JOURNAL OF PALLIATIVE MEDICINE

Volume 8, Number 5, 2005 Palliative Care Review

© Mary Ann Liebert, Inc.

Terminal Care: The Last Weeks of Life

WILLIAM M. PLONK, Jr., M.D.1 and ROBERT M. ARNOLD, M.D.2

Life is pleasant. Death is peaceful. It’s the transition that’s troublesome.

—Isaac Asimov

ABSTRACT

Background: The care of patients in their last weeks of life is a fundamental palliative care
skill, but few evidence-based reviews have focused on this critical period.
Method: A systematic review of published literature and expert opinion related to care in
the last weeks of life.
Results: The evidence base informing terminal care is largely descriptive, retrospective, or ex-
trapolated. While home deaths and hospice use are increasing, medical care near death is be-
coming more aggressive and hospice lengths of stay remain short. Though the prediction of im-
pending death remains imprecise, studies have identified several common terminal signs and
symptoms. Decreased communication near death complicates the determination of patient
wishes, and advanced directives prior to the terminal stage are recommended. Anorexia and
cachexia are common in dying patients but there is no evidence that this process is painful or
responsive to intervention. While there is general consensus that artificial nutrition is not ben-
eficial in dying patients, the use of artificial hydration is controversial, especially in the setting
of delirium. Breathlessness has been shown to benefit from oral and parenteral opioids but not
anxiolytics. Accumulation of respiratory tract secretions (death rattle) is common and usually re-
sponds to antimuscarinics. Physical pain typically decreases toward death but its assessment in
dying patients is difficult. Terminal delirium may occur in up to one-third of patients, may have
a reversible cause, and may respond to antipsychotics or benzodiazepines. Palliative sedation is
controversial but widely used, especially internationally. Caregiver stress and bereavement may
benefit from improved communication and hospice involvement.
Conclusion: While the terminal care literature is characterized by varying quality, numer-
ous knowledge gaps, and frequent inconsistencies, it supports several common clinical in-
terventions. More research is needed to resolve controversies, define effective therapies, and
improve the outcomes of dying patients.

INTRODUCTION why. As physicians, we can be the primary cause

O NE HUNDRED PERCENT of our patients will die.
Ten percent will die suddenly, but 90% will
at some point need terminal medical care.1 Mod-
ern medical science is poor at predicting how or
when they will die, and even worse at explaining
of suffering in their last weeks of life, or the pri-
mary cause of its relief.2 Which role we choose
depends on both our knowledge of terminal care
and our approach to it. Experience suggests that
we have at our disposal the tools to make every
death better, at least marginally. A comfortable

1Division of General Medicine, Geriatrics, and Palliative Care, Department of Internal Medicine, University of Vir-

ginia Health System, Charlottesville, Virginia.

2Section of Palliative Care and Medical Ethics, Division of General Internal Medicine, University of Pittsburgh Med-

ical Center, Pittsburgh, Pennsylvania.

