Br.J. Anaesth. (1976), 48, 691
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM G. D. GALE SUMMARY
Both methohexitone and diazepam i.v. are used widely to produce anaesthesia and sedation for short procedures in dentistry. The pharmacology of these agents suggests a much longer duration of action than would appear desirable and, in recent years, several papers (Doenicke et al., 1966; Brown and Dundee, 1968; Grove-White and Kelman, 1971) have attempted to assess the duration of recovery from these agents and have confirmed prolonged residual effects. The present study in dental and surgical outpatients was designed to measure the recovery times from methohexitone and from diazepam, and to compare them with recovery times after halothane and nitrous oxide administered for both short and long periods. PROCEDURES TO BE COMPARED
(1) Methohexitone anaesthesia Methohexitone was given i.v. to 16 patients undergoing dental extraction. The dose was assessed by the anaesthetist on the basis of his clinical experience and ranged from 1.07 to 1.79 mg/kg (mean 1.51 mg/kg). The duration of anaesthesia ranged from 2.5 to 10 min (mean 4.6 min). (2) Short-duration halothane anaesthesia Halothane in 70-80% nitrous oxide in oxygen was given to seven patients undergoing dental extraction and two patients undergoing minor surgery. The duration of anaesthesia ranged from 3 to 12 min (mean 6.2 min). G. D. GALE, M.B., B.S., F.F.A.R.C.S., F.R.C.P.(C), D.(OBST.),
R.C.O.G., Department of Anaesthesia, The Royal Victoria Infirmary, Newcastle Upon Tyne NEL 4LP. Present address: Department of Anaesthesia, Toronto General Hospital, 101 College Street, Toronto, Canada M5G 1L7.
(3) Long-duration halothane anaesthesia Halothane in 70-80 °/% nitrous oxide in oxygen was given to eight patients undergoing minor surgery. The duration of anaesthesia ranged from 20 to 60 min (mean 32 min). (4) Diazepam sedation A single i.v. injection of diazepam was given to eight patients undergoing conservative dentistry, at a rate of 4 mg/min until slurred speech and drooping of the eyelids occurred. The mean dose was 0.31 mg/kg (range 0.28-0.51 mg/kg). In addition, the patients received local analgesia. The dental treatment was prolonged (range 20-69 min; mean 47 min). (5) Control group Eleven subjects were tested hourly for 4 h on one day and once on the next day to determine the effects of repetition on the performance tests. Details of the groups are summarized in table I. In all the anaesthetic techniques atropine was given at the discretion of the anaesthetist. METHOD OF ASSESSMENT
The motor and cognitive tests (table II) were performed by the patients before, and serially after, anaesthesia so that performance could be compared before and after anaesthesia within the group and also with a control group receiving no anaesthesia or sedation. The recovery phase was defined as beginning when the drug administration ceased. Therefore recovery began when the inhalation anaesthetic ended or when the i.v. injection of diazepam or methohexitone was completed. The tests were performed on the methohexitone and halothane groups at 15-25 min, 25-50 min and 50-75 min after the start of recovery.
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Five motor and six cognitive tests were performed once before and then serially after anaesthesia with halothane and nitrous oxide of both short and long duration, methohexitone anaesthesia, and diazepam sedation with local anaesthesia. An untreated control group was also tested. The results suggest that, in the first hour, recovery was most rapid after short-duration halothane and nitrous oxide, was less rapid after methohexitone alone and was least rapid after long-duration halothane and nitrous oxide. Recovery after diazepam with local anaesthesia was prolonged and was incomplete at 3 h.
BRITISH JOURNAL OF ANAESTHESIA
692
TABLE I. Details of groups and procedures. Treatment time refers to the length of the dental or surgical treatment Number
Range
M
F
Mean
Range
Mean
Range
16 9 8 8 11
32.4 25.7 30.3 28.5 33.1
19-59 14-41 14-^15 17-43 17-56
9 6 1 2 6
7 3 7 6 5
68.2 66.1 62.0 60.8 77.3
51-118 45.5-93 45.5-88 52-68 54-95.5
4.6 6.2 31.9 47.6 —
2.5-10 3-12 20-60 20-69.5 —
—auditory —visual —slow —rapid
Cognitive tests Arithmetic
Treatment time (min)
Mean
Motor tests
1. 2. 3. 4. 5.
Weight (kg)
subjects
TABLE II. Tests used as indices of recovery from anaesthesia and sedation
1. Reaction time 2. 3. Static ataxia 4. Tracking 5.
Sex
—columns correct —columns attempted Word naming —time score Colour naming —time score Incongruous colour-words—time score 6. —error score
Tracking This paced, complex co-ordination test was similar to the pursuit meter described by Hughes, Forney and Richards (1965). The apparatus comprised a circular turntable which revolved once every 56 s and carried a paper disk with a spiral of 240 small circular targets divided radially into 25 segments. The targets rotated slowly near the centre and progressively faster near the periphery. The subject viewed the moving targets through a slit in the lid of the apparatus and was asked to hit targets with a pencil thus making a spiral line through the targets. Errors occurred when targets were missed and these were converted into the percentage of possible errors in each segment. The results are presented as slow tracking (the first 13 segments) and rapid tracking (the last 12 segments).
