异丙酚脑摄取研究

异丙酚是高脂溶性的新型静脉麻醉药，其麻醉作用靶器官为大脑。本文综述研究异丙酚的脑摄取理论及有关的动物和人体研究结果，进一步其脑摄取与药效学的关系。     

静脉注射异丙酚对内毒素血症大鼠心功能的影响

目的 评价静脉注射异丙酚对内毒素血症大鼠心功能的影响.方法 健康雄性Wistar大鼠32只,体重250～300g,随机分为4组(n=8):对照组(C组)、内毒素组(L组)、内毒素+异丙酚组(L+P组)及异丙酚组(P组).L组、L+P组静脉注射内毒素10g/kg,C组和P组注射等量生理盐水,注射后60min,L+P组和P组静脉注射异丙酚10mg/kg,C组和L组给予等量生理盐水,30min后下腔静脉取血并处死大鼠.于注射内毒素前、注射内毒素后30、60、61、62、63、65、70、80及90min时记录心率(HR)、左室收缩压(LVSP)及左室内压力变化最大速率(±dp/dtmax);并计算L+P组和P组心功能指标变化幅度,测定血清肿瘤坏死因子-α(TNF-α)浓度.结果 与注射内毒素前比较,L组注射内毒素后心功能指标均降低,L+P组注射异丙酚后HR、LVSP、±dp/dtmax降低,P组注射异丙酚后HR、LVSP、±dp/dtmax降低(P＜0.05);与注射内毒素后60min时比较,L+P组注射异丙酚后HR、LVSP、-dp/dtmax降低,+dp/dtmax升高(P＜0.05).与L组比较,L+P组注射异丙酚后HR、LVSP、-dp/dtmax降低(P＜0.05).与P组比较,L+P组注射异丙酚后HR、LVSP、±dp/dtmax变化幅度减小(P＜0.05).与C组比较,L组、L+P组TNF-α浓度升高(P＜0.05);L+P组低于L组(P＜0.05).结论 静脉注射异丙酚不加重内毒血症大鼠心功能的抑制.     

异丙酚脑摄取研究

异丙酚是高脂溶性的新型静脉麻醉药,其麻醉作用靶器官为大脑。本文综述研究异丙酚的脑摄取理论及有关的动物和人体研究结果,进一步其脑摄取与药效学的关系。     

恒速静脉输注异丙酚时脑摄取的研究

目的研究恒速静脉输注异丙酚时脑摄取与输注速率、输注时间的关系.方法14例ASAⅠ～Ⅱ级择期手术患者,随机分为A、B两组,恒速静脉输注异丙酚的速率分别为6、12mg.kg-1@h-1,持续30～35min.于给药后不同时点同步采取桡动脉及颈内静脉球部血样,以高效液相色谱-荧光法检测异丙酚的血药浓度.结果恒速静脉输注异丙酚起始15min,两组桡动脉血药浓度(Ca)随时间逐渐升高,15min后维持恒定不变;A组颈内静脉球部血药浓度(Cijbv)静注异丙酚30min期间随时间升高,但低于相应Ca(P＜0.05),30～35min时维持恒定,并接近于Ca;而B组Cijbv静注异丙酚20min期间随时间升高,但低于相应Ca(P＜0.05),20～30min时维持恒定,并接近于Ca;脑摄取达稳态前各时点累积桡动脉、颈内静脉球部血药浓度-时间曲线下累积面积差(AUCa-v)组间差异显著(P＜0.05).结论恒速静脉输注异丙酚麻醉脑摄取达平衡前,异丙酚摄取量呈速率和时间依赖性.异丙酚脑摄取动态平衡滞后于动脉血药浓度的平衡.人脑对异丙酚基本无代谢或代谢极少.     

