Clinical Review

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

The authors review evaluation and treatment strategies of the cancer patient presenting with nausea and vomiting—underscoring that the two are not always linked and are not always due to chemotherapy.

While a frequent presentation in patients with cancer, symptoms are not always treatment-related and may signal a more serious cause.


 

References

Nausea and vomiting is common in cancer patients and a frequent presentation in the ED. When evaluating nausea and vomiting, the clinician should be aware that the two are not always linked—nausea may present without vomiting and vice versa. Nausea is “an unpleasant sensation of the need to vomit and is associated with autonomic symptoms,” whereas vomiting is “the forceful propulsion of abdominal contents via the contraction of the abdominal musculature and diaphragm.”1 Whether these symptoms present together or independently of each other, both can result in serious metabolic disturbances, internal injury, malnutrition, and poor quality of life. In addition, nausea and vomiting can result in patient withdrawal from potentially beneficial treatment.2 Based on the current literature, this article reviews and provides recommendations on appropriate assessment and treatment of the cancer patient presenting to the ED with nausea and/or vomiting.

Epidemiology

In 2007, the US Nationwide Emergency Department Sample database noted 122 million ED visits, 1.6 million of which were due to nausea and vomiting.3 In contrast, a small study from the United Kingdom cited 18% of ED visits in one of its centers were due to nausea and/or vomiting, demonstrating that the percentage of patients presenting with these symptoms can vary greatly.4

The incidence of cancer-related nausea and vomiting in the ED is unknown. Although EDs affiliated with large cancer centers see many cases of cancer-associated nausea and vomiting, presentations to noncancer-center EDs are becoming more prevalent due to increases in community-based cancer care.5 While the number of cancer patients is rising and the general population is aging,6 there is now less incidence of breakthrough chemotherapy-induced nausea and vomiting (CINV), which is a common cause of cancer-related nausea and vomiting. Older studies quote a 40% to 60% rate of breakthrough CINV; however, with the advent of newer antiemetic prophylaxis, by 2013 the incidence had decreased to about 28%.7 As such, the net effect may be a stable or decreased number of ED visits. In one study of patients with breakthrough CINV, 64% were treated inpatient, 26% outpatient, and 10% in the ED. The study, however, does not note how many of these inpatient visits originated in the ED, highlighting that this is an area in need of further study.8

Current knowledge about the epidemiology and etiology of non-CINV comes from end-of-life (EOL) palliative-care literature treatment guidelines, which are organized by cause (etiology-based antiemetic treatment [EBAT]).9-11 Although one systematic review found that the EBAT approach “cannot be shown to be more effective than using a single antiemetic at effective doses,”12 the etiologic framework is useful and can be applied to non-EOL patients. According to a systematic review on the prevalence of symptoms, nausea in advanced cancer patients ranged from 6% to 68%.6 Another review on cancer-related nausea and vomiting that cited studies conducted in the 1990s showed patients had increased nausea and vomiting as they approach EOL—ranging from 36% upon entering palliative-care programs to 71% in the final week of life.13 However, another systematic review citing more recent studies contradicts these findings, stating that in the last 2 weeks of life, nausea was less common (17%) than in patients who were not at the last 2 weeks of life (31%);14 the same was true of vomiting (20% vs 13%). This data perhaps implies that treatment of nausea and vomiting has improved over time for EOL patients. The same review also found that women were more likely to experience nausea and vomiting than men,14 a finding also seen in a 2011 prospective study of antiemetics for breakthrough CINV vomiting.15

When evaluating patients with cancer-associated nausea and vomiting, it is important to remember that these symptoms rarely occur in isolation. Most patients present with between seven and 15 other complaints, such as pain, weakness, fatigue, anorexia, constipation, dry mouth, early satiety, and dyspnea.16

Pathophysiology

To understand nausea and vomiting, it is helpful to review the emetic pathway. There are four areas that stimulate the central vomiting center located in the medulla oblongata. These are the cerebral cortex, the vestibular nucleus, the intestinal tract, and the chemoreceptor trigger zone (located on the floor of the fourth ventricle). With sufficient input from any of these to the vomiting center, nausea occurs, followed by the vomiting reflex. It is known that each of the input zones, as well as the vomiting center itself, have receptors for various substances, including the following:1,13,17-20

· Cerebral cortex: gamma-aminobutyric acid, histamine type 1 (H1)

· Vestibular nucleus: muscarinic acetylcholine receptor (AChM), H1

· Intestinal tract: 5 hydroxytryptamine type 3 (5-HT3) or serotonin type 3 receptors, 5 hydroxytryptamine type 4 (5-HT4) or serotonin type 3 receptors, dopamine type 2 (D2)

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