ClinicalEarlyOnsetSepsis

Morethanjustthelabs

StephenMessierMDFAAPNeonatologist

Phonecall–We’vegotTrouble

•  RiverCity,IADr.HaroldHill(Locums)•  39week,GBSneg,NSVD5hoursold,•  Apgars81,95•  AsymptomaQc,VSS

– NoTachycardia– NoTachypnea– NoTempinstability

•  PEnormal

Labs

18 33 1029.3 324 I:T0.23

53 51 5 Dr.Hill:“IgetCBCsonallofmynewbornsto

bethorough.”

NowWhat?

Case2

•  8houroldfmr405wk26yoG1P0•  GBS(-),12hrROM•  Mec,Forceps•  Intub,sucQoned,nothingbelowcords(6thEd)•  Neopuff2min,RAby6min.•  Apgars2155910•  NmlCordgases

MaternalHx

•  GBSneg•  Uncomplicatedpregnancy•  NonfoulsmellingamnioQcfluid•  ROM12hours•  Tmax100.3oF•  NoanQbioQcs

HOL4

•  Temp:Normal•  HR:Normal•  RR:Normal•  ErythroEyeOintment,VitK,HepBgiven

Moreinfo

•  PE: Allnormal•  Breasbeeding:20min,10min,20min

CBCat8HOL

18.6 54 2529.6 250 11 5 I:T0.32

52.4

Drawnforlow5minuteApgarscore

Nowwhat?

MoreCBCs

HOL12HOL27DOL3

15.1 40 3523.5 226 21 5 43.1 14.7 58 1521.3 --- 22 4 41.7 CRP24.2 15.6 54 815 --- 23 5

43.8

QuesQonstoaskYourself

•  IsthiskidsepQc?– HowconfidentamIwithmyanswer?– Whatismyrisktoleranceforsepsis?

•  WhatinformaQonwillhelpmeanswerthefirstquesQon?

•  Whoneedsfurtherworkup?•  Howdoesmyworkuparriveatthatanswer?

DefiniQons

•  EarlyonsetSepsis– Preterm<72hours– Term<7days

•  Lateonsetsepsis– >72hoursinNICU(Preterm)–  7-90daysinTerm

StandardPlayers

•  GBS•  E.Coli•  S.Aureus•  S.Pneumo•  Enterococcus•  Enterobacter•  Listeria•  Fungal/Viral

>70%ofinfecQons

RiskofEarlyOnsetSepsis(EOS)

•  Baselinerisk:0.5-1/1000births

•  Increasedriskforprematurity– Dependsondegreeandifprematurelabor

RiskFactorsforEOS

•  MaternalRiskFactors

– ClinicalChorioamnioniRs– GBSColonizaQonatQmeofdelivery– GBSBacteruriaduringthepregnancy– GBSdiseaseinapriorpregnancy–  ROM>18hourspriortodelivery–  IntrapartumFever–  PretermDelivery

ClinicalChorioamnioniQs

•  Maternalfever>100.4oF(twice)or>101oF•  MaternalTachycardia>100bpm•  FetalTachycardia>160bpm•  Uterinetenderness•  PurulentorfoulsmellingamnioQcfluid•  MaternalLeukocytosis

RelaQveRiskofDev.ClinicalChorio

•  ProlongedROM–  >12hours 5.8–  >18hours 6.9

•  ProlongedLabor–  2ndstage>2hrs3.7 –  Act.Labor>12hrs4.0

•  DigitalExamsanerROM–  >3exams 2to5

•  GBS(+) 1.7to6.2•  Bact.Vag. 1.7•  EtOH/Tob 7.9•  MecStaining1.4to2.3•  Int.Monitor 2.0•  Epidurals 4.1

DiagnosisandManagementofClinicalChorioamnioniRsClinPerinatol.2010Jun;37(2):339–354

BiggestRiskFactorsforEOS

•  IncreasedriskforChorio 15-20x

•  Increasedriskforsonsigns ~20-30x

•  Increasedriskforillinfant ~80xorhigher

ClinicalSymptoms

•  Unstable/abnormalVSoutsideofthe4hourtransiQon

•  PoorFeeding•  DecreasedacQvity•  Apnea•  Seizures•  RespiratoryDistress(GrunQng,RetracQons)

SoyoususpectinfecQon…

•  BLOODCULTURE–  Othercultures?

•  CBC•  CRP

•  Othermarkers?

•  Screeningtests•  Separatethesick,fromthenotsick.

•  So,nowanasideonscreeningtests

“The Square”

A

True Positive

B

False Positive

C

False Negative

D

True Negative

SensiRvity= A/(A+C)[TP/allthosewithdisease]Specificity= D/(B+D)[TN/allthosewithoutdisease]PPV= A/(A+B)[TP/allposiQves]NPV= D/(C+D)[TN/allnegaQves]

Diagnosis Test Result

True negative

False positive

True positive

False negative 100%-

Sensitivity

100%-

Specificity

Disease - centric

Diagnosis Test Result

False positive

True positive

True negative

False negative

100%-PPV

100%-NPV

Patient - centric

So? What’s most important to you?

