Anaesthesia, 1991, Volume 46, pages 553-556
Intra-operative patient-controlled sedation Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl
G. A. OSBORNE, G. E. RUDKIN, N. J . CURTIS, D. VICKERS
AND
A. J. CRAKER
Summary The quality of sedation and postoperative recovery have been assessed for intra-operative sedation provided by either patient-controlled sedation with propofol or a standard method using divided doses of midazolam and,fentanyl, in 40 A S A 1 day surgery patients undergoing extraction of third molar teeth under local analgesia. Patient-controlled sedation with propofol produced sedation no deeper than full eyelid closure with prompt response to verbal command, but deeper levels were seen in three patients in the midazolam and fentanyl group. Patient satisfaction was higher in the patient-controlled sedation propofol group for both subjective intra-operative feelings ( p < 0.01) and willingness to have the procedure again in the same manner ( p < 0.05). Amnesia was more limited to intra-operative events (rather than extending into the postoperative period) in the patient-controlled sedation propofol group ( p < 0.0.5). Drug dose was correlated with duration of procedure and surgical digiculty in the patient-controlled sedation propofol group but not in the midazolam and fentanyl group. Postoperative testing included a new computerised test, the FAST index, which indicated a dose-dependent reduction in cognitive function in the midazolam and fentanyl group, which persisted until the time of discharge. Changes in cognitive function in the patient-controlled sedation propofol group in the same postoperative interval were significantly less and not related to propofol dose. Key words Hypnotics, benzodiazepines; midazolam. Anaesthetic techniques; patient-controlled sedation. Anaesthesia; outpatient, recovery. Anaesthetics, intravenous; propofol. Patient-controlled sedation (PCS) with propofol has been shown to provide safe and effective intra-operative sedation for the extraction of third molar teeth under local analgesia.' In that earlier work, amnesia for significant postoperative events was noted to be absent, which is a significant advantage for day surgery patients. Our early clinical experience using PCS with propofol also suggested that postoperative recovery from drug effects was generally rapid and that this was likely to provide further advantages for day surgery. We have undertaken this study to compare the quality of intra-operative sedation provided by PCS with propofol with that for a standard technique, using divided doses of midazolam and fentanyl, and to measure objectively postoperative recovery from drug effects with the two techniques. Psychometric testing used in the study to assess postoperative recovery includes the first anaesthesia-related application of a new computerised test of mental performance, the FAST (frequency accrual speed test) index.'
Patients and methods This study was approved by the Hospital Human Ethics Committee. All operative procedures were carried out by one surgeon (N.C.). Forty fasted, unpremedicated, ASA 1 day surgery patients were randomly allocated to one of the two sedation regimens. All procedures were scored by the surgeon for surgical difficulty and patient cooperation, using analogue scales 0-10; these increased with surgical difficulty and patient cooperation. The obvious differences between the methods of sedation precluded the surgeon from being blinded to the sedation technique. Group 1 Patients received intermittent doses of intravenous midazolam and fentanyl titrated to provide a comfortable patient with half to full eyelid closure and prompt response to verbal command. An arbitrary limit of a total dose of 100 pg fentanyl was not exceeded, but no limit was placed on the total amount of midazolam.
G.A. Osborne, MB, BS, PhD, FFARACS, Staff Specialist, G.E. Rudkin, MB, BS, FFARACS, Senior Staff Specialist, Coordinator Day Surgery Unit, Department of Anaesthesia and Intensive Care, N.J. Curtis, BDS, FDS RCS, Registrar, Oral and Maxillofacial Surgical Unit, D. Vickers, BA, MA, PhD, Associate Professor, A.J. Craker, BSc, Research Assistant, Department of Psychology, University of Adelaide, Royal Adelaide Hospital, North Terrace, South Australia 5000. Accepted 18 October 1990.
+
0003-2409/91/070553 04 $03.00/0
@ 1991 The Association of Anaesthetists of Gt Britain and Ireland
553
G.A. Osborne et al.
