Chapter 72: Nausea and Vomiting

Nausea and vomiting accompany a variety of illnesses. Symptoms may be due to primary GI disorders such as bowel obstruction or gastroenteritis. However, symptoms may also represent pathology of the central nervous system (increased intracranial pressure, tumor), psychiatric conditions (bulimia nervosa, anxiety), endocrine or metabolic abnormalities (diabetic ketoacidosis, hyponatremia), or iatrogenic causes (medications, toxins). Also, nausea and vomiting may be the result of severe pain, myocardial infarction, sepsis, or other systemic illnesses. A comprehensive history and physical examination, as well as the use of various diagnostic modalities, are needed to determine the cause and its complications.

In the United States, the most common cause of acute nausea and vomiting is viral gastroenteritis. Other important considerations are side effects from medication and, in young women, pregnancy.¹

Multiple neurons in the medulla oblongata are activated in a sequential fashion to induce vomiting. The vomiting center is the chemoreceptor trigger zone, located in the area postrema of the fourth ventricle. Chemoreceptors in this area are outside the blood–brain barrier and are stimulated by circulating medications and toxins, including dopaminergic antagonists (levodopa, bromocriptine), nicotine, digoxin, and opiate analgesics. Another important peripheral pathway for emesis is mediated through vagal afferents. Vagal activation is triggered by direct gastric mucosal irritants (such as nonsteroidal inflammatory agents) or increased luminal distention (gastric outlet obstruction, gastroparesis). Vagus activation stimulates neurons in the area postrema and nucleus tractus solitarius. These areas are rich in serotonin receptors and are a major site of action of antiemetic drugs, such as granisetron and odansetron.² Similar receptors are found throughout the gastrointestinal tract, as well as the cortex and limbic system, vestibular system, heart, and genitalia. The anatomic locations and receptor-mediated triggering factors in emesis are shown in Table 72–1.

Efferent pathways in the vagal, phrenic, and spinal nerves control the physiologic event of vomiting through coordinated muscle activity. Three stages of vomiting have been described: nausea, retching, and actual vomiting. Nausea is the unpleasant feeling that precedes vomiting. During nausea, there may be autonomic symptoms of hypersalivation, repetitive swallowing, and tachycardia. The exact physiologic pathway is not well understood but may be related to afferent abdominal vagal stimulation. During retching, there is gastric relaxation and repetitive simultaneous contraction of the diaphragm and abdominal muscles that allow for the development of a pressure gradient. Vomiting is the retrograde expulsion of gastric contents, and it is a response to changes in intra-abdominal and intrathoracic pressure generated by the contraction of the abdominal and respiratory muscles.³

The differential diagnosis of nausea and vomiting is exhaustive, as pathology of almost every organ system may lead to nausea and vomiting (Table 72–2). A thorough history and physical examination will help guide the diagnostic approach to the patient presenting with nausea and vomiting.

HISTORY

Identify the onset and duration of the symptoms. The evaluation for acute symptoms is quite different from the evaluation of a chronic problem. If the problem is chronic, asking the patient the results of any tests that have already been performed will help narrow the diagnostic possibilities. Chronic symptoms are defined as those symptoms present for >1 month.

Frequency of the episodes is helpful to gauge the severity of illness. Ask how many times vomiting occurred and the interval between episodes. Timing of the episodes, such as increased number of episodes in the morning, may suggest pregnancy or a central nervous system cause, whereas postprandial vomiting suggests gastroparesis or gastric outlet obstruction.

The content of the vomitus may be helpful to determine whether an obstruction is present and its location. Esophageal disorders produce vomitus with undigested food particles. Bile is often associated with a small bowel obstruction, whereas vomitus composed of food particles and devoid of bile often represents a gastric outlet obstruction. Large bowel obstruction often is composed of feculent material and has a foul odor.

Because of the number of organ systems that are the potential cause of pathology, it is important to ask the patient about associated symptoms. The presence or absence of abdominal pain is a focal starting point. If pain is present, elicit its location and quality. Pain preceding the nausea and vomiting is most particularly associated with an obstructive process.² Fever or, possibly, diarrhea suggests gastroenteritis. Ask about sick contacts or ingestion of food suspicious for a foodborne illness. A history of recent weight loss is associated with a malignancy or psychiatric component. Any central nervous system sign, such as headache, visual changes, vertigo, or neurologic deficits, may suggest a central cause for the nausea and vomiting. Obtain a thorough past medical history. Always ask about prior abdominal surgeries because the patient is at risk for bowel obstruction from adhesions. Review the patient's medication list to identify a medication with a common side effect of nausea and vomiting, such as nonsteroidal anti-inflammatory agents, cancer chemotherapeutic agents, various antibiotics, various antihypertensives and antiarrhythmics, and oral contraceptives. Other medications at toxic levels are known to cause nausea and vomiting. Examples include acetaminophen, salicylates, and digoxin.