In the diazepam group, dental treatment was pro- Arithmetic longed so that the first test was performed 60 min The method of Smith and Sullivan (1965) was after the i.v. injection of diazepam with subsequent used. Columns of 15 digits from 1 to 9 taken from tests at 90, 120 and 180 min of recovery. tables of random numbers were added. After an initial practice on two columns of figures, as many columns as possible were added in 3 min. An accuracy Auditory and visual reaction times After warning the subject to be ready, there was factor was assessed from the number of columns a variable delay of 2-4 s before the observer synchro- correct, and the total number of columns attempted nously started an auditory or visual signal and a milli- was taken as a speed factor. second counter. The subject then pressed a thumb switch to stop both signal and counter and the re- The colour-word test action time was noted. After two practice attempts, This was a cognitive test (Stroop, 1935) which was 20 auditory and 20 visual reaction times were re- scored on time taken and errors made in three vercorded. The final result is the mean of 20 responses. sions of the test which were progressively more difficult (Jensen and Rohwer, 1966). The subject: 1. Read 100 words, being the names of colours Static ataxia printed in black on a white card. This complex continuous motor test has been used 2. Named 100 blocks of colour: blue, green, red by Eysenck (1960) and was performed using the and orange at random. apparatus described by Vickers (1965) to measure total body sway (cm), antero-posteriorly and laterally, 3. Named 100 colours on the incongruous card. The for 30 s each, with the eyes shut, the heels together words blue, green, red and orange were printed and the feet at an angle of 35-45°. in incongruous colours in a random order. The
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Methohexitone Halothane (short) Halothane (long) Diazepam Controls
Age (yr)
693
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM task was to ignore the word and name the colour of the print. This is similar to the test described by Frankenhaeuser and Post (1965), with orange substituted for yellow because it is easier to see on a white background. RESULTS
Reaction times The auditory reaction time result (fig. 1) at 5075 min showed impairment after methohexitone but not after short or long halothane anaesthesia. It was also impaired 1 h after diazepam, in contrast to the control group which produced a small but not significant improvement on the second test. The visual reaction time showed an improvement in the second
Static ataxia The results of the static ataxia test (fig. 2) showed the most marked impairment immediately after long halothane anaesthesia; impairment was still present in this group at 50-75 min. Impairment was still present 25-50 min after methohexitone, in contrast to the short halothane group result which was not significantly impaired at this stage. Impairment was marked 1 h after diazepam and was still present at 1.5 h. The results of the control group were unchanged on repetition of static ataxia. Tracking Slow tracking (fig. 3) showed slight but not significant improvement on repetition in the control group and at 25-50 min after short halothane and methohexitone anaesthesia. Marked impairment was still present 1 h after both long halothane anaesthesia and diazepam. Rapid tracking showed improvement on repetition in the control group and after short halothane
$8$
Short
Halothane
SB>
Methohexitone
•^
Long Halothane
•
Diazepam
^
Control
E.
i 25
50
1 (min)
1.5
3 24
(h) Recovery time
FIG. 1. Mean differences and SEM between initial result and each subsequent result for auditory reaction time. Positive differences represented a decline in performance and negative differences an improvement. Results after methohexitone were still impaired at 50-75 min.
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Thirteen different indices of recovery were recorded but only 11, shown in table II, were analysed because error scores in word and colour naming were negligible, even after anaesthesia or sedation. Student's t test was used to compare differences before and after anaesthesia and also in the control group. Unless stated otherwise, all differences in performance were statistically significant (P
Long Halothane
B
Diazepam
88
Control
6 5 4 3 2 1
w 25
50
1 (min)
3 24
1.5 (h) Recovery time
FIG. 2. Mean differences and SEM between initial result and each subsequent result for static ataxia.
anaesthesia. The other treated groups showed impairment in the first rapid tracking test after anaesthesia, with subsequent improvement. Arithmetic Adding accuracy (columns correct) improved on repetition in the control group but speed (columns attempted) did not. The only group with impaired accuracy was methohexitone at 15-25 min. However, when comparison was made with the control group, accuracy was impaired after short halothane at 1525 min, after methohexitone at up to 25-50 min, after long halothane at up to 50-75 min and after diazepam at up to 2 h. Speed was depressed after diazepam at up to 1.5 h, but did not change significantly in the other groups. The colour-word test The performance of the control group in the word test time score (fig. 4) improved on repetition. Little change occurred after short halothane, methohexitone and diazepam, but impairment was still present 50-75 min after long halothane.
The colour naming test and, to a greater extent, the incongruous colour-word test snowed greater improvement on repetition in the control group than the word test, reducing the value of these tests for detecting impairment. However, colour naming results still showed impairment 3 h after diazepam and also at 50-75 min after methohexitone when compared with the control group. Impairment was shown in the incongruous colourword test only after diazepam at 1 h by within-group comparison. By comparison with the control group, impairment was present 50-75 min after long halothane, and 1.5 h after diazepam. DISCUSSION
Methods of assessing recovery range from simple tests of crude clinical recovery (Green and Jolly, 1960; Goldman and Kennedy, 1964; Barry, Lawson and Davidson, 1967; Swerdlow and Moore, 1967: Brown and Dundee, 1968) to performance tests designed to detect lesser degrees of functional impairment. The latter are used as a means of measuring the speed and accuracy of central functioning rather than motor ability (Yates, 1973).
