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Overview of managing common non-pain symptoms in palliative care

Overview of managing common non-pain symptoms in palliative care
Literature review current through: Jan 2024.
This topic last updated: Dec 17, 2021.

INTRODUCTION — Most patients with a serious and/or life-threatening illness develop physical and psychosocial symptoms (figure 1) [1]. Appropriate treatment may alleviate, or even eliminate, the majority of symptoms (pain, dyspnea, nausea/vomiting, fatigue, etc) that arise in seriously ill patients. Referral to palliative care at an early stage of an advanced, serious, or life-threatening illness may reduce the symptom burden of patients and prepare family caregivers throughout the disease trajectory.

This topic will provide an overview of the management of common non-pain symptoms in adult palliative care patients [1]. Other related palliative care issues are discussed elsewhere:

(See "Overview of comprehensive patient assessment in palliative care".)

(See "Approach to symptom assessment in palliative care".)

(See "Cancer pain management with opioids: Optimizing analgesia".)

(See "Psychosocial issues in advanced illness".)

Much of the information presented in the following sections is derived from studies of patients with cancer, since this group has been studied more than any other group with advanced life-threatening illness. However, the principles are equally applicable to patients with other advanced life-limiting diseases, such as heart failure, dementia, chronic obstructive pulmonary disease (COPD), end-stage kidney disease (ESKD), and neuromuscular diseases such as amyotrophic lateral sclerosis (ALS). In fact, the prevalence and range of symptoms is remarkably the same across illnesses [2].

Symptom control issues that are unique to patients with heart failure and ESKD are discussed separately. (See "Palliative care for patients with advanced heart failure: Decision support and management of symptoms", section on 'Symptom management' and "Kidney palliative care: Principles, benefits, and core components", section on 'Terminal symptom management'.)

OVERVIEW

Challenges in symptom management — Symptom management of seriously ill patients can be complicated by several factors [3].

Malnutrition, low serum albumin, and decreased renal function may affect the pharmacokinetics of drugs used for symptom control. In addition, seriously ill patients are often frail and tolerate lower doses of drugs compared with other medically or psychiatrically ill patients.

Autonomic nervous system failure increases the risk of some side effects from opioids, tricyclic antidepressants, and phenothiazines, including constipation, dry mouth, nausea, urinary retention, and postural hypotension [4].

Cognitive impairment and use of opioids and other psychoactive drugs increase the risk for delirium or sedation.

Patients with metastatic brain involvement may have lower seizure thresholds, which influences the choice of medications.

Patients may already be on multiple medications or long-term opioid therapy, and the addition of more medications may result in polypharmacy and adverse effects.

Palliative care physicians are in short supply. Additional barriers that may limit access to palliative care services include geographic, socioeconomic, and cultural determinants [2].

Symptom assessment — Seriously ill patients often present with multiple symptoms and may be fatigued or distressed (figure 1). Thus, symptom assessment should be simplified.

Suggested tools – A number of tools have been developed that allow for repeated assessment and graphically display the intensity of different symptoms [5,6]. These tools utilize descriptions of intensity using numbers, words, colors, fingers of the hand, or circles of gradually increasing size. As an example, the Edmonton Symptom Assessment Scale (ESAS) (table 1), the revised ESAS (table 2), and the ESAS-FS, which contains financial and spiritual questions (table 3), are visual analogue scales that have been validated and utilized in multiple palliative care settings [7-9]. (See "Approach to symptom assessment in palliative care", section on 'Assessment and rating instruments for symptoms'.)

Periodic assessment – Periodic symptom reassessment is valuable for identifying or modifying treatment goals, monitoring the response to specific symptomatic interventions, and communicating between members of the health care team.

Prognostic significance – Some symptoms have prognostic significance. Poor performance status (table 4), a measure of a patient’s functional status, has been associated with a short survival in cancer patients. Other symptoms, such as weight loss, dyspnea, fatigue, and pain, have been also associated with poor prognosis in patients with advanced cancer [10,11]. In addition, certain clinical signs, such as pulselessness of the radial artery, respiration with mandibular movement, decreased urine output, Cheyne-Stokes breathing, and the “death rattle,” strongly indicate imminent death within three days [12]. (See "Approach to symptom assessment in palliative care", section on 'Performance status, symptoms, and prognosis' and "Palliative care: The last hours and days of life", section on 'Recognizing the dying patient'.)

Communication — Open and regular communication with both the patient and their loved ones is essential to achieve adequate symptom assessment and palliation. They may have severe emotional, spiritual, and sometimes financial distress. Financial difficulty among cancer patients is one of the most common types of toxicity and is often not assessed [13]. Information regarding findings, medications, and expected changes may need to be repeated several times by health care professionals. The use of graphs, question-prompt lists [14], written material, or audiocassettes of consults can increase recall and satisfaction with information [15]. Written materials such as brochures may improve communication between health care providers and patients as well as their families or caregivers [16,17]. Audiotapes and web-based videoconferencing technology can also be used to inform persons who cannot be present for face-to-face discussions.

