1、持续肾脏替代治疗的局部枸橼酸抗凝,北京协和医院杜斌,ICU中的急性肾脏功能衰竭*: BEST Kidney,患病率1738/29269 (5.7%, 95%CI 5.5 6.0%)危险因素感染性休克(47.5%, 95%CI 45.2 49.5%)住院病死率60.3% (95%CI 58.0 62.6%)*少尿( 84 mg/dL),Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005
2、; 294: 813-818,急性肾功能衰竭的定义: RIFLE标准,Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 20
3、04; 8: R204-R212,ICU的急性肾脏损伤(AKI),Ostermann M, Chang RWS. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 2007; 35: 1837-1843,35.8%,急性肾功能衰竭的治疗(n = 646),Perez-Valdivieso JR, Bes-Rastrollo M, Monedero P, et al. Prognosis and serum creatinine levels in acute renal failur
4、e at the time of nephrology consultation: an observational cohort study. BMC Nephrology 2007; 8: 14-22,持续肾脏替代治疗管路寿命,满足治疗要求降低治疗费用减少重新安装管路的护理时间,18 30 hr,Holt AW, Bierer P, Glover P, Plummer JL, Bersten AD. Conventional coagulation and thromboelastograph parameters and longevity of continuous renal rep
5、lacement circuits. Intensive Care Med 2002; 28: 1649-55.Stefanidis I, Hagel J, Frank D, Maurin N. Hemostatic alterations during continuous venovenous hemofiltration in acute renal failure. Clin Nephrol 1996; 46(3): 199-205.Kox WJ, Rohr U, Waurer H. Practical aspects of renal replacement therapy. Int
6、 J Artif Organs 1996; 19: 100-5.Tan HK, Baldwin I, Bellomo R. Continuous veno-venous haemofiltration without anticoagulation in high-risk patients. Intensive Care Med 2000; 26: 1652-7.,持续肾脏替代治疗的影响因素,血管通路位置中心静脉导管: 口径, 管腔设计血流可靠性血滤管路设计透析膜的生物相容性护理人员的培训及专业技能抗凝效果,持续肾脏替代的抗凝,血滤滤器与管路的抗凝作用,全身抗凝有害作用,持续肾脏替代的抗凝选
7、择,基础疾病现有抗凝措施临床经验,国内文献报告的抗凝方法,CRRT时的肝素抗凝,肝素抗凝的优缺点,优点最常用的抗凝方法临床方案成熟半衰期短过量时鱼精蛋白对抗,缺点出血危险APTT与滤器寿命无关肝素诱导血小板缺乏(HIT),枸橼酸抗凝的原理,局部枸橼酸抗凝的原理,凝血过程需要游离钙参与枸橼酸螯合游离钙, 补充钙离子可以恢复血库使用枸橼酸保存血液采用枸橼酸可以在RRT时进行局部抗凝:血液进入体外循环后即加入枸橼酸血液进入体内前补充游离钙体外循环对血液进行抗凝, 体内血液正常通过测定游离钙监测抗凝,肝素抗凝时的滤器中空纤维,Hofbauer R, Moser D, Frass M, et al. E
8、ffect of anticoagulation on blood membrane interactions during hemodialysis. Kidney Int,低分子肝素抗凝时的滤器中空纤维,Hofbauer R, Moser D, Frass M, et al. Effect of anticoagulation on blood membrane interactions during hemodialysis. Kidney Int,枸橼酸抗凝时的滤器中空纤维,Hofbauer R, Moser D, Frass M, et al. Effect of anticoagu
9、lation on blood membrane interactions during hemodialysis. Kidney Int,血滤终止的原因,Kutsogiannis DJ, Gibney RTN, Stollery D et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005; 67: 2361-2367,滤器寿命的Cox风险比例模型分析,Kutsogian
