Learning Objectives
1. Explain a new or unfamiliar viewpoint on a topic of ethical or professional conduct
2. Evaluate the usefulness of this information for his or her practice, teaching, or conduct
3. Decide whether and when to apply the new information to his or her practice, teaching, or conduct
1 Credit
CME
AMA Journal of Ethics
October 1, 2021
Article Course
Noncurative surgeries intended to relieve suffering
during serious illness or near end of life have been analyzed across
palliative settings. Yet sparse guidance is available to inform clinical
management decisions about whether, when, and which interventions
should be offered when ischemic stroke and other neurological
complications occur in patients whose survival is extended by other
novel disease-modifying interventions. This case commentary examines key
ethical and clinical considerations in palliative neuroendovascular
care of patients with acute stroke.
Mr J is a 64-year-old man with metastatic non-small cell
lung cancer (NSCLC), who, while eating, abruptly developed right
hemiplegia and aphasia. He had been diagnosed 10 months earlier with
NSCLC; his estimated life expectancy was approximately 1 year. After a
course of chemotherapy with pemetrexed and carboplatin, Mr J started
pembrolizumab, an antiprogrammed death-1 immune checkpoint inhibitor
offered possibly to extend his life but not as a cure for his cancer.1,2
Since diagnosis, Mr J has suffered multiple hematologic complications,
including thrombosis and hemorrhage. When brought to an emergency
department, he was confirmed as full code and intubated on arrival due
to poor mental status and aspiration risk. Computed tomography (CT)
imaging of his head and neck revealed normal brain parenchyma and
occlusion of the proximal left middle cerebral artery (MCA), which
supplies blood to most of the brain's left hemisphere, including areas
critical for language and right-side sensorimotor function.3
The mechanism of Mr J's left MCA occlusion was presumed to be
thromboembolism, to which he was predisposed by hypercoagulability of
malignancy, pembrolizumab,4- 6 and intracardiac hemostasis, given his known low left ventricular ejection fraction.
After discussion of acute stroke as a likely a
complication of Mr J's cancer, Mr J's health care proxy, GG, consented
to Mr J undergoing an emergent thrombectomy. This neuroendovascular
procedure is a minimally invasive alternative to more invasive
interventions and is the standard method for thrombectomy for acute
ischemic stroke with large-vessel occlusion using an endovascular
approach. Emergent
thrombectomy utilizes femoral artery access to position an intracranial
catheter system that permits intracerebral thrombus removal, with the
goals of reestablishing blood flow to vascular territory downstream from
an occlusion and enabling salvage of the ischemic penumbra to restore
neurological function and prevent further impairment.7
If thrombectomy is not performed, a large proximal-vessel stroke
typically occurs, potentially leading to extended brain tissue
infarction, cerebral edema, and other symptoms of elevated intracranial
pressure (eg, nausea, vomiting, headache, visual changes, and cranial
neuropathies) that can exacerbate a patient's impairment and suffering.8- 11
Mr J's thrombectomy was uncomplicated and resulted in
rapid and successful left MCA territory reperfusion. A subsequent brain
magnetic resonance (MR) image, however, revealed multifocal infarcts
affecting the left and the right hemisphere of Mr J's brain and
bilateral cerebellar hemispheres, consistent with his presumed
cardioembolic etiology. Mr J was unable to communicate or meaningfully
interact. After neurological examination, Dr N informed GG of key
findings, including bilateral infarcts expected to produce long-term
bilateral weakness, disordered speech, and cognitive impairment. Dr N
also explained to GG that Mr J would likely need life support, including
tracheostomy, gastrostomy, and rehabilitation if he survived much
longer. GG expressed understanding and asked the team to prioritize Mr
J's comfort.
More than 1 in 10 patients who present with acute ischemic stroke are estimated to have comorbid cancer.12,13 As the median survival of patients with cancer improves with novel targeted therapies, the frequency of acute stroke and other neurologic complications in this expanding population is expected to rise.14- 18
Malignancy can predispose patients to ischemic stroke through
hypercoagulability, nonbacterial thrombotic endocarditis, systemic
treatment effects, or, rarely, tumor embolism or angioinvasion.14,19
Since many patients seeking emergency evaluation of acute stroke
symptoms might have comorbid cancer, clarifying ethical questions in
these patients' stroke care, especially for patients near the end of
life, is key. Should clinicians try to preempt or reverse neurological
dysfunction when the end of a patient's life is near? When, to what
extent, and according to whom should thrombectomy for patients with
terminal illness be considered palliative? How should palliative or comfort care goals be set in order to guide appropriate neuroendovascular management decisions in the context of end-of-life care?
