N d V itiNausea and VomitingLin Chang, M.D.

Center for Neurobiology of StressDivision of Digestive DiseasesDivision of Digestive Diseases

David Geffen School of Medicine at UCLA

Diagnosis – Functional Gastroduodenal Disorders

N

Gastroduodenal Disorders

Nausea VomitingForceful oral

l i f

Queasiness or sick sensation; expulsion of

gastric contents;

sick sensation; a feeling of the need to vomit

usually preceded by retchingg

Functional Gastroduodenal Disorders• Functional dyspepsia

• Belching disorders

• Nausea and vomiting disorders

• Rumination syndrome in adults

Functional Dyspepsia

Epigastric pain syndrome (EPS):

Postprandial distress syndrome (PDS): mealsyndrome (EPS): syndrome (PDS): meal-

related FD

Postprandial heaviness or

Early Satiation

Epigastricburning

Epigastric pain fullnessSatiationburningpain

Prevalence of GI symptoms in Functional Dyspepsia PatientsFunctional Dyspepsia Patients

100%

80%

90%

100%

s)

60%

70%

80%

f pat

ient

s

40%

50%

60%

nce

(% o

f

Absent ormildRelevant or

20%

30%

Prev

ale severe

N=700

0%

10%

Fullness Bloating Pain Early Nausea Belching Weight Epigastric Vomiting

N=700

Fullness Bloating Pain Earlysatiety

Nausea Belching Weightloss

Epigastricburning

Vomiting

Tack et al., 2005

Reported Associations of PathophysiologicMechanisms and Symptoms in FDMechanisms and Symptoms in FD

Mechanism Associated SymptomDelayed gastric emptying Postprandial fullness, nausea,

vomitingH iti it t t i E i t i i b l hi i htHypersensitivity to gastric distention

Epigastric pain, belching, weight loss

Impaired accommodation Early satiety, weight losspa ed acco odat o a y sat ety, e g t oss

H. pylori infection Epigastric pain

Duodenal lipid hypersensitivity NauseaDuodenal lipid hypersensitivity Nausea

Duodenal acid hypersensitivity Nausea

U d h i t tilit Bl ti b fUnsuppressed phasic contractility Bloating, absence of nausea

Atypical nonerosive reflux disease Epigastric painyp p g p

Tack J . Gastroenterology 2004; ;127:1239–1255

Guidelines for GE scan• Stop medications which can affect gastric

empyting/motility at least 2 days before the test:empyting/motility at least 2 days before the test:– Prokinetics– OpioidsOpioids– Anticholinergics

• Perform in menstruating women during 1st 10 days of g g ycycle

• Fasting 6 hours prior to test• Diabetics:

– Fasting glucose

Dietary Recommendations for Functional Dyspepsia: What’s the Evidence?y p p

• Efficacy of dietary interventions has not been carefully studied in functional dyspepsiastudied in functional dyspepsia

• Smaller meals may better toleratedP ti t d l f ll– Patients develop fullnessand other symptoms withsmaller volumes of anutrient drink orwater vs controls

• Avoid high-fat meals– Ingestion of fat or intraduodenal lipid infusion leads toIngestion of fat or intraduodenal lipid infusion leads to

more symptoms in patients vs controls

Feinle-Bisset C and Horowitz M. Neurogastroenterol Motil 2006; 18:608

Functional DyspepsiaAcid SuppressionAcid Suppression

• H2RA• H2RA– 11 trials, significant heterogeneity

Unable to determine efficacy– Unable to determine efficacy• PPI

– 8 trials– PPI superior to placebo

• Symptom RR 0.86 (95% C.I. 0.78-0.95)

Talley. Gastroenterology 2005;129:1756-1780

Functional DyspepsiaH Pylori TreatmentH. Pylori Treatment

• 13 trials in 3180 subjects with functional• 13 trials in 3180 subjects with functional dyspepsia

• Treatment superior to placebo– Symptom RR 0.91 (95% C.I. 0.87-0.96)Symptom RR 0.91 (95% C.I. 0.87 0.96)– NNT 17 (95% C.I. 11-33)

Talley NJ Gastroenterology. 2005;129:1756-1780.

