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Approach to symptom assessment in palliative care

Approach to symptom assessment in palliative care
Author:
Victor T Chang, MD
Section Editor:
Thomas J Smith, MD, FACP, FASCO, FAAHPM
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Dec 2022. | This topic last updated: Feb 28, 2022.

INTRODUCTION — Palliative care is an interdisciplinary medical specialty that focuses on preventing and relieving suffering and on supporting the best possible quality of life for patients who are facing a serious and/or life-threatening illness and their families [1]. Although some palliative care skills require subspecialty training to learn and apply, the core elements of palliative care, such as aligning treatment with a patient’s goals and basic symptom management, should be aspects of the care delivered by all practitioners [2]. Palliative care is not limited to end-of-life care and can be provided at the same time as curative or life-prolonging treatments (figure 1). (See "Benefits, services, and models of subspecialty palliative care".)

Patients in the advanced stage of a serious and/or life-threatening illness typically experience multiple symptoms, the most common of which are pain, depression, anxiety, confusion, fatigue, breathlessness, insomnia, nausea, constipation, diarrhea, and anorexia (table 1) [3-7]. These symptoms may result from a number of factors. Among patients with advanced cancer, for example, symptoms may result from the disease (eg, bone pain from metastases, dyspnea from pleural effusions), from treatment (eg, esophagitis with thoracic radiation therapy), from other concurrent conditions (eg, osteoarthritis), or from medications (eg, dry mouth, constipation).

This topic review provides a suggested approach to assessment for the most common physical and psychological symptoms that arise in patients receiving palliative care for an advanced serious and/or life-threatening illness. The principles underlying the comprehensive palliative care assessment (which include domains other than physical and psychologic symptoms) and an overview of treatment for symptoms commonly encountered in a palliative care population are provided elsewhere. (See "Overview of comprehensive patient assessment in palliative care" and "Overview of managing common non-pain symptoms in palliative care".)

GENERAL PRINCIPLES — Patient descriptions of physical symptoms and their severity are the primary data for symptom assessment in palliative care. Exploring patients’ reports of symptoms requires thoroughness, persistence, and patience; this is a fundamental aspect of patient-centered care.

It is important to assess mental status and stamina before starting to elicit information as to the nature and severity of symptoms. Seriously fatigued patients may only be able to answer a few questions briefly, and more than one visit may be necessary. Patients who are confused or delirious will not be able to cooperate fully, making symptom identification and assessment difficult; failure to recognize delirium may lead to inaccurate assessments and inappropriate therapies [8]. (See "Diagnosis of delirium and confusional states".)

Patients with advanced illnesses typically have multiple symptoms, and systematic assessment is preferable to relying on spontaneously described symptoms. A study of patients referred to a palliative medicine program found that there were 10 symptoms for every one symptom that was volunteered by a patient [9]. Health care providers tend to underestimate symptom severity [10,11]. This can lead to missed opportunities for diagnosis and symptom relief. A careful review of symptoms with a focus on common problems in palliative care practice is required. Comprehensive symptom assessment can contribute to significant symptom improvement and better quality of life [12,13].

Each identified symptom should be investigated in regard to its Onset, Palliating and Provoking factors, Quality, Response to previous treatments, Related factors/symptoms, Severity, and Temporality (the OPQRST historical structure for evaluating medical complaints). Of comparable importance, but less emphasized, is understanding the personal meaning of a symptom to the patient and how the symptom affects their psychosocial wellbeing (the MOPQRST mnemonic) (table 2). Sample questions to explore the meaning of specific symptoms include:

“Of the symptoms that have been bothering you, which symptom bothers you the most [14]?” This will identify a primary symptom in one-third of patients who would otherwise be missed.

“How do the symptoms affect you? How much do they interfere with your life? (eg, sleep? daily activities? your sense of wellbeing?)”

“What ideas do you have about the meaning of these symptoms?”

“Do they make you worry about your health/illness? What are your concerns?”

“How are these symptoms affecting your family and friends?”

Discussing symptoms with the patient’s caregivers may also be informative and provide opportunities to be supportive and educate family and friends [15].

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

Availability of time may be the greatest barrier to performing symptom assessment. Many of the aspects discussed below are presented to help the practitioner think about and follow up on a patient’s answers during symptom assessment.

Dimensions of symptom assessment — Dimensions are different aspects of symptoms, such as severity, frequency, level of interference with activities, and level of distress associated with the symptom.

Symptom severity is a useful guide to treatment (eg, pain) and it may also provide some prognostic information (eg, dyspnea). (See 'Performance status, symptoms, and prognosis' below.)

The use of rating instruments that are completed by patients themselves represents a major change in symptom assessment over the last 30 years. In evaluating symptoms, it is helpful to obtain the patient’s rating of severity within a given time frame, such as the last 24 hours. The approach to rating pain relies exclusively on how the patient reports pain, using a verbal or numerical scale. The patient can be asked to make a mark on a 10 cm straight line (Visual Analog Scale [VAS]) (figure 2) or rate severity on a scale of 0 to 10, where 10 is worst. These approaches are based upon psychophysical studies in the field of subjective sensory physiology, where it has been shown that perception of a stimulus is closely related to the strength of the stimulus [16]. For many symptoms, however, there is no clear evidence as to what the optimal cut points are to define symptom severity [17]. (See 'Assessment and rating instruments for symptoms' below.)

Some patients are unable to rate their symptom severity on a numerical scale [18]. An alternative approach is to ask patients for their rating of symptom distress rather than severity and to give them categories of response (eg, bothered not at all, a little bit, somewhat, quite a bit, very much). Some symptoms, such as fatigue, may be rated by patients as mild in severity but severe in distress. The amount and type of interference with daily activities caused by a symptom also can illustrate symptom severity and provide another means of determining therapeutic success.

Symptom change — The patient’s assessment of symptom relief is also important since it drives the therapeutic plan. The definition of the minimum clinically significant differences in symptom instruments for pain, fatigue, and dyspnea has been an important advance in the interpretation of symptom ratings and can be considered to be a 2 point change on an 11 point scale, eg, 0 to 10 (figure 2), or any change in categories of a Likert scale, such as the faces pain scale (form 1) [19-23].

Challenges in symptom assessment — A number of situations raise particular challenges for symptom assessment in palliative care patients:

Patient’s assessment of symptoms may differ from that of the health professional. In general, clinicians (and caregivers) have greater discordance with patients in assessing the severity of subjective symptoms (eg, pain, anxiety) than for objective states, such as the presence of vomiting. Clinicians tend to rate the severity of symptoms lower than patients and family members and tend to tolerate levels of symptom-related distress and suffering that patients find unacceptable [24-28]. By contrast, family members tend to overrate symptoms as well [29-31]. However, where pain is concerned, older family members tend to overrate while younger family members tend to underrate pain [29].

Patients may downplay or not report symptoms (particularly pain) because of fears that worsening symptoms reflect disease progression and that the oncologist will stop treatment. Underreporting may also occur if a patient feels that a symptom such as pain is an inevitable consequence of the disease, its treatment, or dying. In addition, if patients do not receive attention to oft-voiced complaints, they may stop communicating about distress related to that specific complaint.

Symptoms can change over time.

Many symptoms are multifactorial in origin. A comprehensive assessment process will help define all the possible factors that may be causing a specific symptom. (See 'Approach to specific symptoms' below.)

Patients and/or their families or other loved ones may have suffered harm in the health care system and lost trust in the system and/or care providers. This may make them particularly reluctant to discuss psychological symptoms. Particularly in these cases, the assessment interview with the patient and family may itself have therapeutic value in enhancing the care provider relationships with patient and family, eliciting care preferences and developing trust. (See "The initial interview in palliative care consultation".)

Cultural factors may determine which symptoms are acceptable for discussion between patients and clinicians and how patients perceive their symptoms. For example, women from certain cultures may not be comfortable sharing gynecologic complaints with a male clinician [32].

However, at least one study suggests that for most symptoms, culture may have a limited impact on how patient-reported symptoms are ultimately interpreted. In this study, over 1400 patients from five countries (United States, China, Japan, Russia, and Korea) were evaluated for the severity and interference of symptoms related to their cancer and/or treatment using psychometrically validated language versions of the MD Anderson Symptom Inventory [33]. The authors found only limited variations in symptom reporting due to cultural or linguistic variations. The exception to this was with the reporting of nausea and vomiting.

Language can pose barriers. In Europe, the assessment of fatigue may be challenging because the word itself is only found in English and French [34].

Patients may have difficulty communicating. Examples include intubated patients in the intensive care unit, patients who are withdrawn or who have cognitive impairment, and those who are just too ill to voice complaints. As patients near death, symptom assessment becomes more difficult because the majority of patients become noncommunicative and other symptoms, such as restlessness and confusion, may interfere with effective communication. The study of behavioral changes as clues to the presence of pain (eg, grimacing) is an area of ongoing research and forms the basis for observer-based rating instruments such as the Pain Assessment in Advanced Dementia [PAINAD] tool (table 3). A similar tool (the Respiratory Distress Observation Scale) has been developed for assessment of dyspnea (table 4) [35,36]. (See 'Patients unable to self-report' below.)

