Comparison of the Effect-site keO s of Propofol for Blood Pressure and EEG Bispectral Index in Elderly and Younger Patients

Background: Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients.

Methods: A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 [micro sign]g/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (keO) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile.

Results: The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients.     

The influence of age on propofol pharmacodynamics.

BACKGROUND: The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. METHODS: The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. RESULTS: Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. CONCLUSIONS: Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.     

The Influence of Age on Propofol Pharmacodynamics

Background: The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect.

Methods: The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 [micro sign]g [middle dot] kg-1 [middle dot] min-1) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion.

Results: Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min-1. The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 [micro sign]g/ml in volunteers who were 25, 50, and 75 yr old, respectively.     

腹腔镜结直肠手术中滴定靶控输注麻醉的应用

目的探讨以脑电双频指数（B1S）和收缩压为滴定目标、以丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉对腹腔镜结直肠手术中麻醉用药量和麻醉深度的影响。方法选择60例择期腹腔镜结直肠手术患者为研究对象,采用丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉,以BIS维持40～60、收缩压波动不超过基础值的20％为目标,滴定调节两种药物的血浆靶浓度,当BIS与收缩压的变化趋势出现矛盾时首先调节SBP。记录不同时间点的BIS、血压及麻醉药血浆靶控浓度等。结果麻醉诱导后血压基本平稳,BIS维持在60以内,其中在人工气腹建立后和Trendelenburg体位期间,BIS低至35。40之间：整个麻醉过程中患者均无术中知晓。麻醉期间存在手术刺激时,丙泊酚和瑞芬太尼血浆靶浓度的95％C1分别为2．55～2．65mg／L和4．09～4．26μg／L,其中丙泊酚的血浆靶浓度所推荐剂量。结论在腹腔镜结直肠手术中,以BIS结合收缩压为目标进行丙泊酚复合瑞芬太尼滴定靶控输注静脉麻醉,可维持有的麻醉深度,并减少麻醉药的用量。     

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.     

Variation of bispectral index under TIVA with propofol in a paediatric population

BACKGROUND: In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. METHODS: Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). RESULTS: We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. CONCLUSIONS: These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.     

不同硬膜外阻滞对患者异丙酚镇静效应的影响

目的 评价不同硬膜外阻滞对患者异丙酚镇静效应的影响.方法 择期行肠癌根治术患者30例和胃癌根治术患者15例,年龄20～64岁,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将肠癌根治术患者随机分为2组(n=15):生理盐水对照组(Ⅰ组)和腰段硬膜外阻滞组(Ⅱ组);胃癌根治术患者为胸段硬膜外阻滞组(Ⅲ组).Ⅰ组和Ⅱ组于L2.3间隙行硬膜外穿刺置管,Ⅲ组于L9.10间隙行硬膜外穿刺置管,Ⅱ组和Ⅲ组硬膜外注射1.5％利多卡因15 ml(包括试验量3 ml);Ⅰ组给予等容量生理盐水.于硬膜外给药后12 min时TCI异丙酚,血浆靶浓度4μg/ml.于输注异丙酚前记录硬膜外阻滞范围(阻滞脊神经数);分别于输注异丙酚2、3、4、5min时采集动脉血样,测定血浆异丙酚浓度,同时记录各时间点TCI泵计算的异丙酚血浆浓度和BIS值.结果 与Ⅰ组比较,Ⅱ组和Ⅲ组BIS值降低(P＜0.05),血浆异丙酚浓度和异丙酚血浆计算浓度差异无统计学意义(P＞0.05);与Ⅱ组比较,Ⅲ组BIS值降低,硬膜外阻滞范围较广(P＜0.05),血浆异丙酚浓度和异丙酚血浆计算浓度差异无统计学意义(P＞0.05).结论 胸段硬膜外阻滞强化患者异丙酚镇静效应的程度高于腰段硬膜外阻滞.     

老年人脑电双频指数、咪达唑仑血药浓度与镇静深度的相关性研究

目的 探讨老年人手术病人椎管内麻醉后用咪达唑仑镇静,脑电双频谱指数、咪达唑仑血药浓度和镇静深度间的相关关系。方法 44例ASAⅠ-Ⅱ级择期手术病人,不用术前药。分为老年组（61－82岁）和年轻组（19－43岁）,每组22例。为尽快达到稳态血药浓度,采用靶控输注. 咪达唑仑靶浓度从50ng/ml起渐增,直至病人对轻推无反应（意识消失）,每个浓度维持15min。连续记录EEG参数,在每一稳态血药浓度末,记录BIS、95％SEF,桡动脉取血（高效液相色谱法测定咪达唑仑血药浓度,并评定镇静深度（OAA／S评分法）。用Spearman’s等级相关进行相关分析,并计算预测概率（Pk）值。结果 两组BIS（r=0.935-0.955)与镇静水平的相关性优于血药浓度（r=-0.849～-0.870）和95％SEF（(r=0.503-0.571).BIS的Pk值高（0．942－0．972）。在同一镇静评分(OAA/S4-1时）,老年组BIS值明显高于年轻组（P＜0．01）,而血药浓度低于年轻组。结论 BIS在监测咪达唑仑镇静水平及预测意识消失方面有重要价值。在同一镇静评分时,老年人BIS值高于年轻人。     

