As intravenous (i.v.) sedation with midazolam or propofol is sometimes used with regional block in monitored anaesthesia care for ambulatory surgery [1,2], the evaluation of recovery of balance, particularly dynamic balance involving movement of the centre of gravity, is important for safe discharge after sedation. Although many studies have compared the usefulness of propofol in sedation with that of midazolam [3,4], our literature search did not reveal any studies comparing the recovery of dynamic balance after the injection of the two sedatives. Computerized dynamic posturography (CDP) with unpredictable perturbation stimuli is reported to be a sensitive and reliable method for the assessment of dynamic balance after sedation . However, the application of CDP to daily clinical practice may be difficult due to economic considerations and the long test time. Therefore, if simple dynamic balance tests that are well correlated with precise CDP can be introduced, they may be useful in clinical practice.
The purpose of the present study was to compare the recovery of dynamic balance after i.v. sedation with propofol and midazolam, and to investigate the usefulness of simple dynamic balance tests.
Subjects and methods
After informed consent of the subjects and the approval of the Ethics Committee of our institution were obtained, 14 young male volunteers were enrolled in this study. They underwent i.v. sedation with propofol and midazolam for 1 h each at an interval of more than 1 week. The sedation level aimed for was Wilson's sedation score 3 (Table 1) . For propofol sedation, a target controlled infusion (TCI) was started with the initial target blood concentration set at 2.2 μg mL−1 with a TCI pump TE-371 (Terumo Inc., Tokyo, Japan). The TCI control system used was the Diprifusor® (AstraZeneca Pharmaceuticals, Macclesfield, UK) incorporating the pharmacokinetic model of Marsh . Immediately after the target sedation level was achieved during induction, the target blood concentration was manually reset to the same value as the calculated effect-site concentration. Then the infusion rate was automatically regulated to make the calculated blood concentration follow the target blood concentration. For midazolam sedation, midazolam (a total of about 0.07 mg kg−1) was administered in divided small doses over 4–5 min until optimal sedation was achieved, followed by a continuous infusion at two-thirds of the induction dose per hour. To maintain optimal sedation, the target blood concentration of propofol or the continuous infusion rate of midazolam was finely adjusted according to clinical signs and the bispectral index (BIS) (BIS monitor A2000, Aspect Medical Systems, Newton, MA, USA). When subjects continued to open their eyes or responded to verbal commands very slowly, the infusion of propofol and midazolam was changed by 0.1 μg mL−1 or 0.5 mg h−1, respectively.
Precise and simple dynamic balance tests, psychomotor function tests and grip strength test were performed at each time point as described in Figure 1. A dynamic balance test using CDP with unpredictable random perturbation stimuli was performed by a Stability System (Biodex Medical Inc., Shirley, NY, USA) as described previously . Briefly, the subject was instructed to maintain a standing position for 20 s on an unstable platform that tilted in all directions according to changes in body weight applied to the tip of the toes and the heels. The degree of platform tilt from the horizontal line in all directions during the test was expressed as the stability index.
The maximum-speed walking (MSW) test, in which the time required to walk 10 m at the maximum speed was measured , and the timed ‘up & go' (TUG) test were performed as simple dynamic balance tests. In the TUG test, the time required for the subject to stand up from a chair, walk forward 5 m, return to the chair at maximum speed and sit on the chair again was measured . The digit symbol substitution test (DSST) and the Trieger dot test (TDT) were performed as simple tests of psychomotor function. The DSST was performed for 90 s using the Japanese version of the manual for the Wechsler Adult Intelligence Scale-Revised. The subjects drew the appropriate symbol under the digit following predetermined rules. The number of correct answers was scored. In the TDT, a geometric figure was drawn by connecting a series of dots with a ball-point pen. The number of dots left unconnected by the drawn line was scored. The grip strength of a subject's dominant hand was measured with a Smedley Hand Dynamometer (Matsumiya, Tokyo, Japan). The increase in each variable, except DSST and the grip strength test, represents a reduction of function.
This study was designed to have an 80% power of detecting a difference of 0.24° (this score is equivalent to 15% of the baseline score of young subjects in a preliminary study) in stability index between the mean score in propofol sedation and the mean score in midazolam sedation. Data were processed as follows. In the precise and simple dynamic balance, psychomotor function and muscle strength tests, intra-group differences were analysed with χ2 test, and subsequent multiple comparisons were performed with the Wilcoxon signed rank sum test with Bonferroni's test. Inter-group differences in the change from the baseline score were compared with the Wilcoxon signed rank sum test in the precise and simple dynamic balance, psychomotor function and muscle strength tests and BIS. The relationship between CDP and the two simple dynamic balance tests was assessed with correlation coefficient. P values of less than 0.05 were considered significant. Scores are expressed as the mean ± standard deviation.
The mean age, height, body weight and body mass index (BMI) of the subjects were 23.9 ± 1.75 yr (range, 22–28 yr), 170.9 ± 5.7 cm (range, 164–184 cm), 62.5 ± 5.6 kg (range, 54–72 kg) and 21.4 ± 1.8 kg m−2 (range, 19.0–24.9 kg m−2), respectively. The total doses of propofol and midazolam infused during the study period were 4.75 ± 0.91 mg kg−1 and 0.11 ± 0.01 mg kg−1, respectively. The BIS scores were maintained in the range 73–83 during infusion of the sedatives (Fig. 2).