Involved family members and caregivers may be asked by health professionals to assess and rate symptoms (proxy ratings). However, there may be disparities between patient and caregiver symptom assessments or ratings [29,37,38]. For patients with impaired communication, the palliative care consultant may have to balance multiple assessments by family, caregivers, and health care personnel. (See 'Patients unable to self-report' below.)

Care providers (clinicians and nurses alike) may not be aware of the high prevalence of symptoms in these patients, may not have symptom assessment incorporated into their conversations with patients, and may lack knowledge about symptom identification and management. The average number of symptoms ranges from 11 to 18 in a wide variety of illnesses [39-41].

Patients may be very demoralized, tired of being sick, and feeling helpless and hopeless [42], and they simply stop reporting symptoms. (See 'Demoralization' below.)

ASSESSMENT AND RATING INSTRUMENTS FOR SYMPTOMS — Formal multiple symptom assessment tools, especially those that are symptom inventories, like the revised Edmonton Symptom Assessment Scale (table 5), provide a good overview of symptoms in individual patients [43]. In particular, multiple symptom assessment tools are highly effective in the recognition of unreported symptoms, when combined with further patient interviewing to delineate the details of positive responses. When a specific tool has been chosen, it should be used consistently to ensure reliability in the clinical setting.

Many of these symptom assessment tools have been tested for reliability and validity. However, like any other measurement of health outcomes, there are potential errors in assessment [44]. The possibilities for assessment errors include:

Motor, hearing, and visual impairments may impede the usefulness of symptom assessment tools in older adults [45].

Cognitive dysfunction may lead to misleading responses and inaccurate assessment, even when paired with behavioral indicators [8]. The cognitive dysfunction may be quite subtle. (See 'Patients unable to self-report' below.)

Shorter tools may miss symptoms that are important to the patient, and longer tools may be too tiring for patients to complete. (See 'Challenges in symptom assessment' above.)

As the patient’s condition changes, symptom ratings may change as they accommodate to the new condition, even if the symptom has not changed. This is referred to as the phenomenon of response shift. Ratings may also be influenced by other symptoms, especially anxiety and other emotional reactions, which may change over time. (See 'Symptom change' above.)

Interpretation of the “anchors” (0 and 10 on the numerical 0 to 10 scale) may vary between patients, depending upon their previous experience. Caregivers and health care personnel may also interpret the anchors differently. It may be necessary to repeat the definitions of the anchors when asking patients to give a rating.

For numerical scales, the “cut point” is a number that identifies how to categorize severity. Studies have identified cut points of 4 out of 10 (mild versus moderate) and 7 out of 10 (moderate versus severe) for pain [46]; work is ongoing to determine optimal cut points for other symptoms [17,47].

Despite these limitations, a number of validated multiple symptom assessment tools are in wide usage in palliative and end-of-life care settings, including:

The revised Edmonton Symptom Assessment Scale (table 5) [43]

Memorial Symptom Assessment Scale-Short (MSAS) Form (figure 3) and Condensed MSAS [48-50]

MD Anderson Brief Symptom Inventory [51,52]

Rotterdam Symptom Checklist [53]

Symptom Distress Scale [54]

Patient-Reported Outcomes Measurement Information System (PROMIS), as developed by the United States National Institutes of Health (see "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness", section on 'Combined instruments for patient-reported outcomes')

The Your Symptoms Matter symptoms assessment tool, developed and hosted by Cancer Care Ontario

The National Comprehensive Cancer Network (NCCN) Distress Thermometer [55]

Instruments are available that focus on one symptom, such as dyspnea or pain. One example is the Brief Pain Inventory (BPI), a patient self-rating scale that assesses pain intensity and pain interference in various areas of function [56,57]; a short-form version (BPI-SF) is available online. (See 'History' below.)

However, detailed instruments such as these are not available for all symptoms, and patients may not be able to answer the multiple questions from many instruments. Many instruments are now available in languages other than English, which may help with the assessment of symptoms in countries where English is not the primary language. The non-profit organization, Mapi Research Trust, created a database of clinical outcome assessments. The website may provide greater access to assessment tools, including access to tools available in multiple languages.

PERFORMANCE STATUS, SYMPTOMS, AND PROGNOSIS — Performance status is a critical aspect of patient assessment in palliative care. As a general rule, performance status, as assessed by the Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status scales (table 6 and table 7) is a key indicator of prognosis in individuals with advanced terminal disease [58]. The Palliative Performance Scale (PPS) is gaining wide acceptance as a tool for assessing functional levels and as a method of estimating prognosis in patients with advanced cancer [59,60]. The PPS [60,61] may be a better indicator of functional status than other types of performance status scales, including Karnofsky and ECOG, in this population. Comparisons suggest there is considerable overlap [62]. (See "Survival estimates in advanced terminal cancer", section on 'Prognosis in patients receiving palliative care only' and "Survival estimates in advanced terminal cancer", section on 'Performance status'.)

Less well recognized is the relationship between symptoms, performance status, and prognosis. As an example, symptom number and intensity correlate significantly with performance status and prognosis [63]. As a terminal disease progresses, there is often a continual decline in function that is accompanied by increasing number and severity of symptoms (especially fatigue and cachexia) [64].

Other specific clinical signs and symptoms may represent independent prognostic factors in patients with advanced serious or life-threatening disease. As an example, in a systematic review of survival prediction in terminal cancer, the strongest evidence after performance status for an independent association with death was for dyspnea, dysphagia, weight loss, xerostomia, anorexia, and cognitive impairment (delirium) [65]. The following table shows the range of median survivals in patients with various signs and symptoms in univariate analyses from this and other studies (table 8). These findings suggest that for patients with advanced life-threatening diseases, such as those referred to palliative care programs, the presence of these symptoms may help clinicians estimate patient survival.

Dyspnea is a particularly important indicator of shortened survival in a variety of diseases, but especially in terminally ill cancer patients [4,9,48-50,66,67]. In one study, the presence of dyspnea was associated with a median survival of less than 30 days [67]. The impact of dyspnea and other symptoms on prognostic estimates in advanced cancer, and assessment of dyspnea in palliative care patients, are discussed in more detail elsewhere. (See "Survival estimates in advanced terminal cancer", section on 'Clinical signs and symptoms' and "Assessment and management of dyspnea in palliative care", section on 'Symptom assessment'.)

Among dyspneic patients, other findings may help to predict the likelihood of imminent death. As an example, in a retrospective sample of 122 patients with cancer who presented to an emergency department with acute dyspnea, a respiratory rate greater than 28 breaths per minute, heart rate greater than 110 beats per minute, uncontrolled disease, and the presence of metastases were all predictive of death within two weeks; the relative risk for imminent death among patients with a respiratory rate above 28, compared with the overall group, was 12.7 (95% CI 3.1-52.8) [68].

Noisy breathing, also known as the “death rattle,” refers to gurgling breath sounds and is usually a preterminal finding, with death likely in hours to days [69]. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Last hours of life'.)

APPROACH TO SPECIFIC SYMPTOMS — The following is a brief discussion about assessing highly prevalent symptoms in the palliative care patient. More detailed discussions of some of these symptoms are available in related topic reviews.

Pain — The purpose of pain assessment is to obtain a rating of severity and to make a diagnosis of the type of pain and its likely cause [70]. The identification of a specific pain syndrome in cancer patients may lead to a specific management plan. (See "Overview of cancer pain syndromes".)

The first step is to ask the patient about the presence of pain and its severity and to believe the answers. As noted above, there is a great divergence between how patients and professionals evaluate pain severity. In a study of 103 cancer patients, a comparison of Visual Analogue Scale (VAS) pain ratings by health professionals with those of patients showed lower ratings of severe pain by health care professionals more than 70 percent of the time [24].

Pain does not occur just in patients with cancer, however. It is also experienced by a large percentage of patients with end-stage heart failure [71,72], chronic obstructive pulmonary disease (COPD), and cirrhosis [73,74], and it is particularly associated with arthritis [75]. In fact, the prevalence and severity of pain are remarkably consistent across a variety of serious illnesses [76].

The following sections will briefly summarize the components of the pain evaluation. A more detailed discussion is available elsewhere. (See "Assessment of cancer pain".)

History — In eliciting a pain history, initial questions should include site, nature and severity, interference, and relief. In addition, patients may have had (untreated) chronic pains, such as that related to arthritis, that predate the advanced illness [75].

Site – It is always wise to have the patient point to the site of pain to avoid a misunderstanding of anatomical terms.