Steady-state propofol brain:plasma and brain:blood partition coefficients and the effect-site equilibration paradox

Based on volume-flow relationships, CNS agents that are highly lipid soluble (log octanol-water partition coefficient > 2) are expected to have equilibration half-times (T1/2 kE0) that are proportional to brain solubility. Propofol, the most lipophilic anaesthetic in clinical use, has T1/2 kE0 values of 1.7 and 2.9 min in rats and humans, respectively, compared with an expected value of at least 8 min. As a first step in exploring this discrepancy between observed and predicted values, we determined the steady state brain:plasma and brain:blood partition coefficients in rats after a 4-h infusion of propofol. Brain:plasma and brain:blood partition coefficients were 8.2 (SD 1.6) and 3.0 (0.5), respectively. T1/2 kE0 predictions based on brain: blood partitioning in rats are more in agreement with the observed equilibration half-time, suggesting that drug bound to the formed elements of blood participates in the uptake and transfer of propofol to its effect site.      

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.     

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.     

卵巢周期对患者异丙酚镇静效应的影响

目的 评价卵巢周期对患者异丙酚镇静效应的影响.方法 择期拟行妇科腹腔镜手术患者加例,ASA分级Ⅰ或Ⅱ级,年龄20.加岁,体重指数20～25 kg/m2,根据孕酮水平分为卵泡期组(F组,血清孕酮浓度0.31～1.52 ng/ml)和黄体期组(L组,血清孕酮浓度5.16～18.56 ng/ml),每组20例.麻醉诱导时靶控输注异丙酚,初始血浆靶浓度2 μg/ml,达到预期血浆靶浓度后每隔30 s递增0.5μg/ml直至患者意识消失及BIS值降至50.记录患者意识消失时的BIS值、异丙酚血浆靶浓度,记录BIS值降至50时的异丙酚血浆靶浓度.结果 与L组比较,F组意识消失时和BIS值降至50时的异丙酚血浆靶浓度升高(P＜0.05或0.01),意识消失时的BIS值差异无统计学意义(P＞0.05).结论 卵巢周期可影响异丙酚的镇静效应,表现为卵泡期的镇静效应低于黄体期.

Abstract：

Objective To investigate the effect of ovarian cycle on the sedative effect of propofol in patients. Methods Forty ASA Ⅰ or Ⅱ patients, aged 20-40 yr, with body mass index 20-25 kg/m2 , scheduled for elective gynecologic laparoscopic surgery, were divided into 2 groups according to the progesterone level ( n = 20 each): follicular phase group (group F, serum progesterone concentration 0.31-1.52 ng/ml) and luteal phase group (group L, serum progesterone concentration 5.16-18.56 ng/ml). Anesthesia was induced with target-controlled infusion (TCI) of propofol and iv injection of fentanyl and cisatracurium. The initial target plasma concentration (Cp) of propofol was set at 2 μg/ml, after the Cp reached the predetermined level, the Cp increased by 0.5 μg/ml every 30 s until the patients lost consciousness and BIS value was decreased to 50. The BIS value and Cp of propofol was recorded when the patients lost consciousness. The Cp of propofol was also recorded when BIS value was decreased to 50. The patients were tracheal intubated and mechanically ventilated. Anesthesia was maintained with TCI of propofol combined with remifentanil. BIS value was maintained at 45-55 by adjusting the Cp of propofol. Results The Cps of propofol were significantly higher when the patients lost consciousness and when BIS value was decreased to 50 in group F than in group L ( P ＜ 0.05 or 0.01) . There was no significant difference in BIS value when the patients lost consciousness between the two groups (P ＞ 0.05). Conclusion Ovarian cycle can affect the sedative effect of propofol in patients, which shows that the sedative effect during the follicular phase is lower than that during the luteal phase.     

