Nausea and Vomiting

DefinitionTop

Nausea is an unpleasant, painless, subjective sensation of a need to vomit. Vomiting (emesis) is a rapid expulsion of stomach contents through the mouth due to forceful contractions of the abdominal and chest wall muscles. Regurgitation is an effortless passage of gastric contents into the mouth with no mechanisms characteristic of vomiting. Rumination refers to repeated chewing and swallowing of food contents that move back from the stomach to the mouth as a result of a volitional increase in intra-abdominal pressure during or several minutes after a meal.

Causes and PathogenesisTop

Nausea and vomiting are caused by physiologic or pathologic stimuli that activate the vomiting center in the medulla oblongata or the chemoreceptor zone in the fourth ventricle. Nausea is often accompanied by other autonomic symptoms, particularly those related to parasympathetic activation, such as pallor, sweating, salivation, hypotension, and bradycardia (in the vasovagal mechanism).

1. Causes:

1) Drugs (including chemotherapeutic agents [particularly cisplatin and dacarbazine], digoxin, opioids) and toxins (eg, alcohols).

2) Diseases affecting the central nervous system (CNS): Migraine, malignant and other CNS tumors, pseudotumor cerebri, meningitis, encephalitis, cerebrovascular accidents, intracranial hemorrhage.

3) Psychiatric disorders: Depression, anorexia nervosa, bulimia, psychogenic vomiting.

4) Inner ear disorders: Neoplasm, inflammation, Meniere disease, motion sickness.

5) Disorders of the gastrointestinal (GI) tract and peritoneum: Acute infectious gastroenteritis, food poisoning, food hypersensitivity, small intestinal obstruction, superior mesenteric artery syndrome, gastroparesis, irritable bowel syndrome (IBS), peptic ulcer disease (PUD), appendicitis, inflammatory bowel disease (IBD), acute colonic distention, peritonitis.

6) Biliary tract disorders: Cholecystitis, biliary colic.

7) Liver disorders: Hepatitis, cirrhosis, liver failure.

8) Pancreatic disorders: Acute pancreatitis, malignancy.

9) Endocrine disorders: Diabetic ketoacidosis, adrenal crisis, thyroid storm, hyperparathyroidism, hypoparathyroidism.

10) Urinary tract disorders: Uremia, renal colic, pyelonephritis.

11) Other conditions: Myocardial infarction, heart failure, hypotension, superior vena cava syndrome, hypervitaminosis A or D, chronic starvation, acute intermittent porphyria, postoperative nausea and vomiting, radiotherapy.

12) Physiologic causes: Pregnancy; certain olfactory, gustatory, and visual stimuli.

2. Classification of vomiting based on duration:

1) Acute vomiting (1-2 days): Usually caused by infection, drugs, exogenous (alcohol, mushrooms) or endogenous (uremia, diabetic ketoacidosis) toxins.

2) Persistent vomiting (>7 days): A manifestation of a chronic disease, occasionally including psychiatric disorders.

3. Complications of vomiting: Dehydration, electrolyte disturbances (hypokalemia, hypochloremia), metabolic alkalosis, aspiration, aspiration pneumonia, rupture of the esophageal wall (Boerhaave syndrome), linear mucosal tears at the gastroesophageal junction (Mallory-Weiss syndrome), malnutrition.

DiagnosisTop

Establish the duration of vomiting, interval between a meal and the onset of vomiting, characteristics of the vomitus, and other associated symptoms (Table 1). Diagnostic studies depend on the suspected cause; if the initial assessment and diagnostic studies do not suggest an underlying cause and symptoms persist or worsen, try a course of antiemetic and prokinetic treatment and consider further diagnostic workup (eg, excluding metabolic issues [diabetes, thyroid or adrenal disease], electrolyte [calcium, sodium] imbalance) and, depending on the clinical evolution, endoscopy of the upper GI tract or evaluation of its motor function. Psychological assessment may also be considered.

TreatmentTop

Symptomatic Treatment

The provided trade (brand) names are valid for Canada.

1. Management of nausea/vomiting:

1) Correct dehydration and electrolyte disturbances.

2) Establish and treat the underlying condition.

3) Start symptomatic treatment when necessary.

2. The choice of drugs depends on the established or most likely cause of nausea and vomiting as well as the mechanism of action of the drug. Patients may not be able to tolerate oral medications when nauseated, and therefore alternative routes of administration (IM, IV, subcutaneous, rectal, or transdermal) may be more appropriate. Patients with moderate to severe nausea and vomiting may require combination antiemetic therapy; in such cases consider medications with different mechanisms of action to achieve adequate symptomatic relief. Begin with a low dose of antiemetic drugs in elderly patients to reduce the risk of adverse effects.