Type of pain – Among patients with cancer, the specific type of pain may help to elucidate the specific pathophysiology. As examples (see "Assessment of cancer pain", section on 'Inferred pathophysiology and treatment implications'):

Nociceptive pain is sustained predominantly by ongoing tissue injury. Somatic nociceptive pain involves injury to somatic structures like skin, bone, joints, or muscles. It is usually well localized and is often described by patients as “aching,” “stabbing,” or “throbbing” in quality. Visceral nociceptive pain results from distension, injury to, or inflammation of visceral organs. It is usually poorly localized and is characterized as “gnawing” or “crampy” when arising from the obstruction of a hollow viscus (eg, the bowel lumen), or as “aching” or “stabbing” when arising from other somatically innervated visceral structures, such as organ capsules or parietal pleura. Visceral pain can be referred to somatic structures. Further evaluation often yields an abnormal finding that can be identified on physical examination (such as localized tenderness to palpation) or radiographic scans to explain the symptoms.

Neuropathic pain is sustained by abnormal somatosensory processing in the peripheral or central nervous system, or direct damage to nerves. Examples include postherpetic neuralgia, postchemotherapy neuropathy, and phantom pain. Patients may describe unpredictable shooting, burning, numbness, or pruritus. The sensory examination is often helpful if abnormalities such as lack of sensation, increased sensitivity (hyperesthesia), or pain with nonpainful stimuli (allodynia) can be demonstrated.

Depending on the location of the mass, neuropathic pain may be present with nociceptive pain and may not have its signature features of sensory disturbance or shooting pain, but may be gnawing or constant.

Severity and quality of life (QOL) impact – Pain severity guides medication choice and dosage. (See "Cancer pain management: General principles and risk management for patients receiving opioids" and "Cancer pain management with opioids: Optimizing analgesia".)

There are a number of simple ways to assess pain severity, including a faces pain scale (form 1), a VAS (figure 2), or a categorical Likert scale (none, a little, somewhat, quite a bit, very much).

Formal instruments have also been developed to rate pain severity in multiple dimensions. These include the Brief Pain Inventory (BPI; a short-form version of which [BPI-SF] is available online) [56,57], the McGill Pain Questionnaire [77] (a shortened version is available that has been validated in a variety of populations [78,79]), and the Memorial Pain Assessment Card [80]. Both the McGill Pain Questionnaire and the BPI have been translated into several languages. Although many of these tools were developed for patients with cancer, they are equally applicable to patients with other serious and/or life-threatening conditions. (See "Assessment of cancer pain", section on 'Intensity'.)

Another way to evaluate severity is through assessment of the impact of pain on physical and psychological function and quality of life. Family members or other loved ones may be able to provide important information in this regard. Pain can interfere with quality of life by interfering with daily activities, walking, and sleep and by affecting mood. Severe pain may engender a sense of hopelessness and anxiety. Anxiety, in turn, may increase reactions to pain, while fear can decrease pain reactivity [81].

Aggravating and alleviating factors – This includes response to prior treatment(s).

Associated symptoms – This includes paresthesias, weakness, nausea.

Temporal patterns – Temporal assessment of the pain may include information about onset, duration, and fluctuation. Both the extent and duration of relief provided by interventions should be determined.

Most patients with chronic cancer pain experience periodic flares, often referred to as “breakthrough pain.” Breakthrough pain can be caused by inadequate dosing, caused by an unprovoked flare of the underlying pain syndrome, or provoked by a procedure or activity (incident pain). Especially for inpatients, procedural pain is an experience that is often overlooked. Breakthrough pain may result from such routine procedures as dressing changes for pressure ulcers or wounds, positioning for change of bed sheets, or movement in bed for a radiographic study [82]. (See "Assessment of cancer pain", section on 'Pain characteristics' and "Cancer pain management with opioids: Optimizing analgesia", section on 'Management of breakthrough pain'.)

The term “pseudoaddiction” describes a situation in which a patient’s legitimate chronic pain condition is undertreated with pain medication, leading the patient to act in a way that resembles addictive behavior (requesting extra medications and demanding attention); such patients are often labeled as demonstrating “drug-seeking behaviors.” The situation arises when a clinician is reluctant to provide enough of a controlled drug to provide adequate symptom relief for a patient who requires long-term treatment [83-85]. This leads to a patient who is either chronically undertreated or intermittently put into withdrawal. The patient responds with a series of “conditioned behaviors” focused on acquisition of the controlled drug that can appear to indicate aberrant addictive-type behaviors. However, in pseudoaddiction, the behaviors disappear when an adequate amount of the drug is obtained. A careful pain history that emphasizes perceived pain relief may help clarify the issue.

However, it should be noted that the whole concept of pseudoaddiction has been questioned; empirical evidence supporting pseudoaddiction as a diagnosis distinct from opioid addiction has not emerged [86]. Use of the term is accepted for justification of opioid therapy for nonterminal pain in patients who appear to be addicted but, for whatever reason, are not diagnosed with an addiction to opioids. This is a controversial issue, particularly in the era of widespread opioid addition and overdose. (See "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis".)

Patient and family perspective – Patients and their family members or other loved ones should be asked about the meaning of the pain, their understanding of its cause, worries about relief, personal and cultural attitudes, concerns about opioid tolerance and addiction, diversion, and expense. Inquiring about personal experiences with pain earlier in the course of the disease, or in friends and family members can dispel hidden anxieties and misunderstandings.

Special circumstances

Patients with a history of substance abuse — Opioids are widely used for treatment of pain in patients with cancer because of their safety, multiple routes of administration, ease of titration, reliability, and effectiveness for all types of pain (ie, somatic, visceral, neuropathic). However, opioids are also potentially abusable drugs. The public health consequences of opioid abuse drive the imperative that all clinicians assume responsibility for risk management when these drugs are prescribed for legitimate medical purposes. These issues are discussed elsewhere. (See "Cancer pain management: General principles and risk management for patients receiving opioids", section on 'Risk assessment and management for patients receiving opioids'.)

Assessing and managing pain is difficult in patients who have a history of substance abuse. Patients with a history of substance abuse who complain of pain can cause considerable apprehension for their care providers because of fears about the potential for deception, drug abuse, addiction, and diversion [87].

Patients with a remote history of substance use and who have a stable support system are less likely to abuse opioids [88]. In our own experience, these patients appreciate a careful and objective pain evaluation and are generally responsible and appropriate in their use of opioids as a component of their medical treatment. Further inquiry into the circumstances of past substance use is helpful. Sometimes they and their family members are even more concerned about addiction to pain medications than professional staff.

Patients who are actively using “street drugs” at the time of initial evaluation should have a careful and objective pain evaluation. The possibility that they are using street drugs to obtain pain relief should be considered. Even if they have an addiction, their pain is real and assessment needs to focus on ways to both treat their pain and help with their addiction. The initial encounter with the patient is most important, as failure to establish a relationship will make it nearly impossible to obtain an accurate pain history and render trials of medications impossible to interpret. These and other issues that arise when considering the need for acute pain management in patients chronically using opioids are addressed in detail separately. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain".)

Principles of risk management in these patients are outlined in the table (table 9). Psychologic evaluation may be helpful in evaluating underlying psychiatric or personality disorders. Assessment and recognition of substance abuse disorders and risk assessment in patients receiving opioids for management of cancer pain are all discussed in more detail elsewhere. (See "Clinical assessment of substance use disorders" and "Cancer pain management: General principles and risk management for patients receiving opioids", section on 'Risk assessment and management for patients receiving opioids'.)

Patients unable to self-report — Assessment of pain in patients who are unable to self-report is a challenging problem in symptom assessment. The spectrum of patients who have impaired communication includes patients with permanent deficits, such as dementia, and those with more temporary cognitive impairments such as delirium, sedation, or trauma. Patients with impaired ability to self-report pain present across the continuum of care, from intensive care units to clinics, home, and long-term care settings. Individuals who are unable to communicate their pain are at greater risk for underrecognition and undertreatment of pain.

Patients with mild dementia are often able to give a description and rating of their pain. Patients with advanced dementia may express pain by distress behaviors such as restlessness, grimacing, moaning, guarding, and changes in daily activity, but these behaviors are not specific for pain. When such behaviors occur, a physical examination should be performed with attention to the association of the pain behavior with movement, pressure, toileting, hunger, fear, loneliness, or visual impairment.

A hierarchical approach has been proposed for this set of patients, whereby multiple sources of information are integrated by the examiner, starting with patient report, and including reports from observers (proxy reporting of pain), observation of patient behavior, use of behavioral pain assessment tools, and search for potential causes of pain [89]. A number of instruments have been developed to systematically assess pain-related behaviors in nonverbal adults [90-94]. A review of tools to assess pain in nonverbal adults is available [92]. Sufficient evidence has accumulated to support the use of the Pain Assessment in Advanced Dementia [PAINAD] tool (table 3) [93].

An empiric trial of analgesics may be warranted if, after the initial assessment, questions remain as to whether a distress behavior is indicative of pain in a patient with cognitive dysfunction.

