局部枸橼酸抗凝改善CVVHD疗效影响的研究(中英文)

CitrateRegionalAnticoagulationEnhancesCVVHDDelivery（局部枸橼酸抗凝改善CVVHD疗效影响的研究）RichardD.Swartz,MDUniversityofMichiganHealthSystemAnnArborMI48109-0364（美密西根大学医学中心，UM）[e-mail]agulation（局部枸橼酸抗凝）Ca++isindispensableforcoagulationtoproceed（钙离子是凝血过程中不可缺少的凝血因子）CitratechelatesCa++andiseasilyreversedwithfreeCa++（枸橼酸可结合钙，同时其螯和物又易解离释放钙）Citrateisusedinbloodbankingtostorestandingblood（枸橼酸常作为血标本的抗凝剂）Citratepermitsregional(extracorporeal)anticoagulationinRRT:CitrateaddedtobloodasitexitsthebodyandentersdialyzerCa++addedtobloodasitexitsdialyzerandre-entersthebody（肾替代治疗中的枸橼酸局部抗凝方法是：在体外循环滤器前的动脉端输入枸橼酸盐，结合血中离子钙，然后在滤器的静脉端输入氯化钙补充血循环中的钙离子，最后返回体内）PreviousExperiencewithCitrate（枸橼酸抗凝历史回顾）Pinnicketal1983–HD,definedeffective[citrate]0.4mM/L(…用于标准血透,提出枸橼酸抗凝作用的有效钙离子浓度为0.4mM/L)Mehtaetal1990–HDorCAVH,severalprotocolsoutlined(…HD或CAVH应用,发表了数篇有关枸橼酸抗凝的临床应用指南)Flaniganetal1996–HD,ACD-AratherthanconcNa3-Citrate(…HD,发现使用枸橼酸钠混液抗凝优于单纯的枸橼酸三钠溶液)Palsson&Niles1999–CVVH,noextracorpCa++measured(…CVVH中,无须监测体外循环血中钙浓度,证明其使用的安全性)Tolwanietal2000–CVVH,targetextracorpCa++,longerfilterlife(…CVVH,确定体外循环中血钙目标值,进一步延长了滤器的使用寿命)Bunchmanetal2002–CVVHD,Ca-freedialysate(UMprototype)(2002年-CVVHD,首次采用无钙透析液－密西根大学方案)BFR200ml/minDFR2000ml/hrNoCalciumDialysateACD(citrate)2.5%*BFREx-corpCa++0.4mM/LSystemicCa++1.0-1.2mM/LUFR300-500/hrCVVHDwithCitrate–UM2004(CVVHD枸橼酸抗凝流程－UM2004）CaCl2(2%).25%*BFRxx无钙透析液注：DFR_透析液流速UFR_超滤率BFR_血泵流速Ex-corp_体外循环CitrateandDialysateSolutions（枸橼酸和透析液成分组成）Citratesolution:ACD-A(3%mixedNaCitrate+Citricacid)ACD-Asolutionisinexpensive&readilyavailable.Dialysate:Na135mEq/L135mEq/LHCO328mEq/L25mEq/LCl105mEq/L108mEq/LMg1.0mM1.5mMGluc100mg/dlnoglucoseAddPRN:Phosphate1mM/L,K1-4mEq/LCalcium-freedialysatereducestheamountofcitratethatisrequiredtoachievetargetextracorporealCa++(0.4mM/L).（无钙透析液）（枸橼酸溶液：ACD-A为3%的枸橼酸钠和柠檬酸混液。其价廉、使用方便）(无钙透析液不仅能减少ACD-A用量同时也易达到血钙在体外循环浓度目标值0.4mM/L)组方1组方2CitratevsHeparinatUMich–2002FilterLongevityImproved?(枸橼酸与肝素抗凝对照实验－能延长滤器的使用寿命吗?)CitratevsHeparinResults(TimeControl)•First29patientsoncitrate,April-July2002vsFirst29patientsonheparin,Jan-Mar2002•Nodifference:age,gender,primarydiagnosisOverallmortality50%(citrate~heparin)HITdetected6/11(notallpatientstested)（研究结果－时间对照）（枸橼酸与肝素两组：各29例）（两组间在年龄、性别、原发病无差别，两组总死亡率50%,部分患者肝素相关性血小板减少检测6/11例）CitratevsHeparinResults(TimeControl)CITRATE(29)HEPARIN(29)TotaldaysCRRT166137AveDaysCRRT/patient5.9+2.34.6+3.2Totalfilters61160Clottedfilters344Patientswclottedfilters316•HospitalPolicy:mandatoryfilterchangeafter3daysAvefilters/patient*2.2+1.55.3+4.9AveDays/filter*2.4+1.11.2+0.9MedianDays/filter*2.50.9（研究结果－时间对照）(医院强制性规定:一个滤器连续使用3天后必须更换)(发生滤器凝血的患者数)(滤器消耗总数)(滤器凝血发生数)(治疗总天数)(平均每滤器使用天数)SievingCoefficient*duringCVVHDwithcitrate.