Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 ~tg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 ~tg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spon- taneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100~ and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry （http：//www.chictr.org. cn/） （registration number： ChiCTR-IPR- 16008113）.

Bispectral index in predicting the prognosis of patients with coma in intensive care unit

BACKGROUND: The bispectral(BIS) index is a processed electroencephalogram(EEG) parameter with extensive validation and demonstrated clinical utility. The study aimed to investigate the correlation between the BIS index and the prognosis of patients with coma in the ICU.METHODS: A total of 208 patients with coma in the ICU were enrolled in this study. According to the BIS value, the patients were divided into four groups: group I, BIS value 0 to 20; group II, BIS value 21 to 40; group III, BIS value 41 to 60; and group IV, BIS value greater than 60. The difference in BIS values with the differences in prognosis of patients with coma was compared between the four groups, and the prognosis of patients with coma was stratified into consciousness, coma, vegetative state, and brain death. Subsequently, the best cut-off score of BIS values calculated for determining the correlation between BIS value and mental state was proposed.RESULTS: There are no significant differences in the age and APACHE II scores between the four groups(P>0.05). An inverse correlation was observed between BIS value and mental state(r= –0.749, P=0.00). According to the ROC curve, as BIS value was greater than 42.5, there were higher sensitivity and specificity in conscious-coma patients.CONCLUSION: BIS value is correlated with the prognosis of patients with coma in ICU, and BIS value can be a useful marker for estimating the prognosis of comatose patients.

Comparison of Entropy vs. Bispectral Index Anesthetic Depth Monitoring during Isoflurane Anesthesia in Living Donor Liver Transplantation: Observational Study

Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.

The Bispectral Index Interest during General Anesthesia at the University Hospital of Parakou (Republic of Benin) in 2019

Background: The bispectral index (BIS) derived from the electroencephalogram is an additional means of monitoring the depth of narcosis. Objective: To compare the monitoring of the depth of narcosis by the BIS associated with clinical data versus standard monitoring at the University Hospital of Parakou in Benin in 2019. Methods: This was an observational study for descriptive and analytical purposes with prospective data collection, carried out in general surgery and intensive care unit for 4 months. The inclusion criteria were: an age ≥ 18 years, an ASA score ≤ 3, surgery under general anesthesia and informed consent of the patient. Two groups were formed: non-BIS group monitored by clinical parameters (PA, FC, FR, EtCO2, and SpO2) only and BIS group monitored by bispectral index in addition to clinical parameters. Patients were seen 48 hours after the procedure. Results: 36 patients were collected. The mean age was 40.63 ± 16.77 years with a sex ratio of 3. ASA 1 patients represented 86.11% of the sample and ASA2 patients 13.89%. The average doses of Propofol were not significantly reduced in the BIS group (p = 0.555). On the other hand, the period of intraoperative recovery (p-value = 0.007) and the NVPO (p = 0.043;OR = 0.10;95% CI [0.01 - 0.97]) were significantly reduced by the use of BIS. One case of intraoperative memorization (2.78%) was however found in the BIS group. Conclusion: The bispectral index makes it possible to significantly reduce the risk of intraoperative awakening and PONV, and not significantly reduce the consumption of Propofol.

Bispectral index monitoring prevent awareness during total intravenous anesthesia： a prospective, randomized, double-blinded, multi-center controlled trial