554 Group 2
Patients, previously instructed in the use of the patientcontrolled technique, self-administered 0.7 mg/kg intravenous bolus doses of propofol, delivered at 16.7 mg/minute, with a one-minute lockout interval. A modified, commercial, patient-controlled analgesia (PCA) pump' was used after an initial dose of 0.7 mg/kg propofol was given by the anaesthetist before the administration of local analgesia by the surgeon. All patients received oxygen by nasal cannula. Blood pressure, heart rate and haemoglobin oxygen saturation were monitored and recorded during all procedures.' FAST index testing was carried out once before operation, then repeated during recovery when the patient first sat out of bed (no sooner than 30 minutes after arrival in the postoperative recovery room) and again at the time of discharge. P-deletion3 testing was carried out twice before operation (because of known practice effects) and twice after operation. The first postoperative test was at 10 minutes after arrival in the recovery room and the second at the time of discharge. The time from arrival in recovery to first sitting out of bed and the time when ready for discharge were recorded. All patients were followed-up by telephone on the first postoperative day and asked a standard set of questions about peri-operative events. These included memory for intravenous cannulation, administration of local analgesia by the surgeon, extraction of teeth, recovery room events and journey home. Patients were also asked if they felt good, bad or indifferent during the procedure and if they would have the same procedure performed again in the same manner. Patients who used the PCS technique were asked if they liked the method of self-administration. Data related to patient amnesia, intra-operative feelings and willingness to repeat the procedure in the same manner, were tested using the Fisher exact test (two-tailed). Pearson and Spearman correlation coefficients were calcu lated to determine the correlation between drug dose and procedure duration and surgical difficulty respectively. Repeated measures analysis of variance of the psychometric data was performed using program 5v, BMDP Statistical Software, UCLA, California, USA. The FAST index requires the patient to make choices as to which of two adjacent rapidly flashing lights appears to flash more often.2 Each test includes 100 trials and takes about 5 minutes to complete. We have used this new computerised test of mental speed for the first time as a Table 1. Summary data for patients and procedures. Group 1 n = 20 Midazolam/ fentanyl
7 " 6
2 5 cl
-
4
$ 3
5 2 z 1 O
1
2
3
.,
l3mLmL
6 7 4 5 Degree of difficulty
8
9
1
0
Fig. 1. Distribution of scores for surgical difficulty. midazoIam/ PCS propofol (group 2). fentanyl (group 1); 0,
measure of the effect of anaesthetic drugs on postoperative cognitive function. This test is convenient to use and is intended to provide a measure of mental speed that avoids some of the difficulties associated with choice reaction time (CRT)4 and critical flicker frequency (CFF).' For example, CRT measurement may have learning components that can lead to underestimation of postoperative drug effects and may also be subject to speed-accuracy trade-off.
Results Summary data for patients and procedures are shown in Table 1. The two groups are well matched for weight, age, procedure duration, time to sitting in recovery and time when ready for discharge. Three patients in group 1 and one in group 2 were male. The distributions for surgical difficulty (Fig. 1) and patient cooperation (Fig. 2) are reasonably similar for both groups. The average dose of propofol was 5.29 mg/kg (SD 2.68, range 2.10-12.04) while that of midazolam was 0.1 1 mg/kg (SD 0.04, range 0.05-0.16). The mean dose of fentanyl was 1.78 pg/kg (SD 0.28, range 1.00-2.30). Patients in the PCS group made an average of 6.7 (SD 3.8) successful demands and 31.6 (SD 53.6) unsuccessful during an effective lockout period of about 3.5 minutes, as in addition to the 1 minute lockout, most self-administered boluses took about 2.5 minutes to deliver. There was no evidence of cardiovascular or respiratory instability in either group. Haemoglobin oxygen saturation was maintained at 97% or greater for all patients. No patient in the PCS with propofol group was sedated to a level deeper than full eyelid closure with prompt response to verbal command. However, three patients in the midazolam and fentanyl group reached a deeper level where response required mild physical stimulus.
Group 2 n = 20 PCS propofol
7 r
6 m
E
.-
5
t
Mean
SD
Mean
SD
x 4 L
: 3
Age; years Weight; kg Procedure time; minutes Recovery time to sit; minutes Recovery time to discharge; minutes
21.1 59.9
3.8 12.6
21.8 56.3
4.2 6.8
42.7
17.1
47.5
15.7
34.5
9.5
36.5
14.4
125.8
30.1
124.3
37.1
a
5 z
2 I 0
1
2
3
4
5
6
7
8
9
1
0
Potient cooperation
Fig. 2. Distribution of scores for patient cooperation. midazolam/fentanyl (group 1); 0, PCS propofol (group 2).
.,
Intra-operative PCS
555
Table 2. Patient intra-operative subjective feelings.
