Palliative Care in the Acute Care Setting

Palliative care has been defined by the World Health Organization (WHO) as "the active total care of patients whose disease is not responsive to curative treatment. Control of pain, of other symptoms, and of psychological, social and spiritual problems, is paramount. The goal of palliative care is achievement of the best quality of life for patients and their families." Another definition of palliative care is "specialized medical care for people with serious illnesses. This type of care is focused on providing patients with relief from the symptoms, pain, and stress of a serious illness—whatever the diagnosis." ^[1]

Another way to look at palliative care is the concept of a "good death," free of avoidable pain and suffering for the patient and the patient's family. ^[2] At first glance, this definition would seem to have little to do with acute care delivered in a setting such as the emergency department. In fact, while up to 60% of patients die at home in the United States, reportedly as few as 35% of patients want to die at home. Consequently, many patients who are terminally ill present to emergency departments. They may do so when death is imminent, for treatment of an acute illness superimposed on their existing disease, or for symptom control, especially of pain. This article focuses on symptom control.

For more information, see Medscape's Palliative Care Resource Center.

Pain

Pain is the single most prevalent symptom for patients receiving palliative care. The pathophysiology varies with the anatomic location of pain and the underlying disease process. In a large study of patients with cancer who were in palliative care, approximately 55% of pain was somatic in origin, with the remainder nearly equally divided between visceral and neuropathic causes. ^[3]

For example, patients with advanced cancer may have headache due to increased intracranial pressure from tumor masses or from inflammation. Bone pain is the most common source of cancer pain and may occur with either osteoblastic or osteolytic activity. Bone pain can originate directly from bone (direct invasion with microfracture, distortion of the periosteum) or from nerve root compression or muscle spasm in the lesion area. Major pathologic fractures may occur at the site of primary or metastatic tumor.

Abdominal pain in patients with cancer may be due to solid organ masses causing capsular distension. Ascites or tumor mass may lead to uncomfortable abdominal distention and constipation is common. Chest pain is most often due to tumor invasion of bone or other pain-sensitive structures. The pathophysiology of pain in patients who do not have cancer and are in palliative care is a function of the specific nature and anatomic location of the underlying disease process.

Dyspnea

Lung cancer and advanced congestive heart failure (CHF) are common causes of dyspnea in palliative care patients. Sixty-five percent of patients with lung cancer and nearly all patients with heart failure experience dyspnea. In patients with lung cancer, underlying chronic obstructive pulmonary disease (COPD) is an additional common cause of dyspnea. Other causes include pleural effusion, pericardial effusion or tamponade, superior vena cava syndrome, pulmonary embolism, and pneumonia. Worsening dyspnea in patients with heart failure may represent disease progression, but may also be caused by pleural effusion and pericardial effusion or tamponade. Severe anemia is another etiology of dyspnea, but chronic anemia may be well tolerated in this population.

Gastrointestinal

Gastrointestinal (GI) symptoms are also common in the palliative care population. Anorexia, nausea, and vomiting are common symptoms at the end of life, occurring in 62% of terminally ill cancer patients. Nausea and vomiting also occur frequently in other terminal illnesses such as CHF, end-stage renal disease (ESRD), and AIDS.

The most frequently cited etiologies in patients with cancer are chemical abnormalities (eg, metabolic, drugs, infection) in 33%, impaired gastric emptying in 44%, and visceral causes (eg, bowel obstruction, GI bleed, enteritis, constipation) in 31%. A study of 40 patients on a palliative care unit identified 59 reversible etiologies for GI symptoms, with medications (51%) and constipation (19%) presenting most commonly. ^[4]  

In one series, constipation was present in approximately two-thirds of patients, and was principally associated with dehydration and the use of benzodiazepines. ^[5]  Hypercalcemia is a cause of constipation that is common in patients with cancer. Dry mouth is a bothersome symptom that may often be medication related.