1042
TERMINAL CARE
death is possible for almost all of our patients. It
should be one of our primary obligations, and one
of our patients’ primary expectations.
As Sherwin Nuland noted in How We Die, there
is a vast literature on dying but few reliable ac-
counts of the process. In part because of the ethi-
cal and legal issues associated with clinical trials
involving dying patients, there is little controlled
research on which to base our practice. For exam-
ple, benzodiazepines have not been shown to be
beneficial in palliative care patients, but most of us
would find it difficult to do effective end-of-life care
without them. Likewise, corticosteroids might or
might not be effective for malignant bowel ob-
struction; the meta-analysis of trials investigating
their use lacked statistical significance.3
Useful data does exist, however, although much
is retrospective or extrapolated from patients in
earlier stages of illness. In general, the same pal-
liative approaches and treatments used in earlier
stages of the dying process are felt to be effective
in terminal care. Until better research becomes
available, we must rely heavily on this incomplete
data, personal experience, and expert opinion to
guide the care for our patients at the end of life.
Terminal care refers to medical care provided
in the last days to weeks of life. For this discus-
sion, an extensive review of systematic research
related to death, terminal care, and bereavement
published from 1990 through April 2004, and
available on MEDLINE was performed. Where
reliable data were not available, reference was
made to current expert opinion derived from re-
view articles, textbooks, and other published
sources. Graded clinical recommendations using
SORT taxonomy are made based on the best
available evidence and summarized in Table 1.
WHERE WE DIE
This year more than 2 million Americans will
die. Approximately 50% will die in hospitals, 25%
at home, and 25% in nursing homes. Significant
geographic variation in these rates exists, how-
ever. Even among leading hospitals, the rates of
in-hospital Medicare deaths range from 16% to
55%.4 Nationwide, the proportion of patients dy-
ing in hospitals is declining, while the propor-
tions dying at home and in nursing homes are in-
creasing (Table 2). Teno5 estimates that by 2040,
the proportion dying in nursing homes may ap-
proach 50%.
1043
TABLE 1. TERMINAL CARE RECOMMENDATIONS AND
GRADES BY SORT TAXONOMYa
Recommendation Grade
Hospice enrollment should be promoted B
to decrease rates of inhospital deaths,
limit the transfer of dying nursing
home patients, and improve terminal
care outcomes.
Palliative care programs should be B
expanded to improve terminal care
outcomes in institutions.
Advance directives should be encouraged B
to limit the hospital transfer of dying
nursing home patients.
Families should be educated in the C
signs of approaching death.
Routine artificial nutrition is not A
recommended during terminal care.
Routine artificial hydration is not B
recommended during terminal care,
although it may be appropriate in
selected cases.
Oral or parenteral opioids remain the A
primary treatment for terminal
dyspnea.
Oxygen therapy is beneficial in the B
setting of hypoxemia.
Anxiolytics are beneficial in the treatment C
of terminal dyspnea.
Antimuscarinics are effective for the B
treatment of accumulated respiratory
tract secretions.
Opioids titrated to comfort are the A
foundation for treatment of terminal
physical pain.
Benzodiazepines, antipsychotics, and B
phenothiazines are effective for the
treatment of distressing terminal
delirium.
Propafol, midazolam, and barbituates B
are effective for palliative sedation.
Empathy and psychosocial support B
improve caregiver stress and
bereavement outcomes.
aFrom Ebell et al.166
Most Americans want to die at home. Oncol-
ogy population surveys indicate the proportion
preferring a home death is almost 90%, and opin-
ion surveys have documented similar findings in
the general public.7 Social factors may affect
these preferences, however. A survey of recently
hospitalized elderly patients with life-limiting
disease revealed more wanted their terminal care
in the hospital than at home (48% versus 43%).
The primary reasons given for preferring hospi-
tal over home care were their concerns about be-
ing a burden to family and their family’s ability
to provide necessary care. Most preferred nurs-
1044
TABLE 2. SITE OF DEATH OVER TIME,
UNITED STATES, 1989–2001
1989 1993 1997 2001
Hospital 62% 56% 52% 49%
Nursing home 18% 19% 21% 24%
Home 16% 21% 22% 23%
From Brown Atlas of Dying and 1993 Mortality Survey.
<www.chcr.brown.edu/dying>.6
