nausea%20-and-%20vomiting
NAUSEA & VOMITING
Nausea is the sensation felt immediately before vomiting.
Vomiting is a partially voluntary act of forceful expelling of stomach contents up to and out of the mouth that may or may not be preceded by nausea.
Retching or repetitive active contraction of the abdominal muscles occurs between nausea and vomiting.
Management includes correction of clinically relevant metabolic complications, pharmacological therapy and treatment of underlying cause.

Principles of Therapy

  • The underlying cause of nausea and vomiting should be identified and treated properly
  • In patients for whom the primary cause of nausea and vomiting cannot be found easily, treatment should be directed at reduction or elimination of symptoms
  • Oral and IV antiemetic formulations have equivalent effectiveness
  • The lowest, maximally effective dose of antiemetic should be used
  • The toxicity profile of antiemetic agents should be taken into consideration
    • For multidrug regimens, choice of antiemetic therapy will depend on the drug with the greatest emetic risk
  • For women suffering from nausea and vomiting of pregnancy, the severity of symptoms and the patient’s desire for treatment are important considerations in making treatment decisions

Chemotherapy-Related Nausea and Vomiting

  • The goal of treatment is to prevent nausea and vomiting
    • Generally, antiemetic treatment should be started prior chemotherapy to maximally protect against nausea and vomiting
  • The choice of antiemetic agent should be based on the emetogenic potential of a patient’s chemotherapy regimen as well as patient factors and previous experience with antiemetic therapy
  • Patients receiving chemotherapy are at risk of chemotherapy-related nausea and vomiting for at least 4 days after chemo administration and should be protected for this whole duration

Pharmacotherapy

Antihistamines
  • Nausea and vomiting of a labyrinthine origin eg motion sickness, migraine and vertigo may be treated with antihistamines
  • Antihistamines are part of the 1st-line treatment for nausea and vomiting of pregnancy
    • Antihistamines that are considered safe in pregnancy:
      • Cyclizine, Dimenhydrinate, Diphenhydramine, Doxylamine, Hydroxyzine, Promethazine
  • Antihistamines are also useful for acute or breakthrough episodes of nausea and vomiting of pregnancy because of the availability of parenteral and suppository forms
  • Action: Act as Histamine-1 receptor antagonists and exert a central antiemetic effect

Benzodiazepines

  • Alprazolam and Lorazepam may be used as adjunctive components of antiemetic regimens for prevention of chemotherapy-related nausea and vomiting, ie anticipatory chemotherapy-related nausea and vomiting or breakthrough chemotherapy-related nausea and vomiting with anxiety component

Butyrophenones

  • Eg Droperidol, Haloperidol
  • May be used for PONV and anticipatory and acute chemotherapy-related nausea and vomiting
  • Haloperidol is an alternative option to Metoclopramide in patients with advanced cancer 
  • Action: Probably exert a central antidopaminergic effect

Corticosteroids

  • Corticosteroids (eg Dexamethasone, Methylprednisolone, Prednisolone) are used in combination with other antiemetic medications in the treatment of chemotherapy-related nausea and vomiting
    • Given to patients with known potential for delayed emesis after receiving moderately emetogenic chemotherapy
    • May be used to prevent emesis of chemotherapeutic agents of low risk
  • Dexamethasone may be used alone or in combination with other antiemetic agents for prevention of PONV
    • Course of delayed Dexamethasone may be extended as clinically appropriate for patients experiencing extended delayed chemotherapy-related nausea and vomiting
  • Methylprednisolone may be used as a last resort in nausea and vomiting of pregnancy in patients who require enteral or parenteral nutrition because of weight loss
    • Avoid use during the 1st trimester because of possible risk of oral clefting
  • Action: Effect may be due to reduction of prostaglandin formation

Neurokinin-1 (NK-1) Receptor Antagonists

  • Eg Aprepitant, Fosaprepitant, Netupitant, Rolapitant
  • Used in combination with other antiemetic agents for prevention of acute and delayed chemotherapy-related nausea and vomiting
  • Complements the antiemetic action of other available agents
    • Enhances the antiemetic activity of the serotonin 5-HT3 antagonists and Dexamethasone in inhibiting acute and delayed Cisplatin-induced vomiting
  • Action: Selectively blocks the binding of substance P at the NK-1 receptor in the CNS

Phenothiazines

  • Commonly used for severe attacks of nausea and vomiting, including nausea and vomiting associated with vertigo, migraine and motion sickness
  • Availability in various formulations is useful for patients who cannot tolerate oral medications
  • May be given as 2nd-line treatment for nausea and vomiting of pregnancy and are usually employed in severe cases
    • Chlorpromazine, Perphenazine, Prochlorperazine, Promethazine, Trifluoperazine are considered safe to use in pregnancy
  • Levomepromazine is an alternative option to Metoclopramide in patients with advanced cancer 
  • Action: Exert a central antidopaminergic effect in the area postrema of the brain

Prokinetic Agents

  • Eg Domperidone and Metoclopramide
  • Mainly used in gastroparesis and other dysmotility syndromes
  • May be used to prevent delayed chemotherapy-related emesis
  • Metoclopramide is the drug of choice in patients with advanced cancer
    • Considered safe to use in pregnancy and is considered a 2nd-line agent
  • Treatment should be at the lowest effective dose and kept as short as possible, ie up to 5 days (not to exceed 12 weeks), to reduce the risks of neurological, cardiac and other adverse effects
  • Action: Exert an antidopaminergic effect and appear to have some direct and indirect anticholinergic effects
    • Exert prokinetic effects on the esophagus, stomach and upper small intestine

