Final Sepsis Guideline Jan 2012

June2011
ClinicalPracticeGuideline
PediatricSevereSepsis
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis20116
BCCH
ClinicalPracticeGuideline:
PediatricSevereSepsis
Approval
Date
DivisionHead
Name
PeterSkippen
VicePresidentMedicalAffairs
Name
Development
Dec,2011
Signature
Name
Revision1
Signature
Name
Revision2
Signature
Name
Revision3
Signature
NiranjanKissoon
Signature
Name
Signature
Name
Signature
Name
Signature
TableofContents
Introduction .................................................................................................................................................. 4
ScopeandPurpose........................................................................................................................................ 4
TargetUser.................................................................................................................................................... 5
GuidelineSummaryofRecommendations ................................................................................................... 5
Appendices.................................................................................................................................................. 10
AppendixA:Methods ............................................................................................................................. 11
i.Acknowledgements.......................................................................................................................... 11
ii.OriginalGuidelineDevelopmentMemberList ............................................................................... 11
iii.2011GuidelineRevisionMemberList............................................................................................ 11
iv.Literaturesearchstrategy.............................................................................................................. 12
v.Developmentprocess ..................................................................................................................... 12
1.Strengthsandlimitationsofthebodyofevidence................................................................. 12
2.Methodsforformulatingtherecommendations.................................................................... 12
vi.Viewsandpreferencesofthetargetpopulation........................................................................... 12
vii.Dateofguideline........................................................................................................................... 13
viii.Guidelineupdate:procedureforupdatingtheguideline ............................................................ 13
AppendixB:Costutility,costeffectiveness,acquisitioncosts,andimplicationsforbudgets ............... 13
AppendixC:Conflictsofinterest ............................................................................................................ 13
AppendixD:Toolsandresourcesnecessaryforimplementation .......................................................... 14
AppendixE:Barriers,guidelineutilization,andqualityindicators ......................................................... 14
AppendixF:Auditcriteria ....................................................................................................................... 15
AppendixG:Disclaimerandfundingsource........................................................................................... 15
AppendixH:Glossary .............................................................................................................................. 16
References .............................................................................................................................................. 18
Examplesoftools,ordersets,algorithms..19
Introduction
Severesepsisandsepticshockisthemostcommoncauseofdeathinchildrenthroughouttheworld.
TheWorldHealthOrganizationsstatisticsshowthatoftheapproximately9millionchildrenthatdie
eachyearworldwide,approximately70%diefromsepsisanditsrelatedcomplications.
Indevelopedcountries,severesepsisremainsthe4thleadingcauseofdeathinchildrenunder1year
ofageand2ndleadingcauseofdeathinchildrenaged114yearswithamortalityrangingbetween
1220%.Thelast15yearshasseenasignificantchangeintheepidemiologyoforganismswiththe
advent of preventative strategies such as new vaccines. Pneumococcus and hemophilus are now
uncommon, and new emerging strains are becoming more common (e.g. resistant strains of
staphylococcal). As a result, the sepsis syndrome has become a less common presentation in the
busy pediatric emergency departments, and recognition of the septic child is often delayed. The
child who presents with sepsis requires a prompt diagnosis and aggressive treatment to minimize
morbidityandmortality.
Thediagnosisofseveresepsisshouldbebasedonahighdegreeofsuspicionfromatargetedhistory
andphysicalsignsandtreatmentinstitutedassoonasthediagnosisissuspected.Whilelaboratory
confirmation of the diagnosis (microbiological, radiological etc.) may be helpful, reliance on these
tests should not preclude commencing appropriate antibiotic therapy and other necessary life
savingtreatment.Itiscriticalforfrontlinepaediatriciansoremergencyspecialistsfacedwithachild
withpossiblesepsistounderstandthatpediatricsepticshockdiffersfromadultswithsepticshockin
havingahigherincidenceofimpairedcardiacfunction.Thisimpliestheearlierneedforvasopressor
therapy in addition to fluid therapy as essential components of resuscitation. In addition, prompt
attentiontotheunderlyingetiologiesandpredisposingfactorsarenecessary.
It is also important for clinicians to have an understanding of the differential diagnosis of severe
sepsis in the pediatric patient. Other conditions such as disseminated viremia (adenovirus,
enterovirus)andtoxicshocksyndromeareimportanttorecognize.Innewbornchildrenandinfants
withshock,persistentfetalcirculationandcongenitalheartdiseasemayneedtobeexcludedwhile
treating sepsis empirically. In an older child, acute myocarditis may be misdiagnosed as sepsis.
These other conditions require a high index of suspicion in the appropriate clinical setting and
judiciousandtimelyinvestigationsandinterventionstominimizemorbidityandmortality.
TheseguidelinesareaimedatNOTmissingachildpresentingwithseveresepsis.Clinicalsuspicionof
thedifferentialdiagnosisshoulddirecttheastutecliniciantoalsoinvestigateforalternatecausesof
thechildspresentation,andmayalsorequiremodificationofthesuggestedalgorithmspresentedin
thisguideline.
Thisguidelineisasynthesisofcontemporaryknowledgeofdiagnosisandtreatmentapproachesto
themanagementofseveresepsisinchildren.ItislinkedtovarioustoolsdevelopedforuseatBCCH
to guide the clinician through assessment, communication, decisionmaking, and interventions.
Some of the tools are linked to timing sequences to help expedite the care required to mitigate
undesiredoutcomes.
