Figure 2: Recurrent nausea and/or vomiting

26

patient with chronic or

recurrent nausea and/or
vomiting, without co-existing
frequent heartburn

27

25
yes

long-term
long-term
management
management

no

symptom
improvement?

consider
consider
additional
additional
testing
testing

24
treat
treat accordingly
accordingly

2
history
history and
and physical
physical
examination
examination
7

drug- or
substance-induced
nausea/vomiting

3
yes

alarm
features?

15

5
yes

chronic
idiopathic
nausea

cyclic vomiting
syndrome

functional
vomiting

6
elimination
elimination of
of
presumed
presumed
causal
causal agent
agent

symptom
improvement?

no

14

yes

yes

no

consider
consider
manometric
manometric
evaluation/
evaluation/
impedance
impedance

no

upper
upper GI
GI
endoscopy,
endoscopy,
blood
blood tests
tests

21
vomiting
present?

yes

11

9
any
abnormality
identified?

23

yes

22

rumination
syndrome

no
potentially drugor substanceinduced?

17

13

suggestive
of psychological
or neurological
disorder?

no

no

16
suggestive of
rumination
syndrome?

no

no

18
suggestive of
cyclic vomiting
syndrome?

no

19
severely
delayed
emptying?

gastric
gastric
emptying
emptying
test
test

yes

yes
yes

10

20

organic causes eg
pyloric canal ulcer,
hyperthyroidism,
uremia

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12
appropriate
appropriate
testing
testing or
or
referral
referral

manage as
gastroparesis

2009 The Rome Foundation

Recurrentnauseaand/orvomiting
Casehistory
A23yearoldcollegestudentisreferredtoagastroenterologistforrefractory,persistentnausea(Box1,Fig2).
Thehistory(Box2)revealsthatshehadbeenwelluntil14monthsago,whenshebecameprogressively
nauseatedoverthecourseofafewdays.Althoughinitiallypresentseveralhoursperday,overthelastfew
monthsthenauseahasbecomeeverpresent,fromthemomentshewakesupuntilthetimeshegoestobed.
Thenauseaisusuallynotassociatedwithvomitingthoughshehasvomited3or4timesinthelastyear(Boxes
1,13,16,21).Thereisnoheartburn(Box1)orexcessivebelching.Thenauseainterfereswithherappetite,
thoughisnotworsenedaftermealsandisnotrelatedtobowelmovements,postureorexercise.Shehaslost
3kgofweightoverthelast6months.Therearenootheralarmsymptoms(Box3).Shenotesoccasionalmild
intermittentpostprandialfullness,withoutearlysatiationorepigastricpain.ThepatientdoesnottakeNSAIDs
orothermedications,isanonsmokerandusesalcoholonlysporadically.Thereisnohistoryofsubstanceuse
(Box4).Therearenoassociatedvestibular,neurologicalorovertpsychiatricsymptoms(Box11).Thereisno
historyofmigraineandnootherpreviousorcurrentmedicalconditionsthatmayexplainthenausea.Thereis
norelevantfamilyhistoryofgastrointestinaldisease.
Clinicalexaminationisnegative,includingtheabsenceofvascularbruitsovertheabdomen,noneurological
systemabnormalities,andnoalarmsigns(Boxes2,3,11).Bloodtestsincludingthyroidfunctiontestsandtests
forothersystemicormetabolicdisordersarenormal(Boxes8,9).Anabdominalultrasoundperformed12
monthsagowasreportedasnormal.AnupperGIendoscopyperformedduringthelastyearwasalsonormal
(Boxes8,9).A24hoururinarycortisolisnormal.
Overthelastyear,shehastriedseveralprokineticandantiemeticagents(includingmetoclopramide,
domperidone,ondansetron),andalsowasprescribedaPPI,uptotwotimesthestandarddose,without
improvement.Shenowtakesuptofour10mgtabletsofmetoclopramideperday,withlittleoranyeffect,and

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noothermedications.Thegastroenterologistalsoconfirmsthattherearenospecificfeaturestosuggest
ruminationsyndrome(Box13)orcyclicvomitingsyndrome(Box16).andalsorefersthepatientforan
ophthalmologicalexaminationtoruleoutsignsofintracranialhypertension(Box11).Ascintigraphicgastric
emptyingtest(Box18)isthenarranged;thisrevealsahalfemptyingtimeforsolidswithinthenormalrange
(Box19).Adiagnosisofchronicidiopathicnauseaismade(Box22).
Alowdosetricyclicantidepressantisthenprescribedfor8weeks,withadditionofchlorpromazineasa
symptomaticantiemeticagent(Box25).Theoptionofconductingadditionaldiagnosticinvestigations,suchas
abdominalCTscanandMRIofthebrain,incaseofinsufficientresponsetotheproposedtherapy,isdiscussed.

