以血浆作透析液行血液透析联合高容量血液滤过治疗对肝衰竭患者血浆细胞因子的影响

目的 以人体新鲜冰冻血浆作透析液行血液透析(HD-PBD)后继续进行高容量血液滤过(HVHF)，观察其对肝功能衰竭患者血浆细胞因子的影响。 方法 12例肝功能衰竭患者行HD-PBD治疗6 h后，应用同一滤器(AV600)继续行HVHF治疗24 h。分别在治疗前(0 h)及治疗后6、30 h取血，应用酶联免疫吸附法(ELISA)检测TNF-α、IL-1β、IL-6和IL-8的水平，同时观察治疗前后血清胆红素、总胆汁酸(TBA)、血氨、BUN、Scr水平，并监测动脉血气分析和电解质浓度的变化。 结果 (1)HD-PBD对胆红素和TBA的清除较HVHF明显(P < 0.05)；(2)HVHF在清除血氨、BUN、Scr、纠正电解质和酸碱失衡方面比HD-PBD更有效(P < 0.05)；(3)停止HD-PBD后继续行HVHF治疗24 h，胆红素仍有所下降(P < 0.05)；(4)治疗后TNF-α、IL-6和IL-8较治疗前明显下降。 结论 对肝功能衰竭患者，HD-PBD联合HVHF治疗能显著降低血清胆红素、总胆汁酸、BUN、Scr、血氨及部分细胞因子，调节水电解质和酸碱平衡，并且安全、简便、易行和成本低廉。     

不同剂量血液滤过对内毒素休克猪生存时间和细胞因子水平的影响

目的 探讨不同剂量连续性血液滤过（CVVH）对细胞因子的清除作用以及对血浆细胞因子水平的影响。 方法 采用静脉注射内毒素（E.coli O111: B4,15.7 μg/kg）的方法诱导内毒素休克猪模型。将内毒素休克猪按随机数字表法分为对照组(n=6)、 CVVH组 (n=6,前稀释法,等于后稀释法的45 ml·kg-1·h-1）和高容量血液滤过（HVHF）组 (n=6,前稀释法,等于后稀释法的70 ml·kg-1·h-1）。于造模前（基线）、成模时（T0）,成模后1 h（T1）、6 h（T6）、12 h（T12）、24 h（T24）分别测定血浆肿瘤坏死因子α（TNF-α）、白细胞介素（IL）6、IL-10和IL-18水平。 结果 对照组动物平均生存时间为（15.4±5.2） h;CVVH 组为(21.4±7.1) h;HVHF组为（22.4±6.7） h,CVVH组和HVHF组的生存时间显著高于对照组（均P < 0.05）。3组动物的心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）和心排出量（CO）之间差异无统计学意义（P > 0.05）。内毒素休克猪成模后出现BUN和Scr的进行性升高,两治疗组的BUN和Scr水平显著低于对照组（P < 0.05）,但两者之间差异无统计学意义（P > 0.05）。对照组TNF-α和IL-6水平在T1时达高峰,IL-10水平在T0时最高,随后不断下降。IL-18水平在成模后上升,后无明显变化。CVVH组血浆IL-10（T6、T12、T24）水平低于对照组（P < 0.05）。HVHF组TNF-α（T6）和IL-10（T6、T12、T24）水平低于对照组和CVVH组（P < 0.05）,3组的IL-6和IL-18水平差异无统计学意义,IL-6（T6、T12）水平和动物生存时间呈负相关（P < 0.05）。 结论 CVVH和HVHF治疗均能显著延长内毒素休克猪的生存时间。CVVH能有效清除IL-10;HVHF治疗能清除TNF-α和IL-10;但CVVH和HVHF对IL-6和IL-18水平无明显影响;CVVH和HVHF均能有效清除BUN和Scr。IL-6水平是预测内毒素休克预后的独立指标。     