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"E 113
695
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM
Short Halolhane Methohexitone Long Halothane Diazepam Control
10 25
50
1 (min)
1.5
2
3 24
(h) Recovery time
FIG. 3. Mean differences and SEM between initial result and subsequent results for slow tracking. Results after long halothane were still impaired at 50-75 min, but patients felt so well recovered at 25-50 min after short halothane that it was not possible to persuade them to stay for the third test. Learning
Improvement in performance on repetition, under conditions which are otherwise unchanged, may be termed learning, and it has been shown to occur even in simple tapping and dexterity (King, 1954). Learning might be expected in more complex tests such as arithmetic and tracking and it has been shown to occur in the Stroop colour-word test, showing more improvement on repetition in the more complex versions of the test until it reaches a plateau of performance after three repetitions (Jensen and Rohwer, 1966). At this stage changes after drug treatment are demonstrated more easily (Frankenhaeuser and Post, 1965). However, in the present study it was not possible to test the patients more than once before operation, nor was it feasible to perform tests that have been recommended as having absence of learning, such as the flicker-fusion test (Vickers, 1965). Therefore reliance was placed on tests that showed minimal learning. In other tests a comparison was made with the results of a control group. A small improvement in performance occurred between the first and second test in auditory and 57
visual reaction times in the control group, but this was not significant in the auditory response. This may be accounted for by a lack of practice before starting because subsequent results were unchanged. King (1954) found very little reduction in auditory reaction time on repetition. The results following repetition of the static ataxia test were unchanged, although the results of all tests reflect the rather small number of cases in each group. In the control group arithmetic accuracy, but not speed, improved on repetition. The tracking results improved on the second test in both versions of the test, but by a greater degree in the rapid tracking. The colour-word test showed improvement in performance which was progressively greater in degree in words, colours and the incongruous version for up to three repetitions. This is the same as the finding of Jensen and Rohwer (1966), who found also that both the test-re-test interval, and age, did not influence the score significantly. Recovery
The results of the performance tests used suggest that the trend towards recovery, in order, is short
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10 -
696
BRITISH JOURNAL OF ANAESTHESIA 16 -
Short Halothane Methohexitone Long Halothane Diazepam Control
3 24
1.5
1 (min)
(h)
Recovery time
FIG. 4. Mean differences and SEM of the time score in the Stroop word test. The small column at 2 h represents diazepam.
halothane with nitrous oxide, methohexitone, long halothane with nitrous oxide and finally diazepam with local anaesthesia. The treatment times of the methohexitone group and the short halothane group were similar and brief and are therefore compared most appropriately. No impairment was found at more than 25 min after short halothane and nitrous oxide anaesthesia, whereas at 50-75 min after methohexitone the results of two tests were still impaired. The suggestion of a briefer recovery time after short halothane than after methohexitone is in keeping with the observations of Hannington-Kiff (1970). Using a Maddox wing to measure extra-ocular balance, he found that the trend towards recovery in the first half-hour was more rapid after halothane and nitrous oxide than when methohexitone was given in addition to the inhalation agents. The results are also consistent with Vickers' (1965) findings of a recovery time of 45-60 and 60-90 min for methohexitone 1 mg/kg and 2 mg/kg respectively, using pegboard, static ataxia and flicker-fusion tests, and the results
of Grove-White and Kelman (1971) who showed changes in the flicker-fusion test up to 90 min after methohexitone 0.15 mg/kg. More prolonged impairment after methohexitone was found by Doenicke and colleagues (1966), who demonstrated electroencephalographic changes with the potentiating effect of a small dose of alcohol 12 h after methohexitone. However, results which show interpotentiation between barbiturates and alcohol are clearly applicable to these drugs only, and not to halothane or diazepam. At 50-75 min after long halothane and nitrous oxide, the results of four tests were impaired. This is likely to be a result of halothane rather than nitrous oxide because recovery after nitrous oxide alone is very rapid (Eysenck, 1960). There is evidence that recovery time after diazepam is related to the dose. Grove-White and Kelman (1971) demonstrated changes in the flicker-fusion test at up to 90 min after diazepam 0.05 mg/kg. The present study found impairment of two cognitive tests, colour naming and arithmetic accuracy, at 3 h after diazepam at a mean dose of 0.31 mg/kg. It was
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50
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM also found that demonstrable ataxia lasted only 1.5 h. This is in contrast to the findings of Brown and Dundee (1968), who demonstrated ataxia in 30% of subjects at 24 h after diazepam 0.6 mg/kg. These figures suggest that a large dose of diazepam is followed by a much longer recovery time. CONCLUSIONS
ACKNOWLEDGEMENTS
I gratefully acknowledge my indebtedness to Professor E. A. Cooper and Dr W. Ryder for their most generous help and advice with this study and to Professor D. J. Newall and Mrs D. Weightman for advice on statistics. I am grateful to Dr R. D. Savage and Mr D. Watson for their advice on psychometric tests and to the patients and staff at the Dental Hospital and the Royal Victoria Infirmary, Newcastle Upon Tyne, for their co-operation in performing tests. REFERENCES
Barry, C. T., Lawson, R., and Davidson, D. G. D. (1967). Recovery after methohexitone and thiopentone. Anaesthesia, 22, 228. Brown, S. S., and Dundee, J. W. (1968). Clinical studies of induction agents. XXV: Diazepam. Br. J. Anaesth., 40, 108. Doenicke, A., Kugler, J., Schellenberger, A., and Gurtner, T. (1966). The use of the e.e.g. to measure recovery time after intravenous anaesthesia. Br. J. Anaesth., 38, 580. Eysenck, H. J. (1960). Handbook of Abnormal Psychology, 1st edn, pp. 42, 671. London: Pitman. Frankenhaeuser, M., and Post, B. (1965). Objective and Subjective Performance as influenced by Drug-induced Variations in Activation Level. Report from the Psychological Laboratories, the University of Stockholm, No. 184. Goldman, V., and Kennedy, P. (1964). A non-barbituate intravenous anaesthetic. Anaesthesia, 19, 424. Green, R. A., and Jolly, C. (1960). Methohexitone in dental anaesthesia. Br. J. Anaesth., 32, 593. Grove-White, I. G., and Kelman, G. R. (1971). Critical flickers frequency after a small dose of methohexitone, diazepam and sodium 4-hydroxybutyrate. Br.J. Anaesth., 43, 110.