Dyspnea and cough — Dyspnea is a particularly common symptom in patients who have advanced COPD, heart failure, primary lung cancer, or intrathoracic metastatic disease. However, for unclear reasons, it is also a common symptom in patients with no direct lung pathology [95]. As an example, a National Hospice Study found that 24 percent of terminally ill cancer patients had dyspnea in the absence of known cardiopulmonary pathology [96]. (See "Assessment and management of dyspnea in palliative care", section on 'Prevalence'.)

As with pain, dyspnea is defined solely by patient self-report. Attention to the words that patients use in describing their breathing discomfort may provide insight into the underlying clinical condition as well as the basic physiologic mechanisms producing dyspnea. (See "Assessment and management of dyspnea in palliative care", section on 'Symptom assessment'.)

Objective measures, such as respiratory rate, oxygen saturation, and arterial blood gas determination, may not correlate with nor provide a quantitative measure of the degree of dyspnea [97,98]. Physical examination, pulse oximetry, and chest radiograph do not clarify whether the patient has dyspnea, but they may help the clinician to identify likely causes for the symptom (table 10). (See "Assessment and management of dyspnea in palliative care", section on 'Testing to determine underlying cause'.)

Many methods for assessing the severity of dyspnea are based upon functional assessment (ie, studies of tasks and effort) and quantify the amount of exertion required to cause dyspnea. Breathless patients inevitably reduce their activity level to accommodate dyspnea, so questions about limitations in performing specific activities can be used to assess the impact of dyspnea. As an example, the Oxygen Cost Diagram (figure 4) [99] asks patients to identify the level of activity they are unable to perform due to dyspnea, giving clinicians valuable information regarding the functional impact of the symptom. (See "Assessment and management of dyspnea in palliative care", section on 'Symptom assessment'.)

Patient-rated scales of dyspnea intensity have been based upon psychophysical descriptions of the relationship between work and perceived exertion. As an example, the modified Borg scale (table 11) measures the severity of dyspnea using a scale from 0 to 10, anchored by descriptive words; it may be used in conjunction with an exertional test [100]. The most common exertional tests involve having the patient walk for 6 or 12 minutes and then rate their dyspnea afterwards. A correlation between the 0 to 10 numerical scale and a four-level categorical verbal descriptor scale for dyspnea has been observed (0, none; 1 to 4, mild; 5 to 8, moderate; 9 to 10, severe) [101].

For patients with COPD, the frequency and severity of dyspnea can be assessed using validated questionnaires such as the Clinical COPD Questionnaire (table 12) or the Chronic Respiratory Questionnaire (CRQ), a shortened version of which is available [102]. Although these approaches are useful for evaluating symptom severity in patients with COPD, neither is appropriate for patients with advanced serious life-threatening illness and severe dyspnea at rest. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Palliative care for adults with nonmalignant chronic lung disease", section on 'Symptom management in chronic lung disease'.)

None of these tools adequately measure the multidimensionality of dyspnea. A Cancer Dyspnea Scale has been developed in Japan for use in patients with lung cancer and translated into English [103]. Although it appears to reliably measure the sensation and psychologic components of dyspnea, further validation in other palliative care populations is needed.

The prognostic implications of dyspnea, particularly in patients with cancer, are discussed above. (See 'Performance status, symptoms, and prognosis' above.)

Cough is a frequent symptom in palliative care populations. Asthenia, muscle weakness, and the inability to coordinate an effective swallow near the end of life results in ineffective, persistent coughing in an attempt to clear accumulating airway secretions. Among patients with cancer, cough may be attributed to direct or indirect effects of the tumor (table 13). All patients should be evaluated for other potentially treatable causes of cough. A more in-depth discussion of assessment and management of cough and swallowing disorders in palliative care populations is provided separately. (See "Palliative care: Overview of cough, stridor, and hemoptysis in adults" and "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences".)

Patients unable to self-report — A tool, the Respiratory Distress Observation Scale, has been developed for dyspnea assessment in patients who are unable to self-report (table 4) [35].

Fatigue — In the past, the terms “asthenia” and “weakness” were used to describe a subjective sensation of tiredness, while the specific term “fatigue” was used to describe a symptom of tiredness precipitated by effort. However, the terms are often used in the same context, and this broad sense of the term “fatigue” has gained widespread acceptance in the medical literature. (See "Overview of fatigue, weakness, and asthenia in palliative care", section on 'Definition'.)

Fatigue is a highly prevalent and poorly understood symptom in patients with advanced serious and/or life-threatening illness. It is reported by 80 percent of cancer patients overall and by up to 99 percent of patients following radiation therapy or chemotherapy [34]. Fatigue is also prevalent in palliative care patients with advanced life-threatening illness other than cancer, including those with HIV, multiple sclerosis, COPD, and heart failure. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment" and "Palliative care for patients with advanced heart failure: Indications and systems of care" and "Overview of fatigue, weakness, and asthenia in palliative care", section on 'Prevalence'.)

The assessment of fatigue in palliative care patients can be complex given its subjective and multidimensional nature. As such, there is a trend towards multidimensional assessment (ie, asking about different aspects of fatigue, such as muscular weakness of tiredness associated with a sleep disturbance) rather than asking a single question, “Are you tired?” (See "Overview of fatigue, weakness, and asthenia in palliative care", section on 'Clinical assessment'.)

Instruments have been developed for assessment of fatigue in cancer patients which assess both severity and functional impact (eg, the Brief Fatigue Inventory) (table 14) [104], and this subject is addressed in more detail separately. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Clinical assessment'.)

A listing of assessment tools for fatigue in patients with cancer as well as other serious life-threatening illnesses is available in the table (table 15). Questions about fatigue are also present in some symptom assessment instruments for patients with COPD and heart failure. However, in such patients, it can be difficult to separate out fatigue from dyspnea [105]. A combined dyspnea/fatigue instrument has been developed for patients with heart failure [106]. (See "Palliative care for patients with advanced heart failure: Indications and systems of care".)

Fatigue severity can also be quantified using a 0 to 10 visual analog scale such as provided in the revised Edmonton Symptom Assessment Scale (table 5). Ratings of fatigue severity have been shown to be clinically meaningful in patients with cancer in terms of interference with function [107]. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Clinical assessment' and "Overview of fatigue, weakness, and asthenia in palliative care", section on 'Clinical assessment'.)

The cause of fatigue in palliative care patients is typically multifactorial; acute fatigue, which may be caused by acute illness such as infection or cardiac decompensation, must be distinguished from more chronic fatigue, which is more typically (particularly for cancer patients) related to the underlying illness or its treatment. 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. (See "Overview of fatigue, weakness, and asthenia in palliative care", section on 'Causes and pathophysiology'.)

Factors that are often causally related to fatigue should be specifically assessed, including anemia, uncontrolled pain, emotional distress, sleep disturbance, weight loss and malnutrition, electrolyte disturbances (table 16), and the presence of other comorbidities (eg, infection, cardiopulmonary, renal, hepatic, neurologic, or endocrine dysfunction). (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Main contributory factors' and "Cancer-related fatigue: Prevalence, screening, and clinical assessment", section on 'Assess for potentially remediable contributing factors'.)

Dry mouth — Xerostomia, the feeling of a dry mouth, is a highly prevalent symptom in palliative care. Risk factors include medications, mouth breathing, advanced age, and, in cancer patients, a previous history of radiation to the head and neck. A number of medical conditions such as Sjögren’s syndrome, diabetes mellitus, and anxiety states can contribute to this symptom. Dehydration from reduced oral intake may be associated with a dry mouth. Medications are a significant cause of xerostomia in palliative care; in one survey, hospice patients were on a median number of four drugs that were associated with xerostomia [108]. (See "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease", section on 'Dry mouth' and "Management of late complications of head and neck cancer and its treatment", section on 'Salivary gland damage and xerostomia' and "Normal aging", section on 'Oropharynx' and "Stopping nutrition and hydration at the end of life", section on 'Fluid deficits at the end of life'.)

A dry mouth can alter taste and make it difficult for patients to eat and swallow. Patients with xerostomia may also complain of mouth pain and difficulty with speaking [109].

On examination, the presence of dry lips, dry mucosa, dental caries, a coated tongue, and ropy saliva helps confirm the impression of xerostomia. Associated findings of relevance include the presence of thrush, periodontal disease, and herpetic infection. Patients with erythematous candidiasis may have patchy erythema of the dorsal tongue and other mucosal surfaces and angular cheilitis.

While there are objective tests to confirm the presence of xerostomia (eg, measures of saliva production, such as the unstimulated and stimulated [after eating] whole salivary flow rates), these tests are used primarily for research purposes.

Dysphagia — Dysphagia, which is sometimes associated with odynophagia and/or aspiration, occurs regularly in patients with advanced illness, especially in the setting of neurologic disorders (including amyotrophic lateral sclerosis [ALS] and other motor neuron diseases, brain metastases, and leptomeningeal carcinomatosis), as well as cancers of the head and neck, lung, and esophagus. (See "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences" and "Clinical manifestations, diagnosis, and staging of esophageal cancer", section on 'Clinical manifestations' and "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease", section on 'Upper motor neuron symptoms' and "Speech and swallowing rehabilitation of the patient with head and neck cancer", section on 'Aspiration'.)

