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Delirium, confusion, agitation, and restlessness 

Delirium, confusion, agitation, and restlessness
Chapter:
Delirium, confusion, agitation, and restlessness
Author(s):

Debra E. Heidrich

and Nancy K. English

DOI:
10.1093/med/9780199332342.003.0022
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You said you wouldn’t let them take me. I won’t go! Please don’t let them hurt me; I will be good.

SC, a patient experiencing delirium

Key points

  • Delirium, confusion, and agitation are common symptoms in the palliative care setting and are extremely distressing to both patient and family.

  • Identifying patients at risk of developing these symptoms can lead to early recognition and prompt treatment.

  • The etiology of these symptoms is frequently multifactorial; some causes are reversible and others not.

  • The bedside nurse and advanced practice palliative care nurse are central to the assessment and management of patients experiencing delirium.

  • Patient and family education regarding the reasons for these mental changes and how they will be managed is essential.

Case study

Mrs. Rice, a patient with delirium

Mrs. Rice is a 78-year-old widow with advanced stage COPD and moderate dementia. She lives with her adult daughter, Darlene, and Darlene’s husband. Mrs. Rice has been hospitalized three times over the past 6 months with exacerbation of her COPD and pneumonia and required intubation and mechanical ventilation on her last admission. She is now admitted to the hospital in acute respiratory distress, requiring noninvasive ventilator support with a bilevel positive airway pressure (BiPAP) machine. The palliative care team has been consulted to discuss goals of care and to assist with symptom management.

Darlene reports that she noticed Mrs. Rice’s cough was more productive than usual a couple of days ago, but Mrs. Rice did not report any change in her breathing and she did not have a fever. At about 3 AM, Darlene heard her mother calling for help. Mrs. Rice was struggling to breathe and looked frightened. Darlene called 911. When the paramedics arrived, Mrs. Rice became combative and begged Darlene to not let them “take her away.” The paramedics reported they had to restrain Mrs. Rice during transport as she kept pulling off the oxygen mask and tried to hit the paramedic when he was putting the mask back on her. A chest X-ray showed bilateral pneumonia. On admission she was oriented to person only. Her respiratory status continued to deteriorate, and she continued to be very agitated. BiPAP was initiated and she had to be restrained to prevent her from pulling off the BiPAP mask. When Darlene arrived in the emergency department (ED), Mrs. Rice told her, “They’re trying to kill me! Get me out of here.” Darlene and the staff worked to calm Mrs. Rice, with little effect. She was given lorazepam 0.5 mg IV. She became even more agitated. Two additional doses of lorazepam were given. Mrs. Rice slept after the third dose for about 1 hour, during which time she was transferred to a medical unit. When she woke, she again tried to pull of the BiPAP mask. When assessed by the nursing staff, Mrs. Rice appears fearful and tries to pull away. She sometimes refuses to answer questions. She called her daughter by name this morning; this afternoon she is calling her “mom.”

Darlene states, “I know everyone thinks she’s just a crazy old lady, but she never acts like this.” Mrs. Rice was diagnosed with Alzheimer’s dementia about 1 year ago. She is usually oriented to person, place, and time of year, although she often forgets what day of the week it is; she recognizes family and friends, but often can’t remember the names of her grandchildren that she doesn’t see regularly. And, she’s usually very “mild-mannered” and cooperative. If she is “noncompliant” in any way, it is usually just that she forgets to do things. Darlene is both frightened and embarrassed by her mother’s behavior.

Introduction

Delirium is a common neuropsychiatric disorder seen in all healthcare settings, and is frequently underdiagnosed, misdiagnosed, and poorly managed. Often, patients are labeled as “confused” and no further evaluation is performed to determine the cause of this confusion. This is particularly an issue with the elderly, whose confusion is often dismissed as dementia and for those with terminal illness, whose confusion may be accepted as part of disease progression. Patients at highest risk for delirium include those who are elderly, in intensive care units, or postoperative, as well as those with advanced illnesses. This syndrome is associated with significant morbidity and mortality, leading to increased length of hospital and nursing home stays, and risk of earlier death. The experience of delirium is frightening to both patients and their significant others; it impairs quality of living—and quality of dying. Prompt recognition and treatment are essential to improve patient outcomes, especially in the final stages of an illness. This chapter will discuss the prevalence of delirium, its associated symptoms, factors that contribute to delirium, assessment for delirium, interventions to prevent or lessen the severity of delirium, and important patient/family teaching points.

Incidence, prevalence, and outcomes

Delirium is considered the most common and serious cognitive disorder in hospitals and in the palliative care setting.1,2,3 Reported incidence and prevalence rates vary depending on population being studied, criteria used to identify delirium, and setting. The majority of studies focus on the elderly population and the intensive care unit setting. Delirium is reported to be found in 0.5% to 10% of community-based elders, 8.9% to 47% of institutionalized elders, 14% to 56% of hospitalized elderly, 45% of elderly after general anesthesia, 60% to 80% of mechanically ventilated adult patients in intensive care units, 26% to 62% of palliative care admissions, and 58.8% to 88% of persons in the weeks or hours preceding death.1,2,3,4,5,6,7,8,9,10 However, the true incidence of delirium is unknown because it often goes undetected or misdiagnosed. In a retrospective review of 319 patient care notes in three palliative care centers in the United Kingdom, Hey and colleagues found a documented diagnosis of delirium in 0% to 8.4% of charts, but when descriptions in the chart suggestive of delirium were taken into account the prevalence was estimated at 35.7% to 39.2%.11 A systematic review of the literature in 2008 revealed that nurse recognition of delirium ranged from 26% to 83%.12 Factors that contribute to a missed diagnosis include the following12,13,14,15,16:

  • History of a past psychiatric diagnosis or cognitive disorder, such as dementia, to which the symptoms may be attributed

  • Acceptance of confusion is an expected consequence of old age and dying

  • The presence of pain

  • Transient and fluctuating nature of symptoms

  • Imprecise and overlapping use of terminology, such as delirium, acute confusion, and terminal restlessness

  • Inconsistencies in use of and types of assessment tools used to diagnose delirium

Delirium is associated with adverse physical, cognitive, and psychological outcomes. It is associated with short- and long-term decline in cognitive functioning and increases in falls, length of hospital stays, need for institutionalized care after hospitalization, and mortality.3,6,7,8,17,18,19

While not everyone remembers their experience of delirium, those who do report having distressing feelings during the experience, including fear, anxiety, and feeling threatened.20,21,22,23,24 Visual hallucinations of people or animals in the room intertwine with the people who are actually present, to create a confusing and frightening experience. Misinterpretations of real sensory experiences also lead to fear, anxiety, or the sense of being trapped in the experience, as illustrated by the quote at the beginning of this chapter. Procedures like injections may be interpreted as attempts to do harm, and interventions to reorient or reassure delirious patients may be met with suspicion and the fear that everyone is lying to them.20 Feeling threatened, the delirious patient may try to escape from the experience, leading to wandering behavior and falls as well as aggression toward caregivers. After the episode of delirium, persons report feeling humiliated and ashamed of their behavior while delirious. They also report a fear of experiencing delirium again in the future and may exhibit signs of posttraumatic stress disorder.21,23,25 Caregivers also experience distress related to delirium. Family members recall more symptoms of delirium than both the patient and the bedside nurse and are more distressed by the experience.22,23,26,27 Family members know the patient’s baseline cognitive status and spend more time at the beside, so it is not surprising that they witness and, therefore, recall more delirium symptoms. Agitation and delusions/hallucinations are particularly distressing to both family members and nurses.22,28 Interventions to decrease the incidence of delirium and prompt treatment of delirium symptoms may help decrease caregiver distress. And, providing information about delirium and support throughout this difficult time may reduce both acute and long-term distress in family members.23,29

Restlessness or agitation at the end of life, sometimes called “terminal restlessness” or “terminal delirium,” has been viewed as an expected part of the dying process.1,30,31,32,33 However, descriptions of terminal restlessness overlap considerably with the defining characteristics of delirium. It is likely that what is labeled terminal restlessness is actually delirium.1,3,30,33 Importantly, delirium is potentially reversible in some persons, even at the end of life. Two frequently cited studies from 2000 report that up to 50% of delirium episodes in the palliative care setting are reversible.10,34 Leonard and colleagues followed 121 persons diagnosed with delirium in an inpatient palliative care unit; 27% recovered from delirium before death30—fewer than the 50% reported by others, but still significant. Those with reversible delirium tend to be of younger age, have less severe cognitive disturbance, and absence of organ failure as a cause of delirium.30,35 Given this potential for reversibility, a thorough evaluation of treatable causes of delirium is required, followed by appropriate interventions based on the patient’s overall condition and the goals of care.

