Women's Health and Education Center (WHEC)

Gynecologic Oncology

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End-of-Life Care: Symptom Management (Part 1)

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Pain, fatigue and depression comprise a common triad of symptoms, especially at the end of life. Cluster analysis has shown that fatigue is often part of a cluster of symptoms that includes pain, sleep disturbances and anxiety/depression. Among patients with life-limiting disease, physical symptoms have been the cause of the most distress. The presence of multiple symptoms can create challenges in identifying causes, as many symptoms are intricately linked with others, including symptoms in the psychosocial domain. In addition to limited guidance for symptom management, a lack of objective measures for assessment makes the identification of symptoms a challenge. To help ensure that patient’s physical distress is alleviated, when clinicians ask patients about the presence and severity of symptoms, they should also ask which symptom is most troublesome. Although asking open-ended questions about symptoms is helpful, systematic assessment of symptoms is also necessary. It has been recommended that physical assessment be carried out according to symptoms and function rather than thorough a traditional systems approach. An important distinction of palliative care is the focus on dimensions other than the physical. Symptoms are accompanied by the patient’s thoughts and feelings and as such, non-pharmacologic strategies should be used to address the sensory, cognitive, affective and functional components. The healthcare team should talk to the patient and family about priorities for pharmacologic versus non-pharmacologic treatments. As research expands in the field of palliative care, other innovative strategies are becoming scientifically validated. For example, music therapy has a positive effect on many symptoms, including pain, physical discomfort, fatigue, anxiety, mood, spirituality, and quality of life. Optimum treatment of symptoms involves comprehensive assessment and use of drug and non-drug interventions.

The purpose of this document is the best management of symptoms in end-of-life situations. Before initiating a symptom management approach, pharmacologic or non-pharmacologic, clinicians should allow patients time to express their thoughts and concerns. This simple step has led to better outcomes and when carried out in a supportive environment, has been almost as effective as more advanced techniques. Continual reassessment of symptoms is necessary to ensure adequate management of symptoms. It may be helpful for patients or a family member to keep a pain or symptom diary to note which measures have or have not provided relief and the duration of relief. This information will help clinicians determine the efficacy of specific therapeutic options and modify the treatment plan as necessary. The discussion of interventions in this document focuses on the care of adults. This document discusses the symptoms: Fatigue and Weakness; Dyspnea; Constipation; Nausea and Vomiting.

Symptoms Common at the End-of-Life

Similar to pain, other physical and psychological symptoms create suffering and distress. Psychosocial intervention is key to complement pharmacologic strategies. In addition, the use of chaplains, social workers and psychologists is necessary to address suffering. Reimbursement and other financial concerns may be important factors for some families and should be considered in the overall care plan. Therefore, expensive diagnostic tests should be conducted only if the benefits outweigh the family or patient’s financial burden. Criteria for ordering diagnostic tests:

  • Each test ordered should help determine an intervention;
  • If no change in management will result, the test should be questioned for its appropriateness.

Functional Ability: fatigue, immobility, pathological fractures, spinal cord compression, weakness;

Gastrointestinal (GI) Function: anorexia, nausea/vomiting, dysphagia, weight loss, unpleasant taste, ascites;

Bladder Function: incontinence, changes in function or control, bladder spasms;

Bowel Function: constipation, diarrhea, loss of function or control;

Breathing: dyspnea, cough/congestion/rattles, hiccups, altered breathing patterns;

Cognition: insomnia, confusion/dementia/delirium, memory changes;

Mood: depression, anxiety;

Skin Integrity Issues: decubitus, mucositis, candidiasis, pruritis, edema, ascites, hemorrhage/blood loss, herpes zoster;

Other: fever, diaphoresis.