In dysphagia, patients will complain of a bolus getting “stuck” after swallowing and often can point to a site. Aspiration should be suspected when patients start coughing after drinking liquids, with accompanying hoarseness.

Dysphagia may be classified as oropharyngeal or esophageal, and patients may have difficulty with one or both phases of the swallowing mechanism (see "Oropharyngeal dysphagia: Etiology and pathogenesis", section on 'Physiology of swallowing'):

Oropharyngeal dysphagia, also called transfer dysphagia, arises from disorders that affect the function of the oropharynx, larynx, and upper esophageal sphincter. Neurogenic and myogenic disorders as well as oropharyngeal tumors are the most common underlying mechanisms for oropharyngeal dysphagia.

Esophageal dysphagia arises within the body of the esophagus, the lower esophageal sphincter, or cardia and is most commonly due to mechanical causes or a motility disturbance.

The most common causes of dysphagia in palliative care populations are (see "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences", section on 'Etiology of swallowing disorders in palliative care populations'):

Neoplasms (especially head and neck, and esophageal cancer) and posttreatment complications (especially xerostomia)

Neurodegenerative disorders (Parkinson disease, ALS)

Other neurologic disorders (eg, stroke, myopathy, multiple sclerosis)

Chronic illness, general deconditioning, and frailty

Medical conditions such as autoimmune/inflammatory diseases (eg, polymyositis, systemic sclerosis) or candida esophagitis

Medications

A separate but related problem, pain upon swallowing (odynophagia), can result from inflammation, infection, neoplasia, or the effects of cancer treatment. (See "Deep neck space infections in adults" and "Pill esophagitis" and "Esophageal candidiasis in adults" and "Herpes simplex virus infection of the esophagus" and "Evaluation of the patient with HIV, odynophagia, and dysphagia", section on 'Etiology' and "Oral toxicity associated with systemic anticancer therapy" and "Management and prevention of complications during initial treatment of head and neck cancer", section on 'Mucositis' and "Clinical manifestations, diagnosis, and staging of esophageal cancer", section on 'Clinical manifestations'.)

Approaches to the differential diagnosis of dysphagia and suggested workup for patients with esophageal dysphagia and oropharyngeal dysphagia are presented in the algorithms (algorithm 1 and algorithm 2 and algorithm 3). (See "Approach to the evaluation of dysphagia in adults", section on 'Symptom-based differential diagnosis' and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management", section on 'Determining the etiology' and "Approach to the evaluation of dysphagia in adults", section on 'Approach to diagnostic testing'.)

Aspiration — A disordered swallowing mechanism predisposes to aspiration. In addition to dysphagia, other factors that predispose to aspiration include reduced consciousness, which compromises the cough reflex; mechanical disruption of the upper airway or gastrointestinal tract; and recumbent patients who receive large volume tube feedings and feeding gastrostomy. All patients with these conditions should be asked about and observed for cough after swallowing. A history of coughing while eating or drinking is likely to indicate aspiration, but aspiration may also be clinically silent. (See "Aspiration pneumonia in adults" and "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences".)

When aspiration is suspected, bedside assessment includes observation of the patient after swallowing a sample of thin liquids, thick liquids, and solids. In addition to cough, helpful signs include drooling after swallowing, wet or hoarse vocal quality after swallowing, head or neck repositioning while swallowing, and multiple attempts to swallow a bolus. When evaluated with formal swallowing studies, some of these patients will be found to have laryngeal penetration. In such cases, a balance has to be struck between quality of life issues (ie, continue eating despite the high risk for aspiration) and safety considerations (mechanical soft or pureed diets, nasogastric tube, gastrostomy tube, or nothing by mouth). Interestingly, many patients who aspirate when swallowing still are able to swallow small pills without difficulty. (See "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences" and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)

Lack of appetite — Lack of appetite is frequently seen in patients with many kinds of advanced illnesses (eg, heart failure, cancer, COPD, frail older adults) and is often a foremost concern of patients and their families or loved ones.

Although the reliability of subjective assessments of appetite is debated, they are probably the simplest and most practical measures available. Patient-rated assessment measures have been developed in the setting of trials of megestrol acetate for cancer or HIV-related anorexia (eg, Functional Assessment of Anorexia/Cachexia Therapy [FAACT] [110]). Another instrument, the Subjective Global Assessment of Nutrition instrument, has been correlated with nutritional status and caloric intake but requires further validation [111]. A simple vertical VAS measurement has been shown to correlate with nutritional intake in cancer patients in the last few weeks of life [112]. Simply asking about what the patient eats and drinks in a typical day can allow the clinician to estimate caloric intake. Asking if the patient is bothered by lack of appetite will enable the clinician to know if treatment is needed or not. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Assessment'.)

Lack of appetite can be a consequence of chronic fatigue or associated with barely noticeable nausea; depression, pain, xerostomia, and constipation can also contribute. An important and treatable etiology is early satiety due to disorders of gastric motility. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis" and "Diabetic autonomic neuropathy of the gastrointestinal tract".)

Other common considerations include medications (amphetamines, antibiotics, antihistamines, digoxin, ranolazine), depression, taste disturbances, and food aversions. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Anorexia'.)

Decreased appetite is a component of the “failure to thrive” (FTT) syndrome, which is described by the National Institute of Aging as “syndrome of weight loss, decreased appetite and poor nutrition, and inactivity, often accompanied by dehydration, depressive symptoms, impaired immune function, and low cholesterol” [113]. In geriatric practice, FTT describes a point further along a geriatric functional continuum that is closer to full dependence and death, with “frailty as a mid-point between independence and pre-death” [114]. (See "Failure to thrive in older adults: Evaluation".)

Weight loss — Among patients with advanced illness, weight loss may occur even in the setting of a good appetite and adequate caloric intake, as typified by cachexia associated with advanced heart and lung disease, cancer, and HIV and other chronic infections. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Definitions'.)

Weight loss of greater than 5 percent of baseline is generally accepted as significant. Determining whether patients feel they “look like themselves” may lead to a discussion of weight loss. Cachexia is a hypercatabolic state that is characterized by an accelerated loss of skeletal muscle in the context of a chronic inflammatory response, and it should be distinguished from sarcopenia, loss of muscle. In advanced illness, weight loss is not remedied by nutritional supplementation. Important physical findings that support the suspicion of cachexia are temporal wasting, thenar wasting, and dorsal interosseous wasting. (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Cachexia'.)

While cachexia in advanced illness typically reflects a metabolic disorder of uncertain cause and for which treatment is largely ineffective, the usual causes of weight loss, such as loss of appetite, inadequate nutritional intake, and malabsorption, should not be overlooked. In some cases, cancer treatment (eg, androgen deprivation therapy for advanced prostate cancer, tyrosine kinase inhibitors such as sorafenib) may contribute to loss of lean body mass (sarcopenia). (See "Assessment and management of anorexia and cachexia in palliative care", section on 'Definitions' and "Pathogenesis, clinical features, and assessment of cancer cachexia", section on 'Contribution of cancer treatment' and "Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects", section on 'Muscle wasting/sarcopenia'.)

Nausea with or without vomiting — Nausea and vomiting are symptoms that are common near the end of life, and they can cause substantial physical and psychological distress for patients and their families or loved ones [115]. Although vomiting is more easily quantified, nausea has been routinely measured using a visual analog scale in clinical trials of antiemetics in patients with chemotherapy-induced nausea and vomiting (CINV). (See "Approach to the adult with nausea and vomiting" and "Prevention of chemotherapy-induced nausea and vomiting in adults".)

A thorough history and physical examination are essential first steps in the management of these patients to define the severity of the symptoms and identify clues to the underlying etiology. Among patients receiving chemotherapy, nausea and vomiting should not be automatically assumed to represent breakthrough CINV, particularly if symptoms develop at a time point that is not consistent with CINV. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)

From a pathophysiologic standpoint, nausea and vomiting can be vagally mediated through the emesis center in the medulla, systemically mediated through the chemoreceptor trigger zone (CTZ), vestibular, or centrally mediated (figure 5). The differential diagnosis of nausea and vomiting in the adult is broad and includes medications and toxic etiologies (including chemotherapy and opioids), disorders of the gut and peritoneum (including gastroparesis), central nervous system disorders (brain metastases, cranial irradiation), vestibular disorders, and endocrinologic/metabolic causes. (See "Approach to the adult with nausea and vomiting", section on 'Differential diagnosis'.)

The most common causes of nausea and vomiting in palliative care patients are outlined in the table (table 17). Most palliative care patients who are nauseated have more than one contributory factor. This subject is discussed in detail elsewhere. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Patient assessment'.)