ScopeandPurpose
The purpose of this guideline is to enable clinicians to appropriately recognize, manage and
standardize the care delivered to infants, children or youth whohave been diagnosed with or are
suspectedofhavingseveresepsis.
Thisguidelineaddressesthefollowingquestions:
1. Whoistheintendedpatientpopulationthisguidelinewasdevelopedfor?
2. How and where should screening for early identification of suspected or actual severe
sepsis/septicshockoccur?
3. What actions should be taken in the first hour (initial resuscitation phase) once a child is
identifiedasseptic?
4. What end point goals are targeted with the above actions at the end of the first hour of
resuscitation?
5. Whatantibioticsshouldbeused?
6. Howmuchfluidshouldbedelivered?
7. Whatothersupportsshouldthepatientreceive?
8. Whatclinicalactionsshouldbetakeninhours1to6(ongoingresuscitationphase)forapatient
whohasbeenidentifiedasbeingseverelysepticorinsepticshock?
9. Whatendpointgoalsaretargetedbytheendof6hoursofresuscitation?
10. Whattoolsorsupportsareavailabletobeusedtoassistindecisionmakingforpatientcare?
11. WhatresourcesarerequiredtoimplementthisguidelineatBCCHorotherhealthcarecentres?
TargetUser
TheBritishColumbiaChildrensHospital(BCCH)guidelineisappropriateforusebythehealthcare
team in the emergency department, the acute care inpatient setting as well as in the Pediatric
IntensiveCareUnit.
Theguidelineisavailableforuseinotherprovincialhealthcarefacilitiesbutthetoolsprovidedmay
requireadaptationforimplementationasresourcesandsupportsmayvaryfromwhatisavailableat
BCCH.
GuidelineSummaryofRecommendations
SevereSepsisImprovementBundle
TheSevereSepsisImprovementBundleconsistsofapackageofclinicalpracticesthatusedtogether
assist the clinician to rapidly assess and begin implementation of time sequenced interventions,
based upon an approach called Early Goal Directed Therapy. It remains unclear the relative
importance of individual components of the bundle but is based on the premise that use of the
bundleimprovesoutcomes..Thebundlepresentedhereisbaseduponthemostrecentconsensus
guidelines published and the best evidence available in 2011. As of December 2011, there are a
number of active large multicentre randomized clinical trials exploring the efficacy of different
componentsofthebundle,inbothadultandpediatricpopulations.Atthetimeofthenextrevision
ofthisdocument,therewillhopefullybebetterevidencetomoreclearlydefinetheeffectivebundle
components.
InthebundlethereisaSepsisScreeningTooltobeusedinanyclinicalsetting,aninitialOrderSetto
be used by the physician including Empiric Antibiotic recommendations, a Resuscitation Phase
Algorithm,aManagementPhaseAlgorithmforhours1to6,andaCriticalCareOrderSet.
TherecommendationshavebeenassignedaratinglevelbasedontheAmericanCollegeofCritical
Care Medicine working group and the GRADES system (Grades of recommendation, assessment,
developmentandevaluation)usedbytheSurvivingSepsisCampaign.
RatingSystemforRecommendations
TakenfromAmericanCollegeofCriticalCareMedicine2007
LevelI
Convincinglyjustifiableonscientificevidencealone
LevelII
Reasonablyjustifiablebyscientificevidenceandstronglysupportedbyexpert
criticalcareopinion
LevelIII
Adequatescientificevidenceislackingbutwidelysupportedbyavailabledataand
expertopinion
RatingSystemforRecommendations
TakenfromSurvivingSepsisCampaignusingtheGRADEsystem(GradesofRecommendation,Assessment,
DevelopmentandEvaluation)2008
Grade1
Astrongrecommendation:Thisreflectsthatthedesirableeffectsofadherenceto
arecommendationwillclearlyoutweightheundesirableeffects.
Grade2
Aweakrecommendation:Indicatesthatthedesirableeffectsofadherencetoa
recommendationprobablywilloutweightheundesirableeffects
RandomizedControlTrial(RCT)
DowngradedRCTorupgradedobservationalstudies
Welldoneobservationalstudies
Caseseriesorexpertopinion
PracticeRecommendations
ScreeningPhase
TheScreeningPatientsforSepsisToolshouldbeusedinthefollowing
groups:
LevelofEvidence
1. Allpediatricpatientsthatpresenttotheemergencydepartment.
2. AllpediatricpatientsinPICUdaily
3. PediatricpatientsintheacuteinpatientsettingatBCCHandSHHC
thatpresentwithachangeinclinicalstatusorachangeinEscalation
ofPatientCare(EoPC)score.
4. Allpediatricpatientswhopresenttoordeteriorateinoutlying
facilitiesshouldbeinitiallyscreenedusingtheSepsisAlertTool.
ThosepatientswhoareassessedineithertheAmber(intermediate
risk)orRed(highrisk)categoriesshouldbefurtherscreened.
Ifscreeningispositiveforsepsis/severesepsisthen:
Inemergencycallforassistanceandmovetoresuscitationarea
OninpatientunituseEoPCprotocolandaccesssupportstoassist
withcareofthepatient
Itmustbeemphasisedthatallchildrenpresentingwithaclinical
pictureofsepsisshouldbeisolatedandcaredforusingfullbarrier
precautionstoprotectthehealthcareworker.
PracticeRecommendations060minutes
ResuscitationPhase
Goalstobetargeted:
LevelIII
Maintainorrestoreairway,oxygenationandventilation;maintainorrestore
circulationasdefinedbynormalperfusionandbloodpressure;maintainor
restorethresholdheartrate.
