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Symptom Management Series 1.5 ANCC Contact Hours The Management of 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 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 regimens that have been developed with the neuropharmacology and emetogenic PREVALENCE OF NAUSEA potentials of agents in mind, many patients The prevalence of nausea and 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 experience nausea ; 50% of pa- antiemetics in regimens initially selected for oncology tients with heart and 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 intake and ; gynecological, stomach, and this symptom in this patient population. esophageal tumors; such as ; and fluid and 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, , 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 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 , 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 , appetite loss, , and .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. is common, The authors have no conflicts of interest to disclose. resulting from GI , neuropathy from Parkinson 3,9 Copyright B 2018 by The Hospice and Palliative Nurses Association. disease, and/or therapy. Gastroparesis can lead to All rights reserved. constipation and functional , which can DOI: 10.1097/NJH.0000000000000453 also cause nausea,3 and patients often report intermittent

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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 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, , structures.2 A specific anatomical area related to nausea , and adhesions.2,3 and vomiting is the ‘‘vomiting center’’ (VC) in the medulla, which has receptors for , , dopa- 1 Medications Implicated in Nausea mine, and . 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, , anticonvulsants, and nuclei/cerebellum, the 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, , 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. are also involved, sensitive to commonly used as an adjunct for pain and , can also mechanical pressure from the stretching and irritation of lead to 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, , 3,5 toxins, has the serotonin 3, dopamine, histamine, and tumors, and . 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 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 .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 , 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 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 and constipation can also induce or 12 of these receptors. Dopamine is most commonly targeted exacerbate nausea. in patients with con- when managing nausea outside the chemotherapy set- gestive or , due to kidney ting,14 because the dopamine receptor (1) is better studied, failure, or infection such as , , 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. The mnemonic ‘‘VOMIT’’ (Vestibular ap- debility or dementia contribute to this symptom. paratus, Obstruction, Motility/Mind, Infection/, and Toxins/Tumor) can remind providers about possible 18 PATHOPHYSIOLOGY etiologies of nausea. Although this mnemonic does not include receptors involved in nausea, it may prompt the The neurophysiology of nausea and vomiting is com- provider to investigate some of the common causes of nau- plex, involving numerous receptors and circuitry in sev- sea experienced by patients at the end of life.