Hannington-Kiff, J. G. (1970). Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br. Med.J.,3, 132. Hughes, F. W., Forney, R. B., and Richards, A. B. (1965). Comparative effects in human subjects of chlordiazepoxide, diazepam and placebo on mental and physical performance. Clin. Pharmacol. Ther., 6, 139. Jenson, A. R., and Rohwer, W. D., jr (1966). The Stroop colour-word test. Acta Psychol. (Amst)., 25, 36. King, H. E. (1954). Psychomotor Aspects of Mental Disease_ p. 45. Commonwealth Fund: Harvard University Press. Smith, S. E., and Sullivan, T. J. (1965). The effect of cyclobarbitone on mental performance: a teaching experiment. J. Med. Educ, 40, 294. Stroop, J. R. (1935). Interference in serial verbal reaction. J. Exp. Psychol., 18, 643. Swerdlow, M., and Moore, B. A. (1967). A dose duration trial with propanidid. Br. J. Anaesth., 39, 573. Vickers, M. D. (1965). The measurement of recovery from anaesthesia. Br. J. Anaesth., 37, 296. Yates, A. J. (1973). Abnormalities of psychomotor functions; in Handbook of Abnormal Psychology (ed. H. J. Eysenck), 2nd edn, p. 261. London: Pitman. REPRISE DE CONSCIENCE APRES ANESTHESIE AU METHOHEXITONE, A L'HALOTHANE ET AU DIAZEPAM RESUME
Cinq tests moteurs et six tests cognitifs ont ete effectues une fois avant et plusieurs fois en serie apres anesthesie de courte et de longue duree a l'halothane et a l'oxyde azoteux, apres anesthesie au methohexitone, et apres sedation au diazepam avec anesthesie. locale. Un groupe de controle non-traite a egalement ete teste. Les resultats indiquent que pendant la premiere heure, la reprise de conscience a ete la plus rapide apres anesthesie de courte duree a l'halothane et a l'oxyde azoteux, moins rapide apres anesthesie au methohexitone seul et la moins rapide apres anesthesie de longue duree a l'halothane et a l'oxyde azoteux. La reprise de conscience apres sedation au diazepam avec anesthesie locale a ete longue et etait incomplete 3 h apres. DIE WIEDERHERSTELLUNG DES BEWUSSTSEINS NACH METHOHEXITON, HALOTHAN UND DIAZEPAM ZUSAMMENFASSUNG
Es wurden fiinf motorische und sechs Erkenntis-Teste einmal vor, und darauf seriell nach der Narkose mit Halothan und Stickstoff beim kurzen oder anhaltenden Gebrauch, sowie auch bei Narkose mit Methohexiton und bei Diazepamsedierungen durchgefuhrt. Eine unbehandelte Kontrollgruppe wurde ebenfalls getestet. Die Resultate zeigten, dass sich die Patienten am schnellsten nach KurzdauerHalothan und Stickstoff erholten, weniger schnell nach Methohexiton als einzigen Mittel und am langsamsten, nach lange anhaltender Halothan- und Stickstoffgabe. Wiederherstellung nach Diazepam, in Kombination mit Lokalanaesthesie war verzogert und nach 3 Stunden noch unvollstandig.
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The results of this study suggest that the trend towards recovery in the first hour was most rapid after short halothane and nitrous oxide, was less rapid after methohexitone alone and was least rapid after long halothane and nitrous oxide. Recovery after diazepam with local anaesthesia was prolonged and was still incomplete at 3 h. This study suggests that halothane is more suitable than methohexitone for short procedures where a brief recovery time is desirable. It suggests that a progressively longer recovery time should be allowed after methohexitone, longer halothane anaesthesia, and diazepam.
697
BRITISH JOURNAL OF ANAESTHESIA
698 RESTABLECIMIENTO TRAS METOHEXITAL, HALOTANO Y DIAZEPAM SUMARIO
Se efectuaron cinco pruebas motoras y seis pruebas de comprension una vez antes y luego en serie tras la anestesia con halotano y oxido nitroso, de duracion breve y larga, anestesia con metohexital, y sedacion con diazepam con
anestesia local. Tambien se sometio a prueba a un grupo testigo sin tratar. Los resultados sugieren que en la primera hora la recuperacion fue lo mas rapida tras halotano y oxido nitroso de breve duracion, menos rapida tras metohexital solo, y la menos rapida tras halotano y oxido nitroso de larga duracion. La recuperacion tras diazepam con anestesia local fue prolongada y era incompleta a las 3 h.
