Changes of propofol concentration in cerebrospinal fluid during continuous infusion

We studied the changes in the propofol concentration in the cerebrospinal fluid (CSF) in 14 patients, undergoing elective intracranial procedures, who were anesthetized with propofol administered by target-controlled infusion. During anesthesia, fentanyl and cisatracurium were administered as required. After intubation of the trachea, the lungs of the patients were ventilated to normocapnia with an oxygen-air mixture (FIO(2) = 0.33). Arterial blood and CSF samples (from an intraventricular drain) were collected between 90-180 min after the induction of anesthesia. Blood propofol concentrations were stable, between 5.0 +/- 1.89 and 4.5 +/- 1.7 microg/mL (mean +/- SD). There was a significant decrease in the CSF propofol concentration, from 52.2 +/- 35.01 ng/mL at 90 min to 28.6 +/- 21.9 ng/mL at 150 min (P < 0.05). The CSF propofol concentration at 180 min (21.4 +/- 14.0 ng/mL) was not significantly different from the concentration at 150 min. Some possible reasons for this decrease after commencing continuous intraventricular drainage are discussed. IMPLICATIONS: Propofol concentrations in the cerebrospinal fluid in neurosurgical patients Propofol concentration in cerebrospinal fluid of investigated patients decreased significantly after starting intraventricular drainage, despite relatively steady blood propofol concentrations. These results supplement the limited information about propofol pharmacokinetics in the human central nervous system.     

不同剂量异丙酚对家兔肝血流量及肝氧代谢的影响

目的观察输注不同剂量异丙酚对兔肝血流量(BF)和肝氧供需平衡的影响。方法30 只成年雄性健康家兔随机分为高剂量组(n=11,输注异丙酚1.2 mg·kg-1·min-1)、低剂量组(n=10,输注异丙酚0.4mg·kg-1·min-1)和对照组(n=9,输注等容量5%葡萄糖),静脉注射3%戊巴比妥钠麻醉后,气管插管、机械通气,开腹游离门静脉和肝动脉,行颈总动脉、门静脉、肝静脉插管。循环稳定后给药,电磁血流仪连续测定给药后0(给药前即刻)、10、20、30、40、50、60、70、80、90 min的门静脉和肝动脉BF,于给药后0、30、50、70、90 min采颈总动脉、门静脉、肝静脉血各0.5ml作血气分析,计算肝氧供(DO2)、氧耗(VO2)。结果高剂量组在给药后30-90min时肝BF较给药前即刻和对照组增加(P< 0.05或0.01),同期肝DO2、VO2也较对照组增加(P<0.05),肝DO2/VO2组间和组内比较差异无统计学意义。结论高剂量异丙酚可增加肝BF和肝DO2,同时也增加肝VO2,但尚能维持肝DO2/VO2。     

持续静脉输注ATP对腹部手术患者靶控输注异丙酚效应室浓度的影响

目的探讨腹部手术患者麻醉中持续静脉输注ATP对靶控输注异丙酚效应室浓度的影响。方法择期下腹部手术患者60例,ASAⅠ级或Ⅱ级,年龄44～64岁,体重49～87kg,随机分为3组（n=20）：异丙酚组（P组）单纯靶控输注异丙酚维持麻醉;ATP1组和ARP2,组在靶控输注异丙酚的同时,分别以微量泵持续静脉输注ATP 0．4 mg·kg^-1·h^-1和0．6mg·kg^-1·h^-1。术中根据BIS、MAP、HR调整异丙酚血浆靶浓度。当BIS＞55或BIS＜40时则以0．2μg/ml幅度增加或降低异丙酚靶浓度。术中静脉输注芬太尼,并根据需要使用血管活性药物。于麻醉诱导前即刻（T0）、气管插管前即刻（T1）、气管插管后即刻（T2）、切皮前即刻（T3）、切皮后10 min（T4）和60 min（L5）、术毕（T5）、呼之睁眼（L7）以及气管拔管后即刻（L8）记录HR、MAP、SpO2、BIS。记录麻醉全程异丙酚效应室浓度及停止靶控输注后TCI泵所显示的效应室浓度。结果3组一般资料、麻醉时间、芬太尼用量及苏醒时间比较差异无统计学意义（P＞0．05）。3组MAP、HR及SpO2维持在正常范围。术中异丙酚效应室浓度：与P组比较, ATP1组在T4至T8时降低,ATP2组在T1至T8时降低（p＜0．05或0．01）;与ATP1组比较,ATP2组T5至T7时降低（P＜0．05）。结论腹部手术患者麻醉中,BIS维持40～55时,ATP 0．4～0．6 mg·kg^-1·h^-1持续静脉输注可降低靶控输注异丙酚效应室浓度,且随ATP用药量的增加,异丙酚用药量相应减少,且不影响苏醒时间。     