In addition to the negative physical and psychological impacts of this syndrome, there is a significant financial burden, in part due to the increased length of stays in hospital and increased use of long-term care facilities associated with delirium. A study examining 1-year healthcare costs associated with delirium in the elderly estimated the total cost attributable to delirium to be $16,303 to $64,421 per patient, implying that the national burden of delirium on the healthcare systems ranges from $38 billion to $152 billion each year.36 Zaubler and colleagues implemented a multicomponent delirium intervention program for patients over the age of 70 admitted to a general medical floor at a community hospital and showed a 40% reduction in the incidence of delirium, resulting in an annual cost savings of $1.1 million for that facility alone.8 A comprehensive plan that includes prevention, assessment and early detection, and appropriate intervention has the potential to save lives, improve quality of life, and significantly decrease costs.

Definition and key features of delirium

Understanding the many symptoms, syndromes, and diagnoses associated with cognitive changes in persons with an advanced illness can be difficult at best. Terms such as “confusion,” “acute confusion,” “delirium,” and “terminal restlessness” are often used to describe changes in mental status without clear definitions or use of standard psychiatric classifications. The use of imprecise terminology can lead to mislabeling of behaviors, miscommunication among healthcare professionals, and misdiagnoses of cognitive changes. Therefore, the potential for the mismanagement of any cognitive change is extremely high.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for delirium are listed in Box 21.1 .37 Key features are that the disturbances develop over a short period of time, tend to fluctuate in severity during the course of a day, and represent a change from baseline.37,38 There are no diagnostic tests for delirium; the diagnosis is primarily clinical, based on careful observation and awareness of the criteria.17 Because the presentation of symptoms can sometimes be subtle, and symptoms fluctuate throughout the day, nurses, who have more frequent and continuous contact with patients, are key to the early recognition of delirium. However, without education about delirium and use of tools to assist in identifying it, nurses often miss the diagnosis.11,12,14,15 Vasilevskis and colleagues showed that with education and integration of delirium assessment into routine documentation in an ICU, bedside nurse measurements of delirium were valid, reliable, and sustainable over time.39

Source: Adapted from American Psychiatric Association (2013), reference 37.

Disturbance in attention refers to a reduced ability to direct, focus, sustain, and shift attention. In delirium, the disturbed attention is combined with a disturbance in awareness, defined as having a reduced orientation to the environment. Previous versions of the DSM used “disturbances in consciousness” as a criterion for delirium. However, there is no consensus on what is meant by the term “consciousness”; awareness and attention are included in the DSM-5 as these are operational terms to describe consciousness and can be assessed with bedside tests in the clinical setting.38 Patients may be hypoalert, slow to respond, unable to maintain eye contact, or may fall asleep between stimuli, requiring an increased amount of stimuli (touch, calling name) to elicit a response. Conversely, patients may be hyperalert, overreact to stimuli, startle easily, rapidly change from one topic to another in conversation, and exhibit signs of agitation.17,40 In the early stage of delirium, the abnormalities in attention and awareness may be subtle and easily overlooked.40

Changes in cognition in delirium include memory deficit, disorientation, language disturbances, and perceptual disturbances.17,38,40 Disruptions in orientation usually manifest as disorientation to time or place, with time disorientation being the first to be affected. Short-term memory deficits are the most evident memory impairments. Patients may not remember conversations, television shows, or verbal instructions. For example, the person experiencing cognitive changes may remember the nurse visiting, but not anything the nurse said or did. Language disturbances include incoherent or jumbled speech, use of repetitive phrases, abnormally long pauses in the conversation, or difficulty with finding the proper words to convey a message.17,40 Perceptual disturbances are no longer considered essential to the diagnosis of delirium.1 When they are present, these disturbances may include misinterpretations, illusions, or hallucinations. Visual misperceptions and hallucinations are most common, but auditory, tactile, gustatory, and olfactory misperceptions or hallucinations can also occur. Aggressive or combative behavior may occur if the patient misperceives caregivers’ actions as intent to harm.

Development over a short time and fluctuation during the course of the day are important considerations in both identifying delirium and in differentiating it from dementia. In dementia, short-term memory problems occur progressively over months versus over hours or days with delirium. Importantly, persons with dementia are at high risk of developing delirium.4,6,7 Obtaining a history of memory issues from the family is vital to establishing the patient’s baseline, as it is the change from the baseline that indicates delirium in persons with and without dementia. Because the symptoms fluctuate, assessment throughout the course of the day is essential to identify delirium. Family member reports of subtle changes in attention, cognition, or sleep pattern disturbances are indicators that a more thorough assessment is needed.27,29,41,42

Additional clinical features of delirium that are not included in the diagnostic criteria but are frequently present include sleep-wake cycle disruption (73% of cases), hallucinations or perceptual distortions (50%), delusional or fixed false beliefs (30%), and mood lability.35,41 Some of these features help in differentiating delirium from dementia, as persons with dementia do not typically have delusions or hallucinations. Sleep-wake cycle disruptions are more pronounced in persons with delirium and are of new onset. “Sundowning,” or increased confusion and agitation at night, should be viewed as a potential sign of delirium unless this behavior has been present for weeks to months in the person with dementia.

Subtypes of delirium

There are three clinical subtypes of delirium based on arousal disturbance and psychomotor behavior: hyperactive, hypoactive, and mixed.1,17,38,43,44,45 Box 21.2 outlines the characteristics of the subtype categories. There are some variations in the definitions of these subtypes from one author to another, but in general hyperactive delirium is associated with hypervigilance, restlessness, and agitation; the hypoactive subtype is characterized by confusion and somnolence; and the mixed subtype has alternating features of hyperactive and hypoactive delirium. Although psychotic features, such as delusions or hallucinations, are most often associated with hyperactive delirium, these symptoms are present in many patients with hypoactive delirium.44,45 Some patients, may not exhibit enough symptoms to identify a subtype.35,43,44 One study in an inpatient palliative care unit showed that the few subjects (6 of 100) whose delirium fit no subtype had fewer symptoms, were more likely to recover from the delirium, and were more likely to survive greater than 1 month than any other subtype.35 In this study, delirium assessments were done twice weekly. Given the fluctuating nature of delirium, it is not clear whether these subjects may have exhibited symptoms at times that would have placed them in one of the defined categories.

* The symptoms must be a deviation from predelirious baseline.

** Where at least one of either decreased amount of activity or speed of actions is present.

Mixed motor subtype if evidence of both hyperactive and hypoactive subtype in the previous 24 hours.

No motor subtype if evidence of neither hyperactive or hypoactive subtype in the previous 24 hours.

Source: Adapted from Meagher et al. (2008), reference 43.

Subsyndromal delirium is described by some as occurring in those persons who have some symptoms associated with delirium, but are not symptomatic enough to fit the criteria for the diagnosis of delirium. The DSM-5 does not include subsyndromal delirium as a category because it is not clear that this distinction is clinically practical given the fluctuating course of delirium.38 Persons who exhibit these more subtle symptoms are certainly at risk of developing the diagnosable syndrome of delirium. Clinicians need to intervene to eliminate as many factors that contribute to delirium as possible, and they need to monitor these patients routinely for progression to delirium.

Hyperactive delirium is identified more often in the clinical setting than the other subtypes because the symptoms of hypervigilance, restlessness, and agitation attract caregiver attention. However, the hypoactive and mixed forms appears to be more prevalent.2,17,35,40,46 The hypoactive form of delirium is likely underdiagnosed as symptoms are less noticeable, or may be misdiagnosed as depression or fatigue.1,2,7,15,17,40,46,47

An interesting area of study is determining whether the subtype of delirium exhibited by a patient can be associated with its underlying causes and, therefore, assist in identifying reversible causes. Some studies suggest that delirium associated with metabolic factors, organ failure, and older age is hypoactive while delirium associated with substance withdrawal or intoxication is hyperactive.44,48,49 Other studies, however, show no association between subtype and etiology.35,50,51 Variations in the population being studied, assessment tools, and definitions of subtypes account for some inconsistencies in the conclusions of these studies. Until more data are available, no assumptions as to underlying cause can be made solely on subtype of delirium.