Breaking bad news can be difficult for clinicians [18], who may have the perception that disclosing prognostic information will result in depression, loss of hope, and even decreased survival, which is unfounded. Patients who have had end-of-life discussions do not have higher rates of depression [19], loss of hope [20], or decreased survival [21]. Open, honest, and empathetic communication is critical to providing palliative care, and guidelines have been developed to assist clinicians with this important task [22-24]. Such efforts result in improved patient understanding and a more realistic estimate of survival, allowing patients to choose end-of-life care consistent with their own wishes and preferences [25]. In addition, biased, prejudicial, or culturally insensitive language, spoken or written, influences the provider’s perception of patients, negatively impacts treatment plans, and may be especially prevalent in patients with chronic pain, substance use disorder, or psychosocial issues such as body image [26].

Conferences with family or loved ones can facilitate communication between patients and their family caregivers. Results of prospective cohort trials in the intensive care unit setting have shown that such end-of-life conferences are associated with improvement in family/loved ones’ satisfaction, reduction in length of stay, and increased access to palliative care, without an increase in mortality [27,28]. (See "Communication in the ICU: Holding a meeting with families and caregivers".)

Understanding the patient’s values, preferences, and care goals in the context of a serious illness allows the clinician to align the care provided with what is most important to the patient. Discussing goals of care is a unique skill that should be separated conceptually from talking about prognosis or delivering bad news. A cluster randomized clinical trial of a communication intervention (the Serious Illness Care Program) failed to improve goal-concordant care or peacefulness at the end of life, although it did reduce patient depression and anxiety [29]. (See "Discussing goals of care" and "Advance care planning and advance directives".)

FATIGUE — Fatigue (asthenia, weakness) is a common symptom in palliative care, often with multiple contributing causes, although it may be underdiagnosed and undertreated. The major contributors to fatigue in patients with advanced cancer are outlined in the table (table 5). (See "Overview of fatigue in palliative care".)

Assessment – The cause of fatigue in palliative care patients is typically multifactorial. A comprehensive history and physical examination should be undertaken to ascertain the various organ systems affected by the underlying disease and the impact of fatigue on activities of daily living and quality of life, to search for potentially reversible or treatable contributory factors, and to direct the diagnostic workup. Review of all medications (both prescribed and over the counter, including complementary/alternative therapies) is important and may identify side effects or drug-drug interactions contributing to fatigue. (See "Approach to symptom assessment in palliative care", section on 'Fatigue'.)

Assessment of cancer related fatigue is also discussed elsewhere. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Clinical assessment'.)

Causes – Potentially reversible causes are provided in the table (table 6). Anemia is a particularly important contributor in patients undergoing cancer treatment, but it may not be a major factor at the end of life when other contributing factors, such as psychological symptoms, including anxiety and depression, as well as pain, cachexia, side effects of medications, physical inactivity, and infection, may play a greater role. The incidence of treatable hypothyroidism caused by cancer immunotherapy ranges from 4 to 13 percent, depending on the regimen [30]. (See "Overview of fatigue in palliative care", section on 'Etiology' and "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Main contributory factors'.)

Treatment – Management of fatigue includes aggressive treatment of reversible causes. If a specific cause cannot be identified, symptomatic management is appropriate. We counsel all patients as to coping strategies that conserve energy (table 7 and table 8).

There are limited data to support one pharmacologic approach to fatigue over any other [31]. The treatment of fatigue in palliative care is presented elsewhere. (See "Overview of fatigue in palliative care", section on 'Pharmacologic approaches' and "Cancer-related fatigue: Treatment", section on 'Interventions'.)

Nonpharmacologic approaches that may be helpful include moderate exercise (aerobic or resistant), possibly yoga, and cognitive-behavioral therapy. (See "Cancer-related fatigue: Treatment", section on 'Nonpharmacologic interventions' and "Overview of fatigue in palliative care", section on 'Nonpharmacologic approaches'.)

GASTROINTESTINAL SYMPTOMS

Nausea with or without vomiting — The most common causes of nausea and vomiting in palliative care patients are outlined in the table (table 9); most patients have two or more contributing factors. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Pathophysiology and etiology'.)

Patients with cancer — Treatment of reversible causes may include correction of metabolic abnormalities, aggressive bowel care, opioid rotation, and treatment of brain metastases. Specific causes include:

Gastroparesis – Early satiety and vomiting of food eaten several hours earlier suggests gastroparesis. Dietary modification and pharmacologic management (eg, with prokinetics such as metoclopramide) are discussed separately. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Gastroduodenal dysmotility' and "Gastroparesis: Etiology, clinical manifestations, and diagnosis" and "Treatment of gastroparesis".)