Psychological

Anxiety and depression are common psychological symptoms in patients with terminal illnesses. 

Delirium has been reported in an estimated 90% of patients in the last days of life. In a prospective, observational study of advanced cancer patients who presented to the ED, delirium was diagnosed at a rate of at least 9%. However, delirium is frequently missed or misdiagnosed as worsening pain, depression, or anxiety. ^[6]

Approximately 50% to 70% of patients with delirium have hyperactive or mixed subtypes, characterized by restlessness, agitation, or aggressive violent behavior. Agitation can be highly distressing to patients, caregivers, and health care professionals, and poses a significant safety risk to those involved. ^[7]

Because of the fragmented nature of health care in the United States, measuring the number of patients in palliative care is difficult. A current estimate is that more than 500,000 patients are receiving the Medicare benefit for hospice and palliative care. Another estimate is that, in 2000, approximately 20% of patients dying in the United States received hospice care. ^{[8, 9, 10]}

In the United Kingdom, in 2005-2006, approximately 65,000 new patients enrolled in palliative care programs. According to one estimate, approximately 70% of deaths in the developed world are preceded by a condition for which death is predictable in the foreseeable future.

The UK advocates a structured transition to palliative care, but this approach is not always implemented in acute care settings. A study of how transitions to palliative care are managed in the UK found several roadblocks. Health care professionals reported poor communication with patients, as well as the limited ability of junior staff to make care decisions. ^[11]

Cancer is the most common diagnosis among patients in palliative care. The traditional eligibility criterion for hospice care in the United States includes an estimated lifespan of 6 months or less; this reflects the predominance of patients with cancer who are in palliative care. However, lifespan may be easier to determine for cancer than for certain other terminal diseases such as COPD, CHF, severe dementia, and stroke. Many patients request only palliative care early in the course of a fatal, incurable disease. These patients may survive for years rather than 6 months or less.

A 2006 study of the California population found that views on a patient's right to die varied significantly by ethnicity, with whites much more willing to allow a loved one to die than any other ethnic group including African Americans, Asians, and Latinos. ^[12] Once a patient or family requests palliation only, medical care does not differ by ethnicity. Differences may also exist in the ways that cultural groups express pain, and clinicians should consider this.

An article by Smith et al provides a comprehensive discussion regarding cultural issues that clinicians should be aware of while caring for terminally ill patients of Latino heritage. Included are various recommendations on how to effectively utilize interpreters and universal strategies for patient health communication. ^[13]

Patients in palliative care already carry a diagnosis of terminal illness. The focus of the encounter is therefore different than for other patients in acute care settings. New symptoms that may indicate a new disease process should be sought when appropriate. Often though, the focus of the visit is explicitly for relief of long-standing symptoms that are progressive or poorly controlled. Consulting the patient's medical history and treating physicians, when available, is often valuable in learning the details of prior symptoms, diagnostic tests, and treatments.

With the exception of pain, there is poor concordance between symptom questionnaires as completed by the patient and the physician history as recorded in the medical record. ^[14] It is therefore often appropriate to ask specifically about other symptoms such as anorexia, incontinence, gastrointestinal symptoms, respiratory symptoms, or level of functioning, in order to best identify the patient's needs.

Physical examination for patients in palliative care should be based on knowledge of pre-existing diseases and presenting symptoms. As with the history, the primary goal is to determine if a new, acute condition needing further evaluation and management is present or to verify that a preexisting condition needing further symptomatic treatment is responsible for the presenting complaints.

The most common reason to enter palliative care is advanced cancer. According to the Centers for Disease Control and Prevention, in the United States, the most common primary sites as causes of cancer death are (in order) lung, colorectal, breast, and pancreas. ^[15] Other diseases commonly leading to palliative care are as follows:

• HIV/AIDS
• CHF
• COPD
• ESRD
• Liver failure
• Dementia
• Stroke.

