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Conflicts of Interest:

• None

Approach to chronic : A case-based analysis

Gokul Bala, MD Assistant Professor Director of Gastrointestinal Motility Lab Gastroenterology, Hepatology and Nutrition The Ohio State University Wexner Medical Center

Overview Definition

Feeling sick or unpleasant sensation which may or may not lead • Definitions onto vomiting. • Physiology of vomiting Forceful expulsion of gastric contents associated with abdominal Vomiting • Etiology of chronic vomiting muscle contraction. • Clinical history and examination Spasmodic muscular contraction of without any • Diagnostic testing expulsion of gastric contents. • Approach to Chronic vomiting Food brought back in the mouth without abdominal and • Treatment options Regurgitation diaphragmatic muscle contraction. • Case studies Chewing and swallowing of regurgitated food with high abdominal Rumination pressure.

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Physiology of Vomiting Most Common Cases for Chronic Vomiting Cerebral Mechanical gastrointestinal obstruction(small bowel, colon, pylorus, bile duct) cortex Mucosal inflammation(, , duodenum) Peritoneal inflammation(Colitis, cancer) Nausea & Carcinomas(gastric, ovarian, renal, etc) Vomiting Medications(anticholinergics, narcotics, L-dopa, progesterone, Cacb, NSAIDs, Center CTZ GLP analogues) Metabolic(Diabetes, adrenal insufficiency, thyroid disorders, uremia) Nucleus Vestibular (Diabetes, hypothyroidism, postsurgical, idiopathic) Tractus Oropharynx system Solitarius Neurogenic(autonomic, tumor, migraine, seizure, stroke, lactulose intolerance) Psychogenic(eating disorders) Heart Musculoskeletal Gastrointestinal Cannabis/cyclical hyperemesis syndrome system tract Lacy BE, Parkman HP, Camilleri M. Chronic nausea and vomiting: evaluation and treatment. Am J Gastroenterol. 2018 May;113(5):647-659.

Clinical Features: Diagnostic testing: • Vomiting(forceful expulsion and associated with nausea) vs regurgitation(passive and • Abdominal X-ray: Stool burden, gas pattern in obstructive and non- not associated with nausea). obstructive cause. • Insidious onset of nausea in middle aged female- r/o pregnancy. • Medication use: OPIOIDS, NSAIDs, levodopa, anticholinergics. • CT scan: Bowel obstruction. • Bowel pattern and reflux symptoms. • UGI series and SBFT: Gastric and small bowel obstruction. • Type of vomitus: ‒ Regurgitation of undigested food-Achalasia or Zenker’s diverticulum or Rumination. • Upper endoscopy: Mucosal condition of the stomach and gastric outlet ‒ Partially digested food-Gastroparesis or gastric outlet obstruction. obstruction. ‒ Bilious-Small bowel obstruction. • Gastric emptying study: ‒ Feculent-Distal bowel obstruction. - Gastric scintigraphy. • Timing of vomiting: - Wireless transit study. ‒ Early morning: Pregnancy or uremia. -C13 breath testing. ‒ Projectile: Increased intracranial pressure. ‒ Periodic: Cyclical vomiting or cannabis induced hyperemesis. • CNS imaging: in cases of projective vomiting or associated CNS ‒ Postprandial: Gastric outlet obstruction or gastroparesis. symptoms. ‒ During meals: Rumination or . • Specialized gastric motility testing: electrogastrography, antroduodenal • Associated symptoms: colicky abdominal pain, early satiety, associated neurological manometry or endoflip. symptoms.

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Differential diagnosis: Principles of Treatment DDx: Distinguishing Testing Treatment options feature • Treatment is directed towards the cause. Gastroparesis Postprandial Delayed solid Dietary modifications • It would be important to identify triggering factors: symptoms or non- emptying Medications periodic vomiting in Nutritional support - Medications. the absence of Surgical options - drug use anxiety/. obstruction Cyclical vomiting Periodic vomiting Diagnosis of Avoidance of triggers - Menses. syndrome episodes in the exclusion Antiemetics, - bowel pattern. absence of cannabis neuromodulators- use Amitriptyline • Dietary modification and avoidance of triggers are the Cannabis Episodic vomiting Diagnosis of Cessation of cornerstone in the management of chronic vomiting. hyperemesis with cannabis use. exclusion cannabis syndrome • Medications such as prokinetics, anti-emetics and Rumination Effortless Postprandial ESM or Behavioral neuromodulators are often used. syndrome regurgitation antroduodenal therapy(DBT) • In case of profound vomiting with , consider manometry Eating disorder Distorted body image Clinical history Psychiatric care alternative nutrition route. Purging episodes • Watch for micronutrient deficiency.