Anesthesia with continuous infusion of propofol in myasthenic patients]

Anaesthesia with atracurium, fentanyl, and continuous intravenous infusion of propofol in two myasthenic patients is described. There were no intra and postoperative problems and operative conditions were considered excellent. This technique offers a safe alternative to inhalational anaesthesia for patients with myasthenia gravis. Monitoring of neuromuscular function is mandatory. The use of atracurium in myasthenic patients and the influence of propofol on neuromuscular transmission are discussed.     

持续输注丙泊酚药代动力学模型的选择

目的　将四种文献报道的药代动力学模型用于计算机模拟以预测持续输注丙泊酚的 血浆浓度,籍以选择适合中国人的药代动力学模型。方法　选择ASAⅠ～Ⅱ级的择期手术病人16 例,≥65岁(Ⅰ组)病人静脉输注丙泊酚速度60ml/h,<65岁(Ⅱ组)者输注速度75ml/h,抽取动脉血 分析药物血浆浓度,用四种药代动力学模型预测丙泊酚血浆浓度,计算样本加权残差(WR)、绝对值 加权残差(absWR)。结果　Schuttler模型在Ⅰ组病人,中位数加权残差(MDWR)显著小于其他三种 参数(P<0.01),对所有病人输注期间预测浓度 实测浓度的拟合程度最好(P<0.01)。结论　仅 Schuttler药代动力学模型适合用于持续静脉输注丙泊酚期间和停止输注后的药物浓度预测。     

持续泵注曲马多对靶控输注异丙酚血药浓度的影响

目的 观察麻醉中持续泵注曲马多对靶控输注(TCI)异丙酚麻醉血药浓度的影响。方法 随机将ASAⅠ～Ⅱ级病人50例分为两组(各25例),Ⅰ组单纯TCI异丙酚麻醉,Ⅱ组TCI异丙酚麻醉复合曲马多3mg/kg后以0.5 mg·kg-1·h-1持续泵注。以BIS值50±10来调节TCI血药浓度。麻醉中连续观察BIS、MAP、HR、异丙酚血药浓度(CP)、心率变异性(HRV)、LF/HF等指标,以及术中异丙酚用量和麻醉苏醒时间。结果 两组间BIS差异无显著性。Ⅰ组CP仅在切皮和拔管时显著高于Ⅱ组(P<0.05),而异丙酚总用量,苏醒及手术时间两组间差异无统计学意义。Ⅰ组仅在术毕时HRV高于Ⅱ组;切皮时和术中Ⅰ组HR明显高于Ⅱ组;Ⅰ组LF/HF在切皮前及术中较Ⅱ组显著升高。结论 持续泵注曲马多对TCI异丙酚麻醉血药浓度无明显影响,但曲马多的镇痛作用使其较单纯TCI异丙酚麻醉术中自主神经反应性下降,术后恢复期更加平稳。     

Continuous infusion of remifentanil and target-controlled infusion of propofol for coronary surgery in elderly patients: comparison with continuous infusion of remifentanil and propofol

