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Palliative care in chronic progressive neurological disease
Changing perspectives
Seeber, A.A.
Publication date
2019
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Citation for published version (APA):
Seeber, A. A. (2019). Palliative care in chronic progressive neurological disease: Changing
perspectives.
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general introDuCtion anD
outline oF the thesis
WorlDWiDe, ChroniC Progressive neurologiCal Diseases are
leaDing Causes oF Both MortalitY anD DisaBilitY.
1,2Patients
With aMYotroPhiC lateral sClerosis, high graDe glioMas,
MultiPle sClerosis, ParKinson’s Disease anD other MoveMent
DisorDers, Post-stroKe status With DisaBilitY anD DeMentia
are aMongst the Most hanDiCaPPeD Patients in MeDiCal
PraC-tiCe.
3While these Diseases DiFFer in sYMPtoMatologY anD
Disease traJeCtories, theY share a host oF PhYsiCal,
Cogni-tive, eMotional, anD eXistential ProBleMs. to aDDress these
ProBleMs aDeQuatelY is a Challenge For neurologists anD
other healthCare ProFessionals.
4the traDitional Care
aPProaCh oF MeDiCine eMPhasiZes on Cure, Preservation
oF FunCtion anD Prolongation oF liFe anD has the tenDenCY
to leaD to Both over- anD unDertreatMent oF Patients With
ChroniC Progressive Diseases. though there is groWing
eviDenCe that an earlY Palliative Care aPProaCh iMProves
the sYMPtoM ManageMent anD thus QualitY oF liFe oF these
Patients, suCh an aPProaCh is highlY unDerutiliZeD.
5-7in DailY
CliniCal PraCtiCe, QualitY oF liFe Questions usuallY BeCoMe a
MeDiCal PrioritY not earlier than in the last Phase oF liFe.
4,8oBviouslY, there are Certain MoMents anD CirCuMstanCes
During the Course oF a serious illness When the
aPProPri-ateness oF treatMent aiMing at Cure Can Be QuestioneD. in
DailY neurologiCal PraCtiCe, one oF these MoMents is When
treatMent restriCtions are DisCusseD, suCh as stoPPing a
Disease-MoDiFYing MeDiCation, a Do-not-resusCitate orDer
(Dnr) or a no-intensive-Care-treatMent orDer. in this
thesis, We investigate Whether the DisCussion on treatMent
restriCtions CoulD Be the oPPortune MoMent to eXPliCitlY
initiate Palliative Care, With iMProveMent oF the QualitY oF
liFe as the First anD Main oBJeCtive.
Illness trajectories in chronic progressive neurological disease
over the last century tremendous advances in medicine, improved hygiene and demo-graphic changes have contributed to nearly a doubling of the life expectancy in Western World countries and an – ongoing – increase in chronic diseases which interfere with daily activities and have a negative impact on the quality of life.9 Chronic progressive
neurological diseases are amongst the most common of these diseases.2 the vast
majority of them follow one of the three illness trajectories which have been described for chronic diseases in general.10
1. Steady progression with usually a clear terminal phase: e.g. high grade glioma (HGG) and motor neuron disease (MND)
Malignant primary brain tumors (high-grade gliomas, hgg) usually occur after the age of 40 years with a peak incidence between 65 and 75 years of age.11 the majority of
these rapidly growing tumors is associated with a life expectancy of several months to a few years only, despite sophisticated surgical techniques, chemo- and radiother-apy.12,13 Patients with hggs often have a relatively high performance status until the
last phase of life when deterioration may be rather rapid due to symptoms caused by accelerated tumor growth and side effects of anti-tumor treatment (figure 1a).14,15
importantly, the performance status is most often determined by the Karnofsky or Zubrod score which capture the patients’ general well-being and activities of daily life and have not been designed to reveal patients’ cognitive impairments.16 in contrast
to patients with other types of cancer, however, patients with hgg are threatened by significant cognitive deterioration throughout the whole illness trajectory. even up to 79% of patients with hgg have cognitive impairment before treatment, and more than 50% lack full decision-making capacity 4 months after diagnosis.17,18
Motor neuron diseases (MnD) such as amyotrophic lateral sclerosis (als) and progressive muscular atrophy (PMa) manifest at a median age of respectively 61 and 65 years. however, both conditions can already occur in patients in their twenties and as late as in their nineties.19 on average, patients with als die about three years after
symptom onset, due to respiratory failure or aspiration pneumonia as a consequence of dysphagia.20-22 Patients with PMa have a longer median survival of about four years.23
negative prognostic factors are older age, bulbar or respiratory onset, the presence of the behavioral variant of frontotemporal dementia, and recently there is some evidence that the presence of executive cognitive and/or behavioral impairment also has a negative impact on survival.24,25 thirty to fifty percent of patients with als have some
