Catherine Vena
DEFINITION AND INCIDENCE
Patients in palliative care likely are of an advanced age, experience severe exacerbations of chronic illnesses, and use multiple medications—all of which put them at risk for changes in mental and cognitive function. Frequently, the new onset of behavior labeled as “confusion” is indicative of the acute syndrome of delirium. Delirium is a serious neuropsychiatric complication that, unlike dementia, is potentially reversible. It must be properly diagnosed and promptly treated in the palliative care setting (Friedlander, Brayman, & Breitbart, 2004). The presence of delirium is associated with increased mortality and morbidity including prolonged hospital stays, functional decline, long-term care placement, and, in the case of the imminently dying, a distressing and uncomfortable death (Breitbart & Strout, 2000; Ely, Margolin, Francis et al., 2001c; Inouye, Rushing, Foreman et al., 1998; Marcantonio, Simon, Bergmann et al., 2003; McCusker, Cole, Abrahamowicz et al., 2002; Pitkala, Laurila, Strandberg et al., 2005).
Descriptions of behaviors commonly noted in delirious patients can be found in medical writings from the time of Hippocrates to the present (Clary & Krishnan, 2001). Despite this history, terminology has been inconsistent, overlapping, poorly defined, and often adapted to the discipline or specialty observing the condition. Historically, terms such as organic brain syndrome, acute secondary psychosis, exogenous psychosis, and sundown syndrome have been used synonymously with delirium (Lipowski, 1990). A review of the recent literature reveals a continuing use of a variety of terms to characterize delirium, including acute brain failure, acute confusional state, terminal restlessness or agitation, and ICU psychosis (Barber, 2003; Cacchione, Culp, Laing et al., 2003; Maluso-Bolton, 2000; McGuire, Basten, Ryan et al., 2000; Travis, Conway, Daly et al., 2001). The American Psychiatric Association (APA) first established the term “delirium” and defined diagnostic criteria in 1980 (APA, 1980). Increasingly, practitioners from various disciplines have adopted the term. To prevent miscommunication among health care professions, the clinician must always carefully characterize the mental and cognitive status of patients and use the term “delirium” when appropriate.
The most recent diagnostic criteria for delirium from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) are listed in Box 24-1. Based on these criteria, delirium may be defined as an acute and fluctuating organic brain syndrome characterized by global cerebral dysfunction that includes disturbances in attention, level of consciousness, and basic cognitive functions (thinking, perception, and memory) (APA, 2000). Other features commonly associated with delirium include increased or decreased psychomotor activity, disturbances in the sleep-wake cycle, and emotional lability (Burns, Gallagley, & Byrne, 2005). Delirium is frequently unrecognized by clinicians or misdiagnosed (Laurila, Pitkala, Strandberg et al., 2004). The fact that demented, depressed, and anxious patients may develop delirium makes the diagnosis additionally difficult (Insel & Badger, 2002). The diagnosis of delirium is primarily clinical and requires careful observation and a thorough history. Because the signs and symptoms of delirium are nonspecific, the clinician must look for a constellation of findings, identify the rapidity of onset, and assess for associated medical and environmental risks to determine an appropriate diagnosis.
Box 24-1
Disturbance of consciousness with reduced ability to focus, sustain, or shift attention
Change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia
Disturbance develops in a short period of time and fluctuates over the course of the day
Evidence from history, physical examination, or laboratory findings that the disturbance
Is the physiological consequence of a general medical condition
Developed during substance intoxication or medication use
Developed during or shortly after a withdrawal syndrome
Has more than one etiology (e.g., more than one medical condition or a general medical condition plus substance intoxication or medication side effect)
Data from American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: Author.
Key Features of Delirium
Disturbance of Consciousness
Disturbance of consciousness refers to impairments in attention and the ability to be aware of and sustain attention to the environment (APA, 1999b). Attention is typically fluctuating and may present as a change in the level of consciousness that does not reach the level of stupor or coma. Patients may demonstrate slowed or inadequate reactions to stimuli or manifest distractibility. Individuals may be unable to follow conversations or complete simple tasks, may have slow response time, may be unable to maintain eye contact, or may fall asleep between stimuli. Increasing stimuli (touch, sound) may be needed to elicit a response. Conversely, patients may be hyperalert and overattentive to cues or objects in the environment. The ability to focus can be assessed by the patient’s ability to complete a particular task such as spelling the word “world” backward, subtracting serial 7s, or listing the days of the week in reverse order (Tune, 2000).
