Efficacy and safety of propofol target-controlled infusion combined with butorphanol for sedated colonoscopy

BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high doses to achieve the induction of anesthesia in sedated colonoscopy,which has been associated with anesthesia-related adverse events(AEs),including hypoxemia,sinus bradycardia,and hypotension.Therefore,propofol co-administrated with other anesthetics has been proposed to reduce the required dose of propofol,enhance the efficacy,and improve the satisfaction of patients receiving colonoscopy under sedation.AIM To evaluate the efficacy and safety of propofol target-controlled infusion(TCI)in combination with butorphanol for sedation during colonoscopy.METHODS In this controlled clinical trial,a total of 106 patients,who were scheduled for sedated colonoscopy,were prospectively recruited and assigned into three groups to receive different doses of butorphanol before propofol TCI:Low-dose butorphanol group(5μg/kg,group B1),high-dose butorphanol group(10μg/kg,group B2),and control group(normal saline,group C).Anesthesia was achieved by propofol TCI.The primary outcome was the median effective concentration(EC50)of propofol TCI,which was measured using the up-and-down sequential method.The secondary outcomes included AEs in perianesthesia and recovery characteristics.RESULTS The EC50 of propofol for TCI was 3.03μg/mL[95%confidence interval(CI):2.83-3.23μg/mL]in group B2,3.41μg/mL(95%CI:3.20-3.62μg/mL)in group B1,and 4.05μg/mL(95%CI:3.78-4.34μg/mL)in group C.The amount of propofol necessary for anesthesia was 132 mg[interquartile range(IQR),125-144.75 mg]in group B2 and 142 mg(IQR,135-154 mg)in group B1.Furthermore,the awakening concentration was 1.1μg/mL(IQR,0.9-1.2μg/mL)in group B2 and 1.2μg/mL(IQR,1.025-1.5μg/mL)in group B1.Notably,the propofol TCI plus butorphanol groups(groups B1 and B2)had a lower incidence of anesthesia AEs,when compared to group C.Furthermore,no significant differences were observed in the rates of AEs in perianesthesia,including hypoxemia,sinus bradycardia,hypotension,nausea and vomiting,and vertigo,among group C,group B1 and group B2.CONCLUSION The combined use with butorphanol reduces the EC50 of propofol TCI for anesthesia.The decrease in propofol might contribute to the reduced anesthesia-related AEs in patients undergoing sedated colonoscopy.

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients

Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples （1.5 ml） were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters： the central volume of distribution （V1） = 5.4 L, the volume of distribution at steady-state （Vdss） = 195.4 L, systemic clearance （CI1） = 1.10 L/min, and elimination half-life （t1/2 Y） = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance （012） was negatively correlated with patient age, and the volume of slowly equilibrating compartment （V3） was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment （V2） were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.

Relationship between depth of anesthesia and effect-site concentration of propofol during induction with the target-controlled infusion technique in elderly patients

Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. Methods Ninety patients （60-80 years） with an American Society of Anesthesiologists （ASA） physical status of 1-3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 （30 patients in each group）. The patients in Group S1 received propofol with a target plasma concentration of 4.0 pg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 IJg/ml that was raised to 4.0 pg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 pg/ml that was increased stepwised by 1 pg/ml until a target plasma concentration of 4.0 pg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer＇s Assessment of Alertness/Sedation （OANS） score of 1 was achieved, remifentanil （effect-site concentration （Ce） of 4.0 ng/ml） and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure （BP）, heart rate （HR）, and bispectral index （BIS） were recorded. Results When an OAA/S score of 1 was achieved, Ce of propofol were （1.7±0.4） pg/ml, （1.9±0.3） pg/ml, （1.9±0.4） pg/ml and the BIS values were 64±5, 65±8, and 62±8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was （2.8±0.2） pg/ml, （2.8±0.3） pg/ml, （2.7±0.3） pg/ml, and the BIS values were 48±7, 51±7, and 47±5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found （r=-0.580, P 〈0.01）. Systolic blood pressure （SBP） before intubation was significantly lower in Group S1 than in Groups S2 and S3. SBP and HR after intubation in the three groups were significantly increased when compared with pre-intubation values, but they did not exceed baseline values Conclusions During the TCI induction, Ce of propofol with （1.9±0.3） pg/ml may make the elderly patients unconscious. When remifentanil with a Ce of 4.0 ng/ml is added a Ce of propofol with （2.8±0.3） pg/ml is suitable for intubation. The Ce of propofol has a close correlation with the BIS values. Also, a two-step TCI technique seems to be a more suitable method of anesthesia induction in elderly patients compared with the no-stepwise TCI technique and three-step TCI technique.