ing home to hospital care when given that
choice.8
Only one third of terminally ill patients with
cancer achieve their preferred place of death.9
Those who die at home are disproportionately
white, educated, married, female, and enrolled in
hospice or PACE programs. They tend to have
longer survival after cancer diagnosis and a func-
tional decline over less than 5 months (more pro-
longed decline predicts nursing home place-
ment).10–12 The strongest predictor of home death
is, however, living in a locality with fewer hos-
pital beds per capita.13,14 If hospital beds are
available, they will be filled with dying patients.
DYING IN INSTITUTIONS
Approximately 75% of Americans die in institu-
tions, where terminal care is often problematic.
Hospitals traditionally are more focused on cura-
tive than palliative care, and regulatory, staffing,
and privacy issues make effective end-of-life care
in nursing facilities difficult.15,16 Patients in these
settings commonly have significant unmet care
needs. Of the families of patients who died in a
nursing home, 32% felt the patient’s pain was not
adequately addressed and 56% felt emotional sup-
port of the patient was lacking. Of the families of
patients who died in a hospital, 50% thought com-
munication was a problem, 51% wanted more
physician contact, and 80% thought the patient was
not always treated with respect.17 Isolation in in-
stitutions is another pervasive problem. Sulmasy
and Rahm18 found that seriously ill hospitalized
patients with poor prognoses spent on average
over 18 hours per day alone. Do-not-resuscitate
(DNR) orders did, however, significantly increase
the time nurses spent with these patients.19
Predictors of death in a nursing home include
prolonged functional decline, poor performance
status, and increased age.10 Unfortunately, many
dying nursing home residents are transferred un-
PLONK AND ARNOLD
necessarily to hospitals. Enrollment in hospice or
having an advance directive, however, signifi-
cantly decreases the risk of this “terminal trans-
fer.”20,21 Institutional end-of-life care measures can
be improved by hospital-based palliative care pro-
grams and nursing home hospice programs.22,23
Likewise, institutional systematic integrated care
protocols have been shown to improve symptom
control during the last two days of life.24
DEATH AND HOSPICE
Hospice services for terminal care have been
available in the United States since 1974 and have
been funded by Medicare since 1983. Use is steadily
increasing, with approximately 20% of Americans
now dying with hospice, but those patients are be-
ing referred to hospice at later stages in their ill-
nesses. The median length of stay in U.S. hospices
fell from 29 days in 1995 to 20.5 days in 2001, ris-
ing slightly to 22 days in 2003. Approximately 37%
of hospice patients die within a week of enrollment,
and only 7% survive more than 6 months.25
There has been a concurrent trend toward more
aggressive medical treatment near death. In 1996,
19% of Medicare cancer patients receiving che-
motherapy received it in their last 2 weeks of life,
up significantly from 14% in 1993.26 Although in-
hospital death rates are declining, intensive care
unit (ICU) and intensive procedure use is in-
creasing. Between 1985 and 1999, Medicare pa-
tients with at least one ICU admission in their last
6 months of life increased from 31% to 35%, and
the proportion having an intensive procedure
during their last hospitalization increased from
18% to 30%.27 In 2001, 14.4% of Medicare patients
spent more than a week in an ICU during their
last 6 months, up from 13.1% in 1999.28 Goodlin
et al.29 found that even during the last 2 days of
life, 27% of hospitalized patients received venti-
latory support, 18% were restrained, and 12% had
an attempted resuscitation. A study of hospital-
ized patients over 80 years of age showed 63% re-
ceived nonpalliative treatments despite only 30%
wanting such care.30
SIGNS OF IMPENDING DEATH
The recently published Clinical Practice Guide-
lines for Quality Palliative Care emphasize that
families should be educated regarding the signs
and symptoms of approaching death in a devel-
TERMINAL CARE
opmentally, age-, and culturally appropriate
manner.31 Several clinical features have been
identified as indicators of death within days, but
research investigating the reliability of these signs
is scarce. Evidence does show that physicians
consistently overestimate patient survival, and
those most familiar with the patient are often the
least accurate.32,33 One observational study in ter-
minally ill patients with cancer noted that pa-
tients on average developed respirations with