Fatigue can be defined as, “a subjective perception and/or experience related to disease, emotional state and/or treatment. This sensation is multidimensional, is not easily relieved by rest, and has a profound impact on the dimensions of quality of life (QOL) including physical, psychological, social and spiritual well-being. Fatigue is influenced by the cultural context of the individual and is associated with a reduced capacity to carry out expected or required daily activities” (1). Fatigue associated with life-limiting diseases is further defined by its disproportionate relation to recent activity and the lack of recovery with additional sleep (2). Together, persistent fatigue and weakness have a significant impact on the quality of life by negatively affecting functional status, interfering with normal activities, and contributing to emotional distress (3). Fatigue may also cause distress for a patient’s family members, who may interpret this symptom as a sign of the patient “giving up.” As is the case with pain, fatigue is under-reported, under-diagnosed, and under-treated (3). Studies have indicated that approximately half of patients do not report fatigue to their healthcare team (4). Pain, fatigue, and depression comprise a common triad of symptoms, especially at the end of life (4). Cluster analysis has shown that fatigue is often part of a cluster of symptoms that includes pain, sleep disturbances, and anxiety/depression (4). Analysis of 25 symptoms among 922 patients with advanced cancer demonstrated seven clusters. One of those clusters, referred to as the fatigue/anorexia-cachexia cluster, was composed of easy fatigue, weakness, lack of energy, anorexia, early satiety, weight loss, dry mouth, and taste changes (5).

A sense of fatigue and weakness is one of the most common symptoms at the end of life, and patients often consider this symptom to be more troublesome than pain (6). The prevalence of fatigue has been reported to range from 12% to 97% of patients with life-limiting diseases, and the prevalence is fairly consistent across disease settings (7). Fatigue has often been reported to be the symptom that causes patients the most distress (8). Among the most common contributors to fatigue at the end of life are medications, cognitive impairment, malnutrition, direct tumor effects on energy consumption and supply, infection, fluid and electrolyte imbalance, dyspnea, and organ dysfunction.

Ensuring adequate management of pain, dyspnea, and other symptoms is a primary way to help prevent fatigue. The patient should also be advised to conserve energy as much as possible and assistive devices (walkers, canes) may help in this regard. Giving the patient “permission” to rest, encouraging a normal sleep cycle and regular exercise, and managing sleep disturbances can also be of benefit (1),(8).

Assessing fatigue can be a challenge, but as with pain, the patient’s report of how he or she is feeling is the gold standard in the assessment. For patients who speak a language other than English, questions about fatigue should include such words and phrases as “tired,” “weak,” and “lack of energy,” as the word “fatigue” may translate differently in some languages (9). Several tools are available to assess fatigue, but because it usually occurs in a cluster of symptoms, many of these tools are multidimensional instruments, often involving several questions, which can be impractical (9). An easy-to-use instrument is the Brief Fatigue Inventory, which includes four items that ask the patient to rate the severity of fatigue on a scale of 0 (no fatigue) to 10 (“as bad as you can imagine”) (10). The patient is asked to consider the current level of fatigue as well as fatigue experienced within the past 24 hours and to indicate the degree to which fatigue has interfered with activities, mood, relations with other people, and enjoyment of life. Assessment should also include a focused history-taking and evaluation of treatable contributing factors. The history can help in determining whether fatigue and weakness are related to progression or recurrence of disease, and a systems review will help to identify comorbidities that may be playing a role. It is also important to evaluate the patient’s medications list to determine if fatigue or weakness is an adverse effect of a particular drug. A hematocrit and hemoglobin level can demonstrate if anemia is the cause. Talking to the patient about his or her emotional and spiritual health is also essential (8).

Little evidence is available to support guidelines for the management of fatigue during the end of life. Most of the research on non-pharmacologic and pharmacologic treatments has been evaluated in patients during active cancer treatment or long-term follow-up after cancer treatment; few studies have been carried out in the palliative care setting for other life-limiting diseases. The symptomatic treatment of fatigue has been suggested to be more effective than causal treatment (11). Symptomatic treatment focuses primarily on non-pharmacologic approaches and encompasses physical and psychosocial interventions (12). Fatigue may provide a protective effect for patients in the last days or hours of life (12). As such, aggressive treatment of fatigue should not extend to that period, allowing the patient more comfort. Most patients will try to manage fatigue by resting and/or sleeping more often, and many healthcare professionals will also recommend this strategy. However, additional rest and/or sleep usually do not restore energy in patients who have fatigue related to a life-limiting disease (12). Continued lack of exercise may even promote fatigue (12). Aerobic exercise has been found to alleviate fatigue, although much of the research in this area has been conducted in cancer survivors (13). Small studies of patients receiving palliative care have shown that exercise was beneficial in managing fatigue among patients receiving palliative care (13). Several other non-pharmacologic strategies have been recommended.