Pro-kinetics: Anti-emetics: Medications Mechanism Pros Con Medications MOA Pros Cons Metaclopramide D2 Antagonist Improves gastric emptying. Black box warning:>12 weeks Diphenhydramine Antihistamines Useful in mild • Sedative effect. Lowest possible dose (5 mg use of tardive dyskinesia nausea/vomiting. • Anticholinergic S/E. TID before meals). Acute dystonias Hyoscine Anti-cholinergics Cheap and widely available. • Anti-cholinergic side No long‐term study available. Parkinsonism type Useful in mild cases. effects(dry mouth, Efficacy:29‐53%. movements glaucoma,etc). Comparable to Domperidone Associated with QTc interval Phenothiazines/ D1/D2 Antagonist Useful in severe nausea and • EKG changes Domperidone D2 Antagonist Improvement in symptoms Less CNS effects prochlorperazine vomiting. • Psychomotor issues in (54% to 79%). Associated with QTc interval. elderly Drug interaction. Increases Prolactin levels. • Dystonia/Parkinsonism Requires IND for approval. Erythromycin Motilin agonist Useful during acute Tachyphylaxis. Ondansetron 5HT3 antagonists Widely available. • QT prolongation. exacerbation. IV better than Associated with QTc Useful in mild vomiting. • Serotonin syndrome. PO. prolongation. • . Cisapride 5-HT4 agonist Significant improvement in cardiac arrhythmias and Transdermal 5HT3 antagonists Not widely available/cost. • QT prolongation. symptoms. death granisetron Useful in those who cannot • Serotonin syndrome. Requires IND tolerate oral meds. • Constipation. Prucalopride 5-HT4 agonist Improves gastric emptying and and suicidal Aprepitant NK1 receptor Not widely available/cost. • Fatigue. colon transit times. ideations. antagonists Useful in reducing N/V. • Neutropenia. FDA approved for chronic Avoidance in ESRD. Dronabinol Agonist of CB1 and Helpful for N/V when other • Delays gastric constipation. No cardiac toxicity CB therapies have failed. emptying. document. 2

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Neuromodulators: Medications MOA Pros Con Nortriptyline/ TCA Modest improvement in Worsens gastric Amitriptyline N/V and abdominal pain emptying. Anti‐cholinergic side Case studies effects. Constipation. Mirtazapine/B SNRI/ Improves appetite. Suicidal thoughts. uspirone SSRI Improves fundic EKG changes. accommodation. Serotonin syndrome.

Case study 1 Definition: • 42-year-old gentleman with type 2 diabetes(HgbA1c:9.5) on exenatide presenting with recurrent vomiting and nausea for the last 6 months? Gastroparesis is defined as a delay in the What would be the next step? emptying of ingested food in the absence of mechanical obstruction of the stomach or Normal upper endoscopy with moderate food retention in the stomach. duodenum. Bx: negative for H. pylori.

4-hour GES: 43%. What do we do next?

Switch exenatide to insulin+CGM.

Nutrition consult for gastroparesis. Camilleri M, Parkman H, Shafi M, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol 2013;108:18–37.

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Etiology of Gastroparesis Pathophysiology Gastroparesis

Idiopathic Diabetic Post-surgical gastroparesis gastroparesis gastroparesis Cholecystectomy (30-35%) Vagotomy Nissen fundoplication Partial gastrectomy Obesity related surgeries Pancreatectomy

(5-10%) Grover, M et al. Gut. 2019 Dec;68(12):2238-2250.

Clinical Presentation: Diagnostic Testing for Gastroparesis: TABLE 2. Diagnostic Testing for Gastroparesis • Nausea Modality Advantages Disadvantages • Vomiting Gastric scintigraphy Widely available Considered Radiation exposure 4-hour solid phase the “gold standard” for False positives with liquid • Early satiety diagnosis phase only studies • Bloating Wireless motility capsule Avoids radiation exposure Less validated than • Postprandial fullness Smart Pill, given imaging FDA approved for diagnosis scintigraphy Cannot be used in those with • Abdominal pain pacemaker or defibrillator

• Weight loss/weight gain Radiolabeled carbon breath Low cost Lack of standardization test • Constipation and/or diarrhea 13C-labeled octanoic acid or Has primarily been used as a • Wide glycemic fluctuations Sprirulina platensis research tool

Gastroparesis: A Review of Current Diagnosis and Treatment Options. Stein, Benjamin; Everhart, Kelly; Lacy, Brian. Journal of Clinical Gastroenterology. 49(7):550‐558, August 2015.