mandibular movement 8 hours, acrocyanosis 5
hours, and radial pulselessness 3 hours before
death but there was wide individual variation,
with most patients developing these symptoms
less than 2.5 hours before they died. Decreased
consciousness was identified in 84% at 24 hours
and 92% at 6 hours prior to death.34 Development
of a death rattle is predictive of death within 48
hours but typically occurs in less than half of pa-
tients.35 With the exceptions of drowsiness, fa-
tigue, and confusion, symptoms in patients with
cancer followed at home tended to improve in the
last days of life.36 According to expert opinion,
other symptoms of near death include becoming
bedbound, irregular breathing, tolerating sips of
fluid only, and cool or mottled extremities.37,38
COMMON TERMINAL SYMPTOMS
Distressing physical symptoms are common at
the end of life. The SUPPORT study documented
that during their last 3 days of life, 80% of dying
hospitalized patients suffered severe fatigue, 50%
severe dyspnea, and 40% severe pain.39 The most
common symptoms reported by families in the
last week of life were fatigue, dyspnea, and dry
mouth, while the most distressing were fatigue,
dyspnea, and pain.40 In the long-term care set-
ting, dyspnea, pain, and noisy breathing pre-
dominated in the last 2 days of life, while in hos-
pice patients the most distressing symptoms
in the last 24 hours were thought to be pain,
excess respiratory secretions, and agitation.41,42
Anorexia, anxiety, constipation, nausea/vomit-
ing, incontinence, pressure sores, and insomnia
have also been identified as particularly distress-
ing in certain patients.43,44
DECREASED COMMUNICATION
Morita et al.45 found that the capability for
complex communication by dying patients de-
1045
clined from 43% at 5 days to 13% at 1 day prior
to death, and that this capability was significantly
impaired by high-dose opioids. Because of de-
creasing communication, determining a patient’s
wishes during the terminal phase is difficult, as
is predicting patient preferences regarding re-
suscitation and other interventions.46–48 In the
SUPPORT study, 46% of DNR orders were writ-
ten in the last 2 days of life and 53% of physicians
did not know their patients preferred withhold-
ing resuscitation.49 Sulmasy et al.48 found that
one third of the surrogates of terminally ill pa-
tients also could not accurately predict those pa-
tients’ resuscitation preferences. The outcome
benefit of advance directives in terminal care is
unclear. End-of-life clinical decisions are often in-
fluenced less by advance care planning than by
perceived prognosis, quality-of-life issues, and
family preferences.50,51 Nevertheless, addressing
with patients desired goals of care prior to the
terminal phase is recommended on both ethical
and clinical grounds.46
ANOREXIA/CACHEXIA AND TERMINAL
HYDRATION/NUTRITION
Most dying patients lose their appetite
(anorexia) and lose weight (cachexia).52 Family
members and other caregivers may be concerned
the patient is “starving to death” and wish to in-
tervene in the last weeks of life. They can be re-
assured that there is no evidence that providing
nutritional support either enterally or parenter-
ally improves morbidity or mortality in termi-
nally ill patients, including those with advanced
dementia.53,54
There is little evidence that prolonged anorexia
is uncomfortable. McCann and colleagues55 found
that 97% of dying patients who stopped eating ex-
perienced no hunger or hunger only initially.
Anorexia and cachexia (sometimes referred to as
wasting syndromes) appear to be due in part to
proinflammatory cytokines and other humoral fac-
tors which, by inducing catabolism, may help ex-
plain the failure of artificial feeding to improve nu-
tritional parameters in chronically ill patients.56,57
It has been proposed that terminal anorexia ac-
tually may benefit dying patients by inducing a
ketosis that contributes to a sense of well-being
and diminished discomfort.58 Because of its ben-
eficial effects on cell metabolism,
-hydroxybu-
tyrate, the primary ketone in starvation, has even
1046
been suggested as a therapeutic agent.59 While an
attractive theory, evidence for the clinical benefit
of ketosis in dying patients is limited.
The provision of artificial hydration and nutri-
tion (AHN) in terminal care remains a heavily de-
bated clinical, ethical, legal, and religious issue.
Clinical evidence for the benefit of artificial nu-
trition in end-of-life care is poor. In a 1999 review,
Finucane et al.54 found no evidence that tube
feeding in patients with advanced dementia pre-
vented aspiration pneumonia, prolonged sur-
