Symptom Management Series 1.5 ANCC Contact Hours The Management of Nausea at the End of Life Gayathri S. Moorthy, PhD, BSc, RN ƒ MariJo Letizia, PhD, MSN, BSN The evaluation and management of nausea in patients and clear drugs.3 In these populations, the use of the typical near the end of life can be more challenging than that antiemetics recommended in regimens for oncology of nausea in patients undergoing antineoplastic therapies. patientsmaybeineffective. Unlike in the oncology setting in which nausea is primarily managed using antiemetic regimens that have been developed with the neuropharmacology and emetogenic PREVALENCE OF NAUSEA potentials of chemotherapy agents in mind, many patients The prevalence of nausea and vomiting in the end-of-life receiving end-of-life care have nausea of multifactorial population varies. As many as 50% to 60% of patients etiology. Patients also may be older with reduced physiologic 2,4 ability to metabolize and clear drugs. Therefore, typical with advanced cancer experience nausea ; 50% of pa- antiemetics in regimens initially selected for oncology tients with heart and liver failure and 30% to 50% of pa- 2 patients may be ineffective. In this article, the prevalence, tients with renal failure experience this symptom. As manifestation, and pathophysiology of nausea experienced many as 70% of patients may experience moderate to se- by patients near and at the end of life will be reviewed, with vere nausea in the final week of life.3,5 The following in- a focus on pharmacological and nonpharmacological crease this risk: female sex; younger age; history of low interventions that have been found to effectively manage alcohol intake and anxiety; gynecological, stomach, and this symptom in this patient population. esophageal tumors; medications such as opioids; and fluid and electrolyte imbalances that can occur from dehydra- KEY WORDS tion and malnutrition.2,3,6 Near the end of life, nausea can 3 end of life, management, nausea, palliative care, be chronic or occur intermittently with variable severity ; pharmacology because of its unpredictable trajectory, nausea may be inadequately assessed and managed.7 ausea is defined as an ‘‘unpleasant sensory and emotional experience’’1(p88) associated with the ETIOLOGY AND MANIFESTATIONS feeling of fullness in the epigastric and upper OF NAUSEA N 1,2 abdominal area, with or without a need to vomit. Dry heaving or retching can also occur as a result of spasmodic Patients can describe nausea as queasiness or an upset contraction of the abdominal muscles against a closed glottis. stomach and may experience tachycardia, pallor, cold sweat, Nausea with vomiting can be a protective reflex to rid the and diarrhea, which are typical symptoms that arise from a 2 decreased parasympathetic and an increased sympathetic body of an offending agent. 1,3,4 The management of nausea experienced by patients stimulation of the autonomic nervous system. Near the near and at the end of life can present more challenges end of life, nausea may be experienced within a symptom than other populations. Unlike in the oncology setting cluster that includes constipation, appetite loss, bloating, and weight loss.4 Nongastrointestinal (non-GI) symptoms where nausea is managed using antiemetic regimens that 3 have been developed in accordance with the neurophar- such as fatigue, dyspnea, and drowsiness also occur. Nau- macology and emetogenic potential of chemotherapy, pa- sea may also be associated with changes in emotion and cognition, as supported by functional magnetic resonance tients at the end of life may experience nausea because of a 8 multitude of factors. In addition, patients who are older imaging studies. In these patients, nausea may be due to a may have a reduced physiologic ability to metabolize number of disease processes and/or the direct result of medications, as noted hereinafter. Gayathri S. Moorthy, PhD, BSc, RN, is staff nurse, DuPage Medical Group, Lisle, IL. Bowel Dysfunction Associated With Nausea MariJo Letizia, PhD, MSN, BSN, is professor, Loyola University Chicago, IL. Bowel dysfunction is a common cause of nausea in the Address correspondence to MariJo Letizia, PhD, MSN, BSN, School of end-of-life population, the prevalence and severity of which Nursing, Loyola University Chicago, 2160 S First Ave, Maywood, IL 6 3 60153 ([email protected]). increase toward the end of life. Gastroparesis is common, The authors have no conflicts of interest to disclose. resulting from GI malignancies, neuropathy from Parkinson 3,9 Copyright B 2018 by The Hospice and Palliative Nurses Association. disease, and/or opioid therapy. Gastroparesis can lead to All rights reserved. constipation and functional bowel obstruction, which can DOI: 10.1097/NJH.0000000000000453 also cause nausea,3 and patients often report intermittent 442 www.jhpn.com Volume 20 & Number 5 & October 2018 Symptom Management Series nausea that is associated with bloating and relieved by eral areas throughout the body, not all of which have been vomiting.3,5 The clustering of