CYCLIC VOMITING SYNDROME. C. Prakash Gyawali, MD Professor of Medicine Washington University in St. Louis

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1 CYCLIC VOMITING SYNDROME C. Prakash Gyawali, MD Professor of Medicine Washington University in St. Louis

2 Case 26 year old male Symptoms began at age 19 yr 5-6 day episodes of recurrent, severe vomiting with stereotypical course every 3-6 months Frequent hospitalizations with attacks because of dehydration Asymptomatic between episodes Multiple endoscopies and abdominal imaging studies

3 Definition and Clinical Features

4 Adapted from: Rome III criteria, 2006 Cyclic Vomiting Syndrome Recurrent stereotypical periods of acute nausea and vomiting (at least 3 episodes in past year) Symptom-free intervals lasting weeks to months No structural or metabolic explanation for the symptoms Personal history or family history of migraines is supportive of diagnosis

5 Adapted from: Rome III criteria, 2006 Functional Vomiting One or more episodes of vomiting a week No evidence of eating disorder, rumination or major psychiatric disease Absence of self induced vomiting chronic cannabinoid use CNS abnormalities metabolic syndromes Chronic: symptom onset at least 6 months before diagnosis, criteria fulfilled for past 3 months

6 CVS in an Adult GI Practice <1% of out-patient referrals % prevalence All age groups, ethnicities Prakash C & Clouse RE Am J Gastroenterol 1999; Pareek N, Am J Gastroenterol 2007

7 Delay in Diagnosis of CVS <12 years at onset >12 years at onset Before 1995 Since Years 8 8 Years Prakash C, Staiano A, Rothbaum RJ, Clouse RE Am J Gastroenterol 2001

8 Outcome of ER Visits Venketasan T, BMC Emergency Medicine 2010;10:4

9 Phases of Adult CVS Episode Prodrome Inter-episode period Recovery Age at onset 35 ±4 yr Episode duration 6 ± 1 days Inter-episode time 3.1 ± 0.5 months Prakash C & Clouse RE Am J Gastroenterol 1999

10 Associated Clinical Features of CVS Prodrome 30% Precipitants ~50% Alleviants <50% Associated symptoms >70% Nausea Lethargy Anorexia Epigastric pain Headache Infections Menses Pregnancy Large meals Stress Sleep Dark room Anxiety Abdominal pain Photophobia Phonophobia Social withdrawal Headache Prakash C & Clouse RE AJG 1999; Pareek N AJG 2007

11 Other Features of CVS in Adults Clinical characteristic Extensive invasive testing At least one hospitalization Esophageal damage from vomiting Surgical exploration with intervention Prevalence All subjects All subjects 59% 18% Prakash C & Clouse RE Am J Gastroenterol 1999

12 Associated Conditions CVS General Population Migraine 11-40% 9-20% IBS 67% 10-20% Headache 52% unknown Motion sickness 46% unknown Seizure disorder 5.6% 0.5-1% Prakash C & Clouse RE Am J Gastroenterol 1999; Pareek N, Am J Gastroenterol 2007

13 Migraine diathesis Family history of migraine CVS Abdominal migraine Migraine headache 40-82% 65% 62% Prevalence % % 5-20% Vomiting 100% 30-70% 40-70% Abdominal pain 5-80% 100% 10-55% Headache 35-60% 30-50% 100% Matrilineal inheritance Abnormal adrenergic tone Pareek N, Am J Gastroenterol 2007

14 Mechanisms

15 Mechanisms Predispositions Triggers Mitochondrial dysfunction Defective cellular energy production Vomiting response during periods of heightened cellular energy demand Sympathetic autonomic imbalance Abnormal gastric motor response Stimulation of arousal mechanisms CRF release, HPA axis activation Episode of cyclic vomiting syndrome prodrome, vasomotor symptoms, nausea, vomiting, exhaustion

16 Investigation

17 Exclusion of Organic Disease Complete blood count Complete metabolic profile Pancreatic enzymes Urine analysis Pregnancy test Cross-sectional imaging (abdomen, brain) Contrast studies Endoscopy EEG leukocytosis erosive esophagitis