Palliative Thrombectomy Goals
Palliative
care is defined by the World Health Organization (WHO) as “active total
care of patients whose disease is not responsive to curative treatment”
that aims to achieve “the best quality of life for patients and their
families.”20
The Center to Advance Palliative Care (CAPC) conceives of the field as
“specialized medical care for people with serious illnesses [that is]
focused on providing patients with relief from the symptoms, pain, and
stress of a serious illness.… The goal is to improve quality of life …
and [palliative care] can be provided along with curative treatment.”21
Noncurative surgery intended to relieve symptoms in patients with
serious illness or near the end of life has been analyzed in a range of
contexts, particularly in surgical oncology.22- 31
However, invasive neurological procedures intended to address indirect
complications of terminal illnesses (eg, thrombosis due to
hypercoagulability of malignancy) have received little clinical or
ethical attention. Especially in clinical neuroscience, little evidence
is available to guide neuroendovascular intervention decisions with
patients who develop ischemic stroke or other neurological complications
near the end of life.
Although in Mr J's case, thrombectomy did not
appreciably reduce disability near the end of his life, we argue that Dr
N's team's decision to perform thrombectomy was ethically justifiable
based on its concordance with Mr J's goals that the team gleaned through
conversations with GG. As
highlighted by the WHO and CAPC definitions, appropriate palliative
care consists not merely of pain control but of the active total care of
a patient who strives for the best quality of life. To the extent that
neurological symptoms, including sensorimotor dysfunction (eg, weakness
and numbness), headache, delirium, aphasia, dysarthria, imbalance, gait
disturbance, and cranial neuropathies can detract from quality of life,
it is incumbent upon clinicians to diligently address symptoms
throughout a patient's illness.32- 35
Among patients who experience acute ischemic stroke, more severe
neurological impairment has been linked with significantly lower quality
of life.35,36
Neuroendovascular
approaches, such as thrombectomy, are specifically intended to
attenuate or prevent accumulated neurological disability37- 39 and are supported by randomized clinical trials.40,41
The location and type of stroke and the extent of salvageable ischemic
penumbra must be considered case by case in terms of whether foreseeable
benefits of thrombectomy outweigh its risks. Eligibility
criteria for late endovascular treatment trials for patient-subjects
with acute ischemic stroke have included occlusion of proximal MCA or
internal carotid artery on CT imaging or MR angiography, a score greater
than 6 on the National Institutes of Health Stroke Scale up to 24 hours
from the time the patient was last seen well, significant ischemic
penumbra, and factors such as age, baseline modified Rankin Scale score,
and life expectancy. Exclusion criteria have varied by trial and have been a source of practice variation across centers.42 Another source of complexity is that treatment decisions are typically made emergently.
Minimally invasive neuroendovascular interventions can
aptly be considered palliative for a patient with limited life
expectancy and should not be withheld based solely on a patient's
terminal comorbidity. Even if a patient is expected to live only a few
weeks or months, any additional stroke-related neurological impairment
could exacerbate their suffering near the end of life. Many patients who
undergo thrombectomy experience reversal of neurologic impairment or
return to functional independence due to their reduced risk of ischemic
penumbra.40
Successful reperfusion of ischemic penumbra might forestall development
of malignant cerebral edema, cerebral herniation, or other symptoms of
increased intracranial pressure, as evidenced by lower rates of
decompressive hemicraniectomy since the advent of mechanical
thrombectomy.43- 46 Following the ethical principles of doing good and avoiding harm47- 49 likely requires clinicians to offer palliative thrombectomy, even when a patient has incurable comorbidity.