vival, reduced the risk of pressure sores or infec-
tions, improved function, or provided comfort.
More recent studies have confirmed this lack of
benefit in advanced dementia.60–62 A meta-anal-
ysis of studies of both enteral and parenteral nu-
trition in patients with metastatic cancer found
that neither therapy affected morbidity or mor-
tality.63 Enteral feeding tubes have, however,
been associated with increased complication
rates, restraint use, and emergency department
utilization.64,65 Such evidence has led Winter to
argue that unrequested nutritional support of the
terminally ill is both medically and ethically in-
defensible.53
Most authorities consider the discontinuation
of tube feedings to be ethically and legally indis-
tinguishable from their initiation.66,67 Neverthe-
less, artificial nutritional support is typically the
last life-sustaining measure withdrawn, and ap-
proximately 25% of demented nursing home pa-
tients die while still receiving tube feedings.68,69
The data surrounding hydration in dying pa-
tients are more controversial. Some studies cor-
relate dehydration with adverse symptoms such
as thirst,70–72 and some experts argue that par-
enteral hydration prevents and treats some cases
of terminal delirium.73,74 Other authorities argue
that the data does not support a correlation be-
tween dehydration and symptoms and that re-
hydration does not improve patient comfort.58,75
One retrospective study suggested a decrease in
agitated delirium with routine parenteral hydra-
tion, but a more recent follow-up study failed to
confirm this finding.76,77 Two 1997 literature re-
views on this issue reached opposite conclusions,
but both agreed the data were inconsistent.74,78
As with anorexia, some authorities feel that de-
hydration in fact may improve comfort by in-
ducing uremia, hyperosmolality, and endorphin
release.79,80 They point out that patients with end-
stage renal disease who stop dialysis typically ex-
perience less discomfort than patients who die of
PLONK AND ARNOLD
other causes, with 85% experiencing a “good”
death requiring minimal medical intervention.81
As with ketosis, however, additional evidence for
this benefit is scarce.
Finally, some authorities have argued that
intravenous hydration may have numerous
adverse effects including worsening edema,
increasing secretions, and unnecessarily prolong-
ing the dying process.58 Fewer diuretics (and
smaller fluid volumes) were used in patients re-
ceiving hypodermoclysis than those with in-
travenous fluids, but no randomized trials of
parenteral hydration methods have been con-
ducted.82 While there is little objective evidence
of harm, the bulk of current evidence and expert
opinion supports the conclusion that parenteral
hydration is likely not beneficial in the actively
dying patient.
RESPIRATORY CHANGES
Though the true etiology is unknown, changes
in breathing are thought to indicate significant
neurologic compromise near death. Diminished
tidal volume, apneic periods, accessory muscle
use, and Cheyne-Stokes respirations often de-
velop, and reflex breaths may immediately pre-
cede death. These breathing changes can be very
distressing for family and caregivers, who may
fear the patient is suffocating.58 The development
of hypercarbia may induce a beneficial narcosis,
although again there are few data to support this
conjecture. In fact, some studies suggest normo-
carbia with progressive hypoxia induces the least
agitation.83 Oxygen administration likely pro-
vides no benefit in this setting but has not been
studied and is widely used to address family and
caregiver concerns.84
The treatment of breathlessness is, however, one
of the few areas of palliative care for which we have
solid evidence, and seems reasonable to assume
this data can be extrapolated to the terminal phase.
A recent Cochrane review confirmed the benefit of
oral and parenteral opioids in improving breath-
lessness and dyspnea in palliative care patients.85,86
Nebulized opioids, although attractive as a means
of treating breathlessness while limiting side ef-
fects, showed no benefit over nebulized saline in
the Cochrane analysis. Three recent reviews by dif-
ferent authors support the use of oral or parenteral
(but not nebulized) opioids in the palliation of dys-
pnea even in patients with severe underlying lung
TERMINAL CARE
disease.87–89 Opioids also appear to relieve breath-
lessness in stable severe congestive heart failure
(CHF) but showed no benefit in stable severe
chronic obstructive pulmonary disease (COPD) or
interstitial lung disease.90,91 Although they are
widely used, there is limited objective evidence for
