Relationship between bispectral index,auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points

Background. Many anaesthetists are deterred from using totali.v. anaesthesia because of uncertainty over the concentrationof propofol required to prevent awareness. We predicted bloodand effect-site concentrations of propofol at two clinical end-points:loss of consciousness and no response to a painful stimulus. Methods. Forty unpremedicated Caucasian patients were anaesthetizedwith i.v. propofol delivered by a Diprifusor target-controlledinfusion (TCI). Bispectral index (BIS) and auditory evoked potentialindex (AEPex) were measured and blood and effect-site propofolconcentrations were predicted. Logistic regression was usedto estimate population values for predicted blood and effect-sitepropofol concentrations at the clinical end-points and to correlatethese with BIS and AEPex. Results. The effect-site EC₅₀ at loss of consciousness was 2.8 µm ml^–1with an EC₀₅ and an EC₉₅ of 1.5 and 4.1 µm ml^–1,respectively. The predicted EC₅₀ when there was no responseto a tetanic stimulus was 5.2 µm ml^–1 withan EC₀₅ and an EC₉₅ of 3.1 and 7.2 µm ml^–1,respectively. Conclusions. Unconsciousness and lack of response to a painfulstimulus occur within a defined range of effect-site concentrations,predicted by Diprifusor TCI software. Br J Anaesth 2003; 90: 127–31     

Cerebral state index during propofol anesthesia: a comparison with the bispectral index and the A-line ARX index

BACKGROUND: The objective of this study was to prospectively test the Cerebral State Index designed for measuring the depth of anesthesia. The Cerebral State Index is calculated using a fuzzy logic combination of four subparameters of the electroencephalographic signal. The performance of the Cerebral State Index was compared with that of the Bispectral Index and the A-Line ARX Index. METHODS: This study applied raw data from two previously published clinical protocols. The patients in protocol 1 were given a continuous propofol infusion, 300 ml/h, until 80% of burst suppression occurred. In protocol 2, a stepwise increased target-controlled infusion of propofol was administered to patients until loss of response to noxious stimuli while the Observer's Assessment of Alertness and Sedation was registered every 4 min. The Cerebral State Index was calculated off-line from the recorded electroencephalographic data. The Spearman rank correlation coefficient between electronic indices and the effect site concentration of propofol was calculated along with the prediction probability of each index to predict the Observer's Assessment of Alertness and Sedation level. RESULTS: The Spearman rank correlation coefficients between the Cerebral State Index, Bispectral Index, and A-Line ARX Index and the propofol effect site concentration were -0.94, -0.89, and -0.82, respectively, in protocol 1, whereas the prediction probability values between the Cerebral State Index, Bispectral Index, and A-Line ARX Index and the Observer's Assessment of Alertness and Sedation score in protocol 2 were 0.92, 0.93, and 0.91, respectively. CONCLUSION: The Cerebral State Index detects well the graduated levels of propofol anesthesia when compared with the propofol effect site concentration and the Observer's Assessment of Alertness and Sedation score.     

Relationship between clinical endpoints for induction of anesthesia and bispectral index and effect-site concentration values

STUDY OBJECTIVE: To assess the relationship between clinical endpoints for induction of anesthesia and the electroencephalographic (EEG) bispectral index (BIS) and effect-site concentration (C(E)) values when using a target-controlled infusion (TCI) of either thiopental sodium or propofol, by hypothesizing that yawning may be a useful alternative to other commonly used clinical signs for determining loss of consciousness. DESIGN: Randomized observational clinical study. SETTING: Operating room of a university-based hospital.PATIENTS: 60 healthy adult patients (aged 20-50 yrs) scheduled for elective surgery with general anesthesia. INTERVENTIONS: During a TCI of propofol (n = 30) or thiopental (n = 30), clinical endpoints for loss of verbal responsiveness (LOV), loss-of-eyelash reflex (LOE), occurrence of yawning, and apnea were assessed at 15-second intervals. In addition, BIS and C(E) values were recorded at each of the endpoints. MEASUREMENTS AND MAIN RESULTS: In both anesthetic groups, the sequence of occurrence of the clinical endpoints was similar, namely LOV, LOE, yawning, and, lastly, apnea. Compared with LOV and LOE, yawning was associated with lower BIS and higher C(E) values with both anesthetics. The frequency of yawning was higher with thiopental than propofol (83% vs. 63%, respectively). However, the frequency of apnea was higher with propofol than thiopental (77% vs. 53%, respectively). CONCLUSION: The correlation of the clinical endpoints with BIS and C(E) values was highest for LOV. Yawning was as unreliable as LOE for determining the onset of unconsciousness during induction of anesthesia. This clinical sign failed to be observed in 17% and 37% of patients induced with thiopental and propofol, respectively.     

