Performance of the ARX-derived Auditory Evoked Potential Index as an Indicator of Anesthetic Depth: A Comparison with Bispectral Index and Hemodynamic Measures during Propofol Administration

Background: Autoregressive modeling with exogenous input of middle-latency auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed for monitoring anesthetic depth. The aim of the current study was to compare the accuracy of this new index with the Bispectral Index (BIS), predicted effect-site concentration of propofol, and hemodynamic measures.

Methods: Twenty female patients scheduled for ambulatory gynecologic surgery received effect compartment controlled infusion of propofol. Target effect-site concentration was started at 1.5 [mu]g/ml and increased every 4 min by 0.5 [mu]g/ml. At every step, sedation level was compared with monitoring values using different clinical scoring systems and reaction to noxious stimulus.

Results: Bispectral Index, AAI, and predicted propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness. Hemodynamic variables were poor indicators of the hypnotic-anesthetic status of the patient. BIS correlated best with propofol effect-site concentration, followed by AAI. Hemodynamic measurements did not correlate well. No indicators predicted reaction to noxious stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal. This reaction occurred more rapidly with the AAI than with BIS.     

BIS - AAI and clinical measures during propofol target controlled infusion with Schnider's pharmacokinetic model

AIM: The A-line autoregressive index (AAI) and the Bispectral Index Score (BIS) are two commercially available indexes of anesthetic depth widely used in clinical practice. The aim of the current study was to compare the accuracy of AAI, BIS, Schnider's predicted effect-site concentration of propofol (Ce propofol) to assess depth of anesthesia. METHODS: Forty-four patients scheduled for major elective abdominal surgery received target effect-site controlled infusion of propofol. Target effect-site (Ce propofol) was started at 1.5 mug/mL and increased every 4 min by 1.0 microg/mL until 5.5 microg/mL were achieved. At every step sedation level was estimated, using AAI, BIS, Observer's Assessment of Alertness/Sedation scale (OAA/S), loss of eyelash reflex and Ce propofol. RESULTS: We enrolled 44 patients, 20 males and 24 females, ASA I/II 18/26, 48+/-10 years, 68.2+/-9 kg, 165+/-7.1 cm, body mass index (BMI) 25+/-3.5. At increasing Ce propofol BIS-AAI values decreased progressively (BIS range 97-38) (AAI range 97-17). Values of BIS < or = 50, of AAI < or = 48 and of Ce propofol > or = 5.1 resulted in OAA/S=0, while values of BIS < or = 62, AAI < or = 53 and Ce propofol < or = 3.5 resulted in OAA/S=2. Loss of eyelash reflex occurred when values were BIS < or = 64 and AAI < or 61. CONCLUSION: BIS, AAI, propofol site effect concentration revealed information on sedation level and consciousness but no gold standard yet exists because of consistent overlap between 'conscious' and 'not conscious' states.     

Ability of the bispectral index, autoregressive modelling with exogenous input-derived auditory evoked potentials, and predicted propofol concentrations to measure patient responsiveness during anesthesia with propofol and remifentanil

BACKGROUND: This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil. METHODS: Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated. RESULTS: Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables. CONCLUSIONS: Although BIS, AAI, and CePROP were influenced by remifentanil during propofol administration, their ability to detect OAA/S and LORlash remained accurate. Improved performance is obtained when BIS and AAI are measured in conjunction with drug targeted effect-site concentrations. Remifentanil decreases the ability of these independent variables to detect LORnoxious.     

Ability of the Bispectral Index, Autoregressive Modelling with Exogenous Input-derived Auditory Evoked Potentials, and Predicted Propofol Concentrations to Measure Patient Responsiveness during Anesthesia with Propofol and Remifentanil

Background: This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil.

Methods: Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated.

Results: Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables.     

Does cerebral monitoring improve ophthalmic surgical operating conditions during propofol-induced sedation?