Many studies have looked at outcomes related to subtype of delirium and show inconsistent findings.1,17,30,35,44,45,50,52 Again, a lack of consistency in definitions and clinical criteria to identify subtypes may account for some of the variation seen in outcome studies. In some settings, patients with hyperactive delirium did worse; in other studies those with hypoactive delirium had poorer outcomes. In a review of these studies, Meagher concluded that the evidence suggests that persons with hypoactive delirium appear to have a worse prognosis.44 A study of 100 consecutive cases of diagnosed delirium in patients admitted to a palliative care unit supports the conclusion that those with hypoactive delirium have worse outcomes.35

Delirium in the final days of life and deathbed phenomena

Most patients who exhibit signs of the dying process, experience symptoms consistent with delirium.31,32,33,53 In a retrospective review, Chirco, Dunn, and Robinson found delirium usually occurs 24 to 48 hours prior to death, with subtle signs being evident approximately 7 days before death.31 Delirium around the time of death is sometimes referred to as terminal restlessness, terminal delirium, terminal agitation, preterminal restlessness, preterminal delirium, or terminal psychosis. To avoid confusion, the qualifiers “terminal” and “preterminal” should be avoided and standardized assessment tools should be used to diagnose delirium throughout the course of illness, including in the final phase of life.

While delirium may be very frequent at the end of life, restless behaviors in the dying patient should not be accepted as simply “part of the dying process”; reversal of delirium maybe possible even in very advanced stages of illness.30,34,35,53 Keep in mind that the studies that show up to 49% of terminally ill patients may have reversible delirium included all patients admitted during the data collection period.30,34,35 One can speculate that if only patients who exhibit objective signs of the dying process are included, far fewer cases of documented delirium would be reversible. An evaluation to determine reversibility of a delirium is essential to facilitate a conscious, comfortable death whenever possible.

As death draws near, patients’ may experience apparitions of “helpers” or family members who have died and now appear to the patient as “guides” in the transition from life to death. Deathbed visions (DBVs) have been defined as “spiritual, mystical or unexplainable experience[s]‌ or coincidental occurrence[s] that take place in the arena of death.”54 Patients have reported seeing angels, religious figures, spiritual guides and deceased loved ones.54,55,56 It has been reported that 10% of patients are aware and conscious prior to death. Of these, approximately 50% to 60% are reported to have experienced a DBV.57 Fenwick and colleagues in the United Kingdom decided to demystify this phenomenon and record the frequency of end-of-life experiences, including DBVs, by interviewing 38 caregivers about their personal observations of dying patients in nursing and palliative care centers. Sixty-two percent of the caregivers reported that patients or their relatives spoke of DBVs and that it brought comfort to both the patient and the family. The caregivers described DBVs and end-of-life experiences as “intense, subjective experience[s] that held a profound personal meaning for the dying patient.”56

Hospice nurses Callanan and Kelly refer to these kind of phenomena as “nearing death awareness” and define this concept as a special knowledge about the process of dying that may reveal what dying is like, or what is needed to die peacefully.58 Themes of nearing death awareness include describing a place, talking to or being in the presence of someone who is not alive, knowledge of when death will occur, choosing the time of death, needing reconciliation, preparing for travel or change, being held back, and symbolic dreams.

Deathbed phenomena may be differentiated from delirium- related hallucinations or misperceptions by observing verbal and nonverbal behaviors. Persons experiencing DBVs tend to be calm or questioning but not fearful of the visions, are able to focus their attention on the vision and describe the experience coherently to others, may converse with the person(s) in the vision, and are comforted and consoled by this experience.

Pathophysiology and etiology of delirium

The pathophysiology of delirium is not clearly understood. Disturbances in cerebral oxygenation or blood flow, neurotransmitters, cytokine production, and plasma esterase activity have all been identified as potential contributing factors. Diminished blood flow and decreased oxygenation are seen with aging, hypotension, hypoxia, cirrhosis, and sepsis,59,60,61,62,63 and may explain the long-term cognitive changes seen with prolonged delirium.64,65 Acetylcholine deficiency, gamma-aminobutyric acid (GABA) deficiency, and dopamine excess are three of several neurotransmitter disturbances associated with delirium; neurotransmitter changes help to explain delirium associated with the use of medications such as anticholinergics and benzodiazepines, withdrawal from opioids and alcohol, organ system failure, sleep deprivation, and insults to the brain, such as ischemia.44,62,66,67,68,69,70,71 Elevated levels of various cytokines have been shown in patients with delirium associated with sepsis and severe physical stresses such as hip fracture and surgery.64,72,73,74,75,76,77A decrease in the activity of plasma esterases, important drug metabolizing enzymes, has been found in delirium and explains, in part, the mechanism behind medication-induced delirium.71 These various theories to explain delirium are complementary; it is likely an interconnection of several pathological mechanisms that leads to delirium.44,62,71

Delirium usually develops due to the interrelationship between patient vulnerability (predisposing factors) and noxious insults (precipitating factors).78,79,80 Table 21.1 identifies some of the common predisposing and precipitating factors for delirium. While a single precipitating factor in the predisposed patient may be enough to lead to delirium (for example, a single dose of an anticholinergic medication in a patient with dementia), there are often multiple factors involved in the development of delirium. Addressing only a single factor likely will not aid in improving delirium; an approach that addresses as many predisposing and precipitating factors as possible is needed for resolution.78

Table 21.1 Predisposing and precipitating factors for delirium

Predisposing factors

Precipitating factors

  • Demographic characteristics

    • Age of 65 years or older

    • Male sex

  • Cognitive status

    • Dementia

    • Cognitive impairment

    • History of delirium

    • Depression

  • Functional status

    • Functional dependence

    • Immobility

    • Low level of activity

    • History of falls

  • Sensory impairment

    • Visual impairment

    • Hearing impairment

  • Decreased oral intake

    • Dehydration

    • Malnutrition

  • Drugs

    • Treatment with multiple psychoactive drugs

    • Treatment with many drugs

    • Alcohol abuse

  • Coexisting medical conditions

    • Severe illness

    • Multiple coexisting conditions

    • Chronic renal or hepatic disease

    • History of stroke

    • Neurological disease

    • Metabolic derangements

    • Fracture or trauma

    • Terminal illness

    • Infection with human immunodeficiency virus

  • Drugs

    • Sedative hypnotics

    • Narcotics

    • Anticholinergic drugs

    • Treatment with multiple drugs

    • Alcohol or drug withdrawal

  • Primary neurological diseases

    • Stroke, particularly nondominant hemispheric

    • Intracranial bleeding

    • Meningitis or encephalitis

  • Intercurrent illnesses

    • Infections

    • Iatrogenic complications

    • Severe acute illness

    • Hypoxia

    • Shock

    • Fever or hypothermia

    • Anemia

    • Dehydration

    • Poor nutritional status

    • Low serum albumin level

    • Metabolic derangements (e.g., electrolyte, glucose, acid–base)

  • Surgery

    • Orthopedic surgery

    • Cardiac surgery

    • Prolonged cardiopulmonary bypass

    • Noncardiac surgery

  • Environmental

    • Admission to an intensive care unit

    • Use of physical restraints

    • Use of bladder catheter

    • Use of multiple procedures

    • Pain

    • Emotional stress

  • Prolonged sleep deprivation

Source: Adapted from Inouye (2006), reference 71.

Cognitive impairment and dementia are the leading predisposing factors for delirium,3,7,78,81,82,83 and persons with dementia are vulnerable to delirium at lower levels of medical acuity than nondemented persons.4,6,81,84,85 One study showed that persons with dementia had poorer functional and nutritional status than those in the same age group who did not have dementia.86 As both poor functional status and malnutrition are additional predisposing factors for delirium (see Table 21.1), this higher risk of delirium with dementia is not surprising. There likely are other factors (e.g., changes in levels of neurotransmitters and cerebral blood flow) in persons with dementia that also contribute to this increased vulnerability. Nurses must be aware of the increased risk of delirium in patients with dementia, carefully assess for signs of delirium, and work to eliminate or decrease precipitating factors that can be controlled. Too often, changes in behavior are dismissed as signs of the individual’s dementia instead of being identified as signs of delirium. Table 21.2 identifies the factors that help in differentiating dementia from delirium. Knowledge of the patient’s baseline cognitive status is critical for identifying recent changes in cognition and attention.

Table 21.2 Differentiating delirium from dementia

Delirium

Dementia

Onset

Acute or subacute, occurs over a short period of time (hours–days).