Decision Sharing
Patient-centered care requires assessing (1) a patient's
functional status at baseline; (2) their preferences, values, and
goals, perhaps as expressed by surrogates; and (3) their prospects for
recovery.50- 53
Interpreting each stroke not as a discrete new disease but in the
context of a patient's broader health state, relevant comorbidities, and
illness narrative
can foster holistic, goal-concordant intervention and might help avoid
unnecessary discontinuity or fragmentation in a patient's care.54- 57
Clinicians' conversations with patients and surrogates should emphasize
that estimates of an intervention's effects are extrapolated from
studies in which subjects were drawn not from the unique population of
patients with terminal illnesses but from a general population with
minimal preexisting disability. Decision sharing and informed consent
require conveying uncertainty about how well the available evidence
applies to a particular patient.
Equity and Evolving Therapies
Further research on the efficacy of palliative
neuroendovascular care is essential, although the practical and ethical
problems of conducting clinical research in patient-subjects with
advanced illnesses deserve careful consideration.58- 61
In one study of persons with metastatic NSCLC, newly diagnosed patients
whose care plans integrated early palliative care experienced improved
quality of life and mood,62
and the challenges of ensuring goal-concordant palliative care given
the growth of novel interventions in the past decade are actively being
studied.63,64
Equity as an organizational ethical value requires inclusion of all key
stakeholders' perspectives and goals—curative and palliative—when
crafting policy and evaluating downstream implications of decisions to
administer or withhold neuroendovascular interventions in individual
cases.
In the case, Mr J had an acceptable health-related
quality of life and—assuming his comparability to otherwise healthy
patients with acute stroke—a higher chance of making a functional
recovery with treatment than without it, at very low procedural risk.65
While caution must be exercised in generalizing from studies of acute
stroke patients who did not have cancer, the data indicate that patients
treated with thrombectomy for acute proximal MCA occlusion stroke lived
the remainder of their lives with fewer neurologic impairments than if
untreated and with reduced need for aggressive care and
institutionalization following a sentinel cerebrovascular event.64,66- 68
While not a factor in this Mr J's case, do-not-intubate
(DNI) orders are common and worthy of mention here. DNI orders should
not independently influence stroke care decisions “unless otherwise
explicitly indicated,” as emphasized by an American Heart
Association/American Stroke Association statement (Class IIa
recommendation).69 Generally, clinicians should express respect for patients' right to decline interventions70
but should recognize that such interventions can have palliative roles
by preventing debilitating neurological impairment and concomitant
end-of-life suffering.71,72
Palliative radiotherapy, including stereotactic radiosurgery for
patients with advanced cancer with brain metastases, has been pursued,73- 76 as have deep brain stimulation for Parkinson disease management near the end of life77 and palliative decompressive spinal surgery for patients with metastatic spinal cord compression.78- 81
Care Planning
Unlike decisions about specific palliative
interventions, decisions about stroke care are typically made quickly,
given the urgency of acute stroke, its impact on patients' capacity to
participate in decision making, and the exquisite time sensitivity of
implementing acute stroke interventions. Although outcomes data for
specific palliative neuroendovascular interventions are limited, advance
care planning should include surrogate designation and discussion of
minimally invasive intervention preferences, which could help safeguard
value-concordant goal setting and decision sharing later.71,82
Ethically appropriate palliative neuroendovascular care
for patients with acute stroke includes more than pain control and
extends to management of distressing physical, spiritual, emotional, and
psychosocial symptoms.83,84 Recognizing the relatively high frequency of neurological complications among patients with terminal illnesses,12,85- 89 clinicians can implement patient-centered palliative neuroendovascular care with guidance from the ideas in the Table.
Table.
Elements of Ethically Appropriate Palliative Neuroendovascular Care
| Recognize
palliative care as more than pain control; extend it to management of
potentially disabling, distressing neurologic symptoms. |
| Clarify the patient's (or surrogate's) values and goals of care. |
| Avoid assumptions about a patient's values, preferences, or goals. |
| Discuss intended aims, prospective benefits, and possible risks of a neuroendovascular intervention with a patient or surrogate. |
| Explain the range of possible postprocedural outcomes to motivate transparency. |
| Discuss likely outcomes of no neuroendovascular intervention or alternative interventions. |
| Ensure that decision making is sensitive to patient preferences, values, and goals. |
| Clearly document and communicate decisions to colleagues and care team members. |