10、nis DJ, Gibney RTN, Stollery D et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005; 67: 2361-2367,出血或输血的比例,Kutsogiannis DJ, Gibney RTN, Stollery D et al. Regional citrate versus systemic heparin anticoagulation
11、for continuous renal replacement in critically ill patients. Kidney Int 2005; 67: 2361-2367,CRRT时出血的多因素Poisson回归,Kutsogiannis DJ, Gibney RTN, Stollery D et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005; 67: 2
12、361-2367,不同抗凝方法的滤器寿命,Kutsogiannis DJ, Gibney RTN, Stollery D et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2005; 67: 2361-2367,枸橼酸局部抗凝方案,枸橼酸局部抗凝图示,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案说明,血滤机常规预冲肝素
13、盐水根据患者病情选择适当治疗模式CVVHCVVHDCVVHDF,枸橼酸局部抗凝方案,准备枸橼酸抗凝液血液保存液(I) 600 ml/袋广州华南医疗用品有限公司,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案,准备输液泵将输液管路与血滤管路的动脉端相连接最接近患者处(血泵前)根据患者病情, 设置血滤机的常规参数,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案,ACD-A初始泵速为血液流速(BFR)的2.0 2.5%泵速(ml/hr) = 1.2 1.5 x BFR (ml/min)例如
14、BFR = 120 ml/minACD-A泵速 = 144 180 ml/hr,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案,常规情况下选择前稀释方式,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案,置换液中不含钙,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案,准备10%葡萄糖酸钙溶液及注射器泵将输液管路连接至血滤管路静脉端葡萄糖酸钙溶液初始泵速为8.8 11.0 ml/hr (ACD-A泵速的6.1%),R,heater,
15、ACD-A,V,V,PV,PA,UF,BLD,SAD,葡萄糖酸钙,枸橼酸局部抗凝方案: 抗凝监测,Q2h x 4,Q4h x 4,Day 1,Day 2Q 6 8 h,枸橼酸局部抗凝方案: 抗凝监测,R,heater,ACD-A,V,V,PV,PA,UF,BLD,SAD,枸橼酸钙,动脉标本外周静脉或动脉游离钙1.00 1.20 mmol/L,静脉标本滤器后血滤管路游离钙0.20 0.40 mmol/L,枸橼酸局部抗凝方案: 抗凝监测,枸橼酸局部抗凝方案: 抗凝监测,枸橼酸局部抗凝方案: 抗凝监测,每次更换输液部位或管路后1 2小时内应监测离子钙若血泵停止数分钟以上必须关闭ACD-A泵(防止枸橼
16、酸进入患者体内)必须关闭葡萄糖酸钙泵(防止过量钙进入患者体内)若因病情需要停止血滤(如诊断, 更换导管, 手术, 凝血或更换管路), 应在重新开始血滤时按照停止前的速度设置ACD-A及葡萄糖酸钙泵速,枸橼酸局部抗凝方案: 抗凝监测,若HCO3增加 10 mEq/L需要确认ACD-A输注部位正确, 未直接进入患者体内降低ACD-A泵速25%2 4小时后测定HCO3若测定结果仍不正常再次降低ACD-A泵速25%,枸橼酸局部抗凝方案: 抗凝监测,若患者血Na上升10 mEq/L或 155 mEq/L需要确认ACD-A输注部位正确, 未直接进入患者体内降低ACD-A泵速25%2 4小时后测定血Na若测
17、定结果仍不正常输注5%GS,枸橼酸抗凝的并发症: 代谢性碱中毒,主要原因枸橼酸转化为HCO3 (1 mmol枸橼酸能够产生3 mmol的HCO3)次要原因溶液含有35 mEq/L HCO3消化道丢失含有乙酸成分的TPN治疗方法是增加酸负荷生理盐水(pH 5.4),枸橼酸抗凝的并发症: Citrate Lock,总钙增加, 而游离钙不变或降低枸橼酸负荷超过肝脏代谢及CRRT清除能力治疗降低或停止枸橼酸10 30分钟然后按照之前70%的速度开始注意是否忽略大量输血时的枸橼酸负荷,总结,危重病患者常常发生急性肾功能损害(AKI)肾脏替代治疗是重要的治疗手段充分抗凝是保证肾脏替代治疗疗效的重要措施局部枸橼酸抗凝有效, 安全, 禁忌症少,