How Should Medications Be Initiated and Titrated to Prevent and Treat Nausea and Vomiting in Clinical Situations Unrelated to Chemotherapy?

Introduction and Scope of the Problem

Nausea, vomiting, and retching are common and distressing symptoms encountered in patients with advanced illness. Among patients with cancer, up to 70% report these symptoms. Patients with other advanced illnesses may also report these symptoms, including more than half of patients with end-stage kidney disease, end-stage liver disease, and acquired immunodeficiency syndrome.

Nausea, especially when accompanied by emesis, can result in serious complications such as electrolyte imbalances, dehydration, aspiration, Mallory-Weiss tears, and malnutrition. Numerous factors can contribute to nausea and vomiting in persons with advanced illness, including metabolic derangements (e.g., hyponatremia, hypercalcemia, uremia), medications (e.g., opioids, antidepressants, cholinesterase inhibitors), changes in gastric and bowel motility, central nervous system disorders (e.g., increased intracranial pressure, anxiety), and autonomic dysfunction resulting from malnutrition and poor performance status.

Interventions to reduce nausea and vomiting involve careful patient assessment, awareness of the mechanism of emetogenic pathways, and prescribing medications that manage the suspected cause or target pathway receptors either targeted or empiric.

Relevant Pathophysiology

The emetic response involves coordination of various pathways and associated receptors through the physiological control center called the vomiting center ( Fig. 20.1 ). The vomiting center is located in the lateral reticular formation of the medulla and receives central and peripheral input. Central afferents to the vomiting center include the cerebral cortex, higher brainstem, thalamus, hypothalamus, and vestibular system. Peripheral afferents arrive by the vagus and splanchnic nerves from mechanoreceptors and chemoreceptors in the gastrointestinal tract and serosa (see Fig. 20.1 ). Neuroreceptors within each pathway exist and may include acetylcholine, dopamine, serotonin, histamine, opioid, cannabinoid, and neurokinin receptors. The pathogenesis of vomiting involves the trigger of release of neurotransmitters specific to these receptors by emetogenic stimuli. For example, the chemoreceptor trigger zone (CTZ) is located in the area postrema of the fourth ventricle of the brain, where there is effectively no blood–brain barrier, allowing noxious stimuli such as certain medications, bacterial toxins, and/or metabolic products to stimulate dopamine (D ₂ ) receptors in the CTZ to induce nausea and emesis.

Though nausea usually precedes emesis, the pathophysiology of nausea should be considered distinctly. Nausea may occur in the absence of emesis and requires perception while emesis may occur spontaneously. Though not currently well elucidated, nausea may involve neural circuits separate from the emetogenic pathways, as evidenced by differing responses to nausea and emesis seen in response to some therapeutics. It is important to recognize that multiple pathways may contribute to nausea and vomiting ( Table 20.1 ).

Summary of Evidence Regarding Treatment Recommendations