Change in Cognition
Many aspects of cognitive function are impaired in delirium, including orientation, memory, language, thinking, and perception (APA, 1999b; Tune, 2000). Disorientation usually manifests relevant to time or place, with time disorientation being the first to be affected. Disorientation to other persons occurs commonly, but disorientation to self is very rare. Short-term memory deficits are the most evident memory impairments. Immediate memory (over a period of seconds) is demonstrated by the digit span (a healthy older adult should be able to repeat at least five) while anterograde memory (over a period of minutes) is demonstrated by the ability to remember three objects after 5 to 10 minutes (Burns et al., 2005; Goy & Ganzini, 2003). However, because these tests also reflect attention, severe deficits in this area will affect results. Language disturbances include a lack of fluency and spontaneity (long pauses and use of repetitious phrases), a tendency to ramble and switch from topic to topic, and difficulty finding the correct word to use in conversation or naming objects (anomia). Thinking is usually disorganized as evidenced by incoherent speech, deficits in logic, and responses that are irrelevant to questions asked. Perceptual 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. The individual with delirium may have the delusional conviction that the hallucination is real and exhibit emotional and behavioral responses consistent with the hallucination’s content.
Acute Onset and Fluctuating Course
The features of confusion that develops over a short period and fluctuates over the course of the day are important defining criteria for delirium. Symptoms develop over hours or days but are likely to be intermittent in presentation and severity. A typical presentation is worsening of symptoms at night with lucid periods during the day where the patient may function normally (Cole, 2004). Noting the onset of the disturbances in consciousness or cognition assists in differentiating delirium from other syndromes that cause mental status changes, such as dementia.
Etiological Evidence
An important criterion for the diagnosis of delirium is evidence that the changes are a physiological consequence of an underlying medical condition, substance or medication intoxication or withdrawal, or combination of these factors. In palliative and end-of-life care, it may be difficult to identify the exact cause of delirium. An individual may have several potential causes at any one time (see “Etiology and Pathophysiology”). The challenge for the clinician is to identify which of the potential causes is the most likely and then determine the appropriate approach to this problem.
Additional Features of Delirium
Although not required for the diagnosis of delirium, a variety of other features often accompany delirium; these include sleep-wake disturbances, psychomotor activity changes, and emotional lability. The clinician should assess for these symptoms and monitor patients for any changes over time to prevent or at least minimize distress for both patients and their caregivers (Breitbart, Gibson, & Tremblay, 2002).
Sleep-Wake Disturbances
Disturbances in sleep patterns include daytime sleepiness, nocturnal insomnia, disturbed sleep continuity, and excessive dreaming. Some patients may experience a complete reversal of the sleep-wake cycle characterized by diurnal sleep periods and nighttime agitation and insomnia, whereas others may have fragmentation of the circadian sleep-wake cycle characterized by short periods of sleep and waking across the 24-hour day (Burns et al., 2005; Trzepacz, Mittal, Torres et al., 2001).
