Physical Aspects of Care
See ICSI Palliative Care Order Set for specific medications and dosages.
Key Points:
- Anticipate symptom progression, assessing needs and efficacy of interventions as disease progression occurs, and adjust interventions accordingly.
- Use a team approach to care when possible and appropriate.
- Symptom control is important, but suffering is much broader than just physical symptoms.
Physical Aspects of Care
The control of physical symptoms is an important part of palliative care. Common symptoms include, but are not limited to pain, anxiety and depression, anorexia and cachexia, constipation, delirium, diarrhea, dyspnea, fatigue, and nausea and vomiting.
Pain
Control of pain in order to improve quality of life is an important aspect of palliative care.
Pain is a subjective symptom; there is no test to measure pain. Pain is what the patient says it is, and it needs to be addressed adequately in order to improve quality of life. The patient should be actively involved in establishing the goals of palliative pain management, along with family members. The clinician should frequently reassess the patient's desired level of comfort and response to interventions.
Patients and family members should be educated about medication compliance, addiction, tolerance, side effects and appropriate dosing of analgesics. Many patients, as well as family members, believe the use of opioids will create "addicts" and so are reluctant to use opioids for analgesia. All opioids will result in physical dependence, and sudden discontinuation of the opioid may result in symptoms of withdrawal. Physical dependence is not addiction. Addiction, as defined by the Federation of State Medical Boards of the United States, is "a primary, chronic, neurobiologic disease…characterized by behaviors that include the following: impaired control over drug use, craving, compulsive use, and continued use despite harm." Pseudoaddiction may occur when analgesics are prescribed inadequately. When the interval between doses of opioids is too long, a patient's pain relief may wane, resulting in the need to ask for more medication. This request, sometimes perceived as "drug-seeking behavior," is actually a consequence of poor prescribing habits.
Barriers to good pain management in palliative care include discounting a patient's subjective measure of pain, difficulty in assessment of the cognitively impaired, myths believed by both practitioners and patients about opioid therapy, and fears of addiction and hastening death.
A thorough assessment of the patient should distinguish whether the patient has visceral, somatic or neuropathic pain. Recommendations and options for treatment of each type of pain can be found in the National Guideline Clearinghouse (NGC) summaries of the Institute for Clinical Systems Improvement (ICSI) guidelines Assessment and Management of Acute Pain and Assessment and Management of Chronic Pain.
Anxiety and Depression
Affective disorders such as anxiety and depression are common in seriously ill patients, and they adversely affect their quality of life. Not only can they cause physical symptoms such as nausea, dyspnea and insomnia, but conversely, experiencing such symptoms can exacerbate anxiety, as well. Undertreated pain can exacerbate psychological distress.
Benzodiazepines are often helpful in the treatment of anxiety. Lorazepam and oxazepam are preferred since they do not have active metabolites. A significant minority of individuals manifest a paradoxical reaction to benzodiazepines, becoming more agitated. Chronic anxiety frequently responds to the use of serotonin-specific or serotonin-norepinephrine re-uptake inhibitors.
Diagnosing depression can be challenging because many of the typical somatic symptoms such as fatigue, insomnia and anorexia can be caused by the underlying medical illness or by normal grief. Psychological symptoms such as apathy, anhedonia and feelings of worthlessness and hopelessness may suggest the diagnosis. Although a variety of helpful depression assessment questionnaires and tools exist, the clinical interview is still the gold standard for diagnosis of depression [R].
It is important to differentiate grief from depression. Grieving can be an appropriate response to loss, but persistence of the above symptoms mandates consideration of depression. Simply asking a patient, "Are you depressed?" can be a useful screening tool and provides a reasonably sensitive and specific assessment of depression in patients with terminal illnesses [R]. However, this may be preceded by some information to the patient about the difference between clinical depression and appropriate reactive feelings to the situation. The clinician must inquire if the patient is at risk for suicide. There is no evidence that asking the patient about suicide increases the risk that the patient will carry out his or her plan.
In depression, serotonin-specific re-uptake inhibitors are drugs of first choice, including in older and frail patients. However, it may take weeks to fully respond. Psychostimulants such as methylphenidate can produce a more rapid response and are well tolerated in most patients. In patients with a life expectancy of more than a few weeks, a successful therapeutic trial of psychostimulants should be accompanied or followed by an antidepressant medication such as a serotonin-specific re-uptake inhibitor [R]. Because antidepressant drug treatment is usually well tolerated, some expert consensus statements recommend a low threshold for instituting treatment, although evidence from primary studies on the effectiveness of antidepressants at the end of life is poor. Evidence regarding the pharmacologic treatment of anxiety in the palliative care setting is similarly limited [R].