听觉诱发电位指数、脑电双频指数及心血管反应评估"过浅麻醉"的价值

目的通过研究丙泊酚诱导过程中,听觉诱发电位指数(AAI)、脑电双频指数(BIS)及心血管反应与插管体动的关系,探讨上述监测手段是否能够反映“过浅麻醉”。方法35例ASAⅠ~Ⅱ级妇科择期手术患者,以丙泊酚进行诱导,患者入睡后,用压力袖带隔离一侧前臂,静注维库溴铵0·1mg/kg。当丙泊酚靶控输注(TCI)达到设定血浆靶浓度(3·5μg/ml)后行气管内插管。记录隔离侧手臂运动(体动)情况,并以是否发生体动反应为准将患者分为体动组与非体动组。记录患者诱导前、插管前的SBP、DBP、HR、BIS、AAI及插管后2min内上述指标的最大值。结果体动组AAI插管后明显高于插管前(P<0·01),而非体动组插管前、后的差异无显著意义;两组患者BIS插管前、后组内及组间的差异均无显著意义;插管引起的DBP、SBP增高体动组明显大于非体动组(P<0·01),但HR变化两组相似。结论BIS仅是衡量睡眠深度的指标,AAI及BP反映“过浅麻醉”,反映机体对伤害性刺激的反应较BIS敏感。     

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).     

The A-line ARX index may be a more sensitive detector of arousal than the bispectral index during propofol-fentanyl-nitrous oxide anesthesia: A preliminary investigation

PURPOSE: To compare changes in the A-line ARX index (AAI) by the Alaris AEP monitor(TM) with those of the bispectral index (BIS) during propofol-fentanyl-nitrous oxide anesthesia. METHODS: Eighty female patients undergoing partial mastectomy were randomly allocated to AAI or BIS (40 per group). Anesthesia was induced with propofol 2 mg x kg(-1) and fentanyl 3 micro g x kg(-1) during the inhalation of oxygen. A laryngeal mask airway (LMA) #3 was inserted. Anesthesia was maintained with propofol 4 mg x kg(-1) x hr(-1), fentanyl 1 micro g x kg(-1) given at the start of surgery, and nitrous oxide 4 L x min(-1) in oxygen 2 L x min(-1). Blood pressure, heart rate, and AAI or BIS were monitored, including recovery time of the index after disturbance by electrocautery. RESULTS: The AAI but not the BIS increased significantly with LMA insertion and skin incision, while blood pressure and heart rate did not change. The BIS decreased from 87 +/- 7 to 30-60 while the AAI decreased from 75 +/- 8 to 10-25 during anesthesia. The increase of the AAI was larger than that of the BIS at recovery from anesthesia. The variation of the index was smaller in the AAI than in the BIS. Recovery time of the index after electrocautery was significantly longer in the BIS group (21 +/- 9 sec) than that in the AAI group (5 +/- 3 sec). CONCLUSIONS: During propofol-fentanyl-nitrous oxide anesthesia, the AAI responded to LMA insertion or surgical incision, but not the BIS, and the AAI had smaller variations. The AAI recovered faster from the disturbance by electrocautery than the BIS. Thus, the AAI may be a more sensitive and useful detector of arousal than the BIS.     

Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and bothbispectral index (BIS) and SE values is useful for predictingloss of verbal contact and loss of consciousness during steady-stateconditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site-effectconcentration of 1.0 µg ml^–1, and increased by 1.0µg ml^–1 steps every 4 min, up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state site-effectconcentrations were obtained. Propofol site-effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC 2.8(2.8–5.65) µg ml^–1. LVC occurred in 90% ofpatients at a BIS value of 70.2 (70.2–90.2) and an SEvalue of 60.3 (60.3–75.5) and LOC occurred at a BIS valueof 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and higher correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

Relationship between bispectral index and effect-site EC(50) for propofol

Editor—We read with interest the study by Iannuzzi andcolleagues¹ regarding the correlation between propofol effect-siteconcentration and the bispectral index (BIS). In their article,the authors noted that the higher effect-site concentrationsthey obtained were because of the achievement of steady stateconditions and the pharmacokinetic model used. We constructed a graph (Fig.     