Clinicians should talk to the patient and family about the importance of the patient conserving energy through a variety of measures. The patient should be encouraged to adjust daily activities to correspond to times of peak energy, to set priorities for activities, to follow a normal wake-sleep cycle, and to use assistive devices (14). Physical and occupational therapists can help identify assistive devices that will help the patient and can provide instruction in their use. These therapists may also be able to develop programs that will help relieve fatigue. With guidance from the healthcare team, the family and patient can work together to develop a plan that helps the patient enjoy as many favorite activities as possible. Counseling about setting realistic goals for activities and function may also help patients and family members adapt to new daily routines.

Summary of non-pharmacologic management of fatigue: Conserving energy; set priorities for activities; schedule activities for times of peak energy; use assistive devices; delegate less important tasks to others; limiting duration of naps; structuring a daily routine; distraction; reading; socializing; games; music; sleep therapy; sleep restriction; sleep hygiene; stimulus control; nutrition counseling; aerobic exercises; physical and/or occupational therapy; cognitive and behavioral therapy; stress management and relaxation

Treatment of fatigue should begin with management of a contributing factor, if one has been identified. When medications are the underlying cause of the fatigue, nonessential medications should be discontinued, and changing medications or the time of dosing may reduce tiredness during the day. Erythropoietin (Epogen) and darbepoetin (Procrit) have shown benefit for fatigue related to anemia in patients with cancer, human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS), or end-stage renal disease (15). However, it may be four to six weeks before treatment is effective, and the cost of erythropoietin therapy is high (15). However, safety concerns led the U.S. Food and Drug Administration (FDA) to require a boxed warning on the label of erythropoiesis-stimulating agents regarding the increased risk of several adverse events (death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence) among people with chronic kidney disease or cancer. The FDA recommends using the lowest dose sufficient to avoid red blood cell transfusion.

A trial of a tricyclic antidepressant may be appropriate for patients who have fatigue related to sleep disturbances (8). Bupropion, an atypical antidepressant, may also be beneficial for treating fatigue related to depression (16). Studies of medications for the symptomatic treatment of fatigue in the palliative care setting have focused on psychostimulant agents, such as methylphenidate, modafinil, pemoline, and donazepil. Methylphenidate and modafinil have received greater attention than pemoline and donazepil, and the drugs have been studied in different populations (17). None of the drugs has been compared directly with another. Pharmacologic treatment of fatigue should be undertaken only after potential causes of fatigue have been ruled out (17).

When a pharmacologic agent is deemed appropriate, the first-line option is generally methylphenidate (18). A systematic review found that methylphenidate was significantly more effective than placebo for the treatment of cancer-related fatigue (18). This drug has also been reported to be effective for the treatment of fatigue in patients with AIDS and for opioid-induced sedation. An optimal dose has not been defined, but an initial dose of 5–10 mg (given in the morning) has been used, with the dose titrated to 40–60 mg per day (given once in the morning and once at midday). Among the side effects of methylphenidate are nervousness, jitteriness, agitation, arrhythmia, and tachycardia. Modafinil has been evaluated primarily in patients with advanced neurologic diseases, and some findings indicate that the drug may be useful as a treatment option for fatigue in patients receiving palliative care (17),(18). The initial recommended dose is 200 mg per day, which can be titrated to 400 mg per day (19). Major side effects have included agitation, nervousness, sleep disturbances, nausea, and diarrhea. Pemoline has had some benefit for patients with AIDS, but its use is limited by the potential for liver toxicity (19). The findings of one uncontrolled study indicated that donazepil, which is approved for the symptomatic treatment of Alzheimer’s disease, was effective for opioid-induced sedation in patients with advanced cancer.


Dyspnea is defined as a distressing shortness of breath and is frequently called breathlessness. The experience of dyspnea can be extremely frightening. Dyspnea, like pain, is multidimensional in nature, with not only physical elements but also affective components, which are shaped by previous experience. Dyspnea is a subjective sense of breathlessness (shortness of breath) and ranges from experiencing breathlessness on exertion to severe shortness of breath for longer periods of time. Patients may describe dyspnea as “smothering,” “suffocating,” or “drowning.” Dyspnea can have a substantial impact on a patient’s quality of life, not only causing distress for both patients and their families but also restricting the patient’s activities.