Group 1 n
Group 2 n = 20
= 20
Midazolam/fentanyl ~
_
_
_
_
_
_
_
_
_
PCS propofol
~
Good Indifferent Bad
19
11 8 1
1
0
Patients in the group that received PCS with propofol were more satisfied with their sedation, as measured by patient subjective intra-operative feelings (Table 2) and patient willingness to have the same procedure again in the same manner (Table 3). More patients in the PCS propofol group stated they felt 'good' during the procedure (p < 0.01) and more patients stated that they would have the procedure again in the same manner (p < 0.05). All PCS patients said they enjoyed the experience of self-administration of sedation. Peri-operative amnesia was more selective for intra-operative events in patients who received patient-controlled propofol (Table 4). While 30% of the midazolam and fentanyl group had amnesia for recovery room events, no patient who received PCS with propofol was amnesic for postoperative events (p < 0.05). Reasonable correlation existed between the mg/kg dose of self-administered propofol and both procedure duration (r = 0.441; p = 0.052) and surgical difficulty (rs = 0.553; p = 0.016), but no corresponding correlation was seen with total midazolam dose (r = 0.099; p = 0.678 and r, = -0.253; p = 0.270 respectively). Results from psychometric testing
Grouped mean results for FAST index accuracy and number of ps correctly deleted are shown in Figures 3 and 4 respectively, for illustrative purposes only. Statistical analysis of these variables and the number of errors made in the p-deletion tests were analysed using repeated measures analysis of variance with an unstructured covariance matrix. Balancing of the two patient groups for Table 3. Patient willingness to have procedure perrormed in the same manner. ~
Group 2
Group 1 n = 20 Midazolam/fentanyl
n
20 0 0
15
Yes
Indifferent
4
No
1
= 20
PCS propofol
I
I
First postoperative test
Fig. 3. Grouped mean results for FAST index accuracy.
midazolam/fentanyl (group
1);
.;
Second postoperative test
0, PCS propofol (group 2).
various associated factors including surgeon, patient se. and age and surgical difficulty was attempted by experimental design and was found by marginal analysis to have been generally adequate. As a precaution, these factors were included in the formal analysis but no significant effect was detected for any of these factors for the three variables. Four covariates, predrug level of the variable, time after completion of the operative procedure when testing occurred, total midazolam dose (mg/kg) and total propofol dose (mg/kg) were also included in the analysis. These are variables that differ between individuals and cannot be easily balanced across treatment groups before sedation. Specific findings were: FAST index accuracy ( f ) . (% correct). After excluding nonsignificant factors and covariates from the model: group I (midazolam and fentanyl). Mean f = 42.03+0.65 (predrug f)-186.93 (midazolam dose (mg/kg)); group 2 (PCS propofol). Mean f = 28.61 +0.65 (predrug f), i.e. the average FAST index accuracy of the PCS propofol group is approximately 6% units higher than the midazolam and fentanyl group, for any specified level of predrug f, with an average midazolam dose of about 0.1 mg/kg; this difference does not change significantly over the time interval between the two recovery room tests. Number of p s correctly deleted ( p ) . After excluding nonsignificant factors and covariates from the model: group 1 (midazolam and fentanyl). Mean p = 0.225 (recovery time (minutes)) +0.876 (predrug p)-249.3 (midazolam dose (mg/ kg)); group 2 (PCS propofol). Mean p = 0.093 (recovery time (minutes)) + 0.876 (predrug p), i.e. the average number of ps correctly deleted for the PCS propofol group is approximately 24 more than for the midazolam and fentanyl group, 10 minutes after arrival in recovery, for any 10 r
Table 4. Patient amnesia for peri-operative events. Group 1 n = 20
Group 2 n = 20
Midazolam/
PCS propofol
fentanyl
Intravenous cannulation Surgical local analgesia Extractions Postoperative recovery Journey home
1
0
4
4
15
15
6 0
0 0
-40
t
., -50
I
0
I
Second pre-operative test
I
First postoperative test
1 Second postoperative test
Fig. 4. Grouped mean results for number of ps correctly deleted.
midazolam/fentanyl (group 1); 0, PCS propofol (group 2).
556
G.A. Osborne et al.
specified level of predrug p, and average midazolam dose of around 0.1 mg/kg; this difference between the groups decreases with time over the recovery interval tested. Errors made in p-deletion. There was no detectable difference between groups.