细胞黏附分子在高容量血液滤过防治多器官功能障碍中的表达变化及意义

目的研究细胞黏附分子在高容量血液滤过（HVHF）干预多器官功能障碍（MODS）猪模型过程中的表达变化情况。方法18头实验动物被随机分为2组：模型组（M组）实施失血性休克＋内毒素注射“二次打击”，而治疗组（HF组）在二次打击后接受HVHF干预。检测两组中性粒细胞（PMN）表面CD11b、L-选择素（selectin）的表达和血浆中可溶性E选择素（sE-seleetin）、可溶性细胞间黏附分子（sICAM-1）的浓度。结果HVHF治疗开始后，HF组CD11b表达出现下降，在各个时间点与M组比较，差异有统计学意义P〈0．01；治疗组中L-selectin的表达在治疗后24、48h处表达高于M组的表达（P〈0．05）。治疗开始后sE-selectin浓度就出现明显下降，治疗后24h与M组比较差异有统计学意义（P〈0．01），到治疗后48h（P〈0．05）和72h（P〈0．01）已经高于M组水平；治疗后24h，HF组中sICAM-1水平低于M组（P〈0．05），此后维持于较高水平，至治疗后72h高于M组（P〈0．01）。结论HVHF可以间接、双向调节MODS发生过程中细胞黏附分子的表达水平以及PMN、内皮细胞的活化状态。     

高容量血液滤过对外周血细胞因子的影响

目的研究高容量血液滤过(HVHF)对外周血肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素6(IL-6)的清除作用。方法18例重症急性肾功能衰竭(ARF)患者,随机选择10例行HVHF,另8例为对照组,行血液透析(HD)。酶联免疫法检测治疗前和治疗1h、2h、4h、6h和8h时血、超滤液及透析液中TNF-α、IL-1β、IL-6的浓度(单位均为ng/L)。结果(1)HVHF组9/10例、HD组6/8例患者肾功能恢复正常;(2)HVHF组治疗前血TNF-α1784±437、IL-1β960±173、IL-61320±325分别与治疗后4h1267±401、519±127、761±259比较,差异有显著性意义,P＜0.01;超滤液中未能检测出TNF-α,但可持续检测到IL-1β、IL-6;(3)HD组治疗过程中TNF-α、IL-1β、IL-6血中浓度无明显变化,透出液中未检测出上述细胞因子。结论HVHF可通过对流作用清除大量的细胞因子;AN69滤器对细胞因子有吸附作用。     

白细胞滤除对犬体外循环诱发全身炎性反应的影响

目的探讨白细胞滤除对犬体外循环（CPB）诱发全身炎性反应的影响。方法蒙古犬12只，体重25—30kg，随机分为2组（n=6）：对照组（C组）和白细胞滤除组（LD组），C组不使用白细胞滤器，LD组将滤器安装于CPB的静脉回流端，在CPB2min时打开滤器5min。分别于CPB前即刻（T0）、阻断升主动脉后即刻（T1）、阻断升主动脉30min（T2）、开放升主动脉后5min（T3）、停CPB即刻（T4）、停CPB2h（T5）自股静脉抽血，测定白细胞计数和血浆L-选择素、白细胞介紊（IL）-6、IL-8、髓过氧化物酶（MPO）水平。于过滤后30、60、90min时测定滤器内IL-6、IL-8浓度，并在过滤后90min时取滤膜行病理学检查。结果LD组T1时白细胞计数低于C组；两组CPB期间血浆L-选择素、IL-6、IL-8浓度均高于T0，T5时LD组血浆L-选择素、IL-6、IL-8、MPO水平均低于C组。过滤后60、90min时滤器中IL-6、IL-8浓度高过滤后30min；滤器内白细胞滤膜全层布满白细胞，人血面白细胞多于出血面。结论白细胞滤除能抑制犬CPB所引起的全身炎性反应。     