OBJECTIVES: Comparison of the length of mechanical ventilation and postoperative complications after coronary surgery in elderly patients anaesthetised with propofol associated with either alfentanil or remifentanil. STUDY DESIGN: Retrospective study with an historic control group. PATIENTS: Three hundred thirty-eight consecutive patients (75-year-old or more) undergoing isolated coronary surgery. One hundred and fifty seven patients operated between January 1998 and June 2000 received alfentanil (1 microg/kg/minute) with a manually control infusion of propofol, 181 operated between July 2000 and 2002, remifentanil 0.25 microg/kg/minute with target controlled infusion of propofol (target blood concentration: 1.5 to 2 microg/ml). METHODS: The two groups were compared for preoperative and surgical data. The length of mechanical ventilation, stay in ICU and the main postoperative complications were compared between the two groups. RESULTS: Length of mechanical ventilation was significantly reduced in the remifentanil group (6 +/- 9 h vs. 13 +/- 63 h ; p <0.0001), 70% of the patients were extubated before the 6th postoperative hours against 53% in the alfentanil group (p =0.0023). This was not associated with a reduction of stay in ICU or postoperative complications. During surgery, an increased used of vasopressor was observed in the remifentanil group (40.2% vs 2.4% ; p <0.0001) with a postoperative elevation of blood concentration of CKMb (35.7 +/- 38.2 microg/l, vs. 27.7 +/- 31.9 microg/l, p =0.02). CONCLUSION: Elderly patients undergoing coronary surgery were extubated earlier with remifentanil. However, this had no effect on duration of ICU stay but was associated with an increased used of vasopressor.     

Remifentanil concentration during target-controlled infusion of propofol

After institutional approval and with written informed consent, eight surgical patients were infused intravenously with remifentanil at 250 ngkg lean body mass (LBM)(-1) x min(-1) for 30 min. Cardiovascular and respiratory parameters were recorded and arterial blood samples were taken at regular intervals. In each patient, the same protocol was repeated 40 min later during propofol infused to a target concentration of 3.0 microg x ml(-1). Blood concentrations of remifentanil and propofol were assayed using capillary gas chromatography and high performance liquid chromatography techniques respectively. The number of subjects enrolled was determined by testing the successive areas under the remifentanil time-concentration curve (AUC) for significant difference or non-difference using sequential analysis. The median measured propofol concentration was 3.5 (range: 2.6-4.5) microg x ml(-1) which did not change significantly during the second remifentanil infusion. The median AUC during propofol infusion was greater than control in all subjects, although there was considerable variation of 94.4 (64.3-129.6) versus 64.6 (34.8-126.9) ng x ml(-1) x min; P=0.008, n=8. After 30 min, there was no significant difference in remifentanil concentration during propofol infusion when compared with remifentanil alone of 4.6 (3.2-5.7) versus 3.8 (1.6-4.9) ng x ml(-1); P=0.73, n=8. Co-administration of propofol and remifentanil may result in greater remifentanil concentrations than when remifentanil is infused alone.     

Target-controlled infusion of propofol induction with or without plasma concentration constraint in high-risk adult patients undergoing cardiac surgery

BACKGROUND: Calculated plasma (Cp) and calculated effect site concentrations (Ce) of propofol associated with loss of consciousness (LOC) have been studied in young healthy patients. The aim of the study was to evaluate the calculated propofol concentrations required to induce LOC in ASA III adult patients undergoing cardiac surgery using a smooth target controlled infusion of propofol. METHODS: After informed consent, 44 patients were premedicated with 0.5 mg alprazolam orally. Propofol TCI using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor (ThalfKeo of 2.6 min) was used. Propofol Ce was progressively increased by 0.5 micro g/ml until LOC was obtained. The constraint on the maximum gradient between Cp and Ce was either 1 micro g/ml in group 1 or not limited in group 2. Hemodynamic variations were assessed. RESULTS: Mean preoperative left ventricular ejection fractions were 44 +/- 15.4% and 56 +/- 11.4% in groups 1 and 2, respectively (P < 0.01). At LOC, mean Cp was 1.9 micro g/ml in both groups but mean Ce was 1.08 +/- 0.31 and 1.43 +/- 0.42 micro g/ml in groups 1 and 2, respectively (P < 0.01). The mean induction time was 12.8 +/- 7.1 min in group 1 and 8.5 +/- 2.7 min in group 2 (P < 0.05). No episode of hypotension has been observed in either group. CONCLUSION: In ASA III patients undergoing cardiac surgery, smooth propofol TCI induction, using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor, is associated with LOC at a low mean calculated plasma concentration of 1.9 micro g/ml and good hemodynamic stability.     

