异丙酚靶控输注靶浓度与实测浓度的差值分析及系统性能评价

目的 分析靶控输注(TCI)异丙酚靶血浆药物浓度与实测浓度的差值,评价TCI系统性能。方法 61例下腹部择期手术患者,ASA Ⅰ～Ⅱ级。微机连接佳士比3500微量泵,选用Stelpump软件内嵌Tackley药代动力学参数。恒定靶血浆药物浓度(3μg·ml~(-1)变速输注持续1h,间断采集动脉血持续1.5h。应用气相色谱-质谱(GC-MS)法测定异丙酚血浆药物浓度。结果 异丙酚输注期间各时点的实测浓度均明显高于靶浓度,停止输注后各时点的实测浓度均明显低于靶浓度(P<0.05)。输注期间TCI系统偏离度(MDPE)为30.02％、精确度(MDAPE)为31.55％、摆动度(wobble)为21.42％、分散度(divergence)为-0.51％/h。停止输注后TCI系统偏离度为19.71％、精确度为21.63％、摆动度为13.29％、分散度为-0.26％/h。结论 国人应用TCI系统输注异丙酚,其靶血浆药物浓度与实测浓度差异明显。系统偏离度和精确度均大于TCI系统性能要求的范围,摆动度偏大。     

体外循环下异丙酚靶控输注系统的准确性

目的 评价体外循环下异丙酚靶控输注系统的准确性.方法 择期体外循环下行心脏瓣膜置换术患者20例,ASAⅡ或Ⅲ级,年龄25～64岁,体重50～70 kg.静脉注射咪达唑仑、芬太尼和维库溴铵行麻醉诱导,气管插管后机械通气.麻醉维持采用嵌入Tackley药代动力学参数的靶控输注系统输注异丙酚至术毕,血浆靶浓度为1μ/ml.于体外循环前(T1)、体外循环开始后1、5、10、20、40、60 min(T2-7)、体外循环结束后5、10 min(T8,9)时采集桡动脉血样3 ml,采用反相高效液相色谱法测定血浆异丙酚浓度,计算异丙酚靶控输注系统的偏离度、精确度、摆动度及分散度.结果 T1时异丙酚实测浓度高于血浆靶浓度(P<0.05),T2-4时异丙酚实测浓度与血浆靶浓度差异无统计学意义(P>0.05),T5-9时异丙酚实测浓度高于血浆靶浓度(P<0.05).异丙酚靶控输注系统的偏离度为21%、精确度为29%、摆动度为21%及分散度为-0.06%/h.结论 心脏手术患者体外循环时,采用嵌入Tackley药代动力学参数的异丙酚靶控输注系统的准确性超出临床可接受范围.     

小儿瑞芬太尼靶控输注系统的准确性

目的 评价小儿瑞芬太尼靶控输注(TCI)系统的准确性.方法 择期行五官科或泌尿科手术小儿30例,年龄3～12岁,体重10～40 kg,采用随机数字表法,将患儿随机分为2 ng/ml瑞芬太尼组(Ⅰ组)和4 ng/ml瑞芬太尼组(Ⅱ组),每组15例.Ⅰ组和Ⅱ组采用内嵌Minto药代动力学参数的瑞芬太尼TCI系统输注瑞芬太尼,血浆靶浓度分别为2、4 ng/ml,静脉注射异丙酚2 mg/kg,待患儿意识消失后静脉注射维库溴铵0.1 mg/kg诱导气管插管后行机械通气.两组瑞芬太尼血浆靶浓度维持不变,调节异丙酚输注速率,维持脑电双频谱指数45～65或听觉诱发电位指数＜30,间断静脉注射维库溴铵维持肌松.于TCI瑞芬太尼开始后5、10、20、30、40、50、60 min时抽取桡动脉血样,采用高效液相色谱法测定瑞芬太尼血药浓度,计算TCI系统的偏离度、精确度和摆动度.结果 与血浆靶浓度比较,两组瑞芬太尼实测浓度均升高(P＜0.05);Ⅰ组TCI系统的偏离度、精确度和摆动度分别为20.0%、30.0%和25.0%,Ⅱ组分别为17.5%、17.5%和12.5%,与Ⅰ组比较,Ⅱ组TCI系统的精确度和摆动度降低(P＜0.05),偏离度差异无统计学意义(P＞0.05).结论 3～12岁小儿采用内嵌Minto药代动力学参数的TCI系统输注瑞芬太尼时准确性不高.     

