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 relationship between bispectral index and targeted propofol concentration is biphasic in patients with major burns

BACKGROUND: Many pathophysiologic alterations in major burns can cause changes in the distribution of, and perhaps response to, drugs commonly used in anesthesia practice. This study was conducted to assess changes in bispectral index (BIS) caused by increasing the target propofol effect-site concentration during a target-controlled infusion (TCI) in major burns. METHODS: Eighteen patients, ASA physical status 2 or 3, aged from 20 to 55 years old, weighing 50-70 kg, with major burns, scheduled for elective early escharectomy less than a week after injury were recruited. A further 18 ASA physical status class 1 or 2, non-burns, age, sex- and weight-matched adult patients scheduled for elective surgery under general anesthesia were recruited as controls. During anesthesia induction, target propofol effect-site concentrations were increased by increments of 0.5 microg ml(-1) up to 4.5 microg ml(-1). The BIS responses to each target concentration using TCI were compared in both groups. RESULTS: In the burns group, significantly greater BIS values relating to increasing propofol TCI were noted at deeper anesthesia when compared with controls; at > or =3.5 microg ml(-1); mean BIS remained at a plateau of about 50. Patients with burns had higher cardiac indices, and lower hemoglobin and albumin concentrations than the controls. They consumed more vecuronium to maintain the same degree of neuromuscular blockade than the controls. CONCLUSIONS: In major burns, the final biphasic BIS responses appeared to be determined by numerous other variables such as BIS algorithm, TCI performance, and altered propofol pharmacokinetics and pharmacodynamics. According to our results the importance of an individually tailored approach, including careful anesthetic titration, based upon the patient's clinical condition and responses can not be overemphasized.     

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.     

Target-controlled infusion anesthesia with propofol and remifentanil compared with manually controlled infusion anesthesia in mastoidectomy surgeries

Target-controlled infusion (TCI) system is increasingly used in anesthesia to control the concentration of selected drugs in the plasma or at the site of drug effect (effect-site). The performance of propofol TCI delivery when combined with remifentanil in patients undergoing elective surgeries has been investigated. Our aim in this study was to assess the anesthesia profile of the propofol and remifentanil target controlled infusion (TCI) anesthesia as compared to the manually controlled infusion (MCI), in mastoidectomy surgery, where a bloodless field is of utmost importance to the surgeon. Sixty patients, aged 18-60 years ASA I-II enrolled in the study, were divided into two equal groups. Group MCI received propofol and remifentanil by conventional-dose-weight infusion method, and Group TCI received propofol 4 microg/ml and remifentanil 4 ng/ml as effect-site target concentration. The hemodynamic variability, recovery profile, postoperative nausea and vomiting (PONV), surgeons satisfaction were assessed. Results were analyzed by SPSS version 11.5. The two groups were comparable with respect to age, ASA class, sex, weight, basal vital signs, operation time. The blood pressure and pulse were above desired levels in some data points in the MCI Group (P < or = 0.05). The PACU stay time to reach Aldret score of 10 was longer in the MCI Group (42.54 +/- 8 vs 59.01 +/- 6 min) (P < or = 0.05). The PONV was more common in the MCI Group (P < or = 0.05). Surgeon's satisfaction of the surgical field showed no significant differences except when described as "good", more common in the TCI Group. TCI is capable to induce and maintain anesthesia as well as MCI. In some stages of anesthesia, the TCI control of vital signs are better than the MCI. In some stages of anesthesia, the TCI control of vital signs are beter than the MCI. Recovery profile and complication rate and surgeon's satisfactions are more acceptable in the TCI than in the MCI Group.     

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.     

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.     

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.     

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.     

