UCSF Palliative Care Program
ThePalliativeCareApproachtoNausea&Vomiting
PCQNSeptember2016ConferenceCall
KanaY.McKee,MDAssistantProfessorofClinicalMedicine
PalliativeCareProgram,DepartmentofMedicineUniversityofCalifornia,SanFrancisco
UCSF Palliative Care Program
Symptoms:GeneralApproach
§ Canresultfromdiseaseoritstreatment
§ Evaluationbasedongoalsofcare§ Basetreatmentonunderlyingmechanismifpossibleortoreliefofsymptom
UCSF Palliative Care Program
NauseaandVomiting
§ Nausea● Unpleasantsensationofneedtovomit
● Pallor,sweats,tachycardia,diarrhea
§ Commonsx inpatientswithseriousillness:● 40%ofpatientsatEOL● 70%ofpatientswithadvancedcancer
Oneofthemostuncomfortablesymptoms!
UCSF Palliative Care Program
TheTriggersofNausea&Vomiting
§ 1st lineofdefense:OurSenses
§ 2nd lineofdefense:GutChemo- andMechanoreceptors
§ 3rd lineofdefense:Receptorsinthebrain
§ 4th lineofdefense:Memory,LearnedBehavior
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Krakauer E.NEJM2005;352:817-825
UCSF Palliative Care Program
MechanismsofNauseaandVomiting
Chemoreceptortriggerzone(4thventricle)D2,NK1,(5HT3)
Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,
vagal,splanchnicandglossopharyngealnerves
Highercorticalstructures
VestibularsystemAchm,H1
VomitingCenter:(Medulla)Achm,H1,(5HT3)
N/V
UCSF Palliative Care Program
Ms.A
§ Ms.Aisa43year-oldwomanwithmetastaticbreastcancer.
§ Herdiseasehasprogressedrapidlydespiteaggressivetherapy.
§ Sherecentlydevelopedrightarmweaknessandwasfoundtohavebrainmetastasesinadditiontobone,liver,andlungmetastases.
§ Ms.Apresentstoclinictodaycomplainingof2weeksofnauseaandvomiting.
UCSF Palliative Care Program
Ms.A
§ Medications:pamidronate,phenytoin,oxycodoneprn,ibuprofen,omeprazole,anddocusate.
§ Examnotablefortachycardia,drymucosa,normalabdominalexam,andoldrightarmweakness.● Rectalexam:nostool
UCSF Palliative Care Program
Questions
§ WhatarethepotentialcausesofMs.A’snauseaandvomiting?
§ Isthereanyotherworkupyouwouldliketoperform?
§ Howwouldyouapproachatreatmentplan?
UCSF Palliative Care Program
History
§ Onset,frequency,andseverityofnausea§ Carefulmedicationreview§ Underlyingmedicalillnesses
● Ifcancer:type,location,recenttreatments(chemo/XRT/surgery?)
§ Associatedsxs● Gastritis,reflux,constipation?
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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
UCSF Palliative Care Program
UCSF Palliative Care Program
Evaluation
§ Oralinspection§ Abdominalexam§ Rectalexam(r/oimpaction)§ Labs:lytes,BUN,Cr,LFTs,Ca++,druglevels§ Imaging
● KUBorCTabd/pelvis● CTbrain
UCSF Palliative Care Program
Ms.A:DifferentialDiagnosis
§ Medications● pamidronate,oxycodone,ibuprofen,phenytoin
§ Metastases● brain,liver,peritoneum
§ Constipation
§ Metabolic● hyponatremia,uremia,hypercalcemia,liverfailure
UCSF Palliative Care Program
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
UCSF Palliative Care Program
Mechanism-BasedApproachtoInitialManagementofN/V1. ThoroughevaluationtonarrowDDx2. Determineunderlyingpathwayandneuroreceptor3. Chooseantiemetictargetedagainstneuroreceptor4. Initiateantiemeticaround-the-clock5. Titrateantiemetictomaxrecommendeddoseifnausea
persists6. Addadditionalantiemeticaimedatdifferent
neurotransmitterifnauseapersists7. Evaluateforadditionalreversiblemechanisms&treat
UCSF Palliative Care Program
MechanismsofNauseaandVomiting
Chemoreceptortriggerzone(4thventricle)D2,(5HT3),NK1
Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,
vagal,splanchnicandglossopharyngealnerves
Highercorticalstructures
VestibularsystemAchm,H1
VomitingCenter:(Medulla)Achm,H1,(5HT3)
N/V
UCSF Palliative Care Program
ChemoreceptorTriggerZone
§ MostcommoncauseofN/Vnearendoflife§ Mediators
● Dopamine(D2),serotonin(5HT3),NK1§ Etiologies
● Drugs:opioids,digoxin,antibiotics,NSAIDS● Metabolic:hypercalcemia,hyponatremia,uremia,hepaticfailure
● Bacterialtoxins
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ChemoreceptorTriggerZoneTreatment§ Relieveunderlyingetiology