18 Autonomic Dysfunction Exaggerated cardiovascular responses and heart rate variability to postural change (To 1999) Venkatesan et al, Neurogastroenterol Motil 2010;22:1303-e339

19 Gastric Emptying in CVS GET may fluctuate depending on phase of illness rapid during remission, variable during episodes narcotics marijuana diabetes Hejazi RA et al, Neurogastroenterol Motil 2010;22:1298

20 Management

21 Management Goals Fleisher DR et al, BMC Medicine 2005;3:20

22 Abortive Management: Prodrome Lifestyle Changes/Relaxation Techniques Decrease stress (dark, quiet room) Hot bath or hot shower Antimigraine therapies 5-HT 1D agonist (sumatriptan, zolmitriptan, frovatriptan) Antiemetics 5-HT 3 antagonists (ondansetron, granisetron) Antihistamines (diphenhydramine) Phenothiazines (promethazine, prochlorperazine) Anxiolytics Benzodiazepines (lorazepam) Other - High carbohydrate liquids, ibuprofen Abell TL et al, NGM 2008;20:

23 Abortive Management: Emetic Phase Class Example Supportive Dark, quiet surroundings Hydration IV fluids D NS, 1.5 x maintenance Antiemetics 5HT3 antagonists Ondansetron Phenothiazines Promethazine, prochlorperazine Antihistamines Diphenhydramine D 2 antagonists Metoclopramide, domperidone Anxiolytics Benzodiazepines Lorazepam Analgesics NSAIDs Ketolorac parenteral Opioids Hydromorphone IV/PCA, fentanyl Antimigraine 5HT 1B/1D agonist Sumatriptan parenteral Acid suppression Proton pump inhibitors Omeprazole, esomeprazole Abell TL et al, NGM 2008;20:

24 Response of Vomiting Syndromes to Low-Dose TCAs CVS Functional vomiting 80 p=0.02 between groups 60 Subjects (%) % reported improvement in CVS symptoms with TCA therapy - Hejazi R, McCallum R, et al, JCG Complete remission Partial response No improvement Prakash C & Clouse RE 1999

25 Characteristics of Non-Responders Hejazi et al, APT 2010;31:

26 Newer Antiepileptic Drugs for Cyclic Vomiting Syndrome Clouse RE, Sayuk G, Prakash C. Clin Gastroenterol Hepatol 2007

27 Abortive & Maintenance Treatments Abortive treatments Ondansetron (Zofran) Lorazepam (Ativan) Sumatriptan (Imitrex) Promethazine (Phenergan) Diphenhydramine (Benadryl) Erythromycin Narcotic analgesics Maintenance treatments Tricyclic antidepressants Propranolol (Inderal) Cyproheptadine (Periactin) Antiepileptics Topiramate Valproate Phenobarbital

28 Experimental Therapies Mitochondrial Stabilization L-Carnitine 330 mg, 2-3 pills 2-3 times a day Co-enzyme Q10, upto 10 mg/kg/day Autonomic dysfunction α receptor antagonist: Phentolamine, dextromedetomidine Antiemetic NK1 receptor antagonist: aprepitant (Emend) Granisetron patch (Sancuso) Abell TL et al, Neurogastroenterol Motil 2008;20:

29 anxiety level hemodynamic reactivity sedatives anxiolytic* β-blocker clonidine Prodrome 30% Precipitants ~50% Alleviants <50% Associated symptoms >70% Sumatriptan Other triptans Sedatives Analgesics Treat if possible Sleep Dark room Analgesics for pain Sedatives for anxiety Antiemetics IV fluids with dextrose *sertraline, venlafaxine, paroxetine Prakash C & Clouse RE AJG 1999; Pareek N AJG 2007

30 Provide Support Information & Simplify Measures for Acute Treatment carries the diagnosis of cyclic vomiting syndrome. CVSA-USA/Canada symptoms typically respond to intravenous prompt treatment can avoid hospitalization avoid imaging and other investigation

31 Summary CVS occurs in adults, and onset can be at any age Rest, quiet environment, social stability over the diagnosis are important (including simple measures to expedite emergency medical care) Standard antiemetics and anti-migraine treatments can be helpful in breaking episodes; scheduled benzodiazepines are administered early Careful use of tricyclic antidepressants is the most successful prophylaxis

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