持续肾脏替代治疗的局部枸橼酸抗凝ICU的急性肾脏损伤(AKI)OstermannM,ChangRWS.AcutekidneyinjuryintheintensivecareunitaccordingtoRIFLE.CritCareMed2007;35:1837-184335.8%17.20%11.00%7.60%0%20%40%60%AcuteKidneyInjury*FailureInjuryRisk急性肾功能衰竭的治疗(n=646)68.0%7.4%16.8%7.5%0%20%40%60%80%100%非透析IHDCRRTIHD+CRRT患者百分比(%)Perez-ValdiviesoJR,Bes-RastrolloM,MonederoP,etal.Prognosisandserumcreatininelevelsinacuterenalfailureatthetimeofnephrologyconsultation:anobservationalcohortstudy.BMCNephrology2007;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18–30hr1.HoltAW,BiererP,GloverP,PlummerJL,BerstenAD.Conventionalcoagulationandthromboelastographparametersandlongevityofcontinuousrenalreplacementcircuits.IntensiveCareMed2002;28:1649-55.2.StefanidisI,HagelJ,FrankD,MaurinN.Hemostaticalterationsduringcontinuousvenovenoushemofiltrationinacuterenalfailure.ClinNephrol1996;46(3):199-205.3.KoxWJ,RohrU,WaurerH.Practicalaspectsofrenalreplacementtherapy.IntJArtifOrgans1996;19:100-5.4.TanHK,BaldwinI,BellomoR.Continuousveno-venoushaemofiltrationwithoutanticoagulationinhigh-riskpatients.IntensiveCareMed2000;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抗凝方法病例数(%)单药抗凝普通肝素844(37.9)低分子肝素686(30.8)枸橼酸26(1.2)联合抗凝普通肝素+低分子肝素483(21.7)普通肝素+枸橼酸52(2.3)无抗凝137(6.1)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HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt低分子肝素抗凝时的滤器中空纤维HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt枸橼酸抗凝时的滤器中空纤维HofbauerR,MoserD,FrassM,etal.Effectofanticoagulationonbloodmembraneinteractionsduringhemodialysis.KidneyInt血滤终止的原因枸橼酸(n=36)肝素(n=43)管路凝血6(16.7%)23(53.5%)改为IHD1(2.8%)0血管通路问题2(5.6%)0管路断裂或渗漏1(2.8%)0管路打折1(2.8%)0转运至放射科或手术室8(22.2%)8(18.6%)滤器压力高1(2.8%)2(4.7%)其他原因16(44.4%)10(23.3%)KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367不同抗凝方法的滤器寿命KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367CRRT时出血的多因素Poisson回归RR95%CIP值截距0.0010.00001–0.1740.008枸橼酸0.1370.020–0.9590.05LOD评分0.9240.571–1.4940.75AT-III水平6.6470.789–56.0030.08KutsogiannisDJ,GibneyRTN,StolleryDetal.Regionalcitrateversussystemicheparinanticoagulationforcontinuousrenalreplacementincriticallyillpatients.KidneyInt2005;67:2361-2367枸橼酸局部抗凝方案枸橼酸局部抗凝图示RheaterACD-AVVPVPAUFBLDSAD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)600ml/袋广州华南医疗用品有限公司成分分子量含量(g)mmol枸橼酸三钠(二水)294.122.075枸橼酸(一水)210.148.038葡萄糖(一水)198.1724.5120加注射用水至1000mlRheaterACD-AVVPVPAUFBLDSAD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RheaterACD-AVVPVPAUFBLDSAD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)=1.2–1.5xBFR(ml/min)例如BFR=120ml/minACD-A泵速=144–180ml/hrRheaterACD-AVVPVPAUFBLDSAD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RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案置换液中不含钙RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙常规置换液配方0.9%NS2000ml注射用水500ml5%NaHCO3125ml25%MgSO43ml10%CaGlu20ml15%KCl5ml50%GS总量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8.8–11.0ml/hr(ACD-A泵速的6.1%)RheaterACD-AVVPVPAUFBLDSAD葡萄糖酸钙枸橼酸局部抗凝方案:抗凝监测Q2hx4Q4hx4Day1Day2Q6–8h枸橼酸局部抗凝方案:抗凝监测RheaterACD-AVVPVPAUFBLDSAD枸橼酸钙动脉标本外周静脉或动脉游离钙1.00–1.20mmol/L静脉标本滤器后血滤管路游离钙0.20–0.40mmol/L枸橼酸局部抗凝方案:抗凝监测静脉标本游离钙从滤器后静脉取血部位取血ACD-A输注速度调整0.20mmol/L降低5ml/hr0.20–0.40mmol/L维持不变0.41–0.50mmol/L增加5ml/hr0.50mmol/L增加10ml/hr枸橼酸局部抗凝方案:抗凝监测动脉标本游离钙从外周静脉或动脉取血10%葡萄糖酸钙输注速度调整1.45mmol/L降低6.1ml/hr1.21–1.45mmol/L降低3.1ml/hr1.00–1.20mmol/L维持不变0.90–1.00mmol/L增加3.1ml/hr0.90mmol/L推注3.1ml/kg后,增加6.1ml/hr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抗凝的并发症:代谢性碱中毒主要原因枸橼酸转化为HCO3(1mmol枸橼酸能够产生3mmol的HCO3)次要原因溶液含有35mEq/LHCO3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(pH5.4)枸橼酸局部抗凝方案:抗凝监测若HCO3增加10mEq/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10mEq/L或155mEq/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若测定结果仍不正常输注5%GS枸橼酸抗凝的并发症:CitrateLock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