Insidious, often slow and progressive

Course

Fluctuates over the course of the day, worsens at night. Resolves over days to weeks

Stable over the course of the day; is progressive

Duration

If reversible, short term

Chronic and nonreversible

Consciousness

Impaired and can fluctuate rapidly. Clouded, with a reduced awareness of the environment

Clear and alert until the later stages. May become delirious, which will interfere

Cognitive defects

Impaired short-term memory, poor attention span

Poor short-term memory; attention span less affected until later stage

Attention

Reduced ability to focus, sustain, or shift attention

Relatively unaffected in the earlier stages

Orientation

Disoriented to time and place

Intact until months or years with the later stages. May have anomia (difficulty recognizing common objects) or agnosia (difficulty recognizing familiar people)

Delusions

Common, fleeting, usually transient and poorly organized

Often absent

Hallucinations

Common and usually visual, tactile, and olfactory

Often absent

Speech

Often uncharacteristic, loud, rapid, or slow (hypoactive)

Difficulty in finding words and articulating thoughts; aphasia

Affect

Mood lability

Mood lability

Sleep-wake cycle

Disturbed; may be reversed

Can be fragmented

Psychomotor activity

Increased, reduced, or unpredictable; variable depending on hyper/hypo-delirium

Can be normal; may exhibit apraxia

Sources: Adapted from Arnold (2005), reference 87; Milisen et al. (2006), reference 88.

Several studies have identified key factors that increase the risk of delirium in subsets of populations. Despite an incidence rate of 40% to 80% in persons with cancer, delirium is rarely appreciated as a source of symptom distress in oncology settings.1,40,48,89 Table 21.3 outlines the cancer-specific considerations as they relate to the risk factors for delirium, illustrating that persons with cancer have many predisposing risk factors and are exposed to multiple precipitating factors for delirium. Studies of patients undergoing surgery showed that preoperative cognitive deficits, preexisting depression, and impaired vision are common predisposing factors for delirium and that duration of surgery, prolonged intubation, surgery type, and elevated inflammatory markers are frequent precipitating factors for postoperative delirium.84,90,91,92 In the hospice and palliative care setting, poor sleep quality, uncontrolled pain, multiple medications (including high dose opioids), dehydration, infection, dementia, and organ failure are associated with delirium.30,33,41,93,94,95,96 Inouye and colleagues identified five risk factors for persistent delirium in the elderly at discharge from the hospital: dementia, vision impairment, functional impairment, high comorbidity, and use of physical restraints during delirium.97 These studies reinforce the increased vulnerability of persons with underlying dementia or cognitive impairments and demonstrate the multiple precipitating factors common in many care settings.

Table 21.3 Cancer-specific risk factors for delirium

Type of physiological risk factor

Cancer-specific considerations

  • Nutritional deficiencies

    • B vitamins

    • Vitamin C

    • Hypoproteinemia

  • Symptom distress: nausea, emesis, mucositis, diarrhea, pain, and anorexia or cachexia syndrome

  • Surgical alteration of the head and neck region or gastrointestinal tract

  • Nonoral feeding routes: gastrostomy feeding tube and use of total parenteral nutrition

  • Cardiovascular abnormalities

    • Decreased cardiac output states: myocardial infarction, dysrythmias, congestive heart failure, and cardiogenic shock

    • Alterations in peripheral vascular resistance: increased and decreased states

    • Vascular occlusion: emboli and disseminated intravascular coagulopathy

  • Septic shock syndrome

  • Hypercoagulopathy and hyperviscosity

  • Anthracycline-related cardiomyopathy

  • Central-line occlusion

  • Thrombi associated with immobility and paraneoplastic syndromes

  • Disseminated intravascular coagulopathy

  • Cerebral disease

    • Vascular insufficiency: transient ischemic attacks, cerebral vascular accidents, and thrombosis

    • Central nervous system infection: acute or chronic meningitis, brain abscess, and neurosyphylis

    • Trauma: subdural hematoma, contusion, concussion, and intracranial hemorrhage

  • Intracerebral bleed caused by thrombocytopenia

  • Meningeal carcinomatosis

  • Central nervous system edema secondary to brain malignancy or whole-brain radiation therapy

  • Fall risk

  • Malignancy: primary or metastatic involving brain and cranial irradiation

  • Endocrine disturbance

    • Hypothyroidism

    • Diabetes mellitus

    • Hypercalcemia

    • Hyponatremia

    • Hypopituitarism

  • Mantle field radiation therapy

  • Steroid induced

  • Related to bone metastases

  • Syndrome of inappropriate antidiuretic hormone, rigorous hydration, and dehydration

  • Brain tumor in or adjacent to pituitary gland

  • Temperature regulation fluctuation

    • Hypothermia

    • Hyperthermia

  • Absence of customary warm clothes

  • Fever

  • Pulmonary abnormalities

    • Inadequate gas-exchange states: pulmonary disease and alveolar hypoventilation

    • Infection: pneumonia

  • Hypoxemia

  • Anemia

  • Lung metastases

  • Bleomycin-induced pulmonary fibrosis

  • Radiotherapy to chest

  • Chest tubes

  • Neutropenia and immobility

  • Systemic infective process (acute or chronic)

    • Viral

    • Fungal

    • Bacterial: endocarditis, pyelonephritis, and cystitis

  • Prominence of neutropenia

  • Steroids

  • Hypogammaglobunemia

  • Metabolic disturbance

    • Electrolyte abnormalities: hypercalcemia, hypo- and hypernatremia, hypo- and hyperkalemia, hypo- and hypercalcemia, and hyperphosphatemia

    • Acidosis and alkalosis

    • Hypo- and hyperglycemia

    • Acute and chronic renal failure

    • Volume depletion: hemorrhage, inadequate fluid intake, diuretics, and diarrhea

    • Hepatic failure

  • Syndrome of inappropriate antidiuretic hormone

  • Bone metastases

  • Diabetes secondary to steroids

  • Renal malignancy

  • Dehydration and diarrhea secondary to pelvic radiotherapy or chemotherapy

  • Liver primary or metastases with ascites or encephalopathy

  • Tumor lysis syndrome

  • Drug intoxication (therapeutic or substance abuse)

    • Misuse of prescribed medications

    • Side effects of therapeutic medications

    • Drug-drug interactions

    • Drug and herb interactions

    • Improper use of over-the-counter medications

    • Alcohol intoxication or withdrawal

  • Polypharmacy with drugs having anticholinergic or central nervous system effects

  • Inadequate knowledge about geriatric-specific pharmacokinetic considerations in dosing

  • Self-medication with over-the-counter or herbal remedies in the absence of healthcare professional awareness

  • Alcohol withdrawal perioperatively in patients with head and neck cancer

Source: Boyle (2006), reference 89 (used with permission).

Assessment

Comprehensive and ongoing assessment is necessary to identify patients at risk for delirium and for early detection of delirium. During routine assessments, nurses frequently observe behavior changes that are signs of delirium, but often do not “put the pieces together” to recognize this syndrome. Standardized assessment tools for delirium administered by healthcare providers trained in using these tools improves the identification of delirium in the clinical setting.3,11,12,15,39,98 Assessment tools include those designed to screen for delirium symptoms, those designed to make a formal diagnosis of delirium, and those designed to rate the severity of delirium.

The Mini-Mental State Examination (MMSE) is a 20-item screening tool that provides a clinical evaluation of cognitive function but is not specifically designed to assess for delirium and does not differentiate between dementia and delirium.99,100,101 It assesses orientation, attention, recall, and language function. The MMSE is widely used in practice and research, and data support the scoring system to identify the severity of cognitive impairment. The length of this examination and the writing and drawing questions included in it may be cumbersome and difficult to perform in a palliative care population.101 Fayers and colleagues reported that a subset of four items from the MMSE is adequate to screen for delirium and cognitive impairment: current year, date, backward spelling, and copy a design.101 Additional research would be required to support the validity of using only these four items for screening. Whether using the full MMSE or a modification, it may be best to view it as a predictive instrument that directs the clinician to use a delirium assessment instrument for additional information.

Table 21.4 provides an overview of the instruments used to assess delirium. These instruments are reviewed because they distinguish delirium from dementia and assess at least several of the multiple features of delirium. While all of these instruments require further study to determine application across varied settings and among different patient populations, the following have shown good reliability and validity in identifying delirium in selected populations.102,103

  • The Memorial Delirium Assessment Scale (MDAS) is a 10-item tool based on the DSM-IV criteria (which are consistent with the DSM-5 criteria) designed to quantify the severity of delirium.103,104,105 It takes about 10 minutes to administer. The MDAS requires minimal training for use and is appropriate for both clinical practice and research.

