1. 1
    Current diagnosis

    • Any symptom can be in the realm of palliative care. Rapid identification and aggressive management of symptoms are important in maintaining the patient’s quality of life.

    • Palliative care is treatment that is focused on pain and symptom management as well as quality of life for patients and their families. It can be rendered at any point in the course or treatment of illness, whether that illness is life-limiting/threatening or not.

    • Hospice is a philosophy and method of care that is completely focused on symptom management, quality of life for patients and families, and the transition at the end of life.

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    Current therapy

    • Recommend that all adult patients, regardless of current health status, execute advance directives (Living Will, Power of Attorney for Healthcare, Healthcare Surrogate, etc.) to help ensure that their treatment wishes and end-of-life care goals are met.

    • For patients with life-threatening (e.g., progressing cancer) or life- limiting (e.g., patients with severe chronic obstructive pulmonary disease [COPD] or heart failure, requiring dialysis, or residing in a nursing home) illness, consider a Physician Order for Life- Sustaining Treatment (POLST) or Medical Order for Scope of Treatment (MOST) form (the name varies by state). These forms are used to convert the salient points of advance directives into medical orders so that they are immediately actionable by nurses or emergency medical services if the situation arises.

    • Advance Care Planning discussions are billable under Medicare: 99497 for the first 30 minutes and 99498 for each additional 30 minutes.

    • The best palliative care involves an interdisciplinary approach by physicians, nurses, counselors, chaplains, and others for the optimal management of symptoms (whether the suffering is physical, emotional, spiritual, existential, or practical) and family support.

    • Early addition of palliative care to the overall treatment plan can improve survival and quality of life.

    • Cancer pain is an indication for opioid therapy as opioids have proven efficacy in this scenario. For detailed information on opioids, please see Table 1 in the chapter in Section 1 on pain. Multiple modalities may be required for optimal pain control.

    Table 1

    Coanalgesic and Adjuvant Treatments for Pain: Adult Dosages

    • For patients using opioids chronically, initiate a stimulant laxative like sennosides (Senokot, Ex-Lax) or lubiprostone (Amitiza) as the opioid’s companion. Peripheral mu antagonists like methylnaltrexone (Relistor) or naloxegol (Movantik) are indicated for refractory opioid-induced constipation.

    • Control nausea as it can contribute to anorexia, weight loss, and functional decline. The antiserotonergic drugs, e.g., ondansetron (Zofran), granisetron (Kytril), palonosetron (Aloxi), or the combination netupitant/palonosetron (Akynzeo) are superior to the other classes of antiemetics in the settings of chemotherapy administration and postanesthesia. For uncomplicated nausea, prochlorperazine (Compazine) was found to be superior to promethazine (Phenergan).

    • Dyspnea can be improved by providing a fan, a cooler room, and a view to the outside and avoiding confined spaces,. Opioids, benzodiazepines, and/or other agents, depending upon the situation, might be required. Thoracentesis can be palliative when an effusion is the source of dyspnea.

    • Delirium must be evaluated for potential causes. Delirium with or without agitation can occur in up to 80% of patients, depending upon the underlying condition. Medications are common causes, but pain and multiple other conditions can cause it as well. Medications such as haloperidol (Haldol), chlorpromazine (Thorazine, brand discontinued), or olanzapine (Zyprexa, Zyprexa Zydis) can be helpful in many patients, but haloperidol is by far the cheapest alternative and a good place to start.

    • Feeding tubes do not improve outcomes in late-stage dementia and can contribute to suffering.

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  3. 3

    There are over 2.5 million deaths in the United States annually; cardiovascular disease is the top cause followed by all cancers combined, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and chronic liver disease, among others. Any of these disease processes can have a significant symptom burden that worsens with disease progression.

    Life has 100% mortality, so individuals should take the time to plan for it. The consequences of failing to plan for the transition to end-of- life care include increased psychological distress, medical treatments that are inconsistent with individual preferences, increased utilization of healthcare resources that have little therapeutic benefit while being very costly in dollars as well as quality of life, and a more difficult bereavement for survivors.

