肝移植治疗肝肺综合征26例疗效分析

目的探讨肝移植对肝肺综合征（hepatopulmonarysyndrome,HPS）的疗效及HPS患者肝移植围手术期的管理经验。方法回顾性分析2004年3月至2006年1月中山大学附属第三医院肝移植中心行肝移植治疗26例HPS患者的临床资料,观察HPS患者肝移植术后的存活率、低氧血症的治愈率及术后并发症情况。结果HPS患者肝移植术后动脉氧分压随肝功能的好转逐步改善,99mTc大聚合白蛋白肺灌注扫描显示肺分流率明显下降。HPS患者肝移植术后28d的存活率为76．92％（20／26）,1年存活率为61．54％（16／26）,4年存活率为57．69％（15／26）。HPS患者肝移植术后肺部感染的发生率较高,为53．85％（14／26）;其他并发症包括术中术后大出血、伤口迁延不愈并感染、脑出血、高钠血症并高渗透压血症、肾功能障碍、多器官功能衰竭等。结论肝移植可有效延长HPS患者的存活时间和提高存活率,对HPS患者应根据其病理生理特点加强围手术期管理。     

肝肺综合征的肝移植治疗:肝移植术后5年随访和生存分析

目的探讨肝移植治疗肝肺综合征(hepatopulmonary syndrome,HPS)的临床疗效。方法确诊并发HPS的终末期肝病患者31例列为HPS组,按有否进行原位肝移植(OLT)治疗再分为HPS手术组(26例)和HPS未手术组(5例),同时随机选择接受OLT的30例未并发HPS的终末期肝病患者作为对照组(non-HPS手术组)。回顾性分析两组患者术后5年的随访结果和生存情况。结果 HPS手术组术后28d存活率为77%(20/26),半年及1年存活率均为62%(16/26),5年存活率为58%(15/26),明显高于HPS未手术组患者的存活率(0),但其5年存活率低于non-HPS手术组患者的5年存活率(80%)。HPS手术组患者的症状缓解率为77%(20/26)。HPS患者术中、术后并发症包括:大出血、肺部感染、伤口迁延不愈并感染、脑出血、高钠血症、肾功能障碍、多器官功能衰竭等。结论肝移植是治疗合并HPS的终末期肝病患者的唯一有效方法,可延长其存活时间,提高其存活率。     

肝移植术后噬血细胞综合征临床分析

目的分析肝移植术后患者发生噬血细胞综合征（hemophagocytic syndrome,HPS）的危险因素及其临床特点、诊断和预后。方法回顾性分析中山大学附属第三医院肝移植中心772例肝移植受者中发生的1例HPS患者的临床资料,并结合已经报道的13例肝移植术后HPS的临床资料进行文献复习。结果患者,男性、45岁,在肝移植术后36d发生持续性高热、全血细胞减少、凝血功能障碍和血清铁蛋白的水平升高。根据临床表现、实验室检查和骨髓活组织检查结果诊断为HPS。给予积极的肾上腺皮质激素冲击、注射粒细胞集落刺激因子和大剂量的免疫球蛋白治疗,因病情凶险,患者于术后54d死于颅内出血和多器官功能衰竭。在14例肝移植术后HPS患者中,临床表现为发热（14／14）、脾肿大（8／14）;实验室检查发现贫血、血小板减少、白细胞减少、肝脏转氨酶升高（9／14）;71％的患者血清铁蛋白水平升高。HPS的发生与病毒感染（8／14）有关。尽管给予积极的抗感染治疗和免疫抑制剂的减量,但仍有9例患者在术后2个月内死亡。结论肝移植术后HPS的发生与病毒尤其是爱泼斯坦一巴尔病毒（Epstein—Barruirus,EBV）和巨细胞病毒（CMV）感染有关。临床上疑似HPS时,应反复进行骨髓涂片检查,有助于早期确诊。尽管早期积极的合理治疗能够一定程度上控制病情,但总体预后极差。     

内毒素血症及炎症因子在肝肺综合征中的作用及其在肝移植术后的变化

目的探讨内毒素血症及相关炎症因子在肝肺综合征(hepatopulmonary syndrome,HPS)发生、发展机制中的作用及其在肝移植术后的变化。方法回顾性分析2004年1月至2006年4月中山大学附属第三医院肝移植中心拟行同种异体原位肝移植术的279例患者临床资料,其中HPS患者31例列为HPS组,同时随机选取行肝移植术且未合并HPS的终末期肝病患者30例为非HPS组及10例健康志愿者为正常对照组。HPS组、非HPS组和正常对照组分别于术前或治疗前1 d检测血清Toll样受体(Toll like receptor,TLR)2信使核糖核酸(messenger RNA,mRNA)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)mRNA、脂多糖(LPS)、肿瘤坏死因子(TNF)-α及内皮素(endothelin,ET)-1水平,HPS组和非HPS组分别于术后3、7、14、21、28 d检测总胆红素、TLR2 mRNA、TNF-α和ET-1水平。术后随访,记录随访期间的阳性事件和生存时间。结果截止至2008年7月,平均随访时间2.4年(最长4.4年)。目前,HPS组中26例行肝移植术患者存活15例,死亡11例,非HPS组中存活24例。肝移植术前HPS组患者的LPS、TNF-α、ET-1、TLR2 mRNA,iNOS mRNA的表达均明显高于正常对照组(均为P<0.05),但与非HPS组比较差异无统计学意义(P>0.05)。非HPS组患者的TLR2 mRNA和ET-1明显高于正常对照组(P<0.05),其iNOS mRNA、LPS与TNF-α也高于对照组,但无统计学意义(均为P>0.05)。HPS组患者肝移植术后28 d较术前TLR2 mRNA、TNF-α、ET-1水平有所下降(均为P<0.05)。结论 LPS及其相关炎症因子的释放增加在HPS的发生、发展中起着重要的作用。     