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Therapeutic options guided by symptom severity Treatment Algorithm for Suspected Gastroparesis Increased meal frequency, I DM, optimize glycemic control. Trial withdrawal of medications known Suspected gastroparesis decreased mea volume. Aim Balance diet with GP symptoms. to impair gastric emptying (e.g., GLP- for low particle size, fat, and Target plasma glucose < 200 mg/dl 1 analogs, opioids). Step 1: Diagnosis: 4 h Gastric emptying by scintigraphy fiber diet.

Step 2: Exclude latrogenic disease Lifestyle Nutritional assessment with correction Consider enteral nutrition if the patient

Dietary: low fat, low fiber diet Modifications of dietary deficiencies. cannot tolerate oral diet Glycemic control among diabetic Mild

Step 3: Pharmacological Rx: Prokinetic Agents Metoclopramide (recommended Domperidone (basline QTc < 470 ms • Prokinetics: metocloprtamide, erythromycin, domperidone duration < 12 wk due to risk of TD). in men / <450 ms in women). • Antimetics: anti-histamine1, receptors; 5-HT3 antagonists Erythromycin (ambulatory use limited by tachyphylaxis). Step 4: Nutritional support: Enternal formula

Pharmocotherapy Symptom Control Anti-emetic agents Anti-nociceptive agents Step 5: Non-pharmacological Rx Pyloric injection of botulinum toxin Venting gastrostomy, feeding jejunostomy Gastric Electrical Stimulator Parental nutrition May benefit patients with diabetic GP and Gastric electrical stimulation intractable nausea/vomiting Pyloroplasty Surgical Options Partial gastrectomy Therapy Pyloroplasty and subtotal/total gastrectomy,

Interventional Severe may benefit patients with post-surgical GP. Consider gastric bypass in obese patients Camilleri, et al. Clinical Guideline: Management of Gastroparesis. Am J Gastroenterol 2013; 108:18–37 Gastroparesis: A Review of Current Diagnosis and Treatment Options. Stein, Benjamin; Everhart, Kelly; Lacy, Brian. Journal of Clinical Gastroenterology. 49(7):550‐558, August 2015.

Case Study 2: Postprandial esophageal manometry • 26-year-old female with prior hx of chronic and anxiety presented with chronic vomiting. 1. Rise in gastric pressure • She complaints of 2. Reflux of gastric - Postprandial regurgitation of food associated with upset contents 3. Rise in esophageal stomach and associated swallowing the food back again. pressure during reflux - Feeling of Charlie-horse in her chest followed by 4. Relaxation of upper regurgitation of food. esophageal sphincter - Upper endoscopy and 4-hour GES were unremarkable. - She was tried on Nortriptyline, pantoprazole and reglan without much benefit.

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ROME IV Criteria for Rumination Syndrome Further Care..

Table 1 Clinical diagnosis of rumination in adults Rome IV criterion • On Physical therapy. Must include all of the following: • Started on buspirone.

1. Persistent or recurrent regurgitation of recently ingested food into the mouth • Daily pantoprazole was stopped and only can take if with subsequent spitting or remastication and swallowing she has symptoms. 2. Regurgitation is not preceded by retching • 4 weeks following therapy: She has noticed an Criteria fulfilled for the last 3 months with symptom onset at least 6 months before improvement in symptoms - decreased frequency to a diagnosis. 1-2 times every other day. Supportive remarks:

• Effortless regurgitation events are usually not preceded by nausea • Regurgitant contains recognizable food that might have a pleasant taste • The process tends to cease when the regurgitated material becomes acidic Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology 2016;150:1380–1392.

Effect of DBT on Rumination syndrome Case Study 3:

16 patients with rumination were studied with manometry before and • 21-year-old female with prior hx of migraines presenting with after a meal. The postprandial assessment comprised three • Episodic vomiting with normalcy in between these episodes. periods: before, during, and after DB augmented with biofeedback • Often periodic, happens in the early morning, several episodes therapy. of vomiting requiring hospitalization.

Diaphragmatic breathing increased • Underwent EGD and 4-hour GES which were unremarkable. EGJ pressure and restored a negative gastroesophageal pressure gradient). • She was tried on PPI, reglan without much benefit.