PHYSICAL EXAMINATION

Assess vital signs for hypotension and tachycardia. Observe skin turgor, mucous membrane hydration, and capillary refill to assess for dehydration. In children, the most useful predictors of significant dehydration (>5% loss of body weight) are abnormal capillary refill, abnormal skin turgor, absent tears, and abnormal respiratory pattern.⁴ The abdominal examination is particularly important to assess for an emergent problem, as well as to help narrow the differential diagnosis to a possible gastrointestinal cause.⁵ Inspect, auscultate, and palpate the abdomen. (For further discussion of abdominal evaluation, see chapter 71, Acute Abdominal Pain.)

Investigate any other important examination findings particular to various organ systems, as findings may provide valuable information regarding the cause of the nausea and vomiting (Table 72–3).

LABORATORY

After completing a proper history and physical examination, obtain serum and urine studies to help determine the cause of the symptoms and to evaluate for complications. Most often, a CBC as well as electrolyte testing is part of the basic evaluation. Obtain a pregnancy test in a woman in childbearing years who has not had a hysterectomy. Obtain liver function tests and a serum lipase in patients with upper abdominal pain or jaundice. Check thyroid function tests if thyrotoxicosis is suspected. Obtain specific drug levels for possible ingestions or suspected toxicity in patients taking acetaminophen, salicylates, digoxin, or theophylline. Also, obtain ethanol levels and narcotic drug screening tests in patients with suspected intoxication or withdrawal states. A urinalysis may be beneficial in several ways. The specific gravity may be used to help determine the degree of dehydration. The presence of ketones may suggest not only dehydration, but also diabetic ketoacidosis or hyperemesis gravidarum in a pregnant patient. The presence of bilirubinuria may suggest a biliary tract obstruction. Nitrites, leukocyte-esterase, bacteria, and white blood cells may indicate an upper or lower urinary tract infection. Also, red blood cells, in the proper clinical picture, may support a diagnosis of kidney stones. Lastly, an erythrocyte sedimentation rate may be evaluated to search for an inflammatory cause.

IMAGING

Flat and upright abdominal films are useful screening tests for bowel obstruction. Plain radiography is less sensitive than CT scanning, but the radiation dose is <1 mSv, about one tenth the radiation dose of an abdominal CT scan.^6,7 Abdominal CT with PO and IV contrast can diagnose a mechanical obstruction, identify the cause, and visualize visceral and vascular pathology. A noncontrast abdominopelvic CT or renal US are tests of choice if kidney stones are suspected. If the history or physical examination suggest a CNS cause, a CT of the head or MRI of the brain is ordered to evaluate for an intracranial mass or lesion. Other radiographic tests are available but are often ordered for a patient who requires admission to the hospital, or upon consultation with a gastroenterologist. These tests include esophagogastroduodenoscopy, upper GI radiography with barium contrast, small bowel follow-through, enteroclysis, gastric emptying scintigraphy, antroduodenal manometry, and cutaneous electrogastrography.

ANCILLARY TESTING

An abdominal US is helpful to evaluate a patient with associated right upper quadrant or epigastric pain to diagnose possible gallbladder, hepatic, or pancreatic pathology. Hepatobiliary iminodiacetic acid scans are sometimes performed in suspected cases of biliary dysfunction and/or cholecystitis. Suspected testicular torsion would also be diagnosed by US. Obtain an electrocardiogram for suspected myocardial infarction. Measure intraocular eye pressures if glaucoma is a part of the differential diagnosis.

Stabilize the patient, paying attention to the ABCs: airway, breathing, and circulation. After stabilization, provide symptomatic relief (Table 72–4). Definitive management will often require disease-specific treatment. If no clear cause is noted at the outset, an H₁ histaminergic such as promethazine or a serotonin receptor antagonist such as ondansetron may be helpful for initial treatment, pending further workup.⁸ However, promethazine is more sedating, with the potential side effect of vascular damage during IV administration. Recent studies have also compared the efficacy of selective serotonin receptor antagonist (tropisetron, ondansetron) versus other agents in treating nausea and vomiting for undifferentiated ED patients. Serotonin receptor blockers significantly lower the rates of vomiting when compared with metoclopramide.⁹ Both ondansetron and prochlorperazine are equally effective.¹⁰ Patients given either drug must be monitored for akathisia that may develop up to 48 hours after administration. Based on overall safety and efficacy, serotonin receptor antagonists such as ondansetron should be used as first-line therapy for undifferentiated nausea and vomiting in all age groups. For patients in the ED who have no response to ondansetron in 30 minutes, administration of another drug with activity at a different receptor site is more likely to be successful than repeat dosing of ondansetron.¹¹

PATHOPHYSIOLOGY

Cyclic vomiting syndrome (CVS) usually presents in childhood with more than half of cases resolving by the teenage years. The condition is rare in adults. Predisposing mitochondrial DNA mutations (15519T and 3010A) have been found in many patients with CVS. It is more common in females than males. In adults, there is a higher incidence of opiate and tobacco use.

