Palliative and End-of-Life Care

83CHAPTER 12

fluoxetine is 10 mg once a day. In most cases, once-a-day dosing is

possible. The choice of which SSRI to use should be driven by (1) the

patient’s past success or failure with the specific medication and (2) the

most favorable side effect profile for that specific agent. For instance,

for a patient in whom fatigue is a major symptom, a more activating

SSRI (fluoxetine) would be appropriate. For a patient in whom anxiety

and sleeplessness are major symptoms, a more sedating SSRI (paroxetine) would be appropriate. Importantly, it can take up to 4 weeks for

these drugs to have an effect.

Atypical antidepressants are recommended only in select circumstances, usually with the assistance of a specialty consultation.

Trazodone can be an effective antidepressant but is sedating and can

cause orthostatic hypotension and, occasionally, priapism. Therefore,

it should be used before bed and only when a sedating effect is desired

and is often used for patients with insomnia at a dose starting at 25 mg.

Bupropion can also be used. In addition to its antidepressant effects,

bupropion is energizing, making it useful for depressed patients who

experience fatigue. However, it can cause seizures, preventing its use

for patients with a risk of CNS neoplasms or terminal delirium. Finally,

alprazolam, a benzodiazepine, starting at 0.25–1.0 mg tid, can be effective in seriously ill patients who have a combination of anxiety and

depression. Although it is potent and works quickly, it has many drug

interactions and may cause delirium, especially among very ill patients,

because of its strong binding to the benzodiazepine–γ-aminobutyric

acid (GABA) receptor complex.

Unless used as adjuvants for the treatment of pain, tricyclic antidepressants are not recommended. While they can be effective, their

therapeutic window and serious side effects typically limit their utility.

Similarly, monoamine oxidase (MAO) inhibitors are not recommended because of their side effects and dangerous drug interactions.

Delirium (See Chap. 27) • FREQUENCY In the weeks or months

before death, delirium is uncommon, although it may be significantly

underdiagnosed. However, delirium becomes relatively common in the

days and hours immediately before death. Up to 85% of patients dying

from cancer may experience terminal delirium.

ETIOLOGY Delirium is a global cerebral dysfunction characterized by

alterations in cognition and consciousness. It is frequently preceded

by anxiety, changes in sleep patterns (especially reversal of day and

night), and decreased attention. In contrast to dementia, delirium has

an acute onset, is characterized by fluctuating consciousness and inattention, and is reversible, although reversibility may be more theoretical than real for patients near death. Delirium may occur in a patient

with dementia; indeed, patients with dementia are more vulnerable to

delirium.

Causes of delirium include metabolic encephalopathy arising from

liver or renal failure, hypoxemia, or infection; electrolyte imbalances

such as hypercalcemia; paraneoplastic syndromes; dehydration; and

primary brain tumors, brain metastases, or leptomeningeal spread of

tumor. Among dying patients, delirium is commonly caused by side

effects of treatments, including radiation for brain metastases and

medications, such as opioids, glucocorticoids, anticholinergic drugs,

antihistamines, antiemetics, benzodiazepines, and chemotherapeutic

agents. The etiology may be multifactorial; e.g., dehydration may exacerbate opioid-induced delirium.

ASSESSMENT Delirium should be recognized in any terminally ill

patient exhibiting new onset of disorientation, impaired cognition,

somnolence, fluctuating levels of consciousness, or delusions with or

without agitation. Delirium must be distinguished from acute anxiety,

depression, and dementia. The central distinguishing feature is altered

consciousness, which usually is not noted in anxiety, depression, or

dementia. Although “hyperactive” delirium, characterized by overt

confusion and agitation, is probably more common, patients should

also be assessed for “hypoactive” delirium, which is characterized by

sleep-wake reversal and decreased alertness.

In some cases, use of formal assessment tools such as the MiniMental Status Examination (which does not distinguish delirium from

dementia) and the Delirium Rating Scale (which does distinguish

delirium from dementia) may be helpful in distinguishing delirium

from other processes. The patient’s list of medications must be evaluated carefully. Nonetheless, a reversible etiologic factor for delirium is

found in fewer than half of all terminally ill patients. Given that most

terminally ill patients experiencing delirium are very close to death and

often at home, extensive diagnostic evaluations such as lumbar punctures and neuroradiologic examinations are inappropriate.

INTERVENTIONS One of the most important objectives of terminal

care is to provide terminally ill patients the lucidity to say goodbye to

the people they love. Delirium, especially when in combination with

agitation during the final days, is distressing to family and caregivers. A

strong determinant of bereavement difficulties is witnessing a difficult

death. Thus, terminal delirium should be treated aggressively.

At the first sign of delirium, such as day-night reversal with slight

changes in mentation, the physician should let the family members

know that it is time to be sure that everything they want to say has

been said. The family should be informed that delirium is common

just before death.

