异丙酚输注综合征研究进展

由于其药效学和药代学特点,异丙酚已在临床上广泛使用,但使用过程中有可能发生异丙酚输注综合征.最新研究表明该综合征发生机制可能与异丙酚直接抑制线粒体呼吸链或损伤线粒体脂肪酸代谢有关.此文主要对异丙酚输注综合征的相关问题作一综述.     

线粒体功能障碍在胰腺疾病中的研究进展

线粒体功能障碍与胰腺疾病的发生发展关系密切。线粒体内膜呼吸链的电子传递和能量传递在维持细胞正常功能中发挥着重要作用,呼吸链功能失调,细胞内极易进入氧化应激状态,随即产生大量氧化中间产物攻击线粒体蛋白、DNA等,导致线粒体功能障碍,诱发胰腺炎、胰腺癌等疾病。此外,线粒体稳态在维持胰岛β细胞正常功能中起着不可或缺的作用。本...     

靶控输注丙泊酚复合输注芬太尼静脉麻醉的临床应用

全静脉麻醉(TIVA)与静吸复合全麻相比具有许多优点,是一种诱导快速、麻醉过程平稳、苏醒迅速的全凭静脉复合麻醉。靶控输注(TCI)又称目标浓度输注,代表着静脉麻醉给药方法的最新进展。TCI能维持效应室或血浆丙泊酚的浓度在有效的范围,避免有效浓度波动带来的术中知晓、循环抑制、呼吸抑制等并发症。丙泊酚的镇痛作用较弱,常与其他镇痛药联合应用。本研究应用TCI丙泊酚复合恒速输注芬太尼全静脉麻醉,探讨其临床应用的可行性及麻醉特点。     

丙泊酚对脓毒症大鼠肝损伤的保护作用

目的研究丙泊酚对脓毒症大鼠细胞因子的影响和细胞因子对肝线粒体呼吸功能的影响及其机制。方法采用盲肠结扎穿孔(CLP)制作脓毒症模型,将大鼠随机分为假手术组(C组)、盐水组(NS组)和丙泊酚组(P组),模型制作12h后NS组和P组分别给予生理盐水丙泊酚。在给药前和给药4 h后分别取静脉血,并在给药4h后取肝制备肝线粒体和组织匀浆,分别采用Clark氧电极技术测定线粒体呼吸功能,ELISA法检测IL-1β和IL-6,分光光度法测定NO水平。结果NS组的RCR和ADP/O明显低于C组,丙泊酚能改善其呼吸功能;NS组给药前后IL-1β和IL-6水平明显高于C组,而P组给药4 h后的IL-1β和IL-6水平较NS组明显降低,且NS组NO较C组和P组显著升高。结论丙泊酚能通过降低IL-1β和IL-6水平,减少肝组织NO的产生,从而保护线粒体呼吸功能,改善细胞能量代谢。     

丙泊酚靶控输注和人工控制输注用于颅内动脉瘤介入治疗的比较

目的比较丙泊酚靶控输注（TCI）和人工控制输注（MCI）在颅内动脉瘤介入治疗术中麻醉效果、对呼吸循环功能及不良反应发生的影响。方法20例颅内动脉瘤患者。随机分为两组：M组采用丙泊酚MCI；T组采用丙泊酚TCI。分别记录麻醉效果，诱导与苏醒时间，丙泊酚总用量，监测不同时间点的血压（BP），心率（HR），血氧饱和度（SpO2）。记录术中体动、舌后坠、术后不良反应例数。结果两组患者麻醉与苏醒时间差异无显著性（P〉0．05），丙泊酚总用量T组明显大于M组（P〈0．05），T组麻醉效果优于M组（P〈0．05）。丙泊酚诱导后血压下降程度M组大于T组（P〈0．05），术中出现体动及术后不良反应例数M组多于T组（P〈0．05）。结论丙泊酚靶控输注用于颅内动脉瘤介入治疗优于丙泊酚人工控制输注。     

丙泊酚的药效及对脂代谢的影响

目的观察丙泊酚的药效学及对家兔脂代谢的影响。方法家兔12只,随机分为1%丙泊酚组(Ⅰ组)和2%丙泊酚组(Ⅱ组),每组6只。两组丙泊酚单次首次剂量均为6mg/kg,以0.6mg/s从家兔耳缘静脉分别匀速注射,观察和记录家兔头正位反射消失时间。注射完毕后接麻醉注射泵以400μg·kg-1·min-1的速度持续输注丙泊酚6h,记录心率、血压和呼吸等生命体征变化及停药后苏醒时间。并于静注前、静注完毕、持续输注5、30min及1、3、6h和苏醒时分别抽血行血气分析,检测血药浓度及血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)的浓度。结果Ⅰ组家兔血清TG浓度在持续输注1、3和6h与静注前比较均有显著增高(P<0.01),血清TC浓度仅在持续输注6h较静注前增高(P<0.01);Ⅱ组在6h的血清TG浓度高于用药前(P<0.01),但同时点仍低于Ⅰ组(P<0.01)。结论2%丙泊酚与1%丙泊酚的药效相似,但2%丙泊酚能明显延缓脂代谢紊乱的发生时间。     

