Recovery after day-case anaesthesia

Transcription

1 Anaesthesia, 1990, Volume 45, pages Recovery after day-case anaesthesia A 24-hour comparison of recovery after thiopentone or propofol anaesthesia P. J. HEATH, T. W. OGG AND W. R. GILKS Summary Sixty patients who presented for day-case dilatation and curettage were allocated randomly to receive either thiopentone or propofol for induction and maintenance of anaesthesia. One anaesthetist administered all the anaesthetics whilst all assessments were made by one other. The results indicate that early recovery of memory function, critical flicker fusion frequency and subjective feelings of tiredness, drowsiness and alertness were superior in the propofol group. There was a significant difference in subjective feelings of tiredness and drowsiness recorded by the two study groups at 24 hours. Memory function assessed by Wechsler logical memory function passages at 24 hours was impaired in the propofol group in comparison to a group of reference subjects. Key words Anaesthesia; outpatient. Recovery. It has been established that propofol and thiopentone provide a better quality of induction, maintenance and recovery than the two other commonly used intravenous anaesthetic agents. Immediate recovery after propofol anaesthesia is more rapid than with thiopentone, but there are few reports of longer term differences in recovery between the two agent^.^.^ Thiopentone is metabolised slowly and is associated with a hangover effect, which is a disadvantage if the agent is used for day-case anaesthesia. The aim of this study was to examine the recovery of patients during the first 24 hours after anaesthesia with propofol or thiopentone. Method Approval for this double-blind, parallel-group, comparative study was granted by the local District Ethics Committee. Sixty female patients who presented for dilatation and curettage (D and C) and who satisfied the inclusion criteria took part in the study. All were between 18 and 60 years of age, weighed less than 80 kg and were graded ASA 1 or 2. The patients were accompanied home after the procedure and remained there for 24 hours after recovery. Those taking any other medication were excluded from the study. Subjects were recruited on arrival at the day surgery unit and gave written informed consent to participate in the study. The National Adult Reading Test was employed as a measure of Intelligence Quotient at the first testing session only.4 All assessments of recovery were performed preoperatively to establish a baseline, and at 1, 2 and 24 hours after recovery. The 24-hour assessment was made in the patient s home. A Linear Analogue Rating Scale (LARS) was used to assess tiredness, drowsiness, and alertnes~.~ The 10-cm visual analogue scales were marked less tired, less drowsy and less alert at the left end and more tired, more drowsy and more alert at the right end. Each scale was marked in the centre as an indication of the normal sensation for that time of day. Scores were recorded as millimetres from the left end of the scale. Patient recovery was assessed using a portable critical flicker fusion apparatus. The mean value of three increasing and three decreasing fusion frequencies was recorded at each test session. Memory function was assessed by Wechsler logical memory function test passages6 and Bethune s modification of the Williams memory function test. The Wechsler logical memory function test is well established and examines recall for the details of a short story passage immediately after it is read to the subject. There is no visual component to this test. A different Wechsler passage was used at each presentation. Bethune s modification of Williams memory function test employs picture cards displaying nine pictures that are P.J. Heath, FFARCS, Senior Registrar, Anaesthetic Department, Southampton General Hospital, Southampton SO9 4XY. T.W. Ogg, MA, FFARCS, Consultant and Director, Day Case Surgical Unit, Addenbrooke s Hospital, Cambridge CB2 2QQ, W.R. Gilks, MSc, PhD, Statistician, Medical Research Council, Biostatistics Unit, Cambridge CB2 2BW. Accepted 20 February /90/ The Association of Anaesthetists of Gt Britain and Ireland 91 1