Sudden movements from over-sedation during ophthalmic surgery can be detrimental to the eye. Bispectral index (BIS) and middle-latency auditory-evoked potentials (Alaris AEP index, AAI) were reported to be accurate indicators for the level of sedation and loss of consciousness. We assessed these monitors during sedation with special emphasis on preventing over-sedation. One-hundred patients scheduled for elective eye surgery were sedated with target-controlled propofol infusion and randomly allocated to BIS-guided, AAI-guided, BIS/AAI-guided, or clinically guided groups (n = 25 each). The initial target concentration was 0.5 microg x mL(-1) in patients >70 yr and 1.0 microg x mL(-1) in all other patients. The concentration was increased every 3 min by 0.1 or 0.2 microg x mL(-1), respectively until the patient had reached a BIS value of 75 (range 70-90) or an AAI of 40 (range 35-60). The surgeon who was blinded to group allocation assessed treatment quality after the procedure. Sedation was converted into general anesthesia in four patients because of excessive head movements. BIS was out of range 7% of the time vs 58% for AAI. No significant differences in treatment quality were observed among the four groups. We conclude that propofol sedation, guided by BIS or AAI monitoring, did not enhance ophthalmic surgical operating conditions over sedation guided by clinical observation only.     

A comparison of bispectral index and rapidly extracted auditory evoked potentials index responses to noxious stimulation during sevoflurane anesthesia

In 21 patients given sevoflurane anesthesia, we simultaneously compared the abilities of Bispectral Index (BIS) and rapidly extracted auditory evoked potentials index (AAI) to display the effect of an increasing cerebral concentration of sevoflurane, with and without noxious stimulation. In addition to BIS/AAI, hemodynamic variables were monitored. After titrating sevoflurane to BIS = 50-55 during 15 min, the end-tidal concentration of sevoflurane (1.46% +/- 0.20%) was doubled followed by a noxious stimulus, laryngoscopy, applied at random time points within the following 15 min. After the end-tidal concentration of sevoflurane was doubled, a substantial reduction in BIS was observed, whereas only a slight reduction in AAI was seen (P < 0.0001). BIS/AAI responses to laryngoscopy were not attenuated with increasing wash-in of sevoflurane. After noxious stimulation, AAI exceeded the highest recommended value, 25, in 3 cases, whereas BIS did not exceed the recommended threshold, 60, in any of the patients. Response times for BIS and AAI were 44.5 +/- 26 and 47 +/- 31 s, respectively. These results suggest that, at a hypnotic level associated with surgical sevoflurane anesthesia, BIS better displays drug-related alterations in the level of hypnosis than AAI or hemodynamic variables but there is no difference between BIS and AAI in the time to response to a noxious stimulus.     

A comparison of bispectral index and ARX-derived auditory evoked potential index in measuring the clinical interaction between ketamine and propofol anaesthesia

We evaluated the effects of a bolus (0.4 mg.kg-1) and continuous infusion (1 mg.kg-1.h-1) of ketamine on Bispectral Index (BIS) and A-Line(R) ARX Index (AAI) during propofol anaesthesia. We included 15 ASA I patients scheduled for general anaesthesia. Induction was performed by infusion of propofol at 100 ml.h-1 until loss of consciousness. Both BIS and AAI monitors responded appropriately at that time. The calculated effect site concentration of propofol at loss of consciousness was maintained by means of a computer controlled infusion system. A 'pseudo' steady-state effect site concentration was reached after 4 min. After 1 min of baseline measurements, ketamine was administered. BIS values increased from the 3rd to the 8th min after the administration of ketamine. The AAI showed no significant increase or decrease, but between-patient variability increased.     