Nonpharmacologic measures for affective disorders are often beneficial and should not be overlooked. A combination of antidepressant medications, supportive psychotherapy, and patient and family education are considered the gold standard of treatment of depression in palliative care. Cognitive therapy may also be helpful in some circumstances. Studies in psychotherapy in depressed palliative care patients have shown equivocal results, but data are limited by small sample sizes, short follow-up periods, and high diversity of outcome measures used [R].
Anorexia and Cachexia
Anorexia refers to the loss of desire to eat, while cachexia refers to weight loss, especially of lean body mass, which may significantly impair the patient's ability to continue with further therapy. Both these symptoms are found in many severe medical conditions, including cancer, acquired immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease, congestive heart failure, chronic liver and kidney disease, and infections.
Treatable causes of anorexia and cachexia should be identified and addressed. Causes may include pain, depression, gastrointestinal tract dysfunction, and cognitive impairment. Stimulation of appetite through the use of progesterones and corticosteroids may help. One study suggests that doses of 160 mg to 800 mg per day of megestrol acetate have demonstrated a positive effect on appetite and food intake [A]. Other studies have shown that while megestrol produces weight gain, the increase is due to fat and not lean muscle mass [A], [R]. Progestational agents may be associated with an increased risk of thromboembolic events, peripheral edema, hyperglycemia, hypertension, hypogonadism, and adrenal suppression. In order to minimize these adverse effects, doses of megestrol acetate should start at 160 mg daily, and be increased every two weeks until benefit is seen, or until side effects limit further dose escalations [R]. For most conditions, there is scant information about improved quality of life, and no survival benefit has been shown.
Corticosteroids may provide a temporary improvement in appetite and food intake. However, because of significant side effects, these drugs should probably be reserved for the terminally ill, and in those patients who may simultaneously benefit from the antiemetic and analgesic properties of the steroids.
Other agents showing some positive effects on appetite and weight gain include mirtazapine in depression, thalidomide in advanced cancer and AIDS, dronabinol in AIDS and anabolic steroids in chronic obstructive pulmonary disease (COPD) and AIDS [C], [R].
Patients sometimes describe poor appetite when presented food that is unappealing in appearance, consistency or smell. Minimizing dietary and consistency restrictions may tempt the patient to improve his or her intake. Offering small quantities more frequently throughout the day may also promote better intake.
In some cases the patient is less troubled than the family by poor nutritional intake. Clinicians should explore the meaning of feeding in the context of the family's cultural and religious background, and help identify other ways in which the family can participate in caring for the patient.
The role of medical nutrition and hydration (also known as artificial nutrition and hydration - ANH) is not clear-cut. The patient's preferences, either declared at the time of treatment or previously documented in an advance directive, must be respected. In addition, the prognosis of a patient for the acute event, premorbid status, and religious and cultural factors warrant consideration [R].
In the context of a potentially treatable condition, ANH may support an individual who otherwise cannot meet nutritional needs during therapy.
A recent meta analysis of randomized clinical trials studying the effectiveness of nutritional supplementation (either oral, or via enteral or parenteral routes) identified no evidence for clinical benefit in a variety of clinical settings, including cancer, chronic lung or liver disease, and critical care settings [M].
There is no evidence that artificial nutrition and hydration improves outcomes in patients who have severe dementia. Most studies show that total parenteral nutrition in cancer patients receiving chemotherapy actually decreases survival and increases susceptibility to infection [R].
Constipation
Constipation is a common and troublesome symptom for seriously ill patients. Immobility, decreased oral intake, and medications, as well as underlying medical conditions themselves, can contribute to decreased gastrointestinal motility. As many as 95% of patients treated with opioids will experience constipation, and all opioids are associated with constipation. While tolerance to other opioid side effects such as nausea and sedation develops quickly, no tolerance develops to constipation [R].
