Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 microg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean +/- SD. Effect-site propofol concentration at ROC was 1.3 +/- 0.5 microg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 +/- 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 +/- 0.05 microg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 +/- 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 +/- 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 +/- 6.8), time till minimum BIS (4.7 +/- 2.2 min), mean and median BIS during surgery (38.2 +/- 4.5 and 37.8 +/- 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.     

Individual effect-site concentrations of propofol at return of consciousness are related to the concentrations at loss of consciousness and age in neurosurgical patients

Study ObjectiveTo investigate whether a patient's propofol effect-site concentration at return to consciousness (ROC) was related to the propofol effect-site concentration at loss of consciousness (LOC) and to patients' individual demographic parameters.DesignProspective study.SettingOperating room.Patients31 ASA physical status I and II neurosurgical patients with Glasgow Coma Score > 15, and scheduled to receive total intravenous anesthesia with effect-site target controlled infusion (TCI) of propofol and remifentanil.InterventionsA constant propofol infusion was administered until LOC. At LOC, remifentanil started with a plasma concentration target of 2.5 ng mL^?1.Main ResultsPropofol concentration at LOC was 4.9 ± 1 μg mL^?1. At ROC, propofol and remifentanil concentrations were 1.16 ± 0.3 μg mL^?1 and 3.41 ± 1.5 ng mL^?1. Significant correlation was observed between propofol concentrationa at ROC and LOC, between propofol concentration at ROC and patient age (48.7 ± 15 yrs), and between propofol concentrations at ROC and LOC, divided by patient's age.ConclusionsThe correlation between propofol concentrations at ROC and LOC was improved by inclusion of patient age data.     

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia

The bispectral index (BIS) and a sedation score were used todetermine and compare the effect of propofol in the presenceof fentanyl, alfentanil, remifentanil and sufentanil. Seventy-fivenon-premedicated patients were assigned randomly into five groups(15 in each) to receive fentanyl, alfentanil, remifentanil,sufentanil or placebo. Opioids were administered using a target-controlledinfusion device, to obtain the following predicted effect-siteconcentrations: fentanyl, 1.5 ng ml^–1; alfentanil, 100ng ml^–1; remifentanil, 6 ng ml^–1; and sufentanil,0.2 ng ml^–1. After this, a target-controlled infusionof propofol (Diprifusor) was started to increase concentrationgradually, to achieve predicted effect-site concentrations of1, 2, and 4 µg ml^–1. At baseline and at each successivetarget effect-site concentration of propofol, the BIS, sedationscore and haemodynamic variables were recorded. At the momentof loss of consciousness (LOC), the BIS and the effect-siteconcentration of propofol were noted. The relationship betweenpropofol effect-site concentration and BIS was preserved withor without opioids. In the presence of an opioid, LOC occurredat a lower effect-site concentration of propofol and at a higherBIS₅₀ (i.e. the BIS value associated with 50% probability ofLOC), compared with placebo. Although clinically the hypnoticeffect of propofol is enhanced by analgesic concentrations ofµ-agonist opioids, the BIS does not show this increasedhypnotic effect. Br J Anaesth 2001; 86: 523–7     

