anaesthesia

BritishJournalofAnaesthesia83(4):602–7(1999)

Effectofcardiopulmonarybypassonrumprocalcitoninand

C-reactiveproteinconcentrations

fi1*,1,1,r1,n1,1,n2,3

1

1Serviced’Anesthe

´

sie-Re

´

animationandEA1896,Universite

´

ClaudeBernard,LyonI,France.

2LaboratoiredeBiochime,Ho

ˆ

,Lyon,France.

3NuffieldDepartmentofAnaesthetics,RadcliffeInfirmary,OxfordOX26HE,UK

*Correspondingauthor:Serviced’Anesthe

´

sie-Re

´

animation,Ho

ˆ

,

BPLyonMontchat,F-69394Lyoncedex3,France

Wehavemeasuredrumprocalcitonin(PCT)concentrationsaftercardiacsurgeryin36

patientsallocatedtooneofthreegroups:group1,coronaryarterybypassgrafting(CABG)

withcardiopulmonarybypass(CPB)(nϭ12);group2,CABGwithoutCPB(nϭ12);andgroup

3,valvularsurgerywithCPB(nϭ12).SerumPCTandC-reactiveprotein(CRP)concentrations

weremeasuredbeforeoperation,attheendofsurgeryanddailyuntilpostoperativeday8.

SerumPCTconcentrationsincread,irrespectiveofthetypeofcardiacsurgery,withmaximum

concentrationsonday1:mean1.3(SD1.8),1.1(1.2)and1.4(1.2)ngml–1ingroups1,2and

3,respectively(ns).SerumPCTconcentrationsremainedlessthan5ngml–1inallpatients.

rminetheeffectofthe

systemicinflammatoryrespon(SIRS)onrumPCTconcentrations,patientsweredivided

posthoc,withoutconsideringthetypeofcardiacsurgery,intopatientswithSIRS(nϭ19)and

thowithoutSIRS(nϭ17).TheincreainrumPCTwassignificantlygreaterinSIRS(peak

PCT1.79(1.64)ngml–1vs0.34(0.32)ngml–1inpatientswithoutSIRS)(Pϭ0.005).Samples

forPCTandCRPmeasurementswereobtainedfrom10otherpatientswithpostoperative

complications(circulatoryfailurenϭ7;activeendocarditisnϭ2;pticshocknϭ1).Inthe

patients,rumPCTconcentrationsrangedfrom6.2to230ngml–RPconcentrations

increadinallpatients,toperativeincreain

ludethatSIRSinducedbycardiacsurgery,with

andwithoutCPB,influencedrumPCTconcentrationswithamoderateandtransient

postoperativepeakonthefiperativerumPCTconcentration

ofmorethan5ngml–1ishighlysuggestiveofapostoperativecomplication.

BrJAnaesth1999;83:602–7

Keywords:protein,procalcitonin;protein,C-reactive;complications,systemicinflammatory

responsyndrome;heart,cardiopulmonarybypass;surgery,cardiovascular

Acceptedforpublication:May20,1999

Cardiacsurgerycausaninflammatoryresponwith

clinicalandbiologicalchanges.1Thissystemicinflammatory

responsyndrome(SIRS)isaresultofveralstimuli,such

axposureofbloodtonon-physiologicalsurfaces,surgical

trauma,myocardialischaemia–reperfusionandendotoxin

relea.23Becauofthisrespon,conventionalclinical

andbiologicalsignsmaybemisleadinginthediagnosisof

postoperativecomplications,particularlyinfection.

Procalcitonin(PCT)isapolypeptideof116aminoacids

dentified

asaprecursorofhumancalcitoninin1989byGhillaniand

colleagues.4PCT,usuallyundetectableinhealthysubjects,

wasdescribedasaninfectiousmarkerin1993byAssicot

©BritishJournalofAnaesthesia

andcolleagues.5FurtherstudiessuggestedthatPCTisan

early,nsitiveandspecificindicatorofinfection,6–8but

recentinvestigationsshowedincreasinotherconditions

associatedwithsystemicinflammation,suchasvere

trauma,9burns10andheatstroke.11

Inthisstudy,wedeterminedthenormalprofileofPCT

aftervarioustypesofcardiacsurgerywithorwithout

cardiopulmonarybypass(CPB).