Malignant bowel obstruction – For cancer patients with an inoperable malignant bowel obstruction who are not candidates for a colonic stent (in whom a prokinetic agent would be contraindicated), medications can be used to control nausea. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Gastrointestinal obstruction' and "Management of small bowel obstruction in adults", section on 'Malignant obstruction'.)

Treatment related – The approach to nausea and emesis related to antineoplastic therapy (including breakthrough nausea and vomiting), opioid use, and radiotherapy is discussed separately. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Advanced cancer not receiving antitumor therapy' and "Prevention of chemotherapy-induced nausea and vomiting in adults" and "Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment" and "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Nausea and vomiting'.)

Symptomatic treatment for patients in whom a potentially reversible cause cannot be identified are discussed in detail elsewhere. (See "Assessment and management of nausea and vomiting in palliative care", section on 'No obvious cause'.)

Patients with non-cancer conditions — The assessment and management of nausea and vomiting in palliative care patients with diseases other than cancer is discussed in detail elsewhere. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Non-cancer conditions'.)

Constipation — The prevalence of constipation among palliative care populations varies widely from 18 to 90 percent [32-35]. A main source of this variance is how constipation is defined by patients and health care providers.

Risk factors for constipation in patients with a serious or life-threatening illness include advanced disease, older age, hypothyroidism, decreased physical activity, low-fiber diet, depression, and cognitive impairment. Medications that can cause or exacerbate constipation include opioids, acetaminophen, calcium channel blockers, diuretics, anticholinergic drugs, iron, serotonin antagonists, and chemotherapy (vinca alkaloids, thalidomide, vandetanib). There are also neural (eg, epidural spinal cord compression) and metabolic abnormalities (hypercalcemia and hypothyroidism) that may cause or contribute to constipation. Assessment of the palliative care patient with constipation is addressed separately. (See "Approach to symptom assessment in palliative care", section on 'Constipation'.)

Treatment of constipation includes addressing potentially reversible nonpharmacologic factors (table 10), stopping nonessential constipating medications, and pharmacologic interventions (laxative therapy). A Cochrane review of laxatives for constipation in patients receiving palliative care concluded that there was no evidence on whether individual laxatives were more effective than others or caused fewer adverse effects [36].

Laxative options include (table 11):

Senna, a peristaltic stimulant, which may be started initially and titrated (over-the-counter dosing range for sennosides 8.6 to 8.8 mg once daily [maximum 70 to 100 mg/day]) to soften daily bowel movements. Adding docusate does not improve outcomes [37,38].

Stimulant laxatives other than senna (bisacodyl, castor oil) may be helpful short-term agents. Because stimulant laxatives cause intestinal contractions, their use can be limited by abdominal cramps and pain. This can sometimes be avoided by dividing the total dose into smaller, more frequent doses [39,40].

Bulk-forming laxatives (cellulose, psyllium, bran), osmotic laxatives (lactulose, sorbitol, polyethylene glycol, magnesium hydroxide, magnesium citrate), and surfactants (docusate).

Enemas (eg, with soapsuds mineral oil, or milk and molasses) and/or rectal-based laxatives administered as suppositories, which may be indicated for distal fecal impaction or if a patient has not had bowel movement for three days or more. Digital stimulation and manual disimpaction may be necessary if fecal impaction is suspected. Due to discomfort associated with manual evacuations, these interventions should be considered a last resort and may require premedication with pain medications and/or anxiolytics [39].

Patients with refractory opioid-induced constipation may benefit from one of several opioid antagonists. These are discussed in detail elsewhere. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Management of refractory opioid-induced constipation'.)

Xerostomia — Xerostomia, the sensation of a dry mouth, is a common symptom affecting patients with a life-limiting illness. A dry mouth can alter taste and make it difficult for patients to eat and swallow [41]. Patients with dry mouth may be at higher risk of caries and secondary fungal infections. Causes include radiation therapy, chemotherapy, surgery (particularly for head and neck cancers), drugs (anticholinergics, antidepressants, opioids, anxiolytics, antihistamines, beta-blockers), dehydration, and oral infections [42]. (See "Approach to symptom assessment in palliative care", section on 'Dry mouth' and "Oral toxicity associated with systemic anticancer therapy", section on 'Xerostomia' and "Management and prevention of complications during initial treatment of head and neck cancer", section on 'Salivary gland damage and xerostomia'.)

Frequent oral hygiene is the first step in treating xerostomia. Rinsing with cold water, sucking on ice chips, and chewing sugarless gum to increase salivation may provide comfort. For more severe cases, artificial saliva or other oral moisturizers (solution, spray, or gel) may also be useful. Potentially beneficial approaches for patients who have radiation therapy-related xerostomia include acupuncture, cevimeline, and oral pilocarpine. (See "Management of late complications of head and neck cancer and its treatment", section on 'Stimulation of existing salivary flow'.)