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients

Background Sufentanil is a suitable choice for target-controlled infusion （TCI） because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis. Methods Twelve adult patients with American Society of Anesthesiologists （ASA） physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples （1.5 ml） were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample （1.0 ml） was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry （limit of quantitation was 5 pg/ml）. The data were analyzed with the two-stage approach, linear regression and correlation analysis. Results The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows： the volume of central compartment （V1） was 5.4 L, volume of distribution at steady-state （Vdss） was 222.6 L, metabolic clearance （CI1） was 0.84 L/min and elimination half-life （t~/2y） was 389 minutes. Patients＇ age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment （V3） and t1/2 y increased, and rapid distribution clearance （012） decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment （V2） and V3 than female patients. The Vdss and V3 increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood （BE-B）. Conclusions The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.

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.

Concentrations of propofol in cerebral spinal fluid: target-controlled infusion

Background Although the performance of target-controlled infusion (TCI) have been studied extensively, the accuracy and safety of a TCI system that targets the effect site remains to be demonstrated. This study was to investigate the relations of TCI of propofol to its concentrations in cerebral spinal fluid (CSF), the effect-site concentrations and bispectral index (BIS).Methods Twelve mongrel dogs were used for investigations. The target effect-site concentration was set at 3μg/ml and the infusion was lasted for 15 minutes. CSF and blood samples were then collected and propofol concentrations were determined by using high performance liquid chromatography with fluorescence detection. BIS and hemodynamic data were monitored continuously.Results The predicted plasma concentrations were generally overestimated. Median performance error (MDPE) and absolute median performance error (MDAPE) were -10.0% and 29.9% respectively. Propofol CSF concentrations were much lower than its effect-site concentrations. Changes in BIS were consistent with propofol concentrations in CSF, both of which changed direction at 5 minutes while the effect-site concentrations relatively lagged behind. Better correlation ( r2 = 0. 9195) was found between BIS and CSF concentrations, when compared with that between BIS and effect-site concentrations (r2=0. 554).Conclusion With 1% enflurane inhaled, the inconsistency of drug effect to the effect-site concentrations may result from inaccuracy of pharmacokinetic parameters. CSF may show effect-site concentrations more accurately than plasma when using target effect-site concentration infusion.

A New Pharmacokinetic Model of Propofol for Japanese Patients

Target-controlled infusion (TCI) of propofol is used for general anesthesia. However, the only pharmacokinetic parameter commercially used for Japanese patients is weight, and pharmacokinetic models are based on European physical attributes. Drug metabolism also differs in races. This study aimed to identify optimal continuous doses of propofol for Japanese patients and to create a simulated pharmacokinetic (PK) model. Thirty Japanese patients were enrolled. Patients received a constant infusion of 9 mg/kg/h of propofol. Arterial blood samples were collected and the time course of plasma propofol concentrations was modeled using the nonlinear mixed effects model (NONMEM) three-compartmental PK model. We validated the model by intravenously injecting 10 patients with a TCI driver system programmed with the NONMEM model. Our model’s performance was evaluated using the median prediction error (MDPE), median absolute prediction error (MDAPE), and Wobble. We analyzed 320 blood samples for model building and 160 samples for validating our new model. The calculated parameters for the three-compartmental PK model were volume [V1, 3.58;V2, 13.0 + 0.49 × (Age—64);and V3, 186] and elimination clearance [CL1, 0.77 + (WT—54) × 0.04 + (HT—158) × 0.03;CL2, 0.89 + 0.12 × (Age—64);and CL3, 0.98 × exp ((Age—64)/10)]. The new model improved MDPE, MDAPE, and Wobble values (11.5% ± 43.8%, 14.3% ± 33.0%, and 25.0% ± 21.3%, respectively). We created a new pharmacokinetic model for Japanese patients, which is more accurate than the three existing models applied to Japanese populations. Electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.