Patientsandmethods

AfterobtainingapprovalfromtheUniversityEthicsCom-

mittee,westudiedprospectively36patientsundergoing

Procalcitoninaftercardiacsurgery

electivecardiacsurgerywithorwithoutCPB,inwhoman

ion

criteriawereleftventricularejectionfractionlessthan45%

tswereallocatedtooneofthree

groups:group1,coronaryarterybypassgrafting(CABG)

withCPB(nϭ12);group2,CABGwithoutCPB(nϭ12);

andgroup3,valvularsurgerywithCPB(nϭ12).Tostudy

theeffectofpostoperativeSIRSonrumPCT,the

patientswithnocomplicationswereclassifiedposthoc,

irrespectiveofthetypeofsurgery,intothowithpostopera-

tion,

another10patientswhowerepredictedtohaveacomplic-

atedpostoperativecour(emergency,mechanicalcom-

plicationofacutemyocardialinfarction,activeendocarditis)

werealsoincludedandanalydparately.

Afteroralpremedicationwithhydroxyzine100mgand

midazolam0.1mgkg–1,anaesthesiawasinducedwith

midazolam0.05mgkg–1andsufentanil10µgkg–al

intubationwasperformedafteradequateneuromuscular

blockwithpancuronium0.1mgkg–hesiawas

maintainedwithcontinuousinfusionsofpropofolandsufen-

ientsweremonitoredbyECG,puloximetry,

end-tidalcarbondioxidecapnography,systemicarterialline

andrightheartcatheterization(Baxter,Irvine,CA,USA).

Antibioticprophylaxisconsistedofcefazolin30mgkg–1

every8handnetilmicin1mgkg–1every8h.

InpatientsundergoingCPB(groups1and3),after

–1i.v.,moderatehypo-

thermicCPBwasachievedusingahollowfibreoxygenator.

DuringCPB,meanarterialpressurewasmaintainedat

approximately75mmHgwithaperfusionoutputof

2.4litremin–1m–dialprervationwasperformed

withintermittentinfusionofcoldcrystalloidcardioplegic

p2,

surgerywasperformedusingtheOctopustissuestabilizer

(Medtronic,Inc.,MI,USA),avoidingtheuofCPB.12

Afteroperation,clinicalasssment,includingbodytem-

perature,microbiologicalandradiologicalexaminations,

s

definedaccordingtotheclassificationoftheAmerican

CollegeofChestPhysicians/SocietyofCriticalCare

Medicine13whentwoormoreofthefollowingsignswere

prent:bodytemperatureϾ38°CorϽ36°C;persistent

tachycardia(heartrateϾ90beatmin–1);tachypnoea

(Ͼ20bpm);leucocytosis(leucocytesϾ12000glitre–1)or

leucopenia(leucocytesϽ4000glitre–1).Inthe10patients

withpostoperativecomplications,antibiotics,inotropicsup-

port,vasoactiveagentsandtransfusionswereadministered

-

aorticballoonpump(IABP)counterpulsationwasudfor

refractorylowcardiacoutput(LCO).

PCTandCRPmeasurements

Bloodsamplesformeasurementofrumconcentrationsof

PCTandCRPwereobtainedafterinductionofanaesthesia

(baline),attheendofsurgeryanddailyuntilpostoperative

603

1ϭcoronaryartery

bypassgrafting(CABG)withcardiopulmonarybypass(CPB);group2ϭCABG

withoutCPB;andgroup3ϭϭPostoperative

ϭSimplifiaremean(SDorrange)

ormedian[range].*PϽ0.05vsgroup1

Group1Group2Group3

(n⍧12)(n⍧12)(n⍧12)

Age(yr)68(00–00)66(00–00)67(00–00)

Sex(M/F)10/211/18/4

SAPSII(24h)23(6)23(6)25(10)

CPBduration(min)60(15)—100(29)*

Aorticcrossclamping(min)38(12)—78(31)*

Temperature(°C)

POD137.8(0.2)38.0(0.4)37.8(0.4)

POD537.2(0.4)37.2(.02)37.3(0.3)

Mechanicalventilationduration(h)12[6–21]8[6–18]20[6–40]

ICUstay(days)3[3–5]2[1–3]3[2–5]

centrationwasmeasuredbyimmunolumino-

metricassaywiththecommerciallyavailableLumitest

PCT(BrahmsDiagnosticaGmbH,Berlin,Germany).This

testisbadonthereactionoftwoantigen-specificmono-

clonalantibodiesthatbindPCTasantigenatthekatacalcin

er-assayprecisionofthekitis6–

10%andthelowerlimitofdetectionis0.1ngml–

samepersonperformedallsamplesaftercalibrationof

thestandardcurvebythestandardprovidedbyBrahms

RPconcentrationwasmeasuredat

thesametimeusingalarnephelometrictechnique(BN

100,MedgenixDiagnostics,Fleurius,Belgium).