Inactivation of 5-fluorouracil by the liver during continuous regional and systemic infusion in pigs.

During continuous systemic or portal infusion of 5-fluorouracil (5-FU) to anaesthetized pigs, the cytostatic activity was reduced in blood traversing the liver. The liver eliminated between 15 and 50% of the amount 5-FU given per time unit. During jugular infusion the concentration of cytostatic compounds in portal blood was equal to or less than in systemic blood. The cytostatic activity was much higher in portal blood and lower in systemic blood during portal infusion. The findings speak in favour of portal infusions of 5-FU to patients with disseminated cancer in the liver.     

Pain on injection of propofol with or without infusion of carrier fluid

BACKGROUND: Propofol, a popular intravenous (iv) anaesthetic induction agent for brief cases or day surgery, is associated with smooth induction, pleasant sleep, rapid recovery and little postoperative nausea. A major disadvantage is pain at the site of injection. The aim of the present study was to examine the influence of simultaneous iv infusion of carrier fluid on propofol-induced local pain. METHODS: Thirty patients, scheduled for ear-nose-throat or plastic surgery under general anaesthesia, were randomly allocated into two groups. Each patient had two 2 ml iv bolus injections of propofol given at two minutes' interval. In group I (n=15) the first bolus injection was given with no iv carrier fluid and the second one given with a 10 ml iv carrier fluid infused over 10 s. Correspondingly, the patients in group II (n=15) had their first injection with and their second one without the iv carrier fluid. Following each injection of propofol the patients were asked by a blinded investigator to score their pain on a 10-point visual analogue scale, and to report the appearance, maximum and disappearance of pain. After the second assessment of pain, general anaesthesia was induced with more propofol. RESULTS: Pain intensity at the site of propofol injection was found not to be influenced by simultaneous iv infusion of carrier fluid. CONCLUSION: It seems, from the results obtained here, that simultaneous iv infusion of carrier fluid has no particular effect on local pain following iv administration of propofol.     

Arterial baroreflex attenuation during and after continuous propofol infusion

The reduction of arterial blood pressure produced by propofol may be, in part, attributable to impaired baroreflex integrity. The purpose of this study was to investigate arterial baroreflex sensitivity during and after continuous propofol infusion. In urethane anaesthetized rabbits, left renal sympathetic nerves were exposed and placed on a bipolar silver electrode to record renal sympathetic nerve activity (RSNA). Mean arterial pressure (MAP) via a femoral artery and heart rate (HR) by electrocardiogram were continuously recorded. The rabbits were divided into two groups of eight each: Group 1, propofol 5 mg.kg-1 bolus followed by infusion 0.5 mg.kg-1 x min-1; Group 2, propofol 2 mg.kg-1 bolus followed by 0.2 mg.kg-1 x min-1. Phenylephrine pressor and sodium nitroprusside (SNP) depressor tests were carried out before propofol was started (control), at 15 and 30 min during 30 min infusion, and at 15, 30 and 60 min after its discontinuation. The change of RSNA was plotted with respect to every 5 mmHg increment and decrement of MAP to construct sympathetic baroreflex sigmoid curves, and to evaluate baroreflex sensitivity. The baroreflex sensitivity was also evaluated by calculating the ratio of maximum increase of RSNA or HR to SNP-induced maximum decrease of MAP (delta RSNA/delta MAP, delta HR/delta MAP). Despite the same decreases or increases in MAP, RSNA was attenuated after 15 and 30 min of propofol infusion in both groups compared with control (P < 0.05). Decreased delta RSNA/delta MAP gradually returned to the control level 60 min after discontinuation of propofol in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of a continuous infusion of propofol in maintaining anesthesia

