June2011

ClinicalPracticeGuideline PediatricSevereSepsis

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis20116

BCCH ClinicalPracticeGuideline: PediatricSevereSepsis

Approval Date Name Development Dec,2011 Signature Name Signature Name Signature Name Signature Signature Name Signature Name Signature Name Signature DivisionHead PeterSkippen VicePresidentMedicalAffairs Name NiranjanKissoon

Revision1

Revision2

Revision3

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

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
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 3

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.
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 4

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?

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

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.

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis20116

RatingSystemforRecommendations
TakenfromAmericanCollegeofCriticalCareMedicine2007

LevelI LevelII LevelIII

Convincinglyjustifiableonscientificevidencealone Reasonablyjustifiablebyscientificevidenceandstronglysupportedbyexpert criticalcareopinion Adequatescientificevidenceislackingbutwidelysupportedbyavailabledataand expertopinion

RatingSystemforRecommendations TakenfromSurvivingSepsisCampaignusingtheGRADEsystem(GradesofRecommendation,Assessment, DevelopmentandEvaluation)2008 Grade1 Grade2 A B C D PracticeRecommendations ScreeningPhase TheScreeningPatientsforSepsisToolshouldbeusedinthefollowing groups: 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.
7

Astrongrecommendation:Thisreflectsthatthedesirableeffectsofadherenceto arecommendationwillclearlyoutweightheundesirableeffects. Aweakrecommendation:Indicatesthatthedesirableeffectsofadherencetoa recommendationprobablywilloutweightheundesirableeffects RandomizedControlTrial(RCT) DowngradedRCTorupgradedobservationalstudies Welldoneobservationalstudies Caseseriesorexpertopinion

LevelofEvidence

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

PracticeRecommendations060minutes ResuscitationPhase Goalstobetargeted: Maintainorrestoreairway,oxygenationandventilation;maintainorrestore circulationasdefinedbynormalperfusionandbloodpressure;maintainor restorethresholdheartrate. TherapeuticEndpoints: Capillaryrefilllessthanorequalto2seconds,normalpulseswithno differentialbetweenthequalityofperipheralandcentralpulses,warm extremities,urineoutputgreaterthan1mL/kg/hr,normalmentalstatus, normalbloodpressureforage,normalglucoseconcentration. UtilizeInitialOrderSet Monitoring: Pulseoximetry,continuousECG,bloodpressureandpulsepressure.Pulse pressureanddiastolicpressureobtainedviainvasivearterialpressure monitoringmayhelptodistinguishbetweenlowSVR(widepulsepressure) andhighSVR(narrowpulsepressure),temperature,andurineoutput Bloodwork:

LevelIII

LevelIII Grade2C

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

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

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 DeepVeinThrombosis(DVT)Prophylaxis: Prophylaxisisrecommendedforpostpubertalchildrenwithseveresepsis. DVTsoccurinapproximately25%ofchildrenwithafemoralcentralvenous catheter. ArrangetransfertoPICUforcontinuedcareifpatientconditionwarrants PICURecommendations16hoursManagementPhase Allpatientswithadiagnosisofseveresepsisshouldreceiveacompletehead totoeassessment,withaspecificfocusonidentifyingthesourceof infection. Grade1B Grade2C

Grade1C

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

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 Monitoring: Pulseoximetry,continuousECG,continuousintraarterialbloodpressure, temperature(core),urineoutput,centralvenouspressure/Scv02saturation, endtidalCO2. Bloodwork: Serialvenousbloodgases,lactate,coagulationstudies,CBC, glucose/glucometer,electrolytes,BUN,creatinineandanyother investigationsorderedbyphysician,dependingonresponsetotherapy. OtherInvestigations: CardiacECHOtoassesscardiacfunction Otherinvestigationsatthediscretionofthecriticalcarephysiciantoexclude otherdiagnosesinthedifferential. HemodynamicSupport: Ongoingfluidreplacementmayberequiredduetoongoinghypovolemia secondarytodiffusecapillaryleak. Usevasopressor,inotropicorinodilatortherapyaccordingtotheclinical stateofthechild(coldorwarmshock,fluidrefractory,catecholamine refractory). Cardiorespiratoryfailurenotrespondingtoconventionaltherapiesmay requireextracorporeallifesupport(ECLS). Antibiotics: Reassessantimicrobialtherapyafterfinalcultureresultreported/consultID early;usualcourseistypically710daysforconfirmedbacterialsepsis.Ifa viraletiologyisconfirmedandbacterialculturesarenegative,antibiotics shouldbediscontinued.

