神经炎症反应在术后认知功能障碍中作用的研究进展

背景 在老年患者的心脏手术和非心脏手术中,术后认知功能障碍(postoperative cognitive dysfunction,POCD)已经成为一种常见的并发症.POCD导致患者并发症增加,医疗消耗增加,患者病死率升高.近年来大量研究发现POCD各种发病机制都通过一个共同通路即神经炎症. 目的 进一步研究神经炎症反应对POCD发生、发展的作用机制和防治措施.内容 以神经炎症反应为中心,围绕神经炎症、炎症因子、抗炎和炎症抑制反应对POCD的影响进行综述. 趋向 预防性抗炎治疗防止POCD的发生、发展.     

神经炎症反应和中枢神经退行性变与老年患者术后认知功能障碍

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是麻醉手术后尤其是老年患者麻醉术后常见的神经系统并发症. 目的 现在从神经系统炎症反应和中枢功能减退等对POCD的影响作一综述,为防治POCD的发生和发展提供有效的方法. 内容 介绍POCD的发生与炎症反应、磷酸腺苷活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)信号通路的改变、Tau蛋白、β淀粉样蛋白的改变(β-amyloid,A β)、中枢胆碱能系统功能减退等的关系.趋向 更深入研究POCD发生的病理机制,从POCD的发生原理上为预防POCD的发生和获得有效的治疗提供新思路.     

全身麻醉药与术后认知功能障碍及阿尔茨海默病

术后认知功能障碍(POCD)的病因复杂,在老年患者中较多见,但其机制尚未明确.全麻药在POCD发生中的作用及其机制已有许多研究,结果复杂而多样.另外,有一些动物或离体研究表明全麻药可促发阿尔茨海默病(AD)的发病过程并可能因此促发AD的发病和导致POCD.因此,研究全麻药在POCD和术后AD发病中的作用,特别是探求其中可能存在的共同机制是有意义的.     

神经炎症对术后认知功能障碍影响的研究进展

术后认知功能障碍（POCD）是手术和麻醉后的常见并发症,老年患者预后较差。POCD表现为注意力、意识、知觉和判断力下降,并时常伴随情绪和人格行为的异常改变,对患者和其家庭有较大的社会和经济影响。POCD相关机制包括中枢神经炎症和外周炎性因子的共同作用,其中神经炎症在POCD的病理生理发展过程中十分重要,然而神经炎症参与POCD发生与发展的机制尚不明确。本文章就神经炎症及其相关研究机制与POCD的关系做一综述,以期为探究POCD的发病机制和寻找新的潜在靶点提供新思路。     

大麻素在认知功能障碍中的作用

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是手术后常见并发症之一,不仅导致患者康复延迟,增加医疗费用,而且严重影响患者术后生活质量.研究显示POCD的发生可能是多种机制作用的结果,主要与中枢胆碱能系统、应激反应及炎症反应有关.近年来研究发现大麻素系统在认知功能障碍中也扮演着重要角色. 目的 综述大麻素在认知功能障碍中的作用研究进展. 内容 简介POCD以及大麻素系统,总结目前对于大麻素与认知功能关系的研究成果. 趋向 为研究者提供最新信息,期望对于POCD发病机制的研究提供帮助.     

术后认知功能障碍的炎症机制

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是老年患者手术后常见的中枢神经系统并发症.目前POCD的发病机制尚不清楚.POCD的发生影响了患者术后恢复,延长了住院时间,增加了术后并发症的发生率和死亡率;对家庭及社会造成严重的经济负担,POCD将成为一个严重的社会问题.目的 旨在推进POCD的研究,使得这一严重问题得到解决.内容 以往的研究表明,麻醉、手术可能是的POCD主要原因,而老龄则是惟一明确的危险应素,提示中枢神经系统退行性改变与POCD的发生可能有着重要联系,而麻醉和手术加重了这种退行性改变所致的认知功能衰退.趋向 较多研究表明炎症反应在与衰老有关的认知功能减退中起着重要作用,而手术创伤和应激引起的炎症反应是围术期发生的重要病理生理学改变.近年来炎症反应在POCD发生中的作用备受关注,现对POCD发生中炎症反应方面的研究进展进行综述.     

老年人中枢炎症反应与认知功能障碍的相关性研究进展

背景 认知功能障碍好发于老年人群,与手术、感染、创伤以及麻醉等多个危险因素相关,其中术后认知功能障碍(postoperative cognitive dysfunction,POCD)一直受到很多学者的关注.然而有关认知功能障碍确切的病因和机制仍不清楚,临床上也缺乏有效的预防和治疗策略.许多研究发现中枢炎症反应可能是认知功能障碍重要的病理生理机制之一. 内容 回顾老年人中枢炎症反应的发生、神经炎症反应对认知功能的损害以及抗炎策略在认知损害防治方面的研究进展. 目的 为认知功能障碍尤其是POCD病理生理机制的进一步研究奠定良好的基础. 趋向 在认知功能障碍防治方面具有一定的指导意义并为其提供新的思路.     

术后认知功能障碍药物干预的研究进展

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是老年患者术后常见的并发症.POCD显著增加老年患者致残率和致死率,增加医疗成本并降低患者生存质量.目的 对目前POCD药物干预的基础与临床研究作一综述,为POCD的预防和处理寻找药物靶点,并为围术期的应用提供理论依据.内容 概述POCD危险因素,并介绍目前已报道的POCD药物干预相关的动物研究和临床观察数据.趋向 POCD为多因素的术后并发症,目前机制尚未明了,但神经炎症反应是其重要机制之一;一系列具有抗炎效应的药物在动物模型上取得了良好的效果,这为未来POCD临床干预药物的开发和应用奠定了基础,同时也表明POCD的药物干预具有广泛的研究前景和临床应用价值.     

衰老大脑小胶质细胞异常激活与中枢性炎症研究进展

背景 中枢性炎症反应在老年术后认知功能障碍(post operative cognitive dysfunction,POCD)、阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)等慢性神经退行性疾病的发生发展中至关重要,其具体机制尚不明确.目的 阐明衰老大脑小胶质细胞活性改变及其异常激活对中枢炎症反应的加剧作用.内容 对衰老大脑小胶质细胞异常激活及其可能机制进行阐述.趋向 如何抑制衰老大脑小胶质细胞免疫通路的异常激活是今后的研究方向.     

老年患者术后认知功能障碍发病机制的研究进展

术后认知功能障碍(POCD)是与麻醉和手术密切相关的严重并发症之一。随着医疗技术发展和人口老龄化, 接受麻醉和手术的老年患者数量逐步增多。POCD是老年患者术后常见的神经认知并发症, 可通过炎症反应、中枢胆碱能系统、应激反应、自噬功能、微生物-肠-脑轴以及生物节律等途径, 使患者记忆力、理解力、注意力减退, 从而影响老年患者术后快速康复, 延长住院时间, 降低术后生活质量, 甚至增加术后死亡率。阐明老年患者POCD的机制有助于制订有效的防治措施。本研究拟就老年患者POCD发病机制的研究进展进行综述。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.