Laboratory studies are dictated by the suspicion of a specific acute disease that would require treatment if discovered. Many patients may have a high pretest probability of disease yet not require testing. For example, it would often be of little benefit to confirm an elevated serum creatinine level in a patient in palliative care who has end-stage renal disease and presents with an unrelated complaint such as a minor soft tissue infection.

As with laboratory studies, imaging studies should be reserved for the identification of conditions that will change treatment when present. For example, merely documenting known findings such as a lung mass in a patient with lung cancer who has symptoms unrelated to the chest is unnecessary. Conversely, a patient with a cough and a fever may warrant a chest radiograph provided that he or she would wish antibiotic treatment for pneumonia, if discovered.

Common procedures in patients in palliative care include intravenous or subcutaneous clysis fluids for dehydration, thoracentesis for symptomatic pleural effusion, paracentesis for symptomatic ascites, and placement of a urinary catheter for hygienic purposes or to ameliorate obstruction. One study reported on a collaboration of emergency physicians and palliative care specialists in performing sonographically guided paracentesis at home. ^[16]

Nasogastric (NG) tubes may be used temporarily to supplement oral intake. However, they are uncomfortable and significantly increase the risk of aspiration. When patients desire artificial nutrition, arrangements for a semipermanent type of feeding tube, such as a percutaneous endoscopic gastrotomy (PEG) tube, may be considered. An NG tube can be an acceptable short-term bridge to a longer-term solution. A Foley catheter may be used as a short-term replacement for an extruded or blocked gastrotomy tube needing replacement.

Care for patients in a palliative acute care setting is primarily concerned with symptom relief. At times, specific treatment aimed at an acute condition is appropriate. For these situations, other sections of this text or other references should be consulted. This section focuses on treatment strategies for pain, the most common symptom in patients receiving palliative care.

Pain is the most common symptom of patients with cancer who are in palliative care and seeking acute care. Other patients in palliative care may also experience continuous or intermittent pain, and the principles of treatment are the same. The WHO has disseminated a 3-step "ladder" approach to treating pain in patients with cancer. While not specifically formulated for other types of patients in palliative care, the scheme is clearly applicable.

According to the WHO, a patient who experiences pain should promptly receive oral analgesic drugs, starting with nonopioids (aspirin and acetaminophen). If pain persists or increases, progressively stronger drugs are used: a mild opioid (codeine) for mild to moderate pain; then a strong opioid (such as morphine) for moderate to severe pain, until the patient is free of pain. Opioids may be added to nonopioids or substituted for them. To calm fears and anxiety, additional drugs – "adjuvants" – should be used. To maintain freedom from pain, drugs should be given "by the clock" (ie, every 3 to 6 hours), rather than "on demand." ^[17]

This three-step approach of administering the right drug in the right dose at the right time is inexpensive and 80-90% effective. Surgical intervention on appropriate nerves may provide further pain relief if drugs are not wholly effective. ^[17]

The ladder approach has been questioned but is generally considered to be a valuable tool in guiding treatment of chronic cancer pain. The basic principle of reserving opioids for pain that cannot be successfully treated with nonopioids, and continuing nonopioid treatments when possible, is important for both patients with cancer and patients without cancer who are in palliative care settings. For a description of the ladder, see WHO's pain relief ladder.

The time course of pain may be continuous, intermittent, or breakthrough pain. In one study, 48% of patients with cancer had continuous pain, with 75% experiencing breakthrough pain at some time. The other 52% experienced intermittent pain. ^[3] Inadequately treated continuous pain is also common with studies reporting frequent deviation from evidence-based guidelines for treatment. A specific type of inadequately treated chronic pain is known as end-of-dose pain. Each type requires a somewhat different therapeutic approach and, therefore, being able to differentiate them is important.

