Handbook of Clinical Neurology, Vol. 121 (3rd series) Neurologic Aspects of Systemic Disease Part III Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved
Chapter 81
Neurologic aspects of palliative care: the end of life setting EEFJE M. SIZOO1*, WOLFGANG GRISOLD2, AND MARTIN J.B. TAPHOORN3 Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
1
2
Department of Neurology, Kaiser Franz Josep Hospital, Vienna, Austria
3
Department of Neurology, Medical Center Haaglanden, The Hague, Netherlands
INTRODUCTION The concept “palliative care” in neurologic patients is often a matter of debate. The perceived boundaries between active treatment and palliative care are often not well defined as for many neurologic diseases, there are no curative treatment options at present. Some authors suggest that palliative care in specific neurologic diseases describes the whole process of treatment, others associate the term palliative care only with the end of life (EOL) setting. This chapter on neurologic aspects of palliative care will mainly be focused on common aspects of the EOL setting of patients with neurologic diseases. The occurrence and supportive treatment of common neurologic signs and symptoms (such as increasing intracranial pressure, seizures, confusion and cognitive deficits, and disability), advance care planning with the focus on patients with progressive cognitive deficit, as well as EOL decision making will be discussed.
NEUROLOGIC SIGNS AND SYMPTOMS IN THE END OF LIFE PHASE Raised intracranial pressure Raised intracranial pressure may be present in the EOL phase of patients with brain tumors or other space-occupying lesions, such as intracerebral hemorrhage, brain abscess or massive venous infarction. Furthermore, obstruction of the normal cerebrospinal fluid circulation may also result in raised intracranial pressure. Compared to intracranial hemorrhage with an acute rise in intracranial pressure, the increase of intracranial pressure in patients with brain tumors is more gradual. It should be noted, however, that
spontaneous bleeding may occur in (rapidly) growing brain tumors with a similar acute rise in intracranial pressure to that in other causes of intracranial hemorrhage. High intracranial pressure results in (acute) headache, visual disturbances, nausea and vomiting, somnolence, and finally loss of consciousness. Decreasing level of consciousness often impairs the patient’s ability to communicate. In brain tumor patients, headache is a common presenting symptom (30–40%), and a new increase of headache points to a change in the oncologic situation, most often underlying brain edema or tumor recurrence (Behin et al., 2003). Increased intracranial pressure is common in the EOL phase of patients with high-grade gliomas; 36–62% of patients have headaches, and in the last week before death, decreased consciousness is present in 85–94% of patients (Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010).
Seizures Epileptic seizures in the EOL phase are common in patients with brain tumors: 30–58% of patients have seizures in the last month before death (Faithfull et al., 2005; Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010) and may even occur de novo in these patients. In contrast to classic partial or generalized seizures, patients may have nonconvulsive seizures which may easily be mistaken for decreased consciousness. Also, the postictal phase in brain tumor patients may be prolonged with only slow recovery of deficit. Although data on the incidence of seizures in the EOL phase of patients with other neurologic diseases are lacking, one can expect seizures to occur in diseases with progressive cortical damage (e.g., Alzheimer’s disease,
*Correspondence to: Eefje M. Sizoo, M.D., Department of Neurology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. Tel: þ31-20-444-4219, Fax: þ31-20-444-2800, E-mail: [email protected]
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stroke, prion disease). When patients with a history of seizures develop problems with swallowing in the EOL phase – for example due to decreasing consciousness or oral candidiasis – the administration of medication is often withdrawn. Since discontinuation of antiepileptic drugs (AED) may induce seizures, it may be argued that daily AED should be administered via alternative routes (Krouwer et al., 2000). Patients with brain tumors and their partners often fear seizures in the EOL phase (Hildebrand, 2004; Mason, 2003).
Confusion and cognitive deficits Cognitive deficits are common in patients with brain diseases, and are most prominent in patients with dementia, stroke, or brain tumors. Patients with frontal lobe pathology (frontotemporal dementia, frontal brain tumors) may either express disinhibited behavior or present with a lack of motivation and activity. In patients with Alzheimer’s disease, memory deficits are the hallmark, whereas in other degenerative diseases (Parkinson’s disease, multiple stroke patients) mental slowing may be most prominent (Clare, 2010). In particular in brain tumor patients, cognitive deficits are global, not restricted to the brain tumor area, and due to both the disease itself and its treatment (Taphoorn and Klein, 2004). Cognitive deficits may eventually impair and distort personality and negatively influence communication (Lipsman et al., 2007), in particular in the terminal phases of the disease. Furthermore, in the EOL phase patients can be confused or agitated as a result of a delirium, although data on the incidence of a terminal delirium in neurologic patients are lacking. However, delirium is a common symptom in patients dying from systemic cancer (Ross and Alexander, 2001) and is often associated with the presence of brain metastases (Sarhill et al., 2001). The frequency of delirium is considerably higher in patients with primary or metastatic brain tumors (36%) as compared to cancer patients without brain involvement (18%) (Cobb et al., 2000). The presence of delirium, restlessness, or behavioral disturbances will have a negative impact on a peaceful and dignified experience of dying, affecting both the patients and their relatives (Morita et al., 2007; Namba et al., 2007; Bruera et al., 2009). Communication with the terminal neurologic patient may, apart from decreased consciousness and confusion, also be severely hampered due to dysphasia as a result of stroke, brain tumor, or Alzheimer’s disease.