degree of cognitive and/or behavioral impairment which in most cases remains rela-tively mild. in 5-10% there is frank frontotemporal dementia.26,27 the life expectancy
of patients with als can be prolonged by weeks to a few months by administration of the drug riluzole.28 in general, for both patients with als and PMa the steepness of the
2. Gradual decline, punctuated by episodes of acute, life-threatening deterioration and partial recovery: e.g. multiple sclerosis (MS) and Parkinson’s disease (PD) the majority of patients with multiple sclerosis (Ms) develop their first symptoms in early and middle adulthood.29 in general, Ms is less rapidly progressive than hggs
or MnDs.30 a recent population based study showed that on average it takes more
than 29 years before patients need walking aids.31 on the other hand, it appears that
only one third of patients with Ms still works 15 years after symptom onset.32 this can
be explained by various motor and also non-motor symptoms such as fatigue and cognitive impairment which may already interfere with daily life activities in early stages of disease.33,34 For patients with relapsing-remitting Ms disease-modifying
therapy is available which has a beneficial effect on progression when used during the early course of disease.35,36
Parkinson’s disease (PD) is uncommon in people younger than 40 years. the incidence of the disease increases rapidly after the age of 60, with a mean age at diagnosis of 70 Figure 1. Illness trajectories in chronic progressive neurological diseases
years.37 next to the classical motor symptoms of PD, more than two thirds of patients
develop non-motor symptoms such as depression, sleep disturbances, incontinence and cognitive impairment.38 Motor symptoms often show a good to excellent response
to treatment with diseases-specific medication during on average 3 to 7 years, the so-called ‘honeymoon period’. however, non-motor symptoms are associated with a poor outcome at 10 years after diagnosis.39,40 other neurodegenerative movement
disorders such atypical parkinsonism multi-system atrophy (Msa) or progressive nuclear palsy (PsP) also occur after the age of 60. these disorders are less common than PD, show more rapid progression of motor and non-motor symptoms and often have a poor response to anti-Parkinson medication.41,42
in advanced stages, in both Ms and PD progression is increasingly associated with rather unpredictable deteriorations which often necessitate hospital admission and intensive treatment (figure 1C).43 reasons for such deteriorations may e.g. be
intercurrent, ‘trivial’ infections of bladder or respiratory tract or injuries due to falls. Patients may recover from such deteriorations, but do normally not regain their old functional status. as a consequence, the time of terminal phase and death remains somehow unpredictable.
3. Prolonged gradual decline: e.g. post-stroke status with disability and dementia ischemic and hemorrhagic stroke are very common diseases in the elderly, its overall incidence increases dramatically after the age of 55.44 recent estimates rank stroke
as the second most common cause of death and the third most common cause of disability-adjusted life-years worldwide.45 Five-year survival is similar to that of all
cancers combined and heart failure.46 the various types of dementia also occur most
often in the elderly. alzheimer disease (aD) is the most common cause of dementia and one of the leading causes of morbidity and mortality in the aging population.47 globally,
an estimated 47 million people are affected by dementia, and this number is predicted to double every 20 years until 2040.48
the course of decline is well described by the third illness trajectory: the dwindling patient suffering from frailty due to the combination of old age and chronic conditions such as post-stroke status with disability, mild cognitive impairment (MCi) and de-mentia.49,50 over the years, such patients are liable to acquire intercurrent infections
or injuries, due to their overall low level of functioning (figure 1D). in line with that, the individual’s slow deterioration may easily be accelerated by an acute event such as a hip fracture, pneumonia or urinary tract infection.
the outlined illness trajectories do present some challenges. More and more advanced life-supporting and -sustaining treatment options are available, however, such treatments may raise ethical questions, especially toward the end of life. the
unpredictability of the individual patient’s illness trajectory, often combined with impaired communication and cognition, requires timely agreements between physi-cians, i.e. neurologists, and their patients on the extent of curative treatment and the upscaling of symptomatic treatment, to prevent both over- and undertreatment.