2 912 P.J. Heath, T. W. Ogg and W.R. Gilks Table 1. Mean (SD) values for age, weight, heart rate and intelligence quotient (I.Q.) and duration of anaesthesia in the series. P Reference P reference reference Thiopentone Propofol (t-test) group (F-stats) (t-test) (t-test) Age; years 43.0 (8.9) 41.3 (8.9) (8.6) Weight; kg 62.0 (7.4) 61.5 (8.4) (7.5) Heart rate; beats/minute 72.8 (14.0) 73.1 (13.0) (10.7) I.Q (6.9) (9.2) (5.3) Duration of anaesthesia; (minutes) 6.3 (1.9) 6.1 (1.7) given to the subjects for 60 seconds to memorise. The subjects are asked to recall the pictures on the card 10 minutes later. Standard verbal clues are given for those that they are unable to recall and, if still unable to recall any pictures, the subjects are asked to pick the remaining pictures from a card containing the original nine pictures and six distracting pictures. An error score is assigned for the number of pictures that were not recalled at each stage. The maximum error score for each card at each session is 8 I. Bethune s memory function test was modified further to include a fifth test card, the E card. Subjects were shown two cards at each presentation. The second card was always the D card. One of the remaining cards was presented before the D card at each test session. Penalty scoring for the test was as described originally. Subjects were allocated randomly to one of the two test groups and were unaware of the anaesthetic agents administered. Both groups received alfentanil 7.5 pg/kg and were allowed to breathe 70% nitrous oxide in oxygen via a Bain system. Anaesthesia was induced in the propofol group with propofol 2.5 mg/kg and maintained with incremental doses of propofol as indicated clinically. One millilitre of lignocaine 1% plain was added to 20 ml propofol to reduce the pain on injection. Anaesthesia was induced in the thiopentone group with thiopentone 5.0 mg/ kg and maintained with incremental doses of thiopentone administered as required. All patients were nursed in a recovery area after surgery and returned to the main ward 30 minutes after recovery from anaesthesia. Intramuscular metoclopramide 10 mg and paracetamol g orally were prescribed as required. All patients were discharged from the unit within 3 hours of surgery. Two anaesthetists were involved in the study; one administered all the anaesthetics whilst the other, unaware of the agent administered, made all the assessments including those in the patient s home at 24 hours. A group of 30 volunteers from the nursing and ancillary staff were invited to perform the recovery tests. They served as a reference group and helped to identify any learning effect of the tests employed. We refer to this group as a reference rather than a control group because in the context of randomised clinical trials the control group is included in the randomisation. The selection criteria for the reference group were similar to the study groups but personnel with prior knowledge of any of the recovery tests were excluded. Statistical analysis of the data from the two study groups was performed using Student s t-test. One-way analysis of variance was employed when the reference group was included in the analysis.16 Each study group was compared with the reference group using Student s t-test. A p value of less than 0.05 was considered statistically significant. Results Table 1 shows the demographic details and intelligence quotients of patients in the three groups. Tables 2, 3 and 4 record the LARS scores for tiredness, drowsiness and alertness in the three groups at 0, 1, 2, and 24 hours. A score of 50 is the normal feeling for that time of day for each variable. A score of less than 50 suggests less tired, less drowsy and less alert and scores more than 50 more tired, more drowsy and more alert. Differences between the treatment groups were statistically significant 1 hour after recovery for all these variables and at 24 hours for feelings of tiredness and drowsiness. Drowsiness scores were significantly higher in the thiopentone group than the reference group before the study and alertness scores in both study groups were significantly lower than in the reference group at the pre-operative, and one and 2 hour postoperative test sessions. Table 5 shows the error scores for Bethune s modification of Williams memory function test. Higher scores indicate that more errors were made. There was a statistically significant difference between the treatment groups in the performance for new cards one hour after recovery. Both groups performed significantly less well with new cards than did the reference group at one and 2 hours after operation. Patients in the thiopentone group also made more errors than those in the reference group with the D card at one hour. Table 2. Mean (SD) values for tiredness measured by a linear analogue rating scale (mm). Hours Thiopentone Propofol (t-test) group (F-stats) (t-test) (1-test) (8.5) 50.0 (22.0) (16.4) (14.4) 57.4 (20.2) (14.7) <O.OOOl (18.0) 52.0 (25.6) (19.1) (13.4) 39.9 (25.8) (20.3)

