1、CRRT的规范化治疗,浙江省人民医院孙仁华,概述,连续性肾脏替代治疗（continuous renal replacement therapy，CRRT）是指一组体外血液净化的治疗技术，是所有连续、缓慢清除水分和溶质治疗方式的总称。传统CRRT 技术每天持续治疗24 小时，目前临床上常根据患者病情治疗时间做适当调整。CRRT 的治疗目的已不仅仅局限于替代功能受损的肾脏，近来更扩展到常见危重疾病的急救，成为各种危重病救治中最重要的支持措施之一，与机械通气和全胃肠外营养地位同样重要。,血液净化标准操作规程（2010 版）,CRRT,CRRT is any extracorpreal blood p
2、urificattion 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 所谓CRRT也就是指所有每天24小时或接近24小时的缓慢、连续清除水和溶质的治疗方法。,历史,1977年，Kramer等首先提出了连续性动静脉血液滤过(continuous arterio-venous hemofiltration，CAVH) 1979年，Bambauer
3、-Bishoff提出连续性静脉-静脉血液滤过(CVVH) 1980年，Paganini提出缓慢连续性超滤(SCUF) 1984年Geronemus 提出CAVHD，1987-CVVHD 1985年Ronco首次将CAVHDF应用于治疗l例败血症合并MODS患者 1992年Grootendorst 提出高容量血液滤过(high volume hemofiltration，HVHF) 1998年，Tetra等提出连续性血浆滤过吸附(CPFA),主要技术,缓慢连续超滤（slow continuous ultrafiltration，SCUF） 连续性静静脉血液滤过（continuous venove
4、nous hemofiltration，CVVH） 连续性静静脉血液透析滤过（continuous venovenous hemodiafiltration，CVVHDF） 连续性静静脉血液透析（continuous venovenous hemodialysis，CVVHD） 连续性高通量透析（continuous high flux dialysis，CHFD） 连续性高容量血液滤过（high volume hemofiltration，HVHF） 连续性血浆滤过吸附（continuous plasmafiltration adsorption，CPFA）,血液净化标准操作规程（2010
5、版）,总 结,急性肾损伤,急性肾损伤(acute kidney injury，AKI)是指发生急性肾功能异常，包括从肾功能微小改变到最终肾衰竭整个过程。,RIFLE Criteria for Acute Renal Dysfunction,Risk,Injury,Failure,Loss,ESRD,Increased creatinine x1.5 or GFR decrease 25%,End Stage Renal Disease,GFR Criteria*,Urine Output Criteria,UO .3ml/kg/h x 24 hr or Anuria x 12 hrs,UO .
6、5ml/kg/h x 12 hr,UO .5ml/kg/h x 6 hr,Increased creatinine x2 or GFR decrease 50%,Increase creatinine x3 or GFR dec 75% or creatinine 4mg/dl (Acute rise of 0.5 mg/dl),High Sensitivity,High Specificity,Persistent ARF* = complete loss of renal function 4 weeks,Oliguria,“Acute on Chronic” Disease,Creati
7、nine is expressed in mg/dL and (mcmol/L).,AKIN分层标准,Stage Serum creatinine criteria Urine output criteria1 Increase in serum creatinine of more than or equal to 0.3 mg/dl Less than 0.5 ml/kg per( 26.4 mol/l) or increase to hour for more than 6 hoursmore than or equal to 150% to 200% (1.5- to 2-fold)
8、from baseline2 Increase in serum creatinine to Less than 0.5 ml/kg per more than200% to 300% hour for more than 12hours( 2- to 3-fold) frombaseline3 Increase in serum creatinine to Less than 0.3 ml/kg per more than300% ( 3-fold) from hour for 24 hours or baseline(or serumcreatinine of anuria for 12
9、hoursmore than or equato 4.0 mg/dl 354 mol/l with an acuteincreaseof at least 0.5 mg/dl44 mol/l),适应症,肾脏疾病 非肾脏疾病,血液净化标准操作规程（2010 版）,肾脏疾病,重症急性肾损伤（AKI） 伴血流动力学不稳定和需要持续清除过多水或毒性物质，如AKI合并严重电解质紊乱、酸碱代谢失衡、心力衰竭、肺水肿、脑水肿、急性呼吸窘迫综合征（ARDS）、外科术后、严重感染等。 慢性肾衰竭（CRF） 合并急性肺水肿、尿毒症脑病、心力衰竭、血流动力学不稳定等。,血液净化标准操作规程（2010 版）,Acut
10、e renal failure,Asymptomatic, nonoliguric, adequate nutrition possible,(Non)oliguric, haemodynamically stable; life-threathening hyperkalaemia,(Non)oliguric, haemodynamically unstable,High risk of bleeding,No high risk,Expectative,(Increasing) uraemia,IHD#,Unstable,Citrate-CRRT,CRRT,Stable,Algorithm
