高龄心脏死亡器官捐献供体肝移植研究进展

高龄供体供肝作为边缘供肝的一种,在有效解决供肝短缺的同时,也存在诸多高危因素,与肝移植术后并发症及病死率密切相关,但在控制好相关并发症及相关肝脏疾病的基础上,高龄供体肝移植在一定程度上是安全可靠的。本文从高龄肝脏退行性改变、高龄供体肝移植、高龄供体肝移植并发症、高龄供体肝移植高危因素、高龄心脏死亡器官捐献(DCD)供体选择标准思考等,就肝脏随年龄变化特点与高龄供体肝移植的近年研究进展作一综述,同时探究高龄DCD供体肝移植是否安全可行。     

边缘供肝面临的机遇与挑战

随着手术技术和术后免疫抑制治疗的不断突破与成熟,肝移植受者和移植物存活率显著提高,供肝短缺已成为限制肝移植临床发展的主要阻碍,如何扩大供肝来源也成为了当前迫切需要解决的问题。高龄供肝、脂肪变性供肝、病毒性肝炎供肝、心脏死亡器官捐献供肝等常见边缘供肝在临床肝移植中的使用已经取得了一定的突破性进展,但边缘供肝的使用仍存在较多限制。因此,本文对边缘供肝的定义,几种常见边缘供肝的应用及研究进展进行综述,探讨目前边缘供肝面临的机遇与挑战,旨在为临床肝移植供者池的扩大提供参考,造福更多终末期肝病患者。     

脂肪变性供肝在肝移植中的应用现状与进展

肝移植是终末期肝病最有效的治疗措施,但器官供需的严重失衡已经成为制约肝移植进一步发展的关键因素.因此,如何合理使用边缘性供肝已成为肝移植临床的重点.常见的边缘性供肝有脂肪变性供肝、乙肝表面抗原阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间>14 h的肝脏、心脏死亡器官捐献(donation-after-circu...     

供肝短缺形势下的我国肝移植策略

近5年来我国肝移植发展非常迅速,然而,供肝短缺成为制约临床肝移植发展的瓶颈。因此,拓展供肝来源成为目前肝移植临床的重点。活体肝移植在尸体供肝受限的情况下可以很好地扩展供肝来源,且活体供肝具有活力强、冷缺血时间短等优势;劈裂式肝移植可增加15％～28％的供肝数量,有望成为解决供肝短缺的主要手术方式之一;脑死亡供者在西方国家是移植器官的主要来源,在我国亦有广大的应用前景,但脑死亡供者器官移植刚刚起步,有许多问题亟待研究;此外,边缘供肝,包括脂肪变性肝脏、HBsAg阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间超过14h的盱脏等均可用以缓解日益突出的供肝短缺矛盾。     

2010年全国器官移植学术会议纪要(续)

4.亲属活体肝移植和扩大标准的供肝移植:由于供移植的器官来源短缺,亲属活体肝移植和扩大标准的供肝移植日益增多,随之而来的伦理学问题和技术问题更多地出现在交流讨论中.朱志军等介绍了天津市第一中心医院扩大供肝来源的经验:(1)开展新的术式,如活体肝移植、劈离式肝移植、多米诺肝移植;(2)合理使用扩大标准的供肝,如高龄供肝、脂肪肝、华支睾吸虫供肝、肝炎病毒阳性等供肝的使用.汤晓寅等报告,活体部分肝移植术后早期他克莫司(Tac)的用量与植入供肝的体积显著相关,成人活体右半肝移植术后早期的用量约相当于尸体全肝的70%,随着植入供肝的不断再生,至术后28 d可基本接近全肝移植水平.     

边缘供肝应用于肝脏移植的研究进展

目的 探讨边缘供肝的种类及其在肝移植中的应用前景。方法 复习国外有关边缘供肝应用于临床肝移植的最新进展。结果 高龄供体、缺血时限较长供体、脑死亡供体和脂肪肝供体是几种临床意义较大的边缘供肝。结论 虽然边缘供肝的使用给肝脏移植带来负面效应，然而其能扩大供肝来源且疗效确切。     

肝移植中应用边缘供肝的相关研究新进展

供肝短缺是当今制约临床肝移植发展的主要问题。临床上经常遇到脂肪肝供体、高龄供体、乙肝表面抗原阳性供体、冷缺血时限较长等边缘供肝（marginal donor）问题。我们就近年来国外有关边缘供肝在临床肝移植的应用及效果的最新进展做一综述。总体上说边缘供肝可以扩大供肝来源且疗效确切。     

公民逝世后器官捐献供肝肝移植:我国儿童肝移植的新出路

我国是先天性胆道疾病和肝脏疾病的高发国家,部分患儿发展为终末期肝病,因此,儿童肝移植在我国有很大的发展空间。儿童肝移植的供肝类型主要包括尸体全肝、尸体减体积供肝、尸体劈离式供肝和活体供肝。在我国,儿童肝移植以活体肝移植为主,但存在伦理学争议,且不易找到合适的供体,严重限制了我国儿童肝移植的发展。近年我国公民逝世后器官捐献供肝数量不断增加,劈离式肝移植自2010年起得到迅速增长,活体供肝所占比例也随之降低。随着我国公民逝世后器官捐献事业的发展,公民逝世后器官捐献供肝将取代活体供肝成为我国儿童肝移植主要供肝来源。     

辅助性肝移植研究进展

辅助性肝移植足指住保留受体自身全部或部分肝脏的情况下,将供肝植入受体体内.根据供肝植入部位不同,可分为异位辅助性肝移植和原位辅助性肝移植;根据植入肝体积的多少,可分为全肝辅助性肝移植和部分肝辅助性肝移植;供肝可来源于脑死亡供体也可以来源于活体供体.山于原位辅助性肝移植只能移植部分肝脏,故通常称为原位辅助性部分肝移植.辅助性肝移植伴随着肝移植的发展而不断发展,虽然还存在许多尚待解决的问题,但辅助性肝移植独特的优势再次引起肝移植界的广泛关注.     

劈离联合多米诺肝移植的临床应用

供肝短缺是限制肝移植发展的主要障碍, 劈离式肝移植、多米诺肝移植作为特殊类型的肝移植, 可缓解供肝短缺的难题, 缩短受者的等待时间[1, 2]。但国内外鲜见关于劈离式肝移植同时行多米诺肝移植的报道。我院器官移植中心于2021年12月完成1例左右半肝劈离式肝移植, 同时将其中1例患者的病肝作为多米诺供肝完成1例多米诺肝移植, 术后患者均恢复顺利, 现总结经验报告如下。     

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.     

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.     

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.     

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.