Background Awareness is a serious complication of general anesthesia. In China, the incidence of intraoperative awareness was 1% in patients undergoing total intravenous anesthesia （TIVA）. In this study, we compared the incidence of awareness between Bispectral index （BIS）-guided and routine TIVA protocol and evaluated the effect of BIS on preventing awareness. Methods A prospective, randomized, double-blinded, multicenter controlled trial was performed. Patients （〉18 years of age） undergoing TIVA were randomly divided into BIS-guided group （Group A, BIS was monitored and recommended to maintain between 40-60） and control group （Group B, BIS was monitored but the screen was covered）. The intraoperative BIS values were downloaded and the BIS trends of confirmed awareness cases were analyzed to determine whether light anesthesia existed. Results Of the total 5228 patients, 2919 patients were assigned to Group A and 2309 to Group B. Four cases of confirmed awareness （0.14%） were reported in the BIS-guided group and 15 （0.65%） in the control group （P=-0.002, OR=0.21, 95% confidence intervals： 0.07-0.63）. The incidence of possible awareness （0.14% vs. 0.26%, P=0.485） and dreaming （3.1% vs. 3.1%, P=0.986） was comparable between BIS-guided group and the control group. Among the 19 confirmed awareness cases, intraoperative BIS trends of six cases were downloaded and identified. Five of them showed signs of light anesthesia as BIS 〉60 and lasted 19-106 minutes, whereas one case had a stable BIS trend and the values were within 60 during the operation. Another five awareness cases were reviewed for anesthesia procedures, of which improper light anesthesia were confirmed. Conclusions BIS-guided TIVA （BIS was recommended to maintain between 40-60） decreased the risk of awareness compared with routine TIVA. The main reason for awareness was light anesthesia.

Comparison of C50 for Propofol-remifentanil Target-controlled Infusion and Bispectral Index at Loss of Consciousness and Response to Painful Stimulus in Elderly and Young Patients

Background：In this prospective randomized study,we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion （TCI） and the bispectral index （BIS） values at loss of consciousness （LOC） and response to a standard noxious painful stimulus （LOS） in elderly and young patients,respectively.We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.Methods：There were 80 American Society of Anesthesiologists （ASA） physical status Ⅰ Ⅱ unpremedicated patients enrolled in this study,they were divided into elderly group （age ≥65 years,n =40） and young group （aged 18-54 years,n =40）.Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer＇s Assessment of Alertness and Sedation score was 1.The propofol level was kept constant,and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml,and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus.BIS （version 3.22,BIS Quattro sensor） was also recorded.Results：In elderly group,the propofol effect-site C50 at LOC of was 1.5 （1.4-1.6） μg/ml,was significantly lower than that of young group,which was 2.2 （2.1-2.3） μg/ml,the remifentanil effect-site C50 at LOS was 3.5 （3.3-3.7） ng/ml in elderly patients,was similar with 3.7 （3.6-3.8） ng/ml in young patients.Fifty percent of patients lost consciousness at a BIS value of 57.3 （56.4-58.1）,was similar with that of young group,which was 55.2 （54.0-56.3）.Conclusion：In elderly patients,the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients.At same sedation status,predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients.BIS were not affected by age.Low-propofol/high-opioid may be optional TCI strategy for elderly patients.

Comparison of the ability of wavelet index and bispectral index for reflecting regain of consciousness in patients undergone surgery

Background Wavelet index （WLI） is a new parameter for monitoring depth of anesthesia based on Wavelet analysis. We observed the change of WLI and bispectral index （BIS） in patients regain of consciousness （ROC） in the absence of frontalis electromyographic （EMG） interference. The aim of this study was to compare the ability of WLI and BIS for reflecting ROC in patients undergone surgery. Methods Twelve patients who were scheduled for maxillofacial surgeries were enrolled in the study. BIS and WLI values were monitored continually. After being given midazolam and remifentanil, patients were asked to squeeze the investigator＇s hand ever 30 seconds. Patients were continuously given propofol until loss of consciousness （LOC1）. Tunstalrs isolated forearm technique was used to test the surgical consciousness in patients. After total muscle relaxation endotracheal intubations were performed, and the patients were connected to a ventilator. Then, propofol was withdrawn until the patients showed regain of consciousness （ROC1） and an awareness reaction. After the command test, patients were readministered with propofol until loss of consciousness （LOC2）. After surgery, all of the sedatives were withdrawn, and the patients were let to regain consciousness （ROC2）, Results The BIS values of twelve patients at ROC1 after using muscle relaxant were much lower than those at LOC1 and ROC2 without using muscle relaxant, showing statistical significance （P 〈0.05）. Meanwhile, the WLI values of twelve patients at ROC1 after using muscle relaxant were much higher than those at LOC1 and equal to ROC2 without using muscle relaxant, showing statistical significances （P 〈0.05） between ROC1 and LOCI. Conclusions This study showed that under muscle relaxation or facial paralysis, when there is no EMG signal, BIS can not accurately reflect regain of consciousness in surgical patients, but WLI can reflect it accurately. So WLI may have advantages for reflecting state of consciousness in surgical patients.

