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Hypersensi/vityReac/ons:HowToPrepareForThe(Not-So)Unexpected

KaraThomas,RNBSNOCNSkagitRegionalHealth

Objec/ves

•  An/cipateandrecognizehypersensi/vityreac/onsduringchemotherapyandbiotherapyadministra/on

•  Iden/fynursingandpa/entimplica/onsinthepreven/onandmanagementofhypersensi/vityreac/ons

Defini/on

•  Hypersensi)vity(alsocalledhypersensi/vityreac/onorinfusionreac/on)isasetofundesirablereac/onsproducedbythenormalimmunesystem.Thesereac/onsmaybedamaging,uncomfortable,oroccasionallyfatal.

•  Unexpectedandexcessiveresponsesoftheimmunesystemtoaforeignsubstance(an/gen).

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ImmuneSystemReview

•  Thepurposeoftheimmunesystemistoprotect“self”from“non-self”byneutralizing,elimina/ng,ordestroyingforeigninvaders.

ImmuneSystemReview

•  Majoranatomicalstructuresincludesitesforproduc/on,matura/on,prolifera/on,andfunc/onofthecellsoftheimmunesystem:bonemarrow,thymus,lymphnodes,andspleen.

ImmuneSystemReview

•  Whitebloodcellsarethemajorcellsoftheimmunesystem.Thevarioustypesincludegranulocytes(neutrophils,basophils,andeosinophils),macrophages,NKcells,andlymphocytes(BandTlymphocytes).

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ImmuneSystemReview

ImmuneSystem

Adap/ve

Humoral Cell-Mediated

Innate

ImmuneSystemReview

Innate•  Immediateresponse•  Involvesneutrophilsand

macrophages•  Candamagehost/ssue•  Amnesiac

Adap)ve•  Slowerresponse,especially

withfirstexposure(naïve)•  Specifican/genrecogni/on•  Memory:rapidrecallof

an/gen

ImmuneSystemReview

Humoral•  Blymphocytesares/mulated

toproducean/bodies(immunoglobulins)inresponsetoanan/gen.

•  Plasmacellsproducefivetypesofimmunoglobulins:IgG,IgA,IgM,IgD,andIgE.

Cell-Mediated

•  Involvesinterac/onsofHelperandCytotoxicTcells

•  Cytokines:potentglycoproteinmediatorsthatsignalbetweencellsandcoordinatetheimmuneresponse

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TypesofHypersensi/vityI:Allergy/anaphylaxis

–  An/genexposurecausesreleaseofvasoac/vesubstances(histamine,prostaglandins)frommastcellsorbasophils.UsuallyIgEdependent.

–  Bees/ngII:An/bodymediated

–  Anan/genorhaptenthatisin/matelyassociatedwithacellbindstoan/body,leadingtocellor/ssueinjury

–  IgGorIgM:Rh-momIII:Immunecomplexmediated

–  Damageiscausedbyforma/onordeposi/onofan/gen-an/bodycomplexesinvesselsor/ssue

–  Lupus,serumsicknessIV:Delayed

–  An/genexposuresensi/zesTcells,whichthenmediate/ssueinjury–  Contactderma//s,poisonivy

Anaphylac/cReac/on

•  Anan/genisrecognizedasforeign

•  Bodyformsan/bodies(partofadap/veresponse)

•  Mostcommonan/bodyformedduringanallergicreac/onisIgE

•  IgEpromoteshistaminereleasefrommastcells

Manifesta/onofAnaphylaxis

•  Cutaneous:rash,hives,angioedema•  GI:nausea,vomi/ng,diarrhea•  Respiratory:shortnessofbreath,difficultybreathing,wheezing

•  Circulatory:hypotension,chestpain•  Senseofimpendingdoom…..

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AnaphylactoidReac/on

•  An/genisrecognizedasforeign

•  TLymphocytescausereleaseofcytokines

•  Alsocalledcytokinereleasesyndromeorinfusionreac/on

Manifesta/onofCytokineReleaseSyndrome

•  Fever•  Chills•  Headache•  Nausea•  Hypertension•  Fa/gue

•  Canbejustassevereasanaphylaxis

Anaphylac/cvs.Anaphylactoid

•  Despitethetypeofreac/on,thesymptomsandthetreatmentmaylookthesame

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IncidenceofHypersensi/vity

•  Overallincidenceofhypersensi/vityreac/onstochemotherapyorbiotherapyvaries

•  Firstinfusionofrituximab:50%•  Firstinfusionoftrastuzumab:40%•  Firstorsecondinfusionofpaclitaxel:30%•  Sixthorseventhinfusionofcarbopla/n:12%