3 ~~ ~ ~ ~~ ~ ~ Recovery after day-case anaesthesia 913 Table 3. Mean (SD) values for drowsiness measured by a linear analogue rating scale (mm). Hours Thiopentone Propofol (1-test) group (F-stats) (t-test) (1-test) (9.1) 46.4 (21.9) (14.3) I 75.4 (11.7) 57.5 (22.6) 40.1 (13.7) < (23.5) 50.9 (22.9) (17.4) (15.1) 36.3 (23.4) (16.8) Table 4. Mean (SD) values for alertness measured by a linear analogue rating scale (mm). Hours Thiopentone Propofol (t-test) group (F-stats) (1-test) (1-test) (10.5) 40.4 (14.7) (15.8) I 22.2 (13.5) 33.6 (17.7) (15.6) <O.OOOl < 0.00 I (18.5) 39.6 (18.2) (20.1) (16.7) 52.3 (25.8) (20.0) Table 5. Mean (SD) error scores for Bethune s modification of Williams memory function test. Hours Thiopentone Propofol (t-test) group (F-stats) (t-test) (1-test) New card (7.1) (13.5) (12.4) (8.1) D card (7.4) (6.2) (5.9) (4.3) 10.9 (7.5) 18.9 (10.2) 16.7 (11.0) 13.6 (8.1) 15.5 (9.4) 7.7 (6.2) 5.3 (5.3) 3.5 (4.3) < (6.1) (8.4) 11.7 (6.1) 11.7 (8.5) 13.5 (9.5) 5.3 (4.1) 3.2 (4.5) 2.4 (4.1) < Table 6. Mean (SD) for the Wechsler logical memory passage. Pieces of information recalled Hours Thiopentone Propofol (I-test) group (F-stats) (1-test) (I-test) (3.9) 11.8 (4.1) (2.8) (2.4) 8.5 (3.9) (2.5) < <O.OOl (4.8) 13.3 (5.1) (3.6) I (3.4) 11.2 (4.7) (3.3) Table 7. Mean (SD) values for the criticalflickerfusion frequency (Hz) testing in the series. Hours Thiopentone Propofol P (1-test) Reference group P (F-stats) Thiopentone v reference (t-test) Propofol v reference (r-test) 0 I (2.7) 22.9 (2.5) 23.6 (2.5) 24.9 (3.0) -1.7 (2.1) (2.2) 0.3 (2.3) 23.8 (2.4) 23.5 (2.6) 23.9 (2.0) 24.1 (2.8) -0.3 (2.5) 0.1 (2.0) 0.3 (2.2) (3.2) 26.1 (3.6) 26.1 (3.9) 26.1 (3.5) 0.26 (1.6) 0.25 (1.8) 0.21 (2.0)

4 914 P.J. Heath, T. W. Ogg and W.R. Gilks Table 6 shows the number of pieces of information recalled from the Wechsler logical memory function passages at each of the test sessions. There were no significant differences between the treatment groups, although significant differences between the reference and treatment groups emerged at 1 and 24 hours. Patients in the thiopentone group recalled less information than those in the reference groups at the pre-operative test session. Table 7 records the crude critical flicker fusion frequencies for each group at each test session and the mean difference in flicker fusion frequency from the baseline value for each group (Fig. 1). There was a significant difference between the two treatment groups in the difference from baseline at one hour and there was a significant difference between the crude scores for the propofol and reference groups at each test session. Crude scores for the thiopentone group were also significantly different from the reference group at 1 and 2 hours. Discussion Day-case surgery is now practised widely throughout the United Kingdom. The importance of rapid, well-maintained recovery with few postoperative sequelae increases as the service expands, and postoperative day patients should not overburden the primary care services. This will be the case only if such patients are discharged when clinically recovered. Postoperative recovery is of importance if day surgery is to expand with all the advantages that this entails to patients and the health care system. This study was designed to examine differences in recovery after propofol and thiopentone. The use of inhalational agents was avoided and all subjects were anaesthetised for dilatation and curettage. This minimised surgical differences between patients and ensured a small standard deviation in the mean duration of surgery. We believe these are essential requirements to improve the comparability of the study groups and to allow any differences to be attributed to the intravenous anaesthetic agents. Recovery during the first few hours after intravenous anaesthesia was investigated widely.'.8-" Most studies indicate that early recovery after propofol anaesthesia is more rapid than after thiopentone8,i2-l4 but there have been few reports of recovery after the patients have returned home.*.' The statistical analysis of the data in the two treatment groups was by Student's t-test and it was these differences that interested us most. Subsequently, all three groups were examined using analysis of variance (F tests). One-way analysis-of-variance F tests are designed to detect nonspecific differences between the study groups, but are less sensitive than t-tests in detecting differences between two treatment groups. Thus the t-test may indicate a statistically significant difference between the treatment groups that is not supported by the F-test. The t-test, on occasions, failed to demonstrate a statistically significant difference between the groups, but F statistics showed a significant difference when the reference group was also considered. The implication of this is that there is a difference between one or both treatment groups and the reference group. For this reason, Student's t-test was used to compare each treatment group with the reference group. Patients who received thiopentone were significantly more tired and drowsy, and less alert, than those anaesthetised with propofol 1 hour after surgery. No difference -2.0 ' I., I I Baseline I 2 24 Hours Fig. 1. Change in flicker fusion frequency. 