CRRT连续肾脏替代疗法

CRRT,山东大学齐鲁医院 田军,持续肾脏替代治疗（Continuous Renal Replacement Therapy, CRRT),Any extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours/day,危重病人的肾脏替代治疗,持续肾脏替代治疗（Continuous Renal Replacement Therapy)间断血液透析(Intermittent Hemodialysis),持续肾脏替代治疗（Continuous Renal Replacement Therapy, CRRT)的特点,低血压患者：缓慢、温和、耐受性好在较长的时间内，清除大量的水和废物血流动力学不稳定患者耐受性好,CRRT的目的,危重症采用CRRT的目的主要有两大类:一是重症患者并发肾功能损害；二是非肾脏疾病或肾功损害的重症状态，主要用于器官功能不全支持、稳定内环境、免疫调节等。,CRRT溶质清除的原理,对流溶质穿过半透膜的一种方式，溶质和溶媒通过超滤，一起穿透膜移动超滤是血液流经滤器的中空纤维产生正相跨膜压时，出现溶质和溶媒一起穿过半透膜而移动的过程肾小球是超滤的对流清除模式持续血液滤过技术是模拟肾小球的工作方式，作用于膜的超滤液侧的负压越大，跨膜压越大，滤过率越大，某溶质的清除率越大,血液透析滤过,对流（血液滤过）+弥散（血液透析）使用置换液+透析液,SCUF,Syringe pump,Return Pressure,Air Detector,Blood Pump,Access Pressure,Filter Pressure,BLD,Hemofilter,Patient,Effluent Pump,Return Clamp,Pre Blood Pump,Effluent Pressure,CVVH,Return Pressure,Air Detector,Return Clamp,Patient,Access Pressure,Effluent Pump,Syringe Pump,Filter Pressure,Hemofilter,Pre,Post,Post,Replacement Pump,Replacement Pump,Pre Blood Pump,Effluent Pressure,CVVHD,Return Pressure,Air Detector,Return Clamp,Access Pressure,Blood Pump,Syringe Pump,Filter Pressure,Hemofilter,Patient,Effluent Pump,Dialysate Pump,Pre Blood Pump,BLD,Effluent Pressure,CVVH,治疗时机，模式选择，治疗剂量,AKI的定义和分类KDIGO推荐，符合以下情况之一者即可被诊断为AKI： 48小时内血清肌酐（Scr）升高超过26.5 mol/L（0.3 mg/dl）； 7天内Scr 升高超过基线1.5倍； 尿量0.5 ml/（kg?h），且持续6小时以上。AKI分级标准见右表。AKD的定义在AKI指南中，KDIGO引入了AKD的新概念，即符合以下任何条件者即可被诊断为AKD： 符合AKI标准； 3个月内肾小球滤过率（GFR）下降超过35%或Scr升高超过50%； 3个月内GFR下降至60 ml/（min?1.73m2）以下； 肾脏损伤时间短于3个月。,紧急肾脏替代治疗指征,K6.5容量过多严重代谢性酸中毒尿毒症性心包炎药物过量,ARF的辅助检查,Cr，BUN是最常用判断肾功能的指标敏感性差，通常肾小球滤过率下降50%以上才会增高受多种因素影响：营养状况、肌肉损伤、消化道出血、激素治疗等增高水平较绝对值更敏感,CRRT的类型,CVVH Continuous Veno-Venous Hemofiltration CVVHD Continuous Veno-Venous HemoDialysisCVVHDF Continuous Veno-Venous HemoDiaFiltrationSCUF Slow Continuous Ultra Filtration,常用抗凝方法,肝素低分子肝素局部肝素局部枸橼酸盐,生理盐水前列环素前列环素和低分子肝素,ARF预后,病死率与既往肾功能状况、本次发病情况、合并症严重程度与数量有关呼吸衰竭、全身性感染、创伤、腹腔疾病、烧伤 7090%药物性肾病（氨基糖甙、造影剂等）2530%三个或三个以上脏器功能障碍病死率100%,ARF的死亡原因,感染是ARF最主要的死因耐药的G-杆菌、真菌引起的全身性感染其他导致死亡原因心血管功能障碍、呼吸衰竭（VAP），消化道出血,ARF存活者,肾功能恢复正常（约50%GFR可有轻微下降）少尿一般持续1014天少尿期后37天尿量逐渐恢复Cr，BUN在此阶段仍然升高通常不再需要CRRT绝大多数存活者（95%）在30天内恢复肾功能肾功能不能恢复者多为既往肾功能不全和老年患者,RIFLE Stratification in Patients Treated with CRRTBell et al, Nephrol Dial Transplant 2005,Conclusions:,An increased treatment dose from 20 ml/h/kg to 35 ml/h/kg significantly improved survival.a dose of 35 ml/kg/hour was associated with dramatic improvement in survival of nearly 20 %. A delivery of 45ml/kg/hr did not result in further benefit in terms of survival, but in the septic patient an improvement was observed. Our data suggest an early initiation of treatment and a minimum dose delivery of 35 ml/h/kg (ex. 70 kg patient = 2450 ml/h) improve patient survival