Impaired motor functioning and immobility Progressive motor weakness leading to severe disability is the hallmark of patients with amyotrophic lateral sclerosis (ALS). In the EOL phase, these patients become
completely immobile and often unable to swallow and talk (Shoesmith and Strong, 2006; Wood-Allum and Shaw, 2010). Furthermore, paralysis of respiratory muscles causes respiratory insufficiency and is the cause of death in a large proportion of patients with ALS (McCluskey, 2007). Another respiratory abnormality in the terminal (neurologic) patient is the death rattle, caused by the accumulation of saliva in the throat. Other causes of (motor) disability in neurologic patients are brain tumor or stroke. Hemiparesis, but also sensory problems or lack of coordination, may result in immobility. Immobility has a severe negative impact on the patient’s quality of life (Osoba et al., 1997), and is often associated with loss of self-esteem and dignity. Limitations in the capability of personal care, continence, and hygiene are additional burdens. Immobility may lead to bodily pain due to skin ulcerations, spasticity, and limb contractures.
SUPPORTIVE TREATMENT OF NEUROLOGIC SYMPTOMS In the EOL phase, the physician’s duty is to reduce suffering as much as possible. Treatment should be aimed at relieving symptoms, maintaining quality of life, and facilitating a peaceful and dignified way of dying. The proper judgment and logistics (steering) of this situation requires an experienced team of doctors and nurses. Procedures vary among countries and cultures. Of paramount importance for the healthcare team is to stay in touch with the patient and the patient’s family, discussing all relevant issues concerning the EOL phase (Docherty et al., 2008). Especially in this phase, any investigation and treatment should be carefully considered, weighing any benefits against the disadvantages for the patient. In deciding on interventions postponing death, physicians should weigh the potential benefits of treatment against the quality of the patients’ remaining life. These decisions are based on medical and legal issues, but are also influenced by opinions from the family, who may wish to continue therapy as long as possible (Oberndorfer et al., 2008).
Increased intracranial pressure Headache due to increased intracranial pressure should be relieved by treatment with analgesics such as paracetamol and opioids, and nausea can be reduced by antiemetic drugs (Daly and Schiff, 2007). Especially in brain tumor patients, corticosteroids (dexamethasone) may relieve symptoms resulting from high intracranial pressure by reducing vasogenic edema surrounding the tumor. In approximately 70–80% of brain tumor patients significant symptom improvement is noticeable within 6–24 hours following the first dose (Kaal and
NEUROLOGIC ASPECTS OF PALLIATIVE CARE: THE END OF LIFE SETTING Vecht, 2004; Sinha et al., 2004). In selected cases a neurosurgical intervention (such as cerebrospinal fluid drainage) should be considered if corticosteroids are insufficient. In the EOL phase, the majority of brain tumor patients are on permanent corticosteroid treatment (Bausewein et al., 2003; Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010). When consciousness is decreasing and patients are no longer able to swallow, steroids are often discontinued. Acute withdrawal of corticosteroids, however, may result in rebound symptoms of increased intracranial pressure and/or adrenal insufficiency.
Seizures There is a lack of studies concerning seizure management in the EOL phase. As long as patients with a history of seizures are able to swallow, AED should be continued. However, many patients with neurologic diseases develop dysphagia as death approaches, due to pseudobulbar paresis, mesencephalic compression, or decreasing consciousness (White et al., 2008). Oral infections (e.g., candidiasis) are a non-neurologic cause of dysphagia to be considered. Dysphagia may cause problems in taking AEDs, especially in the home care setting. Current recommendations are based on expert opinion and common sense. If patients become unable to swallow, it is suggested the physician should reassess the necessity for continued AED use (Krouwer et al., 2000). Sometimes, AED are prescribed prophylactically, for example, in brain tumor patients without a history of seizures. At present, there is no evidence favoring prophylactic prescription of AED in brain tumor patients (Tremont-Lukats et al., 2008). However, the high incidence of seizures in the EOL phase of brain tumor patients suggests AED should be continued until death in patients with previous seizures. If oral administration is no longer possible, patients can be switched to rectal administration (valproic acid, carbamazepine, and phenobarbital are available as suppositories) (Krouwer et al., 2000) or intranasal or sublingual midazolam or clonazepam. Seizures may be treated with rectal diazepam, subcutaneous midazolam, or sublingual clonazepam (Krouwer et al., 2000). In the hospital setting, intravenous infusion of AEDs may be an option (Krouwer et al., 2000). The management of status epilepticus in the EOL phase may be a difficult decision, since admittance to the intensive care unit should preferably be avoided.
Cognitive deficits and delirium Cognitive deficits, if caused by progressive brain edema in brain tumor patients, may be alleviated with corticosteroids. Studies in various palliative care populations
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yielded recommendations concerning treatment and care of delirious patients in the EOL phase (Breitbart and Alici, 2008). A standard approach to the management of delirium involves a search for possible reversible underlying causes of delirium, such as pain, drugs, or bladder dilatation and metabolic causes (Voltz and Borasio, 1997). When symptoms are refractory, the medication of first choice is usually a neuroleptic drug such as haloperidol (Casarett and Inouye, 2001). However, neuroleptics can lower seizure threshold and should be prescribed very cautiously in patients with frequent seizures (Voltz and Borasio, 1997). In approximately 30% of dying patients with delirium, symptoms are not adequately controlled by antipsychotic medication. In such cases and in patients with disinhibited behavior, sedative drugs (midazolam, lorazepam) are reasonable options. Paradoxical reactions to benzodiazepines in geriatric patients, and prolonged deposit of these drugs in fatty tissue need to be considered. In studies evaluating palliative sedation, delirium is the most common underlying refractory symptom requiring sedation (Engstrom et al., 2007).