RiskFactors

Chemotherapy

• Carbopla/n• Oxalipla/n• Paclitaxel• Docetaxel

Biotherapy

• Rituximab• Cetuximab• Traztuzumab

OtherAgents

• Phase1drugs• IronDextran• Peglo/case

Pa/entRiskFactors•  Failuretotakeprescribedpremedica/onforprophylaxis•  Female•  Firstinfusionofmonoclonalan/body•  Historyorallergies(foods,medica/ons,bees/ngs)•  Historyofasthma•  IVrouteofadministra/on•  Geographicloca/on(higherratesofrxntocetuximabinSEstates)•  Highlymphocytecounts•  Higherthannormalchemotherapyorbiotherapydoses•  Historyofautoimmunedisease•  Historyofpulmonaryinfiltrates,cardiacorpulmonarydysfunc/on•  Mul/plecyclesofdrugs(pla/numagents)•  Age(olderage)•  Primarytumortypesuchaschroniclymphocy/cleukemiaandmantelcell

lymphoma

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Preven/on

•  Obtainandrecordbaselinevitalsigns•  Reviewallergyhistory•  Ensureavailabilityofemergencymedica/ons•  Administertestdoseifindicated•  Slowini/alinfusionrate•  Administerpremedica/ons– An/pyre/c– An/histamine–  Cor/costeroid

Ra/onaleforpremeds

An/pyre/cs:Preventand/ormi/gatefeverduringreac/on

An/histamines:H1blockersmediatetachycardia,pruri/s,rhinnorhea,bronchospasmH2blockersaddmedia/onofflushing,hypotension&headache

Cor/costeroids:Inhibitcytokinerelease,amelioratesymptoms,an/-inflammatory

EmergencyPlan

•  Ifpa/entexhibitssigns/symptomsofHSR:– Stopinfusion– Staywithpa/entandcallforhelp– MaintainopenIVline(withdrawcausa/veagentifpossible)

– Assessairway,breathingandcircula/on– Monitorvitalsigns–  Ifhypotensive,placepa/entinsupineposi/on–  Ifvomi/ng,placepa/entinside-lyingposi/on

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EmergencyPlan

•  Administeremergencymedica/onsasindicated

•  Administeroxygenathighflowrate•  Provideemo/onalsupport•  Documentinterven/onsandresponses•  Con/nuetomonitorassymptomsmayrecur

Pa/entandFamilyTeaching

•  Priortoadministra/on,discusspossibilityofhypersensi/vityreac/on

•  Provideinstruc/ononwhatsymptomstoreport

•  Akeradministra/on,discusspossibilityofdelayedreac/onandhowtomanage

Illustra/on

ImmuneSystem:• Protectselffromnon-self• Neutralize• Eliminate• Destroy

Non-self PremedicatedImmuneSystem:• Lessresponsive• Morepermissive

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SignsandSymptomsofHSR•  Uneasiness,agita/on•  Chest/ghtness•  SOBwithorwithoutwheezing•  Hypotension•  Tachycardia•  Headache•  Itching,localorgeneralized•  Abdominalcramping,diarrhea,nausea•  Periorbitalorfacialedema

ManagementofAnaphylac/cReac/on

•  Akerini/alstabiliza/oniscomplete,con/nuetomonitorpa/ent

•  Providerwillformulateplantocon/nueorabortinfusion,dependingofseverityofreac/on

•  Mayamemptdesensi/za/onprotocol(necessaryforeachsubsequentinfusionofcausa/veagent)

•  AddallergytoEHR

ManagementofCytokineReleaseSyndrome

•  Okenmanagedbyshort-termcessa/onofinfusion

•  Administeraddi/onalhistamineblocker•  Restartinfusionatslowerrate

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AlgorithmforManagingSuspectedHypersensi)vityReac)ons

Pa)entexhibitssignsofhypersensi)vityorinfusionreac)on(Uneasinessoragita/on,pruritus,ur/caria,dyspnea,bronchospasm,hypotension,itching,facialedema,lightheadednessordizziness,abdominalcramping,diarrhea,nausea,vomi/ng)

MildReac)onfacialflushing,rash,lowbackpain,orfallof<30mmHginsystolic

BP

1.Stopinfusionandstaywithpa/ent.2.InfuseIVnormalsalineorfluidasordered.3.MonitorVS,O2satatleastq15minfor1hour.4.Administeraddi/onalhistamineblockersasordered

Response

Con/nuetomonitor.Discussplanw/MD.Resumeinfusionrateat50%ofpreviousrate

Noresponseorsymptomsworsen:Proceedtonumber4.