11、 for the dialytic treatment of acute renal failure according to circumstances IHD = intermittent haemodialysis, CRRT = continuous renal replacement therapy. Delay initiation of dialytic treatment to maximise the odds of native renal recovery, # if no citrate-protocol for CRRT, heparin-free IHD may b
12、e used as alternative treatment.,非肾脏疾病,非肾脏疾病包括多器官功能障碍综合征（MODS）、脓毒血症或败血症性休克、急性呼吸窘迫综合征（ARDS）、挤压综合征、乳酸酸中毒、急性重症胰腺炎、心肺体外循环手术、慢性心力衰竭、肝性脑病、药物或毒物中毒、严重液体潴留、需要大量补液、电解质和酸碱代谢紊乱、肿瘤溶解综合征、过高热等,血液净化标准操作规程（2010 版）,禁忌症,CRRT无绝对禁忌证，但存在以下情况时应慎用。 无法建立合适的血管通路。 严重的凝血功能障碍。 严重的活动性出血，特别是颅内出血。,血液净化标准操作规程（2010 版）,Potential indi
13、cations for CRRT in the ICU,Nonobstructive oliguria (urine output 30 mmol/l) Hyperkalaemia (K+ 6.5 mmol/l or rapidly rising K+)* Suspected uraemic organ involvement (pericarditis/encephalopathy/neuropathy/myopathy),Bellomo and Ronco Crit Care 2000, 4:339345,Potential indications for CRRT in the ICU,
14、Progressive severe dysnatraemia (Na+ 160 or 39.5C) Clinically significant organ oedema (especially lung) Drug overdose with dialyzable toxin Coagulopathy requiring large amounts of blood products in patient with or at risk of pulmonary oedema/ARDS,Any one of these indications constitutes sufficient
15、grounds for considering the initiation of CRRT. Two of the above criteria make CRRT highly desirable. Combined disorders suggest the initiation of CRRT even before some of the above-mentioned limits have been reached. *IHD removes potassium more efficiently than CRRT.However, if CRRT is started earl
16、y enough, hyperkalaemia is easily controlled. For example, a fulminant liver failure patient with adult respiratory distress syndrome (ARDS), an international normalized ratio 3 and spontaneous epistaxis. Unless volume is rapidly removed, as fresh frozen plasma is rapidly given, the patient is very
17、likely to develop pulmonary oedema.,治疗前患者评估,选择合适的治疗对象，以保证CRRT 的有效性及安全性。患者是否需要CRRT治疗应由有资质的肾脏专科或ICU 医师决定。肾脏专科或ICU 医师负责患者的筛选、治疗方案的确定等。,血液净化标准操作规程（2010 版）,CRRT现状调查,Uchino等报道:前瞻性、观察研究结果，2000.9-2001.12， 23个国家、54家ICU、1006例患者的CRRT应用情况。 除1例外均采用V-V通路，CVVH占52.8%，33.1%不抗凝，平均剂量为20.4ml/kg/h，仅11.7%35ml/kg/h。,CRRT现
18、状调查,常用抗凝剂肝素42.9%、枸橼酸9.9%、甲磺酸萘莫司他6.1%、低分子肝素4.4%。 常见并发症为低血压19%，心律失常4.3%，出血3.3%，其中应用低分子肝素者出血为11.4% 医院死亡率为63.8%，存活者中有85.5%肾功能恢复,Age (years) 66 (5174) Reasons to start CRRT Gender (male) 662/1006 (65.8%) Oliguria/anuria 703/1002 (70.2%) Premorbid renal function High urea/creatinine 531/1002 (53.0%) Norma
19、l 590/1006 (58.6%) Metabolic acidosis 437/1002 (43.6%) Chronic impairment 283/1006 (28.1%) Fluid overload 368/1002 (36.7%) Unknown 133/1006 (13.2%) Hyperkalemia 186/1002 (18.6%) SAPS II 48 (3962) Immunomodulation 136/1002 (13.6%) Predicted mortality (%) 41.5 (23.071.4) Others 70/1002 ( 7.0%) Hospita
20、l to ICU (days) 1 (07) ICU mortality 555/1003 (55.3%) ICU to start (days) 1.2 (0.44.1) Hospital mortality 641/ 999 (64.2%) Contributing factors to ARF SMR 1.38 (1.281.50) Sepsis/septic shock 504/1003 (50.2%) Major surgery 377/1003 (37.6%) Low cardiac output 262/1003 (26.1%) Hypovolemia 201/1003 (20.