nausea with early satiety well elucidated.1,3,15 Nausea is believed to include more and epigastric pain may indicate GI irritation and cancer- cerebral involvement and consciousness than vomiting, associated functional dyspepsia syndrome.3 Other less in which a reflex action is triggered by the lower brain common GI causes of nausea include ulcers, ascites, structures.2 A specific anatomical area related to nausea hepatitis, and adhesions.2,3 and vomiting is the ‘‘vomiting center’’ (VC) in the medulla, which has receptors for histamine, acetylcholine, dopa- 1 Medications Implicated in Nausea mine, and serotonin. In 30% to 40% of patients who are nearing the end of life, The VC integrates signals from the other neuronal areas nausea is persistent and not relieved by vomiting.3 In these to coordinate the emetic response. These include the cere- patients, nausea may be secondary to the effects of medi- bral cortex, the limbic system and thalamus, the vestibular cations including opioids, antibiotics, anticonvulsants, and nuclei/cerebellum, the chemoreceptor trigger zone (CTZ) in the fourth ventricle of the brain, and, in the periphery, nonsteroidal anti-inflammatory agents on intracranial re- 1,2,15 ceptors.2,5 Opioid use among those at the end of life, spe- the GI tract. The cerebral cortex has multiple chemo- + cifically those receiving hospice benefits, is estimated at receptors, including -aminobutyric acid, dopamine, sero- 88% to 94%10; nausea tends to be higher in opioid-naive tonin, acetylcholine, and neurokinin-1 (NK-1) receptors patients and improves with continued therapy, but it can that are activated by factors such as smells, anxiety, and persist in some. The abrupt withdrawal of corticosteroids, pain. Mechanoreceptors are also involved, sensitive to commonly used as an adjunct for pain and edema, can also mechanical pressure from the stretching and irritation of lead to adrenal insufficiency that presents as nausea asso- the meninges that can occur with infection, swelling, or ciated with hypotension and abdominal cramps.5 an intracranial mass. Histamine and cholinergic receptors in the cerebellum may be activated by opioids and afferent input from the inner ear. The CTZ, which is unprotected by Intracranial and Other Causes of Nausea the blood-brain barrier and therefore exposed to agents Some patients who are at the end of life experience nausea within the bloodstream such as opioids, metabolites, and related to intracranial factors, including swelling, bleeding, 3,5 toxins, has the serotonin 3, dopamine, histamine, and tumors, and meningitis. These patients tend to experi- NK-1 receptors, which are sensitive to these agents.1,13,15,16 ence nausea and vomiting, especially in the morning, with These same receptors are activated by neurotransmitters headaches.3 The clustering of fear and/or anxiety with nau- 5 released from enterochromaffin cells in the GI tract when sea and small volumes of vomiting can occur. they are exposed to medications, toxins, and radiation.2,17 When movement induces or exacerbates nausea, espe- Histamine and cholinergic mechanoreceptors in the GI sys- cially when accompanied by vertigo and imbalance, the tem are activated by distortion induced by gastroparesis, cause may be vestibular in nature, such as in Meniere dis- 3,11 bowel obstruction, and metastases/masses in the GI tract ease or chronic vestibular dysfunction. Hormonal and and peritoneum.2,17 Activation of GI receptors leads to sig- metabolic alterations related to advanced cancer, renal naling via vagal afferents that either directly innervate the and/or liver failure, and fluid and nutritional deficits can 2,17 2 VC or innervate the VC via the CTZ. Similarly, oropha- also lead to nausea. For example, hypercalcemia, a com- ryngeal irritation can stimulate the CTZ via histamine and mon complication of advanced cancer that occurs in 10% acetylcholine-activating vagal afferents.2,17 to 20% of patients, can cause nausea and vomiting; an as- Treatment of nausea can be based on an understanding sociated dehydration and constipation can also induce or 12 of these receptors. Dopamine is most commonly targeted exacerbate nausea. Hyponatremia in patients with con- when managing nausea outside the chemotherapy set- gestive heart failure or kidney failure, uremia due to kidney ting,14 because the dopamine receptor (1) is better studied, failure, or infection such as esophagitis, gastroenteritis, and 2,5 (2) is present in several of the centrally located nausea sig- sepsis can also lead to nausea. Likewise, excessive oro- naling centers such as the VC where signals are integrated pharyngeal secretions and coughing can cause nausea, 2,5,13,14 and the CTZ that is exposed to systemic toxins and medica- with or without vomiting. Finally, gastroparesis ex- tions, and (3) is present peripherally in the GI tract where it perienced by patients with diabetes and constipation and mediates nausea caused by gastroparesis, constipation, and nutritional deficits related to poor oral intake secondary to 3 bowel obstruction.