Metoclopramide for Functional Dyspepsia

• Dopaminergic antagonist and presynaptic 5HT4 agonist resulting in an increased in ACh release; 5HT3 antagonistincreased in ACh release; 5HT3 antagonist

• Increases LES tone, gastric tone and intragastric pressure and antroduodenal coordination and acceleration of gastric emptyingg y g

• Poor quality, older data suggest effects on gastric emptying1

• No placebo-controlled trials in FD– Less effective than cisapride2

• Can prolong QT interval and increase prolactin• CNS side effects in up to 20%

– Anxiety, drowsiness, depression– Extrapyramidal side effectsExtrapyramidal side effects– Tardive dyskinesia

1Perkel MS et al. Dig Dis Sci 1979; 24:6622Fumagalli I and Hammer B. Scand J Gastroenterol 1994; 29:33

Metoclopramide and Tardive Dyskinesia (TD)Tardive Dyskinesia (TD)

• No prospective dataRi k f TD f t l id i lik l t b 1% h• Risk of TD from metoclopramide use is likely to be

Domperidone for Functional Dyspepsia• 9 double-blind studies (30-60 mg/day)

– Peripheral dopaminergic D2 antagonist

– Improvement in global assessment without clearImprovement in global assessment without clear effects on gastric emptying

Increases serum prolactin levels– Increases serum prolactin levels

• Breast tenderness and galactorrhea in

Prokinetics in Gastroparesis• Metoclopramide is effective for the short-term

t t t f t l ktreatment for up to several weeks– Long-term efficacy not proven

– Black box warning for tardive dyskinesia

D id i ff ti• Domperidone is effective• Erythromycin is most effective if IV (3mg/kg)y y ( g g)

– Some efficacy with oral preparation

Park and Camilleri. Am J Gastroenterol 2006;101:1129–1139

Functional Gastroduodenal Disorders• Functional dyspepsia• Belching disorders• Nausea and vomiting disorders• Nausea and vomiting disorders

– Chronic idiopathic nausea– Functional vomiting– Cyclic vomiting syndrome

• Rumination syndrome in adults

Nausea and Vomiting Disorders

Cyclic Vomiting Syndrome: Diagnostic Criteria*y g y g

• Stereotypical episodes of vomiting regarding onset (acute) and duration (less than oneonset (acute) and duration (less than one week)

• Three or more discrete episodes in the prior yeary

• Absence of nausea and vomiting between i depisodes

*Criteria fulfilled for the last 3 months with symptom onset at y pleast 6 months prior to diagnosis

Tack J et al. Gastroenterology. 2006; 130:1466

Cyclic Vomiting Syndrome: Diagnostic Criteria*Diagnostic Criteria

VomitingVomiting

QuiescentQuiescentperiods

12 months

• Stereotypical episodes of vomiting regarding onset (acute) and duration (< week)

12 months

and duration ( week)• Three or more discrete episodes in the prior year• Absence of nausea and vomiting between episodes• Absence of nausea and vomiting between episodes* Criteria fulfilled for the last 3 months with symptom onset at least 6 months

prior to diagnosis

Tack J et al. Gastroenterology. 2006; 130:1466

Overall Treatment Approach for CVS• Preventive care and medications in between

tt kattacks

• Acute and supportive interventions duringAcute and supportive interventions during attacks

E l i t ti– Early intervention

– IV fluids, electrolytes, antiemetics, analgesics for pain

Li BUK et al. J of Pediatric Gastroenterology and Nutrition 47:379–393

Summary• Nausea and vomiting are common symptoms of

functional gastroduodenal and motility disordersfunctional gastroduodenal and motility disorders

• Vomiting is associated with delayed gastric emptying in FD

• Prokinetics antiemetics and alternativeProkinetics, antiemetics, and alternative treatments can be effective in FD and gastroparesisg p

• Cyclical vomiting syndrome should be treated with preventive and acute care measurespreventive and acute care measures