芬太尼和利多卡因对异丙酚静脉麻醉作用的比较

目的：比较芬太尼和利多卡因对异丙酚催眠作用的影响。方法：160例择期手术病人分为三组，分别采用靶控输注异丙酚（P组，n=30）、异丙酚－芬太尼（PF组,n=52）或异丙酚－利多止因（PL组，n=78）全静脉麻醉。芬太尼和利多卡因目标血药浓度分别为2μg/L、4mg/L。术中行无创血液动力学监测和脑电监测，记录麻醉剂用量及麻醉恢复情况。应用高效液相色谱测定异丙酚、利多卡因血药浓度，放免法测定芬太尼血药浓度。结果：与P组相比，PF组、PL组麻醉诱导意识消失时异丙酚用量ED90、ED50无显著性差异，意识消失时异丙酚血药浓度Cp90和Cp50均明显降低，异丙酚麻醉维持用量分别降低29．9％、23．9％（P＜0．05）。PF组气管插管、切皮前后收缩压（SP）、舒张压（DP）无明显改变，P组、PL组升高，以P组明显（P＜0．05）。三组异丙酚、芬太尼和利多卡因预测误差（PE）、预测误差绝对值的中位数（MDAPE）和预测误差的中位数（MDPE）无明显差异。结论：芬太尼、利多卡因对异丙酚催眠剂量－反应曲线表现为相加作用，浓度－反应曲线表现为协同作用，此差异可能与药代动力学影响有关。芬太尼、利多卡因能减少异丙酚用量，抑制气管插管、切皮的血液动力学反应，以芬太尼作用明显。     

犬颈内动脉和股静脉输注异丙酚药效学的比较

目的比较犬颈内动脉和股静脉输注异丙酚的药效学。方法健康杂种犬8条,每条犬间隔24 h,随机行颈内动脉或股静脉输注异丙酚96 mg^-1·kg^-1·h^-1,直至脑电静息,维持CSI 0～5 60 min停药。于麻醉诱导前（基础值）、气管插管前即刻（意识消失时）、脑电静息10 s、30 min、60 min时、CSI恢复至基础值时和犬苏醒时,记录血液动力学以及呼吸功能指标及相应的异丙酚用量。结果意识消失、CSI 0～3持续10 s、30 min和60 min时,颈内动脉输注异丙酚用量相当于静脉途径给药量的25．4％～30．1％。在脑电静息各时点,颈内动脉输注异丙酚时血液动力学以及呼吸功能指标维持稳定,而静脉给药时明显波动。达脑电静息所用时间和停药后苏醒时间,颈内动脉给药明显短于静脉给药。结论与股静脉给药相比,颈内动脉输注异丙酚麻醉起效快、麻醉效力显著提高、生命体征维持稳定,且麻醉恢复迅速。     

异丙酚对脑创伤家兔血/脑脊液乳酸和葡萄糖含量的影响

目的探讨异丙酚对家兔脑创伤的影响.方法用90只健康新西兰兔(雄性)建立稳定的脑创伤模型.1.将20只家兔随机分为对照组噻胺酮1mg/kg(n=10)与异丙酚(Pro)组噻胺酮1mg/kg+异丙酚30mg@kg-1@h-1.麻醉动物,维持30min(n=10).分别于伤前、伤后4h、24h、48h、72h、1w采集外周静静脉血与脑脊液,测定血/脑脊液乳酸(LA)和葡萄糖(Glu)含量;2.将70只家兔随机分为对照组,伤后24h组、72h组和1w组(输注生理盐水)以及伤后异丙酚治疗24h组、72h组和1w组(异丙酚30mg@kg-1@h-1.静脉滴注,每次维持30min,每天一次)(n=10),分别取脑组织做NSE免疫组织化学染色和病理检查.结果1.两组伤后血/脑脊液LA水平显著高于伤前(P＜0.01),但异丙酚组明显低于同时段对照组水平(P＜0.05或0.01);对照组伤后24h、48h和72h血/脑脊液Glu明显低于伤前,异丙酚组脑脊液Glu仅在伤后24h降低(P＜0.05或0.01),异丙酚组血Glu在伤后4h、24h与对照组比较有明显差异(P＜0.05).2.脑组织NSE免疫组织化学染色和病理检查对照组损伤区及其周围脑组织伤后24h起可见脑组织出血,退行性变,胶质细胞减少,部分区域细胞可见空泡变性;伤后72h可见较多嗜中性细胞浸润;伤后1w脑间质水肿,胶质细胞明显增生,神经元细胞未见NSE表达.异丙酚组在受伤脑组织或其周围损伤明显轻于对照组,部分神经元细胞NSE表达明显.结论异丙酚能够降低脑创伤后血/脑脊液LA含量,对创伤性脑损伤具有一定的保护作用.     