IMPAIRED MOTOR FUNCTIONING AND IMMOBILITY Motor disability in patients with ALS cannot be treated, but swallowing problems can be circumvented by enteral tube feeding and, in case of respiratory failure, (noninvasive) mechanical ventilation may support the patient and reduce dyspnea (Wood-Allum and Shaw, 2010). These measures may prolong life, but clearly have no influence on the course of disease (McCluskey, 2007). Severe sialorrhea as a result of swallowing problems may be treated with medication (e.g., botulin toxin) or radiation of the salivary glands (Guy et al., 2011). Since immobility and spasticity can be painful, positioning and physiotherapy are important aspects of supportive care. If motor disability is caused or aggravated by vasogenic edema surrounding a progressive brain tumor, dexamethasone may effectively, but only temporarily, relieve symptoms in the EOL phase (Kaal and Vecht, 2004).
END OF LIFE DECISIONS EOL decisions include withholding or withdrawing potentially life-prolonging treatment no longer considered to be useful (for example, the withdrawal of food and fluid), alleviation of pain and other symptoms with a potentially life-shortening agent (often opioids), continuous deep sedation, and, in a restricted number of countries, physician-assisted death (van der Heide et al., 2007). Attitudes regarding EOL decisions vary widely among countries and cultures (van der Heide
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et al., 2003). The withdrawal of nutrition in the EOL phase is more readily accepted than fluid withdrawal. The main goal of medical decision making at the EOL is to improve the quality of life of patients through the prevention and relief of suffering, even if this might hasten death. In several countries and cultures, however, the attitude towards the preservation of life, even under grim circumstances, averts any death “hastening” activities. It is often assumed the prescription of opioids and sedative drugs inevitably results in shortening of life. However, there is no evidence that initiation or increasing doses of opioids or sedative drugs at the EOL is associated with precipitation of death (Sykes and Thorns, 2003). In 2010, the American Academy of Neurology (AAN) ethics section discussed the practice of palliative sedation, and the majority of members agreed that terminal sedation was a useful option to reduce suffering (Russell et al., 2010). The use of opioids and sedative drugs in terminally ill patients is increasingly becoming accepted practice in EOL care. In some countries (Switzerland, the Netherlands, Belgium, and Luxemburg), physician-assisted death as euthanasia or physician-assisted suicide are allowed under strict conditions upon a well-considered request. The proportion of patients in whom nonsudden death is preceded by an EOL decision ranged, among six European countries, from 21% (Italy) to 51% (Switzerland) (van der Heide et al., 2007). Considering neurologic diseases, extensive data regarding EOL decisions are available in ALS patients. In these patients, EOL practices are very common, which is probably due to the restricted prognosis and the retained capacity for decision-making until dying (Gordon, 2011). On the other hand, in chronic progressive neurologic diseases such as dementia, advanced stages of Parkinson’s disease, or Huntington’s disease, the course may be protracted. The transition into the EOL phase may be sudden (e.g., due to infection) and unpredictable. Probably for this reason, EOL decision making in dementia is not very well documented and patients often receive poor EOL care, related to the unpredictable course of disease and patients dying as a result of poor intake of food and fluids, cachexia, and dehydration (Ostgathe et al., 2008).
Nontreatment decisions Nontreatment decisions in patients with a dismal prognosis due to any disease are defined as withholding or withdrawing life-sustaining treatment, such as cardiopulmonary resuscitation, antibiotic drugs, and admission to an intensive care unit or to a hospital. Nontreatment decisions in neurologic patients often encompass withholding or withdrawing artificial
administration of fluids and nutrition. Sufficient intake of food and fluids may be restricted in neurologic patients due to dysphagia, decreased consciousness, and cognitive failure. A specific EOL decision for ALS patients is whether or not to start or continue (non)invasive mechanical ventilation (Maessen et al., 2009), whereas in brain tumor patients use of dexamethasone is an important issue in EOL decisions (Pace et al., 2009).
Palliative sedation Palliative sedation is often started in delirious patients in the EOL phase, such as in patients with brain tumors. In high-grade glioma patients it was applied in 13% of cases and even, in a Dutch cohort, as many as 30% (Pace et al., 2009; Sizoo et al., 2012). Compared to brain tumor patients, the figures for palliative sedation in ALS patients are lower, ranging from 3.3% in Italy (Spataro et al., 2010) to 14.8% in the Netherlands (Maessen et al., 2009). Such figures on palliative sedation are not available in patients with dementia, but in a survey studying palliative sedation in Dutch nursing homes, dementia was the underlying disease in 20% of patients (van Deijck et al., 2010).
Euthanasia or physician-assisted suicide Data regarding euthanasia or physician-assisted suicide (PAS) are available in the Netherlands. In a cohort of ALS patients who died between 2000 and 2005, 16.8% opted for euthanasia or PAS (Maessen et al., 2009). Relatives frequently reported that reasons for patients with amyotrophic lateral sclerosis (ALS) to ask for these lifeshortening practices were fear of choking, progressive deterioration, loss of dignity, and being dependent on others (Maessen et al., 2009). Concerning patients with high grade glioma (HGG) and dementia, the cognitive impairment, in particular in the terminal stages, makes patient autonomy questionable. In a population of Dutch HGG patients, euthanasia or PAS occurred in 7% of patients. Cognitive disturbances and decreasing consciousness were reported as reasons for refusing euthanasia or PAS in these patients (Sizoo et al., personal communication). Despite the fact that many patients with dementia have an advance euthanasia directive, life termination hardly ever takes place, and never in incompetent patients (De Boer et al., 2010).