0, thiopentone; m, propofol; control. existed between the two groups at 2 hours, but at 24 hours the thiopentone group was again more tired and drowsy than the propofol group. F statistics failed to demonstrate the difference in feelings of tiredness at 24 hours, but confirmed the other differences. Patients in both treatment groups were significantly less alert than the reference group at pre-operative testing and remained so until the tests at 24 hours. This may reflect a high level of anxiety in the treatment groups in the pre-operative phase, which may also contribute to the differences seen after operation. Subjects are likely to be more relaxed when tested in their own homes at 24 hours. This pattern is similar to that noted for feelings of well-being recorded in a recent study.2 It appears from the 24-hour results for drowsiness and tiredness that propofol is beneficial. The scores in the thiopentone group returned virtually to normal, whilst those for propofol indicate that subjects were less tired and less drowsy than normal. A number of explanations are possible. Propofol produces euphoria in the postoperative period and the observed effect may be the result of subclinical euphoria. These patients may have been awaiting surgery for some time and this may reflect relief that the surgery is over. However, the relief may be masked in the thiopentone group by the hangover that follows thiopentone anaesthesia. A further explanation may be that this is a specific effect of propofol in reducing fatigue in the late postoperative period. The results of the Bethune modification of Williams' memory function test showed a significant difference between the treatment groups in the error scores for new cards at 1 hour. There were no differences between treatment groups at any other time for new cards and the scores for the D card were never significantly different. However, examination of all three groups indicated a highly significant difference in the error scores for new cards presented at 1 and 2 hours. The score in the thiopentone group for the D card was significantly worse than in the reference group at 1 hour. The Bethune memory test examines memory for visually acquired information and the results imply that this is impaired postoperatively at both 1 and 2 hours. Thiopentone results in a greater impairment of memory at 1 hour than does propofol, which may be important if postoperative instructions are given before an early discharge. ' The Wechsler Logical Memory Passages were used to examine the subjects' memory for auditory information. No significant differences were recorded between the treat-

5 Recovery after day-case anaesthesia 915 ment groups. However, highly significant differences were observed at one hour and at 24 hours when the reference group was included in the analysis. Both study groups performed less well than the reference group at 1 hour. There was a significant difference between the groups at 24 hours that appears to result mainly from impairment of memory in the propofol group compared with the reference group; however, there was no significant difference in memory function between the propofol and thiopentone groups. This effect is difficult to explain. Propofol may have a specific inhibitory effect on auditory memory in the late postoperative period. Alternatively, this may be a reflection of the apparent reduction of tiredness and drowsiness in the propofol group in a situation where pressing domestic commitments may preoccupy the subjects whilst listening to the story passages. Such preoccupation is less likely to occur during performance of the other tests because they require input from the subject throughout the test. It should also be remembered that the reference group was included for comparison and is not a true control group. The mean critical flicker fusion frequencies were examined in several ways. Initially, the mean frequencies were tested and there were no significant differences between the treatment groups. There was a significant difference (p < 0.02) in the