LevelIII

LevelIII

LevelII

LevelII LevelII Grade2C Grade1C& Grade1D

Sedation/Analgesia: Grade1D Appropriatesedationandanalgesiaarethestandardofcareforchildrenwho aremechanicallyventilated;thereisnodatatosupportanyparticulardrug orregimen

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 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 DeniseHudson,RNBSN,QualityandSafetyLeaderED, BCCH,Vancouver,BC MaryLouHurley,RNBN,ClinicalNurseEducator Oncology,Haematology,BMTprogram,BCCH, Vancouver,BC GordonKrahn,RTQualityandResearch,PICU,BCCH, Vancouver,BC GeoffreyHung,MDED,BCCH,Vancouver,BC

TracieNorthway,RNMScN,CNCCP(c),Qualityand SafetyLeader,PICUBCCH,Vancouver,BC AleciaRobin,RNCNCCP(c),ClinicalNurse CoordinatorPICU,BCCH,Vancouver,BC PeterSkippen,MDMBBS,FJFICM,FRCPC,MHA SeniorMedicalDirectorAcuteCareServices ClinicalProfessor,DivisionofCriticalCare DepartmentofPediatrics,UBC,BCCH,Vancouver,BC DavidWaller,RN,BA,MSc,ClinicalNurseCoordinator PICU,BCCH,Vancouver,BC

SandyPittfield,MD,FRCP(C) StaffPhysician,CriticalCare,MedicalDirector, ExtracorporealLifeSupportProgram,IntensivistPICU, 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 JenniferDruker,MDMBChB,DCH,FRCPC,Clinical AssociateProfessor,DivisionHead,GeneralPediatrics; Director,ClinicalTeachingUnits,BCCH,UBC, Vancouver,BC PiaDeZorzi,RNBScN,CPON,PPLNursing,BCCH, Vancouver,BC TracieNorthway,RNMScN,CNCCP(c),Qualityand SafetyLeader,PICU,BCCH,Vancouver,BC

SandyPitfield,MD,FRCP(C) StaffPhysician,CriticalCare,MedicalDirector, ExtracorporealLifeSupportProgram,IntensivistPICU, BCCH,Vancouver,BC JaneRiedel,RN,MScN,ClinicalNurseEducator,ED, BCCH,Vancouver,BC

11

BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011

SimonDobson,MD,FRCP(C),ClinicalAssociate Professor,DivisionofInfectiousandImmunological Diseases,DepartmentofPediatrics,UBC,BCCH, Vancouver,BC KarenLeComte,RNMScN.ClinicalNurseEducator, PICU,BCCH,Vancouver,BC

DeborahScott,RNBScN,PPLNursing,BCCH, Vancouver,BC.,ProjectLead

PeterSkippen,MDMBBS,FJFICM,FRCPC,MHA SeniorMedicalDirectorAcuteCareServices ClinicalProfessor,DivisionofCriticalCare DepartmentofPediatrics,UBC,BCCH,Vancouver,BC PeterTilley,MD,InfectiousDiseases,Vancouver,BC

DavidWensley,MD,FRCP(C) MedicalDirectorandDivisionHead DivisionofCriticalCare,BCCH,Vancouver,BC PaulKorn,MDEmergencyDepartment,BCCH, Vancouver,BC TexKissoon,MDFRCP(c),FAAP,FCCM,FACPE,Vice PresidentMedicalAffairs,BCCH&SHHC,Vancouver, BC

DavidWaller,RN,BA,MSc,ManagerED,BCCH, 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
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 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
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 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.

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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.
BCChildrensHospitalClinicalPracticeGuideline:PediatricSevereSepsis2011 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 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.

Fluidrefractory/dopamineresistant shock Catecholamineresistantshock Refractoryshock

Infection

SIRSSystemicInflammatoryResponse

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Sepsis

Sepsis SIRSinthepresenceoforasaresultofsuspectedorproveninfection. Severesepsis Severesepsisoccursuponfailureordysfunctionofatleastoneorgan. 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

OrganDysfunction

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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

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.

Table 1: Abnormal Values by Age Groups 1 mo-1 yr >17.5 or <5 <90 <60 1 yr-5 yr >15.5 or <6 <90 <65

Age Group WBC Systolic BP MAP

0 days-1 wk >34 <65

1wk-1 mo >19.5 or <5 <75 <55

5 yrs-12 yrs >13.5 or <4.5 <100 <65

12 yrs-18 yrs >11 or <4.5 <110 <65

ModifiedDelphi OutcomeMeasures BalancingMeasures ProcessMeasures

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.

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 References
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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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Sepsis Alert!

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