The end stages of chronic, progressive, life-limiting diseases bring a host of difficult symptoms and causes of suffering. There are disease-mediated symptoms, such as pain, dyspnea, fatigue, and loss of mobility, and there are the accompanying emotional states, such as depression, anxiety, and a sense of uselessness. These symptoms and states intertwine and interact in a complex manner, and each one deserves attention.
Of the many symptoms experienced by those at the end of life (EOL), pain is one of the most common and most feared. Pain is often undertreated, even when prevalence rates and syndromes are well understood and the means of relief are within all physicians’ capabilities to provide, directly or through consultation. With careful assessment and a comprehensive plan of care that addresses the various aspects of the patient’s needs, pain can be controlled in the majority of cases. Awareness and provision of basic and specialized interventions can ensure comfort for all patients through the final stages of a terminal illness. This is equally important in order to prevent prolonged and pathologic grief in surviving loved ones.
All the members of a palliative care team play important roles in comprehensive pain management. The roles of both physicians and nurses begin with assessment and continue throughout the development of a plan of care and its implementation. Rehabilitation specialists, clinical pharmacists, psychologists, social workers, and spiritual counselors also provide important elements in helping patients optimize their quality of life, stay comfortable, heal relationships, complete unfinished business, and find peace as they approach death. To provide optimal pain control, all health care professionals must understand the causes and prevalence of pain at the end of life, the treatments used to provide relief, and the barriers that prevent good management. To champion this position there are now multiple guidelines regarding pain assessment and management during this time. One example is from the American College of Physicians, which also, for the first time in the medical literature, defines the EOL period as “a phase of life when someone is living with an illness that will worsen and eventually cause death. It is not limited to the short period of time when the patient is moribund.” This challenges providers to think about EOL pain in a much more upstream fashion as many of these patients will be in this phase of their lives for years.
To illustrate some common scenarios, we present three different fictional, but typical, case studies.
Judith is a frail 81-year-old who lives on her own with assistance from a home care nurse and from a daughter, who lives nearby. She was admitted to the hospital with acute respiratory failure resulting from bronchitis. She has advanced chronic obstructive pulmonary disease (COPD), with general fatigue, a poor appetite, and a sleep disorder. She also reports severe, debilitating pain in the midthoracic region from postherpetic neuralgia (PHN). She also struggles with congestive heart failure (CHF), coronary artery disease, and attendant angina pectoris that is usually relieved with nitrates. Judith says that she has been feeling “pretty low” lately and finds herself becoming irritated at small events. She characterizes her pain as “bad as it can be” ( Fig. 77.1 ). After a 2- to 3-day intensive care unit (ICU) stay, she will be ready for discharge. However, her pain from PHN is still not controlled, and her life expectancy is most likely limited because of her ongoing comorbidities. She does not have a written advance directive. The hospital staff discusses the next step.
Prevalence of Pain at the End of Life
Assessing pain in patients approaching the end of life requires a multifactorial evaluation. It is important to acknowledge and address the prevalence, high incidence, and serious adverse consequences of pain in the end-stage conditions that affect patients with advanced medical illness, such as controlled and uncontrolled cancer, heart disease, human immunodeficiency virus (HIV) disease, neurodegenerative diseases (e.g., amyotrophic lateral sclerosis [ALS] and multiple sclerosis), and end-stage renal and respiratory diseases ( Box 77.1 and Fig. 77.2 ). These conditions may also be accompanied by other pain-producing disorders that may require separate treatments, as in the case mentioned.
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Low back pain from facet joint arthritis and spondylosis
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Osteoarthritis
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Osteoporosis
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Previous bone fractures
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Rheumatoid arthritis
- •
Polymyalgia rheumatica
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Paget’s disease
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Peripheral neuropathies
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Neuropathic pain associated with stroke
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Shingles; postherpetic neuralgia
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Diabetes
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Trigeminal neuralgia
- •
Nutritional neuropathies
- •
Peripheral vascular disease
- •
Coronary artery disease
The prevalence of pain in the terminally ill varies by diagnosis and demographics. Approximately one third of the people who are actively receiving treatment for cancer and two thirds of those with advanced malignant disease experience pain. Almost 75% of patients with advanced cancer who are admitted to the hospital report pain on admission. In a study of cancer patients who were very near the end of life, pain occurred in 54% and 34% at 4 weeks and 1 week prior to death, respectively. Uncontrolled cancer pain also predicts hospital admissions. In an outpatient cancer center, an evaluation of more than 5000 patient encounters where the pain intensity scores were high (7 to 10 on a scale of 0 to 10) demonstrated that 29% of these patients were hospitalized within 30 days of those visits. In another study of more than 13,000 cancer patients in U.S. nursing homes, an average of 30% of the patients reported daily pain. In those patients, pain varied according to age, sex, race, marital status, physical function, depression, and cognitive status.