Remifentanil-propofol vs. sufentanil-propofol: optimal combinations in clinical anesthesia

BACKGROUND: Two opioid regimens, computer-simulated to provide optimal general anesthesia in combination with propofol, were compared using clinical criteria. METHODS: Fifty patients undergoing thyroid surgery were blindly, prospectively and randomly allocated to receive either (a) i.v. remifentanil (1.5 micro g kg-1, followed by 0.2 micro g kg-1 min-1) or (b) i.v. sufentanil (0.2 micro g kg-1 followed by 0.2 micro g kg-1 h-1). Remifentanil infusion was stopped at the last skin suture. Sufentanil infusion was stopped 30 min before the end of surgery. Intravenous propofol was titrated to keep BIS at 50+/-5. Remifentanil and sufentanil groups were compared with regards to (a) propofol delivery, (b) hemodynamic and recovery variables, and (c) effect-site propofol levels during a steady-state period for effect-site remifentanil and sufentanil levels. P<0.05 was significant. RESULTS: Groups were similar in demographic data; types and durations of surgery; total propofol consumption; and response, extubation and emergence times. During the steady-state period for the opioid delivery, the remifentanil and sufentanil effect-site levels were 5.3 ng ml-1 and 0.18 ng ml-1, respectively (potency ratio=30). In both opioid groups, in accordance with previous computer-simulations, the effect-site propofol concentrations remained (a) within a narrow range unaffected by surgical stimuli, (b) significantly smaller in the remifentanil group than in the sufentanil group, but (c) smaller than expected from previous computer-simulations. More patients required ephedrine following induction of anesthesia in the remifentanil compared with the sufentanil group. CONCLUSIONS: The present clinical trial conducted in thyroid surgery is consistent with previous computer-simulated opioid-propofol combinations with respect to intraoperative and recovery variables. Effect-site propofol ranges were, however, lower than expected.     

异丙酚麻醉下瑞芬太尼抑制不同年龄老年患者气管插管和切皮反应的半数有效血浆靶浓度

目的 确定异丙酚麻醉下瑞芬太尼抑制不同年龄老年患者气管插管和切皮反应的半数有效血浆靶浓度(EC50).方法 择期全麻老年患者116例,年龄60～79岁,体重39～82 kg,ASA Ⅰ～Ⅲ级,按年龄及刺激不同分为4组,靶控输注异丙酚,待患者意识消失时靶控输注瑞芬太尼,Ⅰ-TI组(60～69岁,n=33)和Ⅱ-TI组(70～79岁,n=31)第1例患者瑞芬太尼初始血浆靶浓度设为3.5 ng/ml,待效应室浓度与血浆靶浓度达平衡后静脉注射维库溴铵0.1 me,/kg,3 min后行气管插管.Ⅰ-SI组(60～69岁,n=26)和Ⅱ-SI组(70～79岁,n=26)第1例患者气管插管后瑞芬太尼初始血浆靶浓度设为2.5 ng/ml,待效应室浓度与血浆靶浓度达平衡后维持10 min,开始切皮,采用改良序贯法进行试验.发生心血管反应的标准:气管插管或切皮后3 min内平均动脉压或心率较气管插管或切皮前的基础值升高超过20%.计算各组EC50及其95%可信区间(CI).结果 Ⅰ-TI组和Ⅱ-TI组瑞芬太尼抑制气管插管反应的EC50及其95%CI分别为2.90(2.76～3.04)ng/ml和3.16(2.90～3.41)ng/ml,差异无统计学意义(P>0.05);Ⅰ-SI组和Ⅱ-SI组瑞芬太尼抑制切皮反应的EC50及95%CI分别为1.90(1.76～2.04)ng/ml和1.77(1.68～1.85)ng/ml,差异无统计学意义(P>0.05);与Ⅰ-TI组比较,Ⅰ-SI组EC50降低(P<0.05);与Ⅱ-TI组比较,Ⅱ-SI组EC50降低(P<0.05).结论 60～69岁患者靶控输注异丙酚至意识消失时瑞芬太尼抑制气管插管和切皮反应的EC50分别为2.90、1.90ng/ml,70～79岁患者分别为3.16、1.77 ng/ml,不随年龄增加而改变.     