This open, non comparative study was designed to establish a suitable dose regime for propofol when used as the main anaesthetic agent and given as a continuous infusion. Thirty patients (ASA I and II) were studied; five received muscle relaxants and were excluded from the analysis of maintenance and recovery. Immediately after an i.v. bolus dose of fentanyl (2 micrograms X kg-1), anaesthesia was induced in all patients with a mean dose of 2.03 mg X kg-1 propofol. Apnoea at induction was seen in 14 patients, with a mean duration of 151 s (range: 20 to 360 s). Mean, systolic and diastolic arterial pressures and heart rate decreased slightly but statistically significantly following induction. Fourteen patients, four of whom received propofol into a vein of the hand, noted pain on the injection site without venous sequelae immediately nor 24 h after anaesthesia. The mean duration of anaesthesia from induction to the patient ability to obey a simple command was approximately 40 min (range: 10 to 95 min). The mean infusion rate of propofol during maintenance was 0.86 +/- 0.04 mg X kg-1 X min-1. During maintenance, a satisfactory depth of anaesthesia was achieved in 23 patients without any further bolus injection of propofol. The mean time from stopping the infusion to eye opening on verbal command was 6.2 min, whilst that for orientation was 8.4 min. The anaesthesist assessed the quality of recovery as good or adequate in all the patients, who all were satisfied by the anaesthesia. No major adverse reactions occurred during or after anaesthesia and the incidence of minor side-effects was low.     

不同赋形剂异丙酚对患者肝移植术中血脂及肝功能的影响

目的 探讨不同赋形剂异丙酚对患者肝移植术中血脂及肝功能的影响.方法 择期拟行经典式非转流原位肝移植术患者40例,年龄40～64岁,体重50～75 kg,ASA分级Ⅲ或Ⅳ级,采用随机数字表法,将患者随机分为2组(n=20):异丙酚中/长链甘油三酯注射液组(M组)和异丙酚长链甘油三酯注射液组(L组).麻醉诱导:静脉注射盐酸戊乙奎醚1 mg、眯达唑仑0.04～0.06 mg/kg,舒芬太尼0.6～0.8μg/kg和维库溴铵0.10～0.15mg/kg,M组和L组分别静脉注射不同赋形剂的异丙酚1.5～2.0 mg/kg,气管插管后行机械通气.麻醉维持:吸入1%～2%异氟醚、M组和L组分别静脉输注不同赋形剂的异丙酚3～4 mg·kg-1·h-1和顺阿曲库铵0.2～0.3 mg·kg-1·h-1,间断静脉注射舒芬太尼0.2～0.3μg/kg.于入室(T1)、切皮前(T2)、无肝前期末(T3)、无肝期末(T4)、新肝期30 min(T5)、240 min(T6)时采集静脉血样,测定血浆甘油三酯(TG)、总胆固醇(CH)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)浓度及AST、ALT活性,并计算各指标的相对基线变化值.结果 与L组比较,M组T4-6时△TG降低(P＜0.05),△CH、△HDL-C、LDL-C、△AST、△ALT差异无统计学意义(P＞0.05).两组间血浆TG、CH、HDL-C、LDL-C浓度、AST和ALT活性比较差异无统计学意义(P＞0.05).结论 异丙酚中/长链甘油三酯注射液和异丙酚长链甘油三酯注射液虽然对肝功能影响无差异,但异丙酚中/长链甘油三酯注射液对血脂影响小,更有益于肝移植术患者.

Abstract：

Objective To investigate the effect of different excipients of propofol on blood lipids and liver function during orthotopic liver transplantation. Methods Forty ASA Ⅲ- Ⅳ patients aged 40-64 yr weighing 50-75 kg undergoing orthotopic liver transplantation were randomly divided into 2 groups ( n = 20 each): propofol medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (group M) and propofol LCT group (group L). Anesthesia was induced with penehyclidine 1 mg, midazolam 0.04-0.06 mg/kg, sufentanil 0.6-0.8 μg/kg and propofol 1.5-2.0 mg/kg. Tracheal intubation was facilitated with vecuronium 0.10-0.15 mg/kg. The patients were mechanically ventilated. Anesthesia was maintained with 1%-2% isoflurane, continuous infusion of propofol blood samples were collected after admission into the operation room (T1), before skin incision (T2), at the end of pre-anhepatic phase (T3), at the end of anhepatic phase (T4) and 30 and 240 min of neohepatic phase (T5, T6 )for determination of plasma concentrations of triglyceride (TG), total cholesterol (CH), high-density-lipoproteincholesterol (HDL-C), low density-lipoprotein-cholesterol (LDL-C), and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The changes in parameters from baseline values were calculated. Results Compared with group L, △TG was significant1y decreased at T4-6 in group M ( P ＜ 0.05 ) . There was no significant difference in △CH, △HDL-C, △LDL-C, △AST and △ALT,plasma concentrations of TG,CH, HDL-C and LDL-C,and activities of AST and ALT between the two groups ( P ＞ 0.05). Conclusion The effect of the two formulations of propofol on liver function is comparable. Propofol MCT/LCT exerts less effect on blood lipids during liver transplantation and is more suitable for this type of surgery.     