    Cardiopulmonary resuscitation has poor outcomes under the best of circumstances (~ 15%), but it is even worse in patients with late-stage cancer with only about 2% surviving to hospital discharge. Outcomes are also poor for the other noncardiac diseases listed above.

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    Risk Factors

    Factors associated with worse pain or less symptom control are being female, elderly or a child, and race other than white. Lacking advance directives and failing to have such discussions with family members are related to receiving excessive and/or unbeneficial interventions/treatments.

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    A patient’s symptoms can be caused by the underlying disease itself, mechanical encroachment on other organs and structures (e.g., bowel obstruction, neuropathic pain from nerve destruction, bone metastasis), becoming more sedentary or bedbound, medications, and/or tumor necrosis factor, neurokinin-1, and other inflammatory cytokines. Therefore, symptoms may have different etiologies and pathophysiology depending on the underlying disease state. Such a review would be far too extensive for this section.

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    Encourage all adult patients, regardless of current health status, to execute advance directives (Living Will, Power of Attorney for Healthcare, Healthcare Surrogate, etc.) to help ensure that their treatment wishes and end-of-life care goals are met. These discussions are billable under Medicare using CPT 99497 for the first 30 minutes face to face with patient, family members, and/or surrogate; and 99498 for each additional 30 minutes. For patients with life-threatening (e.g., progressing cancer) or life-limiting (e.g., severe COPD or heart failure, dialysis-dependent, or nursing home residents) illness, consider a Physician Order for Life-Sustaining Treatment (POLST) or a Medical Order for Scope of Treatment (MOST) form (forms vary by state).

    They are used to convert the salient points of advance directives into medical orders so that they are immediately actionable by nurses, emergency medical services, and others if the situation arises.

    Ascertain the patient’s/family’s goals of care, and assess whether those goals are realistic under the circumstances. Evaluate whether a particular intervention will help to achieve that goal. For example, if a patient’s goal is to take a child on a special vacation, this cannot be achieved if the patient remains in the hospital receiving chemotherapy that is not working. Another example is a nursing home resident with dementia whose family just wants them “to be kept comfortable.” Placing a feeding tube in advanced dementia does not improve outcomes and might require physical restraints to keep the patient from removing the tube. Therefore, feeding tube placement will negatively impact the goal of comfort.

    When maintaining comfort and improving quality of life become the primary goals, assist patients and their families with the transition to hospice care. Hospice is grossly underutilized with a median length of stay of only 19 days; all of its benefits often cannot be realized in such a short time.

    Palliative and end-of-life care, like all medical care, needs to be influenced by all four major aspects of medical ethics: autonomy (patient/surrogate has the right to pursue aggressive treatment as well as to refuse treatment, even if that treatment could be considered life- sustaining), beneficence (do “good” for the patient), nonmaleficence (“do no harm”), and justice (appropriate distribution of finite resources). These four ethics can come into conflict at times, especially with the emphasis on autonomy above the other three in the healthcare system in the United States. Hospitals and other medical facilities should have specific policies regarding medical futility.

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    Clinical Manifestations

    Common symptoms in palliative care include pain, nausea with or without vomiting, dyspnea, delirium, constipation, dysphagia (cannot swallow food, fluids, or medications), and general functional decline, that is, requiring more assistance with transfers, toileting, and self- care. Anorexia and lack of thirst are very common, notably in the last few hours to days of life, but anorexia can also be a side effect of medications. Intervening with IV fluids or nasogastric feeding can exacerbate symptoms (secretions, dyspnea, pain, nausea) and worsen outcomes. Weight loss is commonly observed.

    As patients enter the last hours of life, they might experience decreased level of consciousness, agitated delirium, mottling of the extremities beginning distally and moving proximally, changes in breathing (Cheyne-Stokes, rapid and shallow, Kussmaul, or agonal), decreased or absent oral intake, and/or skin cool to touch.