The prevalence of dyspnea among adults with life-limiting disease has varied from 10% to 95%, with the highest rates among patients with chronic obstructive pulmonary disease (COPD) and heart failure (20). Psychologic conditions play a role in the development and exacerbation of dyspnea. A study of individuals with lung cancer at the end of life showed that dyspnea was correlated with anxiety, depression, fatigue, and cough and was negatively correlated with coping capacity. Physical causes of dyspnea include pleural effusion, pneumonia, pulmonary embolism, bronchospasm, ischemia, anemia, and ascites.

Measures to reduce anxiety can help to prevent dyspnea or reduce its severity. In addition, patients with heart failure or lung diseases should be advised to conserve energy.

The American College of Physicians recommends that clinicians regularly assess dyspnea in patients receiving end-of-life care (20). However, dyspnea is a poorly understood symptom, and no diagnostic test reliably confirms its presence. Furthermore, research has shown that measured parameters such as respiratory rate, partial pressure of oxygen, blood gases, and pulse oximetry do not always correlate with patients’ perceptions of their degree of shortness of breath (21). Thus, the patient’s self-report is the only reliable tool for assessing dyspnea. Patients can rate the severity of the symptom on a numerical scale similar to a pain scale. The modified Borg scale, which includes a vertical axis labeled 1 to 10 with corresponding verbal descriptions of intensity (weak, moderate, and strong), is an easy-to-use, reproducible tool for assessing dyspnea, and it correlates well with dyspnea during exercise testing (21). In talking to a patient about dyspnea, clinicians should ask about other symptoms, especially concurrent chest pain, and about the activities that cause dyspnea. Questions should also be focused on assessing the patient’s psychologic status.

Physical assessment of the patient should include evaluation of breath sounds, heart rate, respiratory rate, jugular pressure, and functional status. When warranted, such diagnostic tests as chest x-ray, electrocardiography, or pulmonary function studies can help determine an underlying cause to the dyspnea. But the risk-benefit of these tests should be considered, as should the prognosis and the patient’s wishes for such testing.

Prompt management of dyspnea is appropriate for all patients, regardless of disease status. However, the cause of the dyspnea may or may not be responsive to treatment, and the burden of treatment may outweigh the benefit. The outcome is optimal when the underlying cause can be treated. Treatment options for dyspnea can include supplemental oxygen, several non-pharmacologic interventions, and medications. Treatment with oxygen alone may not alleviate dyspnea. Hypoxemia may or may not be a factor in its development, and oxygen has been found to be of equal benefit for patients with or without hypoxemia. Strong evidence supports the use of oxygen and pulmonary rehabilitation for patients with chronic obstructive pulmonary disease (COPD), and the American College of Physicians recommends that supplemental oxygen be considered for individuals with advanced COPD who have hypoxemia. However, the evidence for using oxygen for symptomatic relief of dyspnea is nonexistent for patients with heart failure and is weak for patients with cancer. Some non-pharmacologic interventions may actually be more effective than oxygen; for example, a fan that blows cool air on the patient’s face has been found to be more effective than a 100% non-rebreather face mask in relieving dyspnea. Other factors to consider are comfort and cost; many patients find a nasal cannula to be uncomfortable, and the long-term use of oxygen can be expensive and not reimbursable by all insurances.

Other non-pharmacologic approaches are targeted to promoting better air exchange, addressing emotional factors, and creating a calm environment. Use of a fan and maintaining cooler temperatures can help relieve a sense of breathlessness. Repositioning the patient by elevating the head of the bed or moving him or her to one side can help promote better exchange of air, and pursed lip breathing can help the patient feel more in control of the pace and depth of respiration. When stress is deemed to be a contributing factor, relaxation techniques, distraction, massage, and prayer may be of benefit. In addition, the clinician should refer the patient and/or the family for counseling on family, legal, spiritual, or financial issues, as appropriate. Ways to create a calm environment free of stimulants include:

  • Limit the number of people in the patient’s room;
  • Minimize the amount of healthcare equipment and noise;
  • Open windows;
  • Position the bed so the patient can see outside;
  • Eliminate environmental irritants (e.g., smoke and pet dander);
  • Maintain sufficient air humidity;
  • Play quiet, soothing music.