睡眠障碍患者血浆食欲素A对丙泊酚靶控输注效应室靶浓度的影响

目的观察睡眠障碍患者接受丙泊酚全身麻醉靶控输注效应室靶浓度(target concentration of effect-site,Ce)的变化,探讨血浆食欲素A与丙泊酚Ce的相关性。方法选取2018年6-12月择期手术患者66例,男31例,女35例,年龄40~60岁,ASAⅠ或Ⅱ级,于术前1 d根据PSQI量表得分分为两组:睡眠障碍组(SD组,n=32)和正常睡眠组(NS组,n=34)。入室后常规心电监护、面罩吸氧,留取静脉血检测血浆食欲素A浓度。在BIS监测下进行丙泊酚阶梯式血浆靶控输注,初始血浆靶浓度(target concentration of plasma,Cp)设定为1.0μg/ml,当Ce达到1.0μg/ml后,每30秒以0.2μg/ml递增Cp,并呼唤患者姓名直至意识消失。继续每30秒以0.2μg/ml递增Cp直至BIS<60稳定30 s以上,停止增加Ce稳定5 min后停止输注。停药后每30秒轻拍并呼唤患者姓名直至有反应。记录患者意识消失时丙泊酚Ce(Ce1)、BIS<60稳定30 s以上对应的丙泊酚Ce(Ce2)和苏醒时丙泊酚Ce(Ce3)。采用Pearson检验分析Ce与食欲素A浓度的相关性。结果与NS组比较,SD组丙泊酚Ce1[(2.53±0.26)μg/ml vs(2.38±0.30)μg/ml]、Ce2[(3.30±0.35)μg/ml vs(3.15±0.28)μg/ml]和Ce3[(1.76±0.38)vs(1.59±0.26)μg/ml]浓度均明显升高(P<0.05),血浆食欲素A浓度明显升高[(75.09±16.50)pg/ml vs(39.96±13.78)pg/ml,P<0.05]。NS组血浆食欲素A浓度与Ce1、Ce2、Ce3均存在中度正相关(r=0.636,0.578,0.344),SD组血浆食欲素A浓度与Ce1、Ce2、Ce3也存在中度正相关(r=0.635,0.415,0.467)(P<0.05)。结论术前合并睡眠障碍患者接受丙泊酚全身麻醉需要更高的效应室靶浓度,潜在的机制可能与血浆食欲素A浓度升高有关。     

不同年龄患者靶控输注丙泊酚的血药浓度与脑电双频指数值的相关性

目的研究靶控输注丙泊酚镇静时不同年龄患者的丙泊酚血药浓度与脑电双频指数(BIS)值的相关性。方法60例上腹部手术患者随机分为青壮年组(28~45岁,n=30)和老年组(65~80岁,n=30)。全麻诱导设定丙泊酚血浆靶控浓度3mg/L、雷米芬太尼7μg/L。意识消失后给予维库溴铵0.1mg/kg气管插管后行机械通气。术中雷米芬太尼靶控浓度维持不变,气管插后丙泊酚的靶控浓度降至2.5mg/L,术中调节丙泊酚的量使BIS值维持在45~55,并在调节后5min测定丙泊酚血药浓度。结果两组患者一般情况差异无统计学意义。青壮年组实测丙泊酚血药浓度与BIS值无相关性,老年组呈高度负相关(r=-0.64816)。结论青壮年组丙泊酚实测血药浓度与BIS值无相关性,而老年组有明显的负相关,说明在老年患者实测血药浓度可以评估镇静深度。