BIS监测异丙酚复合瑞芬太尼全麻患儿麻醉深度的准确性

目的 评价脑电双频谱指数(BIS)监测异丙酚复合瑞芬太尼全麻患儿麻醉深度的准确性.方法 择期手术患儿60例,ASA Ⅰ或Ⅱ级,年龄3～8岁,体重14～40kg,随机分为4组(n=15),人室后开放手背静脉,稳定5 min.C组静脉输注0.9%生理盐水0.2 ml·kg-1·h-1;R1组、R2组和R3组分别静脉输注瑞芬太尼0.1、0.3或0.5 μg·kg-1·min-1,瑞芬太尼或生理盐水输注10 min开始靶控输注异丙酚,起始效应室浓度为1 μg/ml,逐渐递增至2、3、4μg/ml.分别于稳定5min、瑞芬太尼静脉输注10min、异丙酚效应室浓度达到l、2、3、4μg/ml稳定1 min及意识消失时记录BIS和警觉,镇静(OAA/S)评分;记录意识消失时间.采用logistic回归法计算意识消失时的BIS50、BIS95和意识消失时异丙酚的EC50、EC95.BIS与OAA/S评分、异丙酚效应室浓度作直线相关分析.结果 C组、R1.组、R2组和R3组BIS与OAA/S评分均呈正相关,r分别为0.89、0.90、0.87、0.82(P<0.05);BIS与异丙酚效应室浓度均呈负相关,r分别为-0.87、-0.90、-0.87、-0.92(P<0.05);与C组比较,其余3组患儿意识消失时异丙酚效应室浓度降低,意识消失时间缩短,R2组和R3组意识消失时BIS升高,BIS50和BIS95升高,异丙酚EC50和EC95降低(P<0.05);与R1组比较,R2组BIS50和BIS95升高,R3组异丙酚EC50和EC95降低(P<0.05).结论 瑞芬太尼复合异丙酚麻醉下,采用BIS监测患儿麻醉深度存在一定局限性.     

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.     

Practical aspects of the use of target controlled infusion with remifentanil in neurosurgical patients: predicted cerebral concentrations at intubation, incision and extubation

Remifentanil has important side effects and it is not easy to know what remifentanil concentrations should be used during different endpoints of anaesthesia. We analyzed the remifentanil predicted effect-site concentrations (RemiCe) at different events during neurosurgical procedures and assessed if the concentrations used were clinically adequate. BIS and haemodynamic parameters were collected every 5 seconds. Predicted cerebral concentration of propofol (PropCe) and RemiCe were analyzed immediately prior to respective stimulus, and 30, 60 and 90 seconds after. RemiCe were 2.2 +/- 0.3, 6 +/- 2.6 and 2.2 +/- 0.9 ng ml(-1) at intubation, incision and extubation, respectively. PropCe observed in the same periods were 5 +/- 1, 2.6 +/- 0.9 and 1 +/- 0.3 microg ml(-1), also respectively. The remifentanil concentrations used in our patients were lower than reported concentrations, while being clinically adequate to minimize the haemodynamic response to stimulation.     

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.     

Narcotrend,bispectral index,and classical electroencephalogram variables during emergence from propofol/remifentanil anesthesia

The aim of this study was to investigate modern and classical electroencephalographic (EEG) variables in response to remifentanil and propofol infusions. We hypothesized that modern EEG variables may indicate the effects of propofol but not of remifentanil. Twenty-five patients were included in the study after the end of elective spine surgery without any surgical stimulation. Baseline values were defined with remifentanil 0.3 microg. kg(-1). min(-1) and target-controlled infusion of propofol 3.0 microg/mL. EEG changes were evaluated 1, 3, 5, 7, and 9 min after the stop of remifentanil infusion, followed by a step-by-step reduction (0.2 microg/mL) every 3 min of target-controlled infusion propofol. Narcotrend (NT; classifying EEG stages from awake to deep anesthesia), bispectral index (BIS), EEG spectral frequency bands (%), 50% (Median) and 95% percentiles (spectral edge frequency), mean arterial blood pressure, heart rate, and oxygen saturation were detected at every time point. The end of remifentanil application resulted in significant increases in %alpha, spectral edge frequency, mean arterial blood pressure, and %theta and decreases in %delta (P < 0.05). NT, BIS, Median, heart rate, and oxygen saturation were unchanged. Decreases in propofol concentration were associated with statistically significant increases in NT and BIS (P < 0.05). Thus, the sedative-hypnotic component of propofol could be estimated by modern EEG variables (NT and BIS), whereas the analgesic component provided by remifentanil was not indicated. However, during conditions without surgical stimulation, neither NT nor BIS provided an adequate assessment of the depth of anesthesia when a remifentanil infusion was used. IMPLICATIONS: We investigated modern and classical electroencephalographic (EEG) variables during emergence from propofol/remifentanil anesthesia. Modern EEG variables indicate changes of infusion in propofol, but not in remifentanil. Thus, modern EEG variables did not provide an adequate assessment of depth of anesthesia when remifentanil was used.     

