全身麻醉药对发育大脑的神经毒性研究进展

背景 每年越来越多的婴幼儿在全身麻醉下接受各种影像学检查和外科手术及重症监护治疗,反复暴露于全身麻醉药物之下.目前,全身麻醉药物是否具有神经毒性这一问题引起了人们的广泛关注. 目的 综述全身麻醉药对发育期大脑产生神经毒性的可能机制及相关研究的最新进展. 内容 就全身麻醉药对发育期大脑产生神经毒性的作用机制、在不同动物实验模型的研究结果、相关临床研究进展及动物实验与临床研究的相关性及局限性等方面内容进行综述. 趋向 目前动物实验及临床研究均不能完全排除全身麻醉药的神经毒性作用,在对全身麻醉药影响神经系统发育的机制深入研究的同时,在儿科手术麻醉时应做到在全面发挥麻醉药治疗作用的同时尽可能降低神经毒性的副作用.     

七氟烷对发育期中枢神经系统毒性的研究进展

背景 七氟烷作为临床上常用的吸入麻醉药,广泛用于儿科手术中.近年来,关于七氟烷发育期中枢神经系统(central nervous system,CNS)毒性的研究成为人们关注的焦点.目的 文章就近年发表的有关七氟烷对发育期CNS毒性相关研究进展作一综述.内容 七氟烷神经毒性与神经保护的双重性;七氟烷与异氟烷对发育期CNS毒性作用的比较;七氟烷对发育期CNS毒性作用的机制研究及预防手段探讨. 趋向 今后的研究重点是开展可靠的临床试验分析、比较各种吸入麻醉药在小儿麻醉中的优劣、明确七氟烷麻醉对幼儿神经发育的影响及可能的治疗手段.     

吸入麻醉药促发育期神经元凋亡的分子机制

背景 长期以来,人们一直认为吸入麻醉药的麻醉作用是可逆的,对中枢神经系统不会遗留任何副作用.近年基础研究发现,实验动物尤其是处于发育期动物,暴露于吸入麻醉药后,可出现记忆、认知功能障碍.这种现象的产生可能与吸入麻醉药导致的神经元凋亡增加有关.目的 综述吸入麻醉药诱导发育期大脑神经元凋亡可能的分子机制.内容 吸入麻醉药可能通过影响神经递质及受体、信号转导通路,并可引起氧化应激反应、β-淀粉样蛋白质集聚,从而导致神经细胞凋亡.趋向 对吸入麻醉药神经毒性防治的研究起推动作用.     

七氟烷对发育中大脑是保护还是损害

背景 七氟烷是一种优良的新型吸入麻醉剂,具有血/气分配系数低,麻醉诱导时间短,麻醉深度易于控制,清醒速度快,肝肾功能影响小,血流动力学稳定等特点.而其所具有的芳香味,使七氟烷在小儿麻醉中更具优势.了解七氟烷对发育中大脑的影响可使麻醉医师在临床应用时扬长避短. 目的 对以往文献进行回顾并综合目前最新研究进展,深入分析七氟烷对发育中大脑的影响. 内容 已有大量关于七氟烷对发育中大脑影响的研究,由于临床试验的局限性,大部分研究都在动物模型上实施,七氟烷对发育中大脑是具有保护作用抑或是损害,其机制是什么,不同的研究者试验结论不一致甚至相悖.趋势 目前关于吸入麻醉药的麻醉作用机制和神经保护、神经毒性作用机制已经深入到分子水平.由于大脑内存在多种信号通路、离子通道以及神经递质,使得七氟烷对大脑影响的机制变得复杂,进行更深入的研究迫在眉睫.     

吸入麻醉药对未成熟大脑神经发育影响的基础研究进展

背景 大多数基础研究都显示孕期或新生儿期暴露于吸入麻醉药会对未成熟大脑产生神经毒性影响.但另有研究显示在某些特殊的临床状态下(如缺血/缺氧性脑损伤),吸入麻醉药反而具有神经保护作用. 目的 评估吸入麻醉药对未成熟大脑神经发育的影响,为临床实践提供参考. 内容 总结近年来有关的基础研究进展,阐述其相关机制,分析各相关因素的影响. 趋向 吸入麻醉药对未成熟大脑神经发育的确切影响至今仍无定论,尚需开展更深入的研究来评估其临床安全性.     