靶控输注丙泊酚用于肥胖患者结肠镜检查时的半数有效血浆靶浓度

目的测定肥胖患者结肠镜检查时复合芬太尼麻醉下TCI丙泊酚的半数有效血浆靶浓度(Cp50)。方法选择需行结肠镜检查患者,男27例,女28例,18.5kg/m2≤BMI24.0kg/m2为正常体重组(N组);BMI≥28.0kg/m2为肥胖组(O组)。两组患者的初始血浆靶浓度均设为3.0μg/ml。入选样本从有体动的上一例患者开始计算,其后各例患者血浆靶浓度根据手术过程中有无体动进行调整,浓度变化间隔为0.5μg/ml,按序贯法进行研究,计算丙泊酚的Cp50及其95%可信区间(CI)。结果复合芬太尼1.0μg/kg时,N组丙泊酚的Cp50及95%CI为2.95(2.68~3.24)μg/ml;O组为2.83(2.62~3.05)μg/ml。结论 TCI丙泊酚复合1.0μg/kg芬太尼用于肥胖患者结肠镜检查时的Cp50为2.83μg/ml,肥胖患者TCI丙泊酚意识消失时的Cp50降低。     

近日节律对靶控输注依托咪酯镇静效应的影响

目的通过上午、下午靶控输注(TCI)依托咪酯麻醉诱导时依托咪酯血浆靶浓度测定,探讨近日节律对TCI依托咪酯镇静效应的影响。方法选择术前未用药患者60例,ASAⅠ或Ⅱ级,随机分为上午组(8:00~10:00,A组,30例)和下午组(14:00~16:00,P组,30例)TCI依托咪酯进行全麻诱导。以血浆靶浓度150 ng/ml为起点,达到预期的血浆靶浓度5 min后,每次增加50 ng/ml,直到患者意识消失(睫毛反射消失及OAA/S评分≤3分,且BIS≤50)。记录BIS为50和意识消失时的依托咪酯血浆靶浓度。结果 BIS达50和意识消失时,两组患者HR、MAP、SpO2、BIS差异均无统计学意义。与P组比较,BIS达50和意识消失时,A组依托咪酯血浆靶浓度明显升高(P0.05)。结论近日节律对依托咪酯的镇静作用有影响,下午组TCI依托咪酯患者BIS达50和意识消失时所需血浆靶控浓度较低。     

手术患者内嵌Schnider药代动力参数异丙酚靶控输注系统准确性的评价

目的 评价手术患者内嵌Schnider药代动力参数异丙酚TCI系统的准确性.方法择期腹腔镜下妇科手术患者40例,ASA分级Ⅰ或Ⅱ级,年龄25～45岁,体重指数20～25 kg/m2.麻醉诱导:TCI异丙酚(血浆靶浓度3μg/ml)和瑞芬太尼(血浆靶浓度4 ng/ml),意识消失后静脉注射罗库溴铵0.6 mg/kg,气管内插管后行机械通气,调整通气参数,维持PETCO2 30～40mm Hg.麻醉维持:TCI瑞芬太尼(血浆靶浓度4 ng/ml),调节异丙酚血浆靶浓度3～5μg/ml,维持BIS值40～45,间断静脉注射阿曲库铵0.2 mg/kg.于建立气腹后15、30、45、60 min时采集静脉血样,采用高效液相色谱-荧光法测定异丙酚血药浓度,计算TCI系统的执行误差、偏离度、精确度、分散度和摆动度.结果 TCI系统的执行误差为21%(13%),偏离度为6.7%(37.4%),精确度为19%(18%),分散度为-0.65%/h(0.82%/h),摆动度为16.3%(15.2%).结论 手术患者内嵌Schnider药代动力参数异丙酚TCI系统的准确性较高,可满足临床要求.