TherapeuticEndpoints:
LevelIII
Capillaryrefilllessthanorequalto2seconds,normalpulseswithno
differentialbetweenthequalityofperipheralandcentralpulses,warm
extremities,urineoutputgreaterthan1mL/kg/hr,normalmentalstatus,
normalbloodpressureforage,normalglucoseconcentration.
Grade2C
UtilizeInitialOrderSet
Monitoring:
Pulseoximetry,continuousECG,bloodpressureandpulsepressure.Pulse
pressureanddiastolicpressureobtainedviainvasivearterialpressure
monitoringmayhelptodistinguishbetweenlowSVR(widepulsepressure)
andhighSVR(narrowpulsepressure),temperature,andurineoutput
Bloodwork:
LevelIII
Ifpossibletakebloodsamplesforbloodculture,venousbloodgas,lactate,
Grade1C
coagulationstudies,CBC,glucose,electrolytes,BUNandcreatininewhen
establishingvenousaccessideallybeforeantibioticadministrationbutshould
notbedelayedduetodifficultiesinestablishingvenousaccess.
Otherlaboratorytests(asorderedbyphysician)foridentificationofthe
sourceofinfection:
urinalysis,nasopharyngealwashforrapidrespiratorypanel(VIRAP),chestx
ray,etc.
ConsiderPICUConsultationseealgorithm
AirwayandBreathing:
Applyoxygen.Airwayandbreathingshouldbecloselymonitored.Lung
complianceandworkofbreathingmaychangeprecipitously.
Intubationmayberequiredforworseningrespiratorydistress,ongoing
hemodynamicinstabilityordecreasingLOC.Ketamineinreduceddoses(0.5
1mg/kg)andRocuronium(1mg/kg)orSuccinylcholine(2mg/kg)are
appropriatemedicationsforintubation.Amoribundchildmayrequireno
medication.EndtidalCO2monitoringisessentialtoconfirmETTisplacedin
thetrachea.ACXRisalwaysrequiredtoconfirmETTpositioninrelationto
thecarina.
Wheneverpossiblevascularvolumeloadingandperipheralorcentral
inotropic/vasoactivedrugsupportisrecommendedbeforeandduring
intubationbecauseofrelativeorabsolutehypovolemia,cardiacdysfunction,
andriskofsuppressingendogenousstresshormoneresponsewithagents
thatfacilitateintubation.
LevelIII
LevelIII
Circulation:
Vascularaccessshouldberapidlyobtained(5minsor3attempts)
Establishintraosseousaccess(IO)ifreliablevenousaccesscannotbe
obtainedin5minutesor3attempts.
FluidResuscitation:
Rapidbolusesof20mL/kg(isotoniccrystalloidor5%albumin)canbe
administeredbypushorrapidinfusiondevicewhileobservingforsignsof
fluidoverload(increasedworkofbreathing,rales,galloprhythmor
hepatomegaly).Childrenwithseveresepsiscommonlyrequire4060mL/kg
inthefirsthour.(Intheabsenceofclinicalimprovementandaconfirmed
diagnosisofsepticshock,repeatedbolusescanbeadministereduptoas
muchas200mL/kginthefirstfewhours)
A5%dextrosecontainingisotonicIVsolutioncanberunatmaintenance
intravenousratestoprovideageappropriateglucosedeliveryandtoprevent
hypoglycaemia.
Inthefluidrefractorypatient,beginaninotrope(lowdoseadrenaline)
infusion.IftheinfusionistobeinfusedthroughaperipheralIVtheinotrope
mustbedeliveredaseitheradilutesolutionorwithacarriersolutionata
lowratetoassurethatitreachestheheartinatimelyfashion.
Peripheraladrenalineinfusiondose:0.01to0.15micrograms/kg/min
Ifthechildhasapreexistingcentralvascularaccessdevice(e.g.Oncologyor
wardpatient),orIntraosseousdevice(IO)thiswouldbethepreferredroute
forvasopressorinfusions.
Centraladrenalineinfusiondose:0.01to0.3micrograms/kg/min.
LevelII
LevelII&
Grade2C
LevelII
Antibiotics:
GradeID
Administerantibioticswithinthefirst30minutesofidentificationideally
afterbloodculturesareobtainedbutshouldnotbedelayedduetodifficulties
inestablishingvenousaccess.RefertotheEmpiricAntibioticTreatment
Guide
HydrocortisoneTherapy:
LevelIII
Ifachildremainsinshockdespiteanadrenalineinfusion,hydrocortisonecan Grade2C
beadministered,preferablyafterobtainingabloodsamplefor
determinationofbaselinecortisolconcentration(toexcluderelativeor
absolutecortisoldeficiency).
ProteinCandActivatedproteinC:
Notrecommended
Grade1B
DeepVeinThrombosis(DVT)Prophylaxis:
Prophylaxisisrecommendedforpostpubertalchildrenwithseveresepsis.
DVTsoccurinapproximately25%ofchildrenwithafemoralcentralvenous
catheter.
Grade2C
ArrangetransfertoPICUforcontinuedcareifpatientconditionwarrants
PICURecommendations16hoursManagementPhase
Allpatientswithadiagnosisofseveresepsisshouldreceiveacompletehead
totoeassessment,withaspecificfocusonidentifyingthesourceof
infection.
Grade1C
UsetheSevereSepsis/SepticShockManagementAlgorithmhour16to
directtherapeuticinterventionsforcareofthepatientonceSevere
Sepsis/SepticShockResuscitationAlgorithm01hriscomplete.