Statisticalanalysis

Resultsareexpresdasmean(SD).Mechanicalventilation

andICUdurationwereexpresdasmedian(range).Data

forgroups1,2,and3wereanalydusingtwo-wayanalysis

ofvarianceforrepeatedmeasures(ANOVA)followedby

Fisher’ribetherelationship

betweenrumPCTconcentrationandrumCRPconcen-

tration,CPBdurationanddurationofaorticclamping,a

linearregressionanalysiswasperformed.PϽ0.05was

consideredsignifiticalanalysiswasperformed

usingStatisticaSoftwarepackage(Statistica,StatSoftInc,

Tulsa,USA).

Results

AsshowninTable1,patientandperioperativedatafor

thowithnocomplicationsdidnotdifferbetweengroups

1,2and3,exceptforCPBanddurationofaorticclamping.

Nopatientingroup1,2or3hadclinical,microbiological

lbodytemperature

mineor

dopamine2.5–5µgkg–1min–1wasudineightpatients

(group1,nϭ3;group2,nϭ2;group3,nϭ3).Noneof

patients,thetracheawaxtubatedwithin48hafter

velopedin19patients(52%),withno

Aouifietal.

Table2DataforpatientswithcomplicationsandrespectiverumPCTandCRPconcentrationsonpostoperativeday1(POD1).AMRϭAcutemitralregurgitation,

AMIϭacutemyocardialinfarction;MVRϭmitralvalvereplacement;AVRϭaorticvalvereplacement;CABGϭcoronaryarterybypassgrafting;LCOϭlowcardiac

output;IABPϭintra-aorticballoonpump

PatientCardiacdiaSurgeryPostoperativecourInfectedCRPPCT

No.(mglitre–1)(ngml–1)

1UnstableanginapectorisCABGSepticshock,inotropicsupport,diedonPOD4Yes35230.0

Ejectionfraction20%(noCPB)

2ActiveendocarditisMVR39°CuntilPOD2Yes23245.7

3ActiveendocarditisMVR39°CuntilPOD3Yes14514.6

4AMRafterAMIMVRCardiogenicshock,IABP,inotropicsupport,haemodialysisNo134111.0

5AMRafterAMIMVRCardiogenicshock,No15656.6

CABGIABP,inotropicsupport,diedonPOD3

6AMRafterAMIMVRLCO,inotropicsupportNo4121.8

7AMRafterAMIMVRLCONo31914.4

IABP,inotropicsupport

8UnstableanginapectorisCABGLCO,inotropicsupportNo1198.9

Ejectionfraction30%

9MitralvalvethrombosisMVRLCO,No2646.7

AorticvalvedysfunctionAVRinotropicsupport,

10UnstableanginaCABGHaemorrhagicshock,massivetransfusion,vasoactiveagentsNo976.2

significantdifferencebetweenthethreegroups(group1,

nϭ5;group2,nϭ7;group3,nϭ7).

The10patientswithcomplications(Table2)hadhigh

postoperativeSAPSIIscores(38Ϯ13points),prolonged

mechanicalventilation(median4days(range4hto57

days)andprolongedadmissiontotheICU(median7(range

4–57)days).Threeofthe10patientsprentedwith

psis(Nos1,2and3;eTable2).

SerumPCTconcentration

BalinerumPCTconcentrationswere0.16(0.08),0.13

(0.10)and0.18(0.07)ngml–1ingroups1,2and3,

respectively(ns).SerumPCTconcentrationincreadsig-

nificantlycomparedwithbalineinallgroupsduringthe

first4daysafteroperation(PϽ0.05vsbalinefromday

1today4).PeakPCTconcentrationsoccurredonday1

(1.3(1.8),1.1(1.2)and1.4(1.2)ngml–1ingroups1,2and

3,respectively)(ns).Afterday1,rumPCTconcentration

decreadprogressivelyandreturnedtobalinevaluesby

day5inallgroups(Fig.1).TheincreainrumPCT

concentrationwassignificantlygreaterinpatientswithSIRS

thaninthowithoutSIRS(Fig.2).Thepeakonday1

was1.79(1.64)ngml–1inthegroupwithSIRScompared

with0.34(0.32)ngml–1ingroupwithnoSIRS(Pϭ0.005).

TherewasnosignificantcorrelationbetweenrumPCT

concentrationandCPBduration(r2ϭ0.16),durationof

aorticclamping(r2ϭ0.14),durationofmechanicalventila-

tion(r2ϭ0.12)ordurationofICUadmission(r2ϭ0.19).

Inallpatientswithnocomplications,rumPCTconcen-

trationremainedlessthan5ngml–1duringthestudy.