复用滤器对联机血流透析滤过溶质清除率及安全性的影响

目的：研究复用滤器对联机血液透析滤过溶质清除率、安全性及氧化应激指标的影响。方法：8例稳定的维持性透析患者分别接受初用和复用滤器的后稀释联机血液透析滤过治疗。测定透析开始后20min和整个治疗时间的透析液侧及血液侧溶质清除率。全面培养法测定透前、透后、透析开始后20min滤器前后细胞因子产生量。高效液相色谱法测定透前、透后血浆及透析液中总抗坏血酸、脱氢抗坏血酸和维生素E含量。结果：两组透析开始后20min及总治疗时间内透析液侧及血液侧小分子物质清除率相似，但复用组β2－微球蛋白（β2－m)吸附清除率明显低于初用组，透析液侧清除率则显著高于初用组。复用组透析液白蛋白含量明显高于初用组，两组透前、透后维生素E水平无显著改变，但透后总抗坏血酸水平均明显下降，其中复用组透析后脱氢抗坏血酸／总抗坏血酸比例较透前明显下降。全血培养法显示，两组彼此之间及透前、透后及透析开始后20min滤器前后细胞因子产生量差异均无显著性意义。初用组及复用组透析中临床症状以及透析后体温无明显差异。结论：复用滤器不影响联机血液透析滤过的溶质清除率，但可增加白蛋白丢失；虽然复用滤器对血液炎症因子产生细胞的激活程度与初用组相似，但有增加氧化应激的危险。     

N-乙酰半胱氨酸对CO2气腹导致急性肾损伤的预防作用

目的探讨N-乙酰半胱氨酸（NAC）对CO2气腹所引起的肾功能损害的保护作用。方法42只成年Wistar大鼠被分为7组，每组6只。组1-4未经NAC处理，其中组1为无气腹对照，组2为1h气腹后24h评估，组3为3h气腹后24h评估，组4为3h气腹后72h评估；组5～7于气腹前2d开始服用NAC直至评估前，其中组5为无气腹对照，组6组为3h气腹后24h评估，组4为3h气腹后72h评估。通过菊粉清除试验检测肾小球滤过率；采用硫代巴比妥酸法（TBARS）评估肾脏氧化应激程度。结果短时间（1h）气腹对肾小球滤过率和血清TBARS无明显影响（组2比组1，P〉0．05）；而长时间（3h）气腹会导致肾小球滤过率明显降低，血清TBARS明显升高（组3和组4比组1，均P〈0．05）。而服用NAC后，长时间（3h）气腹则不再会导致肾小球滤过率的降低和血清TBARS的升高（组6和组7比组5，均P〉0．05）。结论NAC可有效预防因长时间气腹通过诱发氧化应激所导致的肾功能损害。     

高容量血液滤过联合机械通气对犬海水型呼吸窘迫综合征的作用

目的 建立稳定的海水型呼吸窘迫综合征（SW-RDS）犬模型,探讨高容量血液滤过（HVHF）联合机械通气（MV）对海水淹溺后发生SW-RDS的疗效。 方法 采用健康杂种犬10只,随机分为2组：（1）单纯MV组（n=5）：实验犬在模型成功后行MV;（2）HVHF+MV组（n=5）：模型成功后在MV的基础上联合HVHF。两组均连续观察4 h。在气管插管成功稳定15 min后（基础状态）、成模、治疗60 min、120 min、180 min、240 min时记录平均动脉血压（MAP）、心率（HR）、中心静脉压（CVP）,进行动脉血气分析,采集静脉血标本以测血浆渗透浓度;另于基础状态、成模、治疗120 min、240 min采集静脉血标本以测炎性介质（IL-8、IL-6、TNF-α）;实验结束后取肺组织标本行光镜及电镜检查。 结果 （1）在治疗4 h后两组实验犬均存活。（2）血氧分压（PaO2）及氧饱和度（SaO2）均有所上升,HVHF+MV组较MV组改善更明显（P < 0.05）;HVHF+MV组pH、实际碳酸氢根 (AB)、剩余碱（BE）较MV组显著改善（P < 0.05）,恢复至基础状态水平。（3）两组在治疗4 h过程中MAP、HR、CVP均保持稳定,治疗240 min后MAP、HR、CVP与成模时比较差异无统计学意义;两组间相同时间点比较差异亦无统计学意义。（4）MV组在治疗4 h过程中,血浆渗透浓度保持稳定,与成模时比较差异无统计学意义。HVHF+MV组在治疗240 min后血浆渗透浓度较MV组同时间点显著升高（P < 0.05）,较同组成模及治疗180 min时亦显著升高（P < 0.01）。（5）HVHF+MV组血浆炎性介质（IL-8、IL-6、TNF-?琢）在治疗240 min后与MV组同时间点比较显著减少（P < 0.01）;MV组治疗240 min后IL-8、TNF-?琢较成模型时比较明显升高（P < 0.05）。（6）肺组织病理提示,HVHF+MV组肺组织炎性反应、水肿、肺泡上皮损伤等情况较MV组有所改善。 结论 HVHF+MV能明显改善犬SW-RD的低氧血症及纠正酸中毒。HVHF可有效清除循环血炎性介质及多余的水分,从而改善肺组织病理。HVHF对犬SW-RD的mABP、HR、CVP无显著影响。     