Goalstobetargetedfortheunintubatedpatient:
Normalizedvitalsigns:caprefill2seconds,normalpulses,warm
extremities,urineoutput>1mL/kg/hourandanormalpresepticmental
status
AnScv02>70%(ifcentralvenousaccessavailable)
Goalstobetargetedfortheintubatedpatient:
NormalizedVS:caprefill2seconds,normalpulses,warmextremities,
urineoutput>1mL/kg/hourandanormalpresepticmentalstatus(this
willbealteredifsedationorparalyzingagentshavebeenadministered)
AnScv02>70%
UtilizeCriticalCareOrderSet
LevelIII
Monitoring:
Pulseoximetry,continuousECG,continuousintraarterialbloodpressure,
temperature(core),urineoutput,centralvenouspressure/Scv02saturation,
endtidalCO2.
Bloodwork:
Serialvenousbloodgases,lactate,coagulationstudies,CBC,
glucose/glucometer,electrolytes,BUN,creatinineandanyother
investigationsorderedbyphysician,dependingonresponsetotherapy.
LevelIII
OtherInvestigations:
CardiacECHOtoassesscardiacfunction
Otherinvestigationsatthediscretionofthecriticalcarephysiciantoexclude
otherdiagnosesinthedifferential.
LevelII
HemodynamicSupport:
Ongoingfluidreplacementmayberequiredduetoongoinghypovolemia
secondarytodiffusecapillaryleak.
Usevasopressor,inotropicorinodilatortherapyaccordingtotheclinical
stateofthechild(coldorwarmshock,fluidrefractory,catecholamine
refractory).
Cardiorespiratoryfailurenotrespondingtoconventionaltherapiesmay
requireextracorporeallifesupport(ECLS).
LevelII
Antibiotics:
Reassessantimicrobialtherapyafterfinalcultureresultreported/consultID
early;usualcourseistypically710daysforconfirmedbacterialsepsis.Ifa
viraletiologyisconfirmedandbacterialculturesarenegative,antibiotics
shouldbediscontinued.
LevelII
Grade2C
Grade1C&
Grade1D
Sedation/Analgesia:
Grade1D
Appropriatesedationandanalgesiaarethestandardofcareforchildrenwho
aremechanicallyventilated;thereisnodatatosupportanyparticulardrug
orregimen
10
Appendices
AppendixA:Methods
i.Acknowledgements
Thisgroupwouldliketoacknowledgethemanyotherhealthcareprofessionalswhocontributedtothe
developmentofthisguidelinebysharingtheirexpertopinionandbyactingasreviewers.Wewouldalso
liketoacknowledgeJPCollet,MDPhDClinicalProfessorandAssociateHeadofResearch,Departmentof
Pediatrics, UBC, Associate Director Quality and Safety Evaluation and Mir Kaber Mosavian Pour PhD
studentfortheirassistanceindevelopmentoftheframeworktouseforguidelinedevelopment.
ii.2008OriginalGuidelineDevelopmentMemberList
RoxaneCarr,PharmD,BCPS,FCSHP
Supervisor,ClinicalPharmacyCriticalCareServices
DepartmentofPharmacy,BCCH,AssistantProfessor,
parttime,FacultyofPharmaceuticalSciences,UBC
GeoffreyHung,MDED,BCCH,Vancouver,BC
DeniseHudson,RNBSN,QualityandSafetyLeaderED,
BCCH,Vancouver,BC
TracieNorthway,RNMScN,CNCCP(c),Qualityand
SafetyLeader,PICUBCCH,Vancouver,BC
MaryLouHurley,RNBN,ClinicalNurseEducator
Oncology,Haematology,BMTprogram,BCCH,
Vancouver,BC
AleciaRobin,RNCNCCP(c),ClinicalNurse
CoordinatorPICU,BCCH,Vancouver,BC
GordonKrahn,RTQualityandResearch,PICU,BCCH,
Vancouver,BC
PeterSkippen,MDMBBS,FJFICM,FRCPC,MHA
SeniorMedicalDirectorAcuteCareServices
ClinicalProfessor,DivisionofCriticalCare
DepartmentofPediatrics,UBC,BCCH,Vancouver,BC
SandyPittfield,MD,FRCP(C)
StaffPhysician,CriticalCare,MedicalDirector,
ExtracorporealLifeSupportProgram,IntensivistPICU,
BCCH,Vancouver,BC
DavidWaller,RN,BA,MSc,ClinicalNurseCoordinator
PICU,BCCH,Vancouver,BC
JenniferGallagher,RNPICU,BCCH,Vancouver,BC
JaimeWilliams,RNClinicalResourceNurse,PICU
BCCH,Vancouver,BC
iii.2011GuidelineRevisionMemberList
RoxaneCarr,DPharm.BCPS,FCSHP
Supervisor,ClinicalPharmacyCriticalCareServices
DepartmentofPharmacy,BCCH,AssistantProfessor,
parttime,FacultyofPharmaceuticalSciences,UBC
TracieNorthway,RNMScN,CNCCP(c),Qualityand
SafetyLeader,PICU,BCCH,Vancouver,BC
JenniferDruker,MDMBChB,DCH,FRCPC,Clinical
AssociateProfessor,DivisionHead,GeneralPediatrics;
Director,ClinicalTeachingUnits,BCCH,UBC,
Vancouver,BC
SandyPitfield,MD,FRCP(C)
StaffPhysician,CriticalCare,MedicalDirector,
ExtracorporealLifeSupportProgram,IntensivistPICU,
BCCH,Vancouver,BC
PiaDeZorzi,RNBScN,CPON,PPLNursing,BCCH,
Vancouver,BC
JaneRiedel,RN,MScN,ClinicalNurseEducator,ED,
BCCH,Vancouver,BC
11
SimonDobson,MD,FRCP(C),ClinicalAssociate
Professor,DivisionofInfectiousandImmunological
Diseases,DepartmentofPediatrics,UBC,BCCH,
Vancouver,BC
DeborahScott,RNBScN,PPLNursing,BCCH,
Vancouver,BC.,ProjectLead
KarenLeComte,RNMScN.ClinicalNurseEducator,
PICU,BCCH,Vancouver,BC