Serotonin 5-HT3 Antagonists

  • Eg Granisetron, Ondansetron, Palonosetron, Ramosetron, Tropisetron, Dolasetron
  • The serotonin 5-HT3 antagonists may be used for prevention of acute chemotherapy-related nausea and vomiting and both oral and IV forms are equally effective at appropriate doses
    • Palonosetron has been shown to be effective as prophylaxis for both delayed and acute chemotherapy-related emesis
  • These agents may also be used for prevention of PONV
  • Optimal effects can be seen with scheduled dosing and not PRN
  • There is limited data on the safety of serotonin 5-HT3 antagonists in pregnancy
    • Use should be restricted to treatment of refractory nausea and vomiting when other agents that have established safety and efficacy have failed
    • Ondansetron at 8 mg PO 12 hourly, 8 mg IV 12 hourly, or 1 mg/hour IV infusion x 24 hour has been given
  • Action: Primary site of action of these drugs is thought to be on the chemoreceptor trigger zone in the area postrema of the brain, where the highest concentration of 5-HT3 receptors are found

Vitamin Supplementation

Pyridoxine (Vit B6)

  • Has been shown to be effective in treating nausea and vomiting of pregnancy
    • May be more effective in reducing nausea than vomiting
  • May be given as monotherapy or combined with antihistamines, eg Doxylamine

Other Agents

Ginger Root

  • Has been shown to be effective for nausea and vomiting of pregnancy
  • Caution should be exercised when prescribing ginger because there may be variabilities between available preparations
  • Safety data is lacking, though many cultures use ginger as a spice with amounts similar to commonly prescribed therapy

Recommended Antiemetic Agents for Specific Etiologies of Nausea & Vomiting

RECOMMENDED ANTIEMETIC AGENTS FOR SPECIFIC ETIOLOGIES OF NAUSEA AND VOMITING
Etiology of Nausea and Vomiting Recommended Antiemetic Agents
Disorders of Gut Motility
  • Propulsives
Motion Sickness
  • Antihistamines
  • Hyoscine (Scopolamine)
  • Phenothiazines
Postoperative Nausea and Vomiting (PONV)

Prevention

Very High Risk:

  • Combination of antiemetic agents plus
  • Use of total IV anesthesia with Propofol during surgery

Moderate-High Risk:

  • Dexamethasone + serotonin 5-HT3 antagonist or
  • Droperidol + serotonin 5-HT3 antagonist

Mild-Moderate Risk (any one of the following):

  • Dexamethasone
  • Droperidol
  • Hyoscine (Scopolamine)
  • Serotonin 5-HT3 antagonist

Treatment of PONV

  • Use different agent than what was used to prevent PONV

Preferred Agent

  • Serotonin 5-HT3 antagonist
Chemotherapy-related Nausea and Vomiting

High Emetic Risk Chemotherapy

Start 30-60 min before chemotherapy:

  • Neurokinin-1 antagonist + corticosteroid + serotonin 5-HT3 antagonist
  • with or without Lorazepam
  • with or without proton pump inhibitor (PPI) or H2 blocker

May also use an Olanzapine-containing regimen

To Prevent Delayed Nausea and Vomiting

Continue primary treatment for 2-3 days after completion of cycle

Moderate Emetic Risk Chemotherapy

Start 30-60 min before chemotherapy:

  • Serotonin 5-HT3 antagonist + corticosteroid ± Neurokinin-1 antagonist
  • with or without Lorazepam
  • with or without PPI or H2 blocker

May also use an Olanzapine-containing regimen

To Prevent Delayed Nausea and Vomiting

No routine prophylaxis is recommended
On days 2-4 following chemotherapy, may give any 1 of the following with or without Benzodiazepine:

  • Serotonin 5-HT3 antagonist
    • If Palonosetron was used on day 1, no follow-up dosing is needed
  • Corticosteroid
  • Neurokinin-1 antagonist (if given on day 1) ± Dexamethasone
    • If Aprepitant was used on day 1, continue use on days 2 and 3 

Low Emetic Risk Chemotherapy

Start 30-60 minutes before chemotherapy:

  • Single antiemetic agent (eg Dexamethasone, Metoclopramide, Prochlorperazine or a serotonin 5-HT3 antagonist) with or without Lorazepam and with or without PPI or H2 blocker

Minimal Risk Chemotherapy

  • No routine emesis prophylaxis

Breakthrough Nausea and Vomiting

  • Rule out nonchemotherapy-related causes of nausea and vomiting
  • Give an additional antiemetic agent from a different drug class
  • Consider using alternating schedules and alternating routes of administration
    • Round-the-clock administration instead of as required
  • Prior next chemotherapy cycle, identify the antiemetic regimen given on day 1 and postchemotherapy of present cycle that was not helpful to the patient and consider other alternatives
  • If nausea and vomiting is still uncontrolled, consider changing to a higher-level antiemetic regimen
  • Consider giving antacid if with dyspepsia

Anticipatory Nausea and Vomiting

  • Prevent by administering optimal antiemetic therapy during every cycle of therapy
  • Consider behavioral therapy or acupuncture/acupressure
  • Consider giving anxiolytics, eg Alprazolam or Lorazepam

Refractory Nausea and Vomiting

  • May add a Phenothiazine or propulsive to serotonin 5-HT3 antagonist + corticosteroid

Multiple-Day Chemotherapy

  • Chemotherapy days: Treat as acute nausea and vomiting
  • 1-2 days after chemotherapy: Treat as delayed nausea and vomiting

Individualize treatment based on chemotherapy regimen and patient response

Radiation-related Nausea and Vomiting

Radiation Therapy of Upper Abdomen or Total Body Irradiation

Start pretreatment for each day of radiation therapy

  • Granisetron or Ondansetron
  • with or without Dexamethasone
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