Psychomotor Activity
Patients with delirium may also exhibit disturbed psychomotor activity. Continuing research has indicated that there are several subtypes of delirium based on motor activity. These include a hyperactive-hyperalert subtype, a hypoactive-hypoalert subtype, and a mixed subtype that features components of the other two (Camus, Burtin, Simeone et al., 2000; Meagher & Trzepacz, 2000; Ross, Peyser, Shapiro et al., 1991). Patients with hyperactive-hyperalert delirium show evidence of sympathetic nervous system overactivity manifested in restlessness or agitation. This subtype is the most commonly recognized probably due to the expected presentation of agitation and/or inappropriate behavior (Inouye, Foreman, Mion et al., 2001). Characteristics of hyperactive-hyperalert delirium include plucking at bedclothes, wandering, verbal or physical aggression, increased alertness to stimuli, psychosis, and mood lability. Hypoactive-hypoalert patients appear lethargic and drowsy, respond slowly to questions, and do not initiate movement. This type of delirium is characterized by withdrawal from people and usual activities and decreased responsiveness to stimuli. Because they are quiet and withdrawn, the delirium in these patients is often overlooked or attributed to dementia, depression, or senescence (Casarett, Inouye, & American College of Physicians, 2001; Inouye et al., 2001). Differentiating delirium from normal aging processes, dementia, or depression requires careful and repeated assessment. A patient with a mixed subtype shows alternating periods of both types of behavior. Periods of lethargy may be seen as clinical improvements, when in fact the delirium may be continuing and increasing in severity (Clary & Krishnan, 2001; Milisen, Foreman, Godderis et al., 1998). A complete assessment of all symptoms of delirium is required before a change in behavior can be labeled as an improvement.
Emotional Disturbance
Patients with delirium may exhibit emotional disturbances. Anxiety, fear, depression, irritability, anger, euphoria, and apathy are common, with anxiety being the prevailing emotion. The delirious patient may be emotionally labile, rapidly and unpredictably shifting from one emotional state to another (APA, 1999b).
Prodromal and Subsyndromal Signs of Delirium
Some patients have prodromal symptoms such as restlessness, anxiety, irritability, distractibility, or sleep disturbance that progress to overt delirium over 1 to 3 days (APA, 1999b). Recently, Cole and colleagues described a condition known as subsyndromal delirium (SSD) (Cole, McCusker, Dendukuri et al., 2003). The symptoms of SSD are similar to prodromal symptoms, but the patient never progresses to overt delirium. Patients with SSD have the same risk factors and similar outcomes as those with delirium. These findings suggest that delirium is a spectrum disorder in which increasing numbers of symptoms are associated with increasingly adverse consequences. Patients noted to be exhibiting one or more prodromal symptoms or who report feeling “mixed up,” having difficulty judging the passing of time, and having difficulty thinking or concentrating should be assessed for potentially reversible causes of delirium, and appropriate interventions should be initiated.
Prevalence and Outcomes
Researchers have found that the prevalence of delirium ranges from 10% to 80% depending on the population and setting. The palliative care clinician is likely to encounter patients with delirium in a variety of practice settings. In the acute care environment, delirium has been noted in 10% to 30% of general medical and postsurgical patients (Samuels & Neugroschl, 2005; Wise, Hilty, Cerda et al., 2002; Goy & Ganzini, 2003), 40% to 80% of critical care patients (Ely, Inouye, Bernard et al., 2001b; Ely et al., 2001c), and 25% to 50% of cancer inpatients (Fann & Sullivan, 2003). Delirium has also been described in 20% to 45% of patients newly admitted to rehabilitation or skilled nursing facilities (Marcantonio et al., 2003; Pitkala et al., 2005; Samuels & Neugroschl, 2005). From 80% to 90% of terminally ill patients will develop delirium as death approaches (Gagnon, Charbonneau, Allard et al., 2002; Lawlor et al., 2000; Massie, Holland, & Glass, 1983).
The consequences of delirium, including medical and psychosocial morbidity, can be severe for both patients and caregivers. A significant number of patients who recover from delirium remember the episode and report distress from the experience, including anxiety, helplessness, and fear (Breitbart et al., 2002; Laitinen, 1996; Schofield, 1997). Caring for patients with hyperactive delirium has obvious stresses for both families and nurses; however, hypoactive delirium is also stressful, especially for families who regret premature separation from a patient who can no longer communicate (Casarett et al., 2001). Delirium robs patients and families of valuable time. Therefore, because delirium episodes are potentially reversible even in advanced stages of disease, prompt diagnosis and treatment are essential for improving outcomes and quality of life in patients with chronic and advanced illnesses (Lawlor, Fainsinger, & Bruera, 2000).
