the palliative care approach to nausea & vomiting palliative care program the palliative care...

UCSF Palliative Care Program

ThePalliativeCareApproachtoNausea&Vomiting

PCQNSeptember2016ConferenceCall

KanaY.McKee,MDAssistantProfessorofClinicalMedicine

PalliativeCareProgram,DepartmentofMedicineUniversityofCalifornia,SanFrancisco


Symptoms:GeneralApproach

§ Canresultfromdiseaseoritstreatment

§ Evaluationbasedongoalsofcare§ Basetreatmentonunderlyingmechanismifpossibleortoreliefofsymptom


NauseaandVomiting

§ Nausea● Unpleasantsensationofneedtovomit

● Pallor,sweats,tachycardia,diarrhea

§ Commonsx inpatientswithseriousillness:● 40%ofpatientsatEOL● 70%ofpatientswithadvancedcancer

Oneofthemostuncomfortablesymptoms!


TheTriggersofNausea&Vomiting

§ 1st lineofdefense:OurSenses

§ 2nd lineofdefense:GutChemo- andMechanoreceptors

§ 3rd lineofdefense:Receptorsinthebrain

§ 4th lineofdefense:Memory,LearnedBehavior


Krakauer E.NEJM2005;352:817-825


MechanismsofNauseaandVomiting

Chemoreceptortriggerzone(4thventricle)D2,NK1,(5HT3)

Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,

vagal,splanchnicandglossopharyngealnerves

Highercorticalstructures

VestibularsystemAchm,H1

VomitingCenter:(Medulla)Achm,H1,(5HT3)

N/V


Ms.A

§ Ms.Aisa43year-oldwomanwithmetastaticbreastcancer.

§ Herdiseasehasprogressedrapidlydespiteaggressivetherapy.

§ Sherecentlydevelopedrightarmweaknessandwasfoundtohavebrainmetastasesinadditiontobone,liver,andlungmetastases.

§ Ms.Apresentstoclinictodaycomplainingof2weeksofnauseaandvomiting.


Ms.A

§ Medications:pamidronate,phenytoin,oxycodoneprn,ibuprofen,omeprazole,anddocusate.

§ Examnotablefortachycardia,drymucosa,normalabdominalexam,andoldrightarmweakness.● Rectalexam:nostool


Questions

§ WhatarethepotentialcausesofMs.A’snauseaandvomiting?

§ Isthereanyotherworkupyouwouldliketoperform?

§ Howwouldyouapproachatreatmentplan?


History

§ Onset,frequency,andseverityofnausea§ Carefulmedicationreview§ Underlyingmedicalillnesses

● Ifcancer:type,location,recenttreatments(chemo/XRT/surgery?)

§ Associatedsxs● Gastritis,reflux,constipation?


History:LookforPatterns§ Earlysatiety,bloating,reliefofnauseaw/small-volumeemesis

à Gastricstasis§ Colickyabdominalpain,large-volumebiliousemesis

à Gastricobstruction§ Nauseawithcertainsmellsorthesightoffood

à Activationofchemoreceptortriggerzone§ Motion-inducednausea,vertigo

à Vestibular§ Earlymorningnausea,headaches,impairedcognition

à IncreasedICP§ Anxietyoremotionallyinducednausea

à Cortical


Evaluation

§ Oralinspection§ Abdominalexam§ Rectalexam(r/oimpaction)§ Labs:lytes,BUN,Cr,LFTs,Ca++,druglevels§ Imaging

● KUBorCTabd/pelvis● CTbrain


Ms.A:DifferentialDiagnosis

§ Medications● pamidronate,oxycodone,ibuprofen,phenytoin

§ Metastases● brain,liver,peritoneum

§ Constipation

§ Metabolic● hyponatremia,uremia,hypercalcemia,liverfailure


Nausea/VomitingTreatment:2Approaches1. Mechanism-based

● Determinelikelyetiologyandtargetfirstmedicationtothecause§ 80-90%effectiveinthepalliativecarepopulation

● Elegant● Assessesallcausessystematically

2. Empiric● Typicallymultipleetiologies● Startwitha5HT3antagonist(ondansetron)ordopamine

antagonist(eg haloperidol)regardlessofunderlyingetiology

Woodetal.JAMA2007;298:1196-1207DavisandHallerberg JPainSym Man2010;39:756-67


Mechanism-BasedApproachtoInitialManagementofN/V1. ThoroughevaluationtonarrowDDx2. Determineunderlyingpathwayandneuroreceptor3. Chooseantiemetictargetedagainstneuroreceptor4. Initiateantiemeticaround-the-clock5. Titrateantiemetictomaxrecommendeddoseifnausea

persists6. Addadditionalantiemeticaimedatdifferent

neurotransmitterifnauseapersists7. Evaluateforadditionalreversiblemechanisms&treat



Chemoreceptortriggerzone(4thventricle)D2,(5HT3),NK1






N/V


ChemoreceptorTriggerZone

§ MostcommoncauseofN/Vnearendoflife§ Mediators

● Dopamine(D2),serotonin(5HT3),NK1§ Etiologies

● Drugs:opioids,digoxin,antibiotics,NSAIDS● Metabolic:hypercalcemia,hyponatremia,uremia,hepaticfailure