异丙酚脑保护研究进展

许多研究证实,异丙酚能够对缺血性神经损伤提供保护效应。介绍了近年来异丙酚在这方面的研究进展及其产生脑保护的相关机制,并探讨了实现脑保护效应的合适异丙酚浓度以及脑保护临床研究所面临的问题。     

异丙酚脑保护研究进展

许多研究证实，异丙酚能够对缺血性神经损伤提供保护效应。介绍了近年来异丙酚在这方面的研究进展及其产生脑保护的相关机制，并探讨了实现脑保护效应的合适异丙酚浓度以及脑保护临床研究所面临的问题。     

地氟醚复合异丙酚控制性降压对脑氧和糖代谢的影响

目的 通过观察地氟醚复合异丙酚控制性降压期间颅脑手术病人脑动-静脉血氧差和血糖差的变化,探讨其对脑代谢的影响。方法 随机选择18例ASA分级为Ⅰ—Ⅱ级的择期脑瘤手术病人,术中增加地氟醚吸入浓度和异丙酚输注速度使平均动脉压较术前下降30％～40％,维持30～45min。分别测定降压前、中、后,脑动-静脉血氧差和血糖差等指标的变化。结果 与降压前比较,降压期间D（a-jv）O2和CERO2减少（P<0.05）,SjvO2、BGja、BGjv增加（P<0.05）。CaO2、CjvO2、pHa、PHjv、PaO2、PjvO2、SaO2、aHCO3、jvHCO3及D（a-jv）BG等指标降压前、中、后各时相比较,差异无显著性（P>0.05）。结论 地氟醚复合异丙酚控制性降压期间脑氧代谢降低,脑糖代谢无明显变化。     

雷米芬太尼复合丙泊酚静脉麻醉的临床应用

目的观察雷米芬太尼复合丙泊酚静脉麻醉的效果。方法全身麻醉下腰椎手术患者60例,随机均分为雷米芬太尼复合丙泊酚静脉麻醉组(Ⅰ组)和静吸复合麻醉组(Ⅱ组)。雷米芬太尼和丙泊酚的负荷量分别为1μg/kg和1mg/kg,雷米芬太尼以0.5μg·kg-1·min-1速率输注。麻醉中通过增减雷米芬太尼0.1μg·kg-1·min-1输注速率调整麻醉深度。丙泊酚按5∶4∶3方案输注,即5mg·kg-1·h-1输注10min,4mg·kg-1·h-1输注10min,20min后3mg·kg-1·h-1恒速输注。观察两组气管插管反应、麻醉效果、苏醒质量。结果两组麻醉效果相同,均可抑制气管插管反应(P<0.01),且Ⅰ组较Ⅱ组明显(P<0.05)。Ⅰ组苏醒质量较Ⅱ组好(P<0.01),不良反应较Ⅱ组高(P<0.01),术中无知晓。结论雷米芬太尼复合丙泊酚用两个注射泵静脉麻醉,采用负荷量加两种以上速率输注全凭静脉麻醉简便易行。     

颈内动脉输注异丙酚对胶质瘤切除术患者的脑保护作用

目的 探讨颈内动脉输注异丙酚对胶质瘤切除术患者的脑保护作用.方法 择期胶质瘤切除术患者40例和立体定向胶质瘤活检术患者20例,年龄40～64岁,体重48～73 kg.采用随机数字表法,将拟行胶质瘤切除术患者随机分为2组(n=20):颈内动脉给药组(IA组)和静脉给药组(Ⅳ组).拟行立体定向胶质瘤活检术患者为对照组(C组),采用2%利多卡因15～20 ml术野局部浸润麻醉.IA组和Ⅳ组采用异丙酚-瑞芬太尼-罗库溴铵行麻醉诱导.IA组麻醉诱导后行颈内动脉穿刺置管,颈内动脉靶控输注异丙酚.两组术中调整异丙酚和瑞芬太尼靶浓度,维持BIS值40～60.间断静脉注射罗库溴铵.术中取胶质瘤组织标本,采用免疫组化法测定胶质瘤组织水通道蛋白1(AQP1)和AQP4表达.于麻醉诱导前(T1)、切皮时(T2)、术毕时(T3)、拔除气管导管时(T4)记录MAP和HR;记录手术时间、麻醉用药情况.结果 与T1时比较,Ⅳ组T2,3时MAP和HR降低(P＜0.05),IA组各时点MAP和HR比较差异无统计学意义(P＞0.05).与IA组比较,Ⅳ组MAP和HR降低(P＜0.05).与C组比较,IA组和Ⅳ组AQP1和AQP4表达下调(P＜0.05).与Ⅳ组比较,IA组异丙酚用量减少(P＜0.05),AQP1和AQP4表达、瑞芬太尼和罗库溴铵用量、手术时间比较差异无统计学意义(P＞0.05).结论 与静脉输注异丙酚相比,颈内动脉途径给药不仅可减少胶质瘤切除术患者异丙酚的用量,而且对其脑保护作用没有影响.