Abstract：

Objective To evaluate the predictive performance of propofol target-controlled infusion (TCI) system incorporating the Schnider pharmacokinetic parameters in Chinese patients. Methods Forty ASA Ⅰ or Ⅱ patients, aged 25-45 yr, with body mass index 20-25 kg/m2 , scheduled for gynecological laparoscopic surgery un der general anesthesia, were enrolled in this study. Anesthesia was induced with TCI of propofol (target plasma concentration (Cp) 3 μg/ml) and remifentanil (Cp 4 ng/ml) . Propofol was infused by Orchestra TCI system incorporating the Schnider pharmacokinetic parameters. Tracheal intubation was facilitated with rocuronium 0.6 mg/kgafter the patients lost consciousness. The patients were mechanically ventilated. PETCO2 was maintained at 30-40 mm Hg. Anesthesia was maintained with TCI of remifentanil (Cp 4 ng/ml) and propofol (Cp 3-5 μg/ml) and intermittent iv boluses of atracurium 0.2 mg/kg. BIS value was maintained at 40-45. Venous blood samples were obtained at 15, 30, 45 and 60 min after pneumoperitoneum for measurement of blood propofol concentrations by high performance liquid chromatography with fluorescence detector. Performance error, median prediction performance error, median absolute performance error, wobble and divergence of propofol TCI system were calculated. Results The value for performance error was 21 % (13%), for median prediction performance error 6.7 % (37.4%),for median absolute performance error 19% (18%), for divergence - 0.65%/h (0.82%/h) and for wobble 16.3% (15.2% ) . Conclusion The accuracy of propofol TCI system incorporating the Schnider pharmacokinetic parameters is high in Chinese patients and its predictive performance is acceptable clinically.     

老年和成年患者依托咪酯诱导时雷米芬太尼抑制气管插管反应的半数有效血浆浓度

目的测定老年和成年患者依托咪酯诱导时雷米芬太尼抑制气管插管反应的半数有效血浆浓度(Cp50)。方法择期全麻手术患者40例,ASAⅠ或Ⅱ级,年龄19~80岁,体重指数20~30kg/m2,按年龄分为青壮年组(19~64岁)和老年组(65~80岁),每组20例。雷米芬太尼靶控输注5min后,静脉注射0.3mg/kg的依托咪酯,患者意识消失后给予罗库溴铵行气管插管。雷米芬太尼的血浆靶浓度按序贯法确定,相邻血浆靶浓度之间的比率为1.2。结果0.3mg/kg依托咪酯诱导时,老年组和青壮年组雷米芬太尼抑制气管插管的Cp50分别为4.11μg/L和3.37μg/L,95%可信区间分别为3.90~4.34μg/L和3.02~3.75μg/L。结论老年和青壮年患者在复合0.3mg/kg的依托咪酯行麻醉诱导时,雷米芬太尼抑制气管插管反应的Cp50分别为4.11g/L和3.37μg/L。     

瑞芬太尼靶控输注时靶浓度和实测血药浓度的差异-靶控输注系统的性能评价

目的比较瑞芬太尼血浆靶浓度(Cp)6、8 ng·ml-1 复合异丙酚靶控输注(TCI)时瑞芬太尼Cp和实测血药浓度(Cm)的差异,并评价思路高TCI-Ⅰ型系统(Minto药代动力学参数)的性能。方法择期行肺叶或肺段切除术病人36例,ASA Ⅰ或Ⅱ级,年龄40-60岁,体重50-70kg,随机分为2 组,组18例。麻醉诱导:Ⅰ、Ⅱ组瑞芬太尼血浆靶浓度分别为6、8 ng·ml-1,异丙酚效应室靶浓度为3 μg·ml-1,待病人意识消失后静脉注射维库溴铵0.1 mg·kg-1,3 min后行气管插管。麻醉维持:两组瑞芬太尼Cp保持不变,调节异丙酚靶浓度,维持脑电双频指数(BIS)45-55,间断静脉注射维库溴铵维持肌松。分别在瑞芬太尼TCI前及TCI 5、10、20、40、60、90、120 min时用高效液相色谱法测定瑞芬太尼Cm。采用执行误差(PE)、PE的中位数(MDPE)、PE绝对值的中位数(MDAPE)及摆动度评价TCI系统的性能。结果在TCI 5、10、20 min时,两组瑞芬太尼Cm均低于Cp(P<0.05)。Ⅰ、Ⅱ组瑞芬太尼总体血样瑞芬太尼Cm分别为5.1、6.9 ng·ml-1,均低于Cp(P<0.05)。Ⅰ、Ⅱ组MDPE、MDAPE、摆动度分别为-17.2%、29.6%、15.1%和-15.5%、27.8%、12.5%,组间比较差异无统计学意义(P>0.05)。结论瑞芬太尼Cp为6、8 ng·ml-1在国人TCI时,思路高TCI-Ⅰ型系统(Minto药代动力学参数)的精确度在临床可接受范围内,其Cm比Cp低约15%。     

