. CONCENTRATION DE SEUIL DU PROTOXYDE D'AZOTE AFFECTANT LES PERFORMANCES PSYCHOMOTRICES RESUME

En se basant sur les temps de reaction audiovisuels, on n'a decele aucun effet sur les 12 sujets exposes a des concentrations de 1%, 2%, 4% ou 8% de protoxyde d'azote. Au cours d'autres etudes effectuees par la suite sur 30 autres sujets, on a trouve un effet positif sur les performances lorsque les concentrations se sont situees entre 8% et 12% de protoxyde d'azote. De plus, il n'y a eu aucune difference dans le temps moyen de reaction sur les 12 sujets exposes a

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*

course of the study. This factor has been excluded from the present study. All the previous studies on this subject have been reviewed in detail recently by Smith and Shirley (1978), who concluded that small concentrations of nitrous oxide of the order of those encountered in unscavenged operating theatres (nitrous oxide 600 p.p.m. and halothane 10 p.p.m.) probably do not affect those aspects of performance which have been tested so far. This conclusion is supported by the results of the present study. In addition, the results reported in Part I of this work suggest that the threshold concentration of nitrous oxide on those aspects of performance assessed by complex reaction times (Smith and Shirley, 1978) lies between 8 and 12%. In Part I, the exposure to air was not randomized, and the results with air were always obtained first during the experiment. Theoretically, therefore, one may postulate that 8% nitrous oxide may have a detrimental effect on performance which was counteracted by an effect of practice. Our experience with these tests suggests that after two practice routines of at least 200 manoeuvres, there is little difference between two subsequent tests on air at an interval of 1.5 h. Nonetheless, to satisfy such an objection, we subsequently looked for an effect of 8% nitrous oxide on performance as described in Part II by a comparison of 8% nitrous oxide and air in a random, balanced sequence and found no effect (table III). We postulate, therefore, that the most reasonable conclusion to draw from these data is that the threshold concentration for nitrous oxide lies between 8 and 12%. Confidence in these conclusions is strengthened by the close similarity between the results reported here and those obtained by Cook and others (1978a, b), who found that threshold concentrations for an effect of halothane, enflurane and nitrous oxide on performance (using an audiovisual reaction-time test very similar to that of Bruce, Bach and Arbit (1974)) were between 5 and 10% of the MAC value. Our data were obtained with anaesthetists and it is conceivable that they may be tolerant to trace concentrations of anaesthetics, but the fact that the data of Cook and colleagues were obtained with lay subjects renders such an objection unlikely. We cannot account for the differences between our results and those of Bruce, Bach and Arbit (1974) and Bruce and Bach (1975, 1976), apart from suggesting that their subjects may have been influenced subliminally. However, the results of our study would appear to give further support to our belief (Smith

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180 l'air cm a 8% de protoxyde d'azote. On en a conclu que la concentration de semi du protoxyde d'azote permettant d'obtenir un effet sur les performances psychomotrices, telles que determinees par les temps de reaction choisis, se situe probablement entre 8% et 12%. SCHWELLENKONZENTRATION VON STICKOXYD IN IHRER AUSWIRKUNG AUF DIE PSYCHOMOTORISCHE LEISTUNG ZUSAMMENFASSUNG

CONCENTRACION DE UMBRAL DE OXIDO NITROSO QUE AFECTA EL RENDIMIENTO SICOMOTOR SUMARIO

Midiendo los tiempos de reacci6n audiovisual, no se observo efecto alguno en 12 sujetos expuestos a 1, 2, 4 o 8% de oxido nitroso. En estudios posteriores con 30 sujetos, se descubrio un efecto positivo sobre el rendimiento con una concentracion de entre 8% y 12% de oxido nitroso. Ademas, no se produjo una diferencia en el periodo medio de reaccion en 12 sujetos expuestos al aire o a 8% de oxido nitroso. Se concluye que la concentracion de umbral de oxido nitroso que afecta el rendimiento sicomotor, segun lo evaluado mediante los diversos tiempos de reaccion, probablemente se encuentre entre el 8% y el 12%.

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Unter Verwendung audiovisueller Reaktionszeiten wurden keine Wirkungen bei 12 Patienten festgestellt, die 1%, 2%, 4% Oder 8% Stickoxyd augesetzt wurden. Bei Untersuchungen an 30 weiteren Patienten wurde eine positive Wirkung auf die Leistung bei einer Konzentration von zwischen 8% und 12% Stickoxyd festgestellt. Daraus wird geschlossen, dass die Schwellenkonzentration von Stickoxyd fiir eine Wirkung auf die psychomotorische Leistung,

bewertet durch ausgewahlte Reaktionszeitenj wahrscheinlich zwischen 8% und 12% liegt.