PCT臨床應(yīng)用進(jìn)展

PCT臨床應(yīng)用進(jìn)展

北京大學(xué)深圳醫(yī)院ICU

蔡文訓(xùn)

PCT(Procalcitonin)的概述

PCT是無(wú)激素活性的降鈣素前肽物質(zhì),是由116個(gè)氨基酸組成,相對(duì)分子量為13KD的糖蛋白。正常情況下,在甲狀腺濾泡旁細(xì)胞(C細(xì)胞)粗面內(nèi)質(zhì)網(wǎng)內(nèi)翻譯成含141個(gè)AA殘基的降鈣素原前體(Pre-CT),分子量約為16KD。PCT的細(xì)胞來(lái)源生理情況下,甲狀腺的C細(xì)胞是PCT的主要細(xì)胞來(lái)源。正常人血漿PCT水平很低,其值通常<0.1ng/ml。嚴(yán)重感染并有全身表現(xiàn)時(shí),PCT水平明顯升高,有的可超過(guò)100ng/ml。這時(shí)PCT大部分由甲狀腺以外的組織產(chǎn)生。在病理情況下PCT的具體細(xì)胞來(lái)源目前尚不清楚。PCT的代謝在嚴(yán)重感染時(shí),PCT的生成非?？?最初升高后,PCT值的下降取決于其在血漿中的衰減和新生成的PCT間的平衡.PCT的半衰期大約為20~24h。PCT的清除途徑尚不完全清楚,它經(jīng)腎臟排出很少。血漿PCT的腎臟清除率遠(yuǎn)低于1ml/min。因此血漿PCT檢測(cè)也適用于腎衰或人工腎治療的患者。PCT的實(shí)驗(yàn)室檢測(cè)

放射免疫分析法(RIA)三明治免疫發(fā)光法(ILMA)該方法操作簡(jiǎn)單,敏感性高,特異性強(qiáng)此法測(cè)定的低限值為0.1ng/ml,檢測(cè)耗時(shí)約2h。B.R.A.H.M.SPCT-Q-半定量快速實(shí)驗(yàn)該方法具有快速方便、易觀察的特點(diǎn),收取血標(biāo)本后30min即可完成測(cè)定,其低限值為0.5ng/ml。Currentlythediagnosisofbacterialsepsisrequiresisolationandcultureofthecausativeorganism.Adefinitivediagnosiscantakedays,inwhichtimeempiricalantimicrobialtherapyisusuallyCommenced.Mortalityinsepsisremainshighanddelayeddiagnosismaycontributetothis.目前缺乏全身細(xì)菌感染敏感和特異性強(qiáng)標(biāo)志物!!!PCT作為全身嚴(yán)重感染標(biāo)志物的優(yōu)勢(shì)

白細(xì)胞計(jì)數(shù)、體溫、C反應(yīng)蛋白(CRP)及細(xì)胞因子(如IL-1、IL-6、TNF-α)等是臨床上常規(guī)的感染檢測(cè)指標(biāo)。但白細(xì)胞計(jì)數(shù)用于診斷感染的準(zhǔn)確性很低,這是因?yàn)槿硇愿腥炯瓤蓪?dǎo)致白細(xì)胞升高,也可以引起白細(xì)胞減少。Peduzzi等發(fā)現(xiàn),白細(xì)胞升高并非全身性感染的獨(dú)立預(yù)測(cè)指標(biāo),而且一些細(xì)胞因子和粒細(xì)胞集落刺激因子都可引起白細(xì)胞計(jì)數(shù)的改變。PCT作為全身嚴(yán)重感染標(biāo)志物的優(yōu)勢(shì)發(fā)熱是菌血癥的獨(dú)立預(yù)測(cè)指標(biāo),雖然特異性較高,但敏感性僅有5%。研究表明,TNF和IL-1可通過(guò)刺激IL-6產(chǎn)生而導(dǎo)致體溫升高。因此體溫改變也受到多種因素影響。CRP作為一種急性期蛋白質(zhì),在炎癥過(guò)程開(kāi)始8~12h后,才能從血清中檢測(cè)出,明顯遲于PCT水平的升高。而細(xì)胞因子如IL-1、IL-6、TNF-α半衰期很短(數(shù)分鐘至幾小時(shí)),相比而言,PCT的半衰期較長(zhǎng)(20~24h),是一個(gè)理想的感染檢測(cè)指標(biāo)。PCT研究面臨問(wèn)題PCT作為一個(gè)全身嚴(yán)重感染性疾病的輔助和鑒別診斷的實(shí)驗(yàn)室常規(guī)指標(biāo)成為共識(shí),并將得到推廣。但若想對(duì)PCT有更為全面的認(rèn)識(shí),以下問(wèn)題:①炎癥感染時(shí)PCT的確切細(xì)胞來(lái)源②PCT的生物學(xué)作用③PCT的身份認(rèn)定及與其它介質(zhì)間的相互關(guān)系等。國(guó)際上PCT臨床應(yīng)用情況Procalcitoninmeasurementhasbeenclaimedasahelpfulmarkerinbacterialinfectionandsepsis.IthasobtainedFDAapprovalandisnowwidelymarketedintheUnitedStatesandEurope.Pathology(August2007)39(4),pp.383–390實(shí)驗(yàn)結(jié)果一:InexperimentsinvolvinghumanvolunteersinjectedwithEscherichiacolitoxin,Subjectsdescribedsymptomsofchills,fever,rigorsandmyalgiawithin1–3hours.PCTconcentrationsstartedtoriseat4hours,peakedat6hoursandthenplateauedat8–24hours.Incomparisonwithotherinflammatorymarkers,PCTpeakedafterTNF-a(90minutes)andIL-6(3hours).實(shí)驗(yàn)結(jié)果二:thesecytokinesreturnedtobaselineafteronly6and8hours,respectively,givingthemarelativelynarrowtestingwindowtobeuseful.C-reactiveprotein(CRP),whichtakes12–24hourstoriseand20–72hourstoplateau,remainselevatedfor3–7days.Thisislongerthanthe2–3daysittakesPCTconcentrationstonormalise,offeringPCTanaturaladvantageinmonitoringdisease.關(guān)于PCT作為SEPSIS標(biāo)志物討論:ItwasthoughtthatPCTincreasedexclusivelyinbacterialsepsis,asopposedtonon-bacterialcausesofSIRSorlocalisedbacterialinfections,howeverelevationshavebeendocumentedinautoimmunedisease,severetrauma,surgery,heatstroke,andcardiogenicshockaswellasfungalandparasiticinfections.