丙泊酚在不同靶控浓度下罗库溴铵对脑电双频指数的影响

目的 探讨丙泊酚在不同靶控浓度下罗库溴铵对脑电双频指数(BIS)监测麻醉深度的影响.方法 ASA I或Ⅱ级择期手术患者60例,随机均分为四组:用于观察的R2组和R3组和用于对照的C2组和C3组.设定丙泊酚初始效应室浓度(Ce)为4.0 μg/ml,当患者镇静警觉(OAA/S)评分≤1分时置入喉罩,机械通气.调节丙泊酚靶控浓度,使Ce分别维持在2.0 μg/ml(R2、C2组)和3.0 μg/ml(R3、C3组),达到靶浓度后稳定20 min,观察组静注2倍ED95剂量的罗库溴铵0.6 mg/kg,对照组注射生理盐水5 ml.记录丙泊酚诱导前即刻(T1)、静脉注射罗库溴铵或生理盐水即刻(T2)、TOF消失为0时(T3)、TOF的第一个肌颤搐恢复到5%时(L)的BIS、HR、MAP.结果 与T1时比较,T2～T4时BIS明显降低(P<0.05);与T2时比较,T3、T4时R2组BIS值明显下降(P<0.05);在不同的丙泊酚Ce下,T2～T4时R2、C2组的BIS明显高于相对照的R3、C3组(P<0.05).结论 罗库溴铵对BIS的影响与镇静深度有关.丙泊酚靶控浓度维持在较浅的镇静状态下,静脉注射2倍ED95剂量的罗库溴铵可引起BIS下降,但在较深的镇静状态下无明显影响.     

Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration

The bispectral index, a new processed electroencephalographic parameter which may give information on depth of anaesthesia, was used in 58 patients undergoing outpatient gynaecological surgery in order to study if the addition of bispectral index monitoring to standard clinical monitoring could improve the titration of target propofol concentration when using effect-site target-controlled propofol infusion for sedation. In Group 1 ( n  = 30), the bispectral index was recorded but the anaesthetist was unaware of the readings and therefore only classical signs of depth of anaesthesia were used to guide the anaesthetist in controlling the effect-site concentration. In Group 2 ( n  = 28), bispectral index readings were available to the anaesthetist and effect-site concentration was adjusted to ensure that bispectral index was maintained between 40 and 60. Similar propofol induction and maintenance doses, blood and effect-site concentrations and mean bispectral index were found in the two groups. A greater percentage of bispectral index readings lying outside the target range (i.e. < 40 or > 60) and more movement at incision and during maintenance were found in Group 1. There was a trend towards more implicit awareness in patients in Group 1. Bispectral index was found to be useful for measuring depth of sedation when using propofol target-controlled infusion. Propofol dosage could not be decreased but a more consistent level of sedation could be maintained due to a more satisfactory titration of target effect-site concentration.     

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.     

靶控输注异丙酚意识消失时血浆和效应室浓度的EC50与脑电双频谱指数的关系多中心大样本临床研究

目的 研究择期手术患者靶控输注（TCI）异丙酚意识消失时血浆、效应室靶浓度的50%患者意识消失时的药物浓度（EC50）与脑电双频谱指数（BIS）的关系。方法 5家医疗中心405例择期手术患者（国人）,ASAⅠ或Ⅱ级。靶控输注异丙酚,以血浆靶浓度1．2μg/ml为起点,到达预期血浆靶浓度后每30秒递增0．3μg/ml,直至患者意识消失。采用概率单位回归分析计算患者意识消失时异丙酚血浆靶浓度、效应室靶浓度的EC05、EC50和EC95及其所对应的BIS。结果 择期手术患者TCI异丙酚意识消失时异丙酚血浆靶浓度EC05、EC50和EC95分别是2．9μg/ml、3．8μg/ml和4．8μg/ml,效应室靶浓度EC05、EC50和EC95分别是1．3μg/ml、2．2μg/ml和3．2μg/ml,50%患者意识消失的BIS是58,5%和95%患者意识消失的BIS分别是77和40。结论 择期手术患者TCI异丙酚意识消失时血浆靶浓度和效应室靶浓度EC50及95%置信区间分别是3．8μg/ml（3．8～3．9μg/ml）和2．2μg/ml（2．2～2．3μg/ml）, 50%患者意识消失的BIS用95%置信区间是58（58～59）。     

Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations

Purpose  

To examine the relationships between effect-site concentrations and electroencephalographic parameters after the induction of general anesthesia with midazolam.     

