Palliative care aims at the relief from the symptoms and mental stress of people with life-limiting illnesses. The goal is to improve the quality of life for both the person and their family. The relief from suffering conditions is generally made through multidisciplinary assessment and global approach, which can alleviate symptoms and meet personal needs.1,2 Pain, fatigue, dyspnea, delirium, nausea, vomiting and constipation are symptoms which can be frequently found at the end of the patient’s life.3
Delirium is responsible for a high degree of distress both of the patient and of the family members.4,5 It is a psycho-organic syndrome with multifactorial etiologies characterized by an alteration of the state of consciousness with a reduced ability to sustain, maintain or shift the attention, with consequent onset of cognitive and perceptive disorders. It develops over a short period of time (hours or days), it has a fluctuating trend throughout the day and different presentation methods, such as hypoactive, hyperactive and mixed delirium.6
Definition and clinical phenomenology
Delirium is a complex neurocognitive syndrome which is one of the most frequent complication encountered in palliative care.7
Changes of attention and awareness are the essential characteristics of delirium. Attention is the ability to focus mental activity on environmental or internal stimuli, supporting the related behavioral responses and switch attention towards a new stimulus.8 As regards the alteration of consciousness a distiction is needed between content, which is the ability to be aware of the environment and of oneself, and level of consciousness, attributable to the concept of wakefulness.9 The disturbance develops over a short period of time, tends to fluctuate in severity during the course of a day and it is associated to an additional disturbance in cognition.6
Difficulties in finding right words for conversation, filled with expressions such as You know what I mean or synonyms, until confabulation or even substitutions of letters with others, are manifestations of cognitive impairment. Perceptual changes, associated with confusional state, more frequently presented as visual, include perceptual distortions, illusions and hallucinations.8
The diagnosis of delirium is based on clinical assessment and is guided by standard criteria classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), based on the best scientific evidence and experts’ opinions, and in the tenth edition of the International Classification of Diseases (ICD-10).10
Delirium can be classified into different clinical subtypes on the basis of the psychomotor activity and the non-cognitive symptomatology, compared to the usual model.11 Three subtypes of delirium, hyperactive- hyperalert, hypoactive-hypoalert and mixed type are relevant in a palliative care context.8 Hyperactive delirium, characterized by an increase in psychomotor activity, restlessness, illusions, wandering and emotional lability is the form most frequently recognized by a casual observer.12 Hypoactive presentation is characterized by having less psychomotor activity. The absence of destructive and bizarre behavior, lethargy, the reduction of vigilance and apathy negatively affect both correct and timely identification, diagnosis, management and prognosis.11 Since weakness is often typical of terminal ill patients, there is the risk that the hypoactive subtype is misdiagnosed as depression, fatigue or disease progression.13
In terminal phases of the oncological or chronic and non-curable disease, in the last days and hours of life, delirium4 is the manifestation of multi-organ failure associated with irreversible impairments.14
The risk of presenting delirium varies depending on the patient’s characteristics and on the setting of care. Risk for delirium can be divided into predisposing and precipitating factors. Patients at high risk of delirium, because of multiple or severe predisposing factors, can develop delirium even after exposure to minimal precipitating factors (Table 1).4,15,17,18
Delirium, at the end of life, is not only a phenomenon of the older people, but it can appear at any age.12 The data of prevalence and incidence, due to the frequent lack of recognition and screening, are very variable.
According to the Canadian Coalition for Seniors’ Mental Health (CCSMH) guidelines up to 85% of terminally ill patients may experience delirium before they die; The British Geriatric Society (BGS) states that more than 30% of elderly hospitalized patients may suffer from an increase in prevalence in relation to the patient’s criticality. Prevalence on admission in a palliative care programme ranges between 13% and 42%.13
A percentage ranging from one third and to one half of cases of delirium, not associated with organ failure or very serious clinical conditions, is reversible, particularly when they are caused by medication toxicity or metabolic abnormalities, with the exception of the terminal delirium which occurs in the last few days preceding death. It may be a consequence of the dying process and therefore not reversible.4,7
Clinical assessment tools
In addition to the standard diagnostic criteria of the ICD-10 and the DSM-5 (Table 2), several other assessment scales have been developed,11 with the aim of obtaining an early diagnosis, assessing the severity and the course of the symptomatology. 8 It is essential to be aware of the patient’s cognitive performance before admission or upon admission, evaluated at the time of taking charge and collecting information from the family members, in order to have a baseline reference one can compare a potential change.13
The Confusion Assessment Method (CAM), with a sensitivity of 94-100% and a specificity of 90-95%,19 is the most widely used scale for the screening and diagnosis of delirium.10 The CAM comprises nine operationalized criteria and four diagnostic algorithm items.19 It can be administered, in less than 5 minutes, by clinicians and health workers who have been trained in the method7.