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    Diagnosis and prognosis will vary widely depending on the underlying disease processes, but in palliative care, much of the diagnosis (symptom identification) is based on history. Any patient with symptom burden is a candidate for palliative care, whether the symptoms are physical, psychological, spiritual, or existential. The Edmonton Symptom Assessment Scale rates each of 11 different symptoms on a scale of 0 to 3 for a total score of 0 to 33. This scale gives an idea of overall symptom burden. The Karnovsky and Palliative Performance Scales range from 0% (deceased) to 100% (fully functional) rated on ambulation, activity and evidence of disease, self- care, oral intake, and level of consciousness. A score of about 40% is often associated with appropriateness for hospice. Hospice eligibility in the United States is solely based on a life expectancy of 6 months or less if the disease progresses on its expected course. The National Hospice and Palliative Care Organization has devised some prognostic criteria for a variety of diagnoses including dementia, amyotrophic lateral sclerosis, acquired immune deficiency syndrome (AIDS), congestive heart failure, end-stage liver or kidney disease, COPD, and so on. Although not fully validated, the criteria can help guide the clinician in discussions with patients/families. There are various prognostic scoring systems for different disease states, and the Palliative Prognosis Score can help to determine the prognosis for patients with terminal cancer. Additionally, the American Cancer Society has 5-year survival rates for various stages of numerous cancers on its website.

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    Differential Diagnosis

    As this chapter discusses management of symptoms for a plethora of different diseases, the differential diagnosis of all symptomatic disease processes is far beyond its scope. However, when assessing various symptoms, treatment options can be selected based on the probable source. Is the pain new or in a new location, or is it in the same area, radiating, or worsening? Are the nausea/vomiting due to chemotherapy, anesthesia, metabolic disorders, bowel obstruction, anxiety, increased intracranial pressure, or something else? Is the constipation opioid-induced, due to poor intake, a result of using fiber without adequate fluid intake, or caused by another issue altogether? Is the dyspnea due to pleural effusion (may respond to thoracentesis far better than it would respond to medications), anxiety (could use selective serotonin reuptake inhibitors [SSRIs], hydroxyzine, benzodiazepine, cognitive behavioral therapy), airway obstruction (might use bronchoscopy, suction, or bronchodilators rather than other medications), excessive secretions (could treat with anticholinergic medications such as glycopyrrolate or scopolamine), or other cause?

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  10. 10

    To meet the needs of all forms of suffering (physical, emotional/psychological, spiritual, existential), an interdisciplinary approach using physicians, nurses, chaplains, counselors, social workers, and others is essential. For all patients entering palliative care, and especially hospice care, all of their medications should be evaluated for risk and benefit and then prioritized based on the goals of care. In one study, patients with a life expectancy of less than 1 year taking a statin for primary or secondary prevention were randomized to continue or stop the statin. The average number of days until death was 229 after discontinuation versus 190 for continuation; thus survival and quality of life improved at a lower cost. Consider discontinuing statins, some oral hypoglycemic agents (notably sulfonylureas due to risk of hypoglycemia), or oral anticoagulants such as warfarin (Coumadin), apixaban (Eliquis), or dabigatran (Pradaxa) if risks now outweigh benefits. As the end of life approaches, discontinue other medications that are not essential for symptom control or quality of life, have more risks than benefits, or contribute to symptom burden (e.g., cholinesterase inhibitors) at this advanced stage of the disease.

    Clinicians might withhold or withdraw treatments, but they should never withdraw “care.” Providers can change from “doing everything possible to cure a patient” to “doing everything possible to maintain comfort and quality of life.” This is more than semantics. Consider turning off the defibrillator component of a pacer-defibrillator to avoid unnecessary shocks. The pacer can remain on as it can improve some symptoms while not prolonging life.

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    For a detailed review of medications used for pain, especially opioids, see the chapter on pain. This section will focus on cancer pain and end-of-life pain.