the benefit of benzodiazepines in the palliation of
breathlessness.92,93 Oxygen appears to benefit pa-
tients with terminal cancer with hypoxemia but
was no better than room air in nonhypoxemic dys-
pneic patients.94,95 A fan blowing air on the face is
thought to improve breathlessness through stimu-
lation of the trigeminal nerve, although the evi-
dence for this effect in humans is unclear.
ACCUMULATION OF RESPIRATORY
TRACT SECRETIONS
The accumulation of respiratory tract secretions
(ARTS), presumably caused by a declining gag re-
flex and decreased reflexive clearing, may occur as
death approaches and lead to gurgling respira-
tions. This “death rattle” occurs in one fourth to
one half of dying patients, occurs more commonly
in men and patients with brain and lung neo-
plasms, and predicts most (76% in one study) will
die within 48 hours.34,96 Nonpharmacologic inter-
ventions such as discontinuing parenteral fluids,
repositioning, and postural drainage are frequently
recommended but have not been studied system-
atically. Oropharyngeal suctioning is considered
generally ineffective for this condition and may
cause both patient and family discomfort.58
A majority (50%–80%) of patients with ARTS
respond to treatment with antimuscarinics,
though one author contrasts treatment-respon-
sive “real death rattle” resulting from unexpec-
torated secretions from treatment-resistant
“pseudo-death rattle” caused by pulmonary
pathology.34 Subcutaneous hyoscine hydrobro-
mide (scopolamine) was more immediately ef-
fective in one trial than subcutaneous glycopyr-
rolate but glycopyrrolate has a longer duration of
action.97–99 Although case studies and expert
opinion suggest their effectiveness, no controlled
studies of intravenous, oral, sublingual, or trans-
dermal antimuscarinics were identified.100–102
TERMINAL PAIN
Dr. Cicely Saunders correctly noted that pain
at the end of life may be physical, emotional, so-
1047
cial, or spiritual.103 Terminal physical pain is the
most readily quantifiable, but even studies of it
are conflicting. In 1990, Ventafridda et al.104 ar-
gued that pain usually escalated near death, re-
quiring palliative sedation in more than half of
patients. Numerous systematic studies since
then, however, have shown that overall pain
tends to decline in the dying phase. Fainsinger et
al.105 noted a decrease in pain on a visual ana-
logue scale over the last week of life. Ellershaw
et al.24 documented a decrease in uncontrolled
pain from 18% at 24 hours to 8% at 4 hours prior
to death without opioid dose changes. Mer-
cadante et al.106 found that pain and opioid use
in patients dying at home peaked about one
month prior to death. The etiology of this over-
all decline is unknown, although uremia, ketosis,
and the build-up of endorphins or exogenous opi-
oid metabolites may contribute.
Expert consensus holds that some dying pa-
tients, perhaps 1%–2%, do develop “crescendo”
pain in the last hours or days of life, though delir-
ium may be a contributing factor.107,108 While this
subset of terminal pain has not been studied sys-
tematically, opioid rotation, intravenous keta-
mine, and palliative sedation have shown bene-
fit in various case studies.109,110 Each opioid is felt
to influence a unique distribution of receptors
that become downregulated over time; rotation
to a different opioid is thought to improve pain
control by altering the receptor set affected. Sim-
ilarly, ketamine is felt to affect alternate pain re-
ceptors. One small randomized trial did show
that continuing the use of transdermal fentanyl
in the terminal phase improved overall pain con-
trol, though this is likely an opioid class effect.111
Interestingly, the stress of dying (as measured by
postmortem cerebrospinal fluid [CSF] cortisol lev-
els) is not suppressed by either high-dose opioids
or the presence of dementia.112 This finding sug-
gests that it may be our ability to assess pain, rather
than the pain itself, that declines during the termi-
nal phase. The assessment of cognitively impaired
patients has been studied extensively in dementia,
but there remains significant debate on whether
cognitive status influences pain perception.113,114
Similar issues confound the assessment of pain in
dying patients with cognitive decline. Half of pa-
tients with advanced cancer are unable to use com-
mon pain assessment tools.115 Caregiver percep-
tion may not be accurate either, because they tend
to overestimate the symptom intensity of dying pa-
tients and their assessment of the patient’s pain
1048
may be influenced substantially by their own ex-
perience.116,117 Numerous scales to assess discom-