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RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM G. D. GALE SUMMARY
Both methohexitone and diazepam i.v. are used widely to produce anaesthesia and sedation for short procedures in dentistry. The pharmacology of these agents suggests a much longer duration of action than would appear desirable and, in recent years, several papers (Doenicke et al., 1966; Brown and Dundee, 1968; Grove-White and Kelman, 1971) have attempted to assess the duration of recovery from these agents and have confirmed prolonged residual effects. The present study in dental and surgical outpatients was designed to measure the recovery times from methohexitone and from diazepam, and to compare them with recovery times after halothane and nitrous oxide administered for both short and long periods. PROCEDURES TO BE COMPARED
(1) Methohexitone anaesthesia Methohexitone was given i.v. to 16 patients undergoing dental extraction. The dose was assessed by the anaesthetist on the basis of his clinical experience and ranged from 1.07 to 1.79 mg/kg (mean 1.51 mg/kg). The duration of anaesthesia ranged from 2.5 to 10 min (mean 4.6 min). (2) Short-duration halothane anaesthesia Halothane in 70-80% nitrous oxide in oxygen was given to seven patients undergoing dental extraction and two patients undergoing minor surgery. The duration of anaesthesia ranged from 3 to 12 min (mean 6.2 min). G. D. GALE, M.B., B.S., F.F.A.R.C.S., F.R.C.P.(C), D.(OBST.),
R.C.O.G., Department of Anaesthesia, The Royal Victoria Infirmary, Newcastle Upon Tyne NEL 4LP. Present address: Department of Anaesthesia, Toronto General Hospital, 101 College Street, Toronto, Canada M5G 1L7.
(3) Long-duration halothane anaesthesia Halothane in 70-80 °/% nitrous oxide in oxygen was given to eight patients undergoing minor surgery. The duration of anaesthesia ranged from 20 to 60 min (mean 32 min). (4) Diazepam sedation A single i.v. injection of diazepam was given to eight patients undergoing conservative dentistry, at a rate of 4 mg/min until slurred speech and drooping of the eyelids occurred. The mean dose was 0.31 mg/kg (range 0.28-0.51 mg/kg). In addition, the patients received local analgesia. The dental treatment was prolonged (range 20-69 min; mean 47 min). (5) Control group Eleven subjects were tested hourly for 4 h on one day and once on the next day to determine the effects of repetition on the performance tests. Details of the groups are summarized in table I. In all the anaesthetic techniques atropine was given at the discretion of the anaesthetist. METHOD OF ASSESSMENT
The motor and cognitive tests (table II) were performed by the patients before, and serially after, anaesthesia so that performance could be compared before and after anaesthesia within the group and also with a control group receiving no anaesthesia or sedation. The recovery phase was defined as beginning when the drug administration ceased. Therefore recovery began when the inhalation anaesthetic ended or when the i.v. injection of diazepam or methohexitone was completed. The tests were performed on the methohexitone and halothane groups at 15-25 min, 25-50 min and 50-75 min after the start of recovery.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on March 14, 2015
Five motor and six cognitive tests were performed once before and then serially after anaesthesia with halothane and nitrous oxide of both short and long duration, methohexitone anaesthesia, and diazepam sedation with local anaesthesia. An untreated control group was also tested. The results suggest that, in the first hour, recovery was most rapid after short-duration halothane and nitrous oxide, was less rapid after methohexitone alone and was least rapid after long-duration halothane and nitrous oxide. Recovery after diazepam with local anaesthesia was prolonged and was incomplete at 3 h.
BRITISH JOURNAL OF ANAESTHESIA
692
TABLE I. Details of groups and procedures. Treatment time refers to the length of the dental or surgical treatment Number
Range
M
F
Mean
Range
Mean
Range
16 9 8 8 11
32.4 25.7 30.3 28.5 33.1
19-59 14-41 14-^15 17-43 17-56
9 6 1 2 6
7 3 7 6 5
68.2 66.1 62.0 60.8 77.3
51-118 45.5-93 45.5-88 52-68 54-95.5
4.6 6.2 31.9 47.6 —
2.5-10 3-12 20-60 20-69.5 —
—auditory —visual —slow —rapid
Cognitive tests Arithmetic
Treatment time (min)
Mean
Motor tests
1. 2. 3. 4. 5.
Weight (kg)
subjects
TABLE II. Tests used as indices of recovery from anaesthesia and sedation
1. Reaction time 2. 3. Static ataxia 4. Tracking 5.
Sex
—columns correct —columns attempted Word naming —time score Colour naming —time score Incongruous colour-words—time score 6. —error score
Tracking This paced, complex co-ordination test was similar to the pursuit meter described by Hughes, Forney and Richards (1965). The apparatus comprised a circular turntable which revolved once every 56 s and carried a paper disk with a spiral of 240 small circular targets divided radially into 25 segments. The targets rotated slowly near the centre and progressively faster near the periphery. The subject viewed the moving targets through a slit in the lid of the apparatus and was asked to hit targets with a pencil thus making a spiral line through the targets. Errors occurred when targets were missed and these were converted into the percentage of possible errors in each segment. The results are presented as slow tracking (the first 13 segments) and rapid tracking (the last 12 segments).