*Sievingcoefficient=dialysate/bloodsoluteconcentration.Urea**(n=65)0.93+0.04Creatinine**(n=25)0.91+0.05Citrate**(n=3)0.87+0.06**BFR=150-200.Sievingcoefficientunchangedday1vsday3.Thus,clearance(=sievingcoefficientxDFR)1.8L/hr,reliablyandcontinuouslyforupto4days.(CVVHD_ACD-A治疗模式中溶质筛选系数的观察)注:SC=某溶质分别在血液中和透析液中浓度的比（滤器连续使用的第1天与第3天的S.C没有变化,溶质的清除率仍1.8L/hr,因此滤器可连续使用超过4天.)CitrateClearance&RemovalwCVVHD010203040506070Case1Case2Case3Case1Case2Case3Diffusive(弥散清除）Convective(对流清除)CitrateClearance(ml/min)CitrateRemoval(mM/hr)Citratedelivery40mM/hrUFRDFR(CVVHD治疗中枸橼酸廓清率或清除率)(注:UFR为超滤率;DFR指透析液流速)PeakBloodCalciumwCitrateCVVHD00.511.522.53SystTotCaSystIonCaRatioExCorpIonCaMaxChgHighCaMaxChgLowCaBeforeCVVHD(36ml/hr)(30ml/hr)mEq/LmEq/LmM/L(CVVHD_ACD-A治疗模式中血钙峰值变化)BicarbonateDuringCitrateCVVHD010203040ALLRiseNoChgDropBicarbonatemEq/LEndofCVVHDMaxChgby72hr221158Resultssuggestthatthe[HCO3]shouldbelower,~25mEq/L.(CVVHD_ACD-A治疗模式中血HCO3变化)(结果建议:无钙透析液的[HCO3]浓度应下调为～25mEq/L)AdverseEvents&TechnicalErrorsNocalcium:FailuretoconnecttheCaCl2infusion.Citrateinfusion,severehypocalcemiawithin4hr,resuscitated.Accesscatheterports“reversed”(duetopoorflow),butCaCl2notswitchedtoreturn(venous)port.SystCa++decreased,CaCl2adjusted,“labelling”needed.(不良事件及操作不当1)低/无钙:CaCl2输液泵未连接到透析血管路上仅有ACD-A输注,约持续4hr可导致严重低钙血症,复苏等抢救处理中心静脉插管血流↓、导管动、静端口“反向连接”使用，回路压力及血液再循环↑，CaCl2回输受阻或剂量减少当回血管路钙浓度↓，应调整CaCl2输注速率并标记备忘AdverseEvents&TechnicalErrorsExcesscalcium:CVVHDdiscontinuedbutCaCl2pumpnotturnedoff.Progressivehypercalcemia,CVVHDrestarted,Ca++adjusted.(不良事件及操作不当2)高钙/过量：CVVHD已停止治疗但CaCl2泵未关进行性高钙血症，CVVHD重启，注意调整血钙AdverseEvents&TechnicalErrorsVascularinjuryfromcalcium?CaCl2infiltrationorinfusionatthereturnportcouldcausespasmorinjury.NocomplicationswithCaCl2intograft,AVForhubofcatheter.(不良事件及操作不当3)离子钙对血管直接损伤？在穿刺点入口处血管被CaCl2的浸润或直接输入，可能引起局部血管的痉挛或损伤尚未发现CaCl2的输注对移植血管通路、血管内瘘或导管通路管壁损伤等并发症。Conclusions(CVVHD&Citrate)Citrateiseffective,easytouse,rarelycontraindictedCVVHDidealforcitrate,30-50%removalofinitialcitrate-calcium(reducescitrateaccumulation)（结论1）局部枸橼酸抗凝是有效、使用方便，罕见禁忌证枸橼酸是CVVHD理想的抗凝剂，约30～50%枸橼酸-钙螯和物经CVVHD滤器清除（减少枸橼酸体内蓄积）Conclusions(CVVHD&Citrate)Hypercalcemia,bothtotalCalciumandiCa++risewhenchelateismetabolized–(1)reducingBFRdecreaseschelatedelivery;(2)INITIALCaCl2rate0.25%BFR(30ml/hrof2%CaCl2solution)（结论2）高钙血症，当螯和物体内分解↑时，血中的包括总体钙和离子钙均上升－⑴减少血流速从而下调A