Constipation — Constipation is a common symptom that contributes to significant suffering in patients with serious illness, particularly in the terminal phase. A major contributing factor is opioid-induced constipation, but other factors contribute [116]. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Constipation'.)

Risk factors for constipation in patients who have a serious or life-threatening illness include advanced disease, older age, decreased physical activity, low-fiber diet, depression, cognitive impairment, hemorrhoids, and polypharmacy. In addition to opioids, medications which can cause or exacerbate constipation include 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 causes of constipation (eg, hypercalcemia and hypothyroidism).

Determining the presence of constipation can be difficult as the term has varied meanings for different people. For some, it may mean that stools are too hard or too small, or that defecation is too difficult or infrequent. The first three complaints are difficult to quantify in clinical practice; the last can be measured and compared with the general population. (See "Etiology and evaluation of chronic constipation in adults", section on 'Definition of constipation'.)

Definitions of constipation used in different publications have been variable [117]. Formal criteria are available to define chronic functional constipation (the Rome IV criteria) [118], but they are not useful in palliative care as they require that symptom onset should occur at least six months before diagnosis, and symptoms should be present during the last three months. (See "Constipation in the older adult", section on 'Definition of constipation'.)

However, the updated ROME IV criteria do provide usable diagnostic criteria for opioid-induced constipation, a common problem in palliative care populations [118]. In addition, a tool for quantifying opioid-induced constipation, the Bowel Function Index (BFI) (table 18), has been developed and validated [119-121]. Use of this tool is recommended in consensus-based guidelines from the American Academy of Pain Medicine, which have been endorsed by the American Gastroenterological Association [122]. One of the benefits of using this tool is that specific scores can be utilized to define a threshold for considering prescription therapies in patients with previous or current use of first-line interventions [120,122]. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Constipation'.)

Outside of the setting of opioid use, others consider that four domains are pivotal to making a diagnosis of constipation in palliative care [117]:

Any lifelong history of constipation (using the Rome criteria)

Evaluation of physical dysfunction that may impede normal defecation

Subjective sensations (eg, feelings of incomplete defecation or bloating or fullness)

Objective changes (eg, frequency or consistency of stools)

A patient with constipation should be asked when they last had a bowel movement and about any associated symptoms including rectal urgency, rectal pain, fullness or pressure, abdominal distention, and small stool size. In the palliative care setting, patients with constipation may also present with abdominal pain, nausea, vomiting, diarrhea, or oozing of liquid stool with stool incontinence. Consistency of stool (soft or hard) is a helpful detail.

A comprehensive physical examination should be performed that includes a rectal examination to palpate for hard stool, assess for masses, anal fissures, hemorrhoids, sphincter tone, push effort during attempted defecation, prostatic hypertrophy in males, and posterior vaginal masses in females. Rectal examination may demonstrate impaction, or the rectal vault may be empty. (See "Etiology and evaluation of chronic constipation in adults", section on 'Physical examination'.)

If the rectal vault is empty and a diagnosis of malignant bowel obstruction is suspected, radiographic imaging with abdominal radiograph or computed tomography (CT) scan is indicated. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults".)

There is a paucity of evidence and a lack of consensus as to how the severity of constipation is best addressed in palliative care populations. The degree of retention of stool may be difficult to estimate from history and physical examination. A clinical constipation assessment scale has been developed and validated (table 19) [123,124], but this is semi-quantitative at best and does not include objective information about the overall stool load.

Are abdominal radiographs needed? — A number of palliative care clinical guidelines suggest that plain abdominal radiographs may be used as part of the overall assessment of constipation, including severity [125,126]. However, assessing constipation with plain radiographs is poorly validated with available data [127,128], and their utility is debated.

Some have proposed scoring systems for assessing the severity of constipation in terminal cancer patients based upon the amount and distribution of stool in different quadrants of the large bowel [129,130]. Each abdominal quadrant on plain films is assessed for stool content and ranked for 0 to 3, resulting in a severity score from 0 to 12. In both of these studies, the radiographic assessment was performed by specially trained palliative care physicians or gastroenterologists.

On the other hand, others have questioned the assessment of constipation severity based upon plain radiography in palliative care patients. One study of 30 constipated palliative care patients showed little interobserver agreement as to the degree of fecal loading based upon plain abdominal radiographs among four independent clinicians (two palliative care physicians, a registered nurse, and a “junior medical officer” whose specific training was not stated) [131]. In addition, there was poor correlation between clinician-assigned fecal loading scores and objectively measured colon transit times, or with patient self-reported symptoms. A similar lack of correlation between radiographic shadowing on plain abdominal films and objectively measured colon transit times [132] and with patient self-reports [132,133] has been noted by others.

The lack of data to support the routine use of plain radiographs to assess the degree of constipation is reinforced by the American College of Gastroenterology Task Force on Chronic Constipation, which did not include the use of plain radiographs in their recommendations for comprehensive management of constipation, and the American College of Colon and Rectal Surgeons specifically recommends against using plain abdominal radiographs for the assessment of constipation [134,135].

In our view, the use of plain abdominal radiographs should be limited to the following clinical scenarios:

Concern for bowel obstruction or ischemia

A patient with liquid stool in whom severe constipation is thought to be responsible

A patient with a lifelong history of constipation in whom neurogenic causes of reduced bowel motility are a concern in order to detect megacolon or megarectum

Occasionally to monitor the response to laxatives in patients with fecal retention

Swelling in the arms and legs — Peripheral edema, palpable swelling that is produced by expansion of the interstitial fluid volume, is a common complication in patients with advanced organ dysfunction. When massive and generalized, the excess fluid accumulation is called anasarca. Anasarca or just lower-extremity edema can interfere with ambulation and is often a source of pain from stretching of the skin. It may also directly affect the patient’s sense of body image. (See "Clinical manifestations and evaluation of edema in adults".)

Assessment of edema starts with the history which should include questions about area(s) of involvement, associated symptoms (eg, pain), use of medications that may be associated with edematous states (eg, nonsteroidal antiinflammatory drugs [NSAIDs] and gabapentin/pregabalin) or that are being used to treat edema (eg, diuretics), progression of symptoms, and history of medical conditions associated with lymphedema, including surgery and prior radiation therapy, travel, or infection. (See "Pathophysiology and etiology of edema in adults", section on 'Drug-induced edema'.)

The physical examination should be aimed at establishing the pattern of edema (pulmonary, peripheral, ascites, localized) and an assessment of the central venous pressure. The results can indicate the likely cause of edema (table 20). (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Diagnosis' and "Pathophysiology and etiology of edema in adults", section on 'Etiology'.)

For patients with lymphedema, clinical measurements of girth or estimates of lymphedema volume are necessary to establish baseline and to track changes during treatment. Methods to obtain clinical measurements are described in detail elsewhere. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Extremity measurements'.)

A variety of clinical conditions are associated with the development of edema, including heart failure, cirrhosis, hypothyroidism, hypoalbuminemia, and the nephrotic syndrome, as well as local conditions such as venous and lymphatic disease or malignant ascites (table 21). Among patients who are terminally ill with a serious and/or life-threatening illness, the most common causes of chronic lower-extremity edema are venous obstruction, hypoalbuminemia, decreased mobility, fluid retention, and medications including corticosteroids. (See "Pathophysiology and etiology of edema in adults".)

Lymphedema, a specific type of peripheral edema that is usually (but not always) nonpitting, may represent a complication of a cancer or its treatment. 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 [136]. Lymphedema is generally due to disruption of lymphatic flow which may be secondary to injury, surgery, radiation therapy, infection, or malignancy. 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 lymphedema affects both physical and psychological wellbeing as a result of interruption of normal daily activities. Cancer patients with lymphedema are more likely to experience greater disability, poorer quality of life, and greater psychological distress as compared with cancer patients without lymphedema [137]. It may cause patients to feel mental suffering, discomfort, and reduce mobility as well as function [138,139]. (See "Clinical features and diagnosis of peripheral lymphedema".)

Insomnia — Insomnia is a condition of impaired sleep, with difficulties in initiating or maintaining sleep, and/or experiencing sleep as nonrestorative and unrefreshing, despite having the appropriate opportunity for sleep to occur. According to the International Classification of Sleep Disorders, Third Edition (ICSD-3), insomnia is present if the patient reports [140] (see "Evaluation and diagnosis of insomnia in adults", section on 'Diagnostic criteria'):

Difficulty initiating sleep, difficulty maintaining sleep, or waking up too early, despite adequate opportunity and circumstances for sleep

Daytime impairment that is attributable to the sleep difficulties

Insomnia is a very common medical complaint in patients receiving palliative care, with an estimated prevalence of 60 percent or more [141-143]. Insomnia is associated with multiple consequences that have a negative impact on quality of life and the ability to perform normal functions. In addition, insomnia is a strong predictor of the development of psychiatric disorders. (See "Risk factors, comorbidities, and consequences of insomnia in adults", section on 'Adverse outcomes'.)