rate.,Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo study. Lancet . july 00,0,.2,.4,.6,.8,1,0,20,40,60,80,100,days,Recovery from Dialysis Dependence: BEST Kidney Data,Recovery from dialysis dependence,Manuscript under review,Leading the way,CRRT vs. IHD in Renal Recovery,Recent studies suggest that CRRT is superior to IHD with respect to recovery of renal functionImplications go far beyond just “hard” endpoint of renal recovery Need for chronic dialysis impairs quality of lifeIf length of stay (LOS) in ICU can be reduced this will have a major impact on hospital budgetPatients dependent on chronic dialysis will consume significant health care resources and have an impact on the community health care budget,Leading the way,Two methods of high volume hemofiltration (HVHF), with different underlying concepts and results, became prevalent: Continuous high volume hemofiltration (CHVH) providing 50 to 70 ml/kg/h 24 hours a day, intermittent high volume hemofiltration (IHVH) with brief, very high volume treatment at 100 to 120 ml/kg/h for 4 to 8 hours,血液净化治疗非肾脏病的指征,全身炎症反应综合征/脓毒症多器官功能障碍综合征急性呼吸窘迫综合征挤压综合征急性坏死性胰腺炎严重烧伤心肺旁路,电解质紊乱乳酸酸中毒肝功能衰竭急、慢性心力衰竭药物或毒物中毒先天性代谢缺陷急性肿瘤溶解综合征,连续性血液净化在SIRS和MODS中的应用,连续性血液净化在合并ARF的SIRS和MODS的患者治疗中应用越来越广泛，除了用于控制患者的液体平衡、氮质血症和水电解质酸碱平衡之外，还可能纠正脓毒症导致的炎性介质内稳态紊乱，如清除大量释放的补体成分，花生四烯酸代谢产物和细胞因子等，改善血流动力学和器官功能。具体如下：1、通过弥散或对流产生的吸附滤过作用清除促炎和抗炎介质和血管活性物质。 2、与膜接触有关的反应：(1)激活白细胞和前炎症反应； (2)消耗血小板。 3、其他作用：(1)降低血液温度，治疗发热； (2)抗凝可能起到抗炎作用； (3)减轻组织水肿，改善供氧和器官功能； (4)清除乳酸； (5)补充置换液的作用； (6)纠正代谢性酸中毒。,The new concept of purification plasma challenge was then developed to try to decrease mortality.,SIRS AND CRRTYearbook of Intensive Care And Emergency Medicine 2009 Some of the leading theories in this field are provided by current experts in hemofiltration.,First, the peak concentration hypothesis of Ronco and Bellomo postulates that removing the peak cytokine concentration from the blood circulation during the early phase of sepsis could stop the inflammatory cascade and the accumulation of free cytokines, which are the leading cause of organ damage and homeostasis disruption,The second concept is called the threshold immunomodulation hypothesis, also called the Honore concept 9, 10. In this concept, the removal of cytokines does not only affect the cytokine concentration in the blood stream but also in the tissues. Indeed, when cytokine concentrations are reduced in the blood, blood and tissue concentrations may equilibrate to remove the immune components trapped in the organs. This could explain why no crucial reduction in cytokine Concentration is observed in the blood stream during hemofiltration, because cytokines from the organs permanently replace those lost in the blood.,The third