Propofol Concentration during Maintenance of and Emergence from Propofol/Epidural Anesthesia: Comparison between Younger and Elderly Patient]

To investigate the influence of patient age on the sensitivity to propofol, we measured blood propofol concentrations in ten elderly (over 70 years of age) and ten younger (under 60 years of age) patients undergoing elective abdominal surgery during propofol/epidural anesthesia. Bispectral index (BIS) was continuously recorded for monitoring anesthetic effect, and the infusion rate of propofol was controlled to keep BIS at 50 after the induction of anesthesia with propofol. At steady-state before skin incision, propofol concentrations to maintain BIS at 50 in younger and elderly patients were 4.3 +/- 1.6 micrograms.ml-1 and 3.2 +/- 1.3 micrograms.ml-1, respectively, and there was no significant difference. Mean blood propofol concentrations were 4.0 +/- 1.5 micrograms.ml-1 for the younger group and 3.2 +/- 1.7 micrograms.ml-1 for the elderly group at the end of surgery immediately before discontinuation of propofol, and they were 1.9 +/- 0.7 micrograms.ml-1 (BIS = 86 +/- 7) for the younger group and 1.5 +/- 0.8 micrograms.ml-1 (BIS = 84 +/- 3) for the elderly group at the time of eye opening with no significant difference. We found appreciable individual variations in the propofol concentrations both in younger and elderly patients in this study.     

Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

Background: The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect.

Methods: Thirty-one young (18-50 yr) and 33 elderly (> 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fentanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults.

Results: Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) l and 9.6 (7.6-11.7) l in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (k sub e0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05).     

Rapid fluid infusion therapy decreases the plasma concentration of continuously infused propofol

BACKGROUND: Rapid fluid infusion therapy to treat hypovolemia in anesthetized patients is a common practical regimen in daily clinical settings. This study investigated the effect of large volume loading on the plasma concentration of propofol (Cp), hemodynamic parameters, hemoglobin concentration (Hb), hematocrit value (Ht) and the bispectral index (BIS). METHODS: Sixty patients were administered propofol using a target-controlled infusion technique. We studied two independent groups. Half of the patients (group F, n = 30) were administered fentanyl, and the other half (group E, n = 30) epidural administration of mepivacaine for analgesia. After achieving a pseudo-steady state of propofol anesthesia, baseline values of blood pressure, heart rate, Hb, Ht, cardiac output, Cp and BIS were measured, and 10 ml/kg Ringer's solution was infused over 15 min. RESULTS: In group F, Cp was significantly decreased from 2.24 (0.69) [mean (SD)] to 2.07 (0.61) microg/ml and in group E from 2.02 (0.98) to 1.75 (0.51) microg/ml immediately after infusion (P < 0.05). The significant reduction lasted until 30 min in group F, whereas, Cp quickly recovered in group E. Cardiac output was increased only in group F. The dilution ratio demonstrated the prolonged diluting effect in group E and the significant correlation with the rate of decrease in Cp (P < 0.0003, R = 0.21). The BIS value showed no significant change immediately after infusion. CONCLUSION: Large volume loading decreased Cp without a significant change in BIS values. The effect of infusion therapy on the depth of anesthesia might be small and usually negligible during propofol anesthesia.     

The combined effect of age and premedication on the propofol requirements for induction by target-controlled infusion

In this prospective study, we evaluated the combined influence of age and premedication on propofol requirements for the induction of anesthesia and their hemodynamic effects using a target-controlled infusion. We studied 180 patients separated into three age groups: 20-39 yr, 40-59 yr, and more than 59 yr. In each age group, patients were randomly allocated to receive either no premedication (n = 20), fentanyl (2 microg/kg) (n = 20), or midazolam (0.03 mg/kg) plus fentanyl (2 microg/kg) (n = 20). The concentration of propofol targeted for the induction was 5 microg/mL, to be reached in 2 min. The dose, time, and predicted plasma concentration of propofol at hypnosis were measured. Baseline and postinduction heart rate and arterial blood pressure were registered. Computer simulation was used to calculate the effect site propofol concentration at hypnosis. The concentration of propofol, effect site propofol concentration, time, and induction dose and their hemodynamic effect were significantly different among groups with respect to age and premedication. The combined effect of the two factors was additive, but without significant interaction. The propofol requirements were significantly less in the midazolam-fentanyl groups, regardless of age, and among the premedicated patients older than 60 yr compared with the other age groups. We conclude that the combined effect of age and premedication on the requirements of propofol for the induction of anesthesia should be considered when the concentration is targeted with a target-controlled infusion system.     