21、0%) Drug induced 176/1003 (17.5%) Hepatorenal syndrome 73/1003 (7.3%) Obstructive uropathy 20/1003 (2.0%) Others 114/1003 (11.4%),Data are presented as median and interquartile ranges (25th75th percentiles) or percentages; SAPS II,Simplified Acute Physiology score; Hospital to ICU, duration betweenh
22、ospital admission and intensive care unit admission; ICU to start, duration between intensive care unit admission and study inclusion; ARF, acute renal failure; SMR, standardized mortality ratio; ICU, intensive care unit,病人基本情况,Intensive Care Med (2007) 33:15631570,CRRT mode Anticoagulation CVVH 531
23、/1006 (52.8%) Unfractionated heparin 429/1000 (42.9%) CVVHDF 342/1006 (34.0%) Sodium citrate 99/1000 (9.9%) CVVHD 132/1006 (13.1%) Nafamostat mesilate 61/1000 (6.1%) CAVHD 1/1006 (0.1%) Low-molecular-weight 44/1000 (4.4%) Dilution site for replacement fluid heparin Predilution 509/870 (58.5%) Prosta
24、cyclin 11/1000 (1.1%) Postdilution 361/870 (41.5%) Hirudin 9/1000 (0.9%) Filter material Heparin-protamine 6/1000 (0.6%) Polyacrylonitrile 457/975 (46.9%) Others b 3/1000 (0.3%) Polysulfone 209/975 (21.4%) Combination c 7/1000 (0.7%) Polyamide 164/975 (16.8%) No anticoagulation 331/1000 (33.1%) Cell
25、ulose triacetate 89/975 (9.1%) Polymethyl-methacrylate 27/975 (2.8%) Polyarylether-sulfone 14/975 (1.4%) Cellulose diacetate 11/975 (1.1%) Others a 4/975 (0.4%),a 3 Polyester-polymer-alloy, 1 ethylene-vinyl alcohol; b 2 danaparoid, 1 warfarin; c 4 heparin-citrate, 2 heparin-prostacyclin, 1 nafamosta
26、t mesilate-low-molecular-weight heparin,CRRT使用情况,Intensive Care Med (2007) 33:15631570,Hypotension 188/1000 (18.8%) Bleeding 33/997 (3.3%) Indwelling vascular catheter sites 13/997 (1.3%) Intra-abdominal 3/997 (0.3%) Gastrointestinal 3/997 (0.3%) Nostril 3/997 (0.3%) Sternal wound 3/997 (0.3%) Other
27、s a 8/997 (0.8%) Arrhythmia 43/1000 (4.3%) Atrial fibrillation 24/1000 (2.4%) Supraventricular tachycardia 7/1000 (0.7%) Cardiac arrest 4/1000 (0.4%) Bradycardia 3/1000 (0.3%) Ventricular tachycardia 3/1000 (0.3%) Atrial flutter 1/1000 (0.1%) Ventricular fibrillation 1/1000 (0.1%),a Intracranial, lo
28、wer leg, bone marrow aspiration site, oral, and pericardial,并发症,Intensive Care Med (2007) 33:15631570,Venkataraman et al, J Crit Care, 2002,CRRT处方与实际完成的比较,何时开始CRRT？,目前没有统一的标准：“时间”、指标等均不统一。 Getting等报道：早期开始RRT（BUN 42.6mg/dl ）比晚期（BUN 94.5mg/dl）RRT的生存率高（39%-20%）,Intensive Care Med 1999;25:805-813.,All E
29、arly starters: Late starters: p value(n = 100) BUN 60 mg/dl(n = 41) (n = 59)BUN prior to CRRT (mg/dl) 73.2 (39.6) 42.6 (12.9) 94.5 (28.3) 0.0001 Serum creatinine prior to CRRT (mg/dl): nonrhabdomyolysis patients (n = 89)a 3.26 (1.8) 2.69 (1.6) 3.59 (4.3) 0.025 Serum creatinine prior to CRRT (mg/dl)
30、rhabdomyolysis patients only (n = 11) 5.94 (1.2) 5.73 (1.06) 6.50 (1.8) 0.387 Creatinine clearance prior to CRRT (ml/min)b 15.1 (19.3) 17.4 (26.4) 13.4 (11.6) 0.332 Albumin prior to CRRT (g/dl)c 2.61 2.76 2.50 0.049 Oliguric on CRRT day 1 (%) 46.00 56.10 39.00 0.091 Heart rate (beats/min) 110.0 116.