脉冲式高容量血滤对术后急性肺水肿的肺水清除作用

目的：术后急性肺水肿是一较严重的术后并发症,除与液有关外其主要的发生机制为全身炎症反应。纠正低氧和迅速清除肺水是其主要的治疗。当患者血流动力学不稳,血液净化技术目前广泛应用于临床,研究证实脉冲式高容量血液滤过（PHVHF）既有效清除大量体内多余液体,又能清除可溶性炎症介质,改善患者预后。但针对急性肺水肿应用PHVHF临床治疗尚未见报道;本研究旨在探讨PHVHF对ARDS患者的肺血管通透性。肺功能、血流动力学的影响。方法：术后急性肺水肿伴休克少尿患者18例,所有患者均接受了综合治疗;积极治疗休克。采用PHLIPS MP50监护仪,记录患者心电、呼吸及Picco血流动力学参数：血管外肺水、肺血管,通透指数,胸内血容量、心排量。PHVHF方法;前后稀释各50％,血流星200-250ml／min,超滤及抗凝依临床需求需定。72h连续性血液滤过治疗,前后稀释各50％,血流量200—250ml／min．超滤及抗凝临床需求而定。72h连续性血液滤过治疗,其中每日HVHF[85ml（kg·h）]治疗6-8h后,续行CVVH治疗, [35ml/（kg·h）]。结果：本组患者平均置换液流量69.3±8.6升/日。接受PHVHF治疗前后,患者心率、血压改善,HPACHEll评分、SOFA评分显著降低（P〈0．05）,生命体征趋于稳定。PHVHIF治疗后24小时,患者氧合指数、吸氧浓度、气道峰压显著降低,肺顺应性升高（p〈0.5）,PHVHF后48小时、72小时血管外肺水、肺血管通透指数较治疗前显善降低。胸内血容量,全心舒张末容积降低,而心排量趋于稳定。结论：针对创伤和术后急性肺水肿患者。早期应用PVHF可能改善的血流动力学、呼吸功能、肺水肿及肺毛细血管通透性。PHVHF充分利用了早期滤过膜通透性及吸附性能好,而随时间延长HVHF清除率逐渐降低这一特性,临床操作简化,应用前景广泛。     