Dysphagia — Difficulty with swallowing is a common symptom in seriously ill patients, especially those with head and neck cancer, esophageal cancer, or diseases that compromise neurologic function, such as amyotrophic lateral sclerosis (ALS). Dysphagia may also be due to a stricture following radiation therapy for an upper aerodigestive tract cancer.

(See "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences".)

(See "Oropharyngeal dysphagia: Etiology and pathogenesis".)

(See "Management and prevention of complications during initial treatment of head and neck cancer", section on 'Weight loss and malnutrition'.)

(See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease", section on 'Upper motor neuron symptoms'.)

(See "Clinical manifestations, diagnosis, and staging of esophageal cancer", section on 'Clinical manifestations'.)

Patients with dysphagia are at risk for aspiration. A bedside swallowing evaluation may be indicated if patients are noted to cough after swallowing. If abnormal, a barium swallowing study can assist with identifying aspiration. (See "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management", section on 'Assessment'.)

Initial management of dysphagia includes modification of food and fluid consistency. Potentially reversible causes should be sought and treated. Patients treated for head and neck cancer may benefit from swallowing rehabilitation. Radiation therapy may be an option for esophageal obstruction that is caused by a locally advanced esophageal cancer or an extrinsically compressing mediastinal mass. Endoscopic methods of palliation may also be considered (eg, dilation of a stricture, placement of an intraluminal self-expanding stent, or laser ablation in the case of esophageal obstruction). (See "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management" and "Endoscopic stenting for palliation of malignant esophageal obstruction" and "Endoscopic palliation of esophageal cancer".)

Non-oral feeding may be recommended as a temporary solution for severe dysphagia that is expected to improve (eg, patients with head and neck cancer undergoing chemoradiotherapy, acute neurologic dysphagia from a cerebrovascular accident), and it may restore nutrition and hydration for patients with dysphagia after an acute illness such as stroke. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Head and neck cancer' and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Management of swallowing and nutrition' and "Care of patients with advanced dementia", section on 'Oral versus tube feeding' and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management", section on 'Artificial nutrition and hydration'.)

CACHEXIA-ANOREXIA

Causes — Cachexia, a hypercatabolic state defined as accelerated loss of skeletal muscle in the context of a chronic inflammatory response, can occur in the setting of cancer as well as in chronic infection, acquired immunodeficiency syndrome (AIDS), heart failure, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). While loss of appetite (anorexia) with weight loss is common among cancer patients, the profound weight loss suffered by patients with cachexia cannot be entirely attributed to poor caloric intake. (See "Assessment and management of anorexia and cachexia in palliative care".)

In some cases, cancer treatment (eg, androgen-deprivation therapy for prostate cancer, sorafenib) may also contribute to loss of lean body mass. The clinical features and pathogenesis of cancer-associated anorexia-cachexia syndrome are discussed in detail separately. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)

Dietary intake patterns in the seriously ill include decreased frequency of eating, reduction in the variety of foods, and unusually high proportions of liquids [43]. Loss of appetite and change in eating patterns are often distressing, particularly to family members or other caretakers.

We reassure patients and their families or caretakers that loss of interest in food is a natural occurrence as illnesses progress. The social benefits of eating with other loved ones at the dining table as well as the pleasure of tasting food should be emphasized over the nutritional benefits. In clinical practice, dysgeusia may be addressed by reducing red meat intake in favor of more dairy products, marinating meats before cooking and seasoning well to disguise bitter taste, serving foods at room temperature rather than hot, trying tart foods, and encouraging fluids with meals. Strong cooking smells should be avoided at mealtimes.

Approach to management — After potentially reversible causes of anorexia are ruled out (eg, constipation, nausea, mouth discomfort, electrolyte disturbances, depression), symptomatic treatment of cachexia is appropriate. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Clinical assessment'.)

Patients with anorexia should encouraged to eat less if they so desire. Appetite stimulants may be beneficial, in patients with cancer-associated cachexia-anorexia syndrome, although there is a lack of strong evidence for such agents in patients with other types of advanced illnesses [44]. Furthermore, the primary benefits associated with these drugs are increased appetite and modest weight gain, not improved survival or quality of life. Nevertheless, some pharmacologic treatments may be beneficial and are discussed elsewhere. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Treatment'.)

Cannabinoids such as dronabinol are also discussed elsewhere. (See "Management of cancer anorexia/cachexia", section on 'Cannabis and cannabinoids'.)

Limited role for artificial nutrition and hydration — The great majority of patients in the terminal phase of an advanced, serious, or life-threatening illness, such as cancer, experience reduced oral intake before death, either voluntarily or because of loss of appetite, nausea, vomiting, dysphagia, generalized weakness, gastrointestinal tract obstruction, or impaired cognition. Family members and caregivers often experience high levels of emotional distress when a terminally ill patient becomes unable to take fluids and nourishment orally, fearing that dehydration and malnutrition will contribute to suffering and hasten death.