PeterSkippen,MDMBBS,FJFICM,FRCPC,MHA
SeniorMedicalDirectorAcuteCareServices
ClinicalProfessor,DivisionofCriticalCare
DepartmentofPediatrics,UBC,BCCH,Vancouver,BC
DavidWensley,MD,FRCP(C)
MedicalDirectorandDivisionHead
DivisionofCriticalCare,BCCH,Vancouver,BC
PeterTilley,MD,InfectiousDiseases,Vancouver,BC
PaulKorn,MDEmergencyDepartment,BCCH,
Vancouver,BC
DavidWaller,RN,BA,MSc,ManagerED,BCCH,
Vancouver,BC
TexKissoon,MDFRCP(c),FAAP,FCCM,FACPE,Vice
PresidentMedicalAffairs,BCCH&SHHC,Vancouver,
BC
iv.Literaturesearchstrategy
TheBCCHworkinggroupwasawarethatpreestablishedinternationalguidelinesforidentification
andtreatmentofpediatricsepticshockhadbeendevelopedandimplementedsuccessfullyin2002
and revised in 2007. Using search words such as sepsis, septic shock, infection, septicaemia and
AmericanCollegeofCriticalCareMedicineinMEDLINEandCINAHLathoroughsearchwasdoneto
locatethe mostrecentpreexistingpublished guidelines.Thegroupsdecisionwastoincludeonly
thesepreexistingguidelinesastheycontainedathoroughliteraturesearch,andtheevidencehad
been graded and recommendations put forth. Information from The Surviving Sepsis Campaign
website;http://www.survivingsepsis.org/Pages/default.aspxwasalsoreviewed.Articlesnotwritten
inEnglishwereexcludedfromuse.
v.Developmentprocess
1.Strengthsandlimitationsofthebodyofevidence
AmodifiedDelphimethodwasusedbytheAmericanCollegeofCriticalCareMedicinetogradeany
new literature published since the launch of their original 2002 guideline to create updated
recommendations.
The Surviving Sepsis Campaign incorporated the Grades of Recommendation, Assessment,

DevelopmentandEvaluation(GRADES)systemtoguideassessmentofthequalityofevidencefrom
very high (A) to very low (D) and to determine the strength of recommendations. A strong
recommendation indicates that an interventions desirable effect clearly outweigh its undesirable
effects or clearly do not. Weak recommendations indicate that a trade off between desirable and
undesirableislessclear.
The BCCH expert group selected the recommendations made specifically for pediatric patients.
Where no recommendation could be made for the pediatric population, adult recommendations
12
wereconsideredandconsensuswasreachedamongstclinicalexpertsincriticalcareandemergency
medicine.
2.Methodsforformulatingtherecommendations
Based on the information listed above in the inclusion/exclusion section all pediatric
recommendations were accepted by the BCCH expert working group. Recommendations requiring
local adaptation (e.g. medication calculations for pharmacy) were adapted by seeking advice and
consensusfromclinicalexpertswithinBCCH.
vi.Viewsandpreferencesofthetargetpopulation
TheBCCHinterdisciplinaryexpertworkinggroupidentifiedanopportunitytoimprovepatientcare
byinitiatinganaggressivetreatmentprotocolearlyinthehospitalcourseofpatientswhohavebeen
identifiedashavingseveresepsis.
Theviewsandpreferencesofthetargetpopulationhavenotbeensought.
vii.Dateofguideline
The original BCCH Severe Sepsis Guideline, released in 2006, was adapted from the adult severe
sepsisbundlespracticedwithintheCanadianICUCollaborativebyagroupofclinicalexpertsatBCCH
whohadconductedanextensivereviewofthepediatricsepsisliteratureavailableatthattime.In
2008 the BCCH Severe Sepsis Guidelines were reviewed and adapted by a group of BCCH clinical
experts to align with the American College of Critical Care Medicines 2007 severe sepsis
recommendations.Thisupdatedguidelinewasdevelopedinresponsetoaseriesofcriticalincidents
andtherecognitionoftheneedforhealthcareteameducationandimprovedprocessdelivery.
viii.Guidelineupdate:procedureforupdatingtheguideline
Thisguidelinewillbereviewedevery3years(orearlierifnewevidenceispublished)byapanelof
clinicalexpertsatBCCHfromthecriticalcare,emergencyandacuteinpatientsunits.Thisguideline
willbereviewedagainin2014.
AppendixB:Costutility,costeffectiveness,acquisitioncosts,andimplications
forbudgets
TherearenoidentifiedfinancialresourcesrequiredtoimplementthisguidelineatBCCHbecauseas
aquaternaryhealthcarecentreallmedications,equipmentandstaffrequiredtocareforpatients
with multiorgan involvement is in place. Paid time of physician champions, clinical educators and
quality safety leaders to support staff through the learning phase is an extra cost. Eduquick
resourcemoduleshavebeendevelopedandwillbelocatedintheclinicalareasasanextrasupport
forstaff.