ETIOLOGY AND PATHOPHYSIOLOGY
Multiple causes have been identified in the development of delirium. Although delirium can occur in a previously healthy person, it is by far more common in people with premorbid conditions. Furthermore, the etiology of delirium is most likely multifactorial. Inouye’s Multifactorial Model for Delirium, consisting of predisposing factors (vulnerability) and precipitating factors (insults), provides a useful framework for predicting individual susceptibility for the development of delirium as well as for identifying potential factors that may have precipitated delirium (Inouye, 1998). Many potential predisposing and precipitating factors associated with delirium are listed in Box 24-2.
Box 24-2
American Psychiatric Press, Inc.
PREDISPOSING FACTORS
Demographic
Older age
Male gender
Lifestyle
Drug or alcohol dependence
General Health
Frailty
Impairments in perception (vision, hearing)
Poor nutritional status
Insufficient sleep
Depression
Chronic Illness
Neurological disorder (e.g., dementia, Parkinson’s disease, multiple sclerosis, stroke)
AIDS
Cancer
Endocrine disorder (hypothyroidism or hyperthyroidism, Cushing’s disease)
Organ system failure (renal, hepatic)
PRECIPITATING FACTORS
Environment
Physical restraint or immobility
Unfamiliar surroundings
Sensory overload or deprivation
Admission to intensive care unit
Disease Related
Metabolic abnormalities (hypercalcemia, hyponatremia, uremia)
Anemia
Hypoxemia
Infection or sepsis
Liver failure
Acute neurological disorder (hemorrhage, infection, metastasis, edema)
Physical Discomfort
Constipation
Urinary retention
Dyspnea
Pain
Sleep disturbance
Emotional or Spiritual
Anxiety
Guilt
Spiritual distress or unfinished business
Medications
Polypharmacy
Anticholinergics
Opioids (especially meperidine)
Steroids
Chemotherapeutic and immunotherapeutic agents
Sedatives-hypnotics (benzodiazepines, barbiturates)
H 2 blockers
Phenothiazines
Medication Withdrawal
Alcohol
Benzodiazepines
Nicotine
Opioids
Steroids
Data from Burns, A., Gallagley, A., & Byrne, J. (2005). Delirium. J Neurol Neurosurg Psychiatry, 75, 362-367; Clary, G.L. & Krishnan, K.R. (2001). Delirium: Diagnosis, neuropathogenesis, and treatment. J Psychiatric Pract, 7(5), 310-323; Friedlander, M.M., Brayman, Y., & Breitbart, W.S. (2004). Delirium in palliative care. Oncology (Huntington), 18(12), 1541-1550; discussion 1551-1543; Inouye, S.K. (1998). Delirium in hospitalized older patients: Recognition and risk factors. J Geriatr Psychiatry Neurol, 11, 118-125; Johnson, M.H. (2001). Assessing confused patients. J Neurol Neurosurg Psychiatry, 71(Suppl 1), i7-i12; Samuels, S.C. & Neugroschl, J.A. (2005). Delirium. In B.J. Sadock & V.A. Sadock (Eds.). Kaplan & Sadock’s comprehensive textbook of psychiatry (8th ed., pp. 1054-1067). Philadelphia: Lippincott Williams & Wilkins; and Tune, L.E. (2000). Delirium. In C.E. Coffey & J.L. Cummings (Eds.). Textbook of geriatric neuropsychiatry (2nd ed., pp. 441-452). Washington, DC: American Psychiatric Press, Inc.
Very little is known about the underlying pathophysiological mechanisms of delirium, but analysis of symptomatology and known precipitating factors has lead to at least two explanatory models (Breitbart & Cohen, 2000). In the first model, delirium is seen as a global and nonspecific disorder of the brain characterized by generalized dysfunction in cerebral metabolism. The second model proposes that derangements in specific neurotransmitter systems precipitate brain pathology. There is evidence to support both models. Delirium probably represents a variety of disorders in which either specific or multiple interacting neurotransmitter systems (Table 24-1) are impaired as a result of aberrant metabolic activity, hypoxia, or exogenous agents (Samuels & Neugroschl, 2005).