Halland, M., Parthasarathy, G., Bharucha, A.E. and Katzka, D.A. (2016), Diaphragmatic breathing for rumination syndrome: efficacy and mechanisms of action. Neurogastroenterol. Motil., 28: 384- 391. https://doi.org/10.1111/nmo.12737

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Rome Criteria for Cyclical Vomiting Syndrome Management of cyclic vomiting syndrome

Venkatesan, T, Levinthal, DJ, Tarbell, SE, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Venkatesan, T, Levinthal, DJ, Tarbell, SE, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil. 2019; 31(Suppl. 2):e13604. https://doi.org/10.1111/nmo.13604 Motil. 2019; 31(Suppl. 2):e13604. https://doi.org/10.1111/nmo.13604

Disclosures

. Nothing to disclose

Medical Nutrition Therapy for Nausea and Vomiting: a case based approach

Kristen Roberts, PhD, RDN, LD, CNSC, FASPEN Assistant Professor-Clinical, Medical Dietetics Gastroenterology, Hepatology, and Nutrition The Ohio State University Wexner Medical Center

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Objectives Small intestinal bacterial overgrowth . Discuss evidence-based medical nutrition therapy for Cyclic symptom management in those with nausea and vomiting Migraine vomiting syndrome . Differentiate when oral diet is sufficient to meet nutritional Chronic needs nausea and vomiting Functional Gastroparesis dyspepsia

Eating disorders

Nutritional Problems Associated with N/V Enteral Nutrition . Starvation1 Hydration

. Chronic: significant deterioration in body Parenteral mass (adiposity and lean body mass). Nutrition . Intermediate: Metabolic derangements, Dietary Medical decreased EER, episodic illness leads to Modification obesity. Nutrition . Dehydration and electrolyte abnormalities Therapy . Micronutrient deficiencies FODMAPs . Poor nutritional quality of life Trigger food elimination

1Olsen et al. J Cachexia, Sarcopenia and Muscle. 2020. DOI: 10.1002/jcsm.12630

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General Nutrition Recommendations for N/V Case Study #1: Gastroparesis . Keep patient away from strong food odors; remove lid to food served in 54 F with T2DM on metformin. Ha1c 6.7% down GES – 4hr; 11/3/2018 hospital prior to entering room from 7.1% 6 months prior. Findings: . Provide assistance in food preparation so as to avoid cooking odors C/o worsening nausea, abdominal pain and . At 60 minutes after meal consumption, 87% of initial . Eat foods at room temperature intermittent vomiting. Worsening symptoms in the gastric contents were . Keep patient's mouth clean and perform oral hygiene tasks after each morning. GES confirms gastroparesis. retained within the stomach (normal range, 30-90%). episode of vomiting RDN consult for dietary management of T2DM . At 120 minutes after meal . Offer fluids between meals and GP. consumption, 68% of initial gastric contents were . Patient should sip liquids throughout the day retained within the stomach . Cold beverages may be more easily tolerated (normal range, <60%). . Keep low-fat crackers or dry cereal by the bed to eat before getting out of bed . At 240 minutes after meal consumption, 45% of initial . Relax after meals instead of moving around gastric con-tents were . Sit up for 1 hour after eating retained within the stomach Breakfast Lunch Dinner (normal range, <10 %) . Wear loose-fitting clothes Nutrition Care Manual. AND. Accessed 11/16/2020

Particle Size and Food Consistency GP . Emptying is faster for smaller particles and liquid consistencies. Blood Fiber and Adjust diet Liquid Enteral glucose fat . Liquid foods empty at consistency supplement nutrition 1 control modification 200 kcals/hr . Translation for patient care: . Chew your food well . Trial a liquid meal at the ‘worst point’ in 1Neurogastroenterol Motil; 2006;20:8-18 2Neurograstroenterol Motil; 2009:21;492 your day

1 Camilleri M. Gastroenterology 2006.

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Low-Fiber Diet Modified-Fat Diet . Avoid foods with ≥ 3 grams of fiber per serving . Fats are essential for life--Moderation is key for tolerance. . Avoid meals with >5 grams of fiber . 10-15 grams of fat per meal is a good starting point. FOOD GROUPS FOOD TO AVOID FOODS TO CHOOSE FOOD GROUPS FOOD TO AVOID FOODS TO CHOOSE Grains, cereal, pasta Whole grains, brown rice, White bread, white rice, crackers, refined Grains, cereal, Crackers, chips, fried White bread, white rice, crackers, popcorn, potatoes with the skin, grains, pretzels, refined cereals. pasta breading. refined grains, pretzels, refined high fiber cereals, rye bread, cereals. whole wheat breads, corn Fruits, vegetables Fruits, vegetables or Cooked or canned fruits and bread. and legumes legumes that are fried or vegetables with the skin removed. Fruits, vegetables Skins, nuts and seeds of the Cooked or canned fruits and vegetables cooked with excessive Casseroles. Sweet or white potatoes and legumes plant. Avoid uncooked fruits with the skin removed. Casseroles. oil/butter. without the skin. and vegetables. Avoid corn, Sweet or white potatoes without the skin. onion, lentils, peas and beans. Milk and dairy 2% or whole dairy products If tolerated, skim or 1% dairy Milk and dairy Dairy products that are fortified Dairy should be consumed as tolerated products (milk, yogurt, cheese). products (milk, yogurt, cheese). products with fiber. as this is a naturally fiber-free food. Meats, fish, eggs High-fat beef/pork/lamb. Egg whites, skinless chicken or Meats, fish, eggs Tough cuts of meat, processed Baked, broiled, tender meats/fish/poultry, and poultry Avoid meats with visible fat turkey breast, lean and poultry meats (hot dogs, sausage, tofu, ground meats, smooth peanut butter (white-marbling). pork/beef/lamb/veal, liver, fish, cold-cuts). and any style eggs. shrimp and crab. Table is property of ThriveRx Table is property of ThriveRx