The Multidimensional Objective Pain Assessment Tool, (MOPAT) is a valid and reliable tool to assess acute pain in non-communicative patients. The MOPAT can be used over time and across settings and consists of scoring patients' pain levels on two sets of signs from patients: behavioral signs of pain, and physical signs. Behavioral signs include facial expressions, moaning and muscle tension. Physical signs include heart rate, blood pressure, and sweating. ^[18]

Patients in palliative care may present with chronic pain to an acute care setting early in the course of their disease. In that situation, as suggested by the WHO ladder, nonopioids or mild opioids are the most appropriate symptomatic pharmacological treatment. The initial treatment of pain that requires opioids should be with short-acting/rapid-onset preparations. More commonly, patients present with inadequately controlled chronic pain and are already receiving narcotic pain medication. In that circumstance, end-of-dose pain needs to be differentiated from breakthrough pain.

Breakthrough pain is described as an acute pain exacerbation in the setting of chronic pain. A specific precipitating event, such as coughing in a patient with rib metastases, may occur, or it may occur with no identifiable precipitant. Breakthrough pain is best treated with a short-acting narcotic as a "rescue" medication. End-of-dose pain is diagnosed by the characteristic time course. It occurs fairly predictably prior to the next scheduled dose of analgesic. End-of-dose pain is treated by increasing the dosing frequency or switching to a longer-acting narcotic.

When pain relief from a long-acting opioid is inadequate, the primary approach is to increase the dose. Opioids have no ceiling effect and, therefore, no specific maximum dose, whatever amount the patient is receiving. The correct dose is the dose needed to relieve pain. Fear of addiction or respiratory depression is not appropriate in this setting. At times, rather than simply increasing the dose, switching from one opioid preparation to another is reasonable. Side effects may differ with different preparations, and cross-tolerance is incomplete. When switching, begin the new drug at 50% (or more) of the published equianalgesic dose. Less than this dose will almost certainly be inadequate.

Fentanyl intranasal (Lazanda) is approved for breakthrough cancer pain in adults who are tolerant to opioid therapy. ^[19] The drug is available only through a restricted access program. A titration schedule determines the individualized dose for the patient’s breakthrough pain. Healthcare professionals who prescribe to outpatients, patients, pharmacies, and distributors must enroll in the program to prescribe, receive, dispense, and distribute, respectively.

Opioid side effects can be anticipated and treated prophylactically. Nausea and vomiting are common in the first few days after initiating treatment. An antiemetic such as metoclopramide or a serotonin antagonist is often effective and should be prescribed for the first week or so of narcotic treatment.

In certain circumstances, specific types of pain may be targeted with relatively specific therapies. The mechanism of specific pain relief varies and, in some cases, is not well understood. Some pharmacological examples of specific pain treatments are listed in the table below.

Table. Medications and Indications (Open Table in a new window)

Gabapentin is widely prescribed as part of multimodal pain control regimens for both acute and chronic pain, but can have dangerous interactions with opioids. In a population-based study of 5875 patients who were receiving prescription opioids, concomitant prescription gabapentin in a moderate dose (900 - 1799 mg daily) or a high dose (1800 mg or more daily)  was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use. ^[20] Similar results have been reported for pregabalin. ^[21] Gabapentin should be administered cautiously for patients who are receiving opioids or other sedatives. ^[20]

In addition to pharmacologic treatment of pain, nonpharmacologic treatments are available. Radiation, radiofrequency ablation, or surgery may be used to treat a tumor in a specific area that is causing pain. ^[22]

Physical modalities such as splinting or the application of heat or cold may be used. Cold application with ice packs, gel packs, and coolant sprays reduces nerve conduction, muscle spasm, inflammation, and edema. Ice massage, in which skin overlying tender tissue is rubbed with a block of ice, produces analgesia after several minutes. No controlled studies of cold-induced analgesia for treatment of cancer pain have been completed. Cold should be avoided in ischemic and irradiated tissues. ^[22]

Heating has long been  used to relieve muscle, bone, and joint pain. The analgesic effect of heat is due in part to increased blood flow and also decreasing joint stiffness. Heat also induces mental relaxation and relieves stress. Hot packs, heating pads, or hot baths improve cutaneous blood flow and relax muscles and ligaments.

