Based on the diseases frequently encountered in hospice and palliative care, the most common symptoms managed by palliative care practitioners include pain, dyspnea, constipation, nausea and vomiting, anxiety, and delirium. The management of these symptoms is discussed below.
Pain is a very common symptom among patients receiving palliative care, and providing effective pain management is a high priority of palliative care practitioners. A systematic review found that among studies of patients with cancer (any stage), 53% of patients experienced pain.15 Among studies of patients with advanced cancer, 64% of patients experienced pain and more than 30% of patients who experienced cancer-related pain rated it as moderate or severe.15 In an observational study of adults in the last 2 years of life with a variety of terminal diagnoses (eg, cardiac disease, cancer, frailty) the prevalence of moderate or severe pain was 26%; this increased to 46% during the last month of life.16
Developing an effective plan for pain management first requires pain assessment. Ascertaining the time course of a patient’s pain can help to distinguish acute from chronic pain. In addition, assessing the severity of pain at its best and worst throughout the day, as well as with movement and at rest, can provide helpful information in determining a treatment plan.17 Patient descriptions of pain, such as its quality, precipitating or palliating factors, region affected, radiation of the pain (if any), temporal factors associated with the pain (ie, worse at night), and impact on the patient’s ability to function can be extremely helpful in identifying the cause of pain and appropriate treatment. In noncommunicative patients, palliative care practitioners should assess patients for nonverbal indicators of pain such as grimacing, agitation, restlessness, or resistance to personal care.17,18 Family members or caregivers can also provide useful information when assessing pain, as can validated tools such as the Pain Assessment in Advanced Dementia (PAINAD), Checklist of Nonverbal Pain Indicators (CNPI), and the Mahoney Pain Scale.17,18 When assessing a patient’s complaint of pain, a key distinction is between nociceptive pain and neuropathic pain, as drug therapy selection requires an understanding of pain pathophysiology.
Nociceptive pain is commonly described by patients as achy, throbbing, and dull.17 Traditionally, nonopioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory agents (NSAIDs) are often considered first line for pain management. However, among the palliative care patient population, the severity of pain or contraindications to nonopioid agents often necessitate the use of opioid agents such as morphine, oxycodone, or hydromorphone.17 For example, acetaminophen is contraindicated in patients with severe hepatic impairment, while NSAIDs can increase the risk of cardiovascular events and gastrointestinal bleeding and should not be used in patients with renal impairment.17 In patients without contraindications, NSAIDs are helpful for mild to moderate nociceptive pain, especially pain due to inflammatory processes such as pain from bony metastases in advanced cancer.18 Opioids are frequently required for the management of moderate to severe pain in palliative care.18 Although the World Health Organization ladder recommends weak opioid agonists such as tramadol and codeine as an intermediate step between nonopioid analgesics and strong opioids such as morphine and oxycodone, current evidence supports using lower initial doses of strong opioids in place of weak opioids to achieve better results in the management of cancer pain.19,20 Opioid agents do not have a maximum ceiling dose, and should instead be titrated to achieve acceptable pain relief while minimizing unacceptable adverse effects such as sedation and respiratory depression. After initiating opioid therapy, patients should be re-evaluated and doses titrated as required. For patients continuing to experience moderate pain, a dose increase of 25% to 50% is appropriate, while a dose increase of 50% to 100% is reasonable for patients experiencing severe pain.17
Patients often describe neuropathic pain as tingling, sharp, burning, electric shock-like, or numbness. Neuropathic pain is caused by damage to the central or peripheral nervous system itself, rather than actual or potential tissue damage, which is a characteristic of nociceptive pain.21 The distinct pathophysiology underlying neuropathic pain necessitates a different approach to treatment, where adjuvant agents (drugs not originally developed for use as analgesics) are considered first line for pharmacologic management. Evidence-based recommendations for drug treatment of neuropathic pain identify tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and calcium channel alpha-2-delta ligands (gabapentin and pregabalin) as first-line therapies.17,22 Traditional analgesics, such as opioids, are recommended as second-line (tramadol) or third-line therapy (morphine, oxycodone).22
When designing an analgesic regimen, the palliative care practitioner should first conduct a thorough assessment of the patient’s pain to identify the pathophysiology whenever possible. For patients with persistent nociceptive pain, particularly that which is not expected to resolve (eg, pain due to advancing metastatic cancer without targeted interventions such as radiation), scheduling around-the-clock analgesics, rather than as-needed analgesics only is preferable. For patients receiving opioid therapy who require dosing throughout the day to maintain pain control, palliative care practitioners should consider initiation of a long-acting (LA) or extended-release (ER) formulation of an opioid.17 Short-acting opioids should continue to be available for the management of “breakthrough” pain, which the patient may experience despite the LA or extended-release opioid.17 When designing an opioid regimen consisting of LA and short-acting opioids, the basal, or LA, opioid is typically started at a dose representing 50% to 75% of a patient’s total 24 hour opioid requirement, while the breakthrough, or short-acting, opioid is started at a dose representing 10% to 20% of the 24 hour opioid requirement.17,23 If a patient’s description or reason for pain is consistent with a neuropathic pathophysiology, adjuvant agents should be considered, and these agents should always be dosed around-the-clock.