非体外循环冠状动脉旁路移植术后早期血流动力学和心肌损伤的观察

目的观察非体外循环冠状动脉旁路移植术（OPCAB）后早期血流动力学变化及心肌损伤。方法选择20例择期OPCAB患者，连续监测血流动力学变化，并记录麻醉诱导后10min（T0）、血运重建后30min（T1）、2h（T2）、6h（T3）、12h（T4）、24h（T5）的血流动力学参数，同时测定血浆肌酸激酶同功酶（CK-MB）、心肌肌钙蛋白1（cTnI）和N端B型脑钠肽（NT—proBNP）浓度。吻合血管前和血运重建后30min分别取右心房心肌组织透射电镜观察超微结构的变化。结果围术期SBP和DBP无明显变化，但血运重建后HR增快（P〈0．01）、CVP、肺动脉楔压（PCWP）、平均肺动脉压（MPAP）和心指数（cI）升高（P〈0．01），而体循环阻力（SVR）、体循环阻力指数（SVRI）、每搏数（SV）、每搏指数（SVI）和左室每搏功指数（LVSWI）降低，右室每搏功指数（RVSWI）仅在血运重建后2h降低（P〈0．01）。CK-MB和cTnI从血运重建后持续升高（P〈0．05），尤以血运重建后24h为明显。NT-proBNP在血运重建后12h内无显著变化，但在血运重建后24h显著升高（P〈0．01）。透射电镜下见血运重建后肌丝结构较术前模糊，线粒体有变形，结构不清晰，嵴模糊。结论OPCAB血运重建后早期存在心肌损伤和左右心功能下降，以左心为著。     

Pharmacokinetics of vancomycin in patients undergoing haemodialysis and haemofiltration

Vancomycin is widely used for the treatment of infections with Gram-positive bacteria in patients with end-stage renal disease. The concentration of vancomycin in serum, in ultrafiltrate, and in dialysate was measured during nine haemofiltration and seven haemodialysis procedures with high-permeability membranes. The t1/2 of vancomycin was 101 +/- 19 h in the interdialytic and interhaemofiltration period. There was no significant difference between the haemodialysis clearance (55.2 +/- 18.5 ml/min) and the haemofiltration clearance (66.8 +/- 13.6 ml/min). The redistribution phenomenon was about 25% in the post haemofiltration period and only 10% in the post haemodialysis period. Approximately 270 mg of vancomycin was recovered in dialysate or ultrafiltrate. With high-permeability membranes more commonly used in patients with end-stage renal disease, continuous monitoring of vancomycin therapy is recommended.     

Cytokine removal during continuous hemofiltration in septic patients

A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients. Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies, but so far without important effects on their serum concentrations. Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies. In the present study, 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an AN69 membrane. After 12 h, the hemofilter was replaced and the blood flow rate (QB) was switched from 100 ml/min to 200 ml/min or vice versa. Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance. Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane (ranging from 25 to 43% of the prefilter amount), corresponding with a significant fall in the serum concentration of all cytokines. The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines. Adsorption to the AN69 membrane appeared to be the main clearance mechanism, being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter, indicating rapid saturation of the membrane. A QB of 200 ml/min was associated with a 75% increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min. The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes.     

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目的 观察连续性高流量血液滤过(HVHF)治疗严重感染伴有多器官功能障碍综合征(MODS)的临床疗效及安全性.方法 2005-2007年中国医科大学附属第一医院收治的20例确诊为产重感染伴有MODS的病人,平均APPACHEⅡ评分为23.8±8.3,平均SOFA评分为10.6±4.0,在常规治疗的基础上应用HVHF治疗至少3d,血流速度250mL/min,超滤量4L/h,置换液以前稀释方式输入,普通肝素抗凝,每24h更换滤器1次.比较治疗前后病人生命体征、血清尿素氮、肌酐、胆红素、动脉血乳酸、血小板、氧合指数及APPACHEⅡ评分和SOFA评分的变化,并监测治疗过程中的并发症.结果 20例病人在HVHF治疗后生命体征迅速稳定,体温、心率、呼吸频率降低,平均动脉压上升,血清尿素氮、肌酐水平下降,动脉血乳酸降低,血小板计数升高,氧合指数改善,APPACHEⅡ评分及SOFA评分降低,与治疗前相比差异具有统计学意义(P＜0.05),血清胆红素水平在治疗后来见明显改善.治疗过程中病人未见严重的离子及酸碱紊乱及其他并发症的发生.结论 连续性HVHF治疗能够降低严重感染伴有MODs病人的全身炎性反应,改善器官功能水平,未见严重并发症的发生,安全有效.     