应用响应曲面研究丙泊酚与瑞芬太尼在腹腔镜胆囊切除术麻醉中最佳配伍剂量

目的应用响应曲面分析法,观察丙泊酚与瑞芬太尼在镇静作用上的药效学相互作用规律,探讨腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)靶控输注丙泊酚与瑞芬太尼的最佳配伍剂量。方法选择2014~2016年北京大学第三医院择期LC 100例,5例因手术方式改变、1例因术中出现过敏性休克退出研究,94例完成临床观察和随访。选择丙泊酚与瑞芬太尼靶控输注起始配伍浓度,观察靶控输注至警醒/镇静(Observer’s Assessment of Alertness/Sedation,OAA/S)评分≤1分的意识消失时间(time to loss of consciousenss,T LOC),术中根据脑电双频谱指数(bispectral index,BIS)、有创动脉血压和心率(heart rate,HR)调整丙泊酚和瑞芬太尼的靶控输注浓度,维持BIS 40~60、平均动脉压≥60 mm Hg、HR≥50次/min且平均动脉压和HR波动不超过基础值30%。记录停止输注瑞芬太尼与丙泊酚至OAA/S评分≥3分的意识恢复时间(time to recovery of consciousness,T ROC)。以受试者T LOC≤5 min、T ROC≤10 min、术中95%患者药效指标满意为目标,计算丙泊酚与瑞芬太尼在LC术中靶控浓度的最佳配伍范围。结果丙泊酚(2~9μg/ml)与瑞芬太尼(1~10 ng/ml)在T LOC和T ROC的药效上呈协同作用。LC药物靶控浓度的最佳配伍范围:丙泊酚2μg/ml(推荐监测BIS)伍用瑞芬太尼6~10 ng/ml,丙泊酚3μg/ml伍用瑞芬太尼3~5 ng/ml,丙泊酚4μg/ml伍用瑞芬太尼3 ng/ml,丙泊酚4.5μg/ml伍用瑞芬太尼2.6 ng/ml。丙泊酚浓度≥5μg/ml复合小剂量瑞芬太尼,45例中43例BIS<40;靶控输注丙泊酚2μg/ml复合瑞芬太尼6~10 ng/ml,给予气管插管刺激时,25例中2例BIS值呈一过性上升,术中BIS均维持在40~60。3例(3.2%)意识消失前出现呼吸暂停;7例(7.4%)麻醉诱导期间出现循环抑制,其中4例使用血管活性药物;21例(22.3%)主诉注射痛;7例(7.4%)出现多语和不自主活动。术后随访无知晓发生。结论丙泊酚(2~9μg/ml)与瑞芬太尼(1~10 ng/ml)在镇静药效反应呈协同作用;不同的药效反应相结合创建出的丙泊酚与瑞芬太尼最佳配伍剂量范围,可以为LC提供满意的麻醉,并且麻醉诱导和麻醉恢复快速。     

不同效应室靶浓度瑞芬太尼对患者异丙酚镇静效应的影响

目的 探讨不同效应室靶浓度瑞芬太尼对患者异丙酚镇静效应的影响.方法择期全麻手术患者50例,年龄20～55岁,体重48～86 kg,性别不限,ASA分级Ⅰ或Ⅱ级,BMI＜30 kg/m2,采用随机数字表法,将患者随机分为5组(n=10):R0组、R1组、R2组、R3组、R4组.麻醉诱导时R0组～R4组瑞芬太尼效应室靶浓度分别为0、2 4 6和8 ng/ml,异丙酚初始效应室靶浓度2.0 μg/ml,待效应室浓度稳定之后每隔1 min增加0.5 μg/ml,直至BIS值降至50.记录患者意识消失时的BIS值、异丙酚效应室浓度.记录BIS值降至50时的异丙酚效应室浓度、异丙酚总用量及所需时间.结果 与R0组比较,R2组～R4组意识消失时BIS值升高,异丙酚效应室浓度降低,BIS值降至50时异丙酚总用量和异丙酚效应室浓度降低,所需时间缩短(P＜0.05或0.01),R.组上述指标差异无统计学意义(P＞0.05);R2组～R4组意识消失时BIS值和异丙酚效应室浓度、BIB值降至50时异丙酚总用量和异丙酚效应室浓度以及所需时间差异无统计学意义(P＞0.05).结论 瑞芬太尼效应室靶浓度达4 ng/ml时可增强异丙酚的镇静效应,且4、6和8 ng/ml时该作用无差异.