fort in nonverbal patients have been developed and
validated for use in dementia, but the utility of
these scales in the objective assessment of dying pa-
tients has not been studied.118,119
Nonpharmacologic approaches to terminal dis-
comfort such as careful oral and eye care, use of
urinary catheters, and bed cushioning are rec-
ommended empirically by most authorities. Al-
ternative interventions such as music therapy,
aromatherapy, and massage are likewise consid-
ered useful by many but also are without clear
evidence of benefit. Existential and psychosocial
pain have been well described but poorly stud-
ied in the terminal care population. Caregiver in-
terviews suggest they can cause or reinforce
physical pain, just as physical pain may some-
times present as global suffering.120,121
Some observers have questioned the use of
high-dose opioids in terminal care, pointing out
the potential for adverse side effects, especially
sedation and respiratory depression. While
higher opioid doses are associated with these
signs, there is no evidence that they are associ-
ated with increased mortality.122
TERMINAL DELIRIUM
Delirium, characterized by fluctuating distur-
bances in consciousness, cognition, and percep-
tion, occurs in 28% to 83% of patients near the end
of life.123 Terminal delirium, often associated with
signs of decreased perfusion, is commonly divided
into three types: hyperactive (with restlessness, ag-
itation, or hallucinations), hypoactive (with som-
nolence), and mixed (with alternating features of
both).124 It is usually presumed to be multifactor-
ial and often is confused with sedation, dementia,
or near-death awareness. When frequent, both the
psychomotor and cognitive symptoms of hyper-
active delirium are distressing to the majority of
families and may become major obstacles to effec-
tive end-of-life care.122,125 A study in nonactively
dying cancer patients found that while hyperac-
tive delirium was more distressing to caregivers,
both hyperactive and hypoactive delirium were
equally distressing to patients.126
One recent observational study found that psy-
chotic symptoms (hallucinations or delusions) oc-
curred in 35% of dying patients. These experiences
may be either distressing or comforting, may have
PLONK AND ARNOLD
significant psychological importance for patients or
their families, and, if not distressing, may not re-
quire treatment.120,127 Hospice nurses have noted
that some dying patients use symbolic language or
gestures to describe their experiences or request
needs, and these messages may be misunderstood
and medicalized as delirium.128
The moaning, groaning, and grimacing that of-
ten accompany delirium may also be misinter-
preted as physical pain.58 Experts feel that poor
pain management may precipitate terminal delir-
ium (after hip fracture, delirium is more commonly
caused by pain than by pain medications)129 but
that uncontrollable pain rarely develops near death
if it has not previously been a problem. Increasing
opioid dosing or rotating opioids, therefore, may
be reasonable options for the treatment of terminal
delirium if pain control is questionable, but the data
on these interventions is conflicting.58,76,77 While
nonpharmacologic interventions effective for delir-
ium in other settings (including visual and hearing
aids, reorientation, therapeutic activities, sleep en-
hancement, and mobilization) may be useful in ter-
minal delirium, no controlled trials have been con-
ducted.122
While reversible factors such as psychoactive
medications, metabolic disarray, or infection may
be identified in up to half of cases, terminal delir-
ium management typically focuses on symptom
control with medications.72,130 Lorazepam (oral,
buccal, or intravenous) is widely used with good
anecdotal success.58 Haloperidol proved superior
to lorazepam in one small randomized controlled
trial in hospitalized patients with acquired im-
mune deficiency syndrome (AIDS) with delirium,
and other typical and atypical antipsychotics
have shown benefit in treating delirium with
dementia, but it is unclear how these results
translate to the treatment of actively dying pa-
tients.131,132 Two recent reviews of pharmaco-
logic therapy for terminal delirium found the best
evidence for haloperidol and chlorpromazine but
concluded that benzodiazepines, antipsychotics
(typical and atypical), and phenothiazines ap-
peared to be equally effective.133,134
PALLIATIVE SEDATION
In a small minority of cases, multiple agents are
ineffective for severe symptom control and patients
require palliative (or “terminal”) sedation. Mida-
zolam, propafol, or barbiturates are commonly
TERMINAL CARE