Changes in the Bispectral Index in Response to Loss of Consciousness and No Somatic Movement to Nociceptive Stimuli in Elderly Patients

Background： Bispectral index （BIS） is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia.This study compared the BIS changes in response to loss of consciousness （LOC） and loss of somatic response （LOS） to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion （TCI） of propofol and remifentanil.Methods： This study was performed on 52 elderly patients （aged 65-78 years） and 52 young patients （aged 25-58 years）, American Society of Anesthesiologists physical status Ⅰ or Ⅱ.Anesthesia was induced with propofol administered by TCI.A standardized noxious electrical stimulus （transcutaneous electrical nerve stimulation, [TENS]） was applied （50 Hz, 80 mA, 0.25 ms pulses for 4 s） to the ulnar nerve at increasing remifentanil predicted effective-site concentration （Ce） until patients lost somatic response to TENS.Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated.Results： BISLOC in elderly group was higher than that in young patient group （65.4 ＆#177; 9.7 vs.57.6 ＆#177; 12.3） （t =21.58, P 〈 0.0001） after TCI propofol, and the propofol Ce at LOC was 1.6 ＆#177; 0.3 μg/ml in elderly patients, which was significantly lower than that in young patients （2.3 ＆#177; 0.5 μg/ml） （t =7.474, P 〈 0.0001）.As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups （t =8.902 and t =8.019, P 〈 0.0001）.With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOS was the same as the BISLOC in elderly patients （65.6 ＆#177; 10.7 vs.65.4 ＆#177; 9.7）, and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS.Conclusion： In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually.

Evaluation of entropy for monitoring the depth of anesthesia ：ompared with bispectral index： a multicenter clinical trial

Background As a new electroencephalogram （EEG） signal processing technique for monitoring the depth of anesthesia, entropy consists of two indices： reaction entropy （RE） and state entropy （SE）. Our study compared entropy with classical bispectral index （BIS） in reduction of myoelectrical interference and noxious stimuli with EEG signals. Methods Two hundred and eighty patients （ASA I-II, 18-60 years old） undergoing scheduled surgeries from seven medical centers were enrolled. Anesthesia induction was managed with propofol via the target-controlled infusion （TCI） system. The results of BIS, RE, SE, mean arterial pressure （MAP） and heart rate （HR） were recorded before anesthesia induction, at the moment of unconsciousness, before and 2 minutes after administration of muscle relaxant, and before and one and three minutes after the tracheal intubation. Results The values of half maximum effective concentrations （EC50）, 5% effective concentrations （EC05） and 95% effective concentrations （EC95） of propofol effect-site concentration at the onset of unconsciousness were 1.2 （1.1-1.3 μg/ml）, 2.5 （2.4-2.5 μg/ml） and 3.7 （3.7-3.8 μg/ml）, while those of the predicted plasma propofol concentration were 2.8 （2.7-2.9 μg/ml）, 3.9 （3.8-3.9 μg/ml） and 4.9 （4.8-5.0μg/ml）, respectively. The values of BIS, SE and RE were 62, 59 and 63 when 50% of patients lost consciousness, and 79, 80, 85 and 42, 37, 44, respectively, when 5% and 95% of patients were unconscious. The values of BIS, RE and SE dropped two minutes after the injection of muscle relaxant, but there were no significant differences between RE and SE. MAP and HR increased visibly, which indicated a reaction to tracheal intubation; the values of BIS, RE and SE, however, did not display any significant changes. Conclusions This large-sample multicentric study confirmed the values of RE and SE as approximating BIS value, at the onset of unconsciousness during propofol TCI anesthesia. After elimination of myoelectrical activation, all values of RE, SE and BIS decreased significantly and the three indices were less sensitive to noxious stimuli than cardiovascular responses.

