Nausea and Vomiting

1. Nausea and Vomiting Mark Feldman, MD

2. Case Report • A 29 year old woman G1/P0/Ab0 complains of severe, recurrent vomiting, worse in the morning but sometimes in the later part of the day, and failure to gain weight. She is in her 13th week of pregnancy. Her past medical history is negative except for obsessive-compulsive disorder. • What is her diagnosis?

3. Terminology • Nausea: from the Latin naus ( a ship); a very unpleasant sensation that one may soon vomit • Retching: muscular activity of the abdomen and thorax, often voluntary, leading to forced inspiration against a closed mouth and glottis without oral discharge of gastric contents (“dry heaves”) • Vomiting: involuntary contractions of the abdominal, thoracic and GI (smooth) muscles leading to forceful expulsion of stomach contents from the mouth

4. Terminology, cont’d • Regurgitation: effortless return of esophageal or gastric contents into the mouth unassociated with nausea or involuntary muscle contractions. • Rumination: food that is regurgitated in the postprandial period, re-chewed and then re-swallowed

5. VOMITING PATHWAYS Ipecac syrup

6. Inter-subject variability in emesis threshold in humans • 18 healthy volunteers received the same dose of the opiate/dopamine agonist, apomorphine • Apo dose adjusted for weight (0.03 mg/kg s.q.) • Responses among volunteers were heterogeneous: • 16 reported nausea within 6±2 minutes after injection • 14 developed vomiting 8±2 minutes after injection; the other 2 who reported nausea did not vomit • 2 neither reported nausea nor experienced vomiting Cannon,Best,Batson,and Feldman. Behavior Research & Therapy 21:669-73,1983

7. GI tract disorders toxins, infections, obstruction, inflammation, motility disorders Non-GI infections liver, CNS, renal, pneumonia, others Pregnancy Visceral inflammation pancreas, GB, peritoneum Myocardial ischemia or infarction Other CNS disorders migraine, neoplasm, bleed Vestibular disorders Metabolic/endocrine DKA, uremia, adrenal insufficiency, hyper- or hypothyroidism, hyper- or hypoparathyroidism Alcohol intoxication Psychogenic Radiation exposure Medications Common etiologies of nausea and vomiting

8. Gastroduodenal6 PUD (2), FD, DG, GOO,food poisoning Intestinal diseases8 SBO(2), LBO, pseudo-obstruction, gastroenteritis(2), diverticulitis (2) Pancreatitis 6 Biliary disease 5 cholecystitis (3), cholangitis (2) Hepatic disease 5 hepatitis (3), liver masses, ischemia vs. hepatitis Nausea/vomiting as component of CC on teaching service at PHD (75 cases) GI DISEASES (n= 30 )

9. Metabolic11 DKA(6), hypergylcemia, hypo- glycemia, hypercalcemia, hypo-natremia (3) Toxic 5 alcohol, CO, digoxin, lithium, ethylene glycol Miscellaneous4 Malaria, pneumonia, bulimia, diabetic foot ulcer with osteo CNS disease 13 CVA/TIA (4), meningitis (4),seizure (2),primary tumor, brain metastases, toxo/HIV Renal causes 8 uremia (4), UTI ± stones (2), acute renal failure, renal infarct Cardiac 4 cocaine-induced (2), USA, afib Nausea/vomiting as component of CC on teaching service at PHD (75 cases) OTHERS (n=45)

10. Clues to psychogenic vomiting • Usually female and often young • May deny or minimize nausea • Rarely occurs in public or in front of others • Co-existent eating disorder, laxative abuse, diuretic abuse common • Psychological disturbances common • Complications of vomiting may be present

11. Surreptitious vomiting: when to suspect it • Unexplained weight loss • Co-existent eating disorder or other psychological condition • Co-existent laxative and/or diuretic abuse • Electrolyte and/or acid-base disturbances consistent with vomiting, including hypo- kalemic nephropathy • Emetic complications (with denial of vomiting)

12. Cancer chemotherapy e.g. cisplatin Analgesics e.g. opiates, NSAIDs Anti-arrythmics e.g., digoxin, quinidine Antibiotics e.g., erythromycin Oral contraceptives Metformin Anti-parkinsonians e.g., bromcryptine, L-DOPA Anti-convulsants e.g., phenytoin, carbamazepine Anti-hypertensives Theophylline Anesthetic agents Medications that often cause nausea and vomiting

13. Less commonly recognized causes of nausea and vomiting • Rapid weight loss/ body casts (SMA syndrome) • Infectious esophagitis • esp. if immunocompromised • Opiate withdrawal • Herbal preparations • Pregnancy • nausea of early pregnancy • hyperemesis gravidarum • AFLP/ HELLP syndrome

14. Complications of Vomiting • Nutritional • adults: weight loss; kids: failure to gain • Cutaneous (petechia, purpura) • Orophayngeal (dental, sore throat) • Esophagitis/ esophageal hematoma • GE Junctional: M-W tears; rupture (Boorhaave’s) • Metabolic: electrolyte, acid-base, water • Renal: prerenal azotemia; ATN; hypokalemic nephropathy

