Setting targets for sedation with a target-controlled propofol infusion

We studied 30 unpremedicated patients undergoing muscle biopsy under femoral nerve block to determine sedation levels reached with a Diprifusor target-controlled propofol infusion, in order to establish the equivalent of the ED50 for different levels of depth of sedation. Infusion was started at 0.8 microg x ml(-1) and altered by increments of 0.1 microg x ml(-1) after equilibrium between target and calculated concentrations, until the desired level of sedation was reached. The ED50 target propofol concentrations for sedation at sedation levels 2 (drowsy), 3 (drowsy, responds to verbal stimulation) and 4 (responsive to physical stimulation only) were 1.0 microg x ml(-1), 1.6 microg x ml(-1) and 2.1 microg x ml(-1), respectively. At sedation level 3, several patients exhibited spontaneous movement, hindering surgery. Oxygen supplementation is recommended for sedation at level 4.     

A comparison of anaesthesia using remifentanil combined with either isoflurane, enflurane or propofol in patients undergoing gynaecological laparoscopy, varicose vein or arthroscopic surgery

BACKGROUND: Anaesthesia comprising remifentanil plus isoflurane, enflurane or propofol was randomly evaluated in 285, 285 and 284 patients, respectively, undergoing short-procedure surgery. METHODS: Anaesthesia was induced with propofol (0.5 mg x kg(-1) and 10 mg x 10 s(-1)), and a remifentanil bolus (1 microg x kg(-1)) and infusion at 0.5 microg x g(-1) x min(-1). Five minutes after intubation, remifentanil infusion was halved and 0.5 MAC of isoflurane or enflurane, or propofol at 100 microg x kg(-1) x min(-1) were started and titrated for maintenance. RESULTS: Patient demography and anaesthesia duration were similar between the groups. Surgery was performed as daycases (52%) or inpatients (48%). The median times (5-7 min) to extubation and postoperative recovery were similar between the groups. Responses to tracheal intubation (15% vs 8%) and skin incision (13% vs 7%) were significantly greater in the total intravenous anaesthesia (TIVA) group (P<0.05). Fewer patients given remifentanil and isoflurane (21%) or enflurane (19%) experienced > or =1 intraoperative stress response compared to the TIVA group (28%) (P<0.05). Median times to qualification for and actual recovery room discharge were 0.5-0.6 h and 1.1-1.2 h, respectively. The most common remifentanil-related symptoms were muscle rigidity (6-7%) at induction, hypotension (3-5%) and bradycardia (1-4%) intraoperatively and, shivering (6-7%), nausea and vomiting postoperatively. Nausea (7%) and vomiting (3%) were significantly lower with TIVA compared with inhaled anaesthetic groups (14-15% and 6-8%, respectively; P<0.05). CONCLUSION: Anaesthesia combining remifentanil with volatile hypnotics or TIVA with propofol was effective and well tolerated. Times of extubation, postanaesthesia recovery and recovery room discharge were rapid, consistent and similar for all three regimens.     

The effect of two low-dose propofol infusions on the relationship between six-pulse transcranial electrical stimulation and the evoked lower extremity muscle response

BACKGROUND: Transcranial stimulation of the motor cortex using high-voltage electrical stimuli given in train is a method of monitoring the integrity of the motor pathways during thoracoabdominal aortic aneurysm surgery. The purpose of this study was to assess the relationship between the stimulus intensity and the corresponding amplitude of the myogenic motor evoked potential (tcMEP) in response to six-pulse transcranial electrical stimulation during two levels of low-dose propofol infusion and stable fentanyl/nitrous oxide anaesthesia. METHODS: Nine patients (37-78 yr) scheduled to undergo surgery on the thoracoabdominal aorta were studied. After achieving a stable anaesthetic state the output voltage was decreased with 50 V intervals from 350 V to 200 V during a target propofol infusion aimed at a plasma steady-state concentration of 0.7 microg x ml(-1) and increased with 50 V intervals from 200 V to 450 V during a target propofol infusion aimed at a plasma steady-state concentration of 1.4 microg x ml(-1). TcMEPs were recorded from the right tibialis anterior muscle. RESULTS: Doubling the target propofol infusion to 1.4 microg x ml(-1) resulted in a 30-50% decrease in tcMEP amplitude. The largest tcMEP amplitude using the six-pulse paradigm was found during a propofol infusion aimed at a plasma concentration of 0.7 microg x ml(-1) and demanded a stimulus output of 350 V, corresponding to a charge density of 7.5 microC x cm(-2) per phase. CONCLUSION: Doubling the target propofol infusion to 1.4 microg x ml(-1) provides less robust, but still recordable tcMEPs in response to six-pulse electrical stimulation. Safety guidelines are discussed.     