Techniques of extracorporeal cytokine removal: a systematic review of human studies

Abstract

Background and aims: Hypercytokinemia is believed to be harmful and reducing cytokine levels is considered beneficial. Extracorporeal blood purification (EBP) techniques have been studied for the purpose of cytokine reduction. We aimed to study the efficacy of various EBP techniques for cytokine removal as defined by technical measures. Method: We conducted a systematic search for human clinical trials which focused on technical measures of cytokine removal by EBP techniques. We identified 41 articles and analyzed cytokine removal according to clearance (CL), sieving coefficient (SC), ultrafiltrate (UF) concentration and percentage removed. Results: We identified the following techniques for cytokine removal: standard hemofiltration, high volume hemofiltration (HVHF), high cut-off (HCO) hemofiltration, plasma filtration techniques, and adsorption techniques, ultrafiltration (UF) techniques relating to cardiopulmonary bypass (CPB), extracorporeal liver support systems and hybrid techniques including combined plasma filtration adsorption. Standard filtration techniques and UF techniques during CPB were generally poor at removing cytokines (median CL for interleukin 6 [IL-6]: 1.09?mL/min, TNF-alpha 0.74?mL/min). High cut-off techniques consistently offered moderate cytokine removal (median CL for IL-6: 26.5?mL/min, interleukin 1 receptor antagonist [IL-1RA]: 40.2?mL/min). Plasma filtration and extracorporeal liver support appear promising but data are few. Only one paper studied combined plasma filtration and adsorption and found low rates of removal. The clinical significance of the cytokine removal achieved with more efficacious techniques is unknown. Conclusion: Human clinical trials indicate that high cut-off hemofiltration techniques, and perhaps plasma filtration and extracorporeal liver support techniques are likely more efficient in removing cytokines than standard techniques.     

Tailoring high-cut-off membranes and feasible application in sepsis-associated acute renal failure: in vitro studies.

BACKGROUND: As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1beta, IL-1ra, TNF-alpha) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances. METHODS: Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) post-dilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate). RESULTS: In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1beta and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-alpha, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively. CONCLUSIONS: Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.     

不同血液净化模式对高胆红素血症的治疗效果比较

目的 非生物人工肝主要通过血浆置换和胆红素吸附达到暂时改善肝功能的目的,本研究旨在了解不同血液净化模式对高胆红素血症的治疗效果.方法 对6例高胆红素血症患者进行了选择性血浆置换(SPE)、胆红素吸附(PA)及选择性血浆置换加胆红素吸附(SPE+PA)治疗,比较治疗前后总胆红素(TB)和直接胆红素(DB)的下降幅度和清除率.结果 三种治疗模式治疗前后比较,TB和DB水平均显著下降(P＜0.05).TB和DB的清除率以(SPE+ PA)组最大,分别为(37.8±3.9)％和(38.0±3.4)％,与SPE组比为显著差异(P＜0.001).PA组与(SPE+ PA)组比较,TB的清除率均无显著差异(P＞0.05).结论 单纯使用国产胆红素吸附柱(BS330-Ⅱ)治疗可有效降低患者的胆红素水平,联合SPE+ PA治疗,疗效增加不显著.     

Tumor necrosis factor-alpha during continuous high-flux hemodialysis in sepsis with acute renal failure