DECISION MAKING AND ADVANCE CARE PLANNING Confusion, cognitive deficits, communication deficits, and decreasing levels of consciousness are common problems in the EOL phase of many patients with neurologic diseases, although ALS may be regarded as an
NEUROLOGIC ASPECTS OF PALLIATIVE CARE: THE END OF LIFE SETTING exception in this respect. These symptoms may impair the patients’ competence to participate in EOL decision making (Kerrigan and Ormerod, 2010). Given that patient autonomy is increasingly important, and considering that the large majority of brain tumor patients and patients with dementia become incompetent in participating in shared treatment decisions in the EOL phase, advance care planning (ACP) involving the patient and the patient’s family is of major importance (Congedo et al., 2010). The aim is to reach a consensus about possible EOL decisions between all participants, respecting the values of both the patients and their families (Bausewein et al., 2003; Pace et al., 2010). Given the possibility that the patient will become incompetent regarding EOL decision making in the late stages of their illness, it is important to discuss the subject at a relatively early stage. In a randomized controlled trial evaluating ACP in patients with glioblastoma multiforme, patients were asked during treatment about their preferences if their disease became uncontrollable. Of all patients approached, 68% participated in the study, though at least 12% of patients were unwilling to participate and discuss the subject. Patients who participated were assigned to intervention or standard supply of information. Intervention included watching a video explaining different goals of care: life-prolonging care (including cardiopulmonary resuscitation), basic medical care (hospital care), or comfort care (symptom relief). Patients who had watched the video opted for “comfort care only” in more than 90% of cases (El Jawahri et al., 2010). None of the patients felt uncomfortable watching the video. This study underscores the importance and applicability of ACP: the majority of patients are willing to discuss potential EOL scenarios and, once the various treatment options have been made clear, the majority prefer comfort care over life-prolonging treatment. ACP varies among countries and cultures (Jox et al., 2008; Kerrigan and Ormerod, 2010; van Wijmen et al., 2010). In the Netherlands, where euthanasia and PAS are allowed under strict conditions upon a voluntary and well-considered request, ACP is dominated by the issue of euthanasia (van Wijmen et al., 2010). The directives are often written in a very general way, and may apply to patients with systemic cancer and probably for ALS, but become unclear with respect to patients with cognitive impairment or confusion (dementia patients, brain tumor patients). If a patient has a written advance euthanasia directive, ethically the question arises whether the person who made the directive is still the same person once they reach the final life phase. As written advanced directives rarely address the exact clinical situation under which the patient would have asked
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for euthanasia or PAS, these practices will often not be carried out in patients unable to assess their own situation (De Boer et al., 2010; Rurup et al., 2010; Sizoo et al., submitted).
BEREAVEMENT CARE Although bereavement is part of the daily routine in dealing with severely ill or dying patients, comparatively little attention is devoted to this important phase for the caregivers. Doctors have an important role in bereavement, and consultation with relatives and other carers is usually incorporated in the process of treatment (Smeding, 2006). Davies and Clarke have investigated this important, and often neglected issue (Davies and Clarke, 2005). Conversely the analysis of the bereavement process can serve as a feedback for the professional team.
CONCLUSION Palliative care and treatment issues in the EOL phase are important parts of neurologic care. Supportive treatment is aimed at preserving quality of life as long as possible, rather than being aimed at prolonging life as such. End of life decisions are common. In patients with a neurologic disease with a high chance of progressive cognitive decline along the disease process, it is important to anticipate and discuss EOL preferences relatively early in the disease.
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Osoba D, Aaronson NK, Muller M et al. (1997). Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma. J Neurooncol 34: 263–278. Ostgathe C, Gaertner J, Voltz R (2008). Cognitive failure in end of life. Curr Opin Support Palliat Care 2: 187–191. Pace A, Lorenzo CD, Guariglia L et al. (2009). End of life issues in brain tumor patients. J Neurooncol 91: 39–43. Pace A, Metro G, Fabi A (2010). Supportive care in neurooncology. Curr Opin Oncol 22: 621. Ross DD, Alexander CS (2001). Management of common symptoms in terminally ill patients. Part II. Constipation, delirium and dyspnea. Am Fam Physician 64: 1019–1026. Rurup ML, Pasman HR, Onwuteaka-Philipsen BD (2010). [Advance euthanasia directives in dementia rarely carried out. Qualitative study in physicians and patients]. Ned Tijdschr Geneeskd 154: A1273. Russell JA, Williams MA, Drogan O (2010). Sedation for the imminently dying: survey results from the AAN Ethics Section. Neurology 74: 1303–1309. Sarhill N, Walsh D, Nelson KA et al. (2001). Assessment of delirium in advanced cancer: the use of the bedside confusion scale. Am J Hosp Palliat Care 18: 335–341. Shoesmith CL, Strong MJ (2006). Amyotrophic lateral sclerosis: update for family physicians. Can Fam Physician 52: 1563–1569. Sinha S, Bastin ME, Wardlaw JM et al. (2004). Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study. J Neurol Neurosurg Psychiatry 75: 1632–1635. Sizoo EM, Braam L, Postma TJ et al. (2010). Symptoms and problems in the end-of-life phase of high-grade glioma patients. Neuro Oncol 12: 1162–1166. Sizoo EM, Pasman HRW, Buttolo J et al. (2012). Decisionmaking in the end-of-life phase of high-grade glioma patients. Eur J Cancer 48: 226–232. Smeding R (2006). Bereavement. In: R Catani, N Cherny, M Kloke et al. (Eds.), ESMO Handbook of Advanced Cancer Care. Taylor and Francis, London, New York, pp. 243–246. Spataro R, Lo Re M, Piccoli T et al. (2010). Causes and place of death in Italian patients with amyotrophic lateral sclerosis. Acta Neurol Scand 122: 217–223. Sykes N, Thorns A (2003). The use of opioids and sedatives at the end of life. Lancet Oncol 4: 312–318. Taphoorn MJB, Klein M (2004). Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3: 159–168. Tremont-Lukats IW, Ratilal BO, Armstrong T et al. (2008). Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst Rev CD004424. van Deijck RH, Krijnsen PJ, Hasselaar JG et al. (2010). The practice of continuous palliative sedation in elderly patients: a nationwide explorative study among Dutch nursing home physicians. J Am Geriatr Soc 58: 1671–1678. van der Heide A, Deliens L, Faisst K et al. (2003). End-of-life decision-making in six European countries: descriptive study. Lancet 362: 345–350.