Spectral entropy as an electroencephalographic measure of anesthetic drug effect: a comparison with bispectral index and processed midlatency auditory evoked response

BACKGROUND: The authors compared the behavior of two calculations of electroencephalographic spectral entropy, state entropy (SE) and response entropy (RE), with the A-Line ARX Index (AAI) and the Bispectral Index (BIS) and as measures of anesthetic drug effect. They compared the measures for baseline variability, burst suppression, and prediction probability. They also developed pharmacodynamic models relating SE, RE, AAI, and BIS to the calculated propofol effect-site concentration (Ceprop). METHODS: With institutional review board approval, the authors studied 10 patients. All patients received 50 mg/min propofol until either burst suppression greater than 80% or mean arterial pressure less than 50 mmHg was observed. SE, RE, AAI, and BIS were continuously recorded. Ceprop was calculated from the propofol infusion profile. Baseline variability, prediction of burst suppression, prediction probability, and Spearman rank correlation were calculated for SE, RE, AAI, and BIS. The relations between Ceprop and the electroencephalographic measures of drug effect were estimated using nonlinear mixed effect modeling. RESULTS: Baseline variability was lowest when using SE and RE. Burst suppression was most accurately detected by spectral entropy. Prediction probability and individualized Spearman rank correlation were highest for BIS and lowest for SE. Nonlinear mixed effect modeling generated reasonable models relating all four measures to Ceprop. CONCLUSIONS: Compared with BIS and AAI, both SE and RE seem to be useful electroencephalographic measures of anesthetic drug effect, with low baseline variability and accurate burst suppression prediction. The ability of the measures to predict Ceprop was best for BIS.     

Comparison of a new composite index based on midlatency auditory evoked potentials and electroencephalographic parameters with bispectral index (BIS) during moderate propofol sedation

BACKGROUND AND OBJECTIVE: Derived parameters of the electroencephalogram and auditory evoked potentials can be used to determine depth of anaesthesia and sedation. However, it is not known whether any parameter can identify the occurrence of awareness in individual patients. We have compared the performance of bispectral index and a new composite index derived from auditory evoked potentials and the electroencephalogram (AAI 1.61) in predicting consciousness, explicit and implicit memory during moderate sedation with propofol. METHODS: Twenty-one patients with spinal anaesthesia received intraoperatively propofol at the age-corrected C(50) for loss of consciousness and were presented test words via headphones. Bispectral index and AAI 1.61 (auditory evoked potentials, AEP-Monitor2) were recorded in parallel as well as the Observer's Assessment of Alertness/Sedation-score. Postoperatively, testing for explicit and implicit memory formation was performed. RESULTS: Bispectral index and AAI 1.61 correlated well with loss of consciousness defined by an Observer's Assessment of Alertness/Sedation-score of 2 (identical P(K) of 0.87), but did not allow a prediction of postoperative explicit or implicit recall. CONCLUSIONS: Both bispectral index and AAI may be indices of depth of sedation rather than indicators of memory formation, which persists during propofol sedation even after loss of consciousness.     

同等药效学指标下依托咪酯与丙泊酚脑电双频指数值的比较

Objective To measure the predicted plasma and effect-site EC50 and bispeetral index(BIS) of etomidate delivered with TCI,and to compare the difference in BIS value induced by etomidate and propofol at same pharmacodynamics index (EC50 of losing consciousness).Methods Forty seven patients scheduled for surgery were anesthetized with etomidate using TCI.TCL started to get a predicted plasma etomidate concentration of 0.25 mg/L,and increased by 0.03 mg/L every 30 s until patients lost their consciousness.A quantal response model(probit analysis) was used to calculate the predict plasma and effect-site EC50,EC50 and EC95 of etomidate,and the corresponding BIS values were recorded and compared to that induced with propofol reported before.Results The predicted plasma etomidate concentration of EC50 to losing consciousness was 0.59 mg/L with EC05 and EC95 of 0.46,0.71 μg/ml,respectively.The corresponding effect-site concentration of EC50 was 0.51 mg/L with EC05 and EC95 of 0.37 and 0.64 mg/L,respectively.In this study,BIS values to make 50% and 90% of patients losing their consciousness were 44 and 31～56,respectively.The BIS value induced with etomidate(45±10) was markedly lower than that with propofol(58±11) at the same pharmacodynamics index (EC50 of losing consciousness).Conclusion The predicted plasma and effectsite EC50 of etomidate administered with TCI to lose consciousness is 0.59 mg/L and 0.51 mg/L,respectively.The corresponding BIS value with etomidate is markedly lower than that with propofol.     