In other studies of patients admitted to palliative care units, pain often is the dominant symptom, along with fatigue and dyspnea. Until recently it was widely believed that patients dying from nonmalignant disease did not have high levels of pain. However, it is now known that patients dying from cardiac failure, COPD, end-stage renal disease, and other end-stage diseases suffer similar levels of pain to those found in patients with malignant disease. In fact, comparing advanced cancer patients to those with symptomatic congestive heart failure (CHF), it is now clear that the symptom burden is as great, or greater, in the latter. In a multicenter Veterans Administration (VA) study of the symptoms CHF patients experience, it was noted that over 55% of the them had pain, the majority of which rated their pain as moderate to severe. This was more common than the sensation of dyspnea. People at particular risk for undertreatment include older adults, minorities, and women.
An attempt has been made to characterize the pain experience of those with HIV disease because of the frequency for this disorder to be seen in palliative care settings. More than 56% of patients with HIV disease report pain, with the most common manifestations being headache, abdominal pain, chest pain, and neuropathies. Lower CD4 + cell counts and HIV-1 ribonucleic acid (RNA) levels are associated with higher rates of neuropathy. There have been many reports of undertreatment of patients with HIV disease, including those patients with a history of addictive disease.
Prevalence of Pain at the End of Life
Assessing pain in patients approaching the end of life requires a multifactorial evaluation. It is important to acknowledge and address the prevalence, high incidence, and serious adverse consequences of pain in the end-stage conditions that affect patients with advanced medical illness, such as controlled and uncontrolled cancer, heart disease, human immunodeficiency virus (HIV) disease, neurodegenerative diseases (e.g., amyotrophic lateral sclerosis [ALS] and multiple sclerosis), and end-stage renal and respiratory diseases ( Box 77.1 and Fig. 77.2 ). These conditions may also be accompanied by other pain-producing disorders that may require separate treatments, as in the case mentioned.
- •
Low back pain from facet joint arthritis and spondylosis
- •
Osteoarthritis
- •
Osteoporosis
- •
Previous bone fractures
- •
Rheumatoid arthritis
- •
Polymyalgia rheumatica
- •
Paget’s disease
- •
Peripheral neuropathies
- •
Neuropathic pain associated with stroke
- •
Shingles; postherpetic neuralgia
- •
Diabetes
- •
Trigeminal neuralgia
- •
Nutritional neuropathies
- •
Peripheral vascular disease
- •
Coronary artery disease
The prevalence of pain in the terminally ill varies by diagnosis and demographics. Approximately one third of the people who are actively receiving treatment for cancer and two thirds of those with advanced malignant disease experience pain. Almost 75% of patients with advanced cancer who are admitted to the hospital report pain on admission. In a study of cancer patients who were very near the end of life, pain occurred in 54% and 34% at 4 weeks and 1 week prior to death, respectively. Uncontrolled cancer pain also predicts hospital admissions. In an outpatient cancer center, an evaluation of more than 5000 patient encounters where the pain intensity scores were high (7 to 10 on a scale of 0 to 10) demonstrated that 29% of these patients were hospitalized within 30 days of those visits. In another study of more than 13,000 cancer patients in U.S. nursing homes, an average of 30% of the patients reported daily pain. In those patients, pain varied according to age, sex, race, marital status, physical function, depression, and cognitive status.
In other studies of patients admitted to palliative care units, pain often is the dominant symptom, along with fatigue and dyspnea. Until recently it was widely believed that patients dying from nonmalignant disease did not have high levels of pain. However, it is now known that patients dying from cardiac failure, COPD, end-stage renal disease, and other end-stage diseases suffer similar levels of pain to those found in patients with malignant disease. In fact, comparing advanced cancer patients to those with symptomatic congestive heart failure (CHF), it is now clear that the symptom burden is as great, or greater, in the latter. In a multicenter Veterans Administration (VA) study of the symptoms CHF patients experience, it was noted that over 55% of the them had pain, the majority of which rated their pain as moderate to severe. This was more common than the sensation of dyspnea. People at particular risk for undertreatment include older adults, minorities, and women.