不同靶浓度的瑞芬太尼用于七氟醚吸入诱导的对比观察

目的在脑电双频指数(BIS)的监测下,比较不同血浆靶浓度的瑞芬太尼复合七氟醚麻醉诱导对血流动力学的影响,探讨瑞芬太尼合适的麻醉诱导剂量。方法择期全麻手术患者60例,按瑞芬太尼靶浓度不同随机分为3组:3 ng/ml(D1组)、4 ng/ml(D2组)和5 ng/ml(D3组),每组20例。3组均采用七氟醚吸入麻醉诱导。当BIS值达60时静注顺式阿曲库铵辅助插管。分别记录诱导前(T1)、插管前(T2)、插管即刻(T3)、插管后3 min(T4)的平均动脉压(MAP)和心率(HR),以及各组患者意识消失的时间。结果与T1相比,T2各组MAP和HR均有下降,但D3下降更明显(P<0.05);T3时D1组MAP和HR显著快于T1、T2(P<0.05)。3组患者意识消失的时间相比差异无统计学意义。结论靶控输注4ng/ml的瑞芬太尼复合七氟醚诱导血流动力学更平稳,此剂量的瑞芬太尼为合适的诱导剂量。

心肌特异性脂肪酸结合蛋白在不停跳冠状动脉搭桥术中的变化

Objective To appraise the sensitivity of hFABP for myocardial ischemia in patients undergoing off-pump coronary artery bypass grafting among cardiac markers. Methods Thirty-eight consecutive patients undergoing OPCABG were included in a randomized study using standardized operative procedures and myocardial protection. Serial blood samples were taken preoperatively, during anastomoses, at the end of operation, 6 h, 18 h and 36 h postoperatively and tested for hFABP、Troponin I (cTnI)、sCD40L、creatine kinase isoenzyme (CK-MB). Results Six cases (16.7%) were found myocardial injury during the OPCABG by ECG or PAP. Their serial serum hFABP,cTnI,sCD40L,CK-MB were higher than those without myocardial injury. The peak serum level of hFABP was higher and occurred earlier than those of cTnI,sCD40L,CK-MB. Conclusion These results suggest that serum hFABP is an early and sensitive biochemical marker for the diagnosis of myocardial injury in patients undergoing OPCABG.

Clinical evaluation of target controlled infusion system for sufentanil administration

Background Sufentanil target controlled infusion （TCI） provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia during perioperative period. This study evaluated the accuracy and feasibility of TCI system for sufentanil at high concentrations in Chinese surgical patients. Methods Twelve low risk adult patients undergoing elective surgery under general anesthesia were included in this study. Sufentanil was administered with a specific TCI system incorporating the population pharmacokinetic data of sufentanil previously reported, using a target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI duration was 30 minutes. Frequent arterial blood samples were taken during and up to 24 hours after sufentanil TCI for determination of plasma sufentanil concentrations by liquid chromatography-mass spectrometry/mass spectrometry. The changes of circulatory system function during the procedure, recovery profile and adverse effects were recorded. Measured plasma sufentanil concentrations were compared with the values predicted by the TCI system. The bias （median performance error, MDPE）, precision （median absolute performance error, MDAPE） and wobble （variability of performance error） of the sufentanil TCI system were determined. Results All patients had stable cardiovascular variables during induction and maintenance of anesthesia. Time to eye opening and extubation were （5.6±1.7） minutes when TCI set to 4 ng/ml and （7.2±2.3） minutes when set to 6 ng/ml. There was no episode of agitation, muscle rigidity or intraoperative awareness. The bias （MDPE）, precision （MDAPE） and wobble of the sufentanil TCI system were -3.7%, 18.9% and 19.6% respectively during TCI, and the MDPE, MDAPE and wobble were -29.1%, 31.7% and 15.0% respectively after TCI （up to 8 hours）. Conclusions The TCI system programmed for sufentanil at 4 or 6 ng/ml was considered acceptable for clinical use in low risk Chinese surgical patients. But the relatively larger MDPE and MDAPE after TCI suggest improvements of the Dharmacokinetic model are needed.