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PATIENT ASSESSMENT The following antidopaminergics target this receptor and may be used; however, providers must also consider com- A thorough history and patient examination are essential in mon adverse effects including extrapyramidal symptoms attempting to uncover a likely cause(s) of nausea that then (EPS) such as tardive dyskinesia, Parkinsonism, and dysto- guides management. Characteristics of nausea including its nia.9,16 is commonly used to manage nausea, frequency, duration, severity, and related vomiting are noted. although a review of randomized controlled trials (RCTs) in Patient-reported tools, such as the numeric 0 to 10 rating scale the palliative care setting does not provide strong evidence or the Edmonton Symptom Assessment Scale that provides for its efficacy.5,19 may be used in pa- the means of assessing nausea alongside other commonly dis- tients with nausea caused by gastroparesis or involvement tressing symptoms, can be used.1,4 Functional status, symptom of the CTZ,3,14 although efficacy in the end-of-life setting is burden, and goals of care are also assessed by speaking with unknown.5 Likewise, may be useful in the patient and/or proxy. findings are patients whose nausea is multifactorial and in those who noted. Weight change and the presence of postural hypoten- are refractory to other agents, because this tar- sion may suggest fluid and electrolyte imbalances related to gets several receptors,15 but RCT evidence for its efficacy is nausea. with or without hypoactive lacking.20 Olanzapine, a second-generation atypical anti- or absent bowel sounds, tenderness, and/or masses and fecal psychotic that targets the serotonin receptor 3 and histamine impaction are other common causes of nausea.2 receptor sites, may be selected when the cause of nausea is Laboratory testing may include a complete metabolic unknown, when other agents have been attempted, and/or panel, liver enzymes, and urea or bilirubin. Radiologic ex- when EPS are present.16,21-25 aminations may be indicated if obstructions or other pa- thology is expected; findings may lead to therapeutic approaches that can alleviate the burden of this symptom Metoclopramide is an agent deserving of its own cate- at the end of life.2,3 gory in the treatment of nausea. Unlike other more cen- trally acting dopamine antagonists, metoclopramide works TREATMENT STRATEGIES primarily at the dopamine receptors in the GI tract, with some effects on the CTZ.3,16 In the GI tract, metoclo- Many antinausea medications were developed to manage pramide also antagonizes serotonin 3 receptors, activates chemotherapy-induced nausea and vomiting. However, serotonin 4 receptors, and enhances release of acetylcho- most of these have not been scientifically evaluated in line, leading to the activation of the muscarinic receptors the end-of-life population; providers have needed to in- and thus peristalsis in the stomach and small bowel.3,14 stead rely on expert consensus and experience. Classes For these reasons, metoclopramide can be particularly of medications to combat nausea include dopamine antag- beneficial in patients who have nausea related to GI onists, serotonin antagonists, histamine antagonists, mus- causes. Metoclopramide is the only ap- carinic acetylcholine receptor antagonists, NK-1 receptor proved for use in the United States and is often a first-line antagonists, and . For example, the dopamine therapy in patients with gastroparesis.3 Consensus guide- receptor can be targeted with the use of a prokinetic agent lines by the Multinational Association of Supportive Care such as metoclopramide in a patient with constipation; the in Cancer recommend metoclopramide as the drug of histamine receptor can be targeted in a patient who has choice for use in advanced cancer patients without bowel motion-associated nausea. Specific agents and indication obstruction; however, the medication is contraindicated in for use are listed in the Table; those that are used only to patients with GI bleeding and perforations.5 Because of the relieve chemotherapy-related nausea, such as the NK-1 re- risks for EPS, metoclopramide is not approved by the US ceptor antagonists, have been excluded. Antinausea med- Food and Drug Administration for use for more than 12 ications may have broad activity because the receptors that weeks and must be used with extreme caution in frail mediate nausea, especially dopamine and serotonin recep- older adults.2,3 tors, are located in numerous places. If the cause of nausea cannot be determined initially, different agents can be tried Serotonin Antagonists in the Setting of for short periods or agents from different classes can be Palliative Radiation Therapy 2,3,14,18 combined. Of note, combination antinausea therapy Serotonin antagonists, the ‘‘setrons,’’ namely, may not be any more efficacious than monotherapy in pa- and , work by antagonizing the serotonin 3 re- 5 tients with advanced cancer. ceptor in numerous places.3 These agents are recommended for the nausea prophylaxis locally in the GI tract due to can- Antagonists cer therapy26 and to control the accumulation of seroto- Outside the chemotherapy setting, nausea is thought to nin that occurs with bowel obstructions.2 The secondary largely be due to signaling via the dopamine receptor.14 effects of the ‘‘setrons’’ centrally also allow for the control

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TABLE Antinausea Agents for Consideration in End-of-Life Care Adverse Effects/ Antinausea Agent Indications Suggested Regimen Contraindications Dopamine receptor antagonists

Butyrophenone Haloperidol Opioid-induced nausea, PO: 1.5-5 mg q4-6 h More EPS (Haldol) chemical/metabolic nausea, SC: 1-5 mg/d via continuous bowel obstruction SC infusion IV: 0.5-2 mg q3-4 h

Prokinetic agents Gastric stasis, partial bowel PO, ODT, IV: 10-30 mg q4-6 h Restlessness, sedation, fatigue, Metoclopramide (Reglan, obstruction, drug of choice in EPS, esophageal , GI Metozolv ODT) advanced cancer Use cautiously in older adults, higher doses, not approved for use more than 12 wk or with complete bowel obstruction

Phenothiazines Treatment of nausea and PO: 5-25 mg q4-6 h EPS, symptoms, Prochlorperazine (Compazine) vomiting of various causes Rectal: 25 mg q6-8 h sedation, anxiety, IM route may IM: 5 mg/mL q3-4 h cause pain IV: 20-40 mg q4-6 h

Levomepromazine Refractory nausea in PO: 6.25-25 mg q12 h More sedative, anticholinergic palliative care SC: 25-50 mg/d effect, administer cautiously in renal, hepatic impairment, second- or third-line therapy in palliative care, has properties

