1. Nausea and Vomiting

2. Objectives To get a detailed history and associated symptoms To get the DD To recognize and treat typhoid

3. 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?

4. 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

5. 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

6. VOMITINGPATHWAYS Ipecac syrup

7. Common etiologies of nausea and vomiting 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

8. 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

9. 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)

10. Medications that often cause nausea and vomiting 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

11. 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

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

13. 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?

14. 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)

15. Laboratory studies: guided by history and physical Electrolytes, glucose, BUN/creatinine Calcium, albumin, total serum proteins Complete blood count (CBC) Liver Function Tests Pregnancy test Urinalysis Serum lipase  amylase

16. 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

17. Radio-opaque markers still in the stomach 6 hours after meal in a diabetic with nausea

18. ALGORITHMIC APPROACH or marker

19. 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)

20. Drugs with anti- emetic prop- erties and known mechanisms Antihistamines, e.g., meclizine (Antivert R ) –esp. for vestibular disorders Anticholinergics, e.g., scopolamine (Transderm Scop R, Donnatal R ) –esp. for vestibular and GI disorders Dopamine antagonists, e.g.,metoclopramide (Reglan R ) or prochlorperazine (Compazine R ) –esp. for GI disorders Selective serotonin-3 (5HT 3 ) RAs, e.g., odansetron, granisetron, dolasetron –esp. to prevent chemotherapy-induced nausea/vomiting

21. Drugs with anti-emetic properties (continued) Multiple mechanisms of action: Promethazine (Phenergan R )Promethazine (Phenergan R ) –dopamine antagonist –H1 antihistamine –anticholinergic –CNS sedative –prevention of opiate-induced nausea and vomiting Hydroxyzine (Atarax R, Vistaril R )Hydroxyzine (Atarax R, Vistaril R ) –H1 antihistamine –anticholinergic –CNS sedation –prevention of opiate-induced nausea and vomiting

22. Drugs with anti-emetic properties (continued) Uncertain mechanism of action: Trimethobenzamide (Tigan R )Trimethobenzamide (Tigan R ) –blocks apomorphine-induced emesis in dogs –does not block emesis from p.o. CuSO 4 in dogs  probably acts in the chemoreceptor trigger zone (CTZ) of the medulla oblongata Bismuth subsalicylate (Pepto-Bismol R )Bismuth subsalicylate (Pepto-Bismol R )

23. Adjunctive antiemetic agents Dexamethasone (Decadron R )Dexamethasone (Decadron R ) –along with other anti-emetics for prevention of cancer chemotherapy-induced emesis Dronabinol (Marinol R )Dronabinol (Marinol R ) –for prevention of cancer chemotherapy-induced emesis refractory to other agents –[ also for anorexia and weight loss in AIDS]

24. 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.

25. 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