Artificial nutrition — While nutrient supplementation might appear useful, for the vast majority of terminally ill patients, there is no evidence that artificial nutrition prolongs life or improves functional status [45]. However:

For highly selected patients (eg, high-grade bowel obstruction or malabsorption from advanced cancer) who might otherwise have a prognosis that is measured in months, home parenteral nutritional support may be considered after discussion among the health care staff, the patient, and family members or other caretakers [29,46]. After initiation, the use of parenteral nutrition needs periodic reevaluation; if the benefits are outweighed by excessive harms, it should be discontinued.

For other terminal diseases, such as dementia or neurodegenerative disease, in which the patients will not or cannot eat, intervention with a percutaneous endoscopic gastrostomy (PEG) tube may be considered in selected patients; however, evidence of benefit is lacking.

These issues are all discussed in detail elsewhere. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Indications and benefits of nutritional support in cancer patients' and "Gastrostomy tubes: Uses, patient selection, and efficacy in adults" and "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'Patients with cancer at the end of life' and "Stopping nutrition and hydration at the end of life", section on 'Use of artificial nutrition' and "Care of patients with advanced dementia".)

Hydration — The possibility that dehydration may contribute to suffering and hasten death in terminally ill patients has generated debate, but limited data are available [47,48]. Arguments for and against this treatment are provided in the table (table 12).

Practice patterns vary; most cancer patients who die in acute care hospitals receive hydration until death, while most patients who die in hospice or at home receive no fluids. (See "Hospice: Philosophy of care and appropriate utilization in the United States", section on 'Structure'.)

Decisions regarding the use of hydration should be individualized, with discussions involving the patient, family, other caregivers, and other health care professionals. This subject is discussed in detail separately. (See "Stopping nutrition and hydration at the end of life", section on 'Use of artificial hydration'.)

INSOMNIA — Sleep disturbance is a common and distressing symptom for seriously ill patients. Besides adversely affecting quality of life, insomnia can heighten the intensity and awareness of other symptoms, such as pain, anxiety, or delirium.

An Edmonton Symptom Assessment System (ESAS) score of ≥4 has good sensitivity for screening sleep disorder, which often coexists with other symptoms such as pain and depression [49].

Initial management includes treatment of pain and other symptoms as well as limitation or timely dosing of stimulating medications, including steroids or psychostimulants. Nonpharmacologic interventions involve modifying the environment, encouraging healthy sleep-wake cycles, and minimizing disruptions. Pharmacologic interventions are discussed elsewhere. (See "Insomnia in palliative care", section on 'Medications'.)

PSYCHIATRIC SYMPTOMS

Depression — Depression is the most common mental health problem encountered in palliative medicine but can be hard to diagnose, and it is particularly hard to differentiate from demoralization [50]. Depressed mood, sadness, and anticipatory grief are all normal responses in patients facing death. However, feelings of pervasive hopelessness, helplessness, worthlessness, excess guilt, loss of interest, and suicidal ideation (even mild or passive) are among the best indicators of major depression in such patients, as are vegetative signs (sleep disorder, poor concentration, anorexia, and psychomotor retardation) not explained by the underlying medical condition (table 13). (See "Assessment and management of depression in palliative care", section on 'Prevalence of depression in palliative care'.)

A diagnostic interview is the gold standard method for diagnosing depression. However, a simple single question (“Have you been depressed most of the time for the past two weeks?”) and other abbreviated screening methods such as those recommended by the National Comprehensive Cancer Network (NCCN) [51,52] appear to be effective in identifying those patients who require further assessment for depression [53].

Major depression is a treatable condition, even in terminally ill patients. The first step is to relieve uncontrolled symptoms, particularly pain and insomnia. Supportive psychotherapy should be initiated and may be sufficient to treat the condition, although many patients benefit from an approach that combines supportive psychotherapy with education for the patient and their loved ones and the use of antidepressant medication. Treatment is discussed in detail elsewhere. (See "Assessment and management of depression in palliative care", section on 'Treatment' and "Management of psychiatric disorders in patients with cancer", section on 'Depression'.)

Anticipatory grief — Anticipatory grief, a natural and expected reaction to having a life-limiting illness and loss, can and should be distinguished from major depression (table 13). (See "Approach to symptom assessment in palliative care", section on 'Sadness, grief, depression, and demoralization' and "Assessment and management of depression in palliative care", section on 'Assessment and diagnosis'.)

Clinicians can help chronically ill patients by naming grief that is due to losses associated with, and anticipated due to a terminal illness, and by clarifying that these emotions are normal, understandable, and deserve respect and expression. Patients may benefit from reassurance that they are not depressed or “psychiatrically ill.” Clinicians should recognize that, while most grief recedes over time, some aspects of grief will remain present, and they may wax and wane. Education for patient and family caregivers about grief, encouragement of its expression, attention to lifestyle issues like diet and exercise, and engagement with family, friends, and their spiritual and religious community should be provided.