Impact of bispectral index monitoring on stress response and propofol consumption in patients undergoing coronary artery bypass surgery

BACKGROUND: Bispectral Index (BIS)-titrated administration allows a reduction of propofol infusion rates in patients undergoing surgery. Resulting differences in anesthetic depth might affect the stress response to surgery involving neural circuitry not reflected in the electroencephalogram. METHODS: Forty patients scheduled to undergo elective coronary artery bypass grafting receiving a background infusion of remifentanil (0.3 microg . kg . min) were anesthetized with intravenous propofol delivered by target-controlled infusion according to the Marsh pharmacokinetic model under BIS monitoring. In a randomized, prospective design, 20 patients received propofol at a target concentration of 3 microg/ml, whereas in 20 patients propofol was titrated to maintain a BIS value of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and 10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly throughout surgery. RESULTS: BIS monitoring allowed a 30% reduction of propofol infusion rates and a similar decrease in plasma propofol concentrations in the BIS group without affecting the stress response to surgery for the group mean. None of the patients reported awareness during a standardized interview. Interestingly, propofol-remifentanil anesthesia blunted the release of epinephrine and cortisol to bypass surgery completely even when the propofol infusion rate was reduced according to BIS values. CONCLUSIONS: Total intravenous anesthesia using propofol-remifentanil effectively attenuates the neurohumoral stress response to coronary bypass surgery involving cardiopulmonary bypass. Titration of propofol using BIS allows for significant reduction of propofol consumption, with only minor effects on stress response under these conditions.     

丙泊酚镇静下瑞芬太尼对不同年龄患者抑制气管插管反应的半数有效浓度

目的 测定丙泊酚镇静深度下瑞芬太尼抑制不同年龄患者插管反应的半数有效血浆靶控浓度(Cp50)、半数有效实测浓度(Cm50)值、半数有效效应室浓度(EC50)值.方法 60例上腹部手术患者,男37例、女23例,年龄22岁～82岁,分为:青年组(n=20),22岁～44岁,中年组(n=20),45岁～64岁,老年组(n=20),65岁～82岁.所有患者靶控输注丙泊酚、调节丙泊酚靶控输注血浆浓度将脑电双频指数(bispectral index,BIS)目标值定为45～55,待BIS目标值稳定5 min,靶控输注瑞芬太尼.瑞芬太尼的血浆靶控浓度按序贯法确定,输注5 min给予维库溴铵0.1 mg/kg行气管插管,记录血流动力学变化和计算瑞芬太尼Cp50、Cm50、EC50值.结果 3组患者瑞芬太尼抑制插管反应的Cp50和95%CI分别是5.77 μg/L.,4.76 μg/L～7.01 μg/L;4.80 μg/L,3.56 μg/L～6.48 μg/L;4.06 μg,/L,3.52 μg,/L～4.92 μg/L.青年组与中年组、老年组差异有统计学意义(P<0.01),中年组与老年组差异有统计学意义(P<0.05).EC50和95%CI分别是5.90μg/L,4.47 μg/L～7.68 μg/L;4.60 μg/L,3.03 μg/L～5.90 μg/L;4.06 μg/L,2.97 μg/L～5.42 μg/L.青年组与中年组、老年组差异有统计学意义(P<0.05),中年组与老年组差异有统计学意义(P<0.01).Cm50和95%CI分别是4.25 μg/L,2.04 μg/L～6.47 μg/L;3.62 μg/L,1.70 μg/L～5.54 μg/L;3.09 μg/L,1.3μ/L～4.89 μg/L.青年组与老年组差异有统计学意义(P<0.01).3组患者在达到目标BIS值时丙泊酚靶控浓度分别为(3.6±0.6)mg/L、(3.4±0.8)mg/L、(2.7±0.8)mg/L,青年组与老年组差异有统计学意义(P<0.05).结论 丙泊酚复合瑞芬太尼用于抑制气管插管反应,在维持BIS值为45～55时,各年龄组之间的丙泊酚靶控输注血浆浓度、瑞芬太尼的Cp50、Cm50、EC50差异有统计学意义.     

复合异丙酚全麻中麻醉深度指标的相关性

目的 探讨复合异丙酚全麻中麻醉深度指标的相关性。方法 选择ASA Ⅰ～Ⅱ择期手术患者18例,行血压、心率、脑电、心率变异性监测,并测定异丙酚血药浓度。调整异丙酚的泵注速度,使收缩压(SBP)的波动幅度≤20％基础值,双频谱指数(BIS)维持在30～60之间。结果 异丙酚血药浓度与BIS、平均动脉压(MAP)有负相关关系(P<0.01),相关程度为BIS>MAP,心率(HR)与MAP呈正相关(P<0.01);心率变异性低频(LF)、高频(HF)与HR均有负相关关系(P<0.01),LF与HF有正相关关系(P<0.01),LF、HF与MAP、BIS、异丙酚血药浓度无相关关系(P>005)。结论 LF、HF可反映心脏交感、迷走张力的活动变化,而不能反映麻醉的意识状态。可通过BIS、平均动脉压来调整异丙酚血药浓度。     

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.