Other centres who wish to implement these guidelines will have to consider costs for necessary
equipment such as cardiorespiratory monitoring equipment, ventilatory supports such as
13
ventilators and endotracheal tubes, availability of laboratory testing with stat results reporting
(pointofcare),themedicationsrequiredfortreatment,andeithertheclinicalexpertsinmedicine,
nursingandrespiratorytherapywhohavethepropertraining,experienceandwhodemonstrateuse
of professional judgment or the funds to support the education of those individuals required to
providecare.
AppendixC:Conflictsofinterest
There are no conflicts of interest to report; no members of the guideline development team are
involvedinanyresearchorpromotionalactivitiesforoutsidecompanies.
AppendixD:Toolsandresourcesnecessaryforimplementation
Procedures:SeeScreeningPatientsforSepsisTool
SeeInitialOrderSet;CriticalCareOrderSet
Algorithms:SeeSevereSepsis/SepticShockResuscitationPhase01hourAlgorithm
SevereSepsis/SepticShockMaintenancePhase16hoursAlgorithm
OtherResources:SeeEmpiricAntibioticGuideline
SepsisAlertTool
Trainingandlearningpackages:Availableuponrequest:dscott6@cw.bc.ca
Theseareavailableforuseatothercenters;toolsmaybeadaptedtosuitthelearningneedsofthe
intendedaudience.
AppendixE:Barriers,guidelineutilization,andqualityindicators
Barriers
Itisanexpectationthatthisguidelinewillbeusedtoassessandtreatallpatientswhoaresuspected
or diagnosed with severe sepsis. As with any guideline personal preference by practitioners is a
potential barrier to effective rollout across an organization. To mitigate this risk guideline
champions(changeagents)inalldisciplineswillbeengagedearlyintheprocessofimplementation
toberolemodelsandmentorstofellowcolleagues.Amultiphasededucationalstrategythataims
at creating awareness and interest, building knowledge and commitment, promoting action and
adoptionandpursuingintegrationandsustainabilityisrecommendedtobeused(Cullen2011).
Competing interests or other organizational projects are also a barrier to application. Many other
qualityassurance/improvementprojectsareunderwayinmostorganizationsandinmanyindividual
programs in hospitals. Communicating with other project leaders to stagger the timing of
rollout/implementationtoavoidoverloadingpractitionerswouldbeadvisable.
14
Another potential barrier to application could be the clinical setting the patient presents to
(requiredequipmentnotavailable)ortheskilllevelofthosepresenttobeabletoassessandcare
forthepatient.
GuidelineUtilization
The guideline and tools were initially designed to be used in the emergency, PICU and inpatient
unitsatBCCHbyphysiciansandnurses.Theguidelineisavailableforuseinotherfacilitiesbutthe
toolsprovidedmayrequireadaptationforimplementationasresourcesandsupportsmayvaryfrom
whatisavailableatBCCH.
Various tools have been developed for use at BCCH to guide the clinician through assessment,
communication,decisionmaking,andinterventions.Ascreeningtoolhasbeendevelopedforusein
the emergency department or inpatient unit to assist in the determination of a patients status.
Some of the tools are linked to timing sequences to help expedite the care required to mitigate
undesiredoutcomes.
AppendixF:Auditcriteria
Audit or measurement criteria will be collected to assist in understanding if any changes

implemented are leading to an improvement. Audit criteria are one way to understand processes
andsystemsofcare.Threetypesofmeasurescanbeincludedinauditing:Outcome,Balancingand
Process.
Auditing will be done initially on a concurrent basis and then will move to a quarterly
andyearlyscheduleoncetheguidelineiswellestablished.
Process measures to capture: screening completed on all patients in emergency, daily
screening of patients in PICU and screening completed on inpatient units on those
patients who have a change in clinical status (Escalation of Patient Care Score); if
treatmentprescribed,timingofinterventions(timetoantibiotics,bloodcultures,fluids).
Complianceratewithscreeninganduseoftheguidelinecomponentswillbemeasured
(allornothing)aswellaslengthofstay(LOS)forbothinpatientandcriticalcareareas.
AppendixG:Disclaimerandfundingsource
NOTE: A printed copy of this document may not reflect the current, electronic version on the
Intranet.Anydocumentsappearinginpaperformshouldalwaysbecheckedagainsttheelectronic
versionpriortouse.Theelectronicversionisalwaysthecurrentversion.
ThisClinicalPracticeSupportDocumenthasbeenpreparedasaguidetoassistandsupportpractice
for staff working at BCCH/SHHC. While every effort has been made to ensure the accuracy of the
contents at the time of publication, neither the authors nor BCCH give any guarantee as to the
accuracyoftheinformationcontainedinthemnoracceptanyliability,withrespecttoloss,damage,
injuryorexpensearisingfromanysucherrorsoromissioninthecontentsofthiswork.Itisnota
substituteforpropertraining,experienceandtheexerciseofprofessionaljudgment.
15
This document may be produced, reproduced and published in its entirety only, in any form,
including in electronic form, for educational or noncommercial purposes, without requiring the
consentorpermissionofBCCH,providedthatanappropriatecreditorcitationappearsinthecopied
workasfollows:
BCCH(2011).BCCHPediatricSevereSepsisGuideline(Revised).Vancouver,Canada:BritishColumbia
ChildrensHospital.