Fiber supplements are not helpful in these patients, because they cannot achieve adequate fluid intake for them to be effective. Stool softeners and stimulant laxatives, such as bisacodyl and senna are almost always indicated, and patients on scheduled opioids should prophylactically and routinely receive them on a daily basis, unless contraindicated. Polyethylene glycol solutions have been shown to be effective and safe in the general population but have not been well studied in palliative care. Some patients, particularly those with neurogenic bowels, benefit from scheduled suppositories or enemas. Many commonly used agents lack high-quality evidence for effectiveness, but are widely used and generally have minimal toxicity [M], [R].
Patients taking opioids may exhibit additional gastrointestinal symptoms such as bloating, nausea, vomiting, and gastroesophageal reflux, along with constipation. This may represent opiate-induced bowel dysfunction, or opioid-induced constipation. This is a constellation of symptoms mediated through peripheral mu receptors. Oral naloxone has been used. It has very poor bioavailability, but because it crosses the blood-brain barrier it may still cause reversal of analgesia. Newer opioid antagonists that do not cross the blood-brain barrier are in development but not yet clinically available, nor well studied in this population [M].
Delirium
Delirium is a clinical syndrome, not a disease in itself. Its etiology is usually multifactorial and includes central nervous system lesions, drugs, fluid and electrolyte abnormalities, hypoxia and other metabolic abnormalities. It is particularly prevalent in patients with preexisting dementia. Functional dependence, polypharmacy, sensory impairments and the existence of chronic health problems are factors increasing the risk for delirium.
Acute changes in mental status, with disorientation and fluctuations of attentiveness, are hallmarks of delirium. Patients often present with hyperactivity, agitation and combativeness. However, hypoactive delirium marked by lethargy is equally serious.
There are no specific tests, but evaluation should include review of all medications, especially psychoactive drugs: general physical evaluation, including vital signs, hydration status, and oxygenation; pain and recent alcohol or drug use. Particularly in elders, delirium may be the only harbinger of serious illness or complications. A focused search for infection, metabolic abnormalities and other acute illness is necessary.
Treatment of delirium requires correction of underlying abnormalities, as delirium may be reversible in up to 50% of cases in palliative care units. In some elderly patients delirium may be a result of poorly managed pain [R]. When behavioral symptoms threaten the safety of the patient or the ability to provide therapy, psychotropic medications may be used with caution. Haloperidol remains the first drug of choice, with the best evidence base supporting effectiveness. Lower doses are recommended in the elderly. There is little evidence supporting the use of other antipsychotic agents. Benzodiazepines are not recommended for monotherapy because of the risk of paradoxical stimulation, oversedation, and prolongation of delirium, but they can be useful adjuncts if haloperidol alone is not effective.
Note: the U.S. Food and Drug Administration informed health care professionals that the warnings regarding the use of haloperidol have been updated stating that Torsades de Pointes and QT prolongation have been observed in patients receiving haloperidol, especially when the drug is administered intravenously or in higher doses than recommended.
No good evidence exists for the use of other psychotropic drugs for delirium. Non-pharmacologic methods may also be beneficial, such as simple but firm communication, reassurance, reality orientation including an easily visible clock, and the presence of family members [R], although the effectiveness of these methods in the palliative care population has not been well studied.
Delirium is a poor prognostic indicator. In-hospital mortality rates for patients with delirium range from 22% to 76%, and the one-year mortality rates approach 40% [R].
Diarrhea
Diarrhea can be caused by the underlying illness, medications and infections. Diarrhea due to Clostridium difficile must be excluded. When present, this can be difficult to treat, and an individual may require retreatment if symptoms persist.
The presence of diarrhea does not exclude the possibility of bowel impaction, as the effect of gut flora on fecal material can cause liquefaction and subsequent passage of loose stool.
Dyspnea
Dyspnea can be defined as the subjective sensation of difficult breathing and is a common finding in patients with cancer, cardiac disease, advanced respiratory disease and AIDS. Neither the patient's respiratory rate nor the level of oxygenation consistently predicts the severity of dyspnea. A recent review found no well-validated measurement scales for this population [M]. The endpoint for managing dyspnea should be the patient's self-report of diminished breathlessness. Oximetry, pulmonary function tests, chest imaging and other diagnostic evaluations should be performed only if the results would change therapy.