An attempt has been made to characterize the pain experience of those with HIV disease because of the frequency for this disorder to be seen in palliative care settings. More than 56% of patients with HIV disease report pain, with the most common manifestations being headache, abdominal pain, chest pain, and neuropathies. Lower CD4 + cell counts and HIV-1 ribonucleic acid (RNA) levels are associated with higher rates of neuropathy. There have been many reports of undertreatment of patients with HIV disease, including those patients with a history of addictive disease.
Assessing Pain at the End of Life
Assessment of pain, including a thorough history and comprehensive physical examination, guides the choice of diagnostic studies and the development of the pharmacologic and nonpharmacologic treatment plan. The primary source of information in a pain assessment should be a patient’s self-report. Many different pain rating scales are available, ranging from complex multidimensional tools to very simple numeric and picture scales, which can help patients identify pain and then document the efficacy of treatment. Widely used examples of this include the FACES Pain Scale, the McGill Pain Questionnaire, and the Brief Pain Inventory. When using pain scales, be sure to follow the directions for administration carefully.
A pain scale that suits a given patient’s ability to self-report should be part of each patient’s medical record. Health professionals should teach patients and their families to use these scales themselves to help in longitudinal pain assessment and continuity of care. Patients with terminal illnesses should be encouraged to describe their experiences of pain in their own words. However, many patients near the end of life are unable to provide detailed descriptions of their pain character, intensity, or location. Particularly for patients with cognitive impairment, self-assessments may be difficult to interpret. Nevertheless, even in these patients, self-assessments remain the cornerstone of pain management. For these patients, the use of the “pain thermometer” has been validated as a self-report instrument for pain intensity in patients with mild to moderate cognitive impairment.
Judith describes her PHN as a “burning, needling pain” near her spine, spreading out across her back on the right, beneath her axilla, and around to her breast. Her pain subsides sometimes, but rarely goes away altogether. Knowing the character and location of her neuropathic pain allows her caregivers to pinpoint adjuvant pain relief. In contrast, Judith’s angina pain is “a deep, heavy ache” in her chest. She notes that it is intermittent and stressful, because she never knows quite when to expect it. By asking her to keep track of when her angina occurs, her caregivers are able to predict more precisely when it may be triggered and advise her accordingly, perhaps reducing both severity and frequency.
A comprehensive evaluation of pain should include an assessment of the pain intensity, character, frequency, onset, duration, and location as well as a detailed history of pain, a physical and neurologic examination, and psychosocial assessment. Diagnostic evaluation that includes tests to determine the cause of pain are important to corroborate clinical impressions of the cause of pain and mechanisms, but diagnostic workup should neither delay empiric treatment nor add excessive burden to the patient, especially when death is imminent. It also is important to take into account common pain- and advanced illness–related comorbidities, such as sleep disturbances and depression, which can affect pain levels, suffering, and functioning.
Terminally ill patients sometimes complain of pain as a way of expressing other forms of suffering, distress, grieving, anxiety, or depression. When this is the case, psychosocial or spiritual evaluation and intervention will be more effective than analgesics. It is well established that attention and emotion influence pain processing and perception, and conversely inadequately managed pain can lead to anxiety and depression. Therefore, comprehensive assessment is required to determine the optimal plan of care, as specific to pain etiology as possible. Particularly for health care providers unfamiliar with the care of patients near the end of life, involvement of other disciplines (e.g., nursing, social work, chaplaincy) can be very valuable in uncovering other sources of emotional or spiritual suffering that may be confusing the pain assessment.
Differentiating Pain Mechanisms and Choosing Appropriate Therapies at the End of Life
Patients in the terminal stage of an illness often experience multiple mechanisms of pain simultaneously (e.g., both nociceptive and neuropathic). Nevertheless, it is important to differentiate among different types of pain because the type of treatment and its success are largely dictated by the pain mechanism and its original source. In some conditions, especially metastatic cancer, pain is often caused by a complex mix of nociceptive and neuropathic factors. Though neuropathic pain afflicts 7% to 8% of the general population, its effective recognition and management might be wanting given the lack of exposure in medical education on this topic. An evaluation of 104 U.S. medical schools found only 48 of them include neuropathic pain as a required topic and on average only 0.5 hour is spent teaching about it. Evidence-based guidelines are available and should be utilized while keeping in mind that an important strategy for treating EOL patients is using one medication that might treat more than one type of pain or multiple symptoms. For example, an opioid might be helpful for neuropathic pain as well as angina. A tricyclic antidepressant can be employed for both postherpetic neuralgia and a sleep disorder. This strategy is supported in the medically frail population.