No genotoxic effect of propofol in chinese hamster ovary cells: analysis by sister chromatid exchanges

BACKGROUND: In spite of its high placental transfer, propofol is frequently used in general anesthesia and sedation during obstetric and gynecological surgery such as in vitro fertilization. This study investigated whether or not propofol has a genotoxic potential by the sister chromatid exchange assay in vitro. METHODS: Sister chromatid exchanges induced after exposure to propofol were measured in Chinese hamster ovary cells with and without metabolic activation. After propofol (0.2-20 microg ml(-1)) diluted dimethyl sulfoxide was applied for 2 h with or without S9 mix, the cells having been incubated for two metaphases (34 h) in the presence of 5'-bromo-2-deoxyuridine. N-nitrosodimethylamine and mitomycin C were used as positive controls with and without metabolic activation. The chromosomes were stained with the fluorescence plus Giemsa method, and then sister chromatid exchanges in 50 cells were counted for each concentration. RESULTS: Although increasing concentrations of propofol inhibited cell proliferation, no concentrations of propofol used in this study increased the sister chromatid exchange values, with and without metabolic activation. CONCLUSION: It was concluded that there was no indication, from the sister chromatid exchange assay in mammalian cells, of a genotoxic effect of propofol and its metabolites.     

Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN-1)

We investigated the effect of propofol on endothelial cells subjected to the peroxynitrite (ONOO-) donor 3-morpholino sydnonimine (SIN-1). Cells were incubated overnight with 0.5, 1.0 or 2.0 mM SIN-1, with or without 10-3 M propofol (Diprivan). Cytotoxicity, assessed by measuring the release of pre-incorporated 51Cr, increased when the concentration of SIN-1 increased, and was significantly decreased by 10-3 M propofol (90%, 78% and 28% of protection against 0.5, 1.0 and 2.0 mM SIN-1, respectively). Cell protection against 1 mM SIN-1 was tested with 0.03-1.0 mM propofol and this was compared to tyrosine, a target molecule for peroxynitrite. Propofol protected cells in a dose-dependent manner (r = 0.98; p < 0.001) and was as effective as tyrosine. Finally, using high-performance liquid chromatography, we demonstrated that propofol reacted with ONOO- more rapidly than did tyrosine, inhibiting nitrotyrosine formation. In the absence of propofol, 3.5 mM ONOO- with 1 mM tyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was not produced when 5 mM propofol was added. We conclude that propofol protects endothelial cells against the toxicity of ONOO-. The anti-oxidant properties of propofol can be partially attributed to its scavenging effect on peroxynitrite, a property that might be relevant in pathological situations involving a significant contribution of peroxynitrite to tissue damage.     

Closed loop control of anaesthesia: an assessment of the bispectral index as the target of control

We investigated the performance of a closed-loop system for administration of general anaesthesia, using the bispectral index as a target for control. One hundred patients undergoing gynaecological or general surgery were studied. In 60 patients, anaesthesia was maintained by intravenous infusion of a propofol/alfentanil mixture. In 40, an isoflurane/nitrous oxide based technique was used. For each technique, patients were randomly allocated to receive either closed-loop or manually controlled administration of the relevant agents (propofol/alfentanil or isoflurane), with an intra-operative target bispectral index of 50 in all cases. Closed-loop and manually controlled administration of anaesthesia resulted in similar intra-operative conditions and initial recovery characteristics. During maintenance of anaesthesia, cardiovascular and electro-encephalographic variables did not differ between closed-loop and manual control groups and deviation of bispectral index from the target value was similar. Intra-operative concentrations of propofol, alfentanil and isoflurane were within normal clinical ranges. Episodes of light anaesthesia were more common in the closed-loop group for patients receiving propofol/alfentanil anaesthesia and in the manual group for patients receiving isoflurane/nitrous oxide anaesthesia. Convenience aside, the closed-loop system showed no clinical advantage over conventional, manually adjusted techniques of anaesthetic administration.     

依托咪酯、咪唑安定、丙泊酚对心内直视手术病人心肌酶的影响

目的 比较依托咪酯(E)、咪唑安定(M)、丙泊酚(P)对心内直视手术心肌缺血再灌注损伤的保护作用。方法 30例心内直视手术病人,在相同术前药、相似麻醉诱导、维持方案下,变更使用的麻醉镇静药E、M、P。随机分成3组,分别在诱导后、主动脉开放后30min、4h、16h、24h 5个时点测定血清中心肌酶AST(天冬氨酸转氨酶)、LDH(乳酸脱氢酶)、α-HBD(α-羟丁酸脱氢酶)、CK(肌酸磷酸激酶)、CK-MB(肌酸磷酸激酶同工酶)的浓度。结果心肌缺血再灌注后各心肌酶指标均有明显升高,CPK、CK-MB尤为明显,在24h后开始回落,E组的升高幅度明显高M和P组。结论 M和P能降低心肌酶的上升幅度。提示对心肌再灌注损伤比E有较大作用。     