    Pain of All Types

    Opioids have demonstrated efficacy for cancer-related pain in numerous clinical trials. Methadone can be effective when other opioids have failed, but it should be used with caution and by those familiar with its use.

    Bone Pain

    The bone pain due to metastatic lesions is partly due to prostaglandin release; thus coanalgesics like nonsteroidal antiinflammatory drugs or adjuvant medications such as corticosteroids, e.g., dexamethasone or prednisone, can be particularly helpful. Bisphosphonates such as zoledronic acid (Zometa) and pamidronate (Aredia) usually provide analgesia within a week that lasts up to 3 months. Monthly dosing may be required. Additionally, radiopharmaceuticals such as strontium-89 (Metastron), samarium-153 (Quadramet), and phosphorus-32 (Phosphocol P-32) may be helpful for cancer-related bone pain with analgesia usually beginning within 1 to 2 weeks and lasting 2 to 6 months. Their benefit is derived from significant uptake by areas of high bone turnover to provide internal, localized radiation. Radium-223 (Xofigo; indication limited to castration-resistant prostate cancer with bone metastasis) emits alpha radiation rather than the beta radiation of the three agents above, and it is more selective for metastatic lesions. External-beam radiation treatment (EBRT) achieves pain relief in over 75% of patients with analgesia beginning in 1 to 2 weeks and lasting 2 to 6 months. The dosing of radiopharmaceuticals and EBRT is determined by a radiation oncologist. The radiation oncologist might choose a single large fraction of EBRT rather than multiple small fractions if survival is expected to be greater than 3 months or if prolonged treatment will present too much hardship (transportation, increased suffering, time off work for caregivers, etc.) on the patient/family.

    Neuropathic Pain

    Neuropathic pain can have multiple causes, such as nerve invasion/compression, medication toxicities, human immunodeficiency virus (HIV), and complications of diabetes. Adjuvant medications that have proven efficacy, but not necessarily an indication for use by the Food and Drug Administration (FDA), include antidepressants such as amitriptyline (Elavil), duloxetine (Cymbalta), and venlafaxine (Effexor), anticonvulsants like pregabalin (Lyrica) and gabapentin (Neurontin), or, for highly refractory cases (due to significant risk, side effects, and/or legality), ketamine (Ketalar) or cannabinoids. Topical agents like capsaicin (Capzasin-HP, Salonpas Gel Patch Hot) have evidence to support their use in diabetic neuropathy. Highly active antiretroviral therapy can decrease viral load and improve symptoms of AIDS, including those of HIV-related neuropathy.

    Visceral Pain

    Octreotide (Sandostatin) can be used for the severe abdominal cramping and diarrhea associated with carcinoid tumors or VIPomas or off-label for abdominal pain and other symptoms related to malignant bowel obstruction. See Table 1.

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    Dyspnea is a sensation of breathlessness, and the only measure is a patient’s self-report. It does not correlate well with respiratory rate, blood gas measurements, or pulse oximetry. The potential causes are many, and they should be considered before merely managing the symptom. The cause can determine the therapy. Anxiety can be managed with SSRIs or benzodiazepines. Airway obstruction could be relieved by suction or bronchoscopy. Hypoxemia has numerous causes that would have to be considered, but supplemental oxygen could help. Pleural or pericardial effusions could be drained.

    Pneumonia can be treated with antibiotics, pulmonary edema can be managed with diuretics and opioids, and pulmonary embolus can respond to anticoagulants. Transfusions can be helpful for dyspnea due to significant anemia (hemoglobin < 7 g/dL) resulting from hemorrhage or myelosuppression. Bronchospasm usually responds to inhaled β2 agonists. If underlying causes are addressed, either by management or recognizing that treatment would not achieve the goals of care, symptom control is appropriate. Opioids can be helpful for symptom management. Nebulized morphine is no better than saline. Excessive secretions can be managed with scopolamine or glycopyrrolate. The latter is preferred in the elderly as is does not cross the blood-brain barrier. For nonpharmacologic interventions, see Box 1.