Treatment of dyspnea should be focused on treatment of amelioration of the underlying cause, when possible, and managing symptoms. Nonpharmacologic treatment may include repositioning, improving air circulation, maintaining cool room temperatures, psychological support and using relaxation techniques. Pharmacologic methods include oxygen, opioids and anxiolytics. Multiple published studies support the benefits of opioids for dyspnea. Opioids may decrease the ventilatory response to hypoxia and hypercapnia (in patients with these signs) and can decrease anxiety and the subjective sensation of shortness of breath without reducing oxygen saturation. Morphine is usually considered the opioid of choice for dyspnea in patients with cancer and may be administered by the oral, buccal, sublingual, subcutaneous or intravenous route. Limited information is available on nebulized morphine and its efficacy, and one must be cautious about possible bronchospasm with the first dose. Benzodiazepines, such as lorazepam, are useful when anxiety is a significant contributing factor. However, patients need to be monitored for sedation when combining benzodiazepines and opioids [R]. Inhaled corticosteroids may also be beneficial for patients who have an inflammatory component to their dyspnea (such as asthma or COPD) or have lung cancer.
Fatigue
Fatigue may be defined as decreased vitality in physical and/or mental functioning. Patients may identify increased tiredness, and state that rest fails to resolve the fatigue. Fatigue may be a consequence of the primary illness or of the treatments used (such as radiation and chemotherapy).
There are assessment tools for fatigue; some examples include the Memorial Symptom Assessment Scale, the Edmonton Functional Assessment Tool, the Multidimensional Fatigue Symptom Inventory, and the Profile of Mood States.
Managing fatigue includes treating the underlying causes (such as anemia or hypoxia) if possible, as well as using nonpharmacologic and pharmacologic therapy directed toward the symptom itself. Nonpharmacologic treatment includes patient education about fatigue, modifying the activities of daily living, and scheduling rest periods during the day. Clinicians should counsel patients to prioritize activities and pace themselves accordingly. Mild exercise for brief periods may be beneficial in reducing the perception of fatigue for some patients.
Pharmacologic treatment of fatigue includes erythropoietin, psychostimulants and corticosteroids. Erythropoietin should be reserved for those patients with anemia and erythropoietin deficiency due to the high cost of treatment and lack of evidence of benefit in other clinical situations. Psychostimulants such as methylphenidate, dextroamphetamine and modafinil may be beneficial in managing fatigue and are the most commonly used pharmacotherapy for managing fatigue when no correctable underlying cause can be ascertained [R]. Due to significant side effects, corticosteroids should be reserved for terminally ill patients who may also have nausea and vomiting. Medications that may make the patient more tired should be administered at bedtime rather than in the morning. Conversely, stimulating agents should be administered in the morning.
Nausea and Vomiting
Nausea and vomiting can be very debilitating in patients with cancer, AIDS, and hepatic and renal failure. Nausea and vomiting can have a profound effect on quality of life, along with physical and mental function. Causes include drugs, gastrointestinal obstruction, uremia, psychological distress and vestibular stimuli. Triggers, such as smells and drugs, should be eliminated if possible.
Treatment consists of pharmacologic and nonpharmacologic treatment, while evaluating and treating the underlying cause. Nonpharmacologic treatment may include relaxation, acupuncture and transcutaneous electrical wave stimulation. However, the cornerstone of treatment is pharmacologic therapy, although there is a paucity of data on this subject in the palliative care population, and thus most of the support for certain treatments is based on expert opinion rather than primary studies [R]. Neurotransmitters implicated in nausea and vomiting include dopamine, serotonin, histamine and substance P; while peripherally, mechanoreceptors and chemoreceptors located in the gut, liver and viscera play an important role.
Dopamine antagonists used to treat nausea and vomiting include phenothiazines (prochlorperazine, promethazine) and butyrophenones (droperidol, haloperidol), which block dopamine either peripherally or centrally. Metoclopramide may increase gastrointestinal motility in addition to being an antiemetic. Corticosteroids are effective as antiemetics themselves and may augment the effect of other antiemetics. Dronabinol appears to be better tolerated in younger patients. While serotonin receptor antagonists appear to be effective for acute nausea and vomiting due to chemotherapy, their indiscriminate overuse and increased cost is a significant issue.
Table. Suggested Medications Based on Cause of Nausea and Vomiting
Gastrointestinal Stimuli |
Chemical Stimuli |
Psychological Stimuli |
Vestibular Stimuli |
Metoclopramide
Serotonin antagonist
Dopamine antagonist
Proton pump inhibitors
|
Metoclopramide
Corticosteroids
Dopamine antagonist
Olanzapine
Histamine antagonist
Serotonin antagonist
|
Benzodiazepines
Dopamine antagonist
|
Histamine antagonist |