● Bacterialtoxins


ChemoreceptorTriggerZoneTreatment§ Relieveunderlyingetiology

● D/Cmeds,lowerdose,PPIifcan’tstopNSAID● Correctelectrolytes

§ Treatment:● Ondansetron(5HT3)● Haloperidol(potentD2antagonistatCTZ)● Prochlorperazine(D2,H1,Achm,5HT3)● Olanzapine(multipleDsand5HTs,Achm)


Ms.A:DifferentialDiagnosis

§ Medications● pamidronate,oxycodone,ibuprofen,phenytoin

§ Metastases● brain,liver,peritoneum

§ Constipation

§ Metabolic● hyponatremia,uremia,hypercalcemia,liverfailure



Chemoreceptortriggerzone(4thventricle)D2,(5HT3),NK1






N/V


MechanicalStretch,GIIrritation

§ Mediators● 5HT3inGItract,GImechanoreceptors,Vagus nerve(AchM,histamine)

§ Etiologies● Mucosalirritation (e.g.candidiasis,XRT)● Externalirritation(e.g.peritonealcarcinomatosis)● GIstretch (e.g.constipation,obstruction)● Viscus enlargement (e.g.liver,kidney)● Dysmotility (gastric,bowelinfiltration,

opioids,anticholinergics)


MechanicalStretch,GIIrritation:Treatment§ Relieveunderlyingcause

● Treatconstipation,gastroparesis● Antibioticsforcandidiasis● PPIforgastritis

§ Ondansetron (5HT3)● Note:avoidifpatientconstipated

§ Promethazine(Anticholinergic/antimuscarinic)§ Metoclopramide(forgastroparesis,partialbowel

obstruction)§ Olanzapine(multipleDsand5HTs,Achm)



Chemoreceptortriggerzone(4thventricle)D2,5HT3,NK1





VomitingCenter:(Medulla)Achm,H1,

5HT2

N/V



§ Directstimulationofvomitingcenter§ Etiologies:

● Tumor,mets,bleed,edema,infection● Mind:emotions,memory

§ Treatment:● Dexamethasone4-16mgpo/ivperday,divide1-2times/day

● Benzodiazepinesforanticipatorynausea,anxiety-inducednausea,andrefractorynausea

§ Note:NoevidenceforBZDassoleagentfortx ofnausea.

● Dietarychangesfortasteandsmell



Chemoreceptortriggerzone(4thventricle)D2,5HT3,NK1





VomitingCenter:(Medulla)Achm,H1,

5HT2

N/V


VestibularSystem

§ Mediators:HistamineandAcetylcholine§ Associatedwithmovement§ Etiology:

● Tumor,mets atbaseofskull● Middleeardisease● Stroke

§ Treatment:● Diphenhydramine● Scopolaminepatch1.5mgq3d● Promethazine● Meclizine


Mechanism-BasedApproachtoInitialManagementofN/V1. ThoroughevaluationtonarrowDDx2. Determineunderlyingpathwayandneuroreceptor3. Chooseantiemetictargetedagainstneuroreceptor4. Initiateantiemeticaround-the-clock5. Titrateantiemetictomaxrecommendeddoseifnausea

persists6. Addadditionalantiemeticaimedatdifferent

neurotransmitterifnauseapersists7. Evaluateforadditionalreversiblemechanisms&treat


IntractableNauseaandVomiting

§ Combineantiemetics withdifferentmechanismsofaction

§ StartwithATCdosing

§ Addsteroids(dexamethasone)● Unclearmechanismofaction● Lessimpressiveassingleagentsbutquiteeffectiveincombination

withotheragents,suchasOndansetron● Goodforacuteanddelayedemesis


IntractableNauseaandVomiting

§ Nontraditionalantiemetics:● Mirtazapine

§ 5HT3antagonist.15-45mgpo atbedtime.§ Canhelpw/n/v,insomnia,appetite,mood

● Olanzapine§ D2,5HT3,AchM§ Canhelpw/n/v,delirium,anxiety,insomnia,andcachexia

§ Considerbowelobstruction


NauseaandVomitingOtherConsiderations§ Medications

● Routeofadministration● Frequencyofdosing,ATCvs PRN● Anticipatenauseatriggersandpremedicate w/antiemetic.● Cost

§ Food● Small,frequent,attractivemeals● Considerodor,fatcontent● Coolcarbonatedbeverages● Takemedications,exceptantiemetics,aftermeals

§ Acupuncture,Acupressure§ Imagery


NauseaandVomitingOtherConsiderations§ Tetrahydrocannabinol (THC)

● Theactiveingredientofmarijuana§ Marketedasdronabinol§ Moreeffectivethanplaceboinpreventingchemotx-inducedn/v

§ MediatedbycannabinoidreceptorsatVomitingCenterinmedulla

● Sideeffects:§ Drowsiness,orthostatichypotension,tachycardia,drymouth

§ Anxiety,depression,visualhallucinations,andmanicpsychosismayoccurs,especiallyinolderindividualsandpatientswhohaveneverusedmarijuana.

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