The cause is unknown, but it is thought to be related to dysregulation of the neuroendocrine system. Accompanying symptoms of lethargy, anorexia, pallor, abdominal pain, or autonomic symptoms such as sweating and salivation implicate abnormal vagal tone. It has also been suggested that CVS is a functional disorder associated with migraines. Patients commonly have a history of migraines and report a prodrome with nausea and photophobia prior to attacks.¹²

DIAGNOSIS

CVS is characterized by recurrent nausea and vomiting separated by symptom-free periods. Since there is no specific confirmatory test for CVS, diagnosis is clinical and involves excluding other common causes of symptoms. The diagnosis is often delayed for years after multiple ED visits and hospitalizations. Patients may be given the label of  "drug-seeking."  Co-morbid conditions may also include anxiety, depression, and irritable bowel.

CVS has been well described with four phases: 1) Asymptomatic periods of several or many months; 2) Prodrome phase lasting minutes to hours, with lethargy, photophobia, anorexia, sweating, or salivation; 3) Hyperemesis phase, which usually starts in the morning with severe nausea and vomiting, lasting for days to a week with the mean duration being 3.4 days; 4) Finally, recovery phase with improvement in symptoms and energy levels.

The ROME III diagnosis criteria include recurrent episodes of intractable vomiting that is self-limiting, lasting less than 7 days, and without an organic cause. Typically, patients have more than two episodes of vomiting in the past year with symptom-free intervals in between.

ED TREATMENT

Management in the ED is symptomatic, with antiemetics (ondansetron), sedatives (lorazepam), analgesics, and intravenous fluids. For prophylaxis, patients can try to avoid  triggers such as sleep deprivation, diet, and physical or emotional stress. Amitriptyline is the standard for medical prophylaxis and has shown response rates as high as 86%. Other therapies include migraine prophylaxis drugs such as sumatriptan, propranolol, and topiramate. Mitochondrial-targeted therapies such as L-carnitine, coenzyme Q-10, and riboflavin have shown excellent efficacy in combination with amitriptyline and alone.¹³

Britt Long and Alex Koyfman

Gastroparesis is delayed gastric emptying in the absence of an obstructing lesion. This condition, which is typically chronic, is associated with decreased quality of life and increased healthcare utilization, though it is not typically associated with significant mortality.^14–16 The most common cause is ‘idiopathic’ but other causes include diabetes, bariatric and gastric surgery, viral illness, gastroesophageal reflux disease, and non-ulcer dyspepsia.^14–17 Connective tissue or neurologic disease, and even pregnancy, can also be associated with gastroparesis. The incidence appears to be increasing, especially in diabetics.^17–19 Symptoms of gastroparesis typically include early satiety, bloating, postprandial nausea, gastroesophageal reflux, vomiting, and abdominal pain.^14–16 If severe and chronic, patients may develop weight loss, electrolyte abnormalities, and nutritional or vitamin deficiencies. 

Physical examination may reveal a succussion splash, which indicates excessive gastric fluid from delayed emptying or mechanical outlet obstruction.^14–16,20 Significant abdominal tenderness and peritoneal findings should be absent.^14–16,20 Initial investigations include serum electrolytes, liver function studies, serum lipase, and pregnancy test. If concern for mechanical obstruction is present, image with abdominal/pelvic CT. Ultrasonography has been used to diagnose gastroparesis and determine effectiveness of treatment.²¹ Outpatient diagnostics include endoscopy, scintigraphy, electrogastrography, or assessment with the wireless motility capsule.^14–16

Management includes volume resuscitation with electrolyte repletion. Several medications may be used for symptomatic treatment. Prokinetic agents include metoclopramide (dopamine antagonist, 5-20 mg) and erythromycin (motilin receptor agonist, 40-250 mg). Both agents may decrease symptoms and increase gastric emptying. Metoclopramide can decrease nausea, provide analgesia, and act as a prokinetic and is a first line agent. Erythromycin may demonstrate tachyphylaxis and should be a second line medication. Other medications include domperidone (a peripherally selective dopamine D2 receptor antagonist - approved in Canada but as of this writing, not in the U.S.), diphenhydramine, prochlorperazine, and ondansetron. Opioids can treat pain; however, they may result in delayed gastric emptying and are not recommended for first line therapy.^14–16 Haloperidol can treat symptoms of nausea, vomiting, and pain. Haloperidol may be administered IV or IM. One study demonstrated a significant decrease in ED and hospital length of stay, hospital admission, and opioid administration, with no adverse events.²¹ A randomized controlled trial reported haloperidol 5 mg IV significantly reduces pain and nausea.²² Patients whose symptoms improve are appropriate for discharge and follow up with a primary care provider or gastroenterologist for further management.

Acknowledgments: The authors gratefully acknowledge the contributions of Annie T. Sadosty and Jennifer J. Hess, the authors of this subject in the previous edition.