In the context of palliative care, insomnia often coexists with other symptoms, such as pain, depression, and anxiety, and the presence of one often exacerbates the other, contributing to a decrease in quality of life [144]. In addition to physical symptoms, environmental factors, daytime naps, emotional distress, and medication side effects may contribute and should be addressed. This subject is discussed in detail separately. (See "Insomnia in palliative care".)

Psychological and cognitive symptoms — The key psychological symptoms requiring assessment in palliative care patients are depression (as distinct from adjustment reaction and grief), anxiety, and delirium. Clinicians should screen for the multiple factors that increase the prevalence and/or severity of psychological distress (rapidly advancing disease, medications such as interferon or glucocorticoids, metabolic abnormalities, uncontrolled pain, impaired cognition, financial distress) and address them, if possible. Psychological distress frequently lessens with adequate pain relief [145].

Sadness, grief, depression, and demoralization — There is a high frequency of mood disorders in patients with a serious and/or life-threatening illness. As an example, in one meta-analysis, there was a 25 percent combined prevalence of all types of depression and a 38 percent prevalence of mood disorders among palliative care patients [146]. The spectrum of mood disorders and conditions seen in palliative care patients includes sadness, normal grief reaction (including anticipatory grief), pathologic grief, adjustment disorder with depressed features, minor as well as major depression, and demoralization.

Grief versus depression — Grief, a natural and expected reaction to having a life-limiting illness and loss, can and should be distinguished from major depression [147].

A summary of some of the contrasting characteristics of normal grief versus depression in terminally ill patients is provided in a table (table 22), and this subject is discussed in detail elsewhere. (See "Assessment and management of depression in palliative care", section on 'Assessment and diagnosis' and "Bereavement and grief in adults: Clinical features", section on 'Major depression'.)

Unfortunately, depression is frequently unrecognized and undiagnosed in palliative care patients [25,148]. The prevalence, burden, and challenges in recognizing and treating depression in palliative care patients are addressed in detail elsewhere. (See "Assessment and management of depression in palliative care", section on 'Prevalence of depression in palliative care' and "Assessment and management of depression in palliative care", section on 'Burden of depression'.)

Patients with advanced illness may display many of the vegetative signs of depression (sleep disorder, poor concentration, fatigue, lack of appetite) without being depressed, since such symptoms can be caused by the medical condition or its treatment. Patients facing the end of life may also demonstrate significant guilt and preoccupation with death without being depressed. Nevertheless, the presence of these markers in the absence of other causes should lead to the suspicion of depression. Indicators of poor emotional wellbeing, such as a sense of pervasive hopelessness, helplessness, worthlessness, or guilt, may be more useful in making the diagnosis and in assessing suicide risk. Unrelieved symptoms, particularly pain, may contribute to a sense of hopelessness and lead to depression. Loss of independence can contribute to guilt and worthlessness. Among patients with severe pain or other symptoms, a diagnosis of depression should not be made until symptoms are controlled.

The impact of mood disorders in palliative care is underscored by one study which found that mortality rates in cancer patients are up to 25 percent higher in those who experience depressive symptoms [149]. In addition, individuals who suffer from depression are at increased risk of suicide. Passive suicidal ideation (“I’d be better off dead”) should be distinguished from active suicidal ideation (“I’d be better off dead and this is how I’m going to do it”). An expressed desire for a hastened death should not be considered a request for euthanasia, but as a marker for intense distress which requires further exploration [150]. (See "Assessment and management of depression in palliative care", section on 'Burden of depression' and "Physician-assisted dying".)

Screening tools — A variety of screening tools for symptoms of depression are available:

Abbreviated screening instruments (table 23) appear to be as effective as longer instruments to screen for depression. As an example, screening using a simple one question assessment (“Are you depressed?” or “Have you been depressed most of the time for the past two weeks?”) has a negative predictive value (NPV) of 94 percent [151,152] in identifying patients in whom a diagnosis of depression would be excluded on the basis of a full psychiatric interview. Adding a second question that addresses anhedonia (“Have you experienced loss of interest in things or activities that you would normally enjoy?”) increases the NPV to 98 percent [152].

Another simple screening strategy for mood disorder and psychosocial distress utilizes the Distress and Impact Thermometer [153] or other ultra-short methods [154].

Importantly, these brief tools are designed for screening patients who may subsequently need a full diagnostic evaluation for depression. The subject of screening for depression in palliative care patients is discussed in more detail elsewhere. (See "Assessment and management of depression in palliative care", section on 'Simple screening instruments'.)

Demoralization — Demoralization is a mental state of lowered morale and poor coping, characterized by feelings of hopelessness, helplessness, and loss of purpose and meaning; it is distinct from clinical depression [155] and can be precipitated by existential distress [42]. By contrast, depression is a loss of pleasure and interest in the present moment (generalized anhedonia). (See "Assessment and management of depression in palliative care", section on 'Existential concerns and spirituality'.)

Demoralization is a common problem among patients with serious medical illness. One systematic review found the prevalence of demoralization to be around 15 percent in patients with cancer and progressive disease [156]. Despite this, there is a general lack of awareness of demoralization and how and when to intervene [157]. Among the factors that are consistently associated with demoralization are poorly controlled physical symptoms, inadequately treated depression and anxiety, reduced social functioning, unemployment, single status [155], and possibly age and sex [158].

The Demoralization Scale has been used to identify affected patients [159]; it has been revised and revalidated (table 24) [160]. An abbreviated tool to assess for demoralization in palliative care patients has also been developed (the Short Demoralization Scale [161]), which measures five dimensions of demoralization (loss of meaning, helplessness, disheartenment, dysphoria, and sense of failure). However, this tool has not yet been independently validated.

Treatment of demoralization in patients receiving palliative care can include restoring some control (eg, better pain management) or providing meaning (eg, cognitive behavioral therapy, life review, dignity therapy, and meaning-centered psychotherapy); more research is needed in this area [42].

Anxiety — Anxiety is common in patients with an advanced serious or life-threatening illness. As an example, the reported prevalence of anxiety among advanced cancer patients is 18 percent [162]. (See "Overview of anxiety in palliative care".)

Anxiety may also be related to a preexisting anxiety disorder, substance abuse, delirium, or under-treated symptoms, most commonly pain. A single aggregate question (“Have you felt anxious, nervous, uneasy, tense, or frightened in the recent days?”) can be utilized to screen for symptoms of anxiety.

Delirium — Delirium and confusional states are among the most common neuropsychiatric disorders encountered in patients with medical illness, particularly older individuals. According to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of delirium requires each of the following criteria [163]:

Disturbance in attention and awareness that develops quickly (usually hours to days) and tends to fluctuate each day.

Disturbance in cognition (eg, memory, orientation, language, visual spatial ability, and/or perception).

The disturbances in attention, awareness, and cognition are not better explained by another neurocognitive disorder and do not occur in the context of coma.

Evidence from the history, physical examination, or laboratory findings indicate that the disturbances are caused by a general medical condition, substance intoxication or withdrawal, and/or medication side effect.

Subtypes of delirium have been delineated based upon the patient’s psychomotor behavior and level of arousal [163,164]:

Hypoactive subtype – Psychomotor retardation, lethargy, and decreased level of arousal.

Hyperactive subtype – Restlessness, agitation, and hypervigilance. Mood lability, failure to cooperate with care, and psychotic features may also be present.

The mnemonic FACT provides a summary of the diagnostic criteria of delirium:

Fluctuating cognitive deficit(s) with acute onset

Attention deficits, and either

Consciousness level disturbance; or

Thought disorganization

Delirium is the most common neuropsychiatric complication seen in patients with advanced cancer nearing the end of life and can result in distress for patients, family members, and health care providers. (See "Palliative care: The last hours and days of life", section on 'Delirium'.)

It is also a marker for shortened survival in hospitalized and institutionalized patients [80,165,166]. (See 'Performance status, symptoms, and prognosis' above.)

Delirium in cancer patients is frequently missed and is often misdiagnosed as akathisia, anxiety, dementia, depression, or psychosis [167,168].

For many terminally ill patients with COPD, end-stage kidney disease, heart failure, and other serious life-threatening diseases, global cerebral dysfunction without a definable reversible cause, manifested as delirium, is the final common complication that precedes death. However, for many palliative care cancer patients, a number of factors may contribute to the development of delirium, many of which are potentially reversible [169]. Some of the most frequent contributors are [170]:

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

Brain tumor/metastases/cerebral edema

Cancer treatment (chemotherapy, radiation therapy) (see "Overview of neurologic complications of conventional non-platinum cancer chemotherapy" and "Clinical features and diagnosis of psychiatric disorders in patients with cancer: Overview")

Psychotropic drugs (tricyclic antidepressants, benzodiazepines) and anticholinergics

Metabolic (increased calcium, decreased sodium, renal failure) (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")

Disturbed sleep (in the intensive care unit [ICU] setting), and other causes of sleep deprivation

Sepsis

Paraneoplastic neurologic syndromes (see "Overview of paraneoplastic syndromes of the nervous system" and "Paraneoplastic and autoimmune encephalitis")

Many of the risk factors for delirium are already present in patients with advanced terminal illnesses, although many patients improve with treatment of specific causes. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Delirium'.)