Discussion This study indicates that PCS with propofol can provide sedation with safety, effectiveness and patient satisfaction that compares favourably with a well known, standard technique. This is encouraging for the patient-controlled technique, since the surgical extraction of third molar teeth under local analgesia has higher requirements for sedation than many other procedures. Advantages related to more selective amnesia and more rapid postoperative recovery from drug effects observed in the PCS group may be due more to the use of propofol than the patient-controlled technique. The relative contributions of the drug and the patient-controlled technique to any of the apparent advantages seen so far can be more precisely determined in further studies. It is possible that the effectiveness of the patient-controlled technique can be improved by further modification of patient-controlled pump parameters. The psychometric testing in this study showed that patients who received PCS with propofol recovered more quickly from drug effects than patients who received the standard sedation technique with divided doses of midazolam and fentanyl. Midazolam had a dose dependent effect on both FAST index (cognitive function) and pdeletion (attention level) but there was no dose dependent effect for propofol for either test. The FAST index results suggest that while there was little residual drug effect on cognitive function after 30 minutes in the postoperative recovery room in patients who received patient-controlled propofol, patients who received midazolam and fentanyl were significantly affected at 30 minutes postoperatively to an extent that persisted to the time of discharge, on average about 2 hours after operation. The effect of midazolam and fentanyl sedation on cognitive function, which persisted up to the time of discharge for day patients, suggests that patients so affected may have impaired performance in important everyday tasks, and further work is required to determine the duration and significance of this effect. P-deletion, a well known test of attention level, was tested earlier in the recovery period when postoperative performance (number of ps correctly deleted) was reduced in both groups (midazolam and fentanyl more than PCS propofol). However, performance in both groups improved with time in recovery and approached pre-operative levels by the time of discharge; this suggests that the test may not be sensitive in its ability to discriminate between recovery from different drugs used for intra-operative sedation. The lack of drug effect on number of errors made (omitted ps and incorrectly deleted letters) is consistent with previous findings.6 The FAST index appears to be able to measure subtle decreases in cognitive ability. Work to date with the FAST index shows it provides a stable, valid and reliable measure of intellectual performance which is largely theory-neutral. In each of four studies, Vickers et al.’ found that there was a reasonable correlation (averaging 0.45) between FAST
scores across two sessions, conducted one week apart, and that in none of these studies was there a significant difference in performance between the two sessions. In a later study with children, Vickers and McDowell’ found that there was no significant difference between FAST scores in earlier and later sessions, but that there was good correlation (r = 0.69, p < 0.01, n = 28) between FAST scores across the two sessions. These and other studies also provide evidence of validity of the FAST index as an index of mental speed. Vickers et a[.’ found a reasonable correlation ( r = 0.52, p < 0.01, n = 22) between FAST scores and intellectual ability on Raven’s Advanced Progressive Matrices. In addition, Vickers and McDowell’ found a high correlation between FAST scores and the Wechsler Intelligence scale for children (r = 0.69, p < 0.01, n = 28). The ability of the FAST index, as demonstrated in this present study, to discriminate between recovery from different drugs and measure dose-dependent effects, further supports its validity as a measure of cognitive function. The dose-dependent effect of midazolam on postoperative cognitive function gives us hope that more accurate mapping of drug dose and likely effect on cognitive function may be possible. This should be of particular value for day surgery patients. The ability to measure dosedependent effects may mean that drug combinations designed to deliver optimal sedation and recovery characteristics can be explored with the FAST index.
Acknowledgments We are grateful for the valuable advice and assistance provided by P. I. Leppard, Department of Mathematical Statistics, University of Adelaide, who also carried out the repeated measures analysis of variance of the psychometric tests. We are also grateful for the cooperation and assistance provided by the nursing staff in the Day Surgery Unit and the Oral and Maxillofacial Unit of the Royal Adelaide Hospital. D. Vickers acknowledges support from an Australian Research Council grant (A 78615464).
References 1
2
3.
4. 5.
6.