Effects of Unrelieved Pain on the Patient and Caregiver
There is growing evidence that inadequate pain relief might hasten death, not only via the well-recognized morbid effects of increasing physiologic stress, reducing mobility, increasing proclivities toward pneumonia and thromboembolism, and increasing the work of breathing and myocardial oxygen requirements, but also through immune suppression. Pain may lead to a spiritual despair and significant decrease in emotional well-being because the individual’s quality of life is impaired. It is the professional and ethical responsibility of clinicians to focus on and attend to adequate pain relief for their patients and to properly educate patients and their caregivers about analgesic therapies.
Palliative care and hospice programs are charged with caring for not just the patient but the family/caregivers as well. Caregiving is a risk factor for mortality. This carries not only physical consequences but emotional, economic, and social ones. When pain and other distressing symptoms are properly attended and advance directives are completed to guide the caregiver, quality scores for EOL care increase, costs and resource utilization decrease, and caregiver stress is diminished.
Returning to Judith, who has COPD, coronary artery disease, and PHN, it is clear that discussions about care preferences (i.e., advance directives) are optimal before a medical crisis and while there is cognitive capacity for decision making. However, under the current circumstances, a care planning meeting with the attending clinician, consultant clinicians (e.g., palliative care/hospice team), and designated responsible family member is of paramount importance. The team must adequately control her pain before discharge with a follow-up plan in place, or they must transfer her to a skilled facility, such as an inpatient palliative care/hospice unit, where pain management expertise and focused attention are immediately available. Alternatively, with a prognosis of 6 months or less, if Judith prefers to go home immediately, a hospice program with the ability to manage her pain condition should be consulted. Regardless of setting, nonpharmacologic approaches to pain control along with titration of “first-line” agents for neuropathic pain (anticonvulsants, topical local anesthetic, and opioids) should proceed with close monitoring to balance therapeutic and adverse effects.
Grace is a 74-year-old in the late stages of Alzheimer’s disease with severe osteoarthritis in her knees and spine. She lives with her married daughter and two grandchildren. Her daughter and a son living nearby provide her essential care, and until recently she has remained active and ambulatory. She is beginning to experience severe pain from her arthritis, manifest by grimacing, crying, and moaning. The current caregivers are not always sure what she is expressing, but they understand that she is in some distress and are eager to help alleviate it. They meet with their family physician to talk about options. Because Grace is in the far-advanced stage of Alzheimer’s disease, the physician refers her to hospice for comprehensive care and support of her family. During her initial evaluation, the family stresses that their primary goal is to make sure that Mom is comfortable. The hospice nurse evaluates Grace and determines that she responds well to a variety of nonpharmacologic interventions. Her family members express a willingness to use a variety of hands-on and nonpharmacologic techniques to help Grace live her last days relatively free of pain and suffering. Meanwhile, she is started on a regimen of around-the-clock acetaminophen (1000 mg three times daily) with the option for more potent pharmacologic therapies left open.
Nonpharmacologic Approaches to Pain Management in Palliative Care
An important aspect of any management strategy is the use of nonpharmacologic treatments. Various nonpharmacologic approaches to pain are effective in alleviating pain for patients with advanced illness. These include physical interventions, such as positioning and active or passive mobilization (therapeutic exercise); techniques, such as transcutaneous electrical nerve stimulation (TENS), massage, and heat or cold; and complementary and alternative medicine techniques, music, and relaxation or imagery exercises. Table 77.1 offers a list of some of the most common nonpharmacologic interventions.
| Intervention | Details |
|---|---|
| Rehabilitation/physical therapy |
|
| Massage |
|
| Transcutaneous/percutaneous |
|
| Acupuncture | Popular complementary therapy for patients with cancer and other end-stage pain:
|
| Cognitive interventions | Some common cognitive interventions:
|
| Music therapy | Music effectively reduces anxiety and improves mood for:
|
The type of intervention, or combination of interventions, depends on the source and severity of pain as well as the physical condition and receptivity of the patient. In an investigation of the prevalence of complementary and alternative medicine use in an end-of-life population, Tilden and colleagues, through a series of phone interviews with family caregivers of recently deceased patients, found that 53.7% of the deceased used some kind of complementary therapy, were more likely to be younger with college degrees and higher household incomes, and were more likely to have used one or more life-sustaining treatments. Symptom relief was the most frequent reason given for complementary and alternative medicine use. A study by Weiner and Ernst that reviewed common complementary and alternative treatment modalities for the treatment of persistent musculoskeletal pain found that the use of these modalities is increasing in older adults. The study authors concluded that rigorous clinical trials examining efficacy are still needed before definitive recommendations regarding the application of these modalities can be made.