In the diazepam group, dental treatment was pro- Arithmetic longed so that the first test was performed 60 min The method of Smith and Sullivan (1965) was after the i.v. injection of diazepam with subsequent used. Columns of 15 digits from 1 to 9 taken from tests at 90, 120 and 180 min of recovery. tables of random numbers were added. After an initial practice on two columns of figures, as many columns as possible were added in 3 min. An accuracy Auditory and visual reaction times After warning the subject to be ready, there was factor was assessed from the number of columns a variable delay of 2-4 s before the observer synchro- correct, and the total number of columns attempted nously started an auditory or visual signal and a milli- was taken as a speed factor. second counter. The subject then pressed a thumb switch to stop both signal and counter and the re- The colour-word test action time was noted. After two practice attempts, This was a cognitive test (Stroop, 1935) which was 20 auditory and 20 visual reaction times were re- scored on time taken and errors made in three vercorded. The final result is the mean of 20 responses. sions of the test which were progressively more difficult (Jensen and Rohwer, 1966). The subject: 1. Read 100 words, being the names of colours Static ataxia printed in black on a white card. This complex continuous motor test has been used 2. Named 100 blocks of colour: blue, green, red by Eysenck (1960) and was performed using the and orange at random. apparatus described by Vickers (1965) to measure total body sway (cm), antero-posteriorly and laterally, 3. Named 100 colours on the incongruous card. The for 30 s each, with the eyes shut, the heels together words blue, green, red and orange were printed and the feet at an angle of 35-45°. in incongruous colours in a random order. The
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on March 14, 2015
Methohexitone Halothane (short) Halothane (long) Diazepam Controls
Age (yr)
693
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM task was to ignore the word and name the colour of the print. This is similar to the test described by Frankenhaeuser and Post (1965), with orange substituted for yellow because it is easier to see on a white background. RESULTS
Reaction times The auditory reaction time result (fig. 1) at 5075 min showed impairment after methohexitone but not after short or long halothane anaesthesia. It was also impaired 1 h after diazepam, in contrast to the control group which produced a small but not significant improvement on the second test. The visual reaction time showed an improvement in the second
Static ataxia The results of the static ataxia test (fig. 2) showed the most marked impairment immediately after long halothane anaesthesia; impairment was still present in this group at 50-75 min. Impairment was still present 25-50 min after methohexitone, in contrast to the short halothane group result which was not significantly impaired at this stage. Impairment was marked 1 h after diazepam and was still present at 1.5 h. The results of the control group were unchanged on repetition of static ataxia. Tracking Slow tracking (fig. 3) showed slight but not significant improvement on repetition in the control group and at 25-50 min after short halothane and methohexitone anaesthesia. Marked impairment was still present 1 h after both long halothane anaesthesia and diazepam. Rapid tracking showed improvement on repetition in the control group and after short halothane
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Short
Halothane
SB>
Methohexitone
•^
Long Halothane
•
Diazepam
^
Control
E.
i 25
50
1 (min)
1.5
3 24
(h) Recovery time
FIG. 1. Mean differences and SEM between initial result and each subsequent result for auditory reaction time. Positive differences represented a decline in performance and negative differences an improvement. Results after methohexitone were still impaired at 50-75 min.
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Thirteen different indices of recovery were recorded but only 11, shown in table II, were analysed because error scores in word and colour naming were negligible, even after anaesthesia or sedation. Student's t test was used to compare differences before and after anaesthesia and also in the control group. Unless stated otherwise, all differences in performance were statistically significant (P
Long Halothane
B
Diazepam
88
Control
6 5 4 3 2 1
w 25
50
1 (min)
3 24
1.5 (h) Recovery time
FIG. 2. Mean differences and SEM between initial result and each subsequent result for static ataxia.
anaesthesia. The other treated groups showed impairment in the first rapid tracking test after anaesthesia, with subsequent improvement. Arithmetic Adding accuracy (columns correct) improved on repetition in the control group but speed (columns attempted) did not. The only group with impaired accuracy was methohexitone at 15-25 min. However, when comparison was made with the control group, accuracy was impaired after short halothane at 1525 min, after methohexitone at up to 25-50 min, after long halothane at up to 50-75 min and after diazepam at up to 2 h. Speed was depressed after diazepam at up to 1.5 h, but did not change significantly in the other groups. The colour-word test The performance of the control group in the word test time score (fig. 4) improved on repetition. Little change occurred after short halothane, methohexitone and diazepam, but impairment was still present 50-75 min after long halothane.
The colour naming test and, to a greater extent, the incongruous colour-word test snowed greater improvement on repetition in the control group than the word test, reducing the value of these tests for detecting impairment. However, colour naming results still showed impairment 3 h after diazepam and also at 50-75 min after methohexitone when compared with the control group. Impairment was shown in the incongruous colourword test only after diazepam at 1 h by within-group comparison. By comparison with the control group, impairment was present 50-75 min after long halothane, and 1.5 h after diazepam. DISCUSSION
Methods of assessing recovery range from simple tests of crude clinical recovery (Green and Jolly, 1960; Goldman and Kennedy, 1964; Barry, Lawson and Davidson, 1967; Swerdlow and Moore, 1967: Brown and Dundee, 1968) to performance tests designed to detect lesser degrees of functional impairment. The latter are used as a means of measuring the speed and accuracy of central functioning rather than motor ability (Yates, 1973).
