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Palliative Care - Nausea and Vomiting - Fast Facts | NEJM Resident 360

Nausea, vomiting, or both in the setting of serious illness are common, distressing, and debilitating symptoms. An intentional and systematic approach to understanding the contributing factors, pathophysiology, and causes of these symptoms is essential to choosing pharmacologic management. The general approach to the evaluation and treatment of nausea and vomiting is to:

1. obtain a thorough history and physical
2. consider a workup that can include laboratory testing, imaging, or both to investigate the potential underlying cause
3. differentiate the underlying mechanism for nausea/vomiting
4. select a targeted therapy for relief of the symptom(s)

History and Physical Exam

• The history should focus on characterizing the severity, temporality, and any associated symptoms. Specifically, pursuing additional complaints of anorexia/decreased appetite may signify unrecognized nausea.

• A comprehensive bowel history is essential, as constipation is underrecognized by patients and they often mistakenly believe it is linked to the amount of oral intake.

• A thorough review of current medications is needed, as patients with serious illness can have an extensive medication list that is being altered frequently. Common medications that contribute to nausea/vomiting include opioids, antibiotics, antidepressants, digoxin, nonsteroidal anti-inflammatory drugs (NSAIDs), vitamins/supplements, and chemotherapy.

Diagnostic Workup

• Laboratory or imaging studies are not always necessary to determine the underlying cause of nausea/vomiting.

  • However, certain laboratory tests may be helpful, especially if considering metabolic derangements such as hypercalcemia (calcium level), uremia (blood urea nitrogen [BUN] level), liver failure (liver function tests, ammonia level), or renal failure (basic metabolic panel) as the specific source.

• When considering imaging, a plain supine abdominal radiograph may help identify constipation or a bowel obstruction.

  • Special consideration for a patient who is cognitively impaired, delirious, or both may be warranted, because an accurate history of bowel function may not be possible and additional imaging may help identify the source.

  • In oncology patients with refractory nausea, vomiting, or both, an MRI of the brain should be considered to rule out intracranial metastasis.

Etiology

When a cause for a patient’s nausea can be identified, the treatment should be targeted accordingly.

• Drug-induced: If nausea is suspected to be caused by a medication, decreasing, discontinuing, or rotating the drug is appropriate.

• Constipation: If constipation is the primary reason for the patient’s nausea, an enhanced medication regimen to promote bowel motility is first-line therapy, prior to treating empirically with antiemetics.

Once the etiology of the nausea is determined, the antiemetic can be targeted toward the associated neural pathway and neurotransmitters. The four primary neural pathways that stimulate the vomiting center in the medulla should be considered in the differential diagnosis for nausea/vomiting:

1.Vestibular system: Nausea and vomiting are often triggered by motion.
2. Cortex: Nausea and vomiting are triggered by anxiety, meningeal irritation, sensory input, and increased intracranial pressure.
3. Chemoreceptor trigger zone: Nausea and vomiting are triggered by toxins in both the cerebrospinal fluid (CSF) and bloodstream, outside the blood–brain barrier.
4. Peripheral pathways: Nausea and vomiting are triggered by mechanoreceptors and chemoreceptors in the gastrointestinal (GI) tract, serosa, and viscera.

Etiologies, Associated Symptoms, and Physical Exam Findings Associated with Nausea

Potential Etiology/Cause	History and Physical Exam Findings
Bowel obstruction

• Large emesis that relieves symptoms temporarily

• Obstipation

• Crampy abdominal pain

• Abdominal distention

| | Gastric stasis |

• Small, repeated vomitus

• Bloating

• Early satiety

| | Vestibular dysfunction |

• Vertigo

• Dizziness

| | Increased intracranial pressure |

• Symptoms associated with awakening in the morning

• Headaches

• Papilledema

• Neurologic deficits

• Altered mental status

| | Medications |

• Recent medication additions, subtractions, or titrations

| | Constipation |

• Straining/pain with defecation

• Decreased frequency in bowel movements

• Hypoactive bowel sounds

• Abdominal fullness

| | Pancreatitis |

• Epigastric abdominal pain

| | Gastroesophageal reflux disease |

• Sour taste

• Burning chest pain

| | Chemotherapy |

• Recent chemotherapy

| | Metabolic abnormalities |

• Altered mental status

| | Anxiety |

• Little to no vomiting or weight loss

• Anticipatory of triggering event

|

Treatment

A reasonable initial approach for a patient with persistent, uncontrolled nausea is to schedule antiemetic medications for 48−72 hours and have as-needed medication available for breakthrough, much like in the treatment of pain. Once nausea is better controlled, it is appropriate to consider a taper plan for the scheduled regimen, while keeping breakthrough medication available.

In many cases of nausea/vomiting, it may be difficult to determine a single cause, either because of a lack of clear etiologies or more likely because multiple etiologies exist simultaneously. In such cases, it is reasonable to empirically select an antiemetic that targets dopamine (e.g., prochlorperazine or metoclopramide) or serotonin (e.g., ondansetron), as these neurotransmitters are implicated in the chemoreceptor trigger zone and peripheral neural pathways — which are involved in many causes of nausea encountered in clinical practice (e.g., drugs, metabolic derangements, GI concerns).

Medications Used in the Treatment of Nausea

Antiemetic	Class of Medication	Neural Pathway	Adverse Effects
Haloperidol	Butyrophenone	Chemoreceptor trigger zone	EPS
Akathisia
QTc prolongation
Prochlorperazine	Phenothiazine	Chemoreceptor trigger zone
Vestibular	EPS
Akathisia
Sedation
Promethazine	Phenothiazine	Chemoreceptor trigger zone
Vestibular	EPS
Akathisia
Sedation
Metoclopramide	Prokinetic	Chemoreceptor trigger zone
Peripheral	EPS
Akathisia
Cramping
Risk of perforation with complete obstruction
Ondansetron	5-HT3–receptor antagonist	Chemoreceptor trigger zone
Peripheral	QTc prolongation
Constipation
Palonosetron	5-HT3–receptor antagonist	Chemoreceptor trigger zone
Peripheral	QTc prolongation
Constipation
Olanzapine	Atypical antipsychotic	Chemoreceptor trigger zone
Peripheral
Vestibular	Weight gain
Sedation
Orthostatic hypotension
Dexamethasone	Glucocorticoid	Cortex
Peripheral	Mental status changes
Agitation
Hyperglycemia
Immunosuppression
Lorazepam	Benzodiazepine	Cortex	Sedation
Mental status changes
Scopolamine	Anticholinergic	Vestibular	Mental status changes
Sedation
Dry mouth
Urinary retention
Constipation
Hyoscyamine	Anticholinergic	Vestibular	Mental status changes
Sedation
Dry mouth
Urinary retention
Constipation
Meclizine	Antihistamine	Vestibular	Sedation
Dry mouth
Urinary retention
Constipation

Abbreviations: EPS, extrapyramidal side effects; QTc, corrected QT; 5-HT3, 5-hydroxytriptamine type 3

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