When using opioid therapy as part of an analgesic regimen, palliative care practitioners must diligently monitor for and manage opioid adverse effects. Adverse effects frequently associated with opioid therapy include constipation, sedation, and confusion.18 Adverse effects such as nausea, pruritus, urinary retention, and myoclonus may also occur with opioid therapy although they are less common.18 Respiratory depression, the most severe and worrisome opioid adverse effect, is always preceded by sedation and thus can typically be caught early with careful monitoring and slow dose titration. While tolerance occurs to most opioid adverse effects after the initial days of therapy or after an increase in dose, tolerance to opioid-induced constipation never develops.24 Therefore, all patients receiving opioid therapy must be simultaneously initiated on a bowel regimen containing a stimulant laxative.18,19 Although opioid adverse effects are typically similar for all agents within the class, individual patients may respond more or less favorably to a particular drug. If patients experience unacceptable adverse effects with one opioid agent, rotation to another agent within the class may provide analgesia while minimizing adverse effects.19,24
Dyspnea, or the subjective sensation of breathlessness, is a common symptom in the palliative care patient population.25 Although common among patients with advanced cancer, particularly those with lung tumors, dyspnea also occurs in patients with advanced cardiac and pulmonary disease such as heart failure and COPD.26 Whenever possible, treating and reversing the underlying cause of dypsnea is preferred.26 However, in patients with end-stage disease, reversing the underlying cause may no longer be possible, in which case symptoms should be controlled through pharmacologic and nonpharmacologic treatment.25,26
Opioids are first-line agents for the pharmacologic management of dyspnea.25,26 When used for the management of dyspnea, opioids are equally effective given through either the enteral or parenteral route; however, less evidence supports their use through the nebulized route of administration.25,26 The beneficial effect of opioids on dyspnea is postulated to occur through multiple mechanisms: a vasodilatory effect on the pulmonary vasculature, a decrease in oxygen consumption during rest and exertion, and changes in the effects of carbon dioxide, oxygenation, and inspiratory flow resistive loading on ventilation.25
Benzodiazepines have been studied for the management of dyspnea. A 2011 Cochrane review found no evidence of benefit for benzodiazepines in the management of dyspnea.27 Benzodiazepines are considered second- or third-line agents, and are likely most useful in combination with opioid therapy in patients experiencing both dyspnea and related anxiety.25,27
Non-pharmacologic treatment strategies for dyspnea include use of a fan to create air movement across a patient’s face, re-positioning, pulmonary rehabilitation, and complementary therapies such as relaxation strategies. Although commonly requested by patients due to the symptoms of breathless, supplemental oxygen has not been found to be beneficial for patients without hypoxia (PaO2 < 55 mm Hg [<7.3 kPa]).25
Constipation is a common symptom among patients receiving palliative care, due to both disease processes themselves (eg, tumor obstruction due to gastrointestinal cancers, electrolyte abnormalities, and impaired venous flow due heart failure) and the drugs used to manage other symptoms (eg, opioids, TCAs, antiemetics, and anticholinergics).28 Estimates of the incidence of constipation vary widely, from 18% to 90% of patients, due to varying definitions of constipation.28 Constipation generally includes the following symptoms: bowel movements that are difficult, painful, and/or infrequent; hard stools; and a sense of incomplete bowel evacuation.28 The Rome III Criteria define functional constipation as “a functional bowel disorder that presents as persistently difficult, infrequent, or seemingly incomplete defecation, which do not meet [irritable bowel syndrome (IBS)] criteria.”29
Constipation can be managed through nonpharmacological therapies such as increased intake of fluid and fiber, and increased physical activity. However, among the palliative care patient population, pharmacologic therapy with laxatives is generally required. Bulk-forming laxatives such as psyllium are generally not preferred for palliative care patients due to the risk of bowel obstruction or fecal impaction with inadequate fluid intake.28 In a review of randomized controlled trials evaluating laxatives in patients receiving palliative care, no differences in efficacy were found among lactulose, senna, magnesium hydroxide plus liquid paraffin, and docusate plus senna.28 All patients receiving opioids for the management of pain or dyspnea should receive prophylactic stimulant laxatives to prevent opioid-induced constipation.18,19
When designing a therapeutic regimen for a palliative care patient experiencing constipation, it is reasonable to consider agent availability, patient preference, and onset of action, as the evidence does not support increased efficacy of one agent over another. Combination laxative therapy with agents having different mechanisms of action is likely more effective than restricting therapy to a single laxative.19 Peripheral opioid antagonists such as methylnaltrexone, naloxegol, and alvimopan should be reserved for opioid-induced constipation that does not respond to traditional laxative therapy.19