  Pharmacologic Management (22)

Indication Drug Class Drugs
Anxiety Benzodiazepines Lorazepam
Fluid Overload Diuretics Furosemide
Asthma, COPD, airway
Unknown Opioids Morphine
Sputum production Expectorants Guaifenesin
Increased secretions Anticholinergics Atropine
Postnasal drip Antihistamines,

Oxygen use in non-hypoxemic patients may have limited benefit. Studies evaluating oxygen therapy in dyspnea vary in their findings. The need for oxygen for dyspnea at end of life is dependent on the patient’s perception of the need, and their perception of its effect. Many practitioners believe that oxygen is not necessary near the end of life, that it can actually cause discomfort, and that comfort can be better achieved using morphine. Indeed, many patients with dyspnea near death frequently remove their oxygen, and can be kept comfortable without it. It is imperative, however, that patients with dyspnea who do not promptly respond to morphine (or other medications), be given a trail dose of oxygen to assess its effect, regardless of whether or not they are hypoxemic. Fans, open windows and air conditioners that circulate air have been reported to be helpful in the relief of dyspnea. Similarly, cold air directed against the cheek may reduce the perception of breathlessness. Elevation of the head of the bed and the ability of the patient to sit in a forward and upright position reduces choking sensations and promotes expansion of lungs. Placing the patient’s arms on pillows may promote air exchange. Energy conservation is also important to reduce breathlessness and fatigue. It is important that the patient and family are educated regarding the various techniques that may reduce dyspnea. Education regarding the use of cognitive-behavioral, interpersonal and complementary strategies will help give the patient a sense of control and decrease anxiety. Presence and reassurance are also vital.


Constipation is defined as the infrequent passage of stool. Associated symptoms may include rectal pressure, straining, cramps, distension, and/or the sensation of bloating. Constipation is a frequent symptom in patients at the end of life. While constipation occurs in approximately 10% of the general population, its incidence can be as high as 50% to 78% in the ill adults (23). Issues of personal privacy often lead to a reluctance of patients to discuss constipation, so clinicians and other healthcare professionals must initiate the discussion and talk honestly about what to expect and measures to prevent and manage the symptom.

The prevalence of constipation among adults with life-limiting disease ranges from 8% to 70%, and constipation occurs in almost all patients taking opioids (23). Aside from opioids, many other prescribed drugs can contribute to constipation, including tricyclic antidepressants, anticholinergic agents, and antihypertensives (23). Additional factors that may contribute to constipation are diverticuli, inflammatory bowel disease, metabolic conditions (hypercalcemia, hypokalemia, uremia), cerebrovascular disease, diabetes, hypothyroidism, and dehydration (23). For patients with cancer, constipation may be directly due to tumor involvement that causes intestinal obstruction. A diet low in fiber and decreased physical activity also increase the likelihood of constipation.

Prevention of constipation is key, as prophylaxis is more effective than treatment. As such, it is crucial to initiate a prophylactic bowel regimen when treatment with opioids begins [39]. A recommended regimen is a stimulant laxative (such as senna) and a stool softener (such as docusate), as indicated (24). The doses of these drugs can be titrated upward to obtain one soft bowel movement every one to two days. A prophylactic regimen should also be considered when other constipation-causing drugs are prescribed. Many non-pharmacologic approaches are helpful, and patients should be encouraged to plan a diet with adequate fiber, to increase fluid intake, and to engage in physical activity, as appropriate. Family members should be asked to help the patient comply with these measures. Ensuring that the patient has sufficient privacy is also helpful (24).

Several assessment tools for constipation have been useful in research but not in clinical practice (25). Assessment should include a review of the list of medications, a history of bowel habits, and abdominal and rectal examination. In addition to checking the list of prescribed medications to determine if constipation is a side effect, the physician should ask the patient about over-the-counter drugs and herbal remedies, as constipation can be a consequence of aluminum-containing antacids, ibuprofen, iron supplements, anti-diarrhea drugs, antihistamines, mulberry, and flax. A detailed history of bowel habits helps to establish what is considered normal for the individual patient. The patient should be asked about frequency of stool, the appearance and consistency of stools, use of bowel medications, and previous occurrence of constipation. In general, physical examination of the abdomen for tenderness, distention, and bowel sounds can rule out intestinal obstruction as the cause of constipation. A rectal examination can identify the presence of stool, fecal impaction, or tumor. Imaging of the abdomen (by plain x-ray or computerized tomography) may be appropriate to confirm the presence of obstruction. Consideration of the patient’s prognosis and preferences for care should be factored into a decision to carry out diagnostic testing.