Funding through the Childrens Hospital Foundation was used to support the development of this
clinicalpracticesupportdocument.
AppendixH:Glossary
AmericanCollegeofCriticalCareMedicinedefinitionsforshock
Coldorwarmshock
Fluidrefractory/dopamineresistant
shock
Catecholamineresistantshock
Refractoryshock
Infection
SIRSSystemicInflammatoryResponse
Decreasedperfusionmanifestedbyaltereddecreasedmentalstatus,
capillaryrefillgreaterthanorequalto2seconds(coldshock)orflash
capillaryrefill(warmshock),diminished(coldshock)orbounding(warm
shock)peripheralpulses,mottledcoolextremities(coldshock),or
decreasedurineoutputlessthan1mL/kg/hr
Shockpersistsdespitegreaterthanorequalto60mL/kgfluidresuscitation
(whenappropriate)anddopamineinfusionto10g/kg/min
Shockpersistsdespiteuseofthedirectactingcatecholamines;adrenalineor
noradrenaline
Shockpersistsdespitegoaldirecteduseofinotropicagents,vasopressors,
vasodilatorsandmaintenanceormetabolic(glucoseandcalcium)and
hormonal(thyroid,hydrocortisone,insulin)homeostasis
Asuspectedorproven(bypositiveculture,tissuestain,orpolymerasechain
reactiontest)infectioncausedbyanypathogenORaclinicalsyndrome
associatedwithahighprobabilityofinfection.Evidenceofinfectionincludes
positivefindingsonclinicalexam,imaging,orlaboratorytests(e.g.,white
bloodcellsinanormallysterilebodyfluid,perforatedviscus,chest
radiographconsistentwithpneumonia,petechialorpurpuricrash,or
purpurafulminans)
Thepresenceofatleasttwoofthefollowingfourcriteria,oneofwhich
mustbeabnormaltemperatureorWBCcount:
Coretemperatureofgreaterthan38.5oCorlessthan36oC.
Tachycardia,definedasameanheartrategreaterthan2Standard
Deviations(SD)abovenormalforageintheabsenceofexternal
stimulus,chronicdrugs,orpainfulstimuli;orotherwiseunexplained
persistentelevationovera0.5hrto4hrtimeperiodORforchildren
lessthan1yearold:bradycardia,definedasameanheartrateless
than10thpercentileforageintheabsenceofexternalvagalstimulus,
Bblockerdrugs,orcongenitalheartdisease;orotherwise
unexplainedpersistentdepressionovera0.5hrtimeperiod.
Meanrespiratoryrategreaterthan2SDabovenormalforageor
mechanicalventilationforanacuteprocessnotrelatedtounderlying
neuromusculardiseaseorthereceiptofgeneralanesthesia.
WBCelevatedordepressedforage(notsecondarytochemotherapy
inducedleucopenia)orgreaterthan10%immatureneutrophils.
16
Sepsis
Sepsis
SIRSinthepresenceoforasaresultofsuspectedorproveninfection.
Severesepsis
Severesepsisoccursuponfailureordysfunctionofatleastoneorgan.
OrganDysfunction
Cardiovasculardysfunction
Despiteadministrationofisotonicintravenousfluidbolusgreaterthanor
equalto40mL/kgin1hr
DecreaseinBP(hypotension)lessthan5thpercentileforageorsystolic
BPlessthan2SDbelownormalforage
OR
NeedforvasoactivedrugtomaintainBPinnormalrange(dopamine
greaterthan5g/kg/minordobutamine,adrenaline,ornoradrenaline
atanydose)
OR
Twoofthefollowing
Unexplainedmetabolicacidosis:basedeficitgreaterthan5.0mEq/L
Increasedarteriallactategreaterthan2timesupperlimitofnormal
Oliguria:urineoutputlessthan0.5mL/kg/hr
Prolongedcapillaryrefill:greaterthan4seconds
Coretoperipheraltemperaturegapgreaterthan3oCorpalpable
difference
AND
Femoraldorsalispedispulsegradient
nodifference++
weakDP+
absentDP0
Respiratory
PaO2/FiO2<300inabsenceofcyanoticheartdiseaseorpreexisting
lungdisease
OR
PaCO2greaterthan65mmHgor20mmHgoverbaselinePaCO2
OR
Provenneedorgreaterthan50%FiO2tomaintainsaturationgreater
thanorequalto92%
Needfornonelectiveinvasiveornoninvasivemechanicalventilation
Neurologic
GlasgowComaScorelessthanorequalto11
OR
AcutechangeinmentalstatuswithadecreaseinGlasgowComaScore
greaterthanorequalto3pointsfromabnormalbaseline
Hematologic
Plateletcountlessthan80,000/mm3oradeclineof50%inplatelet
countfromhighestvaluerecordedoverthepast3days
OR
Coagulation:Internationalnormalizedratio(INR)greaterthan2
Renal
Serumcreatininegreaterthanorequalto2timesupperlimitof
normalforageor2foldincreaseinbaselinecreatinine
Hepatic
Totalbilirubingreaterthanorequalto70micromoles/L(notapplicable
17
fornewborn)
OR
ALT2timesupperlimitofnormalforage
CTAS : Abnormal Heart Rate and Respiratory Rate by Age Groups (CTAS 2008)
(Canadian Triage and Acuity Scale)
Age Group
HR
RR
Birth 3 mo
<90 or >180
<30 or >60
3 mo - 6mo
<80 or >160
<30 or >60
6 mo 1 yr
<80 or >140
<25 or >45
1 yr 3 yr
<75 or >130
<20 or >30
6 yr
<70 or >110
<16 or >24
=>10 yr
<60 or >90
<14 or >20
Table 1: Abnormal Values by Age Groups
Goldstein B, Giroir B, Randolph A: International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr. Crit. Care Med 2005,
6(1):2-8.