Cardiac anesthesia induction by low target plasma concentration setting of propofol using target-controlled infusion

BACKGROUND: Propofol-anesthesia administerd using target-controlled infusion (TCI) has been proposed for cardiac surgery. But, moderate target concentration of propofol during induction using TCI has not been studied in detail. METHODS: Thirty patients scheduled for cardiac surgery under cardiopulmonary bypass (CPB) and TCI propofol anesthesia were randomly divided into two groups to receive a computer-controlled infusion of propofol with target concentrations of 1.5 or 2.0 micro/g x ml(-1) [1.5 microg x ml(-1) group (n=15) and 2.0 microg x ml(-1) group (n=15)]. Mean arterial pressure (MAP), heart rate (HR) and bispectral index scale (BIS) values were recorded at 5 time points during induction of anesthesia. RESULTS: MAP was significantly lower in 2.0 microg x ml(-1) group compared with 1.5 microg x ml(-1) group. In both groups, a rise of BIS value did not occur during tracheal intubation. CONCLUSIONS: We have demonstrated that propofol TCI at a target concentration of 1.5 microg x ml(-1) is effective for hemodynamic stability during induction of anesthesia in patients for cardiac surgery under CPB.     

人工流产术患者复合异丙酚时靶控输注瑞芬太尼的药效学

目的 探讨人工流产术患者复合异丙酚4.5 μg/ml时靶控输注瑞芬太尼的药效学.方法 拟行人工流产术患者135例,年龄18～30岁,ASAI级,孕6～10周.随机分为9组(n=15):瑞芬太尼效应室靶浓度分别为0.5、0.8、1.1、1.4、1.7、2.0、2.3、2.6和2.9 ng/ml(Ⅰ组～Ⅸ组).各组异丙酚效应室靶浓度均为4.5 μg/ml.采用概率单位回归分析法,计算麻醉效果达优时瑞芬太尼效应室靶浓度EC50、EC95及其95%可信区间(CI)和呼吸抑制时瑞芬太尼效应室靶浓度EC50、EC95及其95%CI.结果 麻醉效果达优时瑞芬太尼的效应室靶浓度EC50为1.67 ng/ml,其95%CI为1.45～1.90 ng/ml,EC95为3.88 ng/ml,其95%CI为3.08～5.89 ng/ml;呼吸抑制时瑞芬太尼效应室靶浓度EC50为2.44 ng/ml,其95%CI为2.28～2.64 ng/ml,EC95为3.36 ng/ml,其95%CI为2.99～4.34 ng/ml.麻醉效果达优时瑞芬太尼的效应室靶浓度EC95高于呼吸抑制时效应室靶浓度EC95(P＜0.05).结论 人工流产术患者复合异丙酚4.5 μg/ml时,麻醉效果达优时瑞芬太尼的效应室靶浓度EC50、EC95,分别为1.67、3.88 ng/ml,呼吸抑制时瑞芬太尼的效应室靶浓度EC50、EC95,分别为2.44、3.36 ng/ml.     