As with prevention, the goal of treatment should be one soft bowel movement every one to two days (26). Data from randomized controlled trials are insufficient for recommending treatment of constipation in the palliative care setting. There are several choices of laxatives, including stimulant laxatives, osmotic laxatives, stool softeners, and prokinetic agents (see table below). Minimal differences in effectiveness have been found among individual laxatives, and the choice of a laxative should be made on an individual basis. In general, the use of a stimulant laxative plus a stool softener is recommended. If constipation persists, bisacodyl (10–15 mg, two to three times daily) can be given to reach the goal of one non-forced bowel movement every one to two days. If constipation still persists, rectal bisacodyl, oral polyethylene glycol, lactulose, magnesium hydroxide, or magnesium citrate can be considered. A prokinetic agent (metoclopramide) can be used if gastroparesis is suspected.

  Pharmacologic Management of Constipation

Class of Drug Mechanism of Action Drugs Typical Dose Onset of Action
Irritate bowel and increase peristaltic activity Senna 1-2 tabs PO, at bedtime 8 to 12 hours
Bisacodyl 1-2 tabs, PO, at bedtime 6 to 12 hours
Draw water into bowel; stimulate peristalsis and increase bulk Lactulose 15-30 mL PO, 2 times per day 1 to 6 hours
Magnesium hydroxide 30-45 mL PO, 1 to 3 times per day 24 to 48 hours
Magnesium citrate 8 oz. PO, daily 24 to 72 hours
Stool softeners Facilitate dissolution of fat in water and increase content of stool Docusate 1-2 capsules or tablets PO, 1 to 2 times per day 24 to 72 hours
Prokinetic agents Increase peristaltic activity and stool movement Metoclopremide 10-20 mg PO/IV, every 6 hours 0.5 to 1 hour (PO)
1 to 3 min (IV)

  PO: orally; IV: intravenous

Non-pharmacologic interventions are important adjuncts to laxatives. Fluid intake, a diet high in fiber, and regular exercise are important contributors to improved bowel function (24),(25). These measures should be encouraged when the patient’s health and functional status allow. Patients and families should be informed that it is essential to increase fluid intake if the diet is high in fiber or if fiber supplements or bulk laxatives are taken. Without adequate fluid, constipation may be increased by these measures. Enemas may be helpful for patients with fecal impaction, but in general, this approach should be avoided.

In summary, patient complaints of constipation (or in some cases if defecation is <3 times a week); assess patient to confirm constipation and exclude malignant intestinal obstruction. Assess the causes and if correctable treatment of the causes. If it is not correctable – start the treatment of the constipation. First-line of treatment is with oral laxatives: combination of a softener (e.g. polyethylene glycol and electrolytes or lactulose) and a stimulant (e.g. senna or sodium picosulphate) according to patient needs (refer to prescribing instructions for recommendations) – if improvement of symptoms occurs, continue with regimen. If there is no improvement of symptoms, second-line of treatment: rectal suppository and enema (refer to prescribing table for options). Consider use of peripherally-specific opioid antagonist, e.g. methylnaltrexone, if patient is taking an opioid. Improvement of symptoms – continue with regimen. If no improvement of symptoms; third-line of treatment: manual evacuation. Consider use of a peripherally-specific opioid antagonist, e.g. methylnaltrexone, if patient taking an opioid. Non-pharmacologic interventions are important adjuncts to laxatives, and the interventions used as prophylaxis are recommended for ongoing management.


Nausea is the unpleasant sensation of feeling the need to vomit. It can occur alone or with vomiting, a neuromuscular reflex. Nausea and vomiting can exacerbate pain and contribute to insomnia, fatigue, anorexia, and asthenia. It can also limit activities and cause distress for the patient and family. Nausea is the result of stimulation of one of several pathways: the chemoreceptor trigger zone (located in the medulla), the cortex of the brain, the vestibulocochlear nerve, or the gastrointestinal tract (27).