Aside from their objective efficacy, a medical sociologic study by Garnett on the use of complementary therapies by palliative care nurses sees these therapies as an “emotional inoculation” that builds resiliency and an important bond between patient and caregiver. Nonpharmacologic interventions often comfort the patient while involving and empowering family and other caregivers. The necessity of feeling effective for caregivers should not be overlooked—it can have a direct effect on the experience of the patient as well as the emotional survival of the family caregiver in particular. A study by Keefe and colleagues on the self-efficacy of family caregivers of cancer patients found that caregivers who rated their self-efficacy as high reported much lower levels of caregiver strain as well as lower negative mood and higher positive mood. Caregiver self-efficacy in managing the patient’s pain was related to the patient’s physical well-being. When the caregiver reported high self-efficacy, the patient reported having more energy, feeling less ill, and spending less time in bed.
Rehabilitation and Physical Therapy
Functional rehabilitation and physical therapy techniques in appropriately selected patients can add to quality of life even in the face of limited life expectancy. In the case presented, Grace typifies patients who respond well to nonpharmacologic pain interventions. A study by Montagnini and colleagues, assessing the use of physical therapy in a hospital-based palliative care setting, found that a significant proportion demonstrated improvement in function after 2 weeks. The study authors found that patients with a diagnosis of dementia were most likely to show improvement in functional status and concluded that physical therapy assessment and use were uncommon in the studied group, but when implemented, 56% of the patients benefited.
Massage
Research suggests that patients with cancer, particularly in the palliative care setting, are increasingly using aromatherapy and massage. There is good evidence that these therapies may reduce anxiety for short periods. A study by Soden and colleagues was designed to compare the effects of 4-week courses of aromatherapy with massage and massage alone on physical and psychological symptoms in patients with advanced cancer. The study authors were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control, anxiety, or quality of life, but sleep scores improved significantly in both groups, and there were statistically significant reductions in depression scores in the massage group, suggesting that patients with high levels of psychological distress respond best to these therapies. When massage has been evaluated for impact in treating osteoarthritis of the knee, it has been found to lower pain scores and improve functionality. In this 8-week study with 125 participants receiving either usual care or weekly massage regimens, it was reported that there is an increasing effect with greater total time of massage until a plateau was reached at 60 minutes per week.
Acupuncture and Transcutaneous Nerve Stimulation (TENS)
These modalities may be effective in selected patients based on meta-analyses of the literature and findings of National Institutes of Health (NIH) consensus panels. When looked at for osteoarthritis of the knee, TENS has been found to require further study based on a Cochrane review. Patients with the following characteristics appear to benefit most from acupuncture: a diagnosis of osteoarthritis, living in a multiperson household, being female, and failing other therapies. For percutaneous procedures, appropriate cautions, skilled certified practitioners, and fastidious aseptic techniques are required to protect patients and staff from untoward adverse outcomes. Similarly, for therapies involving electrical stimulation, awareness of implanted devices (pumps, stimulators, implantable cardioverter defibrillators, or pacemakers) and precautions to prevent malfunction must be taken.
Cognitive Interventions
Simple psychological interventions can have a significant impact on pain. As an example, Paqueta and colleagues explored the idea that everyday emotion regulation through self-supporting maintenance or change in positive and negative emotions can help reduce pain intensity in the hospitalized older adult. Emotion regulation was found to be prospectively related to pain intensity for both overall emotion and anxiety-specific regulation. The study authors suggested that promoting emotion regulation as a self-management strategy could contribute to cost-effective pain management in general or targeted older adult populations.
Music Therapy
There is growing interest in the therapeutic use of music. The difficulties inherent in the medical treatment of this population make the use of music, as a noninvasive therapeutic modality, attractive. Five studies with a total of 175 participants in a Cochrane review suggested a benefit for patients near the EOL, though the results were subject to a high risk of bias. Music is often used to enhance well-being, reduce stress, and distract patients from unpleasant symptoms. Although there are wide variations in individual preferences, music appears to exert direct physiologic effects through the autonomic nervous system.
Choosing the Best Approach
Although pain at the EOL is often thought to come from cancer or HIV, discomfort from osteoarthritis needs much more attention. An observational study of more than 4700 older adult decedents found the prevalence of pain in the last month of life to be 60% in those with arthritis and 26% in those without ( P < 0.001). A combination of treatments is usually most effective when using nonpharmacologic approaches to pain management. When cognition is compromised, constant vigilance for the presence of pain by monitoring behavior and nonverbal cues that deviate from a patient’s baseline is advised. If the presence of pain is unclear, it might be warranted to attempt analgesic intervention. Similar to pharmacotherapy, multimodal approaches offer the potential benefit of additive and synergistic effects. Because nonpharmacologic therapies need to be tailored to individual likes, dislikes, and effectiveness, knowledge of the various modalities, management of expectations, open-mindedness, and a “trial-and-error” approach should be embraced.