31、8 105.3 0.001 Mean blood pressure (mmHg) 88.0 87.8 88.2 0.915 Cardiac index (l/min per m2) 5.07 4.95 5.15 0.525 Stroke volume (ml) 91.8 85 96.6 0.056 Oxygen delivery index (ml O2/min per m2) 738.8 707.6 760.4 0.239 Patients meeting SIRS criteria prior to CRRT (%) 91.20 94.60 88.90 0.345 Hospital day
32、 of CRRT initiation 15.8 (23.4) 10.5 (15.3) 19.4 (27.2) 0.0001,a Because of a different serum creatinine response, rhabdomyolysis patients are analyzed separately from nonrhabdomyolysis patients b Two-hour early morning timed collections (incomplete data, n = 70) c Incomplete data (n = 91),Gettings
33、et al., Intensive Care Med 1999,Gettings et al., Intensive Care Med 1999,All Early starters Late starters p valueHospital LOS (days) 50.3 (43.4) 46.5 (37.0) 53.0 (47.4) 0.459 Duration of CRRT period (days)a 19.2 (16.5) 17.7 (15.1) 20.2 (17.5) 0.448 Number of CRRT daysb 18.8 (16.3) 17.6 (15.2) 19.6 (
34、17.1) 0.546 Survival (%)c 28.0 39.0 20.30 0.041 Recovery of renal function in survivors (%) 96.40 100 91.60 0.248,a Time course of CRRT period from start to finish (includes days without CRRT) b Actual number of days where CRRTwas employed c Of survivors (n = 28), 16 were early starters and 12 were
35、late starters,Gettings et al., Intensive Care Med 1999,早期开始CRRT？,Demirkilic等回顾性分析3413例心脏外科手术病人，其中61例需CRRT治疗（CVVHDF），分为二组；27例在Cr5mg/dl或K5.5mEq/l时开始CRRT治疗，平均术后2.61.7天；34例在尿量100ml/8h即开始，平均术后0.90.3天。 结果：早期和晚期组ICU和医院死亡率分别为：17.6-48.1%，23.5-55.5%,J Card Surg 2004 ;19:17-20,早期开始CRRT？,Elahi等报道了类似结果，1264例心脏外科
36、手术病人，64例需CRRT治疗（CVVH），分二组：28例（晚期组），BUN84mg/dl或Cr2.8mg/dl或K6.0mEq/L开始，平均术后2.62.2天；36例早期组尿量100ml/8h即开始，平均术后0.80.2天 结果：早期组和晚期组，医院死亡率为22%vs43%,Eur J Cardiothorac Surg,治疗时机的选择,急性单纯性肾损伤患者血清肌酐354mol/L，或尿量0.3ml/(kg.h)，持续24 小时以上，或无尿达12 小时 ；急性重症肾损伤患者血清肌酐增至基线水平23 倍，或尿量0.5ml/(kg.h), 时间达12 小时，即可行CRRT。,血液净化标准操作规程
37、（2010 版）,治疗时机的选择,对于脓毒血症、急性重症胰腺炎、MODS、ARDS 等危重病患者应及早开始CRRT 治疗。 当有下列情况时，立即给予治疗：严重并发症经药物治疗等不能有效控制者，如容量过多包括急性心力衰竭，电解质紊乱，代谢性酸中毒等。,血液净化标准操作规程（2010 版）,应用CRRT原因,Louise等进行的随机、多中心流行病学调查显示：116例ICU患者应用CRRT原因分别为：少尿或无尿62%，尿毒症难以控制22.4%，液体负荷过重6%，高钾血症3.5%，严重酸中毒2.6%，多因素3.5%。 Van Bommel主张早期CRRT指征为少尿24小时，无尿12小时；BUN25-3
