Nausea%20-and-%20vomiting Diagnosis

• 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 characteristics 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

• 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), urinalysis, standard blood chemistry
• Other tests to be done would depend on the diseases being considered:
  
  • 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

• 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
  • Ultrasound examination

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

• A labyrinthine system-related disorder brought about by chronic repetitive movements, which stimulate afferent neural pathways and lead to activation of the brain stem nuclei, which set off the GI and somatic aspects of vomiting
• Autonomic stimulation gives rise to pallor, salivation and diaphoresis
• Other diseases that affect the labyrinthine system and produce nausea and vomiting are Meniere’s disease, viral labyrinthitis and labyrinthine tumors

Nausea and Vomiting of Pregnancy

• A common condition that affects about ¾ of pregnant women
  
  • 50-80% 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
• 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
• 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
• May lead to significant complications including the following:
  • Rupture of the esophagus
  • Acute tubular necrosis
  • Wernicke’s encephalopathy secondary to Thiamine deficiency
  • Hyperthyroxinemia with low 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, gastroparesis, intestinal obstruction, pancreatitis, achalasia
  • Neurologic diseases: Migraines, CNS tumors,  vestibular lesions, lymphocytic hypophysitis
  • Genitourinary tract diseases: Pyelonephritis, kidney stones, uremia
  • Other conditions: Ovarian torsion, degenerating uterine leiomyoma, hydatidiform mole, diabetic ketoacidosis, drug-related toxicity, eating disorders, psychologic conditions, labyrinthitis, motion sickness, hyperthyroidism, hyperparathyroidism, Addison's disease

Please see Nausea & Vomiting in Pregnancy disease management chart for further information

Risk Factors for PONV

The presence of certain risk factors is predictive of a patient’s likelihood of experiencing PONV and should be used to assess patient's risk and to guide management 

• Patient factors
  • Female gender
  • Young age
  • Nonsmoker
  • History of motion sickness
  • Previous episode of PONV
  • Postoperative opioid use
• Surgical factors
  • Craniotomy
  • Laparoscopy
  • Laparotomy
  • Major breast surgery
  • Otolaryngological procedures
  • Plastic surgery
  • Strabismus surgery
  • Bariatric surgery
  • Gynecological surgery
  • Cholecystectomy
• Anesthetic risk factors 
  • General versus regional anesthesia 
  • Duration of anesthesia    
  • Use of volatile anesthetics and nitrous oxide                        
  • Postoperative opioids

PONV Risk Score

• The Apfel simplified risk score uses 4 risk factors: Female gender, history of PONV and/or motion sickness, nonsmoking status and postoperative opioid use; each risk factor is scored with 1 point 
  • The emesis potential of 0, 1, 2, 3 and 4 risk factors is approximately 10%, 20%, 40%, 60% and 80%, respectively
• Risk categories may be classified as low (0-1 risk factor), medium (2 risk factors) or high (≥3 risk factors)

Approaches to Decrease Baseline PONV Risk 

• Minimize intraoperative and postoperative opioids by using multimodal analgesic regimens
• Preferentially use regional anesthesia over general anesthesia
• Use Propofol for anesthesia induction and maintenance
• Avoid nitrous oxide in surgeries lasting >1 hour and volatile anesthetics
• Use Sugammadex rather than Neostigmine in reversing neuromuscular blockade
• Hydrate patients adequately

Incidence of Chemotherapy-Related Nausea and Vomiting 

• 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 female gender, younger age, previous chemotherapy-related nausea and vomiting, history of alcohol use, motion sickness or morning sickness during pregnancy, presence of anxiety

Effects of Chemotherapy-Related Nausea and Vomiting 

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

Classification of Chemotherapy-Related Nausea and Vomiting

Acute-onset Nausea and Vomiting 

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

Delayed-onset Nausea and Vomiting 

• Arises >24 hours after chemotherapy administration

Anticipatory Nausea and Vomiting 

• A conditioned response which occurs before patients receive their next chemotherapy treatment
• 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

Breakthrough Nausea and Vomiting 

• Nausea and vomiting that arises in spite of preventive treatment and/or needs rescue with antiemetic therapy

Refractory Nausea and Vomiting 

• Symptoms that occur during subsequent chemotherapy sessions when antiemetic prophylaxis and/or rescue has failed during previous treatment sessions

Classification of Chemotherapeutic Agents According to Emetogenic Potential¹ 

• 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

High (Emetic Risk >90%) 

• IV agents: Anthracycline/cyclophosphamide combination, Carboplatin (AUC ≥4), 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, Melphalan (≥0.14 g/m²), Sacituzumab govitecan-hziy, Streptozocin

Moderate (Emetic Risk Between >30-90%) 

• IV agents: Azacitadine, Bendamustine, Busulfan, Carboplatin (AUC <4), Carmustine (≤0.25 g/m²), Clofarabine, Cyclophosphamide (≤1.5 g/m²), Cytarabine (>0.2 g/m²), Dactinomycin, Daunorubicin, Dinutuximab, Doxorubicin (<0.06 g/m²), Epirubicin (≤0.09 g/m²), Idarubicin, Ifosfamide (<2 g/m² per dose), Irinotecan, Lurbinectedin, Melphalan (<0.14 g/m²), Methotrexate (≥0.25 g/m²), Oxaliplatin, Temozolomide, Trabectedin

Oral Antineoplastic Agents with Moderate to High Emetic Risk 

• Azacytidine, Busulfan (≥0.004 g/day), Ceritinib, Cyclophosphamide (≥0.1 g/m²/day), Estramustine, Etoposide, Fedratinib, Mitotane, Niraparib, Olaparib, Procarbazine, Rucaparib, Temozolomide (>0.075 g/m²/day)

Low (Emetic Risk Between 10-30%) 

• IV agents: Cytarabine (0.1-0.2 g/m²), Docetaxel, Etoposide, 5-Fluorouracil, Gemcitabine, Liposomal Doxorubicin, Methotrexate (>0.05-<0.25 g/m²), Mitomycin, Mitoxantrone, Paclitaxel, Pemetrexed, Topotecan

Minimal (Emetic Risk <10%) 

• IV agents: Alemtuzumab, Avelumab, Bevacizumab, Bleomycin, Cetuximab, Cladribine, Cytarabine (<0.1 g/m²), Fludarabine, Ipilimumab, Methotrexate (≤0.05 g/m²), Nivolumab, Pembrolizumab, Pertuzumab, Ramucirumab, Rituximab, Temsirolimus, Trastuzumab, Vinblastine, Vincristine, Vinorelbine

Oral Antineoplastic Agents with Minimal to Low Emetic Risk 

• Abemaciclib, Capecitabine, Chlorambucil, Erlotinib, Everolimus, Fludarabine, Hydroxyurea, Imatinib (≤0.4 g/day), Melphalan, Methotrexate, Neratinib, Regorafenib, Ribociclib, Sunitinib, Thalidomide, Topotecan, Vemurafenib

¹List of chemotherapeutic agents shown above is not exhaustive. Please refer to available guidelines from health authorities for the complete list.

Radiation-Induced Nausea and Vomiting

• 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 doses of radiation and a larger amount of irradiated tissue

Classification of Radiotherapy Emetogenic Potential According to Irradiated Site 

High (Emetic Risk >90%)  

• Total body irradiation

Moderate (Emetic Risk Between 30-90%)   

• Craniospinal irradiation, upper abdomen

Low (Emetic Risk Between 10-30%)   

• Cranium, head and neck, thorax, pelvis

Minimal (Emetic Risk <10%)   

• Breast, extremities