| System and Function | Alteration | Precipitating Factors | Sequelae |
|---|---|---|---|
| Cholinergic System | ↓ Acetylcholine (ACh) | Hypoxia, hypoglycemia, thiamine deficiency, anticholinergic medication, increased cytokines | Decreased ability to focus, maintain, or shift attention |
| Attention, arousal, memory, rapid eye movement sleep | Impaired cognition | ||
| Dopamine System | ↑ Dopamine | Opioids, hypoxia, hypoglycemia | Increased motor activity, perceptual impairments, stereo-typical behaviors, mood alteration |
| Movement, memory, motivation, emotional response, perception Dopamine has a reverse-parallel relationship with cholinergic system (decreases in ACh are associated with increases in dopamine) | |||
| γ- Aminobutyric Acid (GABA) System | ↑ GABA activity | Hepatic failure, elevated serum ammonia levels, benzodiazepine intoxication | Hypoactive-hypoalert features |
| Major inhibitory neurotransmitter | ↓ GABA activity | Benzodiazepine, alcohol withdrawal | Hyperactive-hyperalert features |
| Serotonin System | ↓ Serotonin (5-hydroxytryptamine [5-HT]) | Reduced tryptophan (5-HT precursor) availability secondary to illness or surgery (catabolic states, stress) | Impaired memory, somnolence, hypoactive-hypoalert features |
| Modulation of pain, mood, sleep, emotion, cognition, memory, and attention; precursor of melatonin | |||
| ↑ Serotonin | Liver failure, multiple serotonin agonist use | Cognitive dysfunction, tremor, restlessness, sleep disturbance hyperactive-hyperalert features |
ASSESSMENT AND MEASUREMENT
Because of differences in presentation and fluctuation of symptoms, delirium is difficult to detect. In fact, research has shown that clinicians caring for patients do not recognize delirium in a majority of cases (Inouye et al., 2001; Laurila et al., 2004). Because diagnosis depends on recognition of a constellation of symptoms in a temporal context, systematic evaluation of vulnerable patients is warranted. Many delirium assessment scales have been developed, some intended for clinical practice and others for research (APA, 1999b). Several review articles are available to provide an overview of the variety of instruments available for detecting, diagnosing, and rating delirium (Hjermstad, Loge, & Kaasa, 2004; Schuurmans, Deschamps, Markham et al., 2003a; Smith, Breitbart, & Platt, 1995). In general, the steps to a comprehensive plan for early detection and monitoring of delirium include regular screening for the presence of cognitive dysfunction, confirmation of diagnosis, and evaluation of severity over time (Cook, 2004, Hjermstad et al., 2004, Milisen, Steeman, & Foreman, 2004; Schuurmans et al., 2003a). The following section discusses those tools most often used in clinical practice.
Screening Instruments
Screening instruments identify the presence of cognitive impairment but are not diagnostic of delirium. They are very helpful for identifying those patients who require additional evaluation. These scales may also be useful for monitoring improvement or deterioration in cognitive status in patients with delirium.
Mini-Mental State Examination
This is one of the most frequently used tools for the clinical evaluation of cognitive changes. It assesses orientation, instantaneous recall, short-term memory, attention, constructional capacities, and use of language (oral and written). A score of less than 24 of a possible 30 indicates cognitive impairment. Because the Mini-Mental State Examination is widely used in practice and research, data are available to support use of scores to rate the severity of impairment as follows: 24 to 30, no impairment; 18 to 23, mild impairment; and 0 to 17, severe impairment (Tombaugh & McIntyre, 1992).
NEECHAM Confusion Scale
This scale was designed for rapid and unobtrusive assessment and monitoring of acute confusion by the bedside nurse (Neelon, Champagne, Carlson et al., 1996). It can detect changes in mental status as well as physiological and behavioral manifestations of delirium, including those indicative of hypoactive-hypoalert delirium. A score of less than 25 of a possible 30 indicates the presence of cognitive impairment. Repeated measures can be used to monitor changes in mental status (Csokasy, 1999; Milisen et al., 1998; Rapp, 2001).