Propofol and remifentanil effect-site concentrations estimated by pharmacokinetic simulation and bispectral index monitoring during craniotomy with intraoperative awakening for brain tumor resection

Different anesthetic techniques have been suggested for craniotomy with intraoperative awakening. We describe an asleep-awake-asleep technique with propofol and remifentanil infusions, with pharmacokinetic simulation to predict the effect-site concentrations and to modulate the infusion rates of both drugs, and bispectral index (BIS) monitoring. Five critical moments were defined: first loss of consciousness (LOC1), first recovery of consciousness (ROC1), final of neurologic testing (NT), second loss of consciousness (LOC2), and second recovery of consciousness (ROC2). At LOC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 3.6+/-1.2 microg/mL and 2.4+/-0.4 etag/mL. At ROC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.3 microg/mL and 1.8+/-0.3 etag/mL. At NT, predicted effect-site concentrations of propofol and remifentanil were, respectively, 0.9+/-0.3 microg/mL and 1.8+/-0.2 etag/mL. At LOC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.2 microg/mL and 2.5+/-0.2 etag/mL. At ROC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 1.2+/-0.5 microg/mL and 1.4+/-0.2 etag/mL (data are mean+/-SE). A significative correlation was found between BIS and predicted effect-site concentrations of propofol (r=0.547, P<0.001) and remifentanil (r=0.533, P<0.001). Multiple regression analysis between BIS and propofol and remifentanil predicted effect-site concentrations at the different critical steps of the procedure was done and found also significative (r=0.7341, P<0.001).     

Target-controlled infusion of propofol for intraoperative sedation: determination of effect-site concentration and assessment of bispectral index

OBJECTIVES: To determine the effect-site concentration (Ce) of propofol, required to achieving adequate sedation. To assess the efficacy and safety of a target-controlled infusion system during monitored anaesthesia care and to evaluate the ability of bispectral index (BIS) to predict sedation level. Study design. - Prospective clinical study. PATIENTS: Women scheduled for insertion of tension-free vaginal tape under local anaesthetic infiltration. METHODS: After premedication with hydroxyzine, 1% propofol was infused using the Diprifusor system at an initial target plasma concentration (Cc) of 1 microg/ml and then adjusted by steps of 0.2 microg/ml at 5 min intervals. The level of sedation was assessed using the observer's assessment of alertness/sedation (OAA/S) scale; the objective was to obtain an OAA/S level at 4 or 3 (response to verbal stimulation). Ce of propofol and BIS were noted every 5 min. Relation between Ce or BIS and OAA/S scale was analysed by linear regression and probability of prediction (P(K)). RESULTS: Fifty patients aged 62 +/- 12 years were studied. Sedation at level 4 or 3 was observed in all patients. Ce of propofol and BIS to maintain this OAA/S score were, respectively, 1.0 +/- 0.2 microg/ml and 87 +/- 7. There was a linear relation between OAA/S scale and BIS or Ce; however, individual values demonstrate wide variability. The average of P(K) values computed for each patient for the BIS and Ce was 0.84 and 0.83, respectively. CONCLUSIONS: Target-controlled infusion of propofol provides easy and safe management of intraoperative sedation, allowing a fast and precise adjustment of the propofol concentration to the clinical response of the patient.     

Spectral Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect: A Comparison with Bispectral Index and Processed Midlatency Auditory Evoked Response

Background: The authors compared the behavior of two calculations of electroencephalographic spectral entropy, state entropy (SE) and response entropy (RE), with the A-Line(R) ARX Index (AAI) and the Bispectral Index (BIS) and as measures of anesthetic drug effect. They compared the measures for baseline variability, burst suppression, and prediction probability. They also developed pharmacodynamic models relating SE, RE, AAI, and BIS to the calculated propofol effect-site concentration (Ceprop).