theory, which has been proposed by Di Carlo, sheds new light on the mediator delivery hypothesis, in which the use of HVHF with a high volume of crystalloid fluids (3 to 5 l/hour) is able to increase the lymphatic flow by 20 to 40 fold .Indeed, this increase is correlated with the infusion of a high dose of fluids. Since cytokines and other immune components are transported by the lymphatic stream, this could explain their removal even though large amounts of cytokines were not found in ultrafiltration fluid. Thus, the use of high volumes of exchange fluid might be the principal motor of cytokine removal.,although the benefit of early treatment has been shown, initiating RRT before renal injury is not yet recommended. In fact, the best time to start hemofiltration may be the renal injury state (creatinine 2 from baseline or oliguria III 0.5 ml/kg over the preceding 12 hours) from the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification which could represent the best compromise between early initiation and renal impairment,35 ml/kg/h should be the standard hemofiltration dose in ICUs for all patients with AKI, while in some situations, like sepsis, the dose should be increased as a salvage therapy in view of the high mortality rates in these patients. However, more trials are needed before HVHF can be recommended as routine treatment,CRRT过程中监测体液量的目的在于恢复患者体液的正常分布比率。严重的体液潴留或正水平衡可导致死亡率升高，而过度超滤体液也可以引发有效血容量缺乏。Vincent等在24个欧洲国家的198个ICU进行的回顾性观察显示：ICU病死率除与sepsis的发生率相关外，还同年龄和正水平衡密切相关。美国一项儿科ICU单中心回顾性研究中观察到， CRRT治疗前液体过负荷越重，死亡率越高，这意味着液体过负荷对预后有重要影响。基于以上基础，该中心应用利尿剂、小剂量多巴胺及RRT策略控制并发ARF的干细胞移植儿童的液体量，观察发现有效纠正液体过负荷可降低病死率。因此， RRT过程中，在维持生命体征稳定的前提下，应控制液体入量，避免体液潴留。 正水平衡病人死亡率高,急性坏死性胰腺炎,急性坏死性胰腺炎（SAP）的发病机制是胰蛋白酶的大量活化，消化胰腺组织，同时胰蛋白酶进人血液循环，作用于各种不同的细胞，释放出大量血管活性物质（5-羟色胺、组织胺、激肽酶），导致胰腺坏死，炎症反应，血管弥漫性损伤，血管张力改变，引起心血管、肝和肾脏功能不全。急性胰腺炎的治疗进展包括应用单克隆和多克隆抗体，中和及清除各种炎症介质和毒素。Purcaru等提出在胰腺炎毒性物质未进人血液之前采用CBP，同时进行胸腔和腹腔灌洗。已有动物实验资料显示,SAP开始CBP时间的早晚对动物的预后有显著影响。,挤压综合征,挤压综合征是指肌肉丰富的肢体或躯干，受外界重物（如被倒塌的工事，房屋）挤压或固定体位自压1小时以上而造成的肌肉组织创伤，肌肉发生缺血坏死，在此基础上出现肾脏的缺血缺氧，肾血管痉挛，肌红蛋白可变成为不可溶性的血红蛋白，沉淀于肾小管内，从而加速ARF的发展。如处理不当，在解除挤压后，除了局部病变外，还可并发休克，形成危及生命的挤压综合征。二次大战时，死亡率高达90100；1976年，唐山地震后，死亡率在2040。,近年来，由于血液净化技术的临床应用，ARF的死亡率已由50降至10左右，死因主要为化脓性感染。Berns等认为，肌红蛋白分子量是17 800，血液滤过比其它血液净化方式能更有效的清除肌红蛋白，超滤液中可以测到肌红蛋白，血液滤过可以预防挤压综合征患者发生ARF及其它横纹肌溶解所致的ARF。但是，Wakahayae及Shigenoto报告，不管采用何种血液净化方式和肾功能状态如何，肌红蛋白水平都可以迅速下降，提示肌红蛋白存在肾外代谢途径。挤压综合征属高分解代谢，CBP应该早期充分透析，纠正电解质、酸碱失衡，加强营养支持，碱化尿液。另外，积极处理原发病，清除创伤挤压的坏死组织。纠正高钾血症也非常重要。,心脏手术后,心脏手术患者在术前多伴有慢性缺血导致的脏器损伤，术后常并发前负荷过多、急性肾功能损伤以及高钾血症和/或代谢性酸中毒等，氮质血症和液体过负荷是常见并发症。积极地接受CRRT(CVVH、CVVHDF、CVVHD)治疗的患者，有助于代谢和血容量稳定而不引起血液动力学的紊乱102。若并发ARF，其死亡率极高，尽快接受CVVH治疗的存活患者，肾脏功能可完全恢复。回顾性非对照研究发现，心脏外科手术合并急性肾衰患者(血滤前肌酐水平295mmol/L，血滤开始平均间隔为50小时，血滤持续时间平均6.4天)出