    Box 1
    Nonpharmacologic Interventions for Dyspnea

    •   Reassure, work to manage anxiety.

    •   Behavioral approaches: relaxation, distraction, hypnosis.

    •   Limit the number of people in the room.

    •   Open window.

    •   Eliminate environmental irritants.

    •   Keep line of sight clear to outside.

    •   Reduce room temperature, but avoid chilling the patient.

    •   Introduce humidity.

    •   Reposition, elevate the head of the bed, keep patient turned.

    •   Educate and support the family.

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    The treatment of nausea and vomiting depends on the underlying cause. For chemotherapy-related nausea/vomiting, the 5HT3 receptor antagonists are far more effective than other classes of antiemetics.

    The 5HT3 class includes ondansetron, granisetron, dolasetron2 (Anzemet), and palonosetron. Additionally, there is a combination of netupitant/palonosetron, which combines a 5HT3 antagonist for acute-phase nausea/vomiting and a substance P/neurokinin 1 receptor antagonist (NK1RA) for the delayed phase, and it should be given with dexamethasone. Its only indication is for prophylaxis of chemotherapy-related nausea/vomiting, especially with highly emetogenic chemotherapy. The combination demonstrated superiority over palonosetron alone. Rolapitant (Varubi), another NK1RA, has a longer half-life than netupitant with fewer drug interactions. Aprepitant (Emend) is an NK1RA with fosaprepitant (Emend injection) as its IV alternative. Olanzapine was more effective than aprepitant and noninferior to fosaprepitant in the setting of highly emetogenic chemotherapy, while it is far more cost-effective than either NK1RA and serves as a better acute antiemetic that metoclopramide (Reglan). Prochlorperazine was found to be superior to promethazine for uncomplicated nausea/vomiting. See Table 2.

    Table 2


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  14. 14

    Constipation is quite common in palliative care, and it is easier to prevent than to treat. It is one of the primary side effects of opioids that does not attenuate with time. For routine constipation, almost any laxative will do. Polyethylene glycol 3350 (MiraLax, GlycoLax) daily with as-needed sennosides (Senokot) or bisacodyl (Dulcolax) is one example of a simple regimen. If the patient is taking medications that have constipation as a side effect, such as anticholinergic medications, calcium-channel blockers, they should be discontinued if possible.

    Opioid-induced constipation is due to the interaction of opioids with the mu receptors in the gut, thus leading to poor motility. It can be prevented for the most part if a stimulant laxative is initiated simultaneously with the opioid. Senna is safe for long-term use, but bisacodyl can damage the myenteric plexus over time. The chloride- channel activator lubiprostone and the guanylate cyclase activator linaclotide (Linzess) increase intestinal fluid secretion and motility, and the peripheral mu antagonists methylnaltrexone and naloxegol are indicated for use by the FDA to treat refractory opioid-induced constipation. Alvimopan (Entereg) is another peripheral mu antagonist, but its primary indication is for ileus, especially postoperatively. Fiber and bulking agents should be avoided as they can worsen the problem. See Table 3.

    Table 3


    Wtulose (Kristalose) 10-20 g in 4 oz. water PO daily. Ma×irrxiirr 40 g/day

    Magmsiui ciaaie (1.745 g/30 inL) 195-©0 mL/day  PO cbiily or avi&dbid                3ooWday

    Magnesium fry droxicic: {Milk of Magresia), 400 eg bi£is ard 1200 irig/15 mL. 2400——4800 g PO daily or divined bid or gin Polyethy lerx: glycol 3350, 17 g in 8 oz, liqiid PO drily

    Bfiaco  15 ng BBs l-3MD ‹ifiy pmozl0mgsuppositog RR ‹iNypm

    Se   skks8.6mg   ;2M   FDbi4       4   MD Nd

    lotide (Linzess) 145 pg IO daily. 5finxdates cGMP production to irir rewe intesfinal fluid secretion and motility,

    Lit:›ipx›store (Amitiza) 24 pig FO bid Activates chloride channel to increase irtesbnal fluid seciebon aixl tonality.