  • The Delirium Rating Scale (DRS) is a 10-item scale, and the Delirium Rating Scale—Revised-98 (DRS-R98) is a 16-item scale. Both are intended to be used by clinicians with psychiatric training. It looks at symptoms over a 24-hour period and may be used to assess severity of delirium.103,106,107

  • The Confusion Assessment Method (CAM) is based on the DSM–IV criteria for delirium and is designed for use by a trained interviewer to assess cognitive functioning in elderly patients on a daily scheduled basis.108 The CAM and the CAM-ICU (revised for use in the intensive care unit setting) have been evaluated in a number of studies and show good reliability and validity.9,49,102,109,110,111,112 A related tool, the Family Confusion Assessment Method (FAM-CAM), is designed to get family caregiver assessments and has been shown to correlate with a formal CAM evaluation.113

  • Nurses designed the NEECHAM Confusion Scale (NCS) for rapid and unobtrusive assessment and monitoring of acute confusion in hospitalized elderly.102,114 It contains nine scaled items divided into three subscales and takes about 10 minutes to complete. The NCS has been studied in many populations, including nonintubated patients in intensive care units.115

  • The Bedside Confusion Scale (BCS) consists of observation of the level of consciousness and timed recitation of the months of the year in reverse order starting with December, and is designed for use in the palliative care setting.113,116 It requires minimal training and only about 2 minutes to complete. The BCS was found to correlate with the CAM, but it is subject to bias or inappropriate interpretation, and has a limited capacity to assess the multiple cognitive domains influenced by delirium.117

  • The Delirium Observation Screening Scale (DOSS) is based on the DSM-IV criteria and is designed to assist nurses in the early recognition of delirium during routine care.102,118 The original version of the scale has 25 items. After studies on geriatric and hip fracture patients, the scale was reduced to 13 items that can be rated as present or absent in less than 5 minutes.118

  • The Nursing Delirium Screening Scale (Nu-DESC) is an observational 5-item instrument designed to be completed in about 1 minute at the bedside.119 It has been shown to have validity and sensitivity comparable to the MDAS in oncology populations and is a sensitive test in the recovery room to detect delirium.119,120

Table 21.4 Overview of delirium assessment tools

MDAS

DRS

CAM

NCS

BCS

DOS

Nu-DESC

DSM-IV criterion

Acute onset

X

X

X

X

Fluctuating nature

X

X

X

X

Physical disorder

X

X

Consciousness

X

X

X

X

X

Attention/concentration

X

X

X

X

X

Thinking

X

X

X

X

X

X

X

Disorientation

X

X

X

X

X

Memory

X

X

X

X

X

X

Perception

X

X

X

X

X

Purpose

Screening/diagnosis

X

X

X

X

X

X

Symptom severity

X

X

Number of items

10

10

9

9

2

13

5

Time to complete (minutes)

10

Not specified

<5

10

<2

5

1

MDAS, Memorial Delirium Assessment Scale; DRS, Delirium Rating Scale; CAM, Confusion Assessment Method; NCS, NEECHAM Confusion Scale; BCS, Bedside Confusion Scale; DOS, Delirium Observation Scale; Nu-DESC, Nursing Delirium Screening Scale.

Given the fluctuating nature of delirium, every-shift assessment in hospital and nursing home settings, using a simple screening tool such as the CAM, BCS, DOSS, or Nu-DESC is appropriate, especially for high-risk populations. There are no published recommendations on the frequency with which delirium assessment tools should be used in outpatient and home care settings. Too-frequent evaluation for delirium in persons at low risk is burdensome to both the patient and the clinician. It makes sense to complete a baseline evaluation on all patients, and then base the frequency of follow-up assessments on the number of risk factors present for delirium. Simply asking the family, “Do you think [the patient] has been more confused lately?” may serve as a clinical screening tool to determine which patients require a more thorough evaluation.42

Management of delirium

Optimal care of the person at risk for, or experiencing, delirium requires application of evidence-based practice guidelines by an interdisciplinary team that includes both palliative care bedside nurses and advanced practice nurses (APNs). The plan of care must align with the patient and family goals of care. Creation of the plan of care is initiated by the palliative care nurse with the guidance of the palliative care team. The plan should be both proactive, to prevent delirium when possible, and focused on alleviation of suffering for both patient and family. The following management guidelines address interventions appropriate for all types of delirium that commonly occur in patients with serious medical conditions: hyperactive, hypoactive, and mixed-type, as well as irreversible delirium that may occur at the end of life. Deathbed phenomena are discussed as a separate syndrome.

Evidenced-based guidelines focus on primary prevention by implementing risk prevention measures, using reliable and valid delirium screening and assessment tools, and addressing contributing factors for delirium for all patients with serious or advanced medical conditions. Figure 21.1 illustrates a suggested care pathway.


Figure 21.1 Delirium algorithm.

Figure 21.1 Delirium algorithm.

Sources: Adapted from Inouye (2006), reference 71; Irwin et al. (2013), reference 53.

Care of patients at risk for delirium

The correlation between the number of risk factors and the incidence of delirium suggests that a proactive plan of care may reduce the severity of a delirious episode or possibly prevent an acute delirious episode. Five risk factors in the elderly hospitalized patient are predictive of delirium: physical restraints, malnutrition, three medications recently added, indwelling urinary catheter, and any recent medical event such as admission to an emergency room.79,121 McCusker and colleagues demonstrated that an absence of reading glasses and not having access to a glass of water was associated with increased delirium score, while having reading glasses and presence of a family member decreased delirium scores.85 The Hospital Elder Life Program (HELP), developed by Inouye and colleagues, has been shown to decrease the incidence of delirium in the hospitalized elderly in a cost-effective manner and serves as a model for incorporating specific nonpharmacological interventions in the care planning process.8,122,123 To do this, HELP encourages engaging patients in meaningful conversation, providing frequent orientation cues, socialization, and daily exercise. Attention is also given to promoting sleep using methods such as back rubs, warm drinks, and relaxation tapes.

The American College of Critical Care Medicine published revised guidelines for the management of pain, agitation, and delirium in the intensive care unit setting in 2013.9,124 These guidelines, often referred to as the “PAD bundle,” emphasize (1) frequent reorientation and assuring access to eyeglasses and hearing aids, if needed, (2) maintaining patients’ sleep-wake cycles by minimizing environmental and procedural disturbances at night, and (3) advancing patients’ mobility during the day as tolerated, with the goal of getting patients out of bed each day, even when they are intubated and mechanically ventilated.124

Based on the impact of the HELP model of care for hospitalized elderly and the PAD bundle in the ICU, the palliative nursing plan of care includes frequent orientation, normalizing sleep routines, mobilizing the patient, engaging the patient in mentally stimulating activities, maintaining consistent/familiar caregivers, ensuring use of eyeglasses and hearing aids, monitoring fluid and food intake, and monitoring bowel function.8,53,85,122,124,125 Evaluation of and interventions to improve sleep quality cannot be overemphasized as this is both a contributing factor for delirium and one of the earliest signs of a developing delirium.30,41,93 Nurses are key to advocating for the least invasive and least restrictive interventions, for example, avoiding urinary catheters, intravenous lines, and use of restraints whenever possible.

Despite an excellent plan of care that eliminates or minimizes risk factors, delirium may not be preventable in the final stages of life.10,30,35 A study incorporating a multicomponent prevention intervention at two inpatient palliative care centers was ineffective in reducing the incidence or severity of delirium among cancer patients receiving end-of-life care.10 There are several potential reasons this prevention program did not show the anticipated benefits, including that the prevention program used was not as comprehensive as the HELP program (in order to minimize burden for both the family and the bedside nurses) and that the population included only patients with advanced cancer, that is, patients in whom the underlying causes of delirium may not be reversible.10 The benefits and burdens of interventions must be evaluated in all settings and care taken to assure that the plan of care is congruent with the patient and family goals of care throughout the illness trajectory.

This proactive prevention and mitigation approach requires that nurses have a thorough knowledge of the patient’s primary diagnosis, comorbidities, symptoms, prior activity, cognitive status, nutritional status, and prognosis. The physical examination rules out infectious, metabolic, endocrine, cardiovascular, and cerebrovascular disease that could contribute to delirium.46,126 This information along with identifying medications that could contribute to delirium alerts the palliative care team to patients who are at high risk for delirious episodes.33,46,96,127

A review of the patient’s medications is an essential component of delirium risk assessment. Sedative hypnotics, opioids, medications with anticholinergic effects, benzodiazepines, and the use of multiple medications are all potential precipitating factors for delirium.33,95,96,127 With the help of an interdisciplinary review, the medication profile can be streamlined.