Olanzapine (Zyprexa, ) Refractory nausea, nausea in PO: 2.5-10 mg q12-24 h Sedation, reduced seizure cancer patients threshold, increased serum lipids and QT prolongation

Serotonin receptor 3 antagonists

Ondansetron (Zofran) Chemotherapy and PO/ODT: 4-8 mg q8-12 h Constipation, headache, radiation-induced nausea IV: 0.15 mg/kg q12 h clinical efficacy plateaus

Granisetron (Kytril, Sancuso) PO: 1 mg q12 h 7-d transdermal patch: 3.1 mg/24 h IV: 10 mcg/kg q12 h

Histamine receptor antagonists/antihistamines

Diphenhydramine (Benadryl) Vestibular and central nervous PO/IV: 12.5-50 mg q6-8 h Anticholinergic effects, dry system causes mouth, blurred vision, (Atarax) PO/rectal/IV: 12.5-25 mg sedation (less with ), q6-8 h (max dose, 100 mg/d) constipation Cyclizine () PO/SC: 25-50 mg q8 h (max dose, 200 mg/d)

Muscarinic acetylcholine receptor antagonists/anticholinergic

Hyoscine () Advanced cancer, vestibular SL: 200-400 mcg q4-8 h Dry mouth, constipation, , mechanisms SC: 200-400 mcg q4-6 h urinary retention, blurred Cont. SC infusion: vision, agitation, onset of 80-120 mcg/d action of 24 h Transdermal: 500-1500 mcg q72 h

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TABLE Antinausea Agents for Consideration in End-of-Life Care, Continued Adverse Effects/ Antinausea Agent Indications Suggested Regimen Contraindications Other agents

Anxiolytics Anxiety PO/IV: 0.5-1 mg q6-24 h Not FDA approved as antiemetic

Corticosteroids Chemotherapy- and PO/IV: 2-4 mg q6-24 h Infection risk, insomnia, anxiety, Dexamethasone radiation-induced nausea, euphoria, perirectal burning advanced cancer, increased (IV route), hyperglycemia , malignant bowel obstruction

Sandostatin analogues Malignant bowel obstruction, SC: 100-150 mg q8 h Pain at injection site Octreotide (Sandostatin intractable vomiting Cont. IV infusion: 0.2-0.9 mg/d Reduces peristalsis, secretions, 50 mg/mL) IM depot: 20-30 mg q3-4 wk dose reduced with renal, hepatic impairment

Abbreviations: Cont, continuous; EPS, extrapyramidal symptoms; FDA, US Food and Drug Administration; IM, intramuscular; IV, intravenous; ODT, oral dissolving tablet; PO, oral; SC, subcutaneous; SL, sublingual.2,3,5,16

of opioid-related nausea and prolonged nausea that can hydroxyzine especially should be used with caution in the occur with serotonergic syndromes such as renal failure.3,26 elderly population.2,3,14,18 Palliative radiation therapy (RT), particularly when de- Cyclizine, having greater antimuscarinic activity, is more livered in a single fraction, may be appropriate at the end effective at reducing mucosal secretions, making it theoret- of life to alleviate symptoms from conditions such as brain ically appropriate in the setting of bowel obstruction.5,18 and bone metastases.27,28 However, nausea and vomiting Although current guidelines support the use of cyclizine are common adverse effects of RT, and rates of nausea in in the palliative care population, there is limited evidence this population continue to be high despite antiemetic pro- to back these recommendations.5,15 Of note, cyclizine can- phylaxis.29 The use of other antiemetics such as the NK-1 not be used with metoclopramide because of competition antagonists and corticosteroids, along with serotonin an- for the same set of receptors.3,15 tagonists, has been found to improve the management of nausea in patients receiving moderately emetogenic RT for bone metastases.30,31 Scopolamine is an anticholinergic agent that can be used In patients at the end of life with nausea not caused by for a range of indications including nausea resulting from RT, serotonin antagonists are used predominantly as increased intracranial pressure, intestinal obstruction, second- or third-line agents because their clinical efficacy and oropharyngeal secretions. This drug works both cen- plateaus over time and they tend to be more expen- trally in the VC and peripherally on the muscarinic recep- sive.3,14,16 When nausea is associated with vomiting, the tors.2,3,14 Transdermal scopolamine allows delivery of oral disintegrating tablet version of ondansetron or the medication over a period of 3 days, but it may not be transdermal patch version of granisetron may be consid- appropriate for acute management because it can take ered. Regardless of the delivery method, the use of seroto- about a day to realize therapeutic effects.2,26 Both the oral nin antagonists needs to be evaluated because they can and transdermal forms of scopolamine can be used alone exacerbate the prevalent symptom of constipation.15,16 or in combination with other antinausea agents.14