Methods: With institutional review board approval, the authors studied 10 patients. All patients received 50 mg/min propofol until either burst suppression greater than 80% or mean arterial pressure less than 50 mmHg was observed. SE, RE, AAI, and BIS were continuously recorded. Ceprop was calculated from the propofol infusion profile. Baseline variability, prediction of burst suppression, prediction probability, and Spearman rank correlation were calculated for SE, RE, AAI, and BIS. The relations between Ceprop and the electroencephalographic measures of drug effect were estimated using nonlinear mixed effect modeling.

Results: Baseline variability was lowest when using SE and RE. Burst suppression was most accurately detected by spectral entropy. Prediction probability and individualized Spearman rank correlation were highest for BIS and lowest for SE. Nonlinear mixed effect modeling generated reasonable models relating all four measures to Ceprop.     

A-line, bispectral index, and estimated effect-site concentrations: a prediction of clinical end-points of anesthesia

Autoregressive modeling with exogenous input of middle-latency auditory evoked potentials (A-Line AEP index, AAI) has been developed for monitoring depth of anesthesia. We investigated the prediction of recovery and dose-response relationship of desflurane and AAI or bispectral index (BIS) values. Twenty adult men scheduled for radical prostatectomy were recruited. To minimize opioid effects, analgesia was provided by a concurrent epidural in addition to the general anesthetic. Electrodes for AAI and BIS monitoring and a headphone for auditory stimuli were applied. Propofol and remifentanil were used for anesthetic induction. Maintenance of anesthesia was with desflurane only. For comparison to AAI and BIS monitor parameters, pharmacokinetic models for desflurane and propofol distribution and effect-site concentrations were used to predict clinical end-points (Prediction probability P(K)). Patients opened their eyes at an AAI value of 47 +/- 20 and a BIS value of 77 +/- 14 (mean +/- sd), and the prediction probability for eye opening was P(K) = 0.81 for AAI, P(K) = 0.89 for BIS, and P(K) = 0.91 for desflurane effect-site concentration. The opening of eyes was best predicted by the calculated desflurane effect-site concentration. The relationship between predicted desflurane effect-site concentration versus AAI and BIS was calculated by nonlinear regression analysis (r = 0.75 for AAI and r = 0.80 for BIS). The correlation between BIS and clinical end-points of anesthesia or the desflurane effect-compartment concentration is better than for the AAI.     

The interaction between fentanyl and propofol during emergence from anesthesia: monitoring with the EEG-Bispectral index

STUDY OBJECTIVE: To investigate the effect of different plasma levels of fentanyl on the concentration of propofol and the Bispectral Index (BIS) required for patients to regain consciousness and orientation following surgery. DESIGN: Prospective, open-label study. SETTING: Operating room of a university hospital. PATIENTS: 28 patients, aging 20 to 50 years, scheduled for elective, 1- to 4-hour surgeries under general anesthesia. INTERVENTIONS: BIS was continuously monitored from bifrontal montage (At1-Fpz and At2-Fpz) using an Aspect A-1,050 EEG system (Aspect, Natick, MA). Anesthesia was induced with bolus injections of fentanyl 2 microg/kg and propofol 2 mg/kg, and maintained with intermittent injections of fentanyl and constant infusion of propofol. Propofol infusion was stopped at the end of surgery. MEASUREMENTS: Consciousness and orientation were assessed as clinical endpoints once every 2 minutes following the end of the surgery. Blood samples were extracted for plasma propofol and fentanyl concentrations (PCp and FCp, respectively), and BIS values were recorded when patients regained consciousness and orientation. Patients were allocated to one of three groups depending on FCp on awakening: Group 1, FCp > 1 microg/L (n = 8); Group 2, FCp < 1 microg/L and >0.45 microg/L (n = 9); and Group 3, FCp < 0.45 microg/L (n = 11). PCp, BIS, recovery time, and other data were compared between the three groups. MAIN RESULTS: Demographic values, duration of surgery, and consumption of propofol and fentanyl were not different between the three groups. Group 3 patients regained consciousness with significantly higher propofol concentration (mean PCp = 3.2 mg/L) compared with those in Groups 1 and 2 (p < 0.05). However, the BIS values at both recovery endpoints were not different among the three groups. CONCLUSIONS: The plasma levels of fentanyl affect the concentrations of propofol required for patients to regain consciousness. The BIS values for wakefulness are unaltered at the different combinations of propofol and fentanyl concentrations. Thus, the BIS appears to be a useful and consistent indicator for level of consciousness during emergence from propofol/fentanyl intravenous anesthesia.     