Because delirium is frequently undiagnosed in the clinical setting,11,15,127 evidenced-based guidelines focus on screening all patients with serious or advanced medical conditions to identification delirium on admission and at early onset. The BCS, the Nu-DESC, or asking the family if the patient has been confused lately (all described in the section on assessment tools) can be added to routine patient assessments. In the home, the FAM-CAM is a helpful tool to document changes in the patient’s behavior.128 Prior to initiating any delirium screening assessment, however, it is important to establish a baseline by questioning the patient and family caregivers about the patient’s preadmission cognitive and emotional status, sleep-wake patterns, and daily care routines. When screening indicates changes associated with delirium, a diagnostic tool, for example, the CAM or DRS, can be administered by the nurse and reported to the interdisciplinary team for further evaluation and intervention.

Because delirium is a medical diagnosis, concern is sometimes raised that bedside nurses are functioning outside their scope of practice by diagnosing delirium. Multiple studies support that the use of tools like the CAM are within the scope of the practice of the bedside nurse. Using this, or a similar tool, nurses can report the patient’s score on the CAM and the formal diagnosis can be made by the physician or APN.

Management of acute delirium

When delirium is present, a detailed workup is essential to identify the underlying cause, when possible. Laboratory examinations include complete blood count, blood urea nitrogen and creatinine levels, liver function, and thyroid function. If an infectious process is suspected, urine culture, chest X-ray, or, possibly, arterial blood gases are evaluated. Serum vitamin B12 and folate levels may reveal nutritional imbalances. Brain imaging and scans could be of value when other more common causes have been ruled out, as several advanced illness pathologies may extend to the brain, for example, cancer and acquired immune deficiency syndrome (AIDS), causing an acute delirium.46,53 All laboratory and imaging tests are initiated only after consideration of what impact the information will have on the plan of care and whether the tests are consistent with patient/family goals.53 For example, if brain metastasis is suspected and the patient would not be a candidate for, or does not want, additional treatment, a brain scan would not be appropriate.

The acronym CHIMBOP can assist the nurse to rule out seven common causes of delirium.117 While this tool does not address all of the potentially reversible causes of delirium, it provides a framework for nurses to begin searching for the etiologies of the delirium.

  • C = Constipation—check for impaction; obtain order for and administer bowel stimulants and stool softeners.

  • H = Hypovolemia, hypoglycemia—encourage oral intake or provide parenteral fluids; treat hypoglycemia.

  • I = Infection—evaluate for signs and symptoms of infection; contact the physician or APN to determine whether antiinfective medications are appropriate at this time.

  • M = Medications—review the patient’s medications for those known to contribute to delirium; discuss minimizing or discontinuing medications, as possible, with the physician, APN, and pharmacist.

  • B = Bladder catheter, bladder outlet obstruction—avoid the use of or remove urinary catheters; check for bladder distension and insert catheter (straight or indwelling) only if required.

  • O = Oxygen deficiency—check oxygen saturation or signs of hypoxia and administer oxygen as indicated.

  • P = Pain—evaluate for and treat pain.

While dehydration is a documented contributing factor for delirium, artificial hydration is not necessarily helpful. Two studies demonstrated that administration of a liter of fluid a day to persons with advanced cancer did not decrease the incidence of delirium, and did not improve symptoms, quality of life, or survival.128,129 A thorough evaluation of the patient’s overall condition is necessary to determine whether a trial of artificial hydration is indicated. And, careful monitoring is required to assure the patient does not experience any uncomfortable symptoms associated with overhydration if artificial hydration is initiated.

Additional measures include providing a safe, quiet, and comforting environment for the patient. If the patient is in an area of high activity, either in the home or hospital, moving the patient to a quiet location may help. Eliminate extraneous noises such as televisions and intercoms that may stimulate the overtaxed brain. And, involve the family.26,85 The voice of a family member or significant other or the touch of their hand can communicate understanding and reassurance to the patient.58,130

Physical restraints should be avoided whenever possible. The use of physical restraints is a recognized independent risk factor for delirium and for its persistence at discharge.97 Restraints should be used only when a patient poses a clear risk of harm to self or others. A better way to ensure patient safety is to arrange for one-on-one observation of the patient. Not only does one-on-one observation promote safety but the presence of a trusted person may also reduce the patient’s anxiety and provide orientation cues. This person becomes part of the treatment plan for delirium.

An acute phase of delirium can last for hours or days. Following resolution of the acute phase of delirium, the nurse should continue assessments and delirium screenings as the patient remains at high risk for a reoccurrence of delirium.46 In the elderly a syndrome referred to as “persistent delirium” may continue in the posthospital period for as long 6 months.46

In the postdelirium state, it is important to debrief the patient about what they remember. As mentioned previously, patients may recall distressing images or feel embarrassed about their behavior. Debriefing the experience can help the patient and caregivers to normalize the event and reduce any stigma that the patient may feel about being out of control and seemingly unaware of their behavior.

Management of delirium at the end of life

When delirium is present in the final hours and days of life, every effort needs to be made to address the presenting symptoms and ensure patient safety. Further invasive testing and examinations may increase the distress and are not recommended. Often this is a time where the search for any underlying cause is limited to only the most common causes of delirium (see CHIMBOP above). Pharmacological interventions are used as discussed in the following section.

Management of deathbed phenomena

As discussed above, deathbed phenomena are usually not distressing to patients. Therefore, a nonpharmacological approach may be the most beneficial. Yet, these behaviors may create some concern on the part of the caregivers who wonder how to respond to the patient who is seeing and speaking to someone who is not visible to others.

The palliative care team can guide caregivers in listening carefully to the patient’s words as they describe their visions. Often a theme emerges in phases such as “please open the door,” “I will be home soon,” or “I will catch the next train.” The nurse can normalize the event by explaining that these experiences are common and that they indicate the patient is preparing for death. And the nurse can teach the family responses that may be helpful, such as “The door is open, you can go on when you are ready”; “We will miss you, but you can go when it’s time”; “They are waiting and will be happy to see you”; or, “It is OK to catch the next train.” The nurse and spiritual caregivers reframe the experience as a sacred passage for the patient, where family and loved ones are offered a time to say good-bye.

Pharmacological management of delirium

Nonpharmacological approaches and interventions to treat or lessen risk factors causing delirium are the first-line treatments for this syndrome.1,46,53,78 No medications have been approved by the US Food and Drug Administration (FDA) for the treatment of delirium, but when pharmacological agents are required, antipsychotic agents are the medications of choice.1,32,40,53,131,132,133 However, the use of antipsychotics for the treatment of delirium is not without controversy. Some clinicians feel that pharmacological management should be used only for those who have severe agitation that interferes with medical treatments, or in patients that pose a danger to themselves.3,78 This approach means that those with hypoactive delirium rarely receive antipsychotics. Others suggest that pharmacological interventions should be considered in all patients with delirium, especially those who have agitation, paranoia, hallucination, or altered sensorium, because of the distressing nature of these symptoms.1,45,53,123,124 Additional support for using antipsychotics for more than the severely agitated is that these medications have been shown to improve both arousal disturbance and impaired cognitive functioning in patients with hypoactive delirium.42,134 And current evidence does not indicate a difference in response rates between clinical subtypes of delirium.133 Clinicians who choose to take a “wait-and-see” approach before using antipsychotics for the delirious patient who is not agitated or having distressing hallucinations should be prepared to act quickly, as the hypoactive, somnolent patient can become agitated very quickly.1 What is clear from the literature is that there is a wide range of prescribing patterns in the use of antipsychotics to manage delirium.33,135 Table 21.5 provides an overview of the more common medications used to treat delirium.