Perioperativedataforthe10patientswithcomplications,

withrespectivePCTandCRPvaluesonday1,areshown

softherumPCTconcentrationprofile

ients(Nos

2and3)withpreoperativeactiveendocarditishadrum

PCTconcentrationsof45.7and14.6ngml–1;PCTconcen-

trationsdecreadrapidlyafterantibiotictreatmentand

centrations

604

Fig1Serumprocalcitonin(PCT)concentrationsinpatientswithno

complicationsaccordingtothetypeofcardiacsurgery(group1,coronary

arterybypassgrafting(CABG)withcardiopulmonarybypass(CPB)(nϭ

12);group2,CABGwithoutCPB(nϭ12);andgroup3,valvularsurgery

withCPB(nϭ12)).Dataaremean(SD).Nodifferencesbetweengroups.

Fig2Serumprocalcitonin(PCT)concentrationsinpatientswithno

emean(SD).

Nodifferencesbetweengroups.*PϽ0.05.

ofmorethan100ngml–1werefoundinapatient(No.1)

ranged

from6.2to111.0ngml–1onday1insixnon-infected

Procalcitoninaftercardiacsurgery

Fig3Serumprocalcitonin(PCT)CTconcentrationsofmorethan5ngml–1were

obrvedinallpatients.*Dead.

patients(Nos4–9)withlowcardiacoutputrequiring

centrationsincread

moderately(6.21ngml–1)onday1inanon-infectedpatient

(No.10)whodevelopedhaemorrhagicshockimmediately

afterCPB,requiringmassivetransfusionsandinotropic

support.

SerumCRPconcentration

Aftersurgery,CRPincreadsignificantlycomparedwith

baline(PϽ0.05fromday1today8inallgroups).Peak

rumCRPconcentrationsoccurredonday1afterCABG

withoutCPB(194(75)mglitre–1)andonday2after

cardiacsurgerywithCPB(158(79)mglitre–1inCABG

withCPBand185(62)mglitre–1invalvularsurgery).

Thereafter,CRPconcentrationsdecreadslowly,buthad

notreturnedtonormalbyday8(Fig.4).Therewasno

significantdifferencebetweensurgicaltechniquesandthere

wasnorelationshipbetweenpeakrumPCTandCRP

concentrationsinpatientswithnocomplications(r2ϭ0.17).

SerumCRPconcentrationdidnotdifferbetweenpatients

withandwithoutcomplications.

Discussion

PCTispropodasaspecificmarkerofinfection,58butit

wasfoundinhighconcentrationsinveralclinicalinsults

withSIRS,suchaspolytrauma9andthermalinjury.10As

cardiacsurgerycausSIRS,weperformedthisprospective

studytoestablishthechangesinthismarkerafterdifferent

dthatcardiacsurgery

caudamoderateandtransientincreainrumPCT

crea

wasnotrelatedtoCPBbutwascaudbySIRStriggered

bythesurgicalprocedure.

TheincreainrumPCTconcentrationaftercardiac

surgerywithCPBsupportsthestudybyMeisnerand

colleagues.14TheyfoundanincreainPCTin59%of

ly,andcontrarytoboth

ourresultsandthoofMeisnerandcolleagues,Boeken

andcolleagues15foundnosignificantincreainrum

PCTaftercardiacsurgeryandconcludedthatcardiacsurgery

withCPBdidnotinflr,inthatstudy,

605

Fig4SerumC-reactiveprotein(CRP)concentrationsinpatientswithno

complicationsaccordingtothetypeofcardiacsurgery(group1,coronary

arterybypassgrafting(CABG)withcardiopulmonarybypass(CPB)(nϭ

12);group2,CABGwithoutCPB(nϭ12);andgroup3,valvularsurgery

withCPB(nϭ12)).Dataaremean(SD).Nodifferencesbetweengroups.

rumPCTwasmeasuredbeforeoperation,10minafter

thebeginningofCPB,attheendofCPB,30minafter

administrationofprotamine,atarrivalintheICUandon

les

wereobtainedonthefiore,it

islikelythatpeakPCTconcentrations,occurringonthe

firstdayafteroperation,weremisdinthisstudy.

AlthoughtheincreainrumPCTconcentrationafter

cardiacsurgerywithCPBhasbeenreportedpreviously,the

similarincreainrumPCTaftercardiacsurgerywithout

CPBdemonstratedinourstudyisanovelfi

previousstudy,Kilgerandcolleagues,16comparingpeak

PCTconcentrationsafterconventionalCABGwithCPB

andafterdirectcoronaryarterybypasswithoutCPB,showed

thatpeakrumPCTconcentrationsweresignificantly

greaterinconventionalCABGthanaftersurgerywithout

heless,inthisstudy,eightof30patients(25%)

intheconventionalCABGgroupreceivedinfusionof

norepinephrinecomparedwithnoneinthenon-CPBgroup.