Effects of epidural anesthesia with 0.2% and 1% ropivacaine on predicted propofol concentrations and bispectral index values at three clinical end points

STUDY OBJECTIVE: To compare the effects of 0.2% epidural ropivacaine and those of 1% epidural ropivacaine on predicted propofol concentrations and bispectral index scores (BISs) at three clinical end points. DESIGN: Randomized double-blind study. SETTING: University hospital. PATIENTS: Thirty-five (35) ASA physical status I and II patients scheduled for elective surgery of the lower abdomen. INTERVENTIONS: Patients were randomly divided into 2 groups to receive epidurally 8 mL of 0.2% or 1% ropivacaine followed by the same solution at a rate of 6 mL/h. MEASUREMENTS: Twenty minutes after starting ropivacaine, a target-controlled infusion of propofol was started to provide a predicted blood concentration of 3 microg/mL; it increased by 0.5 microg/mL every 60 seconds until all 3 clinical end points were reached, as follows: P1, when patients lost consciousness; P2, when patients failed to show pupillary dilation and skin vasomotor reflex to transcutaneous electric stimulation applied to the upper level of loss of cold sensation; and P3, when patients failed to show pupillary dilation and skin vasomotor reflex to transcutaneous electric stimulation applied to C5. MAIN RESULTS: The effective concentration 50 values for both predicted blood and effect-site propofol concentrations were significantly larger in the 0.2% group than in the 1% group at all end points. The BIS at every end point was significantly smaller in the 0.2% group than in the 1% group. CONCLUSIONS: During combined epidural-propofol anesthesia, unconsciousness and lack of response to noxious stimulation occurred at lower predicted concentrations with 1% epidural ropivacaine than with 0.2% epidural ropivacaine. The results also suggest that the BIS may not be a good indicator when propofol anesthesia is combined with epidural anesthesia.     

靶控输注国产与进口异丙酚药效学的比较

目的 比较靶控输注国产与进口异丙酚的药效学.方法 采用随机、双盲、交叉试验设计.择期拟行肌袢代瓣术的双下肢深静脉瓣膜功能不全患者18例,年龄45～55岁,体重指数18.5～22.9 kg/m2,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,患者随机进人流程Ⅰ或流程Ⅱ,一期手术麻醉诱导时应用进口异丙酚,二期手术应用国产异丙酚为流程Ⅰ,反之为流程Ⅱ.异丙酚血浆靶浓度从0.5μg/ml开始,血浆浓度和效应室浓度平衡后,以0.5μg/ml递增,直至效应室浓度达3.5μg/ml,静脉注射瑞芬太尼2μg/kg、罗库溴铵0.6 mg/kg诱导气管插管后行机械通气.记录效应室浓度为0、0.5、1.0、1.5、2.0、2.5、3.0和3.5μg/ml时BIS值、呼吸频率、SpO2和血液动力学指标,患者意识消失时记录异丙酚用量和效应室浓度,采用概率单位法计算5%、50%及95%患者意识消失时的效应室浓度和BIS值,观察不良反应的发生情况.结果 相同效应室浓度国产和进口异丙酚靶控输注时,患者BIS值、呼吸频率、SpO2和血液动力学各指标差异无统计学意义(P＞0.05);5%、50%及95%患者意识消失时国产和进口异丙酚的BIS值和效应室浓度比较差异无统计学意义(P＞0.05);国产和进口异丙酚的药物用量及不良反应发生率比较差异无统计学意义(P＞0.05).结论 国产异丙酚与进口异丙酚具有临床生物等效性.

