• A detailed history and physical exam are crucial in evaluating patients with nausea and vomiting and in determining the underlying cause of nausea and vomiting

• Determine the duration, frequency and severity of nausea and vomiting
  
  • Nausea and vomiting is considered chronic when it lasts >1 month

• Determine when vomiting occurs during the day (timing) and the characteristic of the vomiting process itself
  
  • Eg projectile vomiting may suggest an increased intracranial pressure (ICP) resulting from an intracranial problem 

• Elicit information about the onset of vomiting ie relation to meals
• Investigate the quantity and quality of the vomitus
  
  • Ask if vomitus consists of undigested, partially digested or bilious material
  • Ask about a possible fecaloid character of the vomitus or a putrid odor which is characteristic of intestinal obstruction

• Ask about associated symptoms as these may assist in localizing the underlying disease process:
  
  • Fever, weight loss
  • CNS symptoms: Headache, focal neurologic deficits, neck stiffness, vertigo
  • Abdominal pain, diarrhea
  • Presence of a similar illness in the patient’s family and/or friends

• Ask about concomitant illnesses
  
  • Patient may be suffering from nausea and vomiting related to treatment ie chemotherapy-related nausea and vomiting

• Search for signs of dehydration or weight loss
  
  • Orthostatic hypotension
  • Postural increase in pulse rate

• Search for findings that may suggest autonomic neuropathy
  
  • Postural decrease in blood pressure (BP) without a concomitant increase in pulse rate

• Conduct a careful abdominal examination
  
  • Ascertain if there is abdominal tenderness, together with its specific location
  • Listen for decreased bowel sounds
  • Palpate for abdominal masses

• Conduct a detailed neurologic and psychiatric exam
  
  • Check for cranial nerve abnormalities, gait problems, funduscopic changes and other relevant information

• The rest of the systemic physical exam may also provide other helpful information with regard to the etiology of nausea and vomiting
  
  • Findings suggestive of autonomic neuropathy may be found
  • Exam may reveal signs of systemic diseases causing nausea and vomiting
  • Evidence of self-induced vomiting may be apparent

• Diagnostic tests are done to aid in determining the underlying cause of nausea and vomiting and to assess the effects of nausea and vomiting on a patient
• Basic tests include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), standard blood chemistry
• Other tests to be done would depend on the diseases being considered, eg:
  
  • Serum drug levels for possible drug toxicities
  • Pregnancy test
  • Thyroid-stimulating hormone (TSH) levels for possible thyrotoxicosis or Addison’s disease
  • Fecal occult blood

Tests of Gastric Motor Function

• Gastric emptying time
  
  • Relatively accurate, easy and noninvasive
  • May reveal presence of gastroparesis

• Electrogastrography (EGG)
  
  • A decrease in or the absence of the expected postprandial increase in the EGG amplitude has been shown to correlate with prolonged gastric emptying time and antral hypomotility

• Antroduodenal manometry
  
  • May be useful in identifying patients with primary or diffuse motor abnormalities
  • A normal study may be useful in ruling out dysmotility and pointing the clinical investigation into another direction

• Imaging tests are usually focused on the abdominal area and are done depending on the etiologies of nausea and vomiting being considered eg mechanical gut obstruction
• Abdominal x-rays, barium studies
• Small bowel enema, small bowel follow-through exam
• Endoscopic investigations
• Computed tomography (CT) scan of the abdomen

Gastroparesis

• Functional disorders of gut motility give rise to nausea because of inability to clear food and secretions
• Gastroparesis may be part of the following conditions:
  
  • Postvagotomy and postgastric drainage surgery patients
  • Pancreatic malignancy
  • Systemic diseases eg diabetes mellitus (DM), systemic lupus erythematous (SLE) and other connective tissue diseases
  • Idiopathic gastroparesis

• The dysfunction is documented by tests of gastric motor function
  
  • Clinicians should be careful not to quickly assume that confirmed gastroparesis is the primary cause in itself of a patient’s symptoms

Other Conditions Associated with Disorders of Gut Motility

• Other conditions that may result in gut dysmotility are chronic intestinal pseudo-obstruction, Roux-en-Y syndrome, functional dyspepsia

Nausea and Vomiting of Pregnancy

• A common condition that affects about ¾ of pregnant women
  
  • 25% of women may have nausea only

• May occur at all times of the day (not just in the morning)
• Symptoms usually begin 4-7 weeks after the last menstrual period and cease by 12 weeks in most women
  
  • Symptoms that begin after the 9th week of gestation are not typical of nausea and vomiting of pregnancy

• Increased incidence is noted in the following situations:
  
  • Previous pregnancy with nausea and vomiting
  • Nulliparity
  • Younger age of the mother
  • Obesity
  • Family history of hyperemesis gravidarum
  • Increased placental mass (eg molar or multiple pregnancies)
  • History of motion sickness or migraine

• Nausea and vomiting of pregnancy is self-limiting in most patients and it usually resolves without complications as pregnancy proceeds

Hyperemesis Gravidarum

• Represents the most severe form of nausea and vomiting of pregnancy
• Most common reason for hospital admission during the 1st part of pregnancy
• A diagnosis of exclusion based on typical signs and symptoms and the absence of other causes that may explain the clinical presentation
• Criteria for diagnosis are as follows:
  
  • Persistent vomiting not related to other causes
  • Evidence of weight loss, usually ≥5% of prepregnancy weight
  • Evidence of starvation ie ketonuria
  • Abnormalities of electrolyte levels, thyroid and liver may also be present

• Hyperemesis gravidarum may lead to significant complications, eg the following:
  