靶控输注丙泊酚抑制吞咽反射的半数有效血浆靶浓度

目的 确定TCI丙泊酚时抑制吞咽反射的半数有效血浆靶浓度(Cp50).方法 选择25例鼻窦手术患者,ASA Ⅰ或Ⅱ级,TCI丙泊酚镇静,采用序贯法确定丙泊酚血浆靶浓度.在不同靶浓度下咽部注水诱发吞咽,观察是否出现吞咽动作.用Dixon序贯法公式计算吞咽抑制的Cp50及其95％可信区间(CI).结果 吞咽抑制的Cp50为2.4μg/ml,95％ CI为1.5～3.3 μg/ml.结论 TCI丙泊酚镇静抑制吞咽反射的Cp50为2.4 μg/ml,95％CI为1.5～3.3 μg/ml.     

靶控输注依托咪酯用于全身麻醉维持的可行性研究

目的 探讨靶控输注(TCI)依托咪酯用于全身麻醉维持的可行性.方法 择期全麻手术患者40例,随机分为两组.E组麻醉诱导时TCI依托咪酯和雷米芬太尼;P组TCI丙泊酚和雷米芬太尼.E组术中TCI依托咪酯1～2μg/ml和雷米芬太尼6 ng/ml维持BIS值40～60;P组术中TCI丙泊酚2～4 μg/ml和雷米芬太尼6 ng/ml维持BIS值40～60.检测围术期血糖、血浆皮质醇、醛同酮、促肾上腺皮质激素(ACTH)浓度.记录停药后患者苏醒时间,术后随访术中知晓.结果 两组术中血流动力学均维持稳定.E组术毕皮质醇浓度与术前相比明显降低(P<0.05),术后24 h基本恢复至术前水平,术后48 h较术前明显升高(P<0.05);术毕ACTH浓度与术前相比明显升高(P<0.05),术后24 h基本恢复至术前水平.而P组围术期血浆皮质醇和ACTH浓度均无明显改变.E组苏醒时间长于P组(P<0.05).结论 依托咪酯抑制肾上腺皮质功能,但在24 h内肾上腺皮质即恢复对促肾上腺皮质激素的反应.TCI依托咪酯复合雷米芬太尼可安全用于无肾上腺皮质功能低下患者的全凭静脉麻醉.     

急性等容血液稀释对靶控输注异丙酚血药浓度及系统性能的影响

目的探讨急性等容血液稀释对靶控输注（TCI）异丙酚血药浓度及系统性能的影响。方法择期骨科手术患者35例,ASAⅠ级或Ⅱ级,随机分为稀释组（n=17）和对照组（n=18）。稀释组在麻醉诱导插管后,实施急性等容血液稀释,达稀释目标（Hct 0．25～0．27）10 min后,TCI异丙酚;对照组不行血液稀释,直接TCI异丙酚。设定血浆靶浓度3μg/ml,TCI异丙酚60 min,间断采血180 min,用气相色谱-质谱法测定异丙酚血药浓度并评价TCI系统的性能。结果稀释组的实测血药浓度低于对照组40．8％～73．1％（P＜0．05）。稀释组TCI系统偏离度、精确度和摆动度分别为-8．83％、22．98％和22．12％。结论急性等容血液稀释降低了异丙酚TCI的实测血药浓度,优化了TCI的系统性能。     

丙泊酚靶控输注和异氟醚麻醉对罗库溴铵药效学的影响

目的比较丙泊酚靶控输注（TCI）复合雷米芬太尼全凭静脉麻醉和异氟醚复合雷米芬太尼麻醉对单次插管剂量罗库溴铵肌松效应的影响。方法ASAⅠ或Ⅱ级的择期全麻患者48例，随机均分为丙泊酚（P）组和异氟醚（I）组。麻醉诱导后予0.6mg／kg的罗库溴铵插管；P组和I组麻醉维持分别采用丙泊酚TCI-泵注雷米芬太尼和吸入1 MAC异氟醚-泵注雷米芬太尼。监测脑电双频指数（BIS），使用加速度肌松监测仪观察拇内收肌的收缩反应，记录罗库溴铵的起效时间、无反应时间、肌松维持时间及恢复指数等指标。结果两组之间肌松起效时间、无反应时间及T1 25％时间差异无统计学意义，I组25％四个成串刺激比（TOFr）及恢复指数都比P组明显延长（P〈0．05）。结论单次插管剂量的罗库溴铵在丙泊酚TCI-泵注雷米芬太尼麻醉下肌松维持及恢复无明显变化，而在吸入1 MAC异氟醚-泵注雷米芬太尼麻醉下恢复时间明显延长。     