Table 21.5 Pharmacological treatment of delirium

Class & drug

Starting dose & titration

Usual daily dose

Comments

Typical Antipsychotic

  • Haloperidol

  • 0.5–2 mg PO/SL/SQ/IM/IV

  • every 30 minutes until settled, then up to 20 mg daily given in one or two divided doses, based on dose needed to settle

1–5 mg over 24 hours

  • Most commonly used and studied medication for delirium

  • EPS, especially if dose is > 4.5 mg PO per day

  • Monitor QTc interval

  • Due to long half-life may be able to dose once daily after effective dose established

  • Chlorpromazine

  • 25–50 mg PO/SL/PR/IM/SQ/IV

  • every 1 h until settled, then 25 mg–100 mg 6–8 h ATC or PRN, based on dose needed to settle

  • PO: 50 mg tid

  • SQ: 5–50 mg/h

  • Useful if a more sedating agent is desired

  • Higher risk of anticholinergic side effects than with haloperidol

  • Monitor blood pressure for orthostatic hypotension

  • If using IV route, give by slow push or infusion over 10–15 minutes

Atypical Antipsychotic

Class characteristics:

  • EPS equivalent to or slightly less than those of haloperidol

  • Prolonged QTc interval

  • More expensive than typical antipsychotics

  • Olanzapine

2.5–5 mg PO daily, may increase to 10 mg daily

5 mg bid

  • Available in orally disintegrating tablets

  • Risperidone

0.25–0.5 mg PO twice daily and PRN; may increase by 0.5 mg every other day

1 mg bid

  • Available in orally disintegrating tablets

  • Monitor blood pressure for orthostatic hypotension

  • Quetiapine

12.5–25 mg PO twice daily; may give 12.5 in morning and 25 mg at night, increasing as necessary

50 mg bid

  • Most sedating of this class

  • Preferred agent in patients with Parkinson’s disease

  • Monitor blood pressure for orthostatic hypotension

Benzodiazepine

  • Lorazepam

  • 0.5–1mg PO/IV

  • every 4 h PRN

  • Often worsens delirium

  • Sedating, but can see paradoxical excitation

  • Medication of choice in patients with delirium associated with sedative or alcohol withdrawal or those with neuroleptic malignant syndrome

  • Second-line agent for delirium in patients with Parkinson’s disease

PO, oral; SL, sublingual; PR, rectal; SQ, subcutaneous; IV, intravenous; ATC, around the clock; PRN, as needed; EPS, extrapyramidal symptoms.

Haloperidol is the most widely studied and used antipsychotic for delirium.3,9,46,53,78,131,133,136 After review of the literature, Jackson and Lipman concluded that there is not enough evidence to draw any conclusions about the role of pharmacology in terminally ill patients with delirium but that perhaps haloperidol is the most suitable drug therapy for delirium treatment near the end of life.65 Haloperidol has fewer anticholinergic side effects, is less sedating, and has fewer active metabolites than other typical antipsychotics. There are little data to support the optimal dose or route of administration of haloperidol for delirium, and little is known about the optimal duration of treatment. Typical starting doses are 1 to 2 mg (oral, intramuscularly, intravenously, subcutaneously) for mild agitation, 5 mg for moderate agitation, and 7.5 to 10 mg for severe agitation.3,124 In the elderly, lower doses, for example, 0.25 to 0.5 mg may be sufficient.46,124 Doses are repeated every 30 minutes until the patient is calm but arouses to normal voice.53,124 When symptoms are controlled, the total dose given in the last 24 hours is given once per day or divided for twice-daily administration. Doses above 20 mg per day are not recommended,1 but doses as high as 250 mg in 24 hours have been used.1,53 A systematic review of the literature concluded that doses greater than 4.5 mg per day were associated with more adverse side effects than the atypical antipsychotics.131 Generally, after 2 to 3 days with no evidence of delirium, the medication can be weaned while evaluating for return of symptoms.124 Ideally, during this time other interventions to address the underlying cause(s) of delirium are also used. Long-term use of antipsychotics for persistent delirium has not been studied and increases the risk of adverse events and increases costs.138

Haloperidol can be given by the oral, sublingual, rectal, subcutaneous, intramuscular, or intravenous routes. Parenteral doses are approximately twice as potent as oral doses.1 The oral route is associated with more frequent extrapyramidal side effects than the intravenous route, but the intravenous route is not without problems.131,136 Haloperidol can prolong the QTc interval and has been associated with torsades de pointes (TdP), especially when given intravenously or in higher doses than recommended. In 2007, the FDA issued an alert warning that cases of sudden death, TdP, and QTc prolongation have been reported even in the absence of predisposing factors; this warning included a reminder that haloperidol is not approved for intravenous administration, and recommended ECG monitoring if it is given intravenously.139 Monitoring of QTc intervals is recommended before long-term, high-dose antipsychotic therapy, and there is some support for not initiating treatment with haloperidol administration if the QTc interval is greater than 450 ms.124 However, two published studies, one of 326 elderly patients with delirium and one evaluating safety reports from 1972 to 2010, found no association between use of intravenous haloperidol and increased mortality.140,141 Weckmann and Morrison, in their review of the evidence, concluded that the choice to obtain an ECG should be based on the patient’s overall condition, prognosis, expected mortality, distress level, and goals of care and that the benefits of treating delirium outweigh the risks.124

Chlorpromazine is another typical antipsychotic that may be used to treat delirium. Doses of 25 mg to 50 mg by the oral, sublingual or parenteral route maybe used.53 Chlorpromazine is associated with more anticholinergic side effects, orthostatic hypotension, and sedation than haloperidol. Therefore, it is usually used only when the additional sedation will be of benefit and haloperidol has not been completely effective.

The newer, atypical antipsychotics have the advantage of fewer extrapyramidal side effects, and less effect on QTc interval.53,131 None of these medications are FDA approved for the treatment of delirium, and all of them are more expensive than haloperidol. With the exception of olanzapine, these drugs do not come in a parenteral form. Studies support that haloperidol, risperidone, olanzapine, and quetiapine are equally effective in treating delirium with few adverse events.131,142,143,144 Starting doses are outlined in Table 21.5. First-generation antipsychotics (i.e., haloperidol or chlorpromazine) are considered first-line therapy, unless the patient has Parkinson’s disease, where quetiapine is recommended.137

Several studies evaluating the effectiveness of prophylactic antipsychotics in persons at high risk for delirium, that is, postoperative elderly patients and the intensive care unit setting, have shown a reduction in delirium incidence in subjects who received perioperative antipsychotics.145,146,147,148 Surgery and intensive care unit stays are acute, time-limited events that increase the risk of delirium, providing a more clear rationale for time-limited prophylaxis with antipsychotic medications. The multiple factors contributing to delirium in persons with advanced progressive illnesses are often chronic and cumulative. At this time, the only potential rationale for pharmacological prophylaxis of delirium in the palliative care setting might be for patients who will be exposed to the additional risks of surgery and acute care.

Cholinesterase inhibitors have been studied for the treatment of delirium based on the understanding that disruption of the cholinergic system may be one of the underlying mechanisms of this syndrome. However, there is currently no evidence from controlled trials that the cholinesterase inhibitors are effective in the treatment of delirium.149

Benzodiazepines are not recommended as the first-line treatment of delirium, except for delirium associated with alcohol or sedative-hypnotic drug withdrawal.32,131,132 This class of medications tends to cause oversedation and exacerbate confusion, potentially making delirium worse.150 If haloperidol does not control the agitation of delirium, the clinician may consider switching to chlorpromazine or adding a benzodiazepine, most frequently, lorazepam.32,53,124 The patient must be monitored careful to assure the addition of the benzodiazepine does not make the delirium worse. Irwin suggests that if paradoxical agitation occurs with lorazepam, rapid titration of lorazepam to higher doses will usually overcome this reaction and palliate symptoms.53 Some clinicians will avoid benzodiazepines and treat this as a refractory delirium.

Refractory delirium is often cited as an indication for palliative sedation. Mercandante and colleagues reported that delirium alone (53.1%) or in combination with other symptoms (an additional 16.3%) was the most frequent indicator for palliative sedation in patients with advanced cancer followed at home.151 Caraceni and colleagues followed patients seen by an inpatient palliative care service over a 5-year period and reported that of the 83 patients who required palliative sedation for symptom control, delirium was the indicator 31% of the time.152 Midazolam, pentobarbital, phenobarbital, and propofol have been used for palliative sedation for delirium.53,124,153 See chapter 25 for a discussion of palliative sedation.

Family/caregiver education and support

Family/caregiver education about delirium and its associated risk factors is essential because caregiver assistance is needed to maintain daily routines, decrease risk factors that precipitate delirium, and identify early signs and symptoms of delirium.23,29,53,154 Watching a loved-one spiral into confusion and paranoia is overwhelming to caregivers. Caregivers require education and support to respond to their dying loved-one’s agitation or sudden withdrawal into silence.35,155 Psychosocial and spiritual care are essential components of the continuum of support for the caregivers’ journey with illness and death.