A code for treatment restrictions
the idea that doctors and patients should have an agreement on the appropriate level of curative treatment is widely shared in the Western World countries. soon after cardiopulmonary resuscitation (CPr) had been developed in the early 1960s, it became clear that routine application of CPr on a patient with cardiopulmonary insufficiency often prolonged suffering and the process of dying instead of preserving the quality of life.51 in the 1970s the first guidelines about do-not-resuscitate (Dnr) orders were
established in the united states, and during the following two decades most of the other Western World countries followed.52,53 in the netherlands, awareness of the need
for such agreements in frail patients often suffering from more than one disease, led to the development of the so-called ‘treatment restrictions code’ during the 1990s.54
to enhance the general awareness concerning end-of-life treatment decisions it was even recommended to discuss potential treatment restrictions with all adult patients. Currently, in most Dutch hospitals three different codes are used:
Code A: no treatment restrictions.
Code B: treatment restrictions: for specific treatments it is determined whether or not they will be applied if necessary during admission. the most common treatments discussed are resuscitation, ventilatory support, treatment demanding admission to an intensive care unit, surgery, treatment with antibiotics, inotropics to stabilize circulation, medication to prevent thrombosis, and nutritional support including fluid intake. Particular details can be added.
Code C: only treatment that aims at comfort, such as pain control, prevention of thirst, anxiety and shortness of breath.
the term treatment restriction could erroneously give the impression that treatment codes are exclusively about a reduction of treatment options. however, the aim of the code discussions is to identify which treatment options are appropriate and proportion-ate for the specific patient. this may be one reason why the term ‘treatment restriction’ has been replaced by ‘treatment agreement’ in many hospitals at the same time as our research project took place. the overall idea remains the same: one of the three codes, a, B or C, is supposed to be assigned to every patient, and to be prominently placed on the front page of every patient’s file, such as is the case for allergies, etc.
A palliative care approach for chronic progressive neurological disease
after the turn of the century, the growing awareness of unmet care needs of patients with chronic progressive diseases has also led to a redefinition of palliative care. Developed in the 1960s in the context of terminal, i.e. hospice care for patients with cancer, the contemporary World health organization’s (Who) definition of palliative care reads as follows:
Palliative care
- provides relief from pain and other distressing symptoms; - affirms life and regards dying as a normal process; - intends neither to hasten nor postpone death;
- integrates the psychological and spiritual aspects of patient care;
- offers a support system to help patients live as actively as possible until death; - offers a support system to help the family cope during the patient’s illness and in
their own bereavement;
- uses a team approach to address the needs of patients and their families, including bereavement counseling, if indicated;
- will enhance quality of life, and may also positively influence the course of illness; - is applicable early in the course of illness, in conjunction with other therapies
that are intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications.55
the goals of this care approach fit well with the complex needs of patients with chronic progressive neurological diseases following any of the outlined illness trajectories, and with the needs of their caregivers. this becomes even more compelling with the increasing awareness of the considerable impact of non-motor and non-disease specific symptoms on the quality of life of patients with chronic progressive neuro-logical diseases. not seldom these symptoms occur relatively early in the course of disease.40,56-58
the broadening of the palliative care approach is in keeping with growing evidence that timely input of palliative care improves symptom management and quality of life of patients with various chronic progressive diseases, and of their caregivers, and may even extend survival. 7,59-64 in line with that, the first consensus review on palliative care
in chronic progressive neurological diseases, published in 2016, recommends that the palliative care approach (1) should be integrated early in the disease trajectory; (2) should include communication with patients and families on advance care planning and; (3) should be multidisciplinary to comply with the complex care needs of patients and their families.6 a care model fitting such an approach could look like figure 2.
in this care model, palliative care is offered increasingly alongside treatment to modify disease symptoms and cure complications. the focus lies, from the beginning or at least from an early stage of chronic progressive neurological disease, on enhancement of quality of life and, later on, on quality of dying. this approach requires professional, open communication, including the setting of goals and therapy options throughout the disease trajectory.
The problem: when and how to start palliative care in chronic
progres-sive neurological disease?