15. Post-emetic purpura (“mask phenomenom) Cutis, 1986

16. Mallory-Weiss tear with clot

17. Two tears: one at 7 o’clock opposite other tear at 1 o’clock

18. Esophageal hematoma secondary to forceful emesis Lumen mass Digestive Diseases and Sciences 26: 1019, 1981

19. Electrolyte and acid-base disorders due to vomiting Metabolic alkalosis retention of HCO3- + volume-contraction Hypokalemia renal K+ losses + GI K+ loss +  oral K+intake Hypochloremia gastric chloride losses Hyponatremia free water retention due to volume contraction Typical SMA-6 Pearl: Patients with uremia or Addison’s disease may have normal or even high serum K+ despite vomiting

20. Nausea and Vomiting: Key Historical Questions • How long? • Relationship to meals? • Contents of vomitus? • Associated symptoms • pain in chest or abdomen, fever, myalgias, diarrhea, vertigo, dizziness, headache, focal neurological symptoms, jaundice, weight loss • Diabetes? • When was last menstrual period?

21. Nausea and Vomiting: Key Physical Findings • Vital signs • BP and pulse tilt test • Cardiopulmonary exam • Abdominal exam • Rectal exam • Neurological exam including funduscopic exam (papilledema)

22. Laboratory studies: guided by history and physical • Electrolytes, glucose, BUN/creatinine • Calcium, albumin, total serum proteins • CBC • LFTs • Pregnancy test • Urinalysis • Serum lipase  amylase

23. Radiology studies: guided by history and physical • Plain abdominal films • Abdominal sono or CT if pain is key feature • Head CT or MRI if severe headache, papill-edema, marked hypertension, altered mental status, or focal neurological findings • EGD or upper GI to separate GOO or high duodenal obstruction from gastroparesis • Radiopaque marker emptying studies or radionuclide scintigraphy, esp. if diabetic

24. Chronic vomiting due to gastroparesis associated with a gastric bezoar

25. Test meal: liquid, digestible solid and indigestible solid

26. Radiopaque markers still in the stomach 6 hours after meal in a diabetic with nausea

27. Markers in stomach 24 hours after ingestion in patient with pseudo-obstruction and small cell lung cancer

29. ALGORITHMIC APPROACH or marker

30. Treatment of nausea and vomiting 1. Treat complications regardless of cause e.g., replace salt, water, potassium losses 2. Identify and treat underlying cause, whenever possible 3. Provide temporary symptomatic relief of the symptoms 4. Use preventive measures when vomiting is likely to occur (e.g., cancer chemotherapy, parenteral opiate administration)

31. Drugs with anti- emetic prop-erties and known mechanisms • Antihistamines, e.g., meclizine (AntivertR) • esp. for vestibular disorders • Anticholinergics, e.g., scopolamine (Transderm ScopR, DonnatalR) • esp. for vestibular and GI disorders • Dopamine antagonists, e.g.,metoclopramide (ReglanR) or prochlorperazine (CompazineR) • esp. for GI disorders • Selective serotonin-3 (5HT3) RAs, e.g., odansetron, granisetron, dolasetron • esp. to prevent chemotherapy-induced nausea/vomiting

32. Drugs with anti-emetic properties (continued) Multiple mechanisms of action: • Promethazine (PhenerganR) • dopamine antagonist • H1 antihistamine • anticholinergic • CNS sedative • prevention of opiate-induced nausea and vomiting • Hydroxyzine (AtaraxR, VistarilR) • H1 antihistamine • anticholinergic • CNS sedation • prevention of opiate-induced nausea and vomiting

33. Drugs with anti-emetic properties (continued) Uncertain mechanism of action: • Trimethobenzamide (TiganR) • blocks apomorphine-induced emesis in dogs • does not block emesis from p.o. CuSO4 in dogs  probably acts in the chemoreceptor trigger zone (CTZ) of the medulla oblongata • Bismuth subsalicylate (Pepto-BismolR)

34. Adjunctive antiemetic agents • Dexamethasone (DecadronR) • along with other anti-emetics for prevention of cancer chemotherapy-induced emesis • Dronabinol (MarinolR) • for prevention of cancer chemotherapy-induced emesis refractory to other agents • [ also for anorexia and weight loss in AIDS]

35. Summary • Nausea and vomiting are features of many GI and non-GI diseases and disorders. • Regardless of its cause, treatment of nausea and vomiting should initially focus on replacing volume and electrolyte deficits. Later on, nutritional deficits must be addressed. • Regardless of its cause, nausea and vomiting can cause several life-threatening GI and non-GI complications. • Elucidation of the cause is often possible, and treatment of the underlying cause will usually be successful. • Effective symptomatic therapies for nausea and vomiting are available when the cause is unclear or when the treatment of the underlying cause takes time to work.

36. Follow up on Case Report • The patient was diagnosed with hyperemesis gravidarum. • Her TSH was undetectable, her free T4 and serum T3 were markedly elevated. • Her symptoms resolved in a few weeks, without recurrence. Goodwin et al. Transient hyperthyroidism and hyperemesis gravidarum. Am J Obstet Gynecol 167: 648, 1992 and J. Clin Endocrin Metab 75: 1333, 1992