NEUROLOGIC ASPECTS OF PALLIATIVE CARE: THE END OF LIFE SETTING van der Heide A, Onwuteaka-Philipsen BD, Rurup ML et al. (2007). End-of-life practices in the Netherlands under the Euthanasia Act. N Engl J Med 356: 1957–1965. van Wijmen MP, Rurup ML, Pasman HR et al. (2010). Advance directives in the Netherlands: an empirical contribution to the exploration of a cross-cultural perspective on advance directives. Bioethics 24: 118–126.
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Voltz R, Borasio GD (1997). Palliative therapy in the terminal stage of neurological disease. J Neurol 244 (Suppl 4): S2–S10. White GN, O’Rourke F, Ong BS et al. (2008). Dysphagia: causes, assessment, treatment, and management. Geriatrics 63: 15–20. Wood-Allum C, Shaw PJ (2010). Motor neurone disease: a practical update on diagnosis and management. Clin Med 10: 252–258.
Chapter 81
Neurologic aspects of palliative care: the end of life setting EEFJE M. SIZOO1*, WOLFGANG GRISOLD2, AND MARTIN J.B. TAPHOORN3 Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
1
2
Department of Neurology, Kaiser Franz Josep Hospital, Vienna, Austria
3
Department of Neurology, Medical Center Haaglanden, The Hague, Netherlands
INTRODUCTION The concept “palliative care” in neurologic patients is often a matter of debate. The perceived boundaries between active treatment and palliative care are often not well defined as for many neurologic diseases, there are no curative treatment options at present. Some authors suggest that palliative care in specific neurologic diseases describes the whole process of treatment, others associate the term palliative care only with the end of life (EOL) setting. This chapter on neurologic aspects of palliative care will mainly be focused on common aspects of the EOL setting of patients with neurologic diseases. The occurrence and supportive treatment of common neurologic signs and symptoms (such as increasing intracranial pressure, seizures, confusion and cognitive deficits, and disability), advance care planning with the focus on patients with progressive cognitive deficit, as well as EOL decision making will be discussed.
NEUROLOGIC SIGNS AND SYMPTOMS IN THE END OF LIFE PHASE Raised intracranial pressure Raised intracranial pressure may be present in the EOL phase of patients with brain tumors or other space-occupying lesions, such as intracerebral hemorrhage, brain abscess or massive venous infarction. Furthermore, obstruction of the normal cerebrospinal fluid circulation may also result in raised intracranial pressure. Compared to intracranial hemorrhage with an acute rise in intracranial pressure, the increase of intracranial pressure in patients with brain tumors is more gradual. It should be noted, however, that
spontaneous bleeding may occur in (rapidly) growing brain tumors with a similar acute rise in intracranial pressure to that in other causes of intracranial hemorrhage. High intracranial pressure results in (acute) headache, visual disturbances, nausea and vomiting, somnolence, and finally loss of consciousness. Decreasing level of consciousness often impairs the patient’s ability to communicate. In brain tumor patients, headache is a common presenting symptom (30–40%), and a new increase of headache points to a change in the oncologic situation, most often underlying brain edema or tumor recurrence (Behin et al., 2003). Increased intracranial pressure is common in the EOL phase of patients with high-grade gliomas; 36–62% of patients have headaches, and in the last week before death, decreased consciousness is present in 85–94% of patients (Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010).
Seizures Epileptic seizures in the EOL phase are common in patients with brain tumors: 30–58% of patients have seizures in the last month before death (Faithfull et al., 2005; Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010) and may even occur de novo in these patients. In contrast to classic partial or generalized seizures, patients may have nonconvulsive seizures which may easily be mistaken for decreased consciousness. Also, the postictal phase in brain tumor patients may be prolonged with only slow recovery of deficit. Although data on the incidence of seizures in the EOL phase of patients with other neurologic diseases are lacking, one can expect seizures to occur in diseases with progressive cortical damage (e.g., Alzheimer’s disease,
*Correspondence to: Eefje M. Sizoo, M.D., Department of Neurology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. Tel: þ31-20-444-4219, Fax: þ31-20-444-2800, E-mail: [email protected]
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stroke, prion disease). When patients with a history of seizures develop problems with swallowing in the EOL phase – for example due to decreasing consciousness or oral candidiasis – the administration of medication is often withdrawn. Since discontinuation of antiepileptic drugs (AED) may induce seizures, it may be argued that daily AED should be administered via alternative routes (Krouwer et al., 2000). Patients with brain tumors and their partners often fear seizures in the EOL phase (Hildebrand, 2004; Mason, 2003).