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Figurelegend
1. Nauseaisacommonandsubjectivesymptomandthedifferentialdiagnosisiswide.Inthiscontext,itis
assumedtherearenoknownsystemicororganicdisorderssuchasdiabetesmellitusorconnective
tissuedisease.Nauseamayaccompanygastroesophagealrefluxdisease(GERD)andmayoften
respondtoappropriateGERDmanagement,whichwillgenerallyconsistofPPItherapy.Alsosee
recurrentheartburnalgorithm(1).
2. Adetailedhistoryandclinicalexaminationattheinitialvisitareessential.Thehistoryshouldrecognize
nauseaasanunpleasantsensationoftheimminentneedtovomittypicallyexperiencedinthe
epigastriumorthroat.Vomitingshouldbedistinguishedfromregurgitationorrumination(seebelow).
Duringthehistorytakingandclinicalexamination,abroadlistofpotentialcausesofnauseaand
vomiting,includingorganicgastrointestinaldisorders,medicationsandtoxicagents,endocrine
disorders,neurologicaldisordersandpsychogenicfactorsshouldbeconsidered(1,1114).
3. Alarmfeaturesincludeage,unintentionalweightloss,nocturnalsymptoms,dysphagia,
lymphadenopathy,abdominalmassandevidenceofanemia.Ifanyofthesesymptomsorsignsis
present,promptupperGIendoscopyisindicated,althoughtheyieldmaybelow(3,4).
4. Classesofdrugsthatcommonlycausenauseaand/orvomitingincludeanalgesics,cardiovascular
medications,hormonalpreparations,antibiotics,CNSactivemedications,andcancerchemotherapy.
Cannabisuse/interruptionofusehasbeenimplicatedinchronicorrecurrentnauseaandvomiting(1).
5,6.Ifpotentiallyrelevantmedicationscanbediscontinued,andsymptomsimproveintemporalassociation
withthiscessation,adiagnosisofdrugorsubstanceinducednausea/vomitingmaybeconsidered,although
longertermfollowupwillberequired(12).

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7.Besidescancerchemotherapyagents,opioidanalgesicsandmacrolideantibioticsareimportantcausesof
nauseaandvomiting.Acluetocannabishyperemesisiscompulsivehotbathingorshoweringbehavior.
8

UpperGIendoscopyservesmainlytoexcludeobstructivelesionsandpepticulceration,orrarelyanother
organiclesion.Inyoungpatientswithoutalarmfeatures,empiricantiemetictherapymaybeconsidered
priortoendoscopyandotheradditionalinvestigations.Inthecaseoffrequentvomiting,esophagitismay
bepresent,butthisisaconsequenceofvomitingcausticgastriccontentsandusuallydoesnotexplain
chronicorrecurrentnauseaandvomiting.Relevantbloodteststobeconsideredinadditiontoroutine
hematologyandbiochemicaltests,includeCRPlevel,thyroidfunctiontests,bloodglucoselevel,serum
calcium,andteststoexcludeAddisonsdisease.Celiacdiseasemaybescreenedforinhighprevalence
areas.Furthertestsmayberequireddependingontheresultsoftheseinvestigations.Imaging(small
bowelxrayorCTenterography)maybeusedtoexcludemechanicalobstructionintheupper
gastrointestinaltract(1,12).Inthesettingofrecentmajorweightloss(e.g.recentspinalcordinjury,
anorexianervosa),thesuperiormesentericsyndrome(SMA)maydevelopwherethereiscompressionof
the3rdportionofduodenumbytheaorta;CTisanexcellentdiagnosticmodalityatwhichtimethe
superiormesentericarterytoabdominalaortadistanceshouldbemeasured.

11,12.Neurologicaldisordersthatmaycausechronicorrecurrentnauseaand/orvomitingincludemigraine,
increasedintracranialpressure,labyrinthinedisordersanddemyelinatingdisorders.Usuallythereare
neurologicalsymptomsandsignsthatcluethephysicianintothesepossibilities.Psychologicalconditionsthat
maycausechronicorrecurrentnauseaand/orvomitingincludeanxietydisorders,depression,eatingdisorders
andpsychogenicvomiting.Psychogenicvomitingusuallyoccursinconditionsofmajorpsychologicaldistress
andisnotclearlyrelatedtofoodingestion.Selfinducedvomitingismainlyassociatedwitheatingdisorders.
Appropriatetesting(clinicalneurologicalexamination,exclusionofintracranialhypertensionbyexaminationof
theeyefundusorbyMRIscanofthebrain)and/orreferralmayneedtobeconsidered.