  • Rupture of the esophagus
  • Wernicke’s encephalopathy secondary to Thiamine deficiency
  • Hyperthyroxinemia with low thyroid-stimulating (TSH) levels
  • Depression

Differential Diagnoses for Nausea and Vomiting of Pregnancy

• Nausea and vomiting that begins after the 9th week of gestation is not characteristic of nausea and vomiting of pregnancy and should be investigated further
• Headache, fever, abdominal pain or tenderness are not typical in nausea and vomiting of pregnancy
• Diseases that may present as nausea and vomiting in pregnant patients include the following:
  
  • Pregnancy-related conditions: Preeclampsia, acute fatty liver of pregnancy
  • GI diseases: Gastroenteritis, biliary tract disease, hepatitis, peptic ulcer disease, appendicitis, etc
  • Neurologic diseases: Migraines, CNS tumors
  • Genitourinary tract diseases: Pyelonephritis, kidney stones, uremia
  • Other conditions: Hydatidiform mole, diabetic ketoacidosis, drug-related toxicity, eating disorders, labyrinthitis, motion sickness

• Patient Factors
  • Female gender
  • Nonsmoker
  • Postoperative opioid use
  • Previous episode of PONV
  • History of motion sickness
• Surgical Factors
  •  Craniotomy
  • Laparoscopy
  • Laparotomy
  • Major breast surgery
  • Otolaryngological procedures
  • Plastic surgery
  • Strabismus surgery

• >4 factors present
• Emesis potential >80%

• 3-4 risk factors present
• Emesis potential 40-80%

• 1-2 risk factors present
• Emesis potential 20-40%

• PONV is seen more often in patients who have undergone general anesthesia compared to those who have received regional anesthesia
  • Propofol use decreases the risk of PONV
• Dehydration, pain and anxiety can increase the incidence of PONV

• About 70-80% of cancer patients receiving chemotherapy experience nausea and vomiting
• The incidence and severity of nausea and vomiting following chemotherapy are influenced by the following factors:
  • Chemotherapeutic agents used
  • Dosage of chemotherapeutic agents
  • Schedule and route of administration
  • Radiation therapy target
  • Individual patient propensities eg gender, age, previous chemotherapy, history of alcohol use

• Poor compliance or withdrawal from chemotherapy
• Malnutrition, anorexia, metabolic imbalances
• Decreased level of functioning
• Esophageal tears

• Occurs within a few minutes to several hours after chemotherapy administration
• Usually peaks after 5-6 hours and resolves within 24 hours

• Arises >24 hours after chemotherapy administration

• A conditioned response which occurs before patients receive their next chemotherapy treatment
•  Anticipatory nausea and vomiting usually occurs when patients have had a previous unpleasant experience with chemotherapy
• Younger patients are more prone to anticipatory nausea and vomiting because they have poorer emesis control and they usually receive more aggressive chemotherapy regimens

• Nausea and Vomiting that arises in spite of preventive treatment

• Symptoms that occur during subsequent chemotherapy sessions when antiemetic prophylaxis has failed during previous treatment sessions

• The type of antiemetic treatment regimen that a patient needs depends on the emetogenic potential of the chemotherapeutic agents that a patient is receiving
  • The risk of nausea and vomiting for chemotherapeutic agents with high emetic risk lasts for about 3 days and with moderate emetic risk 2 days after the final dose of chemotherapy

• IV agents: Carmustine (>0.25 g/m²), Cisplatin, Cyclophosphamide (>1.5 g/m²), Dacarbazine, Doxorubicin (≥0.06 g/m²), Epirubicin (>0.09 g/m²), Ifosfamide (≥2 g/m² per dose), Mechlorethamine, Streptozocin

• IV agents: Bendamustine, Busulfan, Carboplatin, Carmustine (≤0.25 g/m²), Cyclophosphamide (≤1.5 g/m²), Cytarabine (>0.2 g/m²), Daunorubicin, Doxorubicin (<0.06 g/m²), Epirubicin (<0.09 g/m²), Idarubicin, Ifosfamide (<2 g/m² per dose), Irinotecan, Melphalan, Methotrexate (≥0.25 g/m²), Oxaliplatin, Temozolomide

• Busulfan (≥0.004 g/day), Cyclophosphamide (≥0.1 g/m²/day), Etoposide, Procarbazine, Temozolomide (>0.075 g/m²/day)

• IV agents: Cytarabine (0.1-0.2 g/m²), Docetaxel, Etoposide, Fluorouracil, Gemcitabine, Liposomal Doxorubicin, Methotrexate (<0.25-0.05 g/m²), Mitomycin, Mitoxantrone, Paclitaxel, Pemetrexed, Topotecan

• IV agents: Bevacizumab, Bleomycin, Cladribine, Cytarabine (<0.1 g/m²), Fludarabine, Ipilimumab, Methotrexate (≤0.05 g/m²), Peginterferon, Pertuzumab, Rituximab, Trastuzumab, Vincristine, Vinblastine, Vinorelbine

• Capecitabine, Chlorambucil, Erlotinib, Everolimus, Fludarabine, Hydroxyurea, Imatinib, Melphalan, Methotrexate, Regorafenib, Sunitinib, Thalidomide, Topotecan, Vemurafenib

• Patients receiving whole body or upper abdominal radiation therapy have the greatest chance of developing nausea and vomiting after the procedure
  • The rapidly dividing cells of the intestinal tract are especially sensitive to radiation
• The potential for postradiation nausea and vomiting is increased by a higher total and daily fractional dose of radiation and a larger amount of irradiated tissue