1) Antihistamines:

a) Dimenhydrinate (eg, Gravol): For prevention of vomiting, use 50 to 100 mg orally 30 to 60 minutes before the occurrence of a triggering factor (short periods of travel, anesthesia, a poorly tolerated drug); the dose may be repeated if necessary. For treatment of vomiting, use 50 to 100 mg orally, rectally, IM, or IV every 4 to 6 hours up to a maximum of 400 mg/d in adults. Although not available in this form in Canada, in treatment of motion sickness dimenhydrinate is also used as a chewing gum (3 portions 20 mg each chewed one by one every 30 min, up to 7 portions/d; start prophylaxis ~1 h before travel).

b) Diphenhydramine (eg, Benadryl): Diphenhydramine 25 to 50 mg taken orally 30 to 60 minutes in advance of travel can be considered as an alternative to dimenhydrinate for the management of nausea secondary to motion sickness. It could be given IM or IV (usually as an adjunct in treatment of allergic reactions).

c) Doxylamine succinate/pyridoxine (eg, Diclectin): Doxylamine succinate/pyridoxine is commonly prescribed for the management of mild nausea and vomiting in early pregnancy. The recommended dose is 2 tablets taken orally at bedtime plus 1 tablet in the morning and midafternoon. This is a delayed-release formulation and therefore optimal efficacy is achieved when the medication is taken on a routine basis.

2) Anticholinergics: Scopolamine: For prevention of motion sickness, scopolamine 1.5 mg as a transdermal patch may be applied ≥4 hours prior to travel. Each scopolamine patch can be worn for a maximum of 72 hours, and therefore it has the advantage of a longer duration of action compared with dimenhydrinate and diphenhydramine. A scopolamine transdermal patch may also be applied the night before or on the day of a planned surgery to mitigate postoperative nausea and vomiting.

3) Phenothiazines:

a) Chlorpromazine: For the management of nausea and vomiting, use 12.5 to 25 mg orally every 4 to 6 hours as needed or 25 to 50 mg IV or IM every 3 to 4 hours as needed.

b) Thiethylperazine (not available in Canada) 6.5 mg orally or rectally 1 to 4 times a day. It may also be administered IV, IM, or subcutaneously.

c) Levomepromazine (not available in Canada) usually 25 mg orally tid to qid or subcutaneously ≤25 mg/d.

d) Prochlorperazine: For the management of migraine-related nausea, motion sickness, or drug-induced nausea, prochlorperazine 5 to 10 mg orally qid as needed may be used. The agent may also be administered IV or IM at a dose of 5 to 10 mg every 3 to 4 hours as needed up to a maximum daily dose of 40 mg.

e) Promethazine (antihistamine and antipsychotic agent): In patients with motion sickness use 25 mg administered orally 30 to 60 minutes before travel. The dose may be repeated in 8 to 12 hours if required. For nausea and vomiting unrelated to motion sickness, promethazine 12.5 to 25 mg orally every 4 to 6 hours as needed may be used.

4) Haloperidol is most useful in the treatment of vomiting caused by metabolic disturbances and adverse effects of drugs (including opioids). It can also be used in the setting of postoperative nausea and vomiting. The recommended dose is 0.5 to 2 mg every 12 hours as needed administered orally, IM, IV, or subcutaneously. Haloperidol prolongs the QTc interval and should be used with caution in patients taking other medications that also cause QTc prolongation.

5) Prokinetics:

a) Metoclopramide is typically used in the setting of nausea and vomiting related to gastroparesis, migraines, or drug-induced nausea and vomiting (including chemotherapy and opioids). Metoclopramide is commonly administered at a dose of 10 mg orally, IV, or IM tid to qid. The dose may be increased to 20 mg in rare instances where 10 mg in inadequate (do not exceed 0.5 mg/kg/d). Metoclopramide should only be prescribed for short-term use (max, 5 days) to minimize the risk of adverse effects such as extrapyramidal symptoms.

b) Domperidone: For symptoms related to gastroparesis, domperidone can be used at a dose of 5 to 10 mg orally tid. Avoid domperidone in patients with a prolonged QTc interval.

c) Itopride (not available in Canada) 25 to 50 mg orally tid is used to treat functional dyspepsia, also in patients receiving palliative care.

d) Other prokinetics are sometimes used in palliative care, for instance, erythromycin administered orally or IV, usually ~3 mg/kg tid up to a maximum of 4 g/d.

6) Serotonin 5-HT3 receptor antagonists:

a) Ondansetron: For the prevention and treatment of postoperative nausea and vomiting, ondansetron 4 to 8 mg administered IV or orally every 8 hours as needed may be used. Ondansetron is also indicated for the prevention and treatment of nausea and vomiting related to emetogenic chemotherapy or radiotherapy.

b) Palonosetron and granisetron are mainly used in the prophylaxis and treatment of nausea and vomiting caused by chemotherapy or radiotherapy. Both medications may be administered orally or IV.

7) IV glucocorticoids: Dexamethasone and methylprednisolone are used mainly in patients with elevated intracranial pressure or to reduce edema of a tumor causing intestinal obstruction. Glucocorticoids may be used as add-on antiemetic agents in the postoperative setting when other agents are ineffective, although both dexamethasone and methylprednisolone can increase the risk of hyperglycemia and postoperative infection. Dexamethasone is the most commonly prescribed glucocorticoid for the management of chemotherapy-induced nausea and vomiting and it is particularly effective in the prevention of delayed nausea and vomiting.

8) Neurokinin 1 (NK1) receptor antagonists: Aprepitant, netupitant, and fosaprepitant are used as add-on agents in the prevention of both acute and delayed nausea or vomiting caused by highly emetogenic chemotherapy. Aprepitant and netupitant are oral NK1 receptor antagonists, while fosaprepitant is available as an IV formulation.

TablesTop