RUDKINGE, OSBORNE GA, CURTISNJ. Intraoperative patientcontrolled sedation. Anaesthesia, (in press). VICKERSD, MCDOWELL A. Individual differences in the rate of accrual of information: the FAST (frequency accrual speed test) index. In: MULLERF, ed. Proceedings of the Sixth Annual Meeting of the International Society for Psychophysics. Wurzburg. Wurzburg: Institut fur Psychologie. Universitat Wurzburg, 1990: 251-6. DIXON RA, THORNTON JA. Tests of recovery from anaesthesia and sedation: intravenous diazepam in dentistry. British Journal of Anaesthesia 1973; 4 5 207-15. SMITHEE. Choice reaction time: an analysis of the major theoretical positions. Psychological Bulletin 1968; 69 77-1 10. SMITHJM, MISIAKH. Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects-a review. Psychopliurmacology 1976; 47: 175-82. L, ZUURMONV WWA, BALKVA, VAN DISH, VAN LEEUWEN PAULEAA. Multidimensionality of psychological recovery from anaesthesia: analysing six recovery tests. Anaesthesia
1989; 44: 889-92. 7. VICKERSD, FOREMAN EA, NICHOLSMER, INNES NJ, GOTT RE. Some experimental tests of the application of an uncertainty model to a time-limited expanded judgement task. In: VICKERSD, SMITHPL, eds. Human information processing: measure. mechanisms and models. Proceedings of the XXIV Congress of Psychology, Vol 2. Amsterdam: Elsevier, 1989:
253-65.
Intra-operative patient-controlled sedation Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl
G. A. OSBORNE, G. E. RUDKIN, N. J . CURTIS, D. VICKERS
AND
A. J. CRAKER
Summary The quality of sedation and postoperative recovery have been assessed for intra-operative sedation provided by either patient-controlled sedation with propofol or a standard method using divided doses of midazolam and,fentanyl, in 40 A S A 1 day surgery patients undergoing extraction of third molar teeth under local analgesia. Patient-controlled sedation with propofol produced sedation no deeper than full eyelid closure with prompt response to verbal command, but deeper levels were seen in three patients in the midazolam and fentanyl group. Patient satisfaction was higher in the patient-controlled sedation propofol group for both subjective intra-operative feelings ( p < 0.01) and willingness to have the procedure again in the same manner ( p < 0.05). Amnesia was more limited to intra-operative events (rather than extending into the postoperative period) in the patient-controlled sedation propofol group ( p < 0.0.5). Drug dose was correlated with duration of procedure and surgical digiculty in the patient-controlled sedation propofol group but not in the midazolam and fentanyl group. Postoperative testing included a new computerised test, the FAST index, which indicated a dose-dependent reduction in cognitive function in the midazolam and fentanyl group, which persisted until the time of discharge. Changes in cognitive function in the patient-controlled sedation propofol group in the same postoperative interval were significantly less and not related to propofol dose. Key words Hypnotics, benzodiazepines; midazolam. Anaesthetic techniques; patient-controlled sedation. Anaesthesia; outpatient, recovery. Anaesthetics, intravenous; propofol. Patient-controlled sedation (PCS) with propofol has been shown to provide safe and effective intra-operative sedation for the extraction of third molar teeth under local analgesia.' In that earlier work, amnesia for significant postoperative events was noted to be absent, which is a significant advantage for day surgery patients. Our early clinical experience using PCS with propofol also suggested that postoperative recovery from drug effects was generally rapid and that this was likely to provide further advantages for day surgery. We have undertaken this study to compare the quality of intra-operative sedation provided by PCS with propofol with that for a standard technique, using divided doses of midazolam and fentanyl, and to measure objectively postoperative recovery from drug effects with the two techniques. Psychometric testing used in the study to assess postoperative recovery includes the first anaesthesia-related application of a new computerised test of mental performance, the FAST (frequency accrual speed test) index.'
Patients and methods This study was approved by the Hospital Human Ethics Committee. All operative procedures were carried out by one surgeon (N.C.). Forty fasted, unpremedicated, ASA 1 day surgery patients were randomly allocated to one of the two sedation regimens. All procedures were scored by the surgeon for surgical difficulty and patient cooperation, using analogue scales 0-10; these increased with surgical difficulty and patient cooperation. The obvious differences between the methods of sedation precluded the surgeon from being blinded to the sedation technique. Group 1 Patients received intermittent doses of intravenous midazolam and fentanyl titrated to provide a comfortable patient with half to full eyelid closure and prompt response to verbal command. An arbitrary limit of a total dose of 100 pg fentanyl was not exceeded, but no limit was placed on the total amount of midazolam.
G.A. Osborne, MB, BS, PhD, FFARACS, Staff Specialist, G.E. Rudkin, MB, BS, FFARACS, Senior Staff Specialist, Coordinator Day Surgery Unit, Department of Anaesthesia and Intensive Care, N.J. Curtis, BDS, FDS RCS, Registrar, Oral and Maxillofacial Surgical Unit, D. Vickers, BA, MA, PhD, Associate Professor, A.J. Craker, BSc, Research Assistant, Department of Psychology, University of Adelaide, Royal Adelaide Hospital, North Terrace, South Australia 5000. Accepted 18 October 1990.
