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Treatment of Nausea and Vomiting


General principles

  • Most cases of nausea and vomiting are self-limiting, resolve spontaneously, and require only symptomatic therapy.
  • Antiemetic therapy is indicated in patients with electrolyte disturbances secondary to vomiting, severe anorexia or weight loss, or progression of disease either owing to refusal of continued therapy or poor nutritional status.

Nonpharmacologic management

  • For patients with simple complaints, perhaps related to food or beverage consumption, avoidance or moderation of dietary intake may be preferable.
  • Nonpharmacologic interventions are classified as behavioral interventions and include relaxation, biofeedback, self-hypnosis, cognitive distraction, guided imagery, and systematic desensitization.
  • Psychogenic vomiting may benefit from psychological interventions.

Pharmacologic management

  • Antiemetic drugs (over-the-counter and prescription) are most often recommended to treat nausea and vomiting. Provided that a patient can and will adhere to oral dosing, a suitable and effective agent can often be selected; however, for certain other patients, oral medications may be inappropriate because of their inability to retain any appreciable oral ingestion. In these patients, the rectal or injectable route of administration might be preferred.
  • Information concerning commonly available antiemetic preparations is compiled in Table Presentation of Nausea and Vomiting.
  • For most conditions, a single-agent antiemetic is preferred; however, for those patients not responding to such therapy and those receiving highly emetogenic chemotherapy, multiple-agent regimens are usually required.
  • The treatment of simple nausea and vomiting usually requires minimal therapy. Both over-the-counter and prescription drugs useful in the treatment of simple nausea and vomiting are usually effective in small, infrequently administered doses.
  • The management of complex nausea and vomiting may require aggressive drug therapy, possibly with more than one antiemetic agent.

Drug class information

Antacids

  • Single or combination over-the-counter antacid products, especially those containing magnesium hydroxide, aluminum hydroxide, and/or calcium carbonate, may provide sufficient relief from simple nausea or vomiting, primarily through gastric acid neutralization.
TABLE. Presentation of Nausea and Vomiting
General
Depending on severity of symptoms, patients may present in mild to severe distress
Symptoms
Simple: Self-limiting, resolves spontaneously and requires only symptomatic therapy
Complex: Not relieved after administration of antiemetics; progressive deterioration of patient secondary to fluid-electrolyte imbalances; usually associated with noxious agents or psychogenic events
Signs
Simple: Patient complaint of queasiness or discomfort
Complex: Weight loss; fever; abdominal pain
Laboratory tests
Simple: None
Complex: Serum electrolyte concentrations; upper/lower Gl evaluation
Other information
Fluid input and output
Medication history
Recent history of behavioral or visual changes, headache, pain, or stress
Family history positive for psychogenic vomiting
  • Common antacid dosage regimens for the relief of nausea and vomiting include one or more small doses of single- or multiple-agent products.

Antihistamines, Anticholinergics

  • Histamine2 antagonists (cimetidine, famotidine, nizatidine, ranitidine) may be used in low doses to manage simple nausea and vomiting associated with heartburn.
  • Antiemetic drugs from the antihistaminic-anticholinergic category may be appropriate in the treatment of simple symptomology.
  • Adverse reactions that may be apparent with the use of the antihistaminic-anticholinergic agents primarily include drowsiness or confusion, blurred vision, dry mouth, urinary retention, and possibly tachycardia, particularly in elderly patients.

Phenothiazines

  • Phenothiazines are most useful in patients with simple nausea and vomiting or in those receiving mildly emetogenic doses of chemotherapy.
  • Rectal administration is most preferred when parenteral administration is impractical or oral medications cannot be retained and are therefore ineffective.
  • In many patients, low doses of phenothiazine drugs may not be effective, while larger doses may produce unacceptable risks.
  • Problems associated with these drugs include troublesome and potentially dangerous side effects, including extrapyramidal reactions, hypersensitivity reactions with possible liver dysfunction, marrow aplasia, and excessive sedation.