Antihistamines Other Agents Histamine antagonists include , hydroxy- The anxiolytic lorazepam, the corticosteroid dexametha- zine, and cyclizine. These agents block the histamine recep- sone, and the somatostatin analog octreotide can be tors in the vestibular nucleus, cerebral cortex, CTZ, and VC used independently or in combination with others listed and therefore are not only effective for movement-induced previously. Lorazepam is not approved by the US Food and nausea but also for nausea caused by increased intracra- Drug Administration as an antinausea or antiemetic agent, nial pressure and CTZ irritation, such as with opioids.3,5 but because it acts on the cortical structures to manage nau- All 3 drugs are sedating and have anticholinergic adverse sea related to anxiety, it can be effective for anticipatory effects including blurred vision, headaches, confusion, con- nausea.2,3,14 Dexamethasone works via the central cortico- stipation, and urinary retention; diphenhydramine and steroid receptors in a yet-unclear mechanism with variable

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efficacy.3 In practice, dexamethasone is seldom used as a incongruent with the goals of care at the end of life.14 In first-line therapy because of the increased risk for infection patients at a high risk for surgical complications, the endo- and sepsis and the need for tapering to minimize withdrawal scopic or radiological insertion of percutaneous venting symptoms and adrenal insufficiency.2,3,16 Although tempo- gastrostomy tubes and enteral stents may offer relief of nau- rarily effective in relieving increased intracranial pressure, sea and other symptoms associated with bowel obstruc- headaches, and nausea in patients with , dexameth- tions; however, these are not without their own risks asone is also thought to be inappropriate at the end of life including migration, perforation, and obstruction.14 Such because the withdrawal of steroids is not associated with interventions may be inconsistent with patient preferences an increase in symptom severity.32 Palliative care experts and goals of care. generally consider steroid use as potentially inappropri- Because oral or intravenous fluids of more than 1 L/d ate in the last days of life; in contrast, haloperidol, meto- may improve nausea, hydration can be a part of the treat- clopramide, and levomepromazine are deemed more ment regimen as long as the patient does not have pain, appropriate.33 abdominal distension, and vomitingVall symptoms Octreotide is not considered an antinausea agent, but indicative of bowel obstruction.14 Hypodermoclysis, a sim- it may help reduce nausea, vomiting, and pain in patients ple but underused method of administering hydration with complete bowel obstructions. Octreotide acts on via the subcutaneous route, has also been recommended somatostatin receptors in the brain, pituitary gland, and in the treatment of nausea near the end of life because it GI tract to reduce and gastrin secretion, in turn has several advantages over the intravenous route in- reducing GI secretions and peristalsis and decreasing ob- cluding less cost and lower risk for infection and blood structive symptoms.2,34 Octreotide may be more effective clots.14,36 than scopolamine.2 However, likely because of only low- Complementary and alternative therapies may be con- level evidence for its benefit in malignant bowel obstruc- sidered for the management of nausea, including relaxa- tion,34 current consensus guidelines recommend that tion, imagery, distraction, and self-hypnosis; integrative octreotide be used with another antiemetic to manage nau- therapies such as acupuncture, acupressure, , and sea and vomiting in advanced cancer patients with malig- aromatherapy might also be suggested.2 Many of these nant bowel obstruction.5 therapies have primarily been studied in patients who ex- In summary, selecting an antinausea agent at the end perience nausea and vomiting after chemotherapy37,38; of life is dependent on the likely cause of nausea; an un- there is little evidence that they relieve nausea from other derstanding of the related pathophysiology is essential. etiologies. Although the evidence for complementary ap- Generally, a single medication is optimized for therapeu- proaches in the management of nausea per se in patients tic effect at reducing nausea, before another agent from a at the end of life is not strong, providers may consider them different class is added.13,14 The provider must address especially if requested by patients. underlying reversible causes of nausea including consti- pation, dehydration, hypercalcemia, and adverse effects ROLE OF PROVIDERS IN TIMELY from medications. For example, a bowel program must be ASSESSMENT AND DISCUSSIONS initiated when an opioid is prescribed. ABOUT PREFERENCES Nonpharmacologic Treatments The multifactorial nature of nausea and its prevalence at Although pharmacological interventions are often the first- the end of life, as well the lack of well-designed studies line approach to manage nausea, some nonpharmacological in the end-of-life population about management of this interventions may help alleviate this symptom. For exam- symptom, are clear. Added to these challenges are inad- ple, if certain sounds, smells, sights, foods, and motion ex- equate assessment of nausea, the use of antinausea med- acerbate nausea, these should be avoided.2 Guidelines ications that are inappropriate, and late referral to hospice. from the National Comprehensive Cancer Network suggest However, admission to hospice in itself should not be palliative RT to the brain to relieve nausea caused by brain viewed as a magic bullet. A recent longitudinal cohort study metastases and referral to mental health providers for pa- of more than 149 000 Medicare beneficiaries served by tients with suspected psychogenic causes of nausea.35 577 hospices led to the finding of variations in quality of Interventions including surgery for nausea caused by care between hospices that affected where patients died bowel obstruction tend not to yield significant gains for and whether they received intensive therapy at the end patients near the end of life regardless of the type of sur- of life.39 When patients expressed their preference regard- gical technique used or position of obstruction.14 Particularly ing site of death, a significant reduction of emergency de- in patients with multiple obstructions, poorer performance partment visits and hospitalization was noted; likewise, status related to age, metastases, ascites, and cachexia, such more frequently monitored symptoms led to a reduction invasive methods may in fact result in painful complications in intensive medical care.