+
0003-2409/91/070553 04 $03.00/0
@ 1991 The Association of Anaesthetists of Gt Britain and Ireland
553
G.A. Osborne et al.
554 Group 2
Patients, previously instructed in the use of the patientcontrolled technique, self-administered 0.7 mg/kg intravenous bolus doses of propofol, delivered at 16.7 mg/minute, with a one-minute lockout interval. A modified, commercial, patient-controlled analgesia (PCA) pump' was used after an initial dose of 0.7 mg/kg propofol was given by the anaesthetist before the administration of local analgesia by the surgeon. All patients received oxygen by nasal cannula. Blood pressure, heart rate and haemoglobin oxygen saturation were monitored and recorded during all procedures.' FAST index testing was carried out once before operation, then repeated during recovery when the patient first sat out of bed (no sooner than 30 minutes after arrival in the postoperative recovery room) and again at the time of discharge. P-deletion3 testing was carried out twice before operation (because of known practice effects) and twice after operation. The first postoperative test was at 10 minutes after arrival in the recovery room and the second at the time of discharge. The time from arrival in recovery to first sitting out of bed and the time when ready for discharge were recorded. All patients were followed-up by telephone on the first postoperative day and asked a standard set of questions about peri-operative events. These included memory for intravenous cannulation, administration of local analgesia by the surgeon, extraction of teeth, recovery room events and journey home. Patients were also asked if they felt good, bad or indifferent during the procedure and if they would have the same procedure performed again in the same manner. Patients who used the PCS technique were asked if they liked the method of self-administration. Data related to patient amnesia, intra-operative feelings and willingness to repeat the procedure in the same manner, were tested using the Fisher exact test (two-tailed). Pearson and Spearman correlation coefficients were calcu lated to determine the correlation between drug dose and procedure duration and surgical difficulty respectively. Repeated measures analysis of variance of the psychometric data was performed using program 5v, BMDP Statistical Software, UCLA, California, USA. The FAST index requires the patient to make choices as to which of two adjacent rapidly flashing lights appears to flash more often.2 Each test includes 100 trials and takes about 5 minutes to complete. We have used this new computerised test of mental speed for the first time as a Table 1. Summary data for patients and procedures. Group 1 n = 20 Midazolam/ fentanyl
7 " 6
2 5 cl
-
4
$ 3
5 2 z 1 O
1
2
3
.,
l3mLmL
6 7 4 5 Degree of difficulty
8
9
1
0
Fig. 1. Distribution of scores for surgical difficulty. midazoIam/ PCS propofol (group 2). fentanyl (group 1); 0,
measure of the effect of anaesthetic drugs on postoperative cognitive function. This test is convenient to use and is intended to provide a measure of mental speed that avoids some of the difficulties associated with choice reaction time (CRT)4 and critical flicker frequency (CFF).' For example, CRT measurement may have learning components that can lead to underestimation of postoperative drug effects and may also be subject to speed-accuracy trade-off.
Results Summary data for patients and procedures are shown in Table 1. The two groups are well matched for weight, age, procedure duration, time to sitting in recovery and time when ready for discharge. Three patients in group 1 and one in group 2 were male. The distributions for surgical difficulty (Fig. 1) and patient cooperation (Fig. 2) are reasonably similar for both groups. The average dose of propofol was 5.29 mg/kg (SD 2.68, range 2.10-12.04) while that of midazolam was 0.1 1 mg/kg (SD 0.04, range 0.05-0.16). The mean dose of fentanyl was 1.78 pg/kg (SD 0.28, range 1.00-2.30). Patients in the PCS group made an average of 6.7 (SD 3.8) successful demands and 31.6 (SD 53.6) unsuccessful during an effective lockout period of about 3.5 minutes, as in addition to the 1 minute lockout, most self-administered boluses took about 2.5 minutes to deliver. There was no evidence of cardiovascular or respiratory instability in either group. Haemoglobin oxygen saturation was maintained at 97% or greater for all patients. No patient in the PCS with propofol group was sedated to a level deeper than full eyelid closure with prompt response to verbal command. However, three patients in the midazolam and fentanyl group reached a deeper level where response required mild physical stimulus.