Corticosteroids

  • Corticosteroids have been used successfully in the management of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting with few problems.
  • Reported adverse effects included mood changes ranging from anxiety to euphoria as well as headache, a metallic taste in the mouth, abdominal discomfort, and hyperglycemia

Metoclopramide

  • Metoclopramide increases lower esophageal sphincter tone, aids gastric emptying, and accelerates transit through the small bowel, possibly through the release of acetylcholine.
  • Because the adverse reactions to metoclopramide include extrapyramidal effects, intravenous diphenhydramine, 25 to 50 mg, should be administered prophylactically or provided on-call for its anticipated need.

Cannabinoids

  • When compared with conventional antiemetics, oral nabilone and oral dronabinol were slightly more effective than active comparators in patients receiving moderately emetogenic chemotherapy regimens.
  • The efficacy of cannabinoids as compared to SSRIs for chemotherapy-induced nausea and vomiting has not been studied. They should be considered for the treatment of refractory nausea and vomiting in patients receiving chemotherapy.
  • Adverse reactions include euphoria, drowsiness, sedation, somnolence, dysphoria, depression, hallucinations, and paranoia.

Substance P/Neurokinin 1 Receptor Antagonists

  • Substance P is a peptide neurotransmitter in the neurokinin family whose preferred receptor is the NK1 receptor. Substance P is believed to be the primary mediator of the delayed phase of chemotherapy-induced nausea and vomiting and one of two mediators of the acute phase of chemotherapy-induced nausea and vomiting.
  • Aprepitant is the first approved member of this class of drugs and is indicated as part of a multiple drug regimen for prophylaxis of nausea and vomiting associated with high-dose cisplatin-based chemotherapy.
  • Numerous potential drug interactions are possible; clinically significant drug interactions with oral contraceptives, warfarin and oral dexamethasone have been described.

Selective Serotonin Receptor Inhibitors (Ondansetron, Granisetron, Dolasetron, and Palonosetron)

SSRIs act by blocking presynaptic serotonin receptors on sensory vagal fibers in the gut wall.

Chemotherapy-induced nausea and vomiting

The emetogenic potential of the chemotherapeutic agent or regimen is the primary factor to consider when selecting an antiemetic for prophylaxis of chemotherapy-induced nausea and vomiting.

  • Patients receiving level 2 regimens can receive dexamethasone 8 to 20 mg intravenous or PO as a prophylactic agent. Prochlorperazine 10 mg intravenous or PO is also an option for adult patients.
  • Adult and pediatric patients receiving level 3 through 5 regimens should receive a corticosteroid in combination with a SSRI.
  • Ondansetron can be administered intravenously 30 minutes prior to chemotherapy. The least effective intravenous dose should be used, with a range of 8 to 32 mg. Oral therapy is preferred; 8 to 24 mg should be given 30 minutes prior to chemotherapy.
  • In adults and children, at least 2 years of age, granisetron should be infused intravenous in a dose of 10 mcg/kg for 5 minutes, beginning within 30 minutes before the initiation of chemotherapy, only on the day(s) chemotherapy is given. Oral doses of 1 to 2 mg may be used in adults
  • Dolasetron may be administered to adults as a single dose of 1.8 mg/kg, or as a fixed dose of 100 mg intravenously for 30 seconds, or infused (diluted) for 15 minutes. For children 2 to 16 years of age, dolasetron may be given 1.8 mg/kg up to 100 mg.
  • Aprepitant, a substance P/NK1 receptor antagonist given in combination with an SSRI and a corticosteroid (125 mg PO day 1, 80 mg PO days 2 and 3) has been shown to effectively control acute and delayed nausea and vomiting associated with high dose cisplatin-based chemotherapy.
  • Palonestron 0.25 mg intravenous for 30 seconds, 30 minutes prior to chemotherapy is another SSRI option for prophylaxis of chemotherapy-induced nausea and vomiting.
  • Adult patients who experience nausea and vomiting despite prophylaxis should receive prochlorperazine, lorazepam or a corticosteroid as treatment for breakthrough symptoms. Chlorpromazine, lorazepam or corticosteroids are recommended for pediatric patients. SSRIs are not superior to conventional antiemetics in the treatment of breakthrough nausea or vomiting.
  • Dexamethasone with metoclopramide or a SSRI is recommended for the prevention of delayed emesis in adults.