Abstract：

Objective To investigate the effects of different target effect-site concentrations (Ces) of remifentanil on the sedative effect of propofol. Methods Fifty ASA Ⅰ or Ⅱ patients aged 20-55 yr weighing 48-86 kg with body mass index ＜ 30 kg/m2 were randomly divided into 5 groups ( n = 10 each) . Anesthesia was induced with TCI of remifentanil (Ce = 0, 2, 4, 6 and 8 ng/ml in groups R0-R4 respectively) and propofol. The initial Ce of propofol was 2.0 μg/ml in the 5 groups, and then the Ce of propofol increased by 0.5 μg/ml every 1 min until BIS value decreased to 50. BIS value and Ce of propofol were recorded as the patient lost consciousness. The effect-site concentration and consumption of propofol and the time required were recorded when BIS value decreased to 50.Results BIS value was significantly increased, while the effect-site concentration of propofol was significantly decreased as the patient lost consciousness, and the effect-site concentration and consumption of propofol were significantly decreased and the time required was shortened when BIS value decreased to 50 in R2-R4 groups compared with group R0 (P ＜ 0.05 or 0.01) . Conclusion The sedative effect of propofol can be enhanced when the Ce of remifentanil reaches 4 ng/ml, and the effects are comparable when the Ce of remifentanil reaches 4, 6 and 8 ng/ml.     

The effect-site concentration of remifentanil blunting cardiovascular responses to tracheal intubation and skin incision during bispectral index-guided propofol anesthesia

We sought to determine the effect-site concentration of remifentanil blunting sympathetic responses to tracheal intubation and skin incision during bispectral index (BIS)-guided propofol anesthesia. Forty-one ASA physical status I-II patients, aged 20-65 yr and undergoing major abdominal surgery, were randomly assigned to one of two groups: tracheal intubation (group TI, n = 20) or skin incision (group SI, n = 21). All patients received a target-controlled infusion of propofol of 4 microg/mL, which was then adjusted to maintain a BIS value ranging between 40 and 50. The effect-site concentration of remifentanil blocking the sympathetic responses to tracheal intubation and skin incision in 50% of cases (Ce50) was determined using an up-and-down sequential allocation method. The mean (95% confidence interval [CI]) Ce50 of remifentanil was 5.0 ng/mL for TI (95% CI, 4.7-5.4 ng/mL) and 2.1 ng/mL for SI (95% CI, 1.4-2.8 ng/mL). This study shows that effect-site concentrations of remifentanil of 5 ng/mL and 2 ng/mL are effective in blunting sympathetic responses to tracheal intubation and skin incision in 50% of patients when combined with a BIS-guided target controlled infusion of propofol.     

Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index

STUDY OBJECTIVE: To identify and quantify the interaction between propofol and remifentanil during surgical procedures with a bispectral index (BIS) of 50 that was chosen as a continuous surrogate measure for "adequate depth" of anesthesia. DESIGN: Prospective, open-label study. SETTING: Department of orthopedics of a university hospital. PATIENTS: 20 patients undergoing orthopedic surgery. INTERVENTIONS: Anesthesia was induced and maintained with propofol and remifentanil, both administered by target-controlled infusion (TCI). Initial target concentrations of propofol (1.5-8 microg/mL) and remifentanil (2-15 ng/mL) were chosen and alternated in order to maintain the BIS between 45 and 55. If constant target concentrations had been maintained for 20 minutes and the BIS did not depart from the desired range, blood samples were taken to determine propofol concentrations, and the BIS value was recorded. Isobolographic interaction models were fitted to the infusion rates of remifentanil and propofol, predicted target concentrations of both drugs, and measured propofol concentrations versus predicted remifentanil concentrations. MAIN RESULTS: The isobole for the interaction of propofol and remifentanil in the concentration range investigated (propofol 1.5-8 microg/mL and remifentanil 1-30 ng/mL) is a concave up hyperbola ((0.15. C(prop))(3.13). C(rem) = 1) with C(prop) = propofol plasma concentration [microg/mL] and C(rem) = remifentanil blood concentration [ng/mL]). Use of predicted (=TCI target) concentrations or the respective infusion rates did not alter the general shape of the interaction isobole.Conclusions: The interaction between propofol and remifentanil for maintenance of a BIS value between 45 and 55 during surgery is synergistic. This finding applies regardless of whether measured concentrations (for propofol), predicted concentrations of the infusion device, or infusion rates are used as model input. Notably, the interaction isobole of the (clinically readily available) infusion rates provides a useful dosing recommendation for the coadministration of propofol and remifentanil during maintenance of anesthesia.     