Group 2 n = 20 PCS propofol
7 r
6 m
E
.-
5
t
Mean
SD
Mean
SD
x 4 L
: 3
Age; years Weight; kg Procedure time; minutes Recovery time to sit; minutes Recovery time to discharge; minutes
21.1 59.9
3.8 12.6
21.8 56.3
4.2 6.8
42.7
17.1
47.5
15.7
34.5
9.5
36.5
14.4
125.8
30.1
124.3
37.1
a
5 z
2 I 0
1
2
3
4
5
6
7
8
9
1
0
Potient cooperation
Fig. 2. Distribution of scores for patient cooperation. midazolam/fentanyl (group 1); 0, PCS propofol (group 2).
.,
Intra-operative PCS
555
Table 2. Patient intra-operative subjective feelings.
Group 1 n
Group 2 n = 20
= 20
Midazolam/fentanyl ~
_
_
_
_
_
_
_
_
_
PCS propofol
~
Good Indifferent Bad
19
11 8 1
1
0
Patients in the group that received PCS with propofol were more satisfied with their sedation, as measured by patient subjective intra-operative feelings (Table 2) and patient willingness to have the same procedure again in the same manner (Table 3). More patients in the PCS propofol group stated they felt 'good' during the procedure (p < 0.01) and more patients stated that they would have the procedure again in the same manner (p < 0.05). All PCS patients said they enjoyed the experience of self-administration of sedation. Peri-operative amnesia was more selective for intra-operative events in patients who received patient-controlled propofol (Table 4). While 30% of the midazolam and fentanyl group had amnesia for recovery room events, no patient who received PCS with propofol was amnesic for postoperative events (p < 0.05). Reasonable correlation existed between the mg/kg dose of self-administered propofol and both procedure duration (r = 0.441; p = 0.052) and surgical difficulty (rs = 0.553; p = 0.016), but no corresponding correlation was seen with total midazolam dose (r = 0.099; p = 0.678 and r, = -0.253; p = 0.270 respectively). Results from psychometric testing
Grouped mean results for FAST index accuracy and number of ps correctly deleted are shown in Figures 3 and 4 respectively, for illustrative purposes only. Statistical analysis of these variables and the number of errors made in the p-deletion tests were analysed using repeated measures analysis of variance with an unstructured covariance matrix. Balancing of the two patient groups for Table 3. Patient willingness to have procedure perrormed in the same manner. ~
Group 2
Group 1 n = 20 Midazolam/fentanyl
n
20 0 0
15
Yes
Indifferent
4
No
1
= 20
PCS propofol
I
I
First postoperative test
Fig. 3. Grouped mean results for FAST index accuracy.
midazolam/fentanyl (group
1);
.;
Second postoperative test
0, PCS propofol (group 2).
various associated factors including surgeon, patient se. and age and surgical difficulty was attempted by experimental design and was found by marginal analysis to have been generally adequate. As a precaution, these factors were included in the formal analysis but no significant effect was detected for any of these factors for the three variables. Four covariates, predrug level of the variable, time after completion of the operative procedure when testing occurred, total midazolam dose (mg/kg) and total propofol dose (mg/kg) were also included in the analysis. These are variables that differ between individuals and cannot be easily balanced across treatment groups before sedation. Specific findings were: FAST index accuracy ( f ) . (% correct). After excluding nonsignificant factors and covariates from the model: group I (midazolam and fentanyl). Mean f = 42.03+0.65 (predrug f)-186.93 (midazolam dose (mg/kg)); group 2 (PCS propofol). Mean f = 28.61 +0.65 (predrug f), i.e. the average FAST index accuracy of the PCS propofol group is approximately 6% units higher than the midazolam and fentanyl group, for any specified level of predrug f, with an average midazolam dose of about 0.1 mg/kg; this difference does not change significantly over the time interval between the two recovery room tests. Number of p s correctly deleted ( p ) . After excluding nonsignificant factors and covariates from the model: group 1 (midazolam and fentanyl). Mean p = 0.225 (recovery time (minutes)) +0.876 (predrug p)-249.3 (midazolam dose (mg/ kg)); group 2 (PCS propofol). Mean p = 0.093 (recovery time (minutes)) + 0.876 (predrug p), i.e. the average number of ps correctly deleted for the PCS propofol group is approximately 24 more than for the midazolam and fentanyl group, 10 minutes after arrival in recovery, for any 10 r
Table 4. Patient amnesia for peri-operative events. Group 1 n = 20
Group 2 n = 20
Midazolam/
PCS propofol
fentanyl
Intravenous cannulation Surgical local analgesia Extractions Postoperative recovery Journey home
1
0
4
4
15
15
6 0
0 0
-40
t
., -50
I
0
I
Second pre-operative test
I
First postoperative test
1 Second postoperative test
Fig. 4. Grouped mean results for number of ps correctly deleted.
midazolam/fentanyl (group 1); 0, PCS propofol (group 2).