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"E 113
695
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM
Short Halolhane Methohexitone Long Halothane Diazepam Control
10 25
50
1 (min)
1.5
2
3 24
(h) Recovery time
FIG. 3. Mean differences and SEM between initial result and subsequent results for slow tracking. Results after long halothane were still impaired at 50-75 min, but patients felt so well recovered at 25-50 min after short halothane that it was not possible to persuade them to stay for the third test. Learning
Improvement in performance on repetition, under conditions which are otherwise unchanged, may be termed learning, and it has been shown to occur even in simple tapping and dexterity (King, 1954). Learning might be expected in more complex tests such as arithmetic and tracking and it has been shown to occur in the Stroop colour-word test, showing more improvement on repetition in the more complex versions of the test until it reaches a plateau of performance after three repetitions (Jensen and Rohwer, 1966). At this stage changes after drug treatment are demonstrated more easily (Frankenhaeuser and Post, 1965). However, in the present study it was not possible to test the patients more than once before operation, nor was it feasible to perform tests that have been recommended as having absence of learning, such as the flicker-fusion test (Vickers, 1965). Therefore reliance was placed on tests that showed minimal learning. In other tests a comparison was made with the results of a control group. A small improvement in performance occurred between the first and second test in auditory and 57
visual reaction times in the control group, but this was not significant in the auditory response. This may be accounted for by a lack of practice before starting because subsequent results were unchanged. King (1954) found very little reduction in auditory reaction time on repetition. The results following repetition of the static ataxia test were unchanged, although the results of all tests reflect the rather small number of cases in each group. In the control group arithmetic accuracy, but not speed, improved on repetition. The tracking results improved on the second test in both versions of the test, but by a greater degree in the rapid tracking. The colour-word test showed improvement in performance which was progressively greater in degree in words, colours and the incongruous version for up to three repetitions. This is the same as the finding of Jensen and Rohwer (1966), who found also that both the test-re-test interval, and age, did not influence the score significantly. Recovery
The results of the performance tests used suggest that the trend towards recovery, in order, is short
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10 -
696
BRITISH JOURNAL OF ANAESTHESIA 16 -
Short Halothane Methohexitone Long Halothane Diazepam Control
3 24
1.5
1 (min)
(h)
Recovery time
FIG. 4. Mean differences and SEM of the time score in the Stroop word test. The small column at 2 h represents diazepam.
halothane with nitrous oxide, methohexitone, long halothane with nitrous oxide and finally diazepam with local anaesthesia. The treatment times of the methohexitone group and the short halothane group were similar and brief and are therefore compared most appropriately. No impairment was found at more than 25 min after short halothane and nitrous oxide anaesthesia, whereas at 50-75 min after methohexitone the results of two tests were still impaired. The suggestion of a briefer recovery time after short halothane than after methohexitone is in keeping with the observations of Hannington-Kiff (1970). Using a Maddox wing to measure extra-ocular balance, he found that the trend towards recovery in the first half-hour was more rapid after halothane and nitrous oxide than when methohexitone was given in addition to the inhalation agents. The results are also consistent with Vickers' (1965) findings of a recovery time of 45-60 and 60-90 min for methohexitone 1 mg/kg and 2 mg/kg respectively, using pegboard, static ataxia and flicker-fusion tests, and the results
of Grove-White and Kelman (1971) who showed changes in the flicker-fusion test up to 90 min after methohexitone 0.15 mg/kg. More prolonged impairment after methohexitone was found by Doenicke and colleagues (1966), who demonstrated electroencephalographic changes with the potentiating effect of a small dose of alcohol 12 h after methohexitone. However, results which show interpotentiation between barbiturates and alcohol are clearly applicable to these drugs only, and not to halothane or diazepam. At 50-75 min after long halothane and nitrous oxide, the results of four tests were impaired. This is likely to be a result of halothane rather than nitrous oxide because recovery after nitrous oxide alone is very rapid (Eysenck, 1960). There is evidence that recovery time after diazepam is related to the dose. Grove-White and Kelman (1971) demonstrated changes in the flicker-fusion test at up to 90 min after diazepam 0.05 mg/kg. The present study found impairment of two cognitive tests, colour naming and arithmetic accuracy, at 3 h after diazepam at a mean dose of 0.31 mg/kg. It was
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50
RECOVERY FROM METHOHEXITONE, HALOTHANE AND DIAZEPAM also found that demonstrable ataxia lasted only 1.5 h. This is in contrast to the findings of Brown and Dundee (1968), who demonstrated ataxia in 30% of subjects at 24 h after diazepam 0.6 mg/kg. These figures suggest that a large dose of diazepam is followed by a much longer recovery time. CONCLUSIONS
ACKNOWLEDGEMENTS
I gratefully acknowledge my indebtedness to Professor E. A. Cooper and Dr W. Ryder for their most generous help and advice with this study and to Professor D. J. Newall and Mrs D. Weightman for advice on statistics. I am grateful to Dr R. D. Savage and Mr D. Watson for their advice on psychometric tests and to the patients and staff at the Dental Hospital and the Royal Victoria Infirmary, Newcastle Upon Tyne, for their co-operation in performing tests. REFERENCES
Barry, C. T., Lawson, R., and Davidson, D. G. D. (1967). Recovery after methohexitone and thiopentone. Anaesthesia, 22, 228. Brown, S. S., and Dundee, J. W. (1968). Clinical studies of induction agents. XXV: Diazepam. Br. J. Anaesth., 40, 108. Doenicke, A., Kugler, J., Schellenberger, A., and Gurtner, T. (1966). The use of the e.e.g. to measure recovery time after intravenous anaesthesia. Br. J. Anaesth., 38, 580. Eysenck, H. J. (1960). Handbook of Abnormal Psychology, 1st edn, pp. 42, 671. London: Pitman. Frankenhaeuser, M., and Post, B. (1965). Objective and Subjective Performance as influenced by Drug-induced Variations in Activation Level. Report from the Psychological Laboratories, the University of Stockholm, No. 184. Goldman, V., and Kennedy, P. (1964). A non-barbituate intravenous anaesthetic. Anaesthesia, 19, 424. Green, R. A., and Jolly, C. (1960). Methohexitone in dental anaesthesia. Br. J. Anaesth., 32, 593. Grove-White, I. G., and Kelman, G. R. (1971). Critical flickers frequency after a small dose of methohexitone, diazepam and sodium 4-hydroxybutyrate. Br.J. Anaesth., 43, 110.
