1、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 purificattion therapy i
2、ntended 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-Bishoff提出连续性静脉-静脉血液滤过(C
3、VVH)1980年，Paganini提出缓慢连续性超滤(SCUF)1984年Geronemus 提出CAVHD，1987-CVVHD1985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 venovenous hemofiltration，CVVH）连续性静静
4、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 版）,总 结,急性肾损伤,急性肾损伤(acute kidney inj
5、ury，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/hx 24 hr or Anuria x 12 hrs,UO .5ml/kg/hx 12 hr,UO 50%,Increase crea
6、tinine x3or GFR dec 75%or creatinine 4mg/dl(Acute rise of 0.5 mg/dl),HighSensitivity,HighSpecificity,Persistent ARF* = complete loss of renal function 4 weeks,Oliguria,“Acute on Chronic” Disease,Creatinine is expressed in mg/dL and (mcmol/L).,AKIN分层标准,Stage Serum creatinine criteria Urine output cri
7、teria 1 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 hours more than or equal to 150% to 200% (1.5- to 2-fold) from baseline 2 Increase in serum creatinine to Less than 0.5 ml/kg per more than200% to 300% ho
8、ur for more than 12hours ( 2- to 3-fold) frombaseline 3 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 hours more than or equato 4.0 mg/dl 354 mol/l with an acute increaseof at least 0.5 mg/dl 44
9、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）,Acute renal failure,Asymptomatic,nonoliguric,adequate nutrition possible,(Non)oliguric,haemodyna
10、mically 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 for the dialytic treatment of acute renal failure according to circumstancesIHD = intermittent h
11、aemodialysis, 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 be 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
12、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 indications for CRRT in the ICU,Nonobstructive oliguria (urine output 30 mmol/l)Hyperkalaemia (K+ 6.5 mmo
13、l/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,Progressive severe dysnatraemia (Na+ 160 or 39.5C)Clinically significant organ oedema (especially lung)
14、Drug overdose with dialyzable toxinCoagulopathy requiring large amounts of blood products in patient with or at risk of pulmonary oedema/ARDS,Any one of these indications constitutes sufficient grounds for considering the initiation of CRRT. Two of the above criteria make CRRT highly desirable. Comb
15、ined 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 early enough, hyperkalaemia is easily controlled. For example, a fulminant liver failure patient with adult re
16、spiratory 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 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
17、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
18、活者中有85.5%肾功能恢复,Age (years) 66 (5174) Reasons to start CRRTGender (male) 662/1006 (65.8%) Oliguria/anuria 703/1002 (70.2%)Premorbid renal function High urea/creatinine 531/1002 (53.0%)Normal 590/1006 (58.6%) Metabolic acidosis 437/1002 (43.6%)Chronic impairment 283/1006 (28.1%) Fluid overload 368/100
19、2 (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%)Hospital 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
20、.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 (20.0%)Drug induced 176/1003 (17.5%)Hepatorenal syndrome 73/1003 (7.3%)Obstructive uropathy 20/1003 (2.0%)Others 114/1003 (11.4
21、%),Data are presented as median and interquartile ranges (25th75th percentiles) or percentages; SAPS II,Simplified Acute Physiology score; Hospital to ICU, duration betweenhospital admission and intensive care unit admission; ICU to start, duration between intensive care unit admission and study inc
22、lusion; 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 AnticoagulationCVVH 531/1006 (52.8%) Unfractionated heparin 429/1000 (42.9%)CVVHDF 342/1006 (34.0%) Sodium citrate 99/1000 (9.9%)CVVHD 132/1006 (13.1%)
23、 Nafamostat mesilate 61/1000 (6.1%)CAVHD 1/1006 (0.1%) Low-molecular-weight 44/1000 (4.4%)Dilution site for replacement fluid heparinPredilution 509/870 (58.5%) Prostacyclin 11/1000 (1.1%)Postdilution 361/870 (41.5%) Hirudin 9/1000 (0.9%)Filter material Heparin-protamine 6/1000 (0.6%)Polyacrylonitri
24、le 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%)Cellulose triacetate 89/975 (9.1%)Polymethyl-methacrylate 27/975 (2.8%)Polyarylether-sulfone 14/975 (1.4%)Cellulose diacetate 11/975 (1.1%)Othe
25、rs 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 nafamostat 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%)Indwell
26、ing 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%)Others 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%)Bradyc
27、ardia 3/1000 (0.3%)Ventricular tachycardia 3/1000 (0.3%)Atrial flutter 1/1000 (0.1%)Ventricular fibrillation 1/1000 (0.1%),a Intracranial, lower 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
28、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 Early 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) 0.0001Serum creatini
29、ne prior to CRRT (mg/dl):nonrhabdomyolysis patients (n = 89)a 3.26 (1.8) 2.69 (1.6) 3.59 (4.3) 0.025Serum creatinine prior to CRRT (mg/dl)rhabdomyolysis patients only (n = 11) 5.94 (1.2) 5.73 (1.06) 6.50 (1.8) 0.387Creatinine clearance prior to CRRT (ml/min)b 15.1 (19.3) 17.4 (26.4) 13.4 (11.6) 0.33
30、2Albumin prior to CRRT (g/dl)c 2.61 2.76 2.50 0.049Oliguric on CRRT day 1 (%) 46.00 56.10 39.00 0.091Heart rate (beats/min) 110.0 116.8 105.3 0.001Mean blood pressure (mmHg) 88.0 87.8 88.2 0.915Cardiac index (l/min per m2) 5.07 4.95 5.15 0.525Stroke volume (ml) 91.8 85 96.6 0.056Oxygen delivery inde
31、x(ml O2/min per m2) 738.8 707.6 760.4 0.239Patients meeting SIRS criteria prior to CRRT (%) 91.20 94.60 88.90 0.345Hospital day of CRRT initiation 15.8 (23.4) 10.5 (15.3) 19.4 (27.2) 24小时，无尿12小时；BUN25-30mmol/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
32、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 50200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,