BIS Monitoring on Intraoperative Awareness： A Meta-analysis

Intraoperative awareness is a very serious complication of general anesthesia. Several studies have evaluated the potential association between bispectral index （BIS） and intraoperative awareness, however, the results obtained were controversial. Therefore, we performed a metaanalysis to further assess the association between the BIS monitoring and the incidence of intraoperative awareness. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to Feb. 2017. A total of five studies with 17 432 cases and 16 749 controls were included. An odds ratio （OR） and a 95% confidence interval （CI） were calculated to examine the strength of the association. The results showed that in the overall analysis, the association between the BIS monitoring and the incidence of intraoperative awareness was not significant （OR=0.58, 95% CI= 0.22-1.58, P=0.29）. A stratified analysis by comparing different anesthesia methods revealed that BIS monitoring group showed a lower incidence of intraoperative awareness in patients with intravenous anesthesia when compared with non-BIS monitoring group （OR=0.20, 95% CI=0.08-0.49, P=-0.0004）, whereas there was no statistically significant difference in the incidence of intraoperative awareness between BIS and non-BIS monitoring groups in patients with inhalation anesthesia （OR=1. 13, 95% CI=0.56- 2.26, P=-0.73）. In conclusion, our meta-analysis showed that BIS monitoring had no appreciable advantage in the reduction of the intraoperative awareness incidence in inhalation anesthesia, while showed a remarkable superiority in intravenous anesthesia.

Anesthetic considerations for the patients with off-pump coronary artery bypass grafting

New surgical techniques for coronary artery bypass graft （CABG） have been explored in order to minimize disfiguring scars, avoid cardiopulmonary bypass and decrease hospital residence and costs etc. Improved surgical expense can perform the procedures in some high-risk patients such as poor left ventricular function, redo CABG, advanced age and renal dysfunction etc. Intraoperatively there is an obligatory period of myocardial ischemia, which may lead to significant hemodynamic consequences. It is a quite challenge to anesthetist in managing the intraoperative patient.

性别和年龄对异丙酚-雷米芬太尼靶控输注下意识和疼痛反应消失EC_(50)及BIS值的影响——多中心研究

Objective To study the effect of gender and ages on predict blood and effect-site EC50 for propofol and remifentanil TCI and bispectral index at loss of consciousness and response to a standard noxious painful stimulus. Methods 405 ASA Ⅰ-Ⅱunpremedicated Chinese patients in 5 medical centers for elective operation were involved. Patients were allocated to 4 groups according to ages (group1: 18<age<30, group2: 30≤age<40, group3: 40≤age<50, group4: 50≤age<65). The propofol was started a predict blood concentration of 1.2 mg/L delivered by Diprifusor, and increased by 0.3 mg/L every 30 s until patients lost their consciousness. After that, effect-site concentration of propofol kept constant and infused remifentanil a predict blood concentration of 2.0 μg/L and increased by 0.3 μg/L every 30 s until they lost response to a standard noxious stimulus. Bispectral index was measured. Probit regression was used to estimate population values for predicted blood and effect-site propofol and remifentanil concentrations at the two clinical end-points and BIS. Results The effect-site and the predict blood propofol concentrations EC50 of male and female were similar. The predict blood and effect-site propofol concentrations EC50 of younger were higher than that of older and BIS values were lower. The blood and effect-site remifentanil ancentrations EC50 at no response to painful stimulus of male and female were similar. The blood and effect-site remifentanil concentrations EC50 and BIS values at this point of each group were similar. 50% of male and female patients lost their consciousness at a BIS value with 54.0 and 59.0 respectively; and at loss of response to painful stimulus with 60.8 and 67.3 respectively. Conclusion Gender didn’t affect the predicted propofol and remifentanil blood and effect-site concentration but affected the BIS values. The propofol concentrations of older were lower than that of younger. And that of remifentanil were not different between younger and older.