Brain tumors may alter the relationship between bispectral index values and propofol concentrations during induction of anesthesia

STUDY OBJECTIVE: To compare propofol-predicted effect-site concentrations (PropCe) and bispectral index (BIS) of the electroencephalogram during induction of anesthesia in patients with small brain tumors and to analyze BIS and PropCe at loss of consciousness (LOC). DESIGN: Prospective investigation. SETTING: Operating theater of a university hospital. PATIENTS: 26 ASA physical status I and II patients, 13 of whom were scheduled for nontumor spinal surgeries, and the other 13, for brain surgery for small brain tumor removal. INTERVENTIONS: Anesthesia was induced with a propofol 1% constant infusion rate of 200 mL/h until LOC. MEASUREMENTS: BIS, PropCe, heart rate, and mean arterial pressure were analyzed at the beginning of the propofol infusion and every 30 seconds during induction. MAIN RESULTS: The BIS values were significantly higher in patients with brain tumors in the period from 150 to 210 seconds, with PropCe similar to patients without brain tumors. Loss of consciousness occurred 3.6 +/- 0.8 minutes in patients without brain tumors and 3.9 +/- 0.7 minutes in patients with brain tumors. No differences were observed between groups in the time to LOC (3.6 +/- 0.8 in group 1 vs 3.9 +/- 0.7 in group 2) or in BIS at LOC (48.7 +/- 11.4 in group 1 vs 58.6 +/- 21.7 in group 2). CONCLUSIONS: For similar propofol concentrations, patients with small brain tumors show higher BIS values on induction of anesthesia with propofol.     

Correlation of bispectral index and Guedel's stages of ether anesthesia

Bispectral index (BIS) analysis is a method of electroencephalograph (EEG) analysis based on the interfrequency phase relationships of the EEG, designed to quantify anesthetic hypnosis. The BIS was created after concurrent collection of EEG and clinical data from a large number of patients anesthetized with various drugs over a prolonged period and then performing a Fourier analysis followed by a bispectral calculation. The clinical stages of anesthetic depth are very well demonstrated in etherized patients. In this study, we studied the BIS changes during various stages of ether anesthesia and quantified the hypnotic depth during the surgical stage of ether anesthesia. The values for BIS under various stages and planes of ether anesthesia were recorded in 21 patients listed for short surgical procedures. During diethyl ether anesthesia, BIS initially increased and subsequently decreased. During surgical anesthesia, a BIS value of 30 was observed. IMPLICATIONS: For the first time, bispectral index (BIS) has been studied in patients being anesthetized solely with ether. Ether both causes an increase and decrease in BIS during induction and emergence. The index observed during the surgical stage of ether anesthesia is probably the correct value for the depth of hypnosis because no other volatile anesthetic can produce the true anesthetic state when used alone. This value could be taken as the value to be attained when balanced anesthesia is being practiced.     

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EC50及BIS值的影响--多中心研究

静脉麻醉药的EC50(effective concentration50,EC50)是指使50%的患者意识消失或对疼痛刺激无反应时的血浆或效应室药物浓度。靶浓度控制输注(tar-get controlled infusion,TCI,)药物可以实现药物浓度即时监测,还可以根据临床需要随时调节靶浓度[1]。研究认为脑电双频谱指数(bispectral index,BIS)能够较好地监测异丙酚麻醉下的意识状态,防止产生术中知晓。一般认为随年龄增长,患者所需的麻醉药物浓度或剂量减少,且性别之间也有差异。但在异丙酚-雷米芬太尼TCI下,年龄和性别对其用药浓度的影响尚不明确,本研究旨在研究性别和年龄对在异…     

The utility of bispectral index monitoring in general anesthesia

BACKGROUND: The Bispectral Index (BIS), a parameter derived from the electroencephalograph, has been shown to correlate with increasing sedation and loss of consciousness. This study was designed to investigate whether using BIS would improve anaesthetic drug management and immediate recovery after anaesthesia. METHODS: 160 patients undergoing abdominal surgery were studied. The patients were randomised to receive either propofol or sevoflurane anaesthesia. In each group 40 patients were anaesthetised with BIS monitoring and 40 without BIS. In BIS groups, propofol and sevoflurane dose was adjusted to achieve a target BIS values between 40-60 during the whole procedure. Drug consumption, intraoperative responses, times of recovery after anaesthesia and a "Clinical Quality Scale of Recovery" score were recorded from blinded observators. RESULTS: Demographic data were similar between groups. BIS monitoring improved the immediate recovery after propofol anaesthesia, while no significant differences were observed in patients receiving sevoflurane. The consumption of both propofol and sevoflurane significantly decreased (30 and 40%, respectively). There was no significant differences in the incidence of intraoperative responses between groups. The BIS groups had a higher percentage of patients with better ICU assessments. CONCLUSIONS: BIS monitoring decreased the consumption of both propofol and sevoflurane and facilitated the immediate recovery after propofol anaesthesia. Intraoperative course was not changed. These findings indicate that the use of BIS may be a valuable guide of the intraoperatively administration of propofol and sevoflurane.