全身麻醉药物对发育大脑小胶质细胞影响的研究进展

近年来，全身麻醉药物对发育大脑的影响成为关注的焦点。全身麻醉药物可造成动物胎儿及幼崽随着生长发育出现短期及长期认知功能障碍，而临床中回顾性研究结果与动物实验结果尚不一致。因此，全身麻醉药物对发育大脑有无影响尚无统一定论。小胶质细胞作为中枢神经系统免疫细胞在发育的不同阶段表现不同形态，执行不同的功能，在神经元损伤修复、神经炎症、神经网络构建等方面发挥重要作用。本文将常用全身麻醉药物包括吸入麻醉药、静脉麻醉药、阿片类药物等对发育大脑小胶质细胞的影响机制做一综述。     

麻醉相关神经毒性及其对动物远期行为的影响

背景 大量动物实验已证实麻醉导致发育期动物神经细胞死亡增加,复合麻醉或多次麻醉更可能影响动物的远期行为.目的 综述麻醉神经毒性及其影响动物远期行为的可能机制,介绍其在灵长类动物的近期研究.内容 介绍目前较为公认的麻醉相关神经毒性的主要观点,分析其可能机制与动物远期行为障碍的可能关系,以及麻醉神经毒性在灵长类的研究进展. 趋向 麻醉相关神经毒性已经不容忽视,有必要深入研究麻醉药物对发育期脑的神经毒性.     

麻醉药对发育期大脑毒性作用的研究进展

背景 麻醉药广泛应用于各种手术的临床麻醉,其神经毒性一直是麻醉学领域的研究热点.越来越多的证据使麻醉学领域开始质疑麻醉药对于发育期婴幼儿的安全. 目的 研究麻醉药和神经毒性之间的关系,从而在临床中采取必要措施来避免麻醉药对于大脑的神经毒性. 内容 回顾麻醉药对于发育期大脑的影响,总结导致神经毒性的可能机制,并对近年来的实验和临床研究进行分析. 趋向 由于前瞻性随机临床试验的操作难度大,因此很难在短期内对麻醉药和神经毒性关系的临床研究取得实质性进展.     

全身麻醉药发育神经毒性的机制及其防治研究进展

背景 越来越多的动物研究显示全身麻醉药能够导致发育神经元的凋亡,流行病学研究亦表明,患儿在3岁前接受长时间或/和多次全身麻醉发生术后认知功能障碍的风险明显增加;然而,全身麻醉药导致发育神经元毒性的机制尚未阐明,临床上也缺乏有效的防治措施.目的 通过综述全身麻醉药导致发育神经元毒性的可能机制,探讨可能的防治措施.内容全身麻醉药通过不同的分子途经调控发育神经元并能够启动或加速神经元的凋亡.首先,由于发育神经元内Cl-的浓度较高,全身麻醉药激活γ-氨基丁酸A(γ-aminobutyric acid A,GABAA)受体后可促进Cl-由胞内流向胞外,进而导致神经元兴奋性中毒.其次,氯胺酮上调能够渗透钙离子的N-甲基-D天冬氨酸(N-methyl-D-aspanate,NMDA)受体可能会导致钙超载.第三,全身麻醉药抑制前体脑源性神经营养因子(brain derived neurotrophic factor,BDNF)向成熟BDNF(mBDNF)的转化,进而通过P75神经营养因子受体(p75 neurotrophin receptor,p75NTR)通路诱导神经元凋亡.第四,一些全身麻醉药也能够造成活性氧自由基(reactive oxygen species,ROS)的积聚,在钙超载和ROS的共同作用下可导致线粒体功能障碍.全身麻醉药物引起神经网络活动的紊乱也可以导致神经元凋亡和认知功能障碍.越来越多的研究发现靶向相关的离子通道、控制钙超载、减少ROS产物以及减轻神经元凋亡可有效保护全身麻醉药物导致的神经元变性.趋向 全身麻醉药可通过不同的分子途经导致发育神经元凋亡,将这些分子或分子途经作为潜在的靶标可以对全身麻醉药诱发的功能障碍进行防治.     

吸入麻醉药物对男性生殖功能影响的研究进展

吸入麻醉药物的安全性一直是医护人员共同关注的热点,但其对生殖系统毒性报道不多,尤其是对男性生殖系统的影响。以异氟烷为代表的多项临床及基础研究结果表明,吸入麻醉药物可通过不同机制对啮齿类动物的生殖系统产生影响,主要表现为精子数量减少,精子形态结构、活动力异常,精子畸形率增高及激素水平变化等方面。下丘脑-垂体-性腺轴变化、生殖细胞DNA损伤及凋亡增多是吸入麻醉药对生殖系统产生影响的主要机制。本文综述了吸入麻醉药物对男性生殖功能的主要影响及其可能的机制,以期为预防医护人员职业暴露产生的影响奠定理论基础。     

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.