Treatment of psychological disorders may play a role in pain management. Both anxiety and depression can decrease pain thresholds and increase opioid requirements. The ED diagnosis of anxiety or depression may require referral to a mental health provider or pharmacologic treatment with anxiolytics or antidepressants. Anxiolytics can be an extremely important adjunct in achieving pain control acutely, and anxiolytics or antidepressants may play a bigger role in the management of chronic pain.

There are also interventional techniques that are effective for relief of pain. Neurolytic blocks of the sympathetic axis may be used to relieve visceral pain in the abdominal or thoracic cavity. Implantable devices, such as epidural or intrathecal catheters, are beneficial for patients on high-dose opioids when side effects are debilitating. These devices provide analgesia that targets the selected regions and may allow significant reduction in the amount of opioids required. Some authors consider interventional techniques as a "fourth step" on the WHO ladder. ^[23]

Patients with end-stage lung disease or CHF are invariably dyspneic, and 75% of all dying patients experience dyspnea. This may represent a progression of their disease or a complicating illness. In cases of disease progression, palliation is appropriate when the patient desires no further treatment for the primary condition. A simple intervention may be to begin or increase existing oxygen therapy. However, no clear role for supplemental oxygen has been established in the treatment of dyspnea in patients without hypoxemia, and providers should consider the negative effects of oxygen supplementation. Symptom control with medications, exercise, behavioral therapy, treatment of associated anxiety, and the use of fans may be more effective and less costly than oxygen therapy. ^[24]  

Increased dyspnea is often associated with anxiety. The potential exists for a vicious cycle of dyspnea, anxiety, increased respiratory rate and work of breathing, leading to worsening dyspnea. In this situation, medications are appropriate. Concerns about respiratory depressant effects are not well founded and should not be a deterrent. Benzodiazepines are often effective. For patients not already taking opioids, low-dose opioids may relieve dyspnea. For example, codeine, 30 mg orally every 4 hours, may provide relief of mild dyspnea. For those already using opioids, the dose may be increased.

When the evaluation reveals a potentially treatable cause of dyspnea, such as pneumonia, pneumothorax, pleural effusion, or superior vena cava syndrome, the ratio of the risk and discomfort of diagnostic and therapeutic interventions needs to be considered in light of the patient's projected lifespan and the probability of the therapy being successful.

Up to 50% of patients who receive morphine and derivatives develop significant constipation. This is due to narcotic-induced suppression of intestinal motility. A rectal examination should be performed to determine whether fecal disimpaction is needed. Enemas and stimulant cathartics that promote intestinal motility are a logical treatment.

A comparative study of the efficacy of lactulose and senna was conducted in patients with terminal cancer. Both laxatives were found to be equally effective in treating narcotic-induced constipation, but senna was recommended because of its lower cost. ^[25] Stool softening agents may also help prevent narcotic-induced constipation. Bulk-forming laxatives are not appropriate in opioid-induced constipation. They allow the colon to stretch but do not stimulate peristalsis. The use of these agents may result in bowel "pseudo obstruction."

A relatively new agent, methylnaltrexone bromide (Relistor), is an opioid antagonist indicated for opioid-induced constipation. Relistor is a peripherally acting agent and is able to reverse the undesired peripheral affects of opiates, such as constipation, without diminishing the analgesic nature of the drug class. In two clinical trials reported on the package insert, Relistor was shown to reverse opioid-induced constipation in 48-62% of patients within 4 hours. ^[26] A review published in 2011 also concluded that subcutaneous methylnaltrexone is effective in combating constipation in palliative care patients. ^[27] Relistor is administered as a subcutaneous injection and is dosed in a weight-based fashion. It is typically used every other day if needed.