Target controlled infusion (TCI): applications of the "TCI visual" program in anesthesia and sedation with propofol

BACKGROUND: Systems for Target Controlled Infusion accepting not only patient' data, like Diprifusor, but also a pharmacokinetic model have not been available in Italy in the last years. Therefore a program which controls a Pilot Anesthesia Vial pump and accepts any pharmacokinetic model was developed and applied to propofol infusion for anaesthesia and sedation. METHODS: Two versions of the Visual TCI program have been developed. The first, at intervals, supplies the anaesthetist with the values for the pump; the second directly interacts with the pump. The program also supplies the anaesthetist with the current amount of drug in each compartment and with the estimated awakening time. DESIGN: preliminary prospective study. SETTING: operatory theatre and Intensive Care Unit in a University Hospital. Patients: 6 patients undergoing total intravenous anaesthesia with propofol and fentanyl for abdominal surgery; 6 patients undergoing sedation with propofol in an Intensive Care Unit (the first 4-hour period was taken into account). Interventions: propofol infusion was regulated by the Visual TCI program. The first version was employed in three patients of each group and the second one in the others. Hypo- and hypertensive episodes (systolic pressure less than 80 mmHg or higher than basal value plus 25%) were recorded during anaesthesia and sedation. Propofol concentration was measured in plasma three times at defined intervals and per cent differences between measured and computer-calculated values (Predictive error, PE) were calculated. RESULTS: No hypo- or hypertensive episodes were recorded. PE was 27.4 +/- 17.9%. CONCLUSIONS: The program was easily employed, caused no inconvenience, and its use was associated with a remarkable cardiovascular stability. PE distribution was acceptable on the ground of the criteria reported in the literature. The program can be applied to drugs other than propofol, with both two and three compartment pharmacokinetic models and the anaesthetist can choose the most suitable model for the patient.     

Target controlled infusion: TCI

Progress in computing technology has allowed the development of target controlled infusion devices, with drugs delivered to achieve specific predicted target blood drug concentrations. Target controlled infusion (TCI) system has been developed as a standardised infusion system for the administration of opioids, propofol and other anaesthetics by target controlled infusion. A set of pharmacokinetic parameters has been selected using computer simulation of a known infusion scheme. The selected model is incorporated into a computer-compatible infusion pump. Clinical trials with such systems have provided appropriate target concentrations for the administration of target controlled infusion of anaesthetic drugs. The technique of TCI strongly influences the development of intravenous anaesthesia and opens a scenario of new and exciting applications in peri-operative anaesthetic management. The launch of 'Diprifusor' as the first commercially available TCI system for propofol was the cornerstone of a successful research period within the last decade, which evaluated the pharmacokinetic foundations of computer assisted intravenous drug delivery. Nowadays TCI technology is becoming a part of routine anaesthesia technique for the practitioner rather than a research tool for specialists and those who are enthusiasts of intravenous anaesthesia. Besides clinical application in anaesthesia, target controlled systems will play a significant role as research tools in the evaluation of drug interactions in anaesthesia and in the development of new control techniques for the administration of sedative and analgesic drugs in the peri-operative period.     

雷米芬太尼用于胆囊腹腔镜手术麻醉

目的评价雷米芬太尼靶控输注（TCI）全凭静脉麻醉（TIVA）的诱导和术后苏醒过程。方法ASAⅠ～Ⅱ级择期行胆囊腹腔镜切除手术病人40例,随机分为芬太尼（F组）和雷米芬太尼（RF组）两组,每组20例。观察麻醉诱导气管插管及拔管期的SBP、DBP、HR、术中血液动力学变化;术毕停药后病人自主呼吸恢复时间、呼之睁眼时间、拔管时间、离开恢复室时间及疼痛状况、恶心呕吐等不良反应。结果在插管后即刻、插管后5minRF组SBP、DBP、HR的变化均明显小于F组（JP〈0．01）;在切皮、麻醉维持期间两组病人血液动力学变化基本相似。两组病人从手术结束到呼之睁眼和拔除气管导管的时间及血管活性药物的用量基本相似。RF组术后疼痛的例数明显多于F组（P〈0．05）。结论依托咪酯和雷米芬太尼TCI TIVA的诱导更加平稳,苏醒质量高。但由于雷米芬太尼消除半衰期短,术后镇痛应及时建立。