Demoralization — Demoralization is a psychiatric syndrome characterized by feelings of hopelessness and helplessness, and by a loss of purpose and meaning in patients with a terminal illness; it may be distinct from clinical depression [54] and precipitated by existential distress [55]. (See "Assessment and management of depression in palliative care", section on 'Existential concerns and spirituality'.)

Among the factors that are consistently associated with demoralization are poorly controlled physical symptoms, inadequately treated depression and anxiety, reduced social functioning, unemployment, and single status [54]. Treatment of demoralization in patients receiving palliative care can include cognitive-behavioral therapy, dignity therapy, meaning-centered psychotherapy, and access to spiritual care, but more research is needed in this area [55]. (See "Assessment and management of depression in palliative care", section on 'Existential psychotherapy'.)

DELIRIUM — For many seriously ill patients, delirium is a common complication [56]. It can result in distress for patients, family members, caretakers, and health care providers, and it is associated with adverse outcomes including among patients undergoing treatment for cancer [48,57,58].

Contributing factors — A number of factors may contribute to the development of delirium in patients with advanced terminal illness, including:

Opioid-induced neurotoxicity. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Somnolence and mental clouding'.)

Undertreated pain.

Brain tumor/metastases.

Cancer treatments (chemotherapy, radiation therapy). (See "Overview of neurologic complications of conventional non-platinum cancer chemotherapy" and "Overview of neurologic complications of platinum-based chemotherapy" and "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders".)

Psychotropic drugs (tricyclic antidepressants, benzodiazepines), other drugs with anticholinergic properties [59], and glucocorticoids. Low-dose olanzapine may reduce psychologic effects when given with steroids [60].

Metabolic factors (hypercalcemia, hyponatremia), dehydration, or failure of a vital organ or system (eg, renal failure, hypotension). (See "Hypercalcemia of malignancy: Mechanisms" and "Clinical manifestations of hypercalcemia" and "Overview of the treatment of hyponatremia in adults" and "Diagnostic evaluation of adults with hyponatremia".)

Paraneoplastic syndromes. (See "Overview of paraneoplastic syndromes of the nervous system" and "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

Other causes, especially in older or frail patients may include thiamine deficiency, infection, hip fracture, pulmonary embolism, or constipation.

Diagnosis — Several tools are available for screening for delirium, including the Memorial Delirium Assessment Scale (MDAS) (form 1A-B) [61] and the Confusion Assessment Method (CAM) (table 14) [62].

Diagnosis is discussed in detail elsewhere. (See "Diagnosis of delirium and confusional states" and "Palliative care: The last hours and days of life", section on 'Delirium' and "Patients with cancer: Clinical features and diagnosis of cognitive impairment and delirium", section on 'Delirium'.)

Treatment — Measures to address contributing factors are the first line of treatment and may include a change in the type of opioid, hydration, or the management of metabolic or infectious complications. Hyperactive symptoms improve within three to five days in most patients if the underlying etiology is corrected.

There is limited evidence from clinical trials regarding optimal drug therapy for treatment of mild to moderate delirium in terminally ill patients [63-67]. Treatment is discussed in detail elsewhere:

(See "Management of psychiatric disorders in patients with cancer".)

(See "Management of neuropsychiatric symptoms of dementia".)

(See "Palliative care: The last hours and days of life", section on 'Delirium'.)

(See "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Management'.)

Patients who are in the last days to hours of life who fail to improve with medical management of delirium may benefit from aggressive parenteral sedation. (See "Palliative care: The last hours and days of life", section on 'Palliative sedation for patients with refractory symptoms' and "Palliative sedation", section on 'Administration'.)

DYSPNEA AND OTHER RESPIRATORY SYMPTOMS — Dyspnea is a common symptom in seriously ill patients (figure 1) [68]. It is particularly common in patients who have pulmonary disease; however, it is also a common symptom in seriously ill patients who have no evident cardiopulmonary pathology. From a pathophysiologic standpoint, the sensation of dyspnea may arise from increased ventilatory demand, impairment of the mechanical process of ventilation, or both. A physiologic classification of the causes of dyspnea is presented in the table (table 15). (See "Assessment and management of dyspnea in palliative care", section on 'Pathophysiology'.)

Many patients with dyspnea due to one of the identifiable causes improve dramatically with specific treatments, such as anticoagulation for pulmonary embolism, antibiotics for pneumonia, or red blood cell transfusion for anemia. In other cases, the goal of the treatment in seriously ill patients is to improve the subjective sensation as expressed by the patient, rather than alleviation of the underlying condition.