Suppressed ex vivo endotoxin (ET)-induced production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), in isolated mononuclear cells (PBMCs) is associated with fatal outcome in severe sepsis. PBMCs from surviving patients, but not those from nonsurviving patients, recover their capacity to produce normal amounts of TNF-alpha. We tested the influence of two modalities of continuous renal replacement therapy (CRRT) on ex vivo-induced whole-blood production of TNF-alpha and inhibitory TNF-soluble receptor type I (TNFsRI) in 12 patients with acute renal failure and sepsis (APACHE II score 22 to 30). METHODS: Standard continuous venovenous hemofiltration (CVVH; 36 liters of bicarbonate substitution fluid per day) was performed in 7 patients using polyamid hemofilters (FH66; Gambro). In an additional five patients, we performed daily 18 hours of high-flux hemodialysis (CHFD) using polysulfon F60S dialyzers (Fresenius) and 75 liters of bicarbonate dialysate using the GENIUS single-pass batch dialysis system. Samples were separated from the blood circuit as well as from the ultrafiltrate/spent dialysate lines at the start, during, and end of treatment. Whole-blood samples were incubated with 1 ng/ml of ET for three hours at 37 degrees C. Ultrafiltrate or dialysate samples were incubated with donor whole blood in the presence of ET to measure suppressing activity in ultrafiltrate and spent dialysate. RESULTS: At the start of CRRT, ET-induced whole-blood TNF-alpha production was suppressed to approximately 10% of that in normal controls. During CVVH, median ET-induced TNF-alpha production increased from 0.35 ng/ml at the start to 1.2 ng/ml at three hours, but decreased to pre-CVVH levels at the end of a 24-hour period. In contrast, in patients on CHFD, the median ET-induced TNF-alpha production was 0.5 ng/ml at the start, 1.1 ng/ml at 3 hours, 1.6 ng/ml at six hours, and 1.5 ng/ml at the end of 18 hours of treatment. The ultrafiltrate obtained after three hours of CVVH did not contain suppressing activity. In CHFD, the spent dialysate as compared with fresh dialysate suppressed ET-induced TNF-alpha production in donor blood by 33% throughout the 18 hours of treatment. Whole-blood production of TNFsRI did not change significantly at any time point during CVVH or CHFD. CONCLUSION: These data suggest that high-volume CHFD is superior to standard CVVH in removing a suppressing factor of proinflammatory cytokine production. As CVVH only transiently improves TNF-alpha production, it is most likely that the putative suppressing factor is removed because of saturable membrane adsorption in CVVH. In CHFD, there is a combination of adsorption and detectable diffusion into the dialysate. It remains to be shown whether a further increase in the volume of dialysate per day is able to not only improve but normalize the cytokine response and improve outcome in septic patients with acute renal failure.     

肝移植术中应用连续静脉-静脉血液透析滤过的麻醉管理

目的总结肝移植术中应用手术床旁连续静脉一静脉血液透析滤过（continuous venovenous hemodiafiltration, CVVHDF）替代治疗的麻醉管理经验。方法回顾性分析2005年至2012年期间在首都医科大学附属北京佑安医院接受肝移植且术中应用CVVHDF替代治疗肝衰竭合并急性肾衰竭的8例患者的临床资料。记录患者术中血流动力学指标、出血量、尿量、补液量、CVVHDF替代治疗时间及手术情况等。测定CVVHDF替代治疗前后血尿素氮（BUN）、血清肌酐（Scr）及血清总胆红素等,计算内生肌酐清除率（Ccr）。术后2周观察转归。计量数据以均数±标准差或中位数（四分位数间距）表示。治疗前后两组Ser、Ccr、BUN和血清总胆红素比较采用独立样本t检验。结果CVVHDF治疗时间（415±197）min,脱水量为50—200ml／h。手术期间总尿量116（60,437）ml,尿量0．18（0．07,0．78）ml／（kg·h）。出血量3950（2200,5225）ml,补液量8837（7690,10012）ml。CVVHDF替代治疗后,Scr和BUN有下降趋势,Ccr有所升高,但差异无统计学意义（均为P〈0．05）。与CVVHDF替代治疗前相比,治疗后的血清总胆红素下降31％,差异有统计学意义（t=2．356,P〈0．05）。2例患者分别于CVVHDF替代治疗2d及6d后,肾功能逐渐恢复;2例死亡,分别死于多器官功能衰竭和原发性移植物失功所致肾衰竭;4例术后继续CVVHDF替代治疗及综合支持治疗。结论对于肝衰竭合并急性肾衰的肝移植手术患者,应用CVVHDF替代治疗,有助于平稳渡过手术期,减轻。肾功能损害,提高生存率。