Benzodiazepines

  • Benzodiazepines (particularly lorazepam) represent the best of the therapeutic alternatives in the treatment of anticipatory nausea and vomiting. Dosage regimens include one dose the night before chemotherapy and multiple doses after each treatment with cytotoxic chemotherapy.

Postoperative nausea and vomiting

  • A variety of pharmacologic approaches are available and may be prescribed as single or combination therapy for prophylaxis of postoperative nausea and vomiting. See Table 26-5 for doses of specific agents.
  • With or without antiemetic therapy, nonpharmacologic methods (including assisting patients with movement and providing particularly close attention to adequate hydration and pain management) may be effective in reducing the potential for emesis and should be universally applied.
  • Selective serotonin antagonists are very effective in the prevention of postoperative nausea and vomiting but are much more expensive than alternative agents.

(Radiation-induced nausea and vomiting)

Patients receiving total or hemibody irradiation or single-exposure, high-dose radiation therapy to the upper abdomen should receive prophylactic doses of granisetron 2 mg or ondansetron 8 mg.

TABLE . Recommended Prophylactic Doses of Antiemetics for postoperative nausea and vomiting
Adult Dose (intravenous) Pediatric Dose (intravenous) Timing of Dosea
Dolasetron 12.5 mg 350 mcg/kg up to 12.5 mg At end of surgery
Cranisetron 0.35– 1 mg At end of surgery
Ondansetron 4– 8 mg 50– 100 mcg/kg up to 4 mg At end of surgery
Dexamethasone 5– 10 mg 150 mcg/kg up to 8 mg Before induction
Droperidol 0.625– 1.25 mg 50– 70 mcg/kg up to 1.25 mg At end of surgery
Dimenhydrinate 1– 2 mg/kg 0.5 mg/kg
aBased on recommendations from consensus guidelines; may differ from manufacturer’s recommendations. postoperative nausea and vomiting, postoperative nausea and vomiting.

Disorders of balance

  • Beneficial therapy for patients with nausea and vomiting associated with disorders of balance can reliably be found among the antihistaminic-anticholinergic agents, particularly transdermal scopolamine.
  • Neither the antihistaminic nor the anticholinergic potency appears to correlate well with the ability of these agents to prevent or treat the nausea and vomiting associated with motion sickness.

Antiemetic use during pregnancy

  • Agents that have commonly been prescribed during pregnancy include phenothiazines (prochlorperazine and promethazine), the antihistaminic-anticholinergic agents (dimenhydrinate, diphenhydramine, meclizine, and scopolamine), metoclopramide, and pyridoxine.
  • The efficacy of antiemetics has been questioned, while the importance of other management plans (including emphasis on fluid and electrolyte management, vitamin supplements, and efforts aimed at reducing psychosomatic complaints) has been addressed.
  • Teratogenicity is a major consideration for the use of antiemetic drugs during pregnancy and is the primary factor that dictates the drug of choice. Of the agents commonly used, dimenhydrinate, diphenhydramine, doxylamine, hydroxyzine and meclizine have no human teratogenic potential.
  • Studies using SSRIs in nausea and vomiting of pregnancy are limited.

Antiemetic use in children

  • The safety and efficacy of SSRIs for the prophylaxis of chemotherapy-induced nausea and vomiting in children has been established but the best doses or dosing strategy have not been determined.
  • For nausea and vomiting associated with pediatric gastroenteritis, there is greater emphasis on rehydration measures than on pharmacologic intervention.

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