The fact that delirium may be reversible in up to 50 percent of cases [169] underscores the importance of early recognition and aggressive evaluation and management.

Multiple instruments have been developed for screening for delirium:

The Confusion Assessment Method (CAM) (table 25) has become a standard screening device in clinical studies of delirium, conducted across multiple settings including emergency departments and in long-term care [171]; a version is available (CAM-ICU) that is validated in patients in the ICU [172,173]. (See "Diagnosis of delirium and confusional states".)

The Memorial Delirium Assessment Scale (MDAS) (form 2A-B) is a 10-item, four-point (0 to 3) observer-rated scale that was designed to quantify the severity of delirium in medically ill patients with serial observations [174,175]. It includes assessment of disturbances in awareness, orientation, short-term memory, digit span, attention capacity, organized thinking, perception, delusions, psychomotor activity, and arousal in a way that reflects all the main diagnostic criteria according to the Diagnostic and Statistical Manual for Mental Illness.

The MDAS has been used and validated for screening and diagnosis of delirium in cancer patients [175] and is able to distinguish patients with delirium from those with other cognitive or noncognitive psychiatric disorders. In one study, a cutoff score of 7/30 on the MDAS yielded the highest sensitivity (98 percent) and specificity (96 percent) for the diagnosis of delirium [175]. In many institutions, this tool has replaced the Mini-Mental Status Examination (MMSE) for assessment and monitoring of delirium.

The bedside confusion scale (ability to recite the 12 months in reverse order and assessment of consciousness state) is another excellent tool to screen and longitudinally follow delirium in palliative care [176]. Serial-sevens and spelling a word such as “farm” or “world” backward are other simple tests of attention. Another bedside test of attention is outlined in the table (table 26). (See "Diagnosis of delirium and confusional states" and "Clinical features and diagnosis of psychiatric disorders in patients with cancer: Overview".)

PHYSICAL EXAMINATION AND INVESTIGATIONS — Both physical examination and investigations may be important in characterizing a symptom and for definitive diagnosis.

When considering new investigations on palliative care patients who may be quite ill (particularly if they are at the end of life), an important consideration is that if the result is not expected to change management of a symptom complex, the investigation should not be done. Sometimes even necessary investigations may have to be eliminated or postponed because of patient frailty.

ONGOING RESEARCH — Several areas that pertain to symptom assessment are actively being studied.

Item response theory – Item response theory (IRT) represents a newer approach to determining the severity of a construct, including symptoms. Originally, IRT was based upon educational testing. If one wanted to determine which grade a high school student was in from answers to questions (items), one would ask a question that might be answerable only by a 12th grader and another that might be answerable by a 9th grader. If one has a wide variety of items that cover all grades (an item bank), then assessment of all the answers can precisely identify what grade the respondent is in. However, this approach is quite time consuming. Another option is to have an interactive interview where a computer helps select items based upon answers as they come in (computerized adaptive testing [CAT]); this results in fewer items needed to assess “severity” or educational level. Another is to select a limited number of items for pencil and paper versions. Potential advantages of IRT are that a smaller number of items can yield as much information as a standard questionnaire, and that the wider range of responses to the IRT questionnaires will avoid “ceiling” and “floor” effects where all participants in a survey answer yes or no to all of the questions. Item banks have been developed and tested for symptom severity and quality of life analysis, and the resulting questionnaires, both computer-assisted and pencil and paper versions, are entering research and clinical applications [177].

Electronic symptom assessment – With electronic capabilities, the next step has been to automate symptom assessment by asking patients to directly respond to symptom questions with an electronic device. This speeds up data entry and allows for rapid analysis and presentation of findings to care providers [178]. To date, answers to electronic versions do not seem to differ from those to paper and pencil versions. Electronic implementation has made possible symptom assessment on a large scale across health networks [179] and the development of web-based systems [180] for patient self-reporting.

Symptoms are common among patients receiving treatment for advanced cancer, but they may be undetected by clinicians. The benefits of enhanced symptom monitoring during routine cancer care using web-based systems to facilitate patient-reported outcomes was shown in a seminal study in which 766 patients receiving active treatment for cancer were randomly assigned to a web-based tool to report 12 common symptoms between visits (which were then shared with nurses if participants reported severe or worsening symptoms) or to usual care at the discretion of the clinician [181,182]. Health-related quality of life improved in more participants in the intervention group (34 versus 18 percent) and worsened in fewer (38 versus 53 percent) [181]. Self-reporting patients had fewer admissions through the emergency department (34 versus 41 percent) and remained on chemotherapy longer (mean 8.2 versus 6.3 months). Patients who self-reported outcomes during treatment also lived significantly longer than did those receiving usual care (31 versus 26 months, p = 0.03) [182].

Moving palliative care upstream – Symptom assessment can be adopted to monitor adverse events during cancer chemotherapy administration for cancer patients. In a single-institution, randomized, controlled trial that compared electronic symptom reporting and monitoring with usual care in patients receiving nonprotocol chemotherapy for metastatic cancer, benefits of electronic symptom reporting were seen in quality of life, emergency department admissions [181], and survival [182]. In other studies where interventions do not follow upon the receipt of an alert, no changes have been seen in quality of life [183]. Ambulatory oncology clinics are another setting where symptom assessment is being implemented.

Development of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) – Adverse event reporting is a critical part of the clinical trials system. A patient-reported-outcome-based adverse event reporting system for clinical trials that will supplement the standard adverse event manual has been developed by the National Cancer Institute (NCI) [184] and validated for adults [185] and in pediatrics [186,187].

Importantly, symptom assessments, whether derived electronically or by patient report, rely upon the willingness of health care professionals to use the findings. This is a potential barrier that is now beginning to receive more attention.

In Ontario, the Edmonton Symptom Assessment Scale (ESAS) is completed before each visit. In a review of charts at a Canadian regional cancer center, as ESAS pain severity scores increased, the number of patients who received a pain intervention increased; 37 percent of patients with severe pain had a pain intervention. However, the clinical context was unclear [188].

In another survey of cancer professionals in Ontario, the ESAS screening results were viewed always or frequently by 79 percent of physicians, 89 percent of nurses, 66 percent of psychosocial staff, and 29 percent of radiotherapists. The response rate to the survey was low [189].

Symptom assessment as the basis of health care delivery – The concept here is that the results of symptom assessment guide the health care system. In one approach, cumulative data on symptom assessment are used by the health care system to improve assessments and interventions at a system level [190]. In another approach, called measurement-based practice, measurements from symptom assessment instruments administered across the system are used by practitioners to assess and set goals for individual patients [191].

Symptom assessment instrument utilization and symptom reports as a measure of palliative care quality.

Symptom burden as an explanatory variable for how the totality of symptoms can influence or are related to other aspects of patient experience [192].

Symptom trajectories over time as a descriptive, predictive, or explanatory variable [64].

Symptom clusters – The co-occurrence of symptoms with an increased frequency is the underlying concept for symptom clusters, which has the potential for grouping or simplifying the many symptoms that can be reported by patients [193].

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".)

SUMMARY

Frequently encountered symptoms in patients with an advanced serious and/or life-threatening illness include pain, dyspnea, fatigue, dry mouth, dysphagia and aspiration, loss of appetite and weight, nausea/vomiting, constipation, edema, depression, anxiety, demoralization, and delirium. An approach to assessment of these symptoms is outlined in the sections above. (See 'Approach to specific symptoms' above.)

Patient descriptions and symptom ratings are the primary data for overall assessment. The use of different dimensions (severity, frequency, distress, interference) may help when patients and families get stuck on trying to describe the impact of a symptom. (See 'Dimensions of symptom assessment' above.)

The patient’s assessment of symptom relief is important and may differ from that of the health professional. (See 'General principles' above.)

Performance status (table 6 and table 7) is a key indicator of prognosis in individuals with advanced terminal disease and is associated with symptom severity. For patients with advanced, serious, life-threatening diseases, such as those referred to palliative care programs, the presence or absence of certain symptoms, particularly dyspnea, may help clinicians provide a more refined estimate of patient survival. (See 'Performance status, symptoms, and prognosis' above.)

A number of validated symptom assessment tools may be useful in palliative care settings, including those that evaluate multiple symptoms, such as the revised Edmonton Symptom Assessment Scale (ESAS) (table 5). Many symptom-specific tools are available, such as the Brief Pain Inventory (BPI). Multisymptom assessment tools definitely yield a higher number of symptoms, and they can be used as checklists. (See 'Assessment and rating instruments for symptoms' above.)

Physical examination and diagnostic investigations should not be performed on patients who are frail and at the end of life unless the result is expected to change management of a symptom complex. (See 'Physical examination and investigations' above.)

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Topic 2196 Version 64.0

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