Peri-intubation hemodynamic changes during low dose fentanyl, remifentanil and sufentanil combined with etomidate for anesthetic induction

Background Although etomidate is associated with very few cardiovascular side-effects and minimal histamine release it has a less inhibitory effect on the pharyngolaryngeal reflex. Hence, blunting the responses to endotracheal intubation is more dependent of opioids for etomidate-based anesthetic induction. This prospective, randomized, double-blinded study was designed to investigate the effects of low dose remifentanil, fentanyl or sufentanil on etomidate induction with respect to hemodynamics, conscious level changes and drug consumption. Methods Ninety unpremedicated and normotensive patients with American Society of Anesthesiologists （ASA） physical status I or II undergoing elective major abdominal surgery were randomly assigned in a double blinded fashion to each of the three groups： groups F, R and S. A bolus dose of fentanyl 1μg/kg, sufentanil 0.1 μg/kg or remifentanil 1 1 μg/kg was given over 60 seconds in groups F, S and R, respectively. In each instance this loading dose was followed by a continuous infusion （0.1, 0.01 or 0.1 μg·kg^-1·min^-1 of fentanyl, sufentanil or remifentanil, respectively）. After 5 minutes from start of opioid infusion, etomidate was titrated at a rate of 20 mg/min to a decrease in bispectral index （BIS） to 50. The time from administration of etomidate to loss of eyelash reflex or to a decrease in BIS to 50 was recorded. The blood pressure and heart rate were also recorded at different five time points. The average maximum percent changes of systolic blood pressure （Imaximal or minimal measuring value-baselinel/baselinex100%） were calculated. Results The time and the dosage of etomidate necessary to loss consciousness were greater in group F （（70.0±15.6） seconds; （0.35±0.05） mg/kg） than in groups S （（52.3±15.9） seconds; （0.26±0.06） mg/kg） and R （（56.2±20.2） seconds; （0.27±0.07） mg/kg） （P 〈0.01）. The three groups took similar time and amount of etomidate to achieve an adequate depth anesthesia （BIS=50）. The average maximum changes of systolic blood pressure were significantly different among the three groups： F, （25±6）% vs R, （13±4）% or S, （12±5）% （P 〈0.001）. The endotracheal intubation caused marked increases in blood pressure and heart rate in groups F and S, but not in group R, respectively （P 〈0.01）. The great hemodynamic changes occurred more frequently in group F than in groups R and S （P 〈0.01）. The incidence of heart rate decreases of more than 30% of the baselines after induction was higher in group R compared with groups F and S （P 〈0.01）. Conclusions In normotensive and unpremedicated young adult patients receiving etomidate induction, low dose remifentanil or sufentanil significantly reduced the time and the amount of etomidate taken to loss unconsciousness compared with low dose fentanyl, but similar time interval and doses of etomidate were required to acquire adequate depth of anesthesia （BIS=50） for these three opioids. Remifentanil was more effective in blunting the cardiovascular responses to endotracheal intubation, nevertheless, accompanying significant lower heart rate after induction.

Response surface analysis of sevoflurane-remifentanil interactions on consciousness during anesthesia

Background Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer＇s assessment of alertness/sedation （OAA/S） and the bispectral index （BIS） by response surface analysis. Methods Totally 65 American Society of Anesthesiologists （ASA） I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion （TCI） system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program. Results Sevoflurane and remifentanil acted synergistically on OANS. Sevoflurane alone could produce OANS 〈1 at a minimal alveolar concentration （MAC） of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OANS score was 〉3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of （1.04＋0.19）% to （1.81＋0.21）% could maintain a BIS between 60 and 40. Conclusions The response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study （remifentanil 〈10 ng/ml, sevoflurane 〈3.4%）, the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.