肝移植治疗儿童重度肝肺综合征一例

正肝肺综合征(hepatopulmonary syndrome,HPS)是慢性肝病的严重并发症之一,指无心肺基础疾病的肝功能不全患者肺内血管扩张与新生,致气体交换功能障碍而出现严重低氧血症[1-3]。成人肝病患者HPS发病率为1. 3%～32. 0%[3-8],呈渐进性发展,预后较差,且缺乏特异性内科治疗药物,肝移植是目前唯一可能根治HPS并逆转肺部病变的方法。儿童肝病患者亦可发生HPS,发病率为3%～     

肝移植术后肺部并发症的监测与处理

目的：总结肝移植术后肺部并发症的监测与处理经验。方法：对7例原位肝移植术后病人，在严密监护下分析呼吸系统并发症的病理生理学变化，探讨处理对策。结果：7例原位肝移植术后病人共出现26例次各种呼吸系统并发症，包括胸腔积液、肺不张、呼吸窘迫综合征(ARDS)、肝肺综合征(HPS)、肺间质水肿、肺感染和呼吸道出血。7例中除1例于术后第8天死于ARDS和MOSF外，余6例均治愈出院。结论：对原位肝脏移植术后病人，严密监测呼吸功能及正确使用呼吸机等综合治疗是肝移植术后的最重要环节。     

肝移植术后真菌感染的防治体会

目前由于各种免疫抑制剂的合理应用,使肝移植术后感染发生率有所下降,但真菌感染仍是主要并发症和死因之一.肝移植术后真菌感染发生率为6%～38%,而其死亡率高达40%～100%[1,2].为了更好地预防和治疗肝移植术后的真菌感染,现就我院器官移植中心的肝移植术后真菌感染的危险因素、预防、诊断、治疗进行回顾性分析.     

肝动脉再血管化联合局部溶栓治疗肝移植术后肝动脉血栓形成

肝动脉血栓形成(hepatic artery thrombosis,HAT)是肝移植术后严重的并发症之一,成人肝移植后HAT的发生率为1%～3%,儿童肝移植中HAT的发生率大于10%[1-3].肝移植术后HAT如果不能及早发现处理,绝大多数需要再次肝移植才能挽救患者生命.本文就我中心肝移植术后HAT的发生情况作一回顾性分析,探讨其处理措施.     

肝移植综合技术的改进与体会

目的:总结本移植中心肝移植综合技术提高的经验.方法:回顾性分析我院两个阶段[1999～2004年和2005～2007年(后期)]因良性终末期肝病行肝移植术病人的生存率.结果:后期的肝移植病人术后1个月、3个月和1年生存率分别为91.9%、85.5%和80.0%,明显高于前期的71.8%、66.7%和64.1%.术后围手术期死亡的病人较多,而术后中远期的生存率变化不大,本中心最长的生存病例已达102个月.结论:肝移植术式的改良、移植肝预先用血浆进行灌注、术后肠内营养的应用及免疫抑制剂的减量或个体化应用是提高肝移植术后生存率的原因.     

供肝匮乏时代的肝移植——从劈离式到两供一受

自1963年Starzl完成了世界首例肝移植之后,肝移植技术逐步成熟,已成为治疗终末期肝病最有效的方法,术后生存率也不断提高,目前病人术后1年生存率超过90%,5年生存率为75%～80%.中国肝移植注册系统(CLTR)统计显示,在约50%是肝癌病人的情况下,我国肝移植病人术后1年生存率已从上世纪90年代的43%升至现在的80%左右,接近国际水平.     

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.     

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.     

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.     

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.     

Intraoperative autotransfusion is associated with modest reduction of allogeneic transfusion in prosthetic hip surgery

Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r²=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.     

缺氧对肾小管上皮细胞分泌外泌体的影响

目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    （1）常氧（21% O₂）及缺氧（1% O₂）分别处理大鼠肾小管上皮细胞（NRK-52E）48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。（2）在共培养实验中,以不同浓度（1、10、50、100、300 mg/L）的常氧外泌体、缺氧外泌体分别干预脂多糖（LPS）诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验（ELISA）法分别检测巨噬细胞白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型氮氧化物合酶（iNOS）水平;使用Western印迹法检测巨噬细胞磷酸化（p）STAT/STAT及细胞因子信号传导抑制蛋白1（SOCS1）的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA（microRNA,miR）的表达差异。 结果    （1）离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。（2）缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌（均P＜0.01）,同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达（均P＜0.01）;对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高（P＜0.05）。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。     

In Vitro Function and Durability Assessment of a Novel Polyurethane Heart Valve Prosthesis

Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy: A controlled randomised trial

Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O₂ flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg^?1· h^?1 vs. 6.6 ± 4.8 μg · kg^?1· h^?1), a lower O₂ supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO₂ was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.