The hospice nurse was able to offer Grace’s family a variety of hands-on and alternative modalities that could be used in addition to pharmacologic interventions to successfully comfort the patient. The nurse found that simple stretches and strengthening and mobilization exercises were effective for reducing the stiffness that was associated with Grace’s musculoskeletal disease. This helped to relax the patient and prevent the usual anxiety that is associated with getting her out of bed in the morning and daily personal care, such as bathing and toileting. A simple TENS unit appeared to ease the patient’s knee pain. The nurse was also able to guide the family in some interventions that reduced Grace’s anxiety and increased the family’s sense of involvement and effectiveness. They found that songs from her youth brought Grace a great deal of pleasure, and her son, a fan of the music, enjoyed spending listening time with her. Physical contact often calmed Grace, and the nurse trained Grace’s granddaughter in simple massage techniques. These interventions seemed to be effective and helped the family to feel that they were contributing to Grace’s care and well-being.
Ben is a 79-year-old with metastatic colon cancer who has just returned to his home in an assisted-living facility postoperatively after a bowel resection. He sees a geriatric nurse practitioner, in collaboration with a family physician, for ongoing primary care. It has become clear that there are widespread metastases, and his oncologist agrees that the current goal of care is comfort only. Ben is still ambulatory and in the early stages of his terminal illness. No further chemotherapy or radiation therapies are indicated, but the patient reports progressive abdominal pain, and symptoms suggestive of intermittent bowel obstruction have developed. Ben refuses further hospitalization and surgery, and prefers noninterventional therapies, if at all possible. A consulting pharmacist and medical director from the local hospice are asked to come in and help the nurse practitioner choose the best pharmacotherapy for pain and bowel-related signs and symptoms, including types of drugs, route of drug administration, and the best way to minimize possible side effects. The explicit goals of care are a comfortable, dignified death, crisis prevention, and self-determined life closure (no prolongation of dying by medical intervention).
Pain Management and Palliative Care for Cancer Patients
Cancer, arguably more than any other disease process, has been the model from which the evidence base has sprung for aggressive attention to pain control and palliation of the whole person and for their families. It is also a driving force for quality improvement measures. Pain is the most frequent complaint for cancer patients presenting to the emergency department. Compared to cancer patients who die in a hospital, those who die at home have higher quality of life scores and their bereaved family members are at less risk for developing psychiatric illness. Because of data such as these, the cancer community has developed evidence-based recommendations on pain management. It is also now recommended that all cancer patients have access to palliative care services so that patient-centered care is seamlessly integrated into standard oncology practice.
Drugs for Pain Relief in Palliative Care
Pharmacologic therapies for pain include nonopioids, opioids, adjuvant analgesics, disease-modifying therapies, and (in some cases) interventional techniques. Intractable pain and symptoms that are not responsive to basic therapeutic techniques, although not common, must be treated appropriately and aggressively. In some highly selective cases, palliative sedation may be warranted. A sound understanding of pharmacotherapy for pain treatment allows the palliative care/hospice team to create a comprehensive plan of care as well as recognize and assess medication-related adverse effects, understand drug-drug and drug-disease interactions, and educate patients and caregivers regarding appropriate medication usage. Recognition of the limits of usual therapies and the ability to muster expert assistance are important skills. This will ensure a comfortable process of dying for the well-being of the patient and for the sake of those in attendance.
Genetic factors, pathologic processes, concurrent medication, and aging all influence drug response and disposition. However, there are also a variety of nonmedical factors that influence responses to drug treatment in patients with far-advanced disease, including the social, environmental, and psychological milieus as well as the general vulnerability of this population. Understanding the clinical pharmacology of the drugs in question is essential for professional caregivers. Commonly, there is a need to use drugs for non–U.S. Food and Drug Administration (FDA)–approved indications or routes of administration, simply because randomized controlled clinical trials have not been performed, because (usually) of financial constraints. Rational polypharmacy (combining drugs with different mechanisms of action to produce additive or synergistic effects and minimize adverse effects) is often necessary, but there is a high potential for drug interactions, so close monitoring is required.
The principles of effective symptom control are always paramount: diagnose the underlying cause of each symptom and tailor the treatment to individual circumstances and clinical context. Keep in mind that normal pharmacokinetics and pharmacodynamics may be considerably altered by end-stage disease states. For example, in patients with chronic liver disease or hepatic metastases, drugs may bypass hepatic metabolism altogether, increasing bioavailability. Similarly, renal clearance is almost always diminished during the dying process, leading to the accumulation of drug metabolites, some of which (e.g., those of morphine) may be toxic.