    Peripheral  My-Receptor Antagonists

    Melhy hultrexone (Eulistoi) 8—12 mg SC god Jxn (or 0.15 irig/kg SC god pm). Maxirtxinx 1 dose/24 lx›irs

    Naloxegol {Movaraik) 25 mg PO daily

    Avoid fil;xzr anct                             ezts irt }›aéenls Laking o}ioids or wit:h Limited Bid iJnlake.

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    There are numerous reasons for patients receiving palliative care to be anxious, whether undergoing painful/unpleasant but curative interventions or progressing toward hospice. Fear and uncertainty about the future are common causes, and they can be related to physical, psychological, social, spiritual, or practical (finances, managing home responsibilities) issues. Excessive alcohol or caffeine use can exacerbate anxiety, which may present with agitation, insomnia, restlessness, sweating, tachycardia, hyperventilation, panic disorder, worry, tension, and/or psychosomatic symptoms. For patients with expectation of cure or longer survival, SSRI or serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants can be beneficial. Venlafaxine has the shortest half-life, and steady state can be reached in 4 to 7 days. Benzodiazepines are helpful for shorter life expectancy, or they can be used until the antidepressants take effect.

    Diazepam (Valium) has avoided as they can worsen the problem.a long duration of action due to numerous active metabolites, but it is slower in onset, as is clonazepam (Klonopin). Alprazolam (Xanax) has very rapid onset but short duration of action. Lorazepam (Ativan) strikes a happy medium between speed of onset and duration of action. Counseling and cognitive behavioral therapy are effective, especially in combination with medications.

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    Delirium is a waxing/waning state of confusion that can be characterized by anxiety, disorientation, cognitive dysfunction, and hallucinations. There is also a catatonic variety of delirium. This condition can be caused by many things, but a short list would include constipation/impaction, hypoxemia, infection, electrolyte abnormalities, medications (including benzodiazepines and opioids), and pain. If a cause is identified and corrected but the patient is still symptomatic, haloperidol, chlorpromazine, or olanzapine can be helpful; however, haloperidol is by far the cheapest alternative and a good place to start.

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    Hiccups (singultus) is a common nuisance that can become quite distressing, especially if persistent (> 48 hours) or intractable (> 1 month). For patients with pain in the chest or abdominal regions, hiccups can make pain difficult to control in addition to being a bothersome symptom that can significantly decrease quality of life.

    Chlorpromazine, at 25 to 50 mg PO qid prn, is the only FDA-approved medication for hiccups, but haloperidol is a viable and much cheaper alternative, as is metoclopramide. Gabapentin and phenytoin (Dilantin) have been used with some success, notably in cases with a central nervous system etiology. Many other medications, including baclofen, have been tried without success. Nonpharmacologic methods, e.g., breath holding, hyperventilation, gargling, are worth trying, but evidence is lacking for any particular intervention.

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    Patients should be reevaluated routinely for the adequacy of pain and symptom control, as well as for their ability to cope with the underlying disease, symptom burden, and functional decline. The family needs to be assessed for additional stressors and coping mechanisms as the family’s adjustment, or lack thereof, can be detrimental to the patient’s condition. If opioids or benzodiazepines are being used, the supply needs to be monitored for any signs of aberrant use. Additionally, patients can be monitored for excessive sedation or respiratory depression.


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    Emergencies do exist within the palliative care and hospice settings. Spinal cord compression, hypercalcemia, superior vena cava syndrome, seizures, airway obstruction, hemorrhage, or acute worsening or crisis in pain or other symptom are examples.

    Management will depend on the patient’s goals of care and stage of illness; however, uncontrolled symptoms should always be addressed.

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    2  Not available in the United  States.

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