靶控输注全凭静脉麻醉与静吸复合麻醉对术后认知功能影响的比较

【目的】比较靶控输注瑞芬太尼和丙泊酚全凭静脉麻醉与地氟醚和芬太尼静吸复合麻醉对术后认知功能的影响。【方法】选择ASAⅠ～Ⅱ级，年龄18～65岁（男27例，女17例）择期行鼻内镜手术的病人44例，随机分两组：靶控输注瑞芬太尼加丙泊酚全凭静脉麻醉组（TCI组）24例，地氟醚加芬太尼静吸麻醉组（DF组）20例。于麻醉诱导前及术后1、3、24h应用mini—mental state（MMS）测试方法评定其认知功能。比较两组术后麻醉苏醒恢复情况及手术后并发症。【结果】①两组病人在相同麻醉深度下，即脑电双频指数（bispeetral index，BIS）术中维持在40～60，各时间点MMS评分组间比较差异无统计学意义（P〉0．05）；组内比较仅在术后1h均较术前显著降低，术后3h即恢复至术前水平。术后1h TCI组有6例（25％）、DF组有9例（42．9％）病人有明显的认知功能降低，术后3hDF组有2例（10％）病人的MMS值较低（〈28分），而TCI组所有病人认知功能已恢复。②TCI组呼吸恢复时间、听从指令时间及定向力恢复时间均早于DF组，差异有统计学意义（P分别为0．02，0．03和0．02）。拔管时间，呼之睁眼时间也早于DF组，但无统计学意义。③TCI组在拔管即刻的OAAS评分高于DF组，有统计学意义（P=0．007）。④两组病人术后恶心呕吐发生率无差异，两组均无术中知晓发生。【结论】靶控输注瑞芬太尼和丙泊酚全凭静脉麻醉用于鼻内镜手术可引起一过性术后认知功能障碍，与地氟醚和芬太尼静吸复合麻醉相似。     

异丙酚和咪达唑仑靶控输注用于硬膜外麻醉病人术中镇静的对比研究

目的 观察异丙酚和咪达唑仑靶控输注（TCI）用于硬膜外麻醉病人术中镇静的效果．为临床工作提供指导。方法 下腹部手术病人40例，ASAⅠ～Ⅱ级，随机分成两组，每组20例。Ⅰ组为硬膜外麻醉复合TCI异丙酚组，Ⅱ组为硬膜外麻醉复合TCI咪达唑仑组。硬膜外麻醉效果满意后开始TCI，利用警觉-镇静（（OAA／S）评分和脑电双频指数（BIS）监测镇静程度，OAA／S评分发生变化时记录即刻的平均动脉压（MAP）、心率（HR）、脉搏血氧饱和度（SpO2）、BIS及血药浓度。术中保持OAA／S评分于3分水平，如病人出现躁动则加深至2分。术中监测不良反应，手术结束前停TCI，观察苏醒时间。结果 不同OAA／S砰分时两组病人MAP、HR、SpO2、BIS均有明显改变，组间比较无显著差异。两组病人不良反应发生率无明显差异。苏醒时间Ⅰ组短于Ⅱ组（t=5．15．P〈0．01）。OAA／S评分与BIS呈正相关（r=0．829、0．871．P〈0、01），BIS与血药浓度呈负相关（r=0．771、0．687，P〈0．01）。结论 异丙酚和咪达唑仑靶控输注用于硬膜外麻醉病人的术中镇静安全有效．BIS与OAA/S评分可有效指导TCI用药，值得临床推广。     

咪达唑仑和丙泊酚用于全身麻醉效果的比较

目的观察比较咪达唑仑和丙泊酚单独或联合用药对全麻诱导及维持的效果、麻醉恢复特性和不良反应的影响。方法选择90例全麻手术病人,随机分为3组。A组:麻醉诱导:咪达唑仑0·2mg·kg-1,麻醉维持:咪达唑仑0·15mg·kg-1·h-1;B组:麻醉诱导:丙泊酚1~2mg·kg-1,麻醉维持:丙泊酚2~4mg·kg-1·h-1;C组:麻醉诱导:咪达唑仑0·1mg·kg-1和丙泊酚0·5mg·kg-1,麻醉维持:咪达唑仑0·1mg·kg-1·h-1和丙泊酚1~2mg·kg-1·h-1。各组病例均附加静注芬太尼1~3μg·kg-1及同时吸入异氟醚1%~1·5%,并用适量维库溴铵维持肌肉松弛,行机械通气。结果比较各组不同时相与麻醉前SBP、DBP、HR、SpO2的变化显示,C组SBP、DBP在插管后及拔管前后较麻醉前的变化差异无统计学意义(P>0·05),A组和B组与麻醉前比较差异均存在统计学意义(P<0·05)。从术毕到病人睁眼的苏醒时间,A组为(34·44±12·35)min,B组为(6·56±5·74)min,C组为(14·64±9·50)min,3组间差异有统计学意义(F=62·21,P=0·000)。苏醒期出现躁动者A组为20%(6/30),B组为30%(9/30),C组为16·67%(5/30)。结论咪达唑仑和丙泊酚联合用于麻醉诱导和维持,可以发挥各自的特点与优势,使麻醉诱导及苏醒恢复期更加平稳,各种不良反应更趋缓和。