Abstract：

Objective To investigate the cerebral protective effect of intracarotid infusion of propofol in patients undergoing resection of cerebral gliomas. Methods Sixty ASA Ⅰ- Ⅲ patients with cerebral glioma aged 40-64 yr weighing 48-73 kg were enrolled in this study. Forty patients undergoing resection of glioma under general anesthesia were randomly divided into 2 groups ( n = 20 each): intracarotid propofol group (group IA ) and intravenous propofol group (group Ⅳ). Twenty patients undergoing biopsy of glioma under local infiltration anesthesia with 2% lidocaine 15-20 md served as control group (group C). In IA and Ⅳ groups anesthesia was induced with TCI of propofol and remifentanil. Tracheal intubation was facilitated with rocuronium 0.6 mg/kg. The patients were mechanically ventilated. PErCO2 was maintained at 35-45 mm Hg. Anesthesia was maintained with TCI of propofol and remifentanil and intermittent iv boluses of rocuronium. In group IA internal carotid artery was cannulated after induction of anesthesia and propofol was administered by TCI via carotid artery while remifentanil was administered by TCI via peripheral vein. BIS was maintained at 40-60 during operation. ECG, MAP, HR, SpO2, PETCO2 and BIS were continuously monitored. MAP and HR were recorded before induction of anesthesia (T1) ,during skin incision (T2 ), at the end of operation (T3), during extubation ( T4 ). The glioma specimens were obtained for microscopic examination and determination of aquaporin 1 and aquaporin 4 ( AQP1, AQP4) expression by immunohistochemistry. Results MAP and HR were significantly decreased at T2 and T3 as compared with the baseline at T1 in group Ⅳ ( P ＜ 0.05), while there was no significant change in MAP and HR after induction of anesthesia in group IA ( P ＞ 0.05). The expression of AQP1 and AQP4 was down-regulated in IA and Ⅳ groups compared with group C (P ＜0.05). The propofol consumption during anesthesia was significantly less in group IA than in group Ⅳ (P ＜0.05). There was no significant diffe-rence in AQP1 and AQP4 expression, the amount of remifentanil and recuronium consumed and duration of operation betweenIA and Ⅳ groups ( P ＞ 0.05). Concltsion Intracarotid propofol can decrease the amount of propofol needed for maintenance of anesthesia as compared with intravenous administration and attenuate brain edema,indicating cerebral protective effect.     

Maturational pharmacokinetics of single intravenous bolus of propofol

BACKGROUND: Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children. METHODS: Newly collected observations following intravenous bolus administration of propofol in preterm and term neonates (n = 9) were compared with earlier reported pharmacokinetic estimates in toddlers and young children. Data are reported by median and range. Mann-Whitney U-test or correlation was used to analyze differences in pharmacokinetic findings between neonates, toddlers and young children. RESULTS: Concentration-time profiles obtained were interpreted by two-stage analysis as a three compartment open model in nine neonates with a median weight of 2.51 (range 0.91-3.8) kg and a median postmenstrual age (PMA) of 36 (range 27-43) weeks. Median clearance (CL) was 13.6 (range 3.7-78.2) ml.min(-1).kg(-1) and median apparent volume of distribution at steady state (V(ss)) was 3.7 (1.33-7.96) l.kg(-1). Following allometric scaling and standardization to 70 kg, median CL was 442 (range 97-2184) ml.min(-1).70 kg(-1). Compared with earlier reported observations in toddlers and children, median clearance (kg.min(-1)) was significantly lower in neonates (P < 0.01) and these differences remained significant after allometric scaling (70 kg.min(-1)) while V(ss) (l.kg(-1)) was significantly lower in neonates (P < 0.01). CONCLUSIONS: Propofol disposition is significantly different in neonates compared with toddlers and young children, reflecting both ontogeny and differences in body composition. Based on the reduced clearance of propofol, a longer recovery time is more likely to occur in neonates.     

芬太尼对异丙酚静脉麻醉药代动力学和药效学的影响

目的 探讨芬太尼对异丙酚静脉麻醉药代动力学和药效学的影响。方法 ２０例开胸手术患者随机分为异丙酚复合芬太尼静脉麻醉组（Ａ组,ｎ＝１０）异丙酚静脉麻醉复合胸段硬膜外阻滞组（Ｂ组,ｎ＝１０）。测定术中和术后病人异丙酚血清浓度。记录意识消失,术后睁眼和定向时间及术后行为评分。结果 Ａ组消除相药代动力学参数Ｔ１／２βＭＲＴ,ＡＵＣ显著高于Ｂ组（Ｐ〈０．０５或０．０１）,Ａ组ＣＬ显著低于Ｂ组（Ｐ〈０．０１）