Investigation On TCI Of Midazolam For Sedation And Anterograde Amnesia In Patients Of Different Ages On The Monitoring Of BIS

BackgroundIt is essential that the patients are assisted sedatives under intraspinal anesthesia to avoid the state of anxiety and terrible memory. For a long time, Droperidol and Benzodiazepine are commonly used in intraoperative sedation clinically. Midazolam is the first clinically used water-soluble benzodiazepine drug. The pharmacological action of midazolam is characterized by the action of antianxiety,sedation,hypnosis and anterograde amnesia. The unique feature of midazolam is its short- acting pharmacokinetic profile. Intravenous infusion administration is adopted clinically for sedation under anesthesia. However, This modus of administration not only can't maintain the stable of sedation and avoid terrible memory but also can affect hemodynamics in patients to a great extent. Target-controlled infusion (TCI) is a new technique that based on the pharmacokinetic and pharmacodynamic of an intravenous drag, anesthetist can set and adjust the target concentration (plasm compartment concentration or effect compartment concentration) and infusion rates are altered automatically according to a pharmacokinetic model. The advantages that TCI has over the current method of continuous infusion pumps are myriad, including ease of use, Maintaining a constant plasma or effect compartment concentration of an intravenous anesthetic requires continuous adjustment of the infusion rate according to the pharmacokinetic properties of the drag. At present, The TCI of propofol or remifentanil is widely used in clinical anesthesia, but there are only a few studies on the TCI of midazolam. Recently, With the electronic computer is widely used in medical field, the monitoring of nervous function is introduced into the monitoring of depth of anesthesia. Bispectral index(BIS) becomes one of the technique in monitoring depth of anesthesia at present. It has been approved that BIS correlated well with the depth of sedation. But, the relationship of anterograde amnesia with BIS and effect-site concentration(Ce) has been not determined recently.ObjectiveIn this study, Under the BIS monitoring, the technique of TCI was used to indicate the depth of midazolam-induced intraoperation sedation of patients undering intraspinal anesthesia. The aim of this study was to determine the appropriate BIS and Ce values during TCI of midazolam for sedation and anterograde amnesia in patients of different ages under intraspinal anesthesia and investigate the relationship of BIS and Ce with levels of sedation and the effectiveness of BIS and Ce in measuring the change of conscious state. Meanwhile, To observe the incidence rate of adverse reaction during the TCI of midazolam.Material and Method1. MaterialSixty ASA I and II patients presenting for elective hypogastric surgery were included in this study. The patients were randomly divided into two groups:(group I ) the young group (20～40yrs old) (n=30) and (group II) the aged group (≥65yrs)(n=30).The patients were excluded from the study if they had handicap of hearing intraspinal anesthesia contraindication,central nervous systerm disease and taking antipsychotic drugs recently.2. Drug and Instrumentation2.1 Midazolam(Batch No.B1246,Basel,F·Hoffmann-La Roche A, Switzerland)2.2 TCI-I pump (Greenbla module, Beijin slog high-tech development company, China)2.3 Multifunction monitor (PHILIPS-1205A,HP company, American)2.4 Multifunction anesthetic machine ( OmedaAspire / 57100, Englewood company, American) 2.5 BIS xp Monitor (A-2000, Aspect medical system, American)3. MethodThe patients were sedated given by TCI of midazolam. TCI was targeted as cascading effect-site concentration(Ce) gradually and Ce of midazolam was set first at 40ng/ml with increment of 10ng/ml until the patients stopped responding to light shaking (OAA/S=1).Each target concentration infusion was maintained for 15 min. The depth of sedation and was assessed with OAA/S score and the test of anterograde amnesia was carried every 5 min. BIS was continuously monitored. The BIS,Ce values and hemodynamic parameters before the time of each OAA/S score(5-1) were recorded.4. Anterograde amnesia TestAnesthetist told the patients to get preoperative preparation concernin anterograde amnesia test. During TCI of midazolam, the test of looking at a type of picture were performed every 5 min after assessment of OAA/S score in patients and ended until the patients stopped responding to shaking. Afer 24 hours, let the tester recall the content on the picture that they had seen during the intraoperative sedation with TCI of midazolam. It was deemed anterograde amnesia that the patients could not actively recall the pictures to their minds.Statistics analysisStatistical package (SPSS 11.0) was used for processing data, The measurement datum were expressed as x|-±s ; The numeration datum were expressed as chi square test; The factor within-subject was analyzed with Kruskal-Wallis variance analysis; The factor between-subject was analyzed with T test; The BIS and Ce were correlated with the OAA/S score using nonparametric Spearman's rank-correlation analysis and To calculate the prediction probability (Pk) values predicting conscious state; a=0.05 was considered that the difference was statistically significant.Result1. Comparison of demographic dataThere were no significant differences between the two groups with respect to sex, body weight and height (P>0.05) ;There were significant differences with respect to age (P<0.05) .2. Comparison of pharmacodynamic2.1 The relationship of anterograde amnesia with Ce,BISWith the increasing value of Ce there was a progressive decrease in BIS value and increase in amnesia rate in each group. At the same level of sedation (OAA/S=4～3), group II exhibited higher BIS value and amnesia rate and lower Ce values than group I (P<0.05); With increasing sedation,the amnesia rate increased significantly, when the patients lost consciousness (OAA/S=2～1), the amnesia rate reached 100% (P>0.05) .When the anterograde amnesia rate reached 100% in the young, the Ce,BIS values were respectively 74.3±21.5ng/ml,61.6±7.9;When the anterograde amnesia rate reached 100% in the aged, the Ce,BIS values were respectively 58.3±12.5ng/ml,82.3±4.2.2.2 The relationship of OAA/S score with Ce,BISThe BIS value positively correlated with OAA/S score in each group, group I: r= 0.846, group II: r=0.812;The Ce value negatively correlated with OAA/S score, group I :r=-0.693,group II r=-0.708 (P>0.05) ;The BIS correlated with OAA/S score better in both groups than Ce (P<0.05) ; The group II received suitable sedation at level 3 of OAA/S score and the group I at level 2. 23 The comparison of PkThe Pk values of BIS,Ce for unconsciousness were respectively above 5%, There were no significant differences between the two groups with respect to Pk (P>0.05) . 2.4 The comparison of the incidence rate of adverse reactionDuring TCI of midazolam there were no significant changes in the incidence rate of respiratory tract obstruction,respiratory depression and intraoperative restlessness (P>0.05) ;The incidence rate hypotension was significantly higher in group I compared to the group II (P<0.05) .Conclusion1. When the anterograde amnesia rate reach 100%, the aged exhibit higher BIS and lower Ce values than the young during TCI of midazolam.2. Ce can effectively evaluate the depth of sedation during TCI of midazolam in patients of different ages and Ce correlated with the depth of sedation worse than BIS in both groups.3. Ce can predict effectively and promptly the change of consciousness state; The ability of prediction of Ce is the same as BIS in the young and the aged.4. The aged can receive suitable sedation at level 3 and the young can receive suitablesedation at level 2 of OAA/S score under intraspinal anesthesia.