•  Because you really want them ALL to be good!

–  SENSITIVITY –  SPECIFICITY –  POSITIVE PREDICTIVE VALUE –  NEGATIVE PREDICTIVE VALUE

•  But real life means you will have to sacrifice something

AsaClinician,ThinklikethisGuy.

•  MaximizeSens/Specwhenstudyingadisease

• MaximizePPV/NPVwhenusingasdiagnosRc

ButthisisaRuleOutSepsis•  YouhaveassumedthepaQentissepQc

EmpiricanQbioQccoverageNowyouneedtoprovethattheyarenot

Because,mostoftheQme,theyarenot…. Exceptwhentheyare.

NegaRvePredicRveValueInapopulaRonwitha20-30xincreasedriskabovethatof

thegeneralpopulaRon.

PredicQvevalues•  PPV:iftestisposiQve,whatisthechancethatthepaQent

hasthedisease–  SerialAbnormalCBCs:25%–  SerialAbnormalCRPs:24%

•  NPV:ifthetestisnegaQve,whatisthechancethatthepaQentdoesnothavethedisease–  SerialNormalCBCs:99.4%–  SerialNormalCRPs:99.7%

•  TheircalculaQonisbasedontheriskpriortodrawingthelab(andwhatyourcutoffsare)

CoFN2012Statement

•  CommonnatureofROSworkupwasdiscussed•  Importanceofgevngitright•  UQlityofCBCandCRPwasdiscussed•  Flowchart•  AbxmaybedisconQnued“at48hoursinclinicalsituaQonsinwhichtheprobabilityofsepsisislow”

•  (Thiswasneverdefined)

Kiser’sstudy

•  Singlecenter,retrospecQvereview•  Lookingatwhoreceivedabxbasedjustonlabeval(eitherabnormalCBCsorabnormalCRPs)

•  28%ofthoseevaluatedROSwereruledinbasedonlyonabnormallabvalues

•  IfabnormalCBCandCRPwasused,only5%wouldbetreatedforafullcourse

•  OvertreaQngabout6xasmanykidsasneededtosafe(andabout20xmorethanactuallyinfected)

Kiserpointsout

•  Risksof5-7daysofabx– Disruptedmaternalbonding– ExposuretoanQbioQcs– Centrallineplacement–  IncreasedCost–  InterrupQonofbreasbeeding– ChangestoMicrobiome–  IncreasedriskofNEC

CoFNrevisedstatement

1.  SymptomaQcneonateswithoutriskforinfecQonwhoimprovein<6hrsmaynotrequiretreatmentbutmustbemonitoredclosely

2.  ChorioamnioniQsincreasestherisk,butthelikelihoodofsepsisissQlllow

3.  IntrapartumanQbioQcsdecreasetheriskofsepsis,butalsothesensiQvityofcultures

CoFNrevisedstatement

4.  LabsshouldneverbeusedasaraQonaltoconQnueanQbioQcsinanotherwisehealthyterminfantat48-72hoursoflife

5.  PhysicalExam(andclinicaljudgement)isasgoodorbezerthanmostlabtestsatrulinginorrulingoutsepsis

It’saMonet

It’saMonet

•  Mostinfantsarenotinfected•  WorkupindicatedinthosewithriskfactorsorsymptomsofinfecRon–  IniRalCBCorCRPdoesnotruleinoroutinfecRon

•  Differencebetweenempiricandtreatmentabx •  Don’tdiscount

–  History–  PE–  PeriodofobservaRon

•  HaveanexitplanforyouranRbioRcs

ProbabilityofNeonatalEarly-OnsetSepsisBasedon

MaternalRiskFactorsandtheInfant'sClinicalPresentaRon

•  RetrospecQvereviewof>300,000charts•  KaiserPermanente•  BasedonWorkofKarenPuopolo,MD,PhDandGabrielEscobar,MD

•  hzps://neonatalsepsiscalculator.kaiserpermanente.org/

“SonSigns”(accordingtoKaiser)

TwoormorephysiologicabnormaliQeslasQngfor>2hrs

<OR> Anyonephysiologicabnormality>4hrs

–  Tachycardia(HR>160)–  Tachypnea(RR>60)–  Temperatureinstability(>100.4˚For<97.5˚F)–  Respiratorydistress(grunQng,flaring,orretracQng)notrequiringsupplementalO2

“FirmerSigns”ofillinfant

•  Hemodynamicinstability– Requiringpressors

•  RespiratoryDistress/Failure– RequiringmechanicalvenQlaQon,CPAP,HFNCetc.

•  Neonatalencephalopathy•  NeedforsupplementaloxygenoutsideoftransiQonperiod

ProbabilityofNeonatalEarly-OnsetSepsisBasedon

MaternalRiskFactorsandtheInfant'sClinicalPresentaRon

•  RetrospecQvereviewof>300,000charts•  KaiserPermanente•  BasedonWorkofKarenPuopolo,MD,PhDandGabrielEscobar,MD

•  hzps://neonatalsepsiscalculator.kaiserpermanente.org/

QuesQons?