If medications are suspected of being a cause of the delirium, unnecessary agents should be discontinued. Other potentially reversible

causes, such as constipation, urinary retention, and metabolic abnormalities, should be treated. Supportive measures aimed at providing a

familiar environment should be instituted, including restricting visits

only to individuals with whom the patient is familiar and eliminating

new experiences; orienting the patient, if possible, by providing a clock

and calendar; and gently correcting the patient’s hallucinations or cognitive mistakes.

Pharmacologic management focuses on the use of neuroleptics and,

in extreme cases, anesthetics (Table 12-7). Haloperidol remains the

first-line therapy. Usually, patients can be controlled with a low dose

(1–3 mg/d), given every 6 h, although some may require as much as

20 mg/d. Haloperidol can be administered PO, SC, or IV. IM injections should not be used, except when this is the only way to address

a patient’s delirium. Olanzapine, an atypical neuroleptic, has shown

significant effectiveness in completely resolving delirium in cancer

patients. It also has other beneficial effects for terminally ill patients,

including antinausea, antianxiety, and weight gain. Olanzapine is

useful for patients with longer anticipated life expectancies because

it is less likely to cause dysphoria and has a lower risk of dystonic

reactions. Additionally, because olanzapine is metabolized through

multiple pathways, it can be used in patients with hepatic and renal

dysfunction. Olanzapine has the disadvantage that it is only available

orally and takes a week to reach steady state. The usual dose is 2.5–5 mg

PO bid. Chlorpromazine (10–25 mg every 4–6 h) can be useful if

sedation is desired and can be administered IV or PR in addition to

PO. Dystonic reactions resulting from dopamine blockade are a side

effect of neuroleptics, although they are reported to be rare when these

drugs are used to treat terminal delirium. If patients develop dystonic

reactions, benztropine should be administered. Neuroleptics may be

TABLE 12-7 Medications for the Management of Delirium

INTERVENTIONS DOSE

Neuroleptics

Haloperidol 0.5–5 mg q2–12h, PO/IV/SC/IM

Thioridazine 10–75 mg q4–8h, PO

Chlorpromazine 12.5–50 mg q4–12h, PO/IV/IM

Atypical neuroleptics

Olanzapine 2.5–5 mg qd or bid, PO

Risperidone 1–3 mg q12h, PO

Anxiolytics

Lorazepam 0.5–2 mg q1–4h, PO/IV/IM

Midazolam 1–5 mg/h continuous infusion, IV/SC

Anesthetics

Propofol 0.3–2.0 mg/h continuous infusion, IV

84PART 1 The Profession of Medicine

combined with lorazepam to reduce agitation when the delirium is the

result of alcohol or sedative withdrawal.

If no response to first-line therapy is observed, a specialty consultation should be obtained with a goal to change to a different medication.

If the patient fails to improve after a second neuroleptic, sedation with

either an anesthetic such as propofol or continuous-infusion midazolam may be necessary. By some estimates, as many as 25% of patients

at the very end of life who experience delirium, especially restless delirium with myoclonus or convulsions, may require sedation.

Physical restraints should be used with great reluctance and only when

patients’ violence is threatening to themselves or others. If restraints are

used, their appropriateness should be frequently reevaluated.

Insomnia • FREQUENCY Sleep disorders, defined as difficulty

initiating sleep or maintaining sleep, sleep difficulty at least 3 nights a

week, or sleep difficulty that causes impairment of daytime functioning, occurs in 19–63% of patients with advanced cancer. Some 30–74%

of patients with other end-stage conditions, including AIDS, heart

disease, COPD, and renal disease, experience insomnia.

ETIOLOGY Patients with cancer may experience changes in sleep efficiency, such as an increase in stage I sleep. Insomnia may also coexist

with both physical illnesses, like thyroid disease, and psychological illnesses, like depression and anxiety. Medications, including antidepressants, psychostimulants, glucocorticoids, and β agonists, are significant

contributors to sleep disorders, as are caffeine and alcohol. Multiple

over-the-counter medications contain caffeine and antihistamines,

which can contribute to sleep disorders.

ASSESSMENT Assessments should include specific questions concerning sleep onset, sleep maintenance, and early-morning wakening, as

these will provide clues to both the causative agents and management

of insomnia. Patients should be asked about previous sleep problems,

screened for depression and anxiety, and asked about symptoms of

thyroid disease. Caffeine and alcohol are prominent causes of sleep

problems, and a careful history of the use of these substances should

be obtained. Both excessive use and withdrawal from alcohol can be

causes of sleep problems.