Breathing training, relaxation, modification in activity level, chest wall vibration, and the use of bathroom aids, portable oxygen, and wheelchairs are tools to improve performance and increase the autonomy of patients and their families or caretakers. Systemic opioids are the most effective pharmacologic agents and the treatment of choice for symptomatic control of dyspnea. In addition, hypoxemic patients may benefit from oxygen supplementation. The assessment and management of dyspnea in the palliative care setting is discussed in detail separately. (See "Assessment and management of dyspnea in palliative care".)

Management of cough, stridor, and hemoptysis in palliative care patients is addressed separately. (See "Palliative care: Overview of cough, stridor, and hemoptysis in adults".)

LYMPHEDEMA — Lymphedema occurs when the lymphatic load exceeds the transport capacity of the lymphatic system, which causes filtered protein-rich fluid to accumulate in the interstitium [5]. Lymphedema is generally due to disruption of lymphatic flow, which may be secondary to injury, surgery, radiation therapy, infection, or cancer. As compared with generalized edematous states, the rate of capillary filtration is normal in patients with lymphedema. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Normal lymphatic system and lymphedema'.)

Chronic edema may have multiple underlying etiologies (table 16). Among patients who are ill with a serious and/or life-threatening illness, the most common causes are venous obstruction, hypoalbuminemia, decreased mobility, fluid retention, and medications including corticosteroids. It can affect both physical and psychological wellbeing and may reduce mobility and function [69-71].

Diuretics such as furosemide are usually of little benefit in chronic lymphedema and may promote the development of volume depletion. They are not indicated. Among patients with refractory lymphedema in the palliative care setting, there are few data to guide optimal management. Options include:

Manual lymphatic drainage [72]

Compression therapy [73,74]

Complete decongestive therapy [75-77]

Exercise

Closed-controlled subcutaneous drainage (lymphcentesis) for lower-extremity lymphedema [78-82]

Elevation of the extremity and skin care

A systematic review concluded that all studies examining specific therapeutic interventions in the palliative setting were small and uncontrolled, and few included objective measures of outcome; all were rated in the category of “effectiveness not established” [83].

The management of lymphedema, including in palliative care populations, is discussed in detail separately. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Complete decongestive therapy'.)

LAST HOURS OF LIFE — Patients and their loved ones may be unprepared for the changes that typically occur during the last hours of life. Health care professionals should explain the expected changes in cognition and physical function before they occur in order to alleviate distress, prevent panic, and decrease the burden of bereavement (table 17).

Estimating time of death – Decreased level of consciousness, Palliative Performance Scale (PPS) ≤20 percent, and dysphagia of liquids had a high frequency during the last three days of life but a low specificity (<90 percent) for death within three days. However, periods of apnea, Cheyne-Stokes breathing, death rattle, peripheral cyanosis, pulselessness of radial artery, respiration with mandibular movement, and decreased urine output occurred less frequently during the last three days of life, but these signs have a high specificity (>95 percent) for death within three days [12]. These discussions are particularly useful for families or caretakers planning a home death or for those closely involved in institutional care. (See "Palliative care: The last hours and days of life", section on 'Preparing the family for physiologic changes in the dying process'.)

Misconceptions – Families, informal caregivers or other loved ones may have misconceptions about the meaning of symptoms at the end of life.

They may interpret facial expressions or other bodily movements as expressions of physical discomfort or emotional distress. Some may believe that patients will wake up and be able to communicate just before dying, a misconception that can result in long-lasting guilt when relatives are not able to be at the bedside at the moment of death.

The gurgling or crackling sounds of air passing over accumulated respiratory and oropharyngeal secretions, which are colloquially termed the “death rattle,” may be interpreted as dyspnea or choking by onlookers. In addition to a health care professional explaining and reassuring the patient’s family that the noises are a natural occurrence of the dying process, proper positioning, allowing patients to suction the secretions when they have the capacity to do so, and anticholinergic medications (table 18) may help to minimize these secretions. Treatments are discussed in detail separately. (See "Palliative care: The last hours and days of life", section on 'Airway secretions'.)

Education to reduce family/caregiver distress – The perception of distress or discomfort in dying patients is associated with increased risk of complicated bereavement in relatives and other loved ones [84]. Family caregivers reported significantly more observed behaviors (grimacing, groaning, shouting, touching or rubbing an area, purposeless movements, and labored breathing) and discomfort in unresponsive terminally ill cancer patients than did bedside nurses [85]. Education on expected symptoms and normal physiological changes at the end of life are needed reduce perceived level of distress by informal caregivers and, potentially, the burden of bereavement. (See "Bereavement and grief in adults: Clinical features" and "Bereavement and grief in adults: Management".)