Effect of subarachnoid anesthesia combined with propofol targetcontrolled infusion on blood loss and transfusion for posterior total hip arthroplasty in elderly patients

Background:Intravertebral and general anesthesia(GA)are two main anesthesia approaches but both have defects.This study was aimed to evaluate the effect of subarachnoid anesthesia combined with propofol target-controlled infusion(TCI)on blood loss and transfusion for total hip arthroplasty(THA)in elderly patients in comparison with combined spinal-epidural anesthesia(CSEA)or GA.Methods:Totally,240 patients(aged>65 years,American Society of Anesthesiologists[ASA]I-III)scheduled for posterior THA were enrolled from September 1st,2017 to March 1st,2018.All cases were randomly divided into three groups to receive CSEA(group C,w=80),GA(group G,n=80),or subarachnoid anesthesia and propofol TCI(group T,w=80),respectively.Primary outcomes measured were intra-operative blood loss,autologous and allogeneic blood transfusion,mean arterial pressure at different time points,length of stay in post-anesthesia care unit(PACU),length of hospital stay,and patient satisfaction degree.Furthermore,post-operative pain scores and complications were also observed.The difference of quantitative index between groups were analyzed by one-way analysis of variance,repeated measurement generalized linear model,Student-Newman-Keuls test or rank-sum test,while ratio index was analyzed by Chi-square test or Fisher exact test.Results:Basic characteristics were comparable among the three groups.Intra-operative blood loss in group T(331.53±64.33 mL)and group G(308.03±64.90 mL)were significantly less than group C(455.40±120.48 mL,F=65.80,P<0.001).Similarly,the autologous transfusion of group T(130.99±30.36 mL)and group G(124.09±24.34 mL)were also markedly less than group C(178.31±48.68 mL,F=52.99,P<0.001).The allogenetic blood transfusion of group C(0[0,100.00])was also significantly larger than group T(0)and group G(0)(Z=2.47,P=0.047).Except for the baseline,there were significant differences in mean arterial blood pressures before operation(F=496.84,P<0.001),10-min after the beginning of operation(F=351.43,P<0.001),30-min after the beginning of operation(F=559.89,P<0.001),50-min after the beginning of operation(F=374.74,P<0.001),and at the end of operation(F=26.14,P<0.001)among the three groups.Length of stay in PACU of group T(9.41±1.19 min)was comparable with group C(8.83±1.26 min),and both were significantly shorter than group G(16.55±3.10 min,F=352.50,P<0.001).There were no significant differences among the three groups in terms of length of hospitalization and post-operative visual analog scale scores.Patient satisfaction degree of group T(77/80)was significantly higher than group C(66/80,%=7.96,P=0.004)and G(69/80,/2=5.01,P=0.025).One patient complained of post-dural puncture headache and two complained of low back pain in group C,while none in group T.Incidence of post-operative nausea and vomiting in group G(10/80)was significantly higher than group T(3/80,/2=4.10,P=0.043)and group C(2/80,x2=5.76,P=0.016).No deep vein thrombosis or delayed post-operative functional exercise was detected.Conclusions:Single subarachnoid anesthesia combined with propofol TCI seems to perform better than CSEA and GA for posterior THA in elderly patients,with less blood loss and peri-operative transfusion,higher patient satisfaction degree and fewer complications.Trial registration:chictr.org.cn:ChiCTR-IPR-17013461;http://www.chictr.org.cn/showproj.aspx?proj=23024.

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.