Confusion and cognitive deficits Cognitive deficits are common in patients with brain diseases, and are most prominent in patients with dementia, stroke, or brain tumors. Patients with frontal lobe pathology (frontotemporal dementia, frontal brain tumors) may either express disinhibited behavior or present with a lack of motivation and activity. In patients with Alzheimer’s disease, memory deficits are the hallmark, whereas in other degenerative diseases (Parkinson’s disease, multiple stroke patients) mental slowing may be most prominent (Clare, 2010). In particular in brain tumor patients, cognitive deficits are global, not restricted to the brain tumor area, and due to both the disease itself and its treatment (Taphoorn and Klein, 2004). Cognitive deficits may eventually impair and distort personality and negatively influence communication (Lipsman et al., 2007), in particular in the terminal phases of the disease. Furthermore, in the EOL phase patients can be confused or agitated as a result of a delirium, although data on the incidence of a terminal delirium in neurologic patients are lacking. However, delirium is a common symptom in patients dying from systemic cancer (Ross and Alexander, 2001) and is often associated with the presence of brain metastases (Sarhill et al., 2001). The frequency of delirium is considerably higher in patients with primary or metastatic brain tumors (36%) as compared to cancer patients without brain involvement (18%) (Cobb et al., 2000). The presence of delirium, restlessness, or behavioral disturbances will have a negative impact on a peaceful and dignified experience of dying, affecting both the patients and their relatives (Morita et al., 2007; Namba et al., 2007; Bruera et al., 2009). Communication with the terminal neurologic patient may, apart from decreased consciousness and confusion, also be severely hampered due to dysphasia as a result of stroke, brain tumor, or Alzheimer’s disease.
Impaired motor functioning and immobility Progressive motor weakness leading to severe disability is the hallmark of patients with amyotrophic lateral sclerosis (ALS). In the EOL phase, these patients become
completely immobile and often unable to swallow and talk (Shoesmith and Strong, 2006; Wood-Allum and Shaw, 2010). Furthermore, paralysis of respiratory muscles causes respiratory insufficiency and is the cause of death in a large proportion of patients with ALS (McCluskey, 2007). Another respiratory abnormality in the terminal (neurologic) patient is the death rattle, caused by the accumulation of saliva in the throat. Other causes of (motor) disability in neurologic patients are brain tumor or stroke. Hemiparesis, but also sensory problems or lack of coordination, may result in immobility. Immobility has a severe negative impact on the patient’s quality of life (Osoba et al., 1997), and is often associated with loss of self-esteem and dignity. Limitations in the capability of personal care, continence, and hygiene are additional burdens. Immobility may lead to bodily pain due to skin ulcerations, spasticity, and limb contractures.
SUPPORTIVE TREATMENT OF NEUROLOGIC SYMPTOMS In the EOL phase, the physician’s duty is to reduce suffering as much as possible. Treatment should be aimed at relieving symptoms, maintaining quality of life, and facilitating a peaceful and dignified way of dying. The proper judgment and logistics (steering) of this situation requires an experienced team of doctors and nurses. Procedures vary among countries and cultures. Of paramount importance for the healthcare team is to stay in touch with the patient and the patient’s family, discussing all relevant issues concerning the EOL phase (Docherty et al., 2008). Especially in this phase, any investigation and treatment should be carefully considered, weighing any benefits against the disadvantages for the patient. In deciding on interventions postponing death, physicians should weigh the potential benefits of treatment against the quality of the patients’ remaining life. These decisions are based on medical and legal issues, but are also influenced by opinions from the family, who may wish to continue therapy as long as possible (Oberndorfer et al., 2008).
Increased intracranial pressure Headache due to increased intracranial pressure should be relieved by treatment with analgesics such as paracetamol and opioids, and nausea can be reduced by antiemetic drugs (Daly and Schiff, 2007). Especially in brain tumor patients, corticosteroids (dexamethasone) may relieve symptoms resulting from high intracranial pressure by reducing vasogenic edema surrounding the tumor. In approximately 70–80% of brain tumor patients significant symptom improvement is noticeable within 6–24 hours following the first dose (Kaal and
NEUROLOGIC ASPECTS OF PALLIATIVE CARE: THE END OF LIFE SETTING Vecht, 2004; Sinha et al., 2004). In selected cases a neurosurgical intervention (such as cerebrospinal fluid drainage) should be considered if corticosteroids are insufficient. In the EOL phase, the majority of brain tumor patients are on permanent corticosteroid treatment (Bausewein et al., 2003; Oberndorfer et al., 2008; Pace et al., 2009; Sizoo et al., 2010). When consciousness is decreasing and patients are no longer able to swallow, steroids are often discontinued. Acute withdrawal of corticosteroids, however, may result in rebound symptoms of increased intracranial pressure and/or adrenal insufficiency.