瑞芬太尼和丙泊酚靶控输注用于老年患者妇科腹腔镜手术麻醉的研究

目的对行妇科腹腔镜手术的不同年龄的患者采用瑞芬太尼、丙泊酚靶控输注进行诱导和维持,观察此麻醉方式的临床疗效。方法60名ASAⅠ～Ⅲ级、行择期妇科腹腔镜手术的患者,分为Ⅰ组（〈65岁）和Ⅱ组（≥65岁）,每组30例。麻醉诱导,Ⅰ组瑞芬太尼靶效应室浓度4 ng/ml,Ⅱ组瑞芬太尼靶浓度2.5 ng/ml,2组丙泊酚血浆靶浓度从2.0μg/ml逐渐升高至意识消失,气管插管后根据脑电双频指数（BIS）和血流动力学参数变化调整丙泊酚和瑞芬太尼的靶浓度。记录患者诱导和维持阶段丙泊酚和瑞芬太尼靶浓度、收缩压（SBP）、舒张压（DBP）、心率（HR）及苏醒时间。结果Ⅱ组患者意识消失时丙泊酚靶血药浓度明显低于Ⅰ组[（2.5±0.4）μg/ml vs（3.2±0.5）μg/ml,t=5.988,P=0.000],维持过程中Ⅱ组平均丙泊酚靶浓度低于Ⅰ组[（2.1±0.5）μg/ml vs（2.7±0.7）μg/ml,t=3.820,P=0.000],维持过程中Ⅱ组瑞芬太尼靶浓度明显低于Ⅰ组[（0.19±0.06）ng/ml vs（0.32±0.06）ng/ml,t=8.391,P=0.000]。2组诱导后SBP明显下降,气管插管后回升,术中维持稳定。2组DBP、HR的波动无统计学意义。2组血管活性药的应用例数差异无显著性。Ⅱ组麻醉恢复时间长于Ⅰ组（P〈0.05）。结论根据监测数据个体化地调整丙泊酚和瑞芬太尼的靶浓度,能够使行妇科腹腔镜手术老年患者的血流动力学波动范围和麻醉深度维持在与中青年近似的水平,但老年患者苏醒时间仍延长。     

Bispectral index, predicted and measured drug levels of target-controlled infusions of remifentanil and propofol during laparoscopic cholecystectomy and emergence

BACKGROUND: Target-controlled infusions (TCI) have been launched as simple, accurate and reliable delivery systems of intravenous drugs. Bispectral index of EEG (BIS) seems promising in measuring hypnotic effect of anaesthetic drugs. The aims of this study were to evaluate the accuracy of TCI systems in patients undergoing laparoscopic cholecystectomy and to correlate measured drug levels to BIS values. Data were analysed for possible gender differences during emergence. METHODS: After written informed consent, 20 patients were enrolled in an open study. Remifentanil was set at 7.5 ng/ml as target throughout the whole procedure, and propofol at 5 microg/ ml at induction and 3 microg/ml after intubation. Values in blood samples of remifentanil and propofol were correlated to the estimated values and to systolic blood pressure and BIS. BIS values and measured drug levels during emergence and emergence time were compared for the two sexes. RESULTS: Measured drug values varied considerably from the set target with a prediction error of -22% for remifentanil and 49% for propofol. The anaesthesia level was regarded as quite deep with a mean BIS during stable surgery of 42 +/- 7, and at this level we found no correlation between measured values of either of the two drugs and BIS. The emergence time was significantly shorter for women (12.6 +/- 2.5 min) than for men (19.0 +/- 4.2 min) (P=0.001), with no significant differences in measured levels of propofol or remifentanil or BIS during the emergence period. CONCLUSION: Present systems for TCI of remifentanil and propofol result in large intra- and interindividual variations in measured drug levels, and measured levels differ from target. There may be possible interaction between the two anaesthetics at a pharmacokinetic level. Within the level of anaesthesia studied here, BIS was not an indicator of the actual drug levels. Women woke up significantly faster than men.     

Effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index guided propofol anestesia in seriously obese patients