used for this purpose because of their ability to be
rapidly titrated to effect but there are no data to
support using one over the others.123,135
The ethics of palliative sedation are complex.
To what extent it departs from usual palliative
care and approaches euthanasia continues to be
widely debated.136 Most experts, however, argue
it is legally and ethically appropriate in cases of
physical or emotional suffering uncontrollable by
other means, and it is widely used internation-
ally.137–139 Palliative sedation has not been shown
to decrease overall survival, so the commonly
evoked ethical doctrine of double effect (life
shortening is acceptable if the intent is suffering
relief) does not apply in its use.140 Concerns re-
garding its potential overuse have been raised,
however. In one study, some Japanese palliative
care units used terminal sedation in more than
half of their patients, and it was used more often
by those physicians less experienced in end-of-
life care.141,142
CAREGIVER STRESS AND
BEREAVEMENT
Recognizing and addressing family and care-
giver stress during the last weeks of life is a crit-
ical role of the palliative care physician.38 Surveys
indicate 20% of caregivers provide full-time or
constant care, 20% quit work or make major life
changes, and 31% lose most or all of their sav-
ings. Caregiver stress increases risks in the care-
giver of insomnia, depression, cancer, and
death.143 Higher stress levels are associated with
dying at home, increased patient distress, in-
creased patient dependence, and increased care-
giver burden.144,145
Despite all preparation, the time of death is of-
ten challenging. Experts recommend reviewing
with caregivers in advance the expected dying
process, the signs of death, and death notification
arrangements.58 The effectiveness of such discus-
sions, however, has not been studied systemati-
cally. Respect for personal preferences, religious
practices, and cultural traditions is also strongly
recommended.146,147
Caregiver stress may not resolve with the loved
one’s death.148,149 Bereavement often worsens
physical and mental health and increases the risks
of depression, insomnia, suicide, substance abuse,
and death.150 Complicated bereavement has been
associated with the death of a child or spouse, sud-
1049
den death, high caregiver stress or burden, younger
age, female gender, preexisting psychological
symptoms, and limited social support.151–153 A de-
creased risk has been associated with caregiver
support before death and death at home.149,154,155
In one retrospective study, hospice length of stay
was not associated with improved bereavement at
6 months, but a more recent prospective study
showed caregivers enrolled in hospice for 3 days
or less had a significantly increased risk of major
depression at 6–8 months compared to those with
longer hospice stays.156,157 Hospice involvement
also has been shown to significantly decrease the
mortality at 18 months of bereaved wives.158 While
counseling and antidepressants are widely used,
reviews of the treatment of complicated bereave-
ment have shown no clear benefit of these inter-
ventions.159,160 Communication with family and
other caregivers after death is appreciated and may
improve bereavement outcomes.161,162 Several re-
cent consensus treatment guidelines for physicians
on bereavement have been published.143,151,163
Excellent communication is essential during
the dying process. Bereaved families identified
improved communication around the time of
death as the single most important means of im-
proving end-of-life care.164 One quarter of fami-
lies across care locations expressed concerns
specifically with physician communication dur-
ing terminal care.17 Physician empathy as death
approached has been shown to reduce caregiver
depression and psychosocial burden.165
CONCLUSION
Our last days can be either our best or our
worst. While knowing the available literature is
useful, approaching death not as a medical fail-
ure but as an essential component of life is prob-
ably more critical to effective terminal care. We
cannot keep our patients from dying, but we can
strive, through both knowledge and compassion,
to make the dying experience as comfortable and
meaningful as possible for our patients, their fam-
ilies, and ourselves.
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Address reprint requests to:
William M. Plonk, Jr., M.D.
Division of General Medicine, Geriatrics
and Palliative Care
Department of Internal Medicine
University of Virginia Health System
Charlottesville, VA 22908
E-mail: wmp9xn@virginia.edu
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