Seizures There is a lack of studies concerning seizure management in the EOL phase. As long as patients with a history of seizures are able to swallow, AED should be continued. However, many patients with neurologic diseases develop dysphagia as death approaches, due to pseudobulbar paresis, mesencephalic compression, or decreasing consciousness (White et al., 2008). Oral infections (e.g., candidiasis) are a non-neurologic cause of dysphagia to be considered. Dysphagia may cause problems in taking AEDs, especially in the home care setting. Current recommendations are based on expert opinion and common sense. If patients become unable to swallow, it is suggested the physician should reassess the necessity for continued AED use (Krouwer et al., 2000). Sometimes, AED are prescribed prophylactically, for example, in brain tumor patients without a history of seizures. At present, there is no evidence favoring prophylactic prescription of AED in brain tumor patients (Tremont-Lukats et al., 2008). However, the high incidence of seizures in the EOL phase of brain tumor patients suggests AED should be continued until death in patients with previous seizures. If oral administration is no longer possible, patients can be switched to rectal administration (valproic acid, carbamazepine, and phenobarbital are available as suppositories) (Krouwer et al., 2000) or intranasal or sublingual midazolam or clonazepam. Seizures may be treated with rectal diazepam, subcutaneous midazolam, or sublingual clonazepam (Krouwer et al., 2000). In the hospital setting, intravenous infusion of AEDs may be an option (Krouwer et al., 2000). The management of status epilepticus in the EOL phase may be a difficult decision, since admittance to the intensive care unit should preferably be avoided.
Cognitive deficits and delirium Cognitive deficits, if caused by progressive brain edema in brain tumor patients, may be alleviated with corticosteroids. Studies in various palliative care populations
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yielded recommendations concerning treatment and care of delirious patients in the EOL phase (Breitbart and Alici, 2008). A standard approach to the management of delirium involves a search for possible reversible underlying causes of delirium, such as pain, drugs, or bladder dilatation and metabolic causes (Voltz and Borasio, 1997). When symptoms are refractory, the medication of first choice is usually a neuroleptic drug such as haloperidol (Casarett and Inouye, 2001). However, neuroleptics can lower seizure threshold and should be prescribed very cautiously in patients with frequent seizures (Voltz and Borasio, 1997). In approximately 30% of dying patients with delirium, symptoms are not adequately controlled by antipsychotic medication. In such cases and in patients with disinhibited behavior, sedative drugs (midazolam, lorazepam) are reasonable options. Paradoxical reactions to benzodiazepines in geriatric patients, and prolonged deposit of these drugs in fatty tissue need to be considered. In studies evaluating palliative sedation, delirium is the most common underlying refractory symptom requiring sedation (Engstrom et al., 2007).
IMPAIRED MOTOR FUNCTIONING AND IMMOBILITY Motor disability in patients with ALS cannot be treated, but swallowing problems can be circumvented by enteral tube feeding and, in case of respiratory failure, (noninvasive) mechanical ventilation may support the patient and reduce dyspnea (Wood-Allum and Shaw, 2010). These measures may prolong life, but clearly have no influence on the course of disease (McCluskey, 2007). Severe sialorrhea as a result of swallowing problems may be treated with medication (e.g., botulin toxin) or radiation of the salivary glands (Guy et al., 2011). Since immobility and spasticity can be painful, positioning and physiotherapy are important aspects of supportive care. If motor disability is caused or aggravated by vasogenic edema surrounding a progressive brain tumor, dexamethasone may effectively, but only temporarily, relieve symptoms in the EOL phase (Kaal and Vecht, 2004).
END OF LIFE DECISIONS EOL decisions include withholding or withdrawing potentially life-prolonging treatment no longer considered to be useful (for example, the withdrawal of food and fluid), alleviation of pain and other symptoms with a potentially life-shortening agent (often opioids), continuous deep sedation, and, in a restricted number of countries, physician-assisted death (van der Heide et al., 2007). Attitudes regarding EOL decisions vary widely among countries and cultures (van der Heide
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et al., 2003). The withdrawal of nutrition in the EOL phase is more readily accepted than fluid withdrawal. The main goal of medical decision making at the EOL is to improve the quality of life of patients through the prevention and relief of suffering, even if this might hasten death. In several countries and cultures, however, the attitude towards the preservation of life, even under grim circumstances, averts any death “hastening” activities. It is often assumed the prescription of opioids and sedative drugs inevitably results in shortening of life. However, there is no evidence that initiation or increasing doses of opioids or sedative drugs at the EOL is associated with precipitation of death (Sykes and Thorns, 2003). In 2010, the American Academy of Neurology (AAN) ethics section discussed the practice of palliative sedation, and the majority of members agreed that terminal sedation was a useful option to reduce suffering (Russell et al., 2010). The use of opioids and sedative drugs in terminally ill patients is increasingly becoming accepted practice in EOL care. In some countries (Switzerland, the Netherlands, Belgium, and Luxemburg), physician-assisted death as euthanasia or physician-assisted suicide are allowed under strict conditions upon a well-considered request. The proportion of patients in whom nonsudden death is preceded by an EOL decision ranged, among six European countries, from 21% (Italy) to 51% (Switzerland) (van der Heide et al., 2007). Considering neurologic diseases, extensive data regarding EOL decisions are available in ALS patients. In these patients, EOL practices are very common, which is probably due to the restricted prognosis and the retained capacity for decision-making until dying (Gordon, 2011). On the other hand, in chronic progressive neurologic diseases such as dementia, advanced stages of Parkinson’s disease, or Huntington’s disease, the course may be protracted. The transition into the EOL phase may be sudden (e.g., due to infection) and unpredictable. Probably for this reason, EOL decision making in dementia is not very well documented and patients often receive poor EOL care, related to the unpredictable course of disease and patients dying as a result of poor intake of food and fluids, cachexia, and dehydration (Ostgathe et al., 2008).