Another brief test for the screening of delirium, is the 4A’s Test (4AT), which has been validated in clinical settings involving dementia patients. It is easy to administer, with a sensitivity of 90% and a specificity of 84%.20
Memorial Delirium Assessment Scale (MDAS) is a scale designed to assess the severity of delirium.
It is composed of ten items yielding a global score ranging from 0 to 30.
The MDAS adequately detects hypoactive psychomotor subtypes of delirium. However, the assessment of arousal disturbance can only include reduced level of consciousness and it does not detect hyperarousal or hypervigilance.19 It is also designed for repeated daily evaluation and to capture short-term fluctuations of symptoms and to document response to treatment. 8
Delirium rating scale-Revised-98 (DRS-R-98) is a severity delirium rating tool. It consists of a 16-item clinician-rated scale, with 13 severity items and 3 diagnostic criteria.8 It has high inter-rater reliability, validity, sensivity and specificity to distinguish delirium from mixed neuropsychiatric populations, including dementia, depression, schizophrenia. It can be used by clinicians and other health workers, such as nurses, who have received an adequate training, for initial assessment and repeated measures.8,14,19
The Family CAM (FAM-CAM) has also been developed as a validated way of determining delirium based on reports by informal caregivers.8
Delirium is identified by clinicians in a high percentage of cases of delirious patients, because of its fluctuating nature and varying behavioral presentations.7,12 It is also due to the lack of formal cognitive assessment as part of routine screening across care setting and due to the fact of not obtaining adequate informant history regarding the patient’s premorbid level of cognition and function.10,12
The philosophy of palliative care is aimed at a global management of the person and their family members, alleviating suffering and improving the quality of life until death.2
First of all it is crucial to establish the goals of care, preferably with the patient himself, if not with the family members14,21
The first aim in the management of delirium is the identification and treatment of potential causes,12,18 bearing in mind that it might have multiple etiologies.22,23
Possible causative factors may be hypoxia, infection, malnutrition, unmanaged pain, dehydration and poor renal and liver function.12 Patient drug therapy should be carefully reviewed since many medications such as sedatives and hypnotics, opioids, anticonvulsants, antiparkinsonians, steroids, antibiotics, selective serotonin reuptake inhibitors (SSRIs) and drugs with anticholinergic effects, may be involved in the onset of acute confusional state.4 However it is not just the medication itself that affects the alteration of cognitive function, but rather dehydratation, use of high doses of drug13 and decreased renal and liver function, with resulting poor metabolism and excretion that lead to toxic levels of medications for the organism.12
Although the identification and treatment of causes is essential, it is not always possible at the end of life. Drug therapy oriented to treatment of symptoms may be required.8 The incidence of delirium is not to be reduced, but one operates on gravity and duration of the episode.24 In a review of the 2012 Cochrane on drug therapy for delirium in terminal ill patients, Candy et al. however report that there is insufficient evidence to drive conclusions on the role of drug therapy because some drugs could lead to the worsening of symptoms and to anticipated death.
Antipsychotics are the treatment of choice to manage the sympotms of delirium, with the exception of alcohol or benzodiazepine withdrawal delirium.4 It is possible to distinguish between typical and atypical antipsychotics. Typical antipsychotics represent a class of drugs which share the property of blocking dopaminergic D2 activity; this results in a block of positive psychotic symptoms. The atypical ones are chacacterized by a specific pharmacological property of serotonin and dopamine.8
Haloperidol is the typical antipsychotic of choice for the management of delirium. It has a high-potential dopamine-blocking agent with few anticholinergic side effects, minimal cardiovascular side effects and no active metabolites. Compared to other antipsychotics, it is characterized by a minor sedative effect.25,26 It can be administered orally and intramuscularly, but the dosage indications in the literature are variable24 and must be modified basing on the patient’s response.8
Benzodiazepines should be considered as second-line treatment when antipsychotics fail and when consciousness sedation is the aim of the therapy.8 In monotherapy, the use of benzodiazepines should be limited only to people with hyperactive delirium caused by withdrawal from alcohol or sedative/hypnotics, as in other conditions they should prolong delirium or worsen its symptoms. When needed, it is appropriate to use benzodiazepines with a short half-life and no active metabolites. Two examples are lorazepam and midazolam. Midazolam has been employed mainly in the palliative care.8 It is in fact the most commonly used drug for palliative sedation.14,27 It has the advantage of being easily absorbed after SC administration, it features a very fast onset of action and short elimination half-life (1.9 +/–0.6 hours) which, allows easily reversible sedation8, but requires continuous infusion.14
In addition to Hui and colleagues’s study, comparing the efficacy of haloperidol use in association with a single dose of lorazepam, versus the use of haloperidol alone, has shown benefits on the control of agitation for 8 hours without additional negative effects.28