Oral naloxone is poorly absorbed from the GI tract and is an oral treatment specific for opioid-induced constipation. The initial dose of 0.4-0.8 mg can be increased gradually to 8 mg/day or higher. However, larger doses may result in opioid withdrawal and exacerbation of pain.

Regardless of the etiology, up to 90% of patients with terminal illness report constipation. Treatment is similar to opioid-induced constipation. Bowel obstruction may present as constipation but these patients will have additional signs or symptoms such as vomiting, abdominal pain or distension, or peritoneal signs that point toward the diagnosis. If the diagnosis is in doubt, plain abdominal films usually help differentiate simple constipation from obstruction. More sophisticated imaging, such as CT scanning, should be used rarely in this population.

Hypercalcemia occurs in 10-20% of patients with lung cancer and is also common in breast cancer and myeloma. The most common symptom is constipation. Many patients may elect not to treat hypercalcemia in the setting of terminal illness. In that case, symptomatic treatment with laxatives and enemas may be helpful.

Nausea and vomiting are common in patients with cancer, CHF, ESRD, and AIDS. This may be a reflexive response to bowel distention from constipation, the most common reversible cause. The second most commonly identified reversible cause of nausea and vomiting is medications. Narcotics often cause nausea and vomiting when treatment is initiated. Tolerance usually develops during the first week of treatment. An antiemetic such as metoclopramide or a serotonin antagonist may be effective. Another narcotic may be substituted. If another medication is suspected, it should be discontinued with substitution as needed. When no specific etiology is identified, an antiemetic should be used.

Anorexia is a common end-of-life phenomenon. Agents that may help include corticosteroids, anabolic steroids, or cannabinoids. Educating patients and their families about the common occurrence of this symptom may be helpful.

Depression and Anxiety

Depressive symptoms are common at the end of life. While many people believe that depression is "normal" among dying patients, it is not an inevitable element of terminal illness and may be treatable. Major depression needs to be differentiated from the expected anger, sadness, and anxiety associated with a serious illness. The degree and persistence of symptoms are a key to considering major depression, which is estimated to occur in fewer than 25% of patients with terminal illness. An open-ended question such as "how much of the time do you feel depressed?" may be the best screening tool. A previous history of depression or a family history increases the likelihood of developing depression in response to a serious illness.

As with other cases of depression, selective serotonin reuptake inhibitors are the mainstay of treatment. Low doses may be started in the acute care setting with upward titration as needed. Therapeutic effects may be delayed for weeks, so these are appropriate when a patient has a prognosis of at least a few months. Some authors have advocated use of stimulants for patients with a very short-term prognosis. ^{[28, 29]} They may be effective within a day or two and may be particularly helpful in patients who have severe fatigue as part of their symptom complex. Dextroamphetamine and methylphenidate are amphetamine stimulants that have been used. Pemoline is a nonamphetamine stimulant that has also been used in this context.

Anxiety is common in patients in palliative care. It is often a component of a depressive syndrome and, in that case, treatment of depression usually results in improvement. Anxiety may also be a primary psychiatric disorder or represent an exaggerated response to the stress and worry associated with a terminal illness. Anxiety disorders may increase the requirements of opioids in acute and chronic pain management, and anxiolytics should be considered as an adjunct in these patients. Benzodiazepines or neuroleptics are reasonable options for the pharmacologic treatment of anxiety.

Delirium

Management of delirium includes identification and management of any potentially reversible causes, coupled with non-pharmacological approaches. For patients who do not respond adequately to these measures, pharmacologic measures may be required.

Haloperidol is often the first-line treatment; other neuroleptics, such as olanzapine, risperidone, and quetiapine, are alternative options. For patients with persistent delirium despite first0-line neuroleptics, the treatment strategies include escalating the dose of the same neuroleptic, rotation to another neuroleptic, or the addition of a second neuroleptic or other agent. ^[30]  In a preliminary trial of hospitalized patients with agitated delirium and advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. ^[7]