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Information sharing can be particularly helpful in re- 14. von Gunten CF, Gafford E. Treatment of non-pain-related symp- ducing distress and increasing the control patients and toms. Cancer J. 2013;19(5):397-404. families experience. Early on in the palliative care or hos- 15. Neoh K, Adkinson L, Montgomery V, Hurlow A. Management of nausea and vomiting in palliative care. Br J Hosp Med (Lond). pice trajectory, the provider should provide information on 2014;75(7):391-392. recognizing the signs of nausea and associated symptoms, 16. Hawkins R, Lynch MT. Nausea and vomiting. In: Dahlin C, Lynch how and when to give/take medications, adverse effects to MT, eds. Core Curriculum for the Advanced Practice Hospice and watch out for, and what to do if current management is in- Palliative Registered Nurse. 2nd ed. Pittsburg, PA: Hospice and 2 Palliative Nurses Association; 2013. adequate. Having a plan and someone with experience 17. Babic T, Browning KN. The role of vagal neurocircuits in the and knowledge to turn to for guidance may reduce the regulation of nausea and vomiting. Eur J Pharmacol. 2014;722: of helplessness that patients and families may expe- 38-47. rience and empower them at a time when such support is 18. Lefkowits C, Solomon C. Palliative care in obstetrics and gynecology. Obstet Gynecol. 2016;128(6):1403-1420. most required. 19. Murray-Brown F, Dorman S. Haloperidol for the treatment of nausea The relative scarcity of evidence regarding the man- and vomiting in palliative care patients. Cochrane Database Syst agement of nausea in the end-of-life population has led Rev. 2015;(11):CD006271. to management practices that may not be adequate in con- 20. Cox L, Darvill E, Dorman S. Levomepromazine for nausea and vomiting in palliative care. Cochrane Database Syst Rev. 2015; trolling this common and troublesome symptom. Although (11):CD009420. it is understandably challenging to perform RCTs in this 21. Kaneishi K, Kawabata M, Morita T. Olanzapine for the relief vulnerable patient population, larger, well-designed con- of nausea in patients with advanced cancer and incomplete trolled studies that compare different agents may offer bowel obstruction. J Pain Symptom Manage. 2012;44(4): 604-607. stronger evidence about treatment options, leading to im- 22. MacKintosh D. Olanzapine in the management of difficult to proved outcomes. control nausea and vomiting in a palliative care population: a case series. J Palliat Med. 2016;19(1):87-90. 23. Atkinson SR. Olanzapine for intractable nausea and vomiting in References palliative care patients not receiving chemotherapy. JPalliat 1. Smith HS, Smith EJ, Smith AR. Pathophysiology of nausea and Med. 2014;17(5):503-504. vomiting in palliative medicine. Ann Palliat Med. 2012;1(2):87-93. 24. Matsumoto K, Kimura S, Takahashi K, et al. Pharmaceutical 2. Lynch M. Nausea and vomiting. 