丙泊酚手控和靶控输注在无痛人流手术麻醉中的临床比较

本研究旨在了解丙泊酚手控(MCI)和靶控输注(TCI)在门诊无痛人流手术静脉麻醉中的效能，对呼吸、循环功能的影响和副作用，并对两种不同麻醉方法作临床对比研究。     

丙泊酚的两种输注方法在纤维结肠镜检查中的比较

随着医学的不断进展和生活水平的提高,丙泊酚麻醉已广泛应用于临床的多项检查和操作。本研究主要观察在纤维结肠镜检查中人工输注丙泊酚与靶控输注丙泊酚的两种给药方式对病人生命体征的影响以及丙泊酚用量、意识消失时间及苏醒时间等,现报道如下。     

瑞芬太尼复合丙泊酚靶控输注在老年腹腔镜胆囊切除术中的应用

目的探讨瑞芬太尼复合丙泊酚靶控输注在老年腹腔镜胆囊切除术(LC)中的应用效果。方法随机将接受LC的70例老年患者分为2组,每组35例。观察组采用瑞芬太尼复合丙泊酚靶控输注麻醉,对照组采用瑞芬太尼复合丙泊酚持续静脉输注麻醉。通过警觉/镇静评分系统(OAA/S)对麻醉效果进行评定,并比较2组患者的呼吸恢复时间、睁眼时间、拔管时间。结果 2组患者术中、术后各个时间段OAA/S评分差异无统计学意义(P0.05);观察组患者的呼吸恢复时间、睁眼时间、拔管时间均优于对照组,差异有统计学意义(P0.05)。结论老年患者LC时应用瑞芬太尼复合丙泊酚靶控输注麻醉效果优秀,安全性高。麻醉撤药后患者苏醒快,利于老年人术后恢复。     

靶控输注丙泊酚全凭静脉麻醉与静吸复合麻醉临床观察

目的探讨靶控输注丙泊酚全凭静脉麻醉在临床麻醉中的应用效果。方法腹腔镜下子宫肌瘤摘除术患者80例,分别采用靶控输注丙泊酚全凭静脉麻醉与静吸复合麻醉临床观察和血流动力学的比较。结果评价其诱导方法、术中情况和术后苏醒过程。结论靶控输注丙泊酚全凭静脉麻醉维持血流动力学稳定、安全、平稳、有效。     

Propofol infusion syndrome

Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. It has been assumed that the pathophysiologic cause is propofol's impairment of oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the mitochondria, leading to lactate acidosis and muscular necrosis. It has been postulated that propofol might act as a trigger substrate in the presence of priming factors. Severe diseases in which the patient has been exposed to high catecholamine and cortisol levels have been identified as trigger substrates. Once the development of propofol infusion syndrome is suspected, propofol infusion has to be stopped immediately and specific therapeutic measures initiated, including cardiocirculatory stabilization and correction of metabolic acidosis. To increase elimination of propofol and its potential toxic metabolites, hemodialysis or hemofiltration are recommended. Due to its possible fatal side effects, the use of propofol for long-term sedation in critically ill patients should be reconsidered. In cases of unexplained lactate acidosis occurring during continuous propofol infusion, propofol infusion syndrome must be taken into consideration.     

Propofol-Infusionssyndrom

Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. It has been assumed that the pathophysiologic cause is propofol’s impairment of oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the mitochondria, leading to lactate acidosis and muscular necrosis. It has been postulated that propofol might act as a trigger substrate in the presence of priming factors. Severe diseases in which the patient has been exposed to high catecholamine and cortisol levels have been identified as trigger substrates. Once the development of propofol infusion syndrome is suspected, propofol infusion has to be stopped immediately and specific therapeutic measures initiated, including cardiocirculatory stabilization and correction of metabolic acidosis. To increase elimination of propofol and its potential toxic metabolites, hemodialysis or hemofiltration are recommended. Due to its possible fatal side effects, the use of propofol for long-term sedation in critically ill patients should be reconsidered. In cases of unexplained lactate acidosis occurring during continuous propofol infusion, propofol infusion syndrome must be taken into consideration.     

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.     