Age Group
WBC
Systolic BP
MAP
0 days-1 wk
>34
<65
ModifiedDelphi
OutcomeMeasures
BalancingMeasures
ProcessMeasures
1wk-1 mo
>19.5 or <5
<75
<55
1 mo-1 yr
>17.5 or <5
<90
<60
1 yr-5 yr
>15.5 or <6
<90
<65
5 yrs-12 yrs
>13.5 or <4.5
<100
<65
12 yrs-18 yrs
>11 or <4.5
<110
<65
The modified Delphi begins with a carefully selected openended

questionnaire that is given to a panel of selected experts to solicit
specificinformationaboutasubjectorcontentarea.Insubsequent
roundsoftheprocedure,participantsratetherelativeimportanceof
individualitemsandalsomakechangestothephrasingorsubstance
oftheitems.Throughaseriesofrounds(typicallythree)theprocess
isdesignedtoyieldconsensus.
These measures indicate whether changes are leading to
improvementandachievingtheoverallaimoftheproject.
These measures help a team to understand the effect of their
changes on the broader system and to understand relationships,
interactions and subsequent tradeoffs between measures. It helps
ensure that a change to improve one part of a system does not
causenewproblemstootherpartsofthesystem.
These measures indicate whether a specific change is having its
intended effect. Changes to several processes in a system may be
neededtoaffectanimprovementintheoverallaimofaproject.The
assumption is that improvements in the process measures will
eventuallyimprovetheoutcomemeasure.
18
References
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PedCritCareMed.(2010).March11epub
AmericanHeartAssociationguidelinesforcardiopulmonaryresuscitationandemergencycardiovascular
careofpaediatricandneonatalpatients.(2005).Part12:Paediatricadvancedlifesupport.
Circulation.112:IV16787.
BoydJHetal.(2011).Fluidresuscitationinsepticshock:apositivefluidbalanceandelevatedcentral
venouspressureareassociatedwithincreasedmortality.CritCareMed;39:259265.
BrierleyJ,CarcilloJA,ChoongKetal.(2009).Clinicalpracticeparametersforhemodynamicsupportof
pediatricandneonatalsepticshock:2007updatefromtheAmericanCollegeofCriticalCare
Medicine.CriticalCareMedicine.37,666688.
CanadianAssociationofEmergencyPhysicians(CAEP)withtheconsentoftheCTASnationalworking
group(NWG).(2008).TheCanadianTriageandAcuityScale:combinedadult/pediatriceducation
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CanadianICUCollaborative(March26,2007).ImprovingpatientcareandsafetyintheICUimprovement
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CenevivaG,PaschallJA,MaffeiF,etal.(1998).Hemodynamicsupportinfluidrefractorypediatricseptic
shock.Pediatrics;102:e19.
COIITTSStudyInvestigators.(2010).Corticosteroidtreatmentandintensiveinsulintherapyforseptic
shockinadults:arandomizedcontrolledtrial.JAMA;303:341348.
CullenL,&Adams,S.(Inreview).Animplementationmodeltopromoteadoptionofevidencebased
practice.2011
CruzATetal.(2011).Implementationofgoaldirectedtherapyforchildrenwithsuspectedsepsisinthe
emergencydepartment.Pediatrics;127:3e758766.
Dalkey,N.C.(1972).TheDelphimethod:anexperimentalapplicationofgroupopinion.InN.C.Dalkey,
D. L. Rourke, R. Lewis, & D. Snyder (Eds.) Studies in the quality of life. Lexington, MA: Lexington
Books.
DellingerRP,LevyMM,CarletJM,BionJ,ParkerMM,JaeschkeR,ReinhartK,AngusDC,BrunBuissonC,
BealeRetal.(2008).SurvivingSepsisCampaign:internationalguidelinesformanagementofsevere
sepsisandsepticshock:2008.CriticalCareMedicine.36,296327.
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GoldsteinB,GiroirB,RandolphA.(2005).Internationalpediatricsepsisconsensusconference:
definitionsforsepsisandorgandysfunctioninpediatrics.Pediatr.CriticalCareMedicine.6(1):28.
HonidenSetal.GlucosecontroversiesintheICU.JIntensiveCareMed.publishedonline30Nov2010.
DOI:10.1177/0885066610387892
MaitlandKetalandFEASTInvestigators.MortalityafterFluidBolusinAfricanChildrenwithSevere
Infection.NEJM2011;May26onlinefirst.
MaerzLetal.(2011).Perioperativeglycemicmanagementin2011:paradigmshifts.CurrOpinCritCare.
17:370375.
ParshuramC,HutchisonJ,MiddaughK.(2009).DevelopmentandinitialvalidationoftheBedside
PaediatricEarlyWarningSystemscore.CriticalCare.13:R135.
TheSAFEStudyInvestigators.(2011).Impactofalbumincomparedtosalineonorganfunctionand
mortalityofpatientswithseveresepsis.IntCareMed;37:8696.
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June2011

The Surviving Sepsis Campaign incorporated the Grades of Recommendation, Assessment,

Audit or measurement criteria will be collected to assist in understanding if any changes

Table 1: Abnormal Values by Age Groups

The modified Delphi begins with a carefully selected openended

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