● D/Cmeds,lowerdose,PPIifcan’tstopNSAID● Correctelectrolytes
§ Treatment:● Ondansetron(5HT3)● Haloperidol(potentD2antagonistatCTZ)● Prochlorperazine(D2,H1,Achm,5HT3)● Olanzapine(multipleDsand5HTs,Achm)
UCSF Palliative Care Program
Ms.A:DifferentialDiagnosis
§ Medications● pamidronate,oxycodone,ibuprofen,phenytoin
§ Metastases● brain,liver,peritoneum
§ Constipation
§ Metabolic● hyponatremia,uremia,hypercalcemia,liverfailure
UCSF Palliative Care Program
MechanismsofNauseaandVomiting
Chemoreceptortriggerzone(4thventricle)D2,(5HT3),NK1
Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,
vagal,splanchnicandglossopharyngealnerves
Highercorticalstructures
VestibularsystemAchm,H1
VomitingCenter:(Medulla)Achm,H1,(5HT3)
N/V
UCSF Palliative Care Program
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)
UCSF Palliative Care Program
MechanicalStretch,GIIrritation:Treatment§ Relieveunderlyingcause
● Treatconstipation,gastroparesis● Antibioticsforcandidiasis● PPIforgastritis
§ Ondansetron (5HT3)● Note:avoidifpatientconstipated
§ Promethazine(Anticholinergic/antimuscarinic)§ Metoclopramide(forgastroparesis,partialbowel
obstruction)§ Olanzapine(multipleDsand5HTs,Achm)
UCSF Palliative Care Program
MechanismsofNauseaandVomiting
Chemoreceptortriggerzone(4thventricle)D2,5HT3,NK1
Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,
vagal,splanchnicandglossopharyngealnerves
Highercorticalstructures
VestibularsystemAchm,H1
VomitingCenter:(Medulla)Achm,H1,
5HT2
N/V
UCSF Palliative Care Program
Highercorticalstructures
§ 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
UCSF Palliative Care Program
MechanismsofNauseaandVomiting
Chemoreceptortriggerzone(4thventricle)D2,5HT3,NK1
Mechanicalstretch,GIirritation5HT3inGItract,mechanoreceptors,
vagal,splanchnicandglossopharyngealnerves
Highercorticalstructures
VestibularsystemAchm,H1
VomitingCenter:(Medulla)Achm,H1,
5HT2
N/V
UCSF Palliative Care Program
VestibularSystem
§ Mediators:HistamineandAcetylcholine§ Associatedwithmovement§ Etiology:
● Tumor,mets atbaseofskull● Middleeardisease● Stroke
§ Treatment:● Diphenhydramine● Scopolaminepatch1.5mgq3d● Promethazine● Meclizine
UCSF Palliative Care Program
Mechanism-BasedApproachtoInitialManagementofN/V1. ThoroughevaluationtonarrowDDx2. Determineunderlyingpathwayandneuroreceptor3. Chooseantiemetictargetedagainstneuroreceptor4. Initiateantiemeticaround-the-clock5. Titrateantiemetictomaxrecommendeddoseifnausea
persists6. Addadditionalantiemeticaimedatdifferent
neurotransmitterifnauseapersists7. Evaluateforadditionalreversiblemechanisms&treat
UCSF Palliative Care Program
IntractableNauseaandVomiting
§ Combineantiemetics withdifferentmechanismsofaction
§ StartwithATCdosing
§ Addsteroids(dexamethasone)● Unclearmechanismofaction● Lessimpressiveassingleagentsbutquiteeffectiveincombination
withotheragents,suchasOndansetron● Goodforacuteanddelayedemesis
UCSF Palliative Care Program
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
UCSF Palliative Care Program
NauseaandVomitingOtherConsiderations§ Medications
● Routeofadministration● Frequencyofdosing,ATCvs PRN● Anticipatenauseatriggersandpremedicate w/antiemetic.● Cost
§ Food● Small,frequent,attractivemeals● Considerodor,fatcontent● Coolcarbonatedbeverages● Takemedications,exceptantiemetics,aftermeals
§ Acupuncture,Acupressure§ Imagery
UCSF Palliative Care Program
NauseaandVomitingOtherConsiderations§ Tetrahydrocannabinol (THC)
● Theactiveingredientofmarijuana§ Marketedasdronabinol§ Moreeffectivethanplaceboinpreventingchemotx-inducedn/v
§ MediatedbycannabinoidreceptorsatVomitingCenterinmedulla
● Sideeffects:§ Drowsiness,orthostatichypotension,tachycardia,drymouth
§ Anxiety,depression,visualhallucinations,andmanicpsychosismayoccurs,especiallyinolderindividualsandpatientswhohaveneverusedmarijuana.
UCSF Palliative Care Program
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