| Background and Objective:Etomidate combined with opioid-based intravenous anesthetic induction is widely used in clinical anesthesia. Etomidate, short-acting non-barbiturates, is widely used in clinic because of its small impact on hemodynamics, mild respiratory depression, large safe range, rapid onset, rapid recovery with the advantages of little accumulation But etomidate has no analgesic effect, so it requires application of opioid. Sufentanil is a newly synthesized potentμreceptor agonist of fentanyl family, and its analgesic potency is 5-10 times to fentanyl. It has little effect on circulation with characteristics of well suppression in tracheal intubation response and intraoperative stress response, with mild respiratory depression, rapid onset during induction, rapid recovery, so clinical application of sufentanil combined with etomidate is gradually expanding. Sufentanil has a sedative effect and may increase anesthetic effects of etomidate, but current literature on this are few.General anesthesia is a complex state, the traditional method of monitoring anesthesia depth depends on the clinical manifestations such as heart rate, blood pressure, body movement, etc. But the specificity of these indicators is not strong, with many interfering factors,so it is difficult to accurately reflect the anesthesia depth. Intraoperative awareness and other adverse reactions can occur easily. It is reported that the incidence of intraoperative awareness in general anesthesia was as high as 0.0015%-0.2%, so the depth of anesthesia monitoring is given more and more attention. Currently considered as the representative of quantitative EEG parameters, bispectral index (bispectral index, BIS) is more reliable indicator for the depth of sedation monitor, which can effectively reduce the incidence of intraoperative awareness.The purpose of this study is to determine the median effective dose (ED50) and half of sleep BIS values (BIS50) of etomidate when combined with sufentanil for anesthesia induction, and to explore the effect of sufentanil on BIS50 and ED50 of etomidate to provide rationale for clinical anesthesia medication.Methods:A total of 72 gynecology patients undergoing selective operation under general anesthesia were recruited. Patients were 30 to 50 years old, ASAⅠ-Ⅱ,with 19 to 24 kg/m2 body mass index. Exclusion criteria included a history of psychiatric diseases, using of spirit and sedative hypnotic drugs, hepatic or renal dysfunction, cardiovascular diseases, Patients who had used psychotropic and sedative hypnotic drugs were excluded. Patients who were allergic to fentanyl, sufentanil and other opioid were also excluded. The subjects were randomly divided into three groups: group I:only etomidate; groupⅡ:etomidate combined with sufentanil 0.5μg/kg; group III:etomidate combined with sufentanil 0.7μg/kg.Patients had normal fasting for 8 hours, forbidden to drink for 4 hours, without premedication. An intravenous cannula was inserted into a left forearm vein when patients arrived at the operating room and then compound sodium lactate solution was given at 10ml/kg/h. Routine monitoring of electrocardiogram (ECG), noninvasive blood pressure, pulse oximetry (SpO2) and heart rate (HR) were performed. Connect Aspect Company A-2000 BIS monitor and the monitoring device and then awake BIS value were recorded after patients taked rest for 5min. Patients in Group I received etomidate by 0.060mg/kg,0.090mg/kg,0.135mg/kg,0.203mg/kg sequential administration, that was the first patient started with the setted highest dose. The basic principle was that if the patient lost consciousness after the patient received etomidate, the second patient was given a reduced dosage of etomidate. If the patient didn't lose consciousness then the third patients increased a dose step. Group II was first given sufentanil 0.5μg/kg, and the administration time was about lmin.4min after sufentanil administrated, etomidate was given 0.040 mg/kg,0.060mg/kg,0.090 mg/kg,0.135mg/kg sequential administration according to the pre-test result. GroupⅢwere given sufentanil 0.7μg/kg, as groupⅡ, etomidate were give four steps by sequential administration. BIS values were automatically recorded by computer every 2s. Observer observed the awareness situation of the patients, recorded the BIS values at loss of consciousness and the BIS minimum values during the process. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) at 1min,2min,3min,5min after administration of drugs were also recorded. Administration time of etomidate was 15s in the trial, OAA/S scale was used to assess the level of sedation. The loss of consciousness end point was defined as an OAA/S score≤2.Etomidate ED50 and 95% confidence interval can be substituted into the following formula:1gED50=ΣnLgX/Σn; Standard error S=d (?), d is the number of the two adjacent doses logarithmic difference. The calculation method of BIS50 is similar to the calculation of ED50.SPSS 15.0 statistical package was used for statistical analysis, parametric variables are expressed as mean±standard deviation. Analysis of variance, correlation and regression analysis were used for analysis correspondingly. The significance level was a=0.05.Result:1. There was no significant difference among groups in age, weight, height (F,=3.781;F2=2.954;F3=4.028;P>0.05)2. Comparison of hemodynamic conditions(1) Intragroup comparison:The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) of three groups after drug administration compared lmin,2min,3min,5min time point were lower than baseline values To, there was significant difference (P< 0.05).According to data, lmin,2min compared with the baseline time point is more lower, the difference was statistically significant(P< 0.05).(2) Intergroup comparison:The baseline indicators To between three groups were not statistically different (P>0.05). The indicators at lmin,2min time point in group III significantly decreased and were statistically different compared with group I (P<0.05).There were no significant difference of the indicators at the other time points between groups (P> 0.05)3. Etomidate ED50 and 95% confidence interval in each groupEtomidate ED50 and 95% confidence interval of groupⅠ, groupⅡ, groupⅢwere 0.105 (0.089-0.124) mg/kg,0.084 (0.070-0.101) mg/kg,0.075 (0.061-0.092) mg/kg respectively. Etomidate ED50 of groupⅡ, groupⅢdecreased significantly compared with groupⅠ4. Etomidate BIS50 and 95% confidence interval in each groupEtomidate BIS50 and 95% confidence intervals of groupⅠ, groupⅡ, groupⅢwere 59 (46.82-74.36),68 (61.81-76.09),72 (63.80-83.34) respectively. The BIS50 of group II and group III is significantly higher compared with group I.5. The correlation between the dose of etomidate and the minimum BIS value:The correlation between the dose of etomidate and the minimum BIS value in three groups was negatively correlated. The correlation coefficients of group I, II, III were r=-0.582, r=-0.770, r=-0.692.In the diagram of the dose of etomidate and the minimum BIS value, we drew a vertical line and extended it and gained a corresponding BIS50, the BIS50 is similar to the results of calculation. Conclusion1. Sufentanil can significantly reduce etomidate's ED50 during induction and increases the sedative effect of etomidate.2. The BIS50 of group etomidate combined with sufentanil is significantly higher compared with group etomidate. The correlation between the dose of etomidate and the minimum BIS value in three groups was negatively correlated. |
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