Nausea and Vomiting in Cancer: It's Not Always the Chemotherapy

· infection

· drugs

· increased intracranial pressure (ICP)

· anxiety

The above causes of nausea and vomiting accounted for 85% of the cases in the study.⁹ Similar results were found in another study, showing that impaired gastric emptying and metabolic/drugs each caused about one third of the cases.¹⁰

Nontreatment-related causes of nausea and vomiting are traditionally divided into the following six broad etiological categories by palliative care practitioners^9,10,13:

1. Biochemical: medications, tumor products, metabolic derangements, comorbidities, including systemic infections, noncancer abdominal illnesses; and silent cardiac ischemia

2. Gastric stasis: tumor, neuropathy, hepatomegaly, ascites

3. Bowel dysmotility/obstruction: tumor, metastases, adhesions, ileus, constipation

4. Intracranial pressure: tumor edema, bleeding, hydrocephalus, leptomeningeal disease

5. Vestibular: opioids, comorbid vestibular problems, brainstem metastases

6. Miscellaneous: anxiety, pain

These classification schemes are designed to help guide the treatment of palliative-care patients (EBAT),^9-11 but very little evidence supports the recommendations.^11-13,17 Expert opinion consensus guidelines favor haloperidol for biochemical etiology and metoclopramide for impaired gastric emptying. In intestinal obstruction, the H₁-blocking antihistamine cyclizine and the anticholinergic hyoscine butylbromide (scopoloamine) are the preferred agents, but dexamethasone and haloperidol are also favored by some. It is believed that increased ICP nausea is best treated with cyclizine and dexamethasone. Vestibular etiologies are treated with cyclizine, and anxiety-mediated nausea should be treated with benzodiazepines.^9,17 As there are often multiple etiologies in a given patient, selection of one agent can be problematic.¹³ Furthermore, no studies have applied these guidelines to ED cancer patients. This framework, however, can assist the EP in forming a differential diagnosis and appropriate workup. On history and physical examination, the EP should look for and consider the following:^13,16

· Small-volume undigested emesis shortly after eating, suggesting gastric emptying impairment

· Bilious or feculent vomitus, large volumes, constipation, and obstipation, suggesting bowel obstruction (evaluate via X-ray or computed tomographic imaging)

· Early morning nausea and headache, suggesting increased ICP

· Nausea associated with head movement or motion, with or without vertigo, (suggesting vestibular disease)

· Current or recent use of opioids, antibiotics, antifungals, anticonvulsants, vitamins, ethanol, and selective serotonin reuptake inhibitors

· Infection, sepsis

· Metabolic abnormalities found on blood tests (for example, renal failure, liver failure, hypercalcemia, hyponatremia, ketoacidosis, osmolar gap, toxins/poisons, Addisonian crisis from steroid withdrawal or adrenal metastases); and/or

· Silent cardiac ischemia (evaluate via electrocardiography and cardiac enzymes)

· Careful consideration of each of the above possibilities will make one less likely to miss other serious causes of nausea and vomiting in the cancer patient with recent chemotherapy.

Opioid-Induced Nausea

Forty percent of cancer patients taking opioids experience nausea, which can adversely impact pain control.²² Opioid-induced nausea is due to constipation, gastroparesis, stimulation of the chemoreceptor trigger zone, and sensitization of the labyrinth, all of which can in turn stimulate the vomiting center.

Regarding the treatment of opioid-induced nausea and vomiting, there is no evidence to support the use of one antiemetic over another. Some weak evidence-based recommendations suggest either changing the medication to a different opioid, or changing the route of administration from oral to subcutaneous and adding coanalgesics such as gabapentin or ketamine to reduce opioid dosages. Though these strategies may be helpful in practice, none of the studies was large enough or thorough enough to support or warrant any formal recommendations in this systematic review.²²

Initial Management and Treatment

As always, attention to the patient’s airway, breathing, and circulation is of utmost importance. Endotracheal intubation should be considered in patients at risk for aspiration—unless a living will or do-not-resuscitate order exists. Maneuvers such as raising the head of the bed or turning the patient on his or her side may help avoid aspiration.

Intravenous (IV) hydration is generally beneficial. The choice and amount of fluid should be based on clinical judgment. Electrolyte imbalances should be corrected. The mainstay of treatment for nausea and/or vomiting is pharmacologic, which is the focus of the next section.

Pharmacologic Management

Prokinetic Agents

Prokinetic agents increase peristalsis and exert an antiemetic effect. Metoclopramide is the best known and most widely available prokinetic agent. Since it is both inexpensive and very effective as an antiemetic, its use in the ED is widespread. Etiology-based antiemetic treatment guidelines list metoclopramide as the antiemetic of choice when gastroparesis or other gastric emptying problems are diagnosed^9,10,13,17 as it exerts both D2 and 5-HT₃ central nervous system (CNS) antiemetic effects, relaxes pyloric tone (D2), and increases peristalsis by stimulating 5-HT₄ serotonin receptors in the gut.