Abstract：

Objective To compare the clinical pharmacodynamics of domestic and imported propofol by target-controlled infusion. Methods This was a prospective,randomized,double-blind,cross-over study. Eighteen ASA Ⅰ or Ⅱ patients aged 45-55 yr undergoing substitute valve operation for severe deep venous were randomly divided into sequential Ⅰ and Ⅱ , in sequence Ⅰ , the imported propofol was applied in the first stage of surgery and then domestic propofol in the second stage surgery, while in sequence Ⅱ the order was reversed. The target plasma concentration of propofol was initially set at 0.5 μg/ml, followed by increments of 0.5 μg/ml when the effect-site concentration and plasma concentrations was balanced, until the predicted effect-site concentrations reached 3.5 μg/ml. BIS value, RR, SpO2 and hemodynamics were recorded at 0,0.5, 1.0,1.5,2.0,2.5,3.0 and 3.5 μg/ml effect-site concentration level, the predicted effect-site concentrations and the BIS value at loss of consciousness in 5%, 50% and 95% of the patients were calculated. Adverse reactions were recorded during the trial period.Results Under the same effect-site concentration,there was no significant difference in BIS value,RR, SpO2 and hemodynamic monitoring indicators between the two drugs( P ＞ 0.05). There was no significant difference in predicted effect-site concentrations of propofol, the BIS value at loss of consciousness in 5%, 50% and 95% of the patients and the incidence of adverse reaction between the two drugs ( P ＞ 0.05). Conclusion The domestic propofol and imported propofol have clinical bioequivalence.     

Propofol effective concentration 50 and its relationship to bispectral index

Sixty unpremedicated healthy adult patients were studied during induction of anaesthesia with intravenous propofol delivered by a 'Diprifusor' target-controlled infusion. Bispectral index (BIS) and spectral edge frequency (SEF95) were measured concurrently with the predicted blood and effect site propofol concentrations. Logistic regression was used to calculate the predicted propofol blood and effect site concentrations required to produce unconsciousness and no response to a noxious stimulus in 50% and 95% of patients and to correlate BIS with these end-points. The Diprifusor TCI software produces anaesthesia at consistent target concentrations. Bispectral index correlates well with clinical end-points and may be useful during propofol anaesthesia.     

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis

We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 microg/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r(2) = 0.76 and 0.93, respectively; P<0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47+/-0.13 microV, mean +/- SD) was significantly (P<0.002) larger than with monaural stimulation (0.35+/-0.11 microV). During unconsciousness, the amplitude was 0.09+/-0.09 microV with monaural and 0.06+/-0.04 microV with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 SE) for monaural and 1.00 (0.00 SE) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. Implications: We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.     

Auditory evoked potentials index versus bispectral index during propofol sedation in spinal anesthesia

Purpose  It is still controversial whether an electroencephalogram could be a useful monitor of sedation levels. The present study was performed to compare the bispectral index (BIS) and the auditory evoked potentials index (AAI) during light sedation with propofol infusion in spinal anesthesia. Methods  Eighty patients, aged 20 to 70 years, scheduled for surgery of the lower extremities under spinal anesthesia were assigned to one of four groups (20 patients each). Patients in the AAI propofol and BIS propofol groups were sedated with propofol infusion at an initial rate of 2 mg·kg⁻¹·h⁻¹. Propofol infusion was controlled to try to keep the observer’s assessment of alertness/sedation (OAAS) scale at 3 or 4. Patients in the AAI control and BIS control groups did not receive propofol. Results  The OAAS scales and the AAI or BIS decreased significantly in all groups during surgery, while the decrease was larger in the AAI propofol and BIS propofol groups. The AAI was significantly lower along with lower OAAS scales. There was no overlap in the AAI between OAAS scale 3 and scale 5 in the AAI propofol group, while in the BIS propofol group, no difference was observed in the BIS among OAAS scales 2, 3, 4, and 5. Conclusion  The AAI, but not the BIS, could discriminate slight changes of consciousness during light sedation with propofol infusion in patients with spinal anesthesia. This work was done at the Department of Anesthesiology, Ofuna Chuo Hospital, Kanagawa, Japan.