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Aprepitant and granisetron 8. Napadow V, Sheehan JD, Kim J, et al. The brain circuitry underlying for the prophylaxis of radiotherapy-induced nausea and the temporal evolution of nausea in humans. Cereb Cortex.2013; vomiting after moderately emetogenic radiotherapy for bone 23(4):806-813. metastases: a prospective pilot study. Curr Oncol. 2014;21(6): 9. DeMaagd G, Philip A. Parkinson"s disease and its management: e760-e767. part 5: treatment of nonmotor complications. PT. 2015;40(12): 31. Li WS, van der Velden JM, Ganesh V, et al. Prophylaxis of radiation- 838-846. induced nausea and vomiting: a systematic review and meta- 10. Dwyer LL, Lau DT, Shega JW. Medications that older adults in analysis of randomized controlled trials. Ann Palliat Med. 2017; hospice care in the united states take, 2007. J Am Geriatr Soc. 6(2):104-117. 2015;63(11):2282-2289. 32. Koekkoek JA, Chang S, Taphoorn MJ. Palliative care at the 11. Evans TH, Schiller LR. Chronic vestibular dysfunction as an unap- end-of-life in glioma patients. Handb Clin Neurol. 2016;134: preciated cause of chronic nausea and vomiting. Proc (Bayl Univ 315-326. Med Cent). 2012;25(3):214-217. 33. Raijmakers NJ, van Zuylen L, Furst CJ, et al. Variation in medi- 12. Shimada A, Mori I, Maeda I, et al. Physicians" attitude toward cation use in cancer patients at the end of life: a cross-sectional recurrent hypercalcemia in terminally ill cancer patients. Support analysis. Support Care Cancer. 2013;21(4):1003-1011. Care Cancer. 2015;23(1):177-183. 34. Obita GP, Boland EG, Currow DC, Johnson MJ, Boland JW. 13. Kreher M. Symptom control at the end of life. Med Clin North Somatostatin analogues compared with placebo and other Am. 2016;100(5):1111-1122. pharmacologic agents in the management of symptoms of

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inoperable malignant bowel obstruction: a systematic review. J tive overview of reviews. Support Care Cancer. 2013;21(10): Pain Symptom Manage. 2016;52(6):901.e1. 919.e1. 2913-2923. 35. Levy M, Smith T, Alvarez-Perez A, et al. Palliative care version 1.2016. 38. Wu X, Chung VC, Hui EP, et al. Effectiveness of acupuncture J Natl Compr Canc Netw. 2016;14(1):82-113. and related therapies for palliative care of cancer: overview of 36. Bruno VG. Hypodermoclysis: a literature review to assist in systematic reviews. Sci Rep. 2015;5:16776. clinical practice. Einstein (Sao Paulo). 2015;13(1):122-128. 39. Aldridge MD, Epstein AJ, Brody AA, Lee EJ, Cherlin E, Bradley 37. Towler P, Molassiotis A, Brearley SG. What is the evidence for EH. The impact of reported hospice preferred practices on the use of acupuncture as an intervention for symptom man- hospital utilization at the end of life. Med Care. 2016;54(7): agement in cancer supportive and palliative care: an integra- 657-663.

For 6 additional continuing education articles related to nausea and vomiting, go to NursingCenter.com/CE.

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