38、0mmol/l,Am J Respir Crit Care Med Vol 162. pp 191196, 2000,治疗模式选择,临床上应根据病情严重程度以及不同病因采取相应的CRRT模式及设定参数。SCUF和CVVH用于清除过多液体为主的治疗；CVVHD用于高分解代谢需要清除大量小分子溶质的患者；CHFD适用于ARF伴高分解代谢者；CVVHDF有利于清除炎症介质，适用于脓毒症患者；CPFA主要用于去除内毒素及炎症介质。,血液净化标准操作规程（2010 版）,CRRT 常用治疗模式比较SCUF CVVH CVVHD CVVHDF血流量（ml/min） 50100 50200 50200 50
39、200透析液流量（ml/min） 1020 1020清除率（L/24h） 1236 1436 2040超滤率（ml/min） 25 825 24 812中分子清除力 血滤器/透析器 高通量 高通量 低通量 高通量置换液 无 需要 无 需要溶质转运方式 无 对流 弥散 对流弥散有效性 用于清除液体 清除较大分 清除小分子 清除中小分子物质 物质 子物质,CRRT剂量,慢性肾衰血透的剂量要求是：kt/V1.2 CRRT的治疗剂量目前尚无统一意见 高容量血液滤过（HVHF）在严重感染、重症胰腺炎（SIRS）中受推崇。,100,90,80,70,60,50,40,30,20,10,0,Group 1(
40、n=146),(,Uf,= 20 ml/h/Kg),Group 2 (n=139),(,Uf,= 35 ml/h/Kg),Group 3 (n=140),(,Uf,= 45 ml/h/Kg),41 %,57 %,58 %,p 0.001,p ns.,p 0.001,CUMULATIVE SURVIVAL VS TREATMENT DOSE,Survival Time (Days),CUMULATIVE PROPORTION SURVIVAL,50,40,30,20,10,0,1.0,.9,.8,.7,.6,.5,.4,.3,.2,.1,.0,Group 1,Group 3,Group 2,(p
41、 = 0.0007),(p = 0.0013),Saudan et al, Kidney Int 2006,Saudan et al, Kidney Int 2006,Bouman研究,Bouman et al., Crit Care Med 2002,Bouman et al., Crit Care Med 2002,Bouman et al., Crit Care Med 2002,Schiffl et al, NEJM 2002,Schiffl研究：IHD剂量与预后关系,Schiffl et al, NEJM 2002,Schiffl研究：IHD剂量与预后关系,Schiffl et al
42、, NEJM 2002,Schiffl研究：IHD剂量与预后关系,Kellum, Nature Clin Pract Nephrol 2007,治疗剂量与预后的关系,Palevsky et al, NEJM 2008; 349 (May 20),不同治疗强度间死亡率比较,RENAL研究：Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Study,KaplanMeier Estimates of the Probability of Death. Mortality at 28 days was
43、 similar in the higher-intensity and lower-intensity treatment groups (38.5% and 36.9%, respectively), and mortality at 90 days was the same (44.7%) in both groups.,N Engl J Med 2009;361:1627-38.,透析剂量,推荐采用体重标化的超滤率作为剂量单位ml/(kgh)。CVVH 后置换模式超滤率至少达到3545 ml/(hkg) 才能获得理想的疗效，尤其是在脓毒症、SIRS、MODS 等以清除炎症介质为主的情况
44、下，更提倡采用高容量模式。,血液净化标准操作规程（2010 版）,血管通路,临时导管常用的有颈内、锁骨下及股静脉双腔留置导管，右侧颈内静脉插管为首选，置管时应严格无菌操作。提倡在B 超引导下置管, 可提高成功率和安全性。带涤纶环长期导管若预计治疗时间超过3 周，使用带涤纶环的长期导管，首选右颈内静脉。,血液净化标准操作规程（2010 版）,抗凝方案,普通肝素：采用前稀释的患者，一般首剂量1520mg，追加剂量510mg/h，静脉注射；采用后稀释的患者，一般首剂量2030mg，追加剂量815mg/h，静脉注射；治疗结束前3060 分钟停止追加。抗凝药物的剂量依据患者的凝血状态个体化调整；治疗时间越长，给予的追加剂量应逐渐减少。,