Gender differences between predicted and measured propofol C(P50) for loss of consciousness

OBJECTIVE: To investigate gender differences in the effective dose of 50% for loss of consciousness (C(P50LOC)) for propofol using Diprifusor, the most commonly used target-controlled infusion system. DESIGN: Prospective, randomized, comparative study. SETTING: University-affiliated hospital. PATIENTS: 50 ASA physical status I and II patients, aged 20 to 50 years, scheduled for minor surgery. INTERVENTIONS: Patients were randomized into two groups of 25 patients each. A target-controlled infusion of propofol (Diprifusor) was maintained at a predetermined target concentration. After a 10-minute steady state, blinded investigators evaluated patients' consciousness using verbal commands. The propofol test concentration was predetermined using a modified version of Dixon's up-and-down method (starting at 2.5 mug/mL; step size of 0.1 microg/mL). MEASUREMENT: Predicted and measured C(P50LOC) values and bispectral index (BIS) were obtained by averaging the crossover midpoint (ie, consciousness to unconsciousness). Those values were analyzed by unpaired t test: P < 0.05 was considered significant. RESULTS: The predicted C(P50LOC) for men was 2.14 +/- 0.10 microg/mL, which was lower than that for women, 2.55 +/- 0.11 microg/mL (P < 0.0001). No significant difference was found for measured C(P50LOC) in men (2.37 +/- 0.41 microg/mL) and in women (2.30 +/- 0.28 microg/mL) or for BIS measurements. CONCLUSION: Predicted C(P50LOC) by Diprifusor for men tended to be underestimated; that for women tended to be overestimated. Our data support a review of Diprifusor (Astra Zeneca, Osaka, Japan) pharmacokinetic parameters to avoid awareness during operation, particularly for women.     

Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening

Reported effect-site concentrations of propofol at loss of consciousness and recovery of consciousness vary widely. Thus, no single concentration based on a population average will prove optimal for individual patients. We therefore tested the hypothesis that individual propofol effect-site concentrations at loss and return of consciousness are similar. Propofol effect-site concentrations at loss and recovery of consciousness were estimated with a target-control infusion system in 20 adults. Propofol effect-site concentrations were gradually increased until the volunteers lost consciousness (no response to verbal stimuli); unconsciousness was maintained for 15 min, and the volunteers were then awakened. This protocol was repeated three times in each volunteer. Our major outcomes were the concentration producing unconsciousness and the relationship between the estimated effect-site concentrations at loss and recovery of consciousness. The target effect-site propofol concentration was 2.0 +/- 0.9 at loss of consciousness and 1.8 +/- 0.7 at return of consciousness (P <0.001). The average difference between individual effect-site concentrations at return and loss of consciousness was only 0.17 +/- 0.32 microg/mL (95% confidence interval for the difference 0.09-0.25 microg/mL). Our results thus suggest that individual titration to loss of consciousness is an alternative to dosing propofol on the basis of average population requirements.     