Although less common than pain and dyspnea, nausea and vomiting are distressing symptoms frequently encountered in the palliative care patient population.30 When evaluating a patient’s complaint of nausea and/or vomiting, the palliative care practitioner should attempt to identify the cause of nausea and/or vomiting to identify potentially reversible causes such as those due to hyperglycemia, electrolyte abnormalities, constipation, or medications.31 Although the evidence base for treatment of nausea and vomiting in the palliative care population is limited, identification of causative factors can also guide rational drug therapy selection.30,31 Causes of nausea and vomiting, and cause-directed therapies, are shown in Table e8-1. If the cause of nausea and/or vomiting is not identifiable or is multifactorial, dopamine antagonists such as haloperidol should be considered for first-line therapy because most symptoms of nausea and vomiting are due gastroparesis or irritation of the chemoreceptor trigger zone.30 Little evidence supports the use of 5-HT3 receptor antagonists outside of chemotherapy-induced and postoperative nausea/vomiting, and thus these agents have a limited role in palliative care.30 Because patients may have multiple causes of nausea and vomiting that respond differently to different agents, use of more than one antiemetic from different classes may be required.30 If symptoms are refractory to first- or second-line therapy, olanzapine may be useful due to its effect on multiple neurotransmitters involved in the emetic pathway.30 Nonpharmacologic therapies for nausea and vomiting include relaxation therapy and distraction, provision of small, frequent meals with adequate liquids, and acupuncture.18
TABLE e8-1Causes of Nausea and Vomiting and Treatment30,31
Anxiety is a common symptom among palliative care patients, and may be an underlying condition, caused by the serious illness itself, or exacerbated by physical symptoms such as pain and dyspnea.18 Communication with patients about their goals of care, and addressing spiritual concerns, discussed later in this chapter, are both essential components of managing anxiety in palliative care patients.18 Other nonpharmacologic tools for managing anxiety, including relaxation techniques and psychotherapy, may also be useful.18
First-line pharmacologic therapy consists of benzodiazepines.18 These agents may be combined with selective serotonin reuptake inhibitors (SSRIs), which have an anxiolytic effect in addition to their antidepressant activity. However, because SSRIs do not achieve efficacy until 4-6 weeks after initiation, they are not appropriate for patients with a life expectancy of less than 1 month.18
Delirium is an acute decline in attention and consciousness combined with cognitive dysfunction and is a common symptom among patients receiving palliative care.18 Among palliative care patients, 13% to 42% of patients have delirium upon admission to a palliative care unit, 26% to 62% of patients have delirium at some point during their admission to a palliative care unit, and 59% to 88% of patients experience delirium during the final weeks preceding death.32 While delirium may be of a hyperactive, hypoactive, or mixed subtype, hypoactive delirium is most common and also more difficult to detect.32
Although often considered an indicator that a patient is approaching the final weeks to days of life, it is important to note that nearly half of delirium cases may be caused by reversible factors and these causes should be assessed and reversed if possible.18,32 Potentially reversible causes of delirium among palliative care patients include: uncontrolled pain; constipation; infections; electrolyte abnormalities; withdrawal from opioids, benzodiazepines, or alcohol; medication adverse effects; and lack of sleep.18 When present, delirium can often be successfully managed or reversed; however, its presence is distressing to patients and caregivers, and can interfere with the assessment and management of other symptoms, such as pain.32 Thus, assessment of delirium is critical to provide good palliative care. Tools such as the Bedside Confusion Scale (BCS), Confusion Assessment Method (CAM), Delirium Rating Scale, and Memorial Delirium Assessment Scale are available to assist in the recognition of delirium and have been validated in the palliative care patient population.32
Non-pharmacologic management of delirium includes patient reorientation, maintenance of a sleep-wake cycle, provision of a familiar environment (presence of family), and provision of assistive devices such as a patient’s glasses and hearing aids.33 Pharmacologic management should begin with avoiding medications that can precipitate or worsen delirium such as benzodiazepines, opioids, anticholinergics, corticosteroids, and beta blockers, as well as correcting reversible causes of delirium.18,33 Drug therapy for the prevention and treatment of delirium has not been supported by existing evidence.33 While some pharmacologic therapies have been found to reduce the rates of delirium among hospitalized patients, an impact on clinical outcomes, such as length of stay and mortality, has not been demonstrated.33 First and second generation antipsychotics are widely used for the management of delirium symptoms among palliative care patients which are not reversible; however, more evidence is required to fully support their place in therapy.18,33