Communicating with Patients, Families, and Other Health Care Professionals
Communicating clearly about pharmacologic pain control with patients, families, and other members of the palliative care/hospice team is essential to providing effective pain management. It is important to be specific about the types of drugs that are available, how they are likely to affect the patient, how they are to be administered, and how they may interact with existing medications. Despite the importance of pain management at the end of life, there are often substantial roadblocks to overcome in getting patients the treatment that they need. Professional health care workers may have unsubstantiated but strong beliefs about analgesic use, especially opioid use, that lead to underprescribing.
Several surveys show that physicians, nurses, and pharmacists express concerns about addiction, tolerance, and side effects of morphine and related compounds. These fears are pervasive among patients and family members as well. Studies have suggested that these fears lead to undermedication and increased pain intensity. Concerns about being a “good” patient or belief in the inevitability of cancer pain lead patients to hesitate in reporting pain. In these studies, less educated and older patients were most likely to express these beliefs.
Often a physician or other providers may be reluctant to offer the patient direct and objective information on his or her health, especially toward the end of life, seeking to “soften the blow” by keeping the details vague. Most patients, however, prefer complete information about their condition. However, patients may wish to defer decision making to the physician or family members. Physicians have a professional duty to determine patients’ medical wishes. As a purely practical matter, by default or situational necessity, this responsibility may fall to the nurse or nurse practitioner. It is important to know that there are helpful tools, such as simple card sorting, that can be used to facilitate this exchange; for example, the five-card Control Preference Scale uses cards to portray different roles in treatment decision making with a statement and a picture.
Dispelling Common Myths About Pain Management
Understanding the barriers that are faced when treating pain can lead professionals to better educate and counsel patients and their families. Patients should be asked whether they are concerned about addiction and tolerance (often described as becoming “used to” or “immune” to the drug). At the end of life, patients may need to rely on family members or other support persons to dispense medications. Studies suggest that patients’ pain experiences and family members’ perceptions about them do not correlate well, leading to inadequate provision of analgesia. The interdisciplinary palliative care/hospice team is essential in the communication effort, with nurses, social workers, chaplains, physicians, volunteers, and others providing support in exploring the meaning of pain and barriers to pain relief. Education, counseling, reframing, and spiritual support are imperative.
Providers can also be concerned about precipitating death with the use of medications such as opioids or benzodiazepines that are used aggressively during the EOL phase or when someone is actively dying (aberrant respirations, hypotension, diminished cognition, low urine output). It has been established that patients have legal and ethical rights to symptom management during this time. Furthermore, and importantly, there is no evidence to suggest that administration of these medications will hasten death. Indeed the opposite has been observed with patients living longer periods of time when symptom-driven medications are delivered compared to those without the medications. The reason for this is unsettled but physiologic-based theories have been published. The provider has a duty to address the ethical, legal, and physiologic rationale for medications with patients and caregivers in this situation.
Overview of Nonopioid and Opioid Therapy in Advanced Disease
This section provides a brief overview of commonly used pharmaceutic agents available in the United States for the treatment of persistent pain associated with advanced disease. Pain-relieving drugs can be categorized as nonopioid analgesics, opioid analgesics, and adjuvant analgesics. Detailed knowledge of these classes of agents is necessary to provide quality palliative care, and although a comprehensive review is beyond the scope of this chapter, links to more detailed lists of all drugs used for pain control throughout the world can be found in Table 77.2 . Of note, newer formulations or delivery systems are coming on to the market regularly. They may have a place in the EOL medication repertoire in the future. For now it is important to recognize that currently none of the new or renovated analgesic agents have been shown to be superior to the medications described in this chapter in the EOL population.