Delirium Observation Screening Scale
Like the NEECHAM, the Delirium Observation Screening Scale (DOS) was developed to assist nurses in early recognition of delirium based on observations during regular care (Schuurmans, Shortridge-Baggett, & Duursma, 2003b). The 25-item scale, based on DSM-IV criteria for delirium, assesses disturbances in consciousness; attention and concentration; thinking, memory, and orientation; psychomotor activity, sleep-wake pattern; mood; and perception. A reduced, 13-item version of the DOS shows promising results (Schuurmans, Donders, Shortridge-Baggett et al., 2002). The DOS is most applicable to inpatient versus outpatient settings since the scale needs to be administered over three consecutive shifts.
Nursing Delirium Screening Scale
The Nursing Delirium Screening Scale was developed for clinical use as a continuous delirium assessment instrument in busy inpatient units (Gaudreau, Gagnon, Harel et al., 2005). The scale contains five items (disorientation, inappropriate behavior, inappropriate communication, illusions or hallucinations, and psychomotor retardation). Each item is rated on a 0-to-2 scale on each of three shifts. Scores above 2 on any shift indicate the possibility of delirium.
Diagnostic Instruments
Diagnostic instruments are used along with the clinical and cognitive evaluation to make a formal diagnosis of delirium. The following are two examples of diagnostic tools.
Confusion Assessment Method
This valid and reliable tool was designed for efficient and effective detection of delirium (Inouye, van Dyck, Alessi et al., 1990). The four core DSM-IV criteria for delirium can be assessed by nonpsychiatric clinicians in less than 5 minutes. A version of the Confusion Assessment Method (CAM) for critical care patients (CAM-ICU) is also available (Ely et al., 2001b, 2001c). The CAM is useful to confirm delirium in patients who score less than 25 on the NEECHAM Confusion Scale or less than 24 on the Mini-Mental State Examination (Rapp, 2001).
Delirium Rating Scale–Revised-98
This scale, a delirium-specific tool, is a revision of the Delirium Rating Scale (DRS) (Trzepacz, 1999; Trzepacz et al., 2001). The DRS-R-98 contains 16 items: 3 are diagnostic in accordance with DSM-IV criteria, and 13 are severity-based on common symptoms found in delirious patients. The scale yields a total score (maximum of 46) that is diagnostic of delirium and a severity score (maximum of 39) that can be used to rate severity of symptoms over time. Higher severity scores indicate increased delirium.
Delirium Symptom Severity Rating Scales
Delirium symptom severity rating scales are designed to rate the severity of this syndrome. After delirium is diagnosed, these tools are useful for monitoring the effectiveness of interventions.
Memorial Delirium Assessment Scale
This scale was designed to quantify the severity of delirium symptoms for use in clinical intervention studies (Breitbart, Rosenfeid, Roth et al., 1997); it is also useful when assessing delirium in clinical populations (Lawlor et al., 2000). The Memorial Delirium Assessment Scale assesses arousal and level of consciousness, cognitive functioning (memory, attention, orientation, disturbances in thinking), and psychomotor activity. Completion requires about 10 minutes. Scores range from 0 to 30, with higher scores indicating more severe delirium.
Delirium Rating Scale–Revised-98
See earlier description.
Delirium Index
The Delirium Index was developed to specifically measure changes in the severity of symptoms in patients already diagnosed with delirium (McCusker, Cole, Bellavance et al., 1998; McCusker, Cole, Dendukuri et al., 2004). The measure is based on direct observation of the patient and does not rely on information from family members, other care providers, or documentation in the medical record. The Delirium Index contains seven items (each scored between 0 and 3) that yield scores between 0 and 21. Symptom domains include attention, thought, consciousness, orientation, memory, perception, and psychomotor activity. Higher scores indicate increased severity.