Nontreatment decisions Nontreatment decisions in patients with a dismal prognosis due to any disease are defined as withholding or withdrawing life-sustaining treatment, such as cardiopulmonary resuscitation, antibiotic drugs, and admission to an intensive care unit or to a hospital. Nontreatment decisions in neurologic patients often encompass withholding or withdrawing artificial
administration of fluids and nutrition. Sufficient intake of food and fluids may be restricted in neurologic patients due to dysphagia, decreased consciousness, and cognitive failure. A specific EOL decision for ALS patients is whether or not to start or continue (non)invasive mechanical ventilation (Maessen et al., 2009), whereas in brain tumor patients use of dexamethasone is an important issue in EOL decisions (Pace et al., 2009).
Palliative sedation Palliative sedation is often started in delirious patients in the EOL phase, such as in patients with brain tumors. In high-grade glioma patients it was applied in 13% of cases and even, in a Dutch cohort, as many as 30% (Pace et al., 2009; Sizoo et al., 2012). Compared to brain tumor patients, the figures for palliative sedation in ALS patients are lower, ranging from 3.3% in Italy (Spataro et al., 2010) to 14.8% in the Netherlands (Maessen et al., 2009). Such figures on palliative sedation are not available in patients with dementia, but in a survey studying palliative sedation in Dutch nursing homes, dementia was the underlying disease in 20% of patients (van Deijck et al., 2010).
Euthanasia or physician-assisted suicide Data regarding euthanasia or physician-assisted suicide (PAS) are available in the Netherlands. In a cohort of ALS patients who died between 2000 and 2005, 16.8% opted for euthanasia or PAS (Maessen et al., 2009). Relatives frequently reported that reasons for patients with amyotrophic lateral sclerosis (ALS) to ask for these lifeshortening practices were fear of choking, progressive deterioration, loss of dignity, and being dependent on others (Maessen et al., 2009). Concerning patients with high grade glioma (HGG) and dementia, the cognitive impairment, in particular in the terminal stages, makes patient autonomy questionable. In a population of Dutch HGG patients, euthanasia or PAS occurred in 7% of patients. Cognitive disturbances and decreasing consciousness were reported as reasons for refusing euthanasia or PAS in these patients (Sizoo et al., personal communication). Despite the fact that many patients with dementia have an advance euthanasia directive, life termination hardly ever takes place, and never in incompetent patients (De Boer et al., 2010).
DECISION MAKING AND ADVANCE CARE PLANNING Confusion, cognitive deficits, communication deficits, and decreasing levels of consciousness are common problems in the EOL phase of many patients with neurologic diseases, although ALS may be regarded as an
NEUROLOGIC ASPECTS OF PALLIATIVE CARE: THE END OF LIFE SETTING exception in this respect. These symptoms may impair the patients’ competence to participate in EOL decision making (Kerrigan and Ormerod, 2010). Given that patient autonomy is increasingly important, and considering that the large majority of brain tumor patients and patients with dementia become incompetent in participating in shared treatment decisions in the EOL phase, advance care planning (ACP) involving the patient and the patient’s family is of major importance (Congedo et al., 2010). The aim is to reach a consensus about possible EOL decisions between all participants, respecting the values of both the patients and their families (Bausewein et al., 2003; Pace et al., 2010). Given the possibility that the patient will become incompetent regarding EOL decision making in the late stages of their illness, it is important to discuss the subject at a relatively early stage. In a randomized controlled trial evaluating ACP in patients with glioblastoma multiforme, patients were asked during treatment about their preferences if their disease became uncontrollable. Of all patients approached, 68% participated in the study, though at least 12% of patients were unwilling to participate and discuss the subject. Patients who participated were assigned to intervention or standard supply of information. Intervention included watching a video explaining different goals of care: life-prolonging care (including cardiopulmonary resuscitation), basic medical care (hospital care), or comfort care (symptom relief). Patients who had watched the video opted for “comfort care only” in more than 90% of cases (El Jawahri et al., 2010). None of the patients felt uncomfortable watching the video. This study underscores the importance and applicability of ACP: the majority of patients are willing to discuss potential EOL scenarios and, once the various treatment options have been made clear, the majority prefer comfort care over life-prolonging treatment. ACP varies among countries and cultures (Jox et al., 2008; Kerrigan and Ormerod, 2010; van Wijmen et al., 2010). In the Netherlands, where euthanasia and PAS are allowed under strict conditions upon a voluntary and well-considered request, ACP is dominated by the issue of euthanasia (van Wijmen et al., 2010). The directives are often written in a very general way, and may apply to patients with systemic cancer and probably for ALS, but become unclear with respect to patients with cognitive impairment or confusion (dementia patients, brain tumor patients). If a patient has a written advance euthanasia directive, ethically the question arises whether the person who made the directive is still the same person once they reach the final life phase. As written advanced directives rarely address the exact clinical situation under which the patient would have asked
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for euthanasia or PAS, these practices will often not be carried out in patients unable to assess their own situation (De Boer et al., 2010; Rurup et al., 2010; Sizoo et al., submitted).
BEREAVEMENT CARE Although bereavement is part of the daily routine in dealing with severely ill or dying patients, comparatively little attention is devoted to this important phase for the caregivers. Doctors have an important role in bereavement, and consultation with relatives and other carers is usually incorporated in the process of treatment (Smeding, 2006). Davies and Clarke have investigated this important, and often neglected issue (Davies and Clarke, 2005). Conversely the analysis of the bereavement process can serve as a feedback for the professional team.
CONCLUSION Palliative care and treatment issues in the EOL phase are important parts of neurologic care. Supportive treatment is aimed at preserving quality of life as long as possible, rather than being aimed at prolonging life as such. End of life decisions are common. In patients with a neurologic disease with a high chance of progressive cognitive decline along the disease process, it is important to anticipate and discuss EOL preferences relatively early in the disease.
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