PCT临床应用进展

PCT临床应用进展

北京大学深圳医院ICU

蔡文训

PCT(Procalcitonin)的概述

PCT是无激素活性的降钙素前肽物质,是由116个氨基酸组成,相对分子量为13KD的糖蛋白。正常情况下,在甲状腺滤泡旁细胞(C细胞)粗面内质网内翻译成含141个AA残基的降钙素原前体(Pre-CT),分子量约为16KD。PCT的细胞来源生理情况下,甲状腺的C细胞是PCT的主要细胞来源。正常人血浆PCT水平很低,其值通常<0.1ng/ml。严重感染并有全身表现时,PCT水平明显升高,有的可超过100ng/ml。这时PCT大部分由甲状腺以外的组织产生。在病理情况下PCT的具体细胞来源目前尚不清楚。PCT的代谢在严重感染时,PCT的生成非常快,最初升高后,PCT值的下降取决于其在血浆中的衰减和新生成的PCT间的平衡.PCT的半衰期大约为20~24h。PCT的清除途径尚不完全清楚,它经肾脏排出很少。血浆PCT的肾脏清除率远低于1ml/min。因此血浆PCT检测也适用于肾衰或人工肾治疗的患者。PCT的实验室检测

放射免疫分析法(RIA)三明治免疫发光法(ILMA)该方法操作简单,敏感性高,特异性强此法测定的低限值为0.1ng/ml,检测耗时约2h。B.R.A.H.M.SPCT-Q-半定量快速实验该方法具有快速方便、易观察的特点,收取血标本后30min即可完成测定,其低限值为0.5ng/ml。Currentlythediagnosisofbacterialsepsisrequiresisolationandcultureofthecausativeorganism.Adefinitivediagnosiscantakedays,inwhichtimeempiricalantimicrobialtherapyisusuallyCommenced.Mortalityinsepsisremainshighanddelayeddiagnosismaycontributetothis.目前缺乏全身细菌感染敏感和特异性强标志物!!!PCT作为全身严重感染标志物的优势

白细胞计数、体温、C反应蛋白(CRP)及细胞因子(如IL-1、IL-6、TNF-α)等是临床上常规的感染检测指标。但白细胞计数用于诊断感染的准确性很低,这是因为全身性感染既可导致白细胞升高,也可以引起白细胞减少。Peduzzi等发现,白细胞升高并非全身性感染的独立预测指标,而且一些细胞因子和粒细胞集落刺激因子都可引起白细胞计数的改变。PCT作为全身严重感染标志物的优势发热是菌血症的独立预测指标,虽然特异性较高,但敏感性仅有5%。研究表明,TNF和IL-1可通过刺激IL-6产生而导致体温升高。因此体温改变也受到多种因素影响。CRP作为一种急性期蛋白质,在炎症过程开始8~12h后,才能从血清中检测出,明显迟于PCT水平的升高。而细胞因子如IL-1、IL-6、TNF-α半衰期很短(数分钟至几小时),相比而言,PCT的半衰期较长(20~24h),是一个理想的感染检测指标。PCT研究面临问题PCT作为一个全身严重感染性疾病的辅助和鉴别诊断的实验室常规指标成为共识,并将得到推广。但若想对PCT有更为全面的认识,以下问题:①炎症感染时PCT的确切细胞来源②PCT的生物学作用③PCT的身份认定及与其它介质间的相互关系等。国际上PCT临床应用情况Procalcitoninmeasurementhasbeenclaimedasahelpfulmarkerinbacterialinfectionandsepsis.IthasobtainedFDAapprovalandisnowwidelymarketedintheUnitedStatesandEurope.Pathology(August2007)39(4),pp.383–390实验结果一:InexperimentsinvolvinghumanvolunteersinjectedwithEscherichiacolitoxin,Subjectsdescribedsymptomsofchills,fever,rigorsandmyalgiawithin1–3hours.PCTconcentrationsstartedtoriseat4hours,peakedat6hoursandthenplateauedat8–24hours.Incomparisonwithotherinflammatorymarkers,PCTpeakedafterTNF-a(90minutes)andIL-6(3hours).实验结果二:thesecytokinesreturnedtobaselineafteronly6and8hours,respectively,givingthemarelativelynarrowtestingwindowtobeuseful.C-reactiveprotein(CRP),whichtakes12–24hourstoriseand20–72hourstoplateau,remainselevatedfor3–7days.Thisislongerthanthe2–3daysittakesPCTconcentrationstonormalise,offeringPCTanaturaladvantageinmonitoringdisease.关于PCT作为SEPSIS标志物讨论:ItwasthoughtthatPCTincreasedexclusivelyinbacterialsepsis,asopposedtonon-bacterialcausesofSIRSorlocalisedbacterialinfections,howeverelevationshavebeendocumentedinautoimmunedisease,severetrauma,surgery,heatstroke,andcardiogenicshockaswellasfungalandparasiticinfections.