INTERVENTIONS The mainstays of any intervention include improvement of sleep hygiene (encouragement of regular time for sleep,

decreased nighttime distractions, elimination of caffeine and other

stimulants and alcohol), interventions to treat anxiety and depression,

and treatment for the insomnia itself. For patients with depression who

have insomnia and anxiety, a sedating antidepressant such as mirtazapine can be helpful. In the elderly, trazodone, beginning at 25 mg at

nighttime, is an effective sleep aid at doses lower than those that cause

its antidepressant effect. Zolpidem may have a decreased incidence

of delirium in patients compared with traditional benzodiazepines,

but this has not been clearly established. When benzodiazepines are

prescribed, short-acting ones (such as lorazepam) are favored over longeracting ones (such as diazepam). Patients who receive these medications

should be observed for signs of increased confusion and delirium.

■ SOCIAL NEEDS AND THEIR MANAGEMENT

Financial Burdens • FREQUENCY Dying can impose substantial

economic strains on patients and families, potentially causing distress.

This is known as financial toxicity. In the United States, which has the

least comprehensive health insurance systems among wealthy countries, a quarter of families coping with end-stage cancer report that care

was a major financial burden and a third used up most of their savings. Among Medicare beneficiaries, average out-of-pocket costs were

>$8000. Between 10% and 30% of families are forced to sell assets, use

savings, or take out a mortgage to pay for the patient’s health care costs.

The patient is likely to reduce hours worked and eventually stop

working altogether. In 20% of cases, a family member of the terminally

ill patient also must stop working to provide care. The major underlying causes of economic burden are related to poor physical functioning and care needs, such as the need for housekeeping, nursing, and

personal care. More debilitated patients and poor patients experience

greater economic burdens.

INTERVENTION The economic burden of end-of-life care should

not be ignored as a private matter. It has been associated with a

number of adverse health outcomes, including preferring comfort

care over life-prolonging care, as well as consideration of euthanasia

or physician-assisted suicide (PAS). Economic burdens increase the

psychological distress of the families and caregivers of terminally ill

patients, and poverty is associated with many adverse health outcomes.

Importantly, studies have found that “patients with advanced cancer

who reported having end-of-life conversations with physicians had significantly lower health care costs in their final week of life. Higher costs

were associated with worse quality of death.” Assistance from a social

worker, early on if possible, to ensure access to all available benefits

may be helpful. Many patients, families, and health care providers are

unaware of options for long-term care insurance, respite care, the Family Medical Leave Act (FMLA), and other sources of assistance. Some

of these options (such as respite care) may be part of a formal hospice

program, but others (such as the FMLA) do not require enrollment in

a hospice program.

Relationships • FREQUENCY Settling personal issues and closing

the narrative of lived relationships are universal needs. When asked if

sudden death or death after an illness is preferable, respondents often

initially select the former, but soon change to the latter as they reflect

on the importance of saying goodbye. Bereaved family members who

have not had the chance to say goodbye often have a more difficult

grief process.

INTERVENTIONS Care of seriously ill patients requires efforts to facilitate the types of encounters and time spent with family and friends

that are necessary to meet those needs. Family and close friends may

need to be accommodated in hospitals and other facilities with unrestricted visiting hours, which may include sleeping near the patient,

even in otherwise regimented institutional settings. Physicians and

other health care providers may be able to facilitate and resolve strained

interactions between the patient and other family members. Assistance

for patients and family members who are unsure about how to create

or help preserve memories, whether by providing materials such as a

scrapbook or memory box or by offering them suggestions and informational resources, can be deeply appreciated. Taking photographs and

creating videos can be especially helpful to terminally ill patients who

have younger children or grandchildren.

Family Caregivers • FREQUENCY Caring for seriously ill patients

places a heavy burden on families. Families are frequently required to

provide transportation and homemaking, as well as other services.

Typically, paid professionals, such as home health nurses and hospice

workers, supplement family care; only about a quarter of all caregiving

consists of exclusively paid professional assistance. Over the past 40

years, there has been a significant decline in the United States of deaths

occurring in hospitals, with a simultaneous increase in deaths in other

facilities and at home. Over a third of deaths occur in patients’ homes.

This increase in out-of-hospital deaths increases reliance on families

for end-of-life care. Increasingly, family members are being called upon

to provide physical care (such as moving and bathing patients) and

medical care (such as assessing symptoms and giving medications) in

addition to emotional care and support.

Three-quarters of family caregivers of terminally ill patients are

women—wives, daughters, sisters, and even daughters-in-law. Since

many are widowed, women tend to be able to rely less on family for

caregiving assistance and may need more paid assistance. About 20% of

terminally ill patients report substantial unmet needs for nursing and

personal care. The impact of caregiving on family caregivers is substantial: both bereaved and current caregivers have a higher mortality rate

than that of non-caregiving controls.

INTERVENTIONS It is imperative to inquire about unmet needs and

to try to ensure that those needs are met either through the family or

by paid professional services when possible. Community assistance

through houses of worship or other community groups often can be

mobilized by telephone calls from the medical team to someone the

patient or family identifies. Sources of support specifically for family