| Web Address | Content |
|---|---|
| www.palliativedrugs.com | Palliative care formulary online |
| www.pallmed.net | Generic site, with drug-compatibility database |
| http://nccam.nih.gov.easyaccess1.lib.cuhk.edu.hk | Information on complementary medicines |
| www.fda.gov/orphan | Information on orphan drugs |
There are several possible methods of approaching pharmacologic pain management for patients with advanced diseases. Patients may require several different medications to deal with a variety of pain syndromes and disease- or treatment-related discomfort. For expedient and thorough treatment, it is often wise to adopt a stepwise approach to the use of pain medications. The World Health Organization (WHO) has developed a simple three-step model for managing cancer pain that can be applied to many different situations. It has been modified over time to adapt to the evolving fields of pain and palliative medicine ( Fig. 77.3 ). This revised approach recommends that mild pain (1 to 3 on a numeric analog scale) should be treated with nonopioid pain relievers, such as aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), with or without adjuvant therapy. Higher pain intensities indicate the use of nonopioid analgesics along with opiate derivatives, such as hydrocodone, oxycodone, or tramadol. If pain is not relieved, then titration of opioids, such as morphine, hydromorphone, and fentanyl, in combination with nonopioid analgesics and adjuvants, is indicated. Refractory pain syndromes often require more invasive techniques, such as spinal opioids, nerve block, or neurostimulation.
Nonopioid Analgesics
Acetaminophen
Acetaminophen has been determined to be one of the safest analgesics for long-term use in the management of mild pain or as a supplement in the management of more intense pain syndromes. It is especially useful in the management of nonspecific musculoskeletal pain or pain associated with osteoarthritis, but it should be considered an adjunct to any chronic pain regimen. It is often forgotten or overlooked when severe pain is being treated in terminally ill patients, but it can be quite effective as a “coanalgesic.” It is important to take into account acetaminophen’s limited anti-inflammatory effect and its hepatic effects. Reduced doses or avoidance of acetaminophen is recommended for patients with renal insufficiency or liver failure, particularly individuals with significant alcohol use. In 2011, one of the manufacturers of acetaminophen announced that the historic 4 grams per day limit placed on it was voluntarily reduced to a lower maximum dose of 3 grams per day for all patients. How this new limit should impact hepatic dysfunction, if at all, is to be determined.
NSAIDs
NSAIDs reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX) and the cascade of inflammatory events that cause, amplify, or maintain nociception. NSAIDs also appear to directly affect the peripheral and central nervous systems. COX has been identified in spinal cord neurons and may play a role in the development of neuropathic pain, but these agents do not appear to be useful in the treatment of neuropathic pain. The “classic” NSAIDs (e.g., aspirin or ibuprofen) are relatively nonselective in their inhibitory effects on the enzymes that convert arachidonic acid to prostaglandins, so gastrointestinal ulceration, renal dysfunction, and impaired platelet aggregation are common. The COX-2 selective NSAIDs rofecoxib and valdecoxib have been taken off the market, and because of potential problems and concerns with gastrointestinal bleeding and thrombosis, celecoxib should be used with caution in high-risk palliative care patients for protracted periods.
NSAIDs are useful in treating many pain conditions mediated by inflammation, including those caused by cancer. These agents cause minimal nausea, constipation, sedation, or effects on mental function, although there is evidence that their use can impair short-term memory in older patients. These agents may be very useful for moderate to severe pain control, either alone or as an adjunct to opioid analgesic therapy. Adding NSAIDs to an opioid regimen may allow a reduced opioid dose when sedation, obtundation, confusion, dizziness, or other central nervous system effects of opioid analgesic therapy alone become problematic. Extended-release formulations are likely to increase compliance and adherence. As with acetaminophen, decreased renal function and liver failure are relative contraindications for NSAID use. Platelet dysfunction or other potential bleeding disorders also contraindicate use of the nonselective NSAIDs because of their inhibitory effects on platelet aggregation, a clear advantage of the coxib class of NSAIDs. If NSAIDs are effective but there is need for prolonged use or there is a history of gastrointestinal complications, proton pump inhibitors can be given to lower the risk of gastrointestinal bleeding. For more information on NSAIDs, see Chapter 41 .
Opioid Analgesics
Opioid analgesics are the most useful agents for the treatment of pain associated with advanced disease, including neuropathic pain. There are few, if any, indications for the mixed agonist-antagonist agents, especially in older patients at end of life. The pure antagonists are used to treat acute overdose and, in selected cases, to prevent opioid-induced bowel dysfunction. The opioids used most commonly in palliative care are morphine, hydromorphone, fentanyl, oxycodone, and methadone.
The only absolute contraindication to the use of an opioid is a history of a hypersensitivity reaction (e.g., rash, wheezing, and edema). Allergic reactions are almost exclusively limited to the morphine derivatives, and the prevalence of true allergic reactions to synthetic opioids is much lower. There is significant inter- and intra-individual variation in clinical responses to the various opioids, so dose titration is the best approach to initial management. Idiosyncratic responses may require trials of different agents in order to determine the most effective drug and route of delivery for any given patient. Table 77.3 lists more specific suggestions regarding optimal selection of opioids in end-of-life care, and Table 77.4 lists the commonly used opioids.
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