Despite the above-described developments, most doctors, including neurologists, still associate ‘palliative care’ with ‘terminal or hospice care’. Medical school, specialist training and daily practice mainly focus on cure and subsequently curative, i.e. dis-ease-directed treatment, even in chronic progressive disease.5,59,65 Consequently,
there is an ongoing unawareness of physicians, including neurologists, of the current palliative care approach. there is widespread unfamiliarity with the need for developing professional skills to communicate bad news and possible treatment restrictions, to timely assess and manage non-motor and non-disease-specific symptoms and to timely refer to specialist palliative care services including hospice admissions.
in-depth interviews in the exploring phase of this research project showed that both medical specialists and patients have difficulties with considering palliative care as a treatment option during the illness trajectory. there are many misconceptions, such as ‘i do not want to diminish hope and harm the relationship with my patient’ to ‘i won’t be in charge of the patient at the time that end-of-life decisions have to be discussed’ and ‘My patient does not want to consider a Dnr order’ or, from the patient perspective, ‘i do not want to disappoint my doctor’.66-69 By now those misconceptions can be refuted
by quantitative and qualitative research data which shows that patients with chronic Figure 2. The pro-active care model for chronic disease
progressive neurological diseases – and their caregivers – suffer from complex problems and unmet care needs, and want to be involved in communication on medical treatment considerations throughout the course of disease.39,56,70-75
looking at the three illness trajectories outlined above, the precise course of chronic progressive disease in the individual patient remains hard to predict. even for doctors with knowledge of the palliative care approach, it is hard to estimate the right moment to discuss withholding a certain medical treatment or shifting the focus of care towards primarily the enhancement of quality of life.7,76 in expert tertiary
cen-tres there is increasing recognition of the palliative care needs of patients with rapidly progressive MnD, from the moment that the diagnosis is given, including timely discussions on treatment restrictions.77 however, palliative care in other progressive
chronic neurological diseases is lagging behind despite the earlier mentioned imminent cognitive impairment of many patients with these diseases, behavioral issues, communications problems and other unmet non-motor and non-disease specific problems.5,78
Research questions and outline of this thesis
our project aimed to investigate whether the discussion on treatment restrictions could be an appropriate and thus helpful tool for neurologists to timely start palliative care for their patients with chronic progressive neurological diseases. after all, in daily clinical practice the discussion on treatment restrictions appears to be the first moment that the neurologist or his patient considers a treatment not opportune anymore. initially, we focused our research on the actual timing and content of discussions on treatment restrictions between neurologists and their patients, and about the consequences of these discussions for the management of the individual patient’s further care.
our first main research questions was:
1. Does the discussion on treatment restrictions with patients suffering from chronic progressive neurological disease mark the start of palliative care?
We started off with a review on existing knowledge about the timing and content of discussions on treatment restrictions in patients with one of the following six chronic progressive neurological conditions: ischemic or hemorrhagic stroke, amyotrophic lateral sclerosis, primary brain tumors, Parkinson’s disease, multiple sclerosis and dementia syndromes. (Chapter 2)
subsequently, we investigated when and how Dutch neurologists discuss treatment restrictions with their patients in daily clinical practice by performing in-depth inter-views and subsequently by obtaining data on the topic via an online survey. (Chapter 3)
one important finding of both the review and the interviews was that many neurological patients are incompetent at the moment that treatment restrictions and codes are dis-cussed. therefore, we also looked at the way in which caregivers, i.e. family members, of incompetent patients were said to be involved in discussions on treatment restric-tions by the neurologists which we had interviewed in depth. (Chapter 4)
We concluded that discussions on treatment restrictions are not appropriate for marking a timely start of palliative care, and therefore we changed the second research question ‘Which recommendations can be given for appropriate timing of discussions on treatment restrictions for the different diseases and illness trajectories?’ to: 2. Which recommendations can be formulated for timely integration of palliative care for the different chronic progressive neurological diseases and illness trajectories? We searched for a care approach which indeed would enable timely integration of palliative care and found such an approach in practice at the tertiary als outpatient clinic where, in general, palliative care starts as soon as the diagnosis is given. By means of non-participating observations of the office hours of the clinic and subsequent in-depth interviews with the patients, we tried to investigate how palliative care is integrated in the medical care of patients with als, how patients experience this policy, and what we can learn from it in order to integrate palliative care on time in the follow-up of patients with other chronic progressive neurological diseases. (Chapters 5 and 6)
a general discussion, including general recommendations for improvement of clinical practice concerning early integration of palliative care by neurologists for their patients with chronic progressive neurological diseases, and suggestions for further research are provided in Chapter 7.
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