Le syndrome de perfusion du propofol

Objective

Propofol is commonly used for sedation of children or adult patients in intensive care unit as an alternative to benzodiazepines for the long-term sedation of mechanically ventiled patient. However, the life-threatening complication of propofol-infusion syndrome (PRIS) may in some case occur. The objective of this article is to review the clinical features, physiopathology and management of PRIS.

Data sources

A PubMed^® database research in English and French languages published until December 2008. Keywords were propofol, propofol infusion syndrome (PRIS), rhabdomyolysis, heart failure, arrhythmias, metabolic acidosis, brain injury, sedation, intensive care.

Data synthesis

PRIS is a rare and potentially lethal complication, especially if there's no early identification of the syndrome. The physiopathology of PRIS mechanism remains unclear, however a dysfunction of mitochondrial respiratory chain could be involved and potential genetic factor may account. Clinical features consist of arrhythmias, metabolic acidosis, lipemia, rhabdomyolisis, myoglobinuria. PRIS has been described classically in children and adults undergoing a long term infusion with propofol (more than 48 hours) at doses higher than 4 mg/kg per hour. However, it can be observed with lower doses and after shorter duration of sedation. Steroids, vasopressors and low carbohydrate intake act as triggering factors. Early recognition of the syndrome improve patient's outcome. Propofol infusion must be avoided in susceptible patients and another sedative agent should be considered. When using prolonged sedation with propofol, arrhythmia and serum triglyceridemia level should be monitored.     

The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment

Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.     

Toxicity of intravenous anaesthetics

Intravenous anaesthetic agents are generally remarkably safe. However, it is clear that propofol infusion syndrome is a real, albeit rare, entity. This often lethal syndrome of metabolic acidosis, acute cardiomyopathy and skeletal myopathy is strongly associated with infusions of propofol at rates of 5 mg/kg/hour and greater for more than 48 hours. There is evidence to support the hypothesis that the syndrome is caused by the failure of free fatty acid metabolism due to inhibition of free fatty acid entry into the mitochondria and also specific sites in the mitochondrial respiratory chain. The syndrome therefore mimics the mitochondrial myopathies. Midazolam causes seizure-like activity in very-low-birthweight premature infants requiring the drug prior to tracheal intubation or during prolonged positive pressure ventilation. This can be successfully reversed with the specific benzodiazepine antagonist flumazenil. Midazolam can also cause paradoxical reactions, including increased agitation, poor co-operation and aggressive or violent behaviour, which has been successfully managed with flumazenil.     

Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis

BACKGROUND: Propofol is an intravenous anesthetic agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism. METHODS: Mouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically relevant concentration), and 300 microm. Cell viability, lactate dehydrogenase, and cell cycle were analyzed to determine the cellular toxicity of propofol to macrophages. After administration of propofol, chemotactic, phagocytic, and oxidative ability and interferon-gamma mRNA production were carried out to validate the potential effects of propofol on macrophage functions. Mitochondrial membrane potential and cellular adenosine triphosphate levels were also analyzed to evaluate the role of mitochondria in propofol-induced macrophage dysfunction. RESULTS: Exposure of macrophages to 3 and 30 microm propofol did not affect cell viability. When the administered concentration reached 300 microm, propofol would increase lactate dehydrogenase release, cause arrest of cell cycle in G1/S phase, and lead to cell death. In the 1-h-treated macrophages, propofol significantly reduced macrophage functions of chemotactic and oxidative ability in a concentration-dependent manner. However, the suppressive effects were partially or completely reversed after 6 and 24 h. Propofol could reduce phagocytic activities of macrophages in concentration- and time-dependent manners. Exposure of macrophages to lipopolysaccharide induced the mRNA of interferon-gamma, but the induction was significantly blocked by propofol. Propofol concentration-dependently decreased the membrane potential of macrophage mitochondria, but the effects were descended with time. The levels of cellular adenosine triphosphate in macrophages were also reduced by propofol. CONCLUSIONS: A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.     

Propofol infusion syndrome in a patient with sepsis

Propofol is widely used for sedation in critically ill patients. Several adult patients, all with acute neurological disorders, have been reported suffering from propofol infusion syndrome, which occurs in patients receiving high-dose propofol and catecholamines and/or steroids. We present a case of a septic patient without neurological illness who developed propofol infusion syndrome.     

Propofol infusion syndrome

The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. There is an association between PRIS and propofol infusions at doses higher than 4 mg.kg(-1).h(-1) for greater than 48 h duration. Sixty-one patients with PRIS have been recorded in the literature, with deaths in 20 paediatric and 18 adult patients. Seven of these patients (four paediatric and three adult patients) developed PRIS during anaesthesia. It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram. Predisposing factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Treatment options are limited. Haemodialysis or haemoperfusion with cardiorespiratory support has been the most successful treatment.