AIM: The aim of this prospective study was to determine the effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index (BIS) guided propofol anesthesia in seriously obese patients. METHODS: Twenty-two patients, female/male 15/7, ASA physical status II - III, aged 29-69 years, body mass index (BMI) 54.5+/-12, undergoing major open bariatric surgery, were enrolled to receive a propofol-remifentanil total intravenous anesthesia. All patients were intubated by using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, anesthesia was started with a target controlled infusion of propofol initially set at 6 microg/mL, then adjusted to maintain a BIS value between 40 and 50. The mean effect site concentration of remifentanil was recorded at different intervals time during surgery: skin incision-opening of peritoneum (T1), bowel resection (T2), cholecystojejunal anastomosis (T3), ileojejunal anastomosis (T4), closing of peritoneum (T5). RESULTS: The mean plasma concentrations of propofol required to maintain a BIS value between 40 and 50 were 4+/-0.55, 3.8+/-0.64, 3.8+/- 0.63, 3.8+/-0.65 and 3.8+/-0.63 microg/mL at T1, T2, T3, T4 and T5 interval time, respectively. The mean values of remifentanil target effect site concentration were 5.2+/-1.3, 7.7+/-1.7, 9.1+/-1.8, 9.7+/- 2.2 and 9.9+/-2.5 ng/mL at T1, T2, T3, T4 and T5 interval time. CONCLUSIONS: This study suggests that tolerance to remifentanil infusion is profound and develops very rapidly in morbidly obese patients submitted to open bariatric surgery during BIS guided propofol anesthesia. The administration of opiates during anesthesia based on target-controlled infusion should include corrections for the development of tolerance.     

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.     

复合异丙酚时不同靶浓度瑞芬太尼对神经外科手术患者脑电双频谱指数的影响

目的 探讨复合异丙酚时不同效应室靶浓度瑞芬太尼对神经外科手术患者脑电双频谱指数(BIS)的影响.方法 择期拟行额颞部开颅手术患者15例,年龄18～64岁,体重50～85 kg,ASA Ⅰ或Ⅱ级.先靶控输注异丙酚,效应室靶浓度为3μg/ml,效应室浓度达预设浓度后靶控输注瑞芬太尼,效应室靶浓度分别为2、3、4、5、6、7、8 ng/ml,效应室浓度依次达预设浓度时记录血压(BP)、平均动脉压(MAP)、心率(HR)和BIS.瑞芬太尼效应室浓度达5 ng/ml时行气管插管和机械通气,于气管插管前即刻和气管插管后即刻记录BP、MAP、HR和BIS.结果 与基础值比较,异丙酚效应室浓度3μG/ml 和瑞芬太尼不同效应室浓度时BIS降低(P<0.05或0.01);与异丙酚效应室浓度3μg/ml时比较,瑞芬太尼效应室浓度≥6 nG/Ml时BIS降低(P<0.05或0.01).结论 复合异丙酚时靶控输注瑞芬太尼效应室浓度≥6 ng/ml时可降低神经外科手术患者的BIS.     

不同靶浓度舒芬太尼对异丙酚全麻患者脑电双频谱指数的影响

目的 评价不同靶浓度舒芬太尼对异丙酚全麻患者脑电双频谱指数(BIS)的影响.方法 择期全麻手术患者50例,ASA Ⅰ或Ⅱ级,年龄18～57岁,随机分为5组(n=10),舒芬太尼效应室靶浓度(Ce)分别设定为0.07、0.10、0.14、0.20、0.28 ng/ml.持续监测BIS、平均动脉压(MAP)、心率(HR)、脉搏血氧饱和度、呼气末二氧化碳分压和心电图.麻醉诱导:异丙酚起始血浆靶浓度(Cp)3.0μg/ml,若Ce与Cp平衡后5 min意识仍未消失,以0.3 μg/ml浓度梯度递增,持续靶控输注(TCI)异丙酚,患者意识消失时记录异丙酚Cp和Ce,并维持该浓度,随后按预设不同Ce TCI舒芬太尼,每分钟记录BIS、HR,收缩压(SP)、舒张压(DP)和MAP.待舒芬太尼Ce与Cp平衡时,静脉注射琥珀酰胆碱1.5mg/kg,行气管插管.结果 各组意识消失时异丙酚Cp、Ce及BIS差异无统计学意义(P>0.05);TCI舒芬太尼后,BIS逐渐降低,当舒芬太尼Cp和Ce平衡时,BIS明显低于TCI舒芬太尼前水平(P<0.05);BIS与舒芬太尼Ce呈负相关(r=-0.419,P<0.05).结论 靶控输注舒芬太尼可进一步降低异丙酚全麻患者的BIS.     

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.     

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.