關(guān)于PCT作為SESIS標(biāo)志物討論:

EmphasisisnowplacedonthelevelofPCTelevation,ratherthantheelevationitselfasthismayprovidesomediscriminationbetweendifferentcauses.關(guān)于PCT作為SESIS標(biāo)志物討論:

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

PCT界定值及臨床意義PCT≥10mg/L)areseeninsystemicbacterialinfectionsmulti-organdysfunctionfollowingtraumaPCT2~10mg/LsuggestiveofsepsisPCT0.5~2mg/Lmakesepsispossiblebutarealsoseeninotherconditions.PCT≤0.5mg/Lsepsisisunlikelywithconcentrationssuchlevelsmaystillbeconsistentwithlocalisedinfections.PCT0.25~0.5mg/Linlowerrespiratorytractinfectionsmaybeseenandwouldwarrantantibiotictreatment.PCT與CPR等作為SEPSIS標(biāo)志物優(yōu)劣:Anupdatedmeta-analysisofadultstudiesintheICUsettingconfirmedthatPCTwassuperiortoCRP,buttheimprovedaccuracywasonlymodest(Q-valueof0.78forPCTversus0.71forCRP).WhilesomestudiesshowatleastequivalentperformancesforCRPcomparedwithPCTinthediagnosisofsepsis,noneoftheotherfrequentlymeasuredanalytessuchasinterleukin-6or-8orneopterin,showedmuchpromise.PCT與CPR等作為SEPSIS標(biāo)志物優(yōu)劣:Thesensitivityofthedifferentcut-offconcentrationsforPCTdependedontheindividualstudy.SomestudiesshowedthatPCTconcentrationcorrelatedwiththeseverityofsepsis,whileCRPwasnotusefulforthatpurpose.PCT與CPR等作為SEPSIS標(biāo)志物優(yōu)劣Consequently,inseverelyillpatientssuchasthosepresentingwithARDSoracuteshock,PCTwassuperiortoCRP.Also,inpatientsintheearlyphaseofinfection,PCTdemonstratedabetterpredictivevaluewhencomparedwithCRP,afindingconsistentwiththeearlierriseofPCTcomparedwithCRPininflammation.結(jié)論:Insepsisdemonstrationofspecificity,cleardecisioncutoffsandtheabilitytopredictoutcomesinanumberdefinedsituationshasnotbeenclearlyshownandPCThasonlybeenshowntohaveanadjunctroleinthissetting.部分研究觀察:DespitethesepromisingresultsandeventheapparentabilityofPCTconcentrationstopredictmortalityinchildrenwithmeningococcalsepticshock,thestatisticsandcut-offsquotedarepopulation-basedandmaynotapplytoindividuals.結(jié)論:AlargenumberofstudieshaveestablishedthatPCTiselevatedinbacterialsepsis.TheelevationseemstobeearlierthanthatseenforCRPandhigherconcentrationsofPCTareseeninbacterialsepsisthaninSIRS.However,weknownowthatPCTisalsoelevatedi