Palliative sedation may be started by clinicians when the patient’s suffering is believed to be very high and symptoms are refractory to drugs.5,29 According to the Italian Society of Palliative care (SICP) protocols, delirium should be considered one refractory symptom and may be therefore suitable for palliative sedation in particular cases.5
Palliative sedation is generally used for a short period of time (on average 2.8 days according to SICP). There is no evidence that the sedation in question affects the reduction of survival. However it must be adequately administrated because incorrect management and pharmacological abuse can lead to an acceleration of death.27
The use of drugs, the level of sedation and the patient’s distress must be carefully evaluated several times a day through assessment scales and reported in the medical records.14
In all the phases of care it is possible to use non-pharmacological interventions in order to prevent delirium or reduce its severity.4 Environments with either too high or too low stimuli can exacerbate delirium. 26 The patient should be kept in a quiet and well lit environment, promoting the presence of tools that favor orientation in time and space. To this purpose, it is important to avoid sensory deprivation, to promote ordinary staff’s approaches and to avoid unnecessary changes of room.7,8,26
Delirium increases the risk of a patient’s fall, but the use of physical restraints should be avoided since it can exaggerate the severity of delirium symptoms and that of patient’s personal suffering. The environment must be therefore free from obstacles, the bed lowered to ground (if required) and the presence of family members should be favored.4,7,8
Experiences of patients and caregivers
The distress caused by delirium may strongly affect the quality of life and the dignity of the patients, reporting feelings of terror, isolation, fear and alienation.30,31 At the same time, family members and caregivers may experience feelings of anxiety, fear, disappointment, sadness, desperation or sense of guilt for not having had enough time to spend with their relatives.8,32,33
Clinicians must be therefore sensitive to the relationship that caregivers and patients need, helping them to understand, and express their experiences, concerns and emotions, maintaining an attitude of empathetic interest, respect and hospitality. The patient and the caregiver must feel welcomed and taken care, thus alleviating distress and promoting hope.33,34
Educational interventions for the family members help them to take actively care of the person, providing earlier detection and treatment of delirium.32 There is evidence that this has also psychological benefits on the family and the patient33,34 (Table 3).4,18,33,35
Nurses play a key role in the prevention, detection and management of delirium, as they are at the front line of care with the patient.36 In order to perform prevention the nurse must be aware of the diagnostic criteria of the DSM-5, the screening and severity tools and be able to use them as well.37 Whenever risk factors or symptoms related to clinical picture of the delirium are identified, the nurse must develop, in collaboration with the interprofessional team and the family, a tailored multi-component prevention plan, including non-pharmacological intervention aimed at their control.35 The Nanda International classification (NANDA-I) of nursing diagnosis includes delirium syndrome within the perception/cognition domain, identifying the diagnosis of Acute Mental Confusion and defining it as a sudden onset of reversible disorders of the state of consciousness, attention, cognitive functions and perception that develop in a short period of time.38 Prevention is the first step of care. If patients at risk are identified it is possible to state the nursing diagnosis Acute Mental Confusion Risk.38 Therefore clinical assessment should be done and documented on a daily bases and whenever changes in cognitive, perceptual, physiological and behavioral functions are observed and reported.35 Individualized nursing care needs to consider personal aspects of the patients, characteristics of their clinical status, their personal life situation and their preferences to promote their participation in their decision making.39 The care plan must be changed continuously basing on the patient’s clinical situation.37 Throughout the care process, the nurse must establish and maintain a supportive therapeutic relationship, a helping relationship with the patient and the family, starting from the individual psychological and social characteristics. This will enable the nurse to better understand them and to support their experiences, concerns and emotions34 (Table 4).38,40,41
Strategies & search and selection criteria
Reference articles for processing the review were selected from databases such as PubMed, Cochrane, Uptodate and Chinal, through Google search engine and the consultation of the Bibliomo catalog. Priority was given to guidelines, systematic reviews and meta-analyzes and only publications from 2004 to 2017 were included. In addition it has been also inclued the ICD-10 published in 1993.
Delirium is a clinical condition of significant relevance and complex management in palliative care. Treatment and management are hindered by frequent underecognition or misdiagnosis, also related to the variable forms of manifestation. An interdisciplinary and personalized approach is required, in order to prevent delirium and identify its causes when developed.
The management of delirium in people at the end of life needs also to take into account the priorities of the care and the patient’s preferences. In some cases, it might be appropriate to avoid invasive diagnostic tests for the identification of causes of delirium, focusing only on the palliation of the symptoms and on improvement of mental and spiritual well-being.