PALLIATIVE SEDATION — For patients at the end of life, palliative sedation is a measure of last resort to alleviate severe symptoms that are refractory to other forms of treatment. It is most commonly utilized for dyspnea, agitated delirium, and convulsions. The intent of palliative sedation is to relieve the burden of otherwise intolerable suffering for terminally ill patients and to do so in such a manner so as to preserve the moral sensibilities of the patient, the medical professionals involved in their care, and concerned family and friends. (See "Palliative sedation".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Palliative care" and "Society guideline links: Dyspnea".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Medical care during advanced illness (The Basics)" and "Patient education: Advance directives (The Basics)")

SUMMARY AND RECOMMENDATIONS

Symptom assessment – Periodic symptom reassessment is valuable for setting treatment goals, monitoring the response to specific symptomatic interventions, and communicating between members of the health care team. Several assessment scales are available, including the Edmonton Symptom Assessment Scale (ESAS) (table 1), the revised ESAS (table 2), and the ESAS-FS (table 3). (See 'Symptom assessment' above.)

Fatigue – Fatigue is common and multifactorial. Management includes treatment of reversible causes, if any are identified (table 6). There are limited data to support one pharmacologic approach to fatigue over any other. (See 'Fatigue' above.)

Nausea and vomiting

In patients with cancer, possible causes include gastroparesis, malignant bowel obstruction, or adverse effects of treatments. if a potentially reversible cause cannot be identified and bowel obstruction is ruled out, symptomatic treatment with prokinetic agents, such as metoclopramide, is often helpful. Haloperidol and olanzapine may also be used. (See 'Patients with cancer' above.)

The assessment and management of nausea and vomiting in palliative care patients with diseases other than cancer is discussed elsewhere. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Non-cancer conditions'.)

Constipation – Treatment of constipation initially starts with addressing underlying, potentially reversible factors (table 10). If a reversible cause cannot be identified and modified, symptomatic treatment, initially with senna, is appropriate. (See 'Constipation' above.)

Xerostomia – Frequent oral hygiene is the first step in treating xerostomia. Rinsing with cold water, sucking on ice chips, chewing sugarless gum to increase salivation, and artificial saliva may provide comfort. Potentially beneficial approaches for patients who have radiation therapy-related xerostomia include acupuncture and oral pilocarpine. (See 'Xerostomia' above.)

Dysphagia – Difficulty with swallowing is a common symptom, especially in patients with head and neck cancer, esophageal cancer, or diseases that compromise neurologic function, such as amyotrophic lateral sclerosis (ALS). Initial management includes modification of food and fluid consistency. Potentially reversible causes should be sought and treated. (See 'Dysphagia' above.)

Decreased oral intake – Reduced oral intake is common due to loss of appetite, generalized weakness, nausea, vomiting, or impaired cognition. There is no evidence that artificial nutrition prolongs life or improves functional status, and it is not indicated for most patients. However, decisions regarding the use of parenteral hydration or nutrition should be individualized and involve the patient, family, and other caregivers, with an assessment of potential benefits and drawbacks. (See 'Limited role for artificial nutrition and hydration' above.)

Insomnia – Sleep disturbance is a common and can adversely affect quality of life, heighten the intensity of pain or anxiety, and contribute to delirium. Initial management includes treatment of pain and other symptoms, limitation or timely dosing of stimulating medications. Nonpharmacologic interventions involve modifying the environment, encouraging healthy sleep-wake cycles, and minimizing disruptions. Pharmacologic interventions are discussed elsewhere. (See 'Insomnia' above and "Insomnia in palliative care", section on 'Medications'.)

Depression – Depression is the most common mental health problem encountered in palliative medicine, often underdiagnosed and undertreated. Depressed mood, sadness, and anticipatory grief are all normal responses in patients facing death. However, feelings of pervasive hopelessness, helplessness, worthlessness, excess guilt, loss of interest, and suicidal ideation (even mild or passive) are among the best indicators of major depression in such patients, as are vegetative signs (sleep disorder, poor concentration, anorexia, and psychomotor retardation) not explained by the underlying medical condition (table 13). (See 'Depression' above.)

Delirium – Delirium can be caused by a number of factors, especially opioids and other drugs. Initial management should include efforts to reverse precipitating causes. Pharmacologic management is discussed elsewhere. (See 'Delirium' above.)

Airway secretions – In the last hours of life, increased airway secretions may be distressing to patients and their loved ones. Proper positioning, allowing patients to suction the secretions when they have the capacity to do so, and judicious use of anticholinergic medications (table 18) may help to minimize these secretions. (See 'Last hours of life' above.)

Last hours of life – Patients and their loved ones may be unprepared for the changes that typically occur during the last hours of life. Health care professionals should explain the expected changes in cognition and physical function before they occur in order to alleviate distress, prevent panic, and decrease the burden of bereavement (table 17). (See 'Last hours of life' above.)

Palliative sedation – Effective treatment will successfully alleviate the majority of symptoms that arise in terminally ill patients. Palliative sedation may be indicated for patients in the last stages of life who have refractory symptoms that cannot otherwise be alleviated by an interdisciplinary palliative care team. (See 'Palliative sedation' above.)

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Topic 2199 Version 64.0

References

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