关于PCT作为SESIS标志物讨论:

EmphasisisnowplacedonthelevelofPCTelevation,ratherthantheelevationitselfasthismayprovidesomediscriminationbetweendifferentcauses.关于PCT作为SESIS标志物讨论:

ThecharacteristicsthatgivePCTatheoreticaladvantageasamarkerofsystemicbacterialinfectionoverothercytokinesareavirtualabsenceinhealth,inductioninsepsisandahalf-lifesuitablefordailymonitoringofdiseaseprogress.Inpractice,itsclinicalusefulnessrequiresthedemonstrationofspecificity,cleardecisioncut-offsandtheabilitytopredictoutcomesinanumberofdefinedsituations.

PCT界定值及临床意义PCT≥10mg/L)areseeninsystemicbacterialinfectionsmulti-organdysfunctionfollowingtraumaPCT2~10mg/LsuggestiveofsepsisPCT0.5~2mg/Lmakesepsispossiblebutarealsoseeninotherconditions.PCT≤0.5mg/Lsepsisisunlikelywithconcentrationssuchlevelsmaystillbeconsistentwithlocalisedinfections.PCT0.25~0.5mg/Linlowerrespiratorytractinfectionsmaybeseenandwouldwarrantantibiotictreatment.PCT与CPR等作为SEPSIS标志物优劣:Anupdatedmeta-analysisofadultstudiesintheICUsettingconfirmedthatPCTwassuperiortoCRP,buttheimprovedaccuracywasonlymodest(Q-valueof0.78forPCTversus0.71forCRP).WhilesomestudiesshowatleastequivalentperformancesforCRPcomparedwithPCTinthediagnosisofsepsis,noneoftheotherfrequentlymeasuredanalytessuchasinterleukin-6or-8orneopterin,showedmuchpromise.PCT与CPR等作为SEPSIS标志物优劣:Thesensitivityofthedifferentcut-offconcentrationsforPCTdependedontheindividualstudy.SomestudiesshowedthatPCTconcentrationcorrelatedwiththeseverityofsepsis,whileCRPwasnotusefulforthatpurpose.PCT与CPR等作为SEPSIS标志物优劣Consequently,inseverelyillpatientssuchasthosepresentingwithARDSoracuteshock,PCTwassuperiortoCRP.Also,inpatientsintheearlyphaseofinfection,PCTdemonstratedabetterpredictivevaluewhencomparedwithCRP,afindingconsistentwiththeearlierriseofPCTcomparedwithCRPininflammation.结论:Insepsisdemonstrationofspecificity,cleardecisioncutoffsandtheabilitytopredictoutcomesinanumberdefinedsituationshasnotbeenclearlyshownandPCThasonlybeenshowntohaveanadjunctroleinthissetting.部分研究观察:DespitethesepromisingresultsandeventheapparentabilityofPCTconcentrationstopredictmortalityinchildrenwithmeningococcalsepticshock,thestatisticsandcut-offsquotedarepopulation-basedandmaynotapplytoindividuals.结论:AlargenumberofstudieshaveestablishedthatPCTiselevatedinbacterialsepsis.TheelevationseemstobeearlierthanthatseenforCRPandhigherconcentrationsofPCTareseeninbacterialsepsisthaninSIRS.However,weknownowthatPCTisalsoelevatedi