TheeightpatientsprentedwithhighpostoperativePCT

values(2.6–9.8ngml–1)andwereprobablyresponsiblefor

modynamicstatusofthe

patientsandthenorepinephrineinfusionrequirementmay

explainthediscrepancieswithourstudy.

Aouifietal.

TheincreainrumPCTconcentrationaftercardiac

surgeryappearedtoberelatedtopostoperativeSIRS,

ggeststhat

PCTisrelatedtothecytokinecascadeandendotoxinrelea

othesisofa

relationshipbetweenPCTandcytokinecascadeissupported

byDandonaandcolleagues17whoestablishedachronology

betweenendotoxin,uthors

showedthathealthysubjectsdisplayarapidincreain

PCTfollowedbyaplateaubetween8and24hafter

creainPCTwaspreceded

byanincreaintumournecrosisfactor-α(TNFα)and

interleukin-6(IL-6)iacsurgery,to

ourknowledge,therearenodataontherelationbetween

heless,duringCPB,

endotoxintranslocationcaudbyatransientormore

prolongedperiodofintestinalhypoperfusioniswidely

documented1819andthindotoxinreleaisassociated

withanincreainTNFα,IL-6andIL-8concentrations.13

Wespeculatethatthepostoperativeinflammatorycascade

isprobablyresponsiblefortheincreainrumPCTafter

iacsurgerywithoutCPB,thecytokinecascade

islessdocumented,butrecentlyFrannandcolleagues20

showedthatcytokineproduction(particularlyIL-6)is

prentwiththesamemagnitudewithorwithoutCPB.

ThissuggeststhattheincreainPCTconcentrationsafter

cardiacsurgerywithoutCPBmayalsoberelatedtothe

cytokinecascade.

ThenormalrangeofrumPCTconcentrationafter

cardiacsurgeryisnotyetdefitudy,overthe8

daysafteroperation,rumPCTconcentrationsremained

lessthan5ngml–1inallpatientswithoutcomplications

andwere6.2–230ngml–1inthe10patientswithcomplica-

pportsthestudybyHenllandcolleagues21

inwhichrumPCTconcentrationsof5.1–14.3ngml–1

weremeasuredonday1aftercardiacsurgeryinnine

patientswhodevelopedacutelunginjuryafteroperation.

ThissuggeststhatrumPCTconcentrationsofmore

than5ngml–1isstronglyindicativeofapostoperative

mstobeanimportantmarkerof

impendingcomplicationsaftercardiacsurgery,particularly

whenconventionalclinicalandbiologicalsignscanbe

difficulttointerpret.

SerumCRPconcentrationincreadmarkedlyinthe

postoperativeperiod,regardlessofthetypeofcardiac

pportstheresultsofFrannandcol-

leagues,20whoshowedthatCRPevolvedsimilarlyafter

thesisofthis

acutephaproteinmaynotbetriggeredbyCPBitlf,but

rtedpreviously

byBoralesaandcolleagues,22theincreainrumCRP

aftercardiacsurgeryoccurssimilarlyincomplicated(includ-

inginfected),mon-

stratesthatrumCRPisaverypoormarkerofpostoperative

complicationsaftercardiacsurgery;indeed,becauofits

prolongedincreaafteroperation,rumCRPemstobe

606

lessufulthanrumPCTfordetectionofimpending

postoperativecomplications.

Insummary,inthis8-daystudy,weestablishedthe

perioperativekineticsofrumPCTafterdifferenttypesof

edthatSIRSinducedbycardiac

surgerywithandwithoutCPBinfluencedrumPCT

concentrationswithamoderateandtransientincreaon

thefirstdayafteroperationfollowedbyarapidreturnto

mstobeanimportantmarkerofimpending

complicationsaftercardiacsurgery,particularlywhencon-

ventionalclinicalandbiologicalsignscanbedifficult

heless,furtherstudiesareneededto

determinetherelevanceofrumPCTfordiscrimination

betweeninfectiousandnon-infectiouscomplicationsafter

cardiacsurgery.

Acknowledgement

WethankDrJeanineGuidolletandMsRaymondePerraudinwhoper-

thankDrMarieCe

´

lardfor

udywassupportedinpartbyfunding

fromBrahmsFrance(BrahmsFranceSRL,Sartrouville,France).

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