Nausea alone affects approximately 6% to 68% of adults with life-limiting disease, and vomiting affects 40% (28). The rate of nausea and vomiting is highest among patients with cancer (27),(28). The cause of nausea and vomiting differs according to which pathway has been stimulated and is often multifactorial. Treatment of nausea and vomiting varies according to the cause.

  Causes of Nausea and Vomiting According to Pathway Stimulated

Pathway Stimulated Causes Class of Drugs for Treatment
Chemoreceptor trigger zone Metabolic disorders (hypercalcemia, hyponatremia, hepatic/renal failure) Dopamine antagonists, corticosteroids
Opioids Dopamine antagonists, anticholinergics
NSAIDs Dopamine antagonists, antihistamines
Cerebral metastases Dopamine antagonists, antihistamines
Cortex of brain Anxiety, increased intracranial pressure, five senses Anxiolytics, corticosteroids
Vestibulocochlear nerve Movement Anticholinergics, muscarinic acetylcholine receptor, antihistamine
Gastrointestinal tract Opioids, ileus, malignant bowel obstruction Prokinetic agents, dopamine antagonists, corticosteroids
Gastroesophageal reflux Antacids

  NSAIDs: non-steroidal anti-inflammatory drugs

The prevention of nausea and vomiting has focused on prophylactic treatment for patients receiving chemotherapy or radiation therapy for cancer. Because most patients at the end of life are not receiving anticancer treatment, these preventive measures will not be discussed here.

A careful review of the medication list, a detailed history, and a physical examination are essential for planning effective treatment. In talking with the patient, the clinician should ensure that the patient is actually experiencing nausea, as patients have used the term nausea to describe other feelings, such as pain, distention, abdominal discomfort, and early satiety (29). The clinician should ask about the onset of the nausea, how frequently it occurs, if there are precipitating factors, and if there is a relationship to food intake. It may be helpful to ask the patient to rate the intensity of nausea on a scale similar to a pain scale (a 10-point numerical scale). Because the cause of nausea and vomiting is often multifactorial, a multidimensional assessment is beneficial, with particular attention paid to such other symptoms as pain, appetite, fatigue, depression, and anxiety. The physical examination should include evaluation for signs of cachexia or malnutrition, assessment of the abdomen for evidence of bowel obstruction, increased bowel sounds, and abdominal distention. In addition, a neurologic examination should be done to determine if there are signs of increased intracranial pressure, papilledema, or autonomic insufficiency (29). Diagnostic testing may include laboratory studies to rule out metabolic disorders, renal impairment, or liver failure, or radiographs of the abdomen to determine if there is obstruction.

Evidence-based guidelines for the management of nausea and vomiting are lacking, and current treatment approaches involve using an antiemetic agent that targets the appropriate pathophysiologic pathway (29). Several classes of pharmacologic agents can be used to manage nausea and vomiting; the main classes of antiemetic agents are dopamine antagonists, prokinetic agents, antihistamines, anticholinergics, and serotonin antagonists (30). Dexamethasone and octreotide are also used, especially in bowel obstruction, and liquid antacids can be used for nausea and vomiting related to gastroesophageal reflux or other dysmotility of the upper gut (30). Non-specific nausea and vomiting should be treated with dopamine antagonists. Clinicians should consider adding a benzodiazepine if anxiety is thought to be a contributor to nausea and vomiting.

  Pharmacologic Management of Nausea and Vomiting

Drug Class Drug Typical Starting Dose Comments
Prokinetic agents Metoclopramide 10-20 mg PO, 4 times a day First choice for chronic nausea
Dopamine antagonists Haloperidol 0.5-2.0 mg PO/IV/SC, 2-4 times per day Useful with bowel obstruction
Prochlorperazine 10-20 mg PO or 5-10 mg IV, 3 to 4 times per day Useful when beginning opioid therapy
Droperidol 0.5-2.5 mg IV, 4 to 6 times per day  
Perphenazine 2-8 mg PO/IV, 4 times per day  
Antihistamines Promethazine 12.5-25 mg IV or 25 mg PO, 4 to 6 times per day  
Diphenhydramine 25-50 mg PO, 4 to 6 times per day  
Anticholinergics Scopolamine 1 patch per 72 hours Useful for vertigo
Glycopyrrolate 0.2 mg SC/IV, 4 to 6 times per day
Hyoscyamine 1-2 tablets or 1-2 tsp (elixir) PO, 6 times per day
Serotonin antagonists Ondansetron 4-8 mg PO, 2 to 3 times per day  
Granisetron 1 mg PO or 10 mcg/kg IV, 1 to 2 times per day  
Corticosteroids Dexamethasone 6-20 mg PO per day May increase the effects of other drugs