The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation

In order to examine whether changes in the bispectral index (BIS) may be an adequate monitor for the analgesic component of anesthesia, we evaluated the effect of remifentanil on the BIS change and hemodynamic responses to laryngoscopy and tracheal intubation. Fifty ASA physical status I patients were randomly assigned, in a double-blinded fashion, to one of five groups (n = 10/group) according to the remifentanil target effect compartment site concentration (0, 2, 4, 8, or 16 ng/mL). The target-controlled infusion (TCI) of remifentanil was initiated 3 min after the TCI of propofol that was maintained at the effect-site concentration of 4 microg/mL throughout the study. After the loss of consciousness and before the administration of vecuronium 0.1 mg/kg, a tourniquet was applied to one arm and inflated above the systolic blood pressure in order to detect any gross movement within the first minute after tracheal intubation, which was performed 3 min after remifentanil TCI began. A BIS value was generated every 10 s. Arterial blood pressure and heart rate (HR) were measured every minute, noninvasively. Measures of mean arterial pressure (MAP), HR, and BIS were obtained before the induction, before the start of remifentanil TCI, before laryngoscopy, and 5 min after intubation. The relationships between remifentanil effect-site concentrations and BIS change or hemodynamic responses (changes in MAP and HR) to intubation were determined by logarithmic regression. BIS values were not affected by remifentanil before laryngoscopy. During this period, MAP and HR decreased significantly (P < 0.01) in the remifentanil 8 and 16 ng/mL groups. Changes in BIS, MAP, and HR were negatively correlated with remifentanil effect-site concentration (P < 0.0001). The number of movers in the remifentanil 0-, 2-, 4-, 8-, and 16-ng/mL groups was, respectively, 10, 9, 7, 1, and 0. Hypotensive episodes (MAP < 60 mm Hg) were noted in 1, 2, and 5 patients in the remifentanil 4-, 8-, and 16-ng/mL groups, respectively. We conclude that the addition of remifentanil to propofol affects BIS only when a painful stimulus is applied. Moreover, remifentanil attenuated or abolished increases in BIS and MAP after tracheal intubation in a comparable dose-dependent fashion. IMPLICATIONS: Bispectral index change is as sensitive as hemodynamic responses after a painful stimulus for detecting deficits in the analgesic component of anesthesia. It may, therefore, be a useful monitor of the depth of anesthesia in patients who are incapable of HR and MAP responses to noxious stimuli because of medications or cardiovascular disease.     

Changes of bispectral index during recovery from general anesthesia with 2% propofol and remifentanil in children

BACKGROUND: The bispectral (BIS) index is a pharmacodynamic measure of the effect of anesthesia on the central nervous system. The aim of this study was to investigate the relationship between BIS index and predicted plasma concentration of propofol delivered by target controlled infusion (TCI) during emergence in children. METHODS: With approval of IRB, 30 patients (2-7 years) were included in this study. Anesthesia was with TCI propofol 3-5 microg.ml(-1) and remifentanil 7.5 ng.ml(-1) to maintain BIS 40-60 and the propofol concentration was fixed at 3 microg.ml(-1) Remifentanil infusion was stopped 10 min before the end of surgery. BIS values were recorded after reducing propofol in decrement of 0.2 microg.ml(-1). BIS values were checked when spontaneous respiration occurred and children were able to obey a command (eye opening or hand grasping). RESULTS: Spearman's correlation analysis showed negative correlation between BIS and propofol plasma concentration (r = -0.559, P < 0.001). When respiration returned, mean BIS was 77.2 +/- 5.3 and propofol plasma concentration 1.6 +/- 0.3 microg.ml(-1) and when a verbal command was obeyed, BIS was 82.4 +/- 5.6 and propofol plasma concentration 1.5 +/- 0.3 microg.ml(-1). CONCLUSIONS: In preschool children, BIS moderately correlated with the predicted plasma concentration of propofol.     

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 microg/ml and increased every 4 min by 0.5 microg/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. CONCLUSION: Bispectral Index, AAI, and predicted propofol effect-site concentration revealed information on the level of sedation and loss of consciousness but did not predict response to noxious stimulus.     

The interaction between propofol and clonidine for loss of consciousness

Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics. Clonidine also reduces the induction dose of IV anesthetics. There is no information, however, regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness, and the interaction between propofol and clonidine. We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5. 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients: Control (n = 35), 2.5 microg/kg Clonidine (n = 36), and 5.0 microg/kg Clonidine (n = 36) groups. Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was administered orally 90 min before the induction of anesthesia in the Clonidine groups. After equilibration between the blood and effect-site for 15 min, a verbal command to open their eyes was given two times to the patients. Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given. Measured serum propofol concentrations in equilibrium with the effect-site at which 50% of the patients did not respond to verbal commands (EC50 for loss of consciousness) were determined by logistic regression. The EC50 +/- SE values in the Control, 2.5 microg/kg Clonidine, and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18, 1.31 +/- 0.12, and 0.91 +/- 0.13 microg/mL, respectively. The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group (P < 0.001). The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness. These results indicate that propofol and clonidine act additively for loss of consciousness. IMPLICATIONS: Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness.     