A simple inquiry from the nurse to the caregiver, “tell me what this is like for you,” provides the opportunity for caregivers to express their needs for support as well as the anguish over seeing a loved one decline physically and mentally. In one study, families described witnessing their loved-one’s confusion as “extreme suffering,” and reported feeling helpless and overwhelmed.27

The goals of caregiver education depend on where the patient resides (home, residential, or acute care) and the stage of their chronic/terminal illness (beginning, middle, end). Consideration is given to caregivers’ ethnicity and level of education and the resources available in the care setting. Education can be directed toward understanding delirium and its possible causes, ways to communicate with the patient (including while ventilated), orientation methods, and how to comfort the patient with touch, familiar sounds, and other sensory aids. Nurses can facilitate referrals to chaplains and social workers who may be available to offer additional support. Written information is helpful for reinforcing education. As an example, a “Quick Information Sheet” about delirium is available in English and Spanish from the Hospice and Palliative Nurses Association.156

Intensive or acute care settings

As discussed above, admission to an intensive care setting increases the risk of delirium in older adults, especially those with cognitive deficits. On admission to an acute care setting, the palliative care team can collaborate with hospital staff to educate family and caregivers on ways to help the patient adapt to the acute care setting. The family should be encouraged to let the staff know if the patient “just isn’t him- or herself, today.” When patients are in an intensive care unit, written material for family members may include scripts and suggestions of things to say to the patient during visits. Modeling possible conversations that may occur between the caregiver and the patient can help caregivers know what to say. For example, “[Patient name], it is [family member’s name] I am here with you. It is Wednesday and it is summertime. You are in the intensive care unit at [hospital name]. [Nurse’s name] is your nurse. She is taking good care of you when I am not here. You are safe and no one will hurt you.” Such scripts can be followed by a short explanation of why simple communication is important during every visit in an acute care setting. The explanation could be as simple as “even though your family member is on a breathing machine and sedated, familiar voices can help him/her feel safe and less anxious.”

The touch of a familiar hand can have a profound impact on a patient who is confused and fearful. Reassure caregivers that their presence is an important component of their loved one’s care. Caregivers may need assistance in pulling chairs close to the bedside so that they can be near and touch their loved one.

Early and timely involvement of the palliative care team can assist in discharge planning and education of families concerning the possibilities of reoccurring delirium as well as how to prevent delirium and monitor for early signs of a potential delirium after discharge. Proactive caregiver education may serve to prevent a delirious episode and readmission into acute care.

Home care setting

In home care settings, caregivers can assist in early identification of changes in the patient’s behavior that may alert the nurse to the onset of delirium. It is not uncommon for patients with advanced diseases to experience a change in sleep patterns, feel anxious or irritable, or forget the days of the week, all of which can be early signs of a delirious episode. The caregiver can be empowered through learning to observe and record specific changes in behavior through the use of a delirium assessment tool. The FAM-CAM, described earlier, provides caregivers with an easy and reliable tool to record behavioral changes.157 Caregivers are not expected to diagnose delirium but rather to keep a consistent record of behaviors. Offering caregivers this opportunity to be involved may help reduce their anxiety about caregiving while alerting the palliative care team of changes forewarning delirium in the patient.

When appropriate, engage the patient in self-reporting about feelings of agitation or confusion or experiences of seeing things or hearing voices, explaining that these are common experiences among other patients with similar problems. Patients often refrain from telling healthcare professionals or even family members that they are seeing things or hearing voices because of the fear of being labeled “crazy.” Frequent questioning of the patient by the healthcare professional can serve to normalize such changes in cognition for both the patient and the caregivers and can therefore make honest communication more comfortable for them.

In acute delirious episodes at home, help the family understand that the radio or television should be avoided, as they may increase the patient’s confusion. Families can be reminded about the importance of touch and that something as simple as a hand massage can comfort the patient and let them know that love and care is present. The familiar smells of cooking and sounds of home also serve to reassure the patient.

Delirium at the end of life

When delirium occurs in the final days or hours of life, the goals of education and support will change because delirium often cannot be resolved at this time. Review the signs of approaching death with the caregivers. This conversation will require extraordinary sensitivity and can be aided with the help of a chaplain. Time is of the essence as caregivers are prepared and supported to express their farewells. Explain the administration and intended outcome of medications used to treat delirium. If the patient experiences refractory delirium and palliative sedation is considered, the palliative care team must review with the family their goals of care, the pros and cons of palliative sedation, and the medications that would be used (see chapter 25). The palliative care team reinforces that the intent of palliative sedation is not to hasten death, but to relieve the extreme suffering of the patient.

Death bed phenomena

Twenty percent of patients will experience DBVs. Often, these can be reassuring to caregivers and some have postulated that they are helpful in bereavement.56 The palliative care team may assist in normalizing these events by informing the family and caregivers that such events are often helpful and that the patient’s seemingly confused communication need not cause alarm. The following scenario helps illustrate how the nurse may support the family: A wife tells the hospice nurse that her husband is talking to his dead sister and is asking her to forgive him. The wife shares that her husband seems afraid and that she has reminded him several times that his sister died in 1985. The wife thinks it is odd because he was always fighting with his sister and she died rather suddenly before their arguments were resolved. The hospice nurse speaks with the patient and tells him to feel free to ask his sister again to forgive him. He calms down, and his wife follows the nurses lead and says, “I know Ellen forgives you. All you have to do is ask her and she will welcome you.” Soon, he becomes calm and smiles and mumbles in conversation with his “sister.” He died peacefully 2 days later.

This is a spiritual time where families/caregivers can be coached to surround their dying loved-one with love and to acknowledge his/her otherworldly visions. This exercise can transform the pain of loss into an experience of death as a magnificent spiritual event. Deathbed visions can provide the opportunity for the palliative care team to model a fearless approach to dying while facilitating a peaceful transition.

Case study

(continued)

Given Mrs. Rice’s change from baseline, the nurse uses the CAM to evaluate for delirium. Mrs. Rice fits the diagnostic criteria for delirium as the mental status change had an acute onset and fluctuates in severity, she is easily distracted when trying to assess her, her answers to questions are often incoherent, she has misperceptions that people are trying to harm her, and she is hyperalert. These mental status changes are interfering with appropriate treatment of her medical condition and they are causing distress to both her and her daughter. The nurse reports the findings from the CAM to the APN, who confirms the diagnosis of delirium after a review of the record and assessing the patient. The APN and bedside nurse sit with Darlene to explain the syndrome of delirium. They tell her that it is common in patients that have as many risk factors as her mother, that it is usually treatable by eliminating as many risk factors as possible in addition to treating the infection and breathing problems. They list the following as likely contributing factors for Mrs. Rice’s delirium: age, dementia, advanced illness, infection, low oxygen, new medications (especially the lorazepam), being restrained (wrist restraints when Darlene is not present to prevent Mrs. Rice from taking off the mask, and restricted by the medical interventions, i.e., BiPAP and intravenous lines), and being in an unfamiliar environment.

A multicomponent plan of care is developed to address the delirium, including providing frequent orientation cues, avoiding restraints, having a family member present as often as possible or using a sitter if the family is unable to be present, keeping staff members as consistent as possible, making sure Mrs. Rice has her eyeglasses on when she is awake, getting her up to a chair during the day, assuring toileting needs (bowel and bladder) are addressed, and promoting uninterrupted sleep at night. The APN also discusses the use of short-term antipsychotic medications to treat the disorganized thinking, frightening misperceptions, and agitation. The lorazepam will be stopped and the APN will review the rest of Mrs. Rice’s medications with the pharmacist to evaluate if others can be eliminated.

Mrs. Rice is started on haloperidol 1 mg IV to be given now, and the nurse may give 0.5 mg IV every 30 minutes, as needed, for agitation over the next two hours, at which time the APN will check back to see how Mrs. Rice is doing. When the APN calls 2 hours after the initial dose of haloperidol, she learns that Mrs. Rice was given one additional dose of haloperidol. Mrs. Rice is sleeping intermittently, is easily arousable, is more cooperative with her mask and treatments, and no longer appears fearful.

The next day, Mrs. Rice is able to transition to a high-flow nasal cannula, which is much more comfortable for her than the BiPAP. She is oriented to person and place, correctly identifies the family members present in the room, and participates in conversations. Darlene reports that the patient’s memory seems about normal for her. The APN discusses with Darlene the importance of maintaining the plan of care both here at the hospital and upon discharge because Mrs. Rice will be at risk for future episodes of delirium. The haloperidol will be continued at the current dose for another 24 hours, then switched to 1 mg oral daily for two days, then discontinued, as long as Mrs. Rice shows no signs of relapsing delirium

It appears the acute medical problems are being well managed, but the underlying COPD will continue to progress. The palliative care team arranges a meeting with Mrs. Rice and Darlene to discuss goals of care now, and for future exacerbations.

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