The scores of the dynamic balance test, MSW test and TUG test were significantly lower in propofol sedation than in midazolam sedation till 40, 60 and 60 min after the end of sedation, respectively (Table 2). The scores of the DSST and the grip strength test were significantly greater with propofol sedation during the first 70 min and at 30 min after the end of sedation, respectively (Tables 2 and 3). There was a close and significant positive correlation between the results of the simple dynamic balance tests and the CDP with midazolam sedation (TUG test vs. CDP: r = 0.66, P < 0.01; MSW test vs. CDP: r = 0.53, P < 0.01), but the correlation was not as close following propofol sedation (TUG test vs. CDP: r = 0.3, P < 0.05; MSW test vs. CDP: not significant).
The recovery of dynamic balance function assessed by CDP after sedation with midazolam has been reported [5,9–11], but there are no reports on propofol sedation. We confirmed that propofol is more suitable than midazolam for i.v. sedation in the outpatient clinic with regard to street fitness using precise and simple dynamic balance tests in the present study.
Custon and colleagues  found that anterior tibialis activation, a medium-latency response, was delayed at 1 h after oral diazepam administration in elderly volunteers; thus, they speculated that diazepam delayed the brainstem-controlled oligosynaptic spinal reflex, resulting in inhibition of balance function. In the present study, the infusion of midazolam may have inhibited dynamic balance function by a similar mechanism. The DSST showed that the recovery was significantly slower after midazolam sedation than after propofol. This result suggests that the difference in the recovery of dynamic balance between the two sedatives is partly associated with a delay in psychomotor functions, such as attention, the capability of prediction and choice of strategy for maintaining balance. In the present study, midazolam caused a significantly greater reduction in grip strength than propofol during and until 30 min after the cessation of sedation. Midazolam is well known to act on the spinal pathway to reduce muscle strength and reflexes from a study on evoked motor extremity responses . Propofol also has a dose-dependent effect on motor evoked potential [14,15]. However, propofol is metabolized rapidly and the concentration used for sedation is low; thus, the reductive effect of propofol on motor function can be distinguished in the recovery period. Therefore, the differences between the two sedatives in the recovery of dynamic balance function may be associated with the difference in muscle relaxant effect in the two sedatives.
In this study, we tried to maintain a constant sedation level on the basis of clinical signs and were able to maintain BIS values in the range 73–83. In sedation with midazolam or propofol, BIS values of 75–89 indicate a sedation level at which the subject has no airway obstruction and responds to verbal stimuli [16,17]. Therefore, we speculate that the desired conscious sedation level was maintained overall in the present study. The BIS values were lower in the propofol group during the last 20 min of sedation. However, this was reversed 10 min after the end of the infusion. These results indicated that recovery from propofol sedation was more rapid.
Previously we reported that the intentional body sway test was useful for the evaluation of recovery from i.v. sedation in the elderly, but was not suitable for young adults . CDP is classified according to the types of postural control as CDP using an intentional postural sway task [11,18,19] and CDP using perturbation stimuli [5,9,10]. As falls may occur in any direction in daily life, multidirectional mechanical perturbation is a desirable stimulus condition for CDP . Such a stimulus also prevents habituation. The CDP performed for young adults in the present study fulfils the conditions mentioned above, and is reported to be a reliable precise test for the evaluation of postural control ability against unpredictable perturbation stimuli . On the other hand, a simple test that is well correlated with a precise CDP is necessary for wide clinical application . The TUG test had results most strongly correlated with those of CDP with perturbation stimuli in midazolam sedation in the present study. The test originated from the ‘Get-up and Go' test developed by Mathias  as a simple balance function test, in which the risk of falls was qualitatively classified using a 5-point scale for the elderly. Padsiadlo and colleagues  measured the time required to complete the actions. Shumway-Cook  used MSW, and Shimada  used MSW and extended the distance from the original 3 m to 5 m. The TUG test has many advantages in clinical use, such as proven differences between fall and non-fall groups, a proven correlation with balance function, good reproducibility, high sensitivity and specificity, applicability to the elderly, short measurement time, low cost and no requirement for wide space [8,22–27]. We used the TUG test with MSW as modified by Shimada . A good correlation between balance and the MSW has also been demonstrated [7,28,29]. The TUG test used in the present study requires rapid acceleration and deceleration, a turn during high-speed walking, and rapid sitting down with a turn. We think the TUG test is more suitable than the MSW test for assessing the entire motor function closely associated with balance function in the ambulatory setting with regard to the actions described above, its stronger correlation coefficient with a reliable CDP, and no requirement for large space.
The TUG and MSW tests both had close and significant positive correlations with CDP after midazolam sedation, but not after propofol sedation in the present study. The exact reasons for this result remain unclear. However, as grip strength recovered within 10–30 min after the end of propofol infusion, the ability to walk with maximum speed seemed to be already recovered at most time points at which dynamic balance tests were performed. Therefore, a small difference in values between before and after sedation may decrease the correlation coefficient between CDP and simple dynamic balance tests in propofol sedation. CDP detected a difference of dynamic balance between midazolam and propofol for 40 min, whereas the MSW and TUG tests showed differences up to 60 min in the present study. This may have derived from the difference of recovery of muscle power between the two sedatives because the performance of the MSW and TUG tests may need more muscle power than CDP.
In summary, both precise and simple dynamic balance tests can detect the difference in the speed of recovery of dynamic balance after midazolam and propofol sedation. The TUG and MSW tests are useful, simple dynamic balance tests, well correlated with precise CDP, for the evaluation of the recovery of dynamic balance from midazolam sedation in younger adults.
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