results of the pre-operative tests when the reference group was included in this analysis. This may reflect an effect of anxiety in reducing critical flicker fusion frequency in the treatment groups, although the difference appears to be the result largely of a difference between the propofol and reference groups. The significance of the difference between the groups increased at one hour (p = ) and the difference remained significant at 2 hours (p = ). The difference between both treatment groups and the reference group was highly significant. Only the difference between the propofol and reference groups was significant at 24 hours. The sensitivity of critical flicker fusion frequency testing may be increased by subtracting each patient s pre-operative fusion frequency from the frequency at each test session. A significant difference was found between the treatment groups at one hour when the data were examined in this way. The differences were significant at both 1 and 2 hours, but not at 24 hours, when the reference group was included in this analysis. Postoperative recovery is complex and it is unreasonable to assume that all neurological functions should recover at the same rate. There have been recent reports of apparent recovery from propofol anaesthesia followed by a further period of unconsciousness.15 Some of the inconsistencies observed in this study may reflect this type of process at a subclinical level, and the effect may be specific to specific neurological functions, e.g. auditory memory, and not confined to propofol anaesthesia. However, it is not surprising that such an effect should be observed with a drug that produces such good early recovery that a later reduction in conscious level is readily apparent. Further investigation in this area is required. Appropriate anaesthetic techniques will assist the expansion of day-case surgical facilities in Britain. The results presented in this paper indicate that propofol is associated with superior subjective recovery from anaesthesia for up to 24 hours after surgery. Acknowledgments We gratefully acknowledge the assistance of Sister D.E. Sutherland and her day unit staff during this project and Dr L. Goldman for his advice on psychological testing. References 1. HEATH PJ, KENNEDY DJ, OGG TW, DUNLING C, GILKS WR. Which intravenous agent for day surgery? A comparison of propofol, thiopentone, methohexitone and etomidate. Anaesthesia 1988; 43: MILLAR JM, JEWKES CF. Recovery and morbidity after daycase anaesthesia. A comparison of propofol with thiopentone-enflurane with and without alfentanil. Anaesthesia 1988; 43: HERBERT M, MAKING SW, BOURKE JB, HART EA. Recovery of mental abilities following general anaesthesia induced by propofol ( Diprivan ) or thiopentone (Abstract). Postgraduate Medical Journal 1985; 61 (Suppl. 3): NELSON HE, O CONNELL A. Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex 1978; HINDMARCH I, GUDGEON AC. The effects of clobazam and lorazepam on aspects of psychomotor performance and car handling ability. British Journal of Clinical Psychology 1980; WESCHLER D. A standardized memory scale for clinical use. Journal of Psychology 1945; I. BETHUNE DW. Test of delayed memory recall suitable for assessing postoperative amnesia. Anaesthesia 198 I ; MACKENZIE N, GRANT IS. Comparison of the new emulsion formulation of propofol with methohexitone for induction of anaesthesia in day cases. British Journal of Anaesthesia 1985; 57: KAY B, HARGREAVES J, SIVALINGAM T, HEALY TEJ. Intravenous anaesthesia for cystoscopy: a comparison of propofol or methohexitone with alfentanil. European Journal of Anaesthesiology 1986; KAY B, HEALY TEJ. Propofol ( Diprivan ) for outpatient cystoscopy. Efficacy and recovery compared with Althesin and methohexitone. Postgraduate Medical Journal 1985; 61 (Suppl. 3): NOBLE J, OGG TW. The effect of propofol ( Diprivan ) and methohexitone on memory after day case anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): MORISON DH, DUNN GL. A comparative study of Diprivan and thiopental as induction agents in dental patients. Anesthesia and Analgesia 1987; 66 S ROLLY G, VERSICHELEN L. Comparison of propofol and thiopentone for induction of anaesthesia in premedicated patients. Anaesthesia 1985; 40: JOHNSTON RG, ANDERSON BJ, NOSEWORTHY TW, SHUSTACK A. Diprivan versus thiopentone for outpatient surgery. Canadian Anaesthetists Society Journal 1986; 33 S Propofol-Convulsions anaphylaxis and delayed recovery from anaesthesia. In: Committee on Safety of Medicines, Current Problems 1989; ARMITAGE P. Statistical methods in medical research. Blackwell Scientific Publications, Oxford, 1971.