556
G.A. Osborne et al.
specified level of predrug p, and average midazolam dose of around 0.1 mg/kg; this difference between the groups decreases with time over the recovery interval tested. Errors made in p-deletion. There was no detectable difference between groups.
Discussion This study indicates that PCS with propofol can provide sedation with safety, effectiveness and patient satisfaction that compares favourably with a well known, standard technique. This is encouraging for the patient-controlled technique, since the surgical extraction of third molar teeth under local analgesia has higher requirements for sedation than many other procedures. Advantages related to more selective amnesia and more rapid postoperative recovery from drug effects observed in the PCS group may be due more to the use of propofol than the patient-controlled technique. The relative contributions of the drug and the patient-controlled technique to any of the apparent advantages seen so far can be more precisely determined in further studies. It is possible that the effectiveness of the patient-controlled technique can be improved by further modification of patient-controlled pump parameters. The psychometric testing in this study showed that patients who received PCS with propofol recovered more quickly from drug effects than patients who received the standard sedation technique with divided doses of midazolam and fentanyl. Midazolam had a dose dependent effect on both FAST index (cognitive function) and pdeletion (attention level) but there was no dose dependent effect for propofol for either test. The FAST index results suggest that while there was little residual drug effect on cognitive function after 30 minutes in the postoperative recovery room in patients who received patient-controlled propofol, patients who received midazolam and fentanyl were significantly affected at 30 minutes postoperatively to an extent that persisted to the time of discharge, on average about 2 hours after operation. The effect of midazolam and fentanyl sedation on cognitive function, which persisted up to the time of discharge for day patients, suggests that patients so affected may have impaired performance in important everyday tasks, and further work is required to determine the duration and significance of this effect. P-deletion, a well known test of attention level, was tested earlier in the recovery period when postoperative performance (number of ps correctly deleted) was reduced in both groups (midazolam and fentanyl more than PCS propofol). However, performance in both groups improved with time in recovery and approached pre-operative levels by the time of discharge; this suggests that the test may not be sensitive in its ability to discriminate between recovery from different drugs used for intra-operative sedation. The lack of drug effect on number of errors made (omitted ps and incorrectly deleted letters) is consistent with previous findings.6 The FAST index appears to be able to measure subtle decreases in cognitive ability. Work to date with the FAST index shows it provides a stable, valid and reliable measure of intellectual performance which is largely theory-neutral. In each of four studies, Vickers et al.’ found that there was a reasonable correlation (averaging 0.45) between FAST
scores across two sessions, conducted one week apart, and that in none of these studies was there a significant difference in performance between the two sessions. In a later study with children, Vickers and McDowell’ found that there was no significant difference between FAST scores in earlier and later sessions, but that there was good correlation (r = 0.69, p < 0.01, n = 28) between FAST scores across the two sessions. These and other studies also provide evidence of validity of the FAST index as an index of mental speed. Vickers et a[.’ found a reasonable correlation ( r = 0.52, p < 0.01, n = 22) between FAST scores and intellectual ability on Raven’s Advanced Progressive Matrices. In addition, Vickers and McDowell’ found a high correlation between FAST scores and the Wechsler Intelligence scale for children (r = 0.69, p < 0.01, n = 28). The ability of the FAST index, as demonstrated in this present study, to discriminate between recovery from different drugs and measure dose-dependent effects, further supports its validity as a measure of cognitive function. The dose-dependent effect of midazolam on postoperative cognitive function gives us hope that more accurate mapping of drug dose and likely effect on cognitive function may be possible. This should be of particular value for day surgery patients. The ability to measure dosedependent effects may mean that drug combinations designed to deliver optimal sedation and recovery characteristics can be explored with the FAST index.
Acknowledgments We are grateful for the valuable advice and assistance provided by P. I. Leppard, Department of Mathematical Statistics, University of Adelaide, who also carried out the repeated measures analysis of variance of the psychometric tests. We are also grateful for the cooperation and assistance provided by the nursing staff in the Day Surgery Unit and the Oral and Maxillofacial Unit of the Royal Adelaide Hospital. D. Vickers acknowledges support from an Australian Research Council grant (A 78615464).
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