The influence of gender on loss of consciousness with sevoflurane or propofol

Studies have suggested that hypnotic requirements for general anesthesia and emergence may be influenced by gender. In this study, we examined the effect of gender on the hypnotic requirement for loss of consciousness (LOC) using either a volatile (sevoflurane) or an IV (propofol) anesthetic. One-hundred-fifteen unpremedicated, ASA physical status I-II patients, aged 18-40 yr old, received either sevoflurane by mask to a predetermined end-tidal concentration (%ET(sevo)) or propofol by target-controlled infusion (effect site) while breathing spontaneously. After sufficient time for equilibration, LOC was assessed by lack of response to mild prodding. The up-down method of Dixon was used to determine the hypnotic target concentration at 50% response (LOC(50)). No statistically significant difference in LOC(50) was noted between men and women for sevoflurane (0.83% +/- 0.1% and 0.92% +/- 0.09% ET, respectively). Men required significantly more propofol than women (2.9 +/- 0.2 versus 2.7 +/- 0.1 microg/mL, respectively). However, there was no difference in the bispectral index (BIS) at LOC for men or women with either hypnotic anesthetic. This investigation identified a small, statistically significant difference in hypnotic requirement at LOC(50) between men and women with propofol but not with sevoflurane. As defined by BIS, men and women had equivalent hypnotic states at LOC(50), indicating that gender had no clinically significant effect on hypnotic requirements. However, BIS at a defined clinical end-point (LOC(50)) was significantly different between the sevoflurane and propofol groups, suggesting that neurophysiological effects of these anesthetics may be different. IMPLICATIONS: Gender affects the dosing requirements for, and response to, many drugs used in anesthetic practice. Loss of consciousness is an early clinical marker of hypnotic drug effect. We found no significant difference to either an inhaled (sevoflurane) or IV (propofol) anesthetic related to patient gender.     

Remifentanil dose/electroencephalogram bispectral response during combined propofol/regional anesthesia

The effect of opioid administration on the bispectral index (BIS) during general anesthesia is controversial. Several investigators have reported BIS to be insensitive to opioid addition, whereas others have found a hypnotic response. We designed this study to examine the effect of remifentanil on BIS during combined regional/general propofol anesthesia under steady-state conditions. After Human Investigations Committee approval, 19 healthy ASA physical status I or II patients were enrolled in a prospective experimental design. Regional anesthesia was initiated and general anesthesia induced by using computer-assisted continuous infusion of propofol. Propofol was incrementally adjusted to a BIS of approximately 60. After 20 min at a stable propofol infusion rate, a remifentanil computer-assisted continuous infusion (effect-site target concentration of 0.5, 2.5, and then 10 ng/mL) was sequentially administered at stepped 15-min intervals. BIS decreased from 56 +/- 2 to 44 +/- 1, 95% spectral edge frequency from 17.9 +/- 0.5 Hz to 15.0 +/- 0.4 Hz, heart rate from 84 +/- 5 bpm to 62 +/- 4 bpm, and mean arterial blood pressure from 93 +/- 4 mm Hg to 69 +/- 3 mm Hg with increasing remifentanil concentration. A significant linear correlation between BIS, 95% spectral edge frequency, heart rate, and log (remifentanil effect-site) concentration was found. The change in baseline BIS was relatively modest but significant, suggesting that remifentanil has some sedative/hypnotic properties, or that it potentiates the hypnotic effect of propofol. IMPLICATIONS: This experiment identified a significant, dose-dependent decrease in bispectral index (BIS), 95% spectral edge frequency, heart rate, and mean arterial blood pressure with increasing remifentanil dose. The change in baseline BIS was relatively modest but significant, suggesting that remifentanil has some sedative/hypnotic properties, or that it potentiates the hypnotic effect of propofol.