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13.Ruminationshouldbesuspectedwhenthereistheeffortlessrepeatedregurgitationoffood(14).Atypical
historyisgenerallysufficienttomakeadiagnosisofruminationsyndrome.Keyelementsarethetimingduring
andshortlyaftermealingestion,thelackofprodromalnausea,therepetitiveandeffortlessappearanceof
foodinthemouth,andtheabilitytoswallowtheregurgitatedmaterialbackintotheesophagus.
14. Incaseofdoubtorneedforadditionalconfirmation,esophagogastricmanometrywithadministrationofa
mealshowsadiagnosticpatternofbriefintragastricpressurerisesthataretransmittedtotheesophagus.
Simultaneousimpedancemonitoringmaydocumentthattheseabdominothoracicstrainspush
intragastriccontentsupintotheesophagustothepharynx(14,15).
15.RomeIIIdiagnosticcriteriaforruminationare:1)persistentorrecurrentregurgitationofrecently
ingestedfoodintothemouthwithsubsequentspittingorremasticationandswallowing,and2)the
regurgitationisnotprecededbyretching,and3)thesecriteriaarefulfilledforthelast3monthswith
symptomonsetatleast6monthspriortodiagnosis(1).
Supportivecriteriaarethatregurgitationeventsarenotusuallyprecededbynausea,thereiscessationof
theprocesswhentheregurgitatedmaterialbecomesacidic,andtheregurgitantcontainsrecognizablefood
withapleasanttaste.
16. Cyclicvomitingshouldbesuspectedwhenthereareepisodesofvomitingwithastereotypicalonsetand
duration.Therearevaryingintervalsofabsenceofvomitinginbetweenepisodes.Nostructuralor
biochemicalcausecanbeidentified(1,13).
17. RomeIIIdiagnosticcriteriaforcyclicvomitingsyndromeare:1)stereotypicalepisodesofvomiting
regardingonset(acute)andduration(lessthanoneweek),and2)threeormoreoftheseepisodesinthe
precedingyear,and3)absenceofnauseaandvomitinginbetweenepisodes,and4)criteriafulfilledfor
thelast3monthswithsymptomonsetatleast6monthspriortodiagnosis(1).

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1820.Gastricemptyingratescanbeassessedusingscintigraphyorbreathtesttechnology.Mildlydelayed
gastricemptyingisanonspecificsignwhichmaypartlydependonthepresenceofnauseaduringthetest.
Severelydelayedemptyingsuggestsgastroparesisasacauseofnauseaand/orvomiting.Thereisnoconsensus
onacutofffor"severely"delayedemptyingusingscintigraphy,enoughtoconsideradiagnosisof
gastroparesis,butwesuggestusingthreetimestheupperlimitofalargenormalsampleasthecutoffvalue.
21.Dependingonthepresenceorabsenceofvomiting,likelydiagnosesarenoweitherchronicidiopathic
nauseaorfunctionalvomiting.
22. RomeIIIdiagnosticcriteriaforchronicidiopathicnauseaare:1)bothersomenausea,occurringatleast
severaltimesaweek,and2)notusuallyassociatedwithvomiting,and3)absenceofabnormalitiesat
endoscopyormetabolicdiseasethatexplainsthenausea,and4)criteriafulfilledforthelast3months
withsymptomonsetatleast6monthspriortodiagnosis(1).
23. RomeIIIdiagnosticcriteriaforfunctionalvomitingare:1)onaverageoneormoreepisodesofvomiting
perweek,and2)absenceofcriteriaforaneatingdisorder,rumination,ormajorpsychiatricdisease
accordingtoDSMIV,and3)absenceofselfinducedinducedvomitingandchroniccannabinoiduseand
absenceofabnormalitiesinthecentralnervoussystemormetabolicdiseasestoexplaintherecurrent
vomiting,and4)criteriafulfilledforthelast3monthswithsymptomonsetatleast6monthspriorto
diagnosis(1).
24. Treatmentforfunctionalnauseaand/orvomitingisbasedonantinauseants,prokineticsorlowdose
antidepressants.Dopamine2receptorantagonistssuchasdomperidone,metoclopramideand
chlorpromazinecanbeconsideredfirstlinedrugs.Metoclopramidecaninduceparkinsonismand
irreversibletardivedyskinesia;chlorpromazinecausessomnolence.Tricyclicantidepressantsaswellas
mirtazapinehavenauseaandvomitingsuppressingpropertiesandcanbeconsideredsecondlinedrugs

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2009 The Rome Foundation

(2,16).Incaseofcyclicvomitingsyndrome,antimigrainedrugscanalsobeconsidered(1,12,13).The
ruminationsyndromeispreferentiallytreatedbybehavioraltherapy(diaphragmaticbreathing)(17).
25,26.Thelongtermmanagement,incaseoftherapeuticresponse,hasnotbeenestablishedforthese
disorders.
27. AdditionaltestsmayincludeabdominalCTscan,smallbowelxrayorCTenterography,antroduodenal
manometry,oresophagealpH/impedancetesting.
Psychosocialproblemssuchasanxietyordepressionmayalsopresentwithnauseaorvomiting.Itisimportant
toconsidertheseearlyoninthecourseofextensiveinvestigations,andtoobtainexpertopinionincaseof
refractoriness.AusefultoolistheRomeIIIpsychosocialalarmquestionnaire(seeAppendixA).Therapeutic
trialsusingantidepressantscanbeconsideredwiththeendpointofbenefitbeingsymptomimprovementor
improveddailyfunctioningeveninthepresenceofthesymptoms.

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2009 The Rome Foundation