SevereReac)onbronchospasm,hypotensionwitha>30mmHgdropin

systolicBP,respiratorydistress,/ghtnessinthethroatoracrossthechest

1.Stopinfusion;infuseIVnormalsaline2.AdministerO2at2-4LperNC.No/fyMD.3.Staywithpa/entandmonitorvitalsigns.4.Placepa/entsupineandelevatelegsifSBP<60mmHg.5.Monitorandmaintainairway.6.Administeremergencymedica/ons:

Histamineblockers–Epinephrine--Cor/costeroids7.Provideemo/onalsupport.

Pa/entImprovesAn/cipateneedforCPR.

Ac/vateemergencyresponse(911orcodeteam).

Post-Reac/onDecisions

•  Properdocumenta/onfacilitatesinformeddecisionmakingaboutthesafetyofsubsequentinfusions

•  Overes/ma/nggradeofreac/onmaylimitfurthertreatmentop/onsbydenyingrechallenge

•  Underes/ma/nggradeofreac/onmayleadtoinadequatevigilanceandpreparednessforpoten/alemergentsitua/onand/orplacepa/entatunnecessaryriskifrechallenged

NCICTCAEGradingAdverseEvent

Grade1 Grade2 Grade3 Grade4 Grade5

Infusion-relatedreac/on

Mildtransientreac/on;infusioninterrup/onnotindicated;interven/onnotindicated

Therapyorinfusioninterrup/onindicatedbutrespondspromptlytosymptoma/ctreatment

Notrapidlyresponsivetosymptoma/cmedica/onand/orbriefinterrup/onofinfusion

Life-threateningconsequences;urgentinterven/onindicated

Death

Na/onalCancerIns/tuteCommonTerminologyCriteriaforAdverseEvents

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Desensi/za/on

•  Differentregimensdependingondrug•  Necessaryforeachsubsequentexposuretocausa/veagent

•  Alteredinfusionrate,concentra/onorboth

ExamplesofDesensi/za/onProtocols

Carbopla)n1/1000oftotaldose1/100oftotaldose1/10oftotaldoseRemainderofdose

Carbopla)nStartinfusionat20ml/hrTitrateby20ml/hrevery15

minutestomaximumrateof264ml/hr

Conclusion

•  Hypersensi/vityreac/onsarefrightening.•  Oncologynursesareuniquelyposi/onedtodirectlyinfluencethemanagementofhypersensi/vityreac/ons.

•  Awareness,prepara/onandcloseobserva/onwillaidinminimizingtheimpactofareac/on.

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ReferencesEisenberg,S.(2013).Infusionreac/ons.InM.Kaplan(Ed.).Understandingandmanagingoncologicemergencies:Aresourcefornurses(pp.199-247).Pimsburgh,PA:OncologyNursingSociety.Infusionreac/onstosystemicchemotherapy.RetrievedfromUpToDate.com,2/4/16.Infusionreac/onstotherapeu/cmonoclonalan/bodiesusedforcancertherapy.RetrievedfromUpToDate.com,

2/8/16.Polovich,M.,Olsen,M.,&Lefebvre,K.B.(Eds.).(2014).Chemotherapyandbiotherapyguidelinesandrecommenda9onsforprac9ce.(4thed.).Pimsburgh,PA:OncologyNursingSociety.Roleofcytokinesintheimmunesystem.RetrievedfromUpToDate.com,2/4/16.Viale,P.H.(2010).Dermatologiccomplica/ons.InJ.Eggert(Ed.),Cancerbasics(pp.378-377).OncologyNursingSociety:Pimsburgh,PA.Viale,P.H.,&Sanchez-Yamamoto,D.(2010).Biphasicanddelayedhypersensi/vityreac/ons:Implica/onsforoncologynursing.ClinicalJournalofOncologyNursing,14(3),347-356.Vogel,W.H.(2012).Infusionreac/ons:Diagnosis,assessment,andmanagement.ClinicalJournalofOncologyNursing,14(2),E10-E21.