Hannington-Kiff, J. G. (1970). Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br. Med.J.,3, 132. Hughes, F. W., Forney, R. B., and Richards, A. B. (1965). Comparative effects in human subjects of chlordiazepoxide, diazepam and placebo on mental and physical performance. Clin. Pharmacol. Ther., 6, 139. Jenson, A. R., and Rohwer, W. D., jr (1966). The Stroop colour-word test. Acta Psychol. (Amst)., 25, 36. King, H. E. (1954). Psychomotor Aspects of Mental Disease_ p. 45. Commonwealth Fund: Harvard University Press. Smith, S. E., and Sullivan, T. J. (1965). The effect of cyclobarbitone on mental performance: a teaching experiment. J. Med. Educ, 40, 294. Stroop, J. R. (1935). Interference in serial verbal reaction. J. Exp. Psychol., 18, 643. Swerdlow, M., and Moore, B. A. (1967). A dose duration trial with propanidid. Br. J. Anaesth., 39, 573. Vickers, M. D. (1965). The measurement of recovery from anaesthesia. Br. J. Anaesth., 37, 296. Yates, A. J. (1973). Abnormalities of psychomotor functions; in Handbook of Abnormal Psychology (ed. H. J. Eysenck), 2nd edn, p. 261. London: Pitman. REPRISE DE CONSCIENCE APRES ANESTHESIE AU METHOHEXITONE, A L'HALOTHANE ET AU DIAZEPAM RESUME
Cinq tests moteurs et six tests cognitifs ont ete effectues une fois avant et plusieurs fois en serie apres anesthesie de courte et de longue duree a l'halothane et a l'oxyde azoteux, apres anesthesie au methohexitone, et apres sedation au diazepam avec anesthesie. locale. Un groupe de controle non-traite a egalement ete teste. Les resultats indiquent que pendant la premiere heure, la reprise de conscience a ete la plus rapide apres anesthesie de courte duree a l'halothane et a l'oxyde azoteux, moins rapide apres anesthesie au methohexitone seul et la moins rapide apres anesthesie de longue duree a l'halothane et a l'oxyde azoteux. La reprise de conscience apres sedation au diazepam avec anesthesie locale a ete longue et etait incomplete 3 h apres. DIE WIEDERHERSTELLUNG DES BEWUSSTSEINS NACH METHOHEXITON, HALOTHAN UND DIAZEPAM ZUSAMMENFASSUNG
Es wurden fiinf motorische und sechs Erkenntis-Teste einmal vor, und darauf seriell nach der Narkose mit Halothan und Stickstoff beim kurzen oder anhaltenden Gebrauch, sowie auch bei Narkose mit Methohexiton und bei Diazepamsedierungen durchgefuhrt. Eine unbehandelte Kontrollgruppe wurde ebenfalls getestet. Die Resultate zeigten, dass sich die Patienten am schnellsten nach KurzdauerHalothan und Stickstoff erholten, weniger schnell nach Methohexiton als einzigen Mittel und am langsamsten, nach lange anhaltender Halothan- und Stickstoffgabe. Wiederherstellung nach Diazepam, in Kombination mit Lokalanaesthesie war verzogert und nach 3 Stunden noch unvollstandig.
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The results of this study suggest that the trend towards recovery in the first hour was most rapid after short halothane and nitrous oxide, was less rapid after methohexitone alone and was least rapid after long halothane and nitrous oxide. Recovery after diazepam with local anaesthesia was prolonged and was still incomplete at 3 h. This study suggests that halothane is more suitable than methohexitone for short procedures where a brief recovery time is desirable. It suggests that a progressively longer recovery time should be allowed after methohexitone, longer halothane anaesthesia, and diazepam.
697
BRITISH JOURNAL OF ANAESTHESIA
698 RESTABLECIMIENTO TRAS METOHEXITAL, HALOTANO Y DIAZEPAM SUMARIO
Se efectuaron cinco pruebas motoras y seis pruebas de comprension una vez antes y luego en serie tras la anestesia con halotano y oxido nitroso, de duracion breve y larga, anestesia con metohexital, y sedacion con diazepam con
anestesia local. Tambien se sometio a prueba a un grupo testigo sin tratar. Los resultados sugieren que en la primera hora la recuperacion fue lo mas rapida tras halotano y oxido nitroso de breve duracion, menos rapida tras metohexital solo, y la menos rapida tras halotano y oxido nitroso de larga duracion. La recuperacion tras diazepam con anestesia local fue prolongada y era incompleta a las 3 h.
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