Case Study #2: SIBO Low FODMAP Diet

67 M hx bladder cancer s/p • Efficacy: 50-75% experience RTx. Presents with excessive symptom improvement* flatulence, intermittent nausea • Nutritional Adequacy: concern and abdominal pain. HBT for inadequate intake due to supports SIBO and patient restriction; inconsistent data Nutrient of Restricted Supporting selecting dietary management. Concern Source Literature • Adherence: High rates of RDN consult placed Calcium Dairy Staudacher adherence (75%) generally et al. 2012 reported, but inconsistently Overall CHO Fruits, veg, Bohn et al. assessed grains, dairy 2015 Fiber Fruits, veg, Bohn et al. whole grains 2015 *In IBS Halmos et al. 2014; Eswaren et al. 2016; Schumann et al 2017; de Roest et al. 2013; O’Keeffe et al. 2018

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IBS: Low FODMAP Diet

Elimination . Restriction of all high FODMAP foods for 2-6 weeks for symptom relief Reintroduction . Systematic reintroduction of FODMAP groups to assess tolerance Personalization . New dietary pattern established and followed long- term Gibson & Shepherd, 2010; Whelan et al. 2018 ©2020 Kate Scarlata, RDN www.katescarlata.com

Case Study #3: Cyclic Vomiting Syndrome Case Study #3: Cyclic Vomiting Syndrome . 24 F newly dx with cyclic vomiting . Dehydration related to vomiting syndrome failed pharmacotherapy . Trial sips of oral rehydration solutions: and dietary management. . 1 liter of G2 with ½ teaspoon salt OR pedialyte in 1-2 ounce portions per sitting. . Consult to RDN who documents: . Do NOT recommend full calorie sports drinks. . 92% of UBW . Most patients require 1-2 liters of fluids per day. . Micronutrient deficiencies . Severe loss of subcutaneous fat and muscle. . Prevent with starting a USP, chewable multivitamin daily until healthy body . + skin rash weight restored1 . +micronutrient deficiencies . Monitor common micronutrient deficiencies by assessing biochemical and physical presentation. Laboratory Assessment Baseline . Data suggest that particularly common micronutrient deficiencies include values iron, folate, thiamine, calcium, magnesium, phosphorus, zinc, and vitamins B12, C, D, E, and K. Serum retinol (20-120 mcg/dL) 8 . Start the discussion of enteral nutrition (EN) early Zinc (55-150 ug/dl) 30 CRP (<3 mg/L) 2 Hasler WL Nausea, Vomiting, and Indigestion. Harrison's Principles of Internal Medicine. 2005.

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When are Supplements and EN Necessary? Nausea and Vomiting Severity and EN

Unintentional weight loss of >10% within 3 months Unable to achieve a healthy body Mild disease: rarely needed weight Repeat hospitalizations for symptoms interfering with oral intake Moderate disease: Liquid supplements and rarely EN Nausea and vomiting impacting the quality of life Severe disease: Liquid supplements • Consider severity of symptoms and start and PEJ may be required liquid supplementation or consider small bowel feeding tube trial1 PEJ is associated with lower complication rates and re-intervention rates compared to PEGJ1,2

Koch et al. Gastroenterol Clin N Amer. 2015;39-57 1Fan et al. Gastrointest Endosco. 2002; 2Toussanit et al. Endoscopy, 2012

Steps to Initiation of Enteral Nutrition Referral to RDN  It’s simple!

. Trial nasojejunal (NJ) feeding tube . Consider home EN start . Avoid if risk for refeeding syndrome . Encourage NPO status. . Place PEJ to restore nutritional balance1 . Use reverse progression of nutritional management to regain full nutritional autonomy

1Sarosiek et al. Gastroenterol Clin N Am; 2015

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