  PO: Orally; IV: intravenous; SC: subcutaneous

In addition to pharmacologic management of nausea and vomiting, other supportive approaches include maintenance of oral hygiene, regular baths to reduce unpleasant odors, and small meals at regular intervals. Cold foods may be better tolerated than hot foods because of decreased smells. Progressive relaxation and cognitive therapy (especially mental imagery) may be of benefit for nausea caused by stimulation of the cortical pathway. Hypnosis and acupuncture have demonstrated some success.

Early Implementation of Palliative Care

Patients with cancer experience many complex issues throughout the trajectory of the disease. These range from physical consequences of cancer and treatment to the psychological, social and spiritual issues associated with living with disease. An individualized, comprehensive, and interdisciplinary approach is needed to reduce patient suffering and ensure appropriate symptom management and support from the time of first diagnosis to end of live. Data from randomized clinical trials prove that patients provided with early palliative care can experience relief of symptoms and improvements in quality of life, mood, satisfaction, resource use, and advance care planning (31). Patients with advanced cancer and their families frequently experience a high burden of suffering regardless of whether the cancer can be cured or controlled. Suffering, in its many forms, is not limited to the last days of life but occurs throughout the course of the disease beginning at diagnosis. Furthermore, patient’s needs may vary across the different stages of the disease trajectory. Many patients with metastatic cancer can live for years after diagnosis, and patients with newly diagnosed advanced cancer often have a high symptom burden. With the growing incidence and prevalence of cancer and the number of patients who live with the consequences of the disease and treatment, a comprehensive but individualized approach is needed to ensure that all patients receive quality cancer care that includes symptom management and consideration of quality of life throughout the course of illness. Palliative care focuses on the relief of suffering in all its forms and on achieving the best possible quality of life for patients and their caregivers. The scope of palliative care varies across sites and locations, ranging from only end-of-life care to the management of symptoms and other distress across the full trajectory of disease from first diagnosis. The most recent definition of palliative care generally advocates a comprehensive, interdisciplinary approach from an early stage of the disease. The focus of palliative care is on the patient and the family, and it emphasizes the coordination of care across settings and providers.


Symptom management is an essential element in any care setting, requiring diligent ongoing assessment and evaluation of interventions. Side effects related to treatment of symptoms must be understood and treated. Fatigue assessment of the whole person remains paramount and includes the consideration of the body as well as the mind and spirit. Treatments for fatigue vary but may include both pharmacologic and non-pharmacologic treatments. When the science and art of palliative care are put into action, a person who faces death from a terminal illness need not suffer agony. The amount dyspnea present may not be related to the extent of disease. Currently, no tool exists other than patient self-report. It therefore helpful to ask about shortness of breath in relation to activities such as “walking at the same speed as someone of your age”, “stopping to catch your breath when walking upstairs,” or “eating”. It is important that the patient and family are educated regarding the various techniques that may reduce dyspnea. Much research is needed to evaluate pharmacologic treatments for dyspnea. Many practitioners believe that oxygen is not necessary near the end of life, that it can actually cause discomfort, and that comfort can be better achieved using morphine. Constipation may be a highly embarrassing issue for the patient and this situation can frequently evolve to a severe problem. Talking frankly and openly regarding this symptom and encouraging discussion helps prevent significant distress. Prevention is the key. The incidence of nausea and vomiting is quite common in advanced disease. Treatment of nausea is dictated by the presumed cause. Any underlying cause should be treated if possible. Interventions that have worked in the past may also be of benefit. Nausea and vomiting can be exceptionally frustrating, painful and exhausting for the patient and family. These symptoms clearly increase suffering and require immediate intervention in ensuring patient comfort.

Suggested Reading

End-of-Life Decision Making


End of Life Care: Pain Assessment and Management



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Published: 20 June 2013

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