Objective Evaluation
Few objective measures are available to detect delirium. Of these, the electroencephalogram (EEG) is the most promising (Katz, Mossey, Sussman et al., 1991; Smith et al., 1995). EEG characteristics of delirium include a slowed rhythm, generalized theta or delta slow-wave activity, and loss of reactivity of the EEG to eye opening and closing. These are paralleled by quantitative EEG findings of increased absolute and relative slow-wave (theta and delta) power, reduced ratio of fast-to-slow band power, reduced mean frequency, and reduced occipital peak frequency. In alcohol and sedative withdrawal, EEG findings may include attenuation of voltage and prominence of beta activity (Katz, Curyto, TenHave et al., 2001). Although these EEG changes are important diagnostic signs of delirium, the absence of abnormalities does not necessarily rule out delirium (Smith et al., 1995). Given that EEG administration requires specialized expertise in obtaining and interpreting data, this evaluation may not be readily available to patients in many settings. Especially in end-of-life care, there is a limited role for the use of an EEG.
HISTORY AND PHYSICAL EXAMINATION
A thorough history and physical examination assist the clinician to identify the presence of delirium, determine potential causes of the delirium, and monitor the severity of this syndrome.
History
Review the recent history of the patient’s mental status changes, including both patient and caregiver observations:
▪ Note reported changes in arousal, level of consciousness, orientation, and cognition.
▪ Note onset of changes and any fluctuation over the course of a day, asking specifically about changes at night.
Review the medical history:
▪ Note the primary palliative or terminal diagnosis as well as coexisting medical conditions.
▪ Note diseases that directly affect the central nervous system and those associated with organ system failure.
Review medications (Boxes 24-2 and 24-3):
Box 24-3
Cimetidine
Prednisolone
Theophylline
Tricyclic antidepressants
Digoxin or lanoxin
Nifedipine
Chlorpromazine
Furosemide
Ranitidine
Isosorbide dinitrate
Warfarin
Dipyridamole
Codeine
Captopril
Data from Burns, A., Gallagley, A., & Byrne, J. (2005). Delirium. J Neurol Neurosurg Psychiatry, 75, 362-367; and Tune, L. E. (2001). Anticholinergic effects of medication in elderly patients. J Clin Psychiatry, 62(Suppl 21), 11-14.
▪ Note medications directly associated with delirium.
▪ Note medications with a potential for toxicity if given in high doses or in the presence of renal or hepatic dysfunction.
▪ Note any recently discontinued or refused medications with a potential for a withdrawal response.
Assess for a history of substance abuse.
Assess for a history of psychiatric disorders, including depression.
Assess sleeping patterns and signs of sleep deprivation.
Physical Examination
The clinician should use one of the screening tools discussed to identify patients with mental status or cognitive changes and a diagnostic tool to confirm the diagnosis of delirium. In addition, a targeted physical examination is essential for identifying the potential cause(s) of the delirium.
▪ Mental status (Box 24-4)
Box 24-4
1. Attention
Subtraction of 7s or 3s from 100
Counting from 20 backward
Reciting months of year backward
2. Orientation
Date, day of the week, time of day
Name and location of place
Identification of familiar persons
3. Memory
Ability to recall three words and three objects after 5 minutes
Digit span
Description of recent events
4. Abstract thinking
Definitions of common words
Interpretation of a simple proverb
Similarities and differences
5. Speed and dynamics of thought
Word fluency
Ask the patient to say as many single words that begin with “F” as possible within 1 minute
6. Perception
Description of the surroundings
Interpretation of photographs or pictures
Modified from Johnson, M.H. (2001). Assessing confused patients. J Neurol Neurosurg Psychiatry, 71(Suppl 1), i7-i12.
Consciousness
Cognition
▪ General survey
Vital signs, especially fever and hyperpnea
Skin color, especially pallor, cyanosis, jaundice
Skin turgor
Pruritus
▪ Respiratory system
Dyspnea or hypoxia
Cough or congestion
▪ Gastrointestinal system
Pain or discomfort
Bowel patterns, including signs of constipation or obstruction
Nausea and vomiting
Pain or discomfort
Urinary output
Signs of retention or obstruction
▪ Musculoskeletal system
Pain or discomfort
Weakness or agitation
Environmental and Psychoemotional Assessment
The following assessment variables are best evaluated by an interdisciplinary team approach involving the advanced practice nurse (APN), social worker, and spiritual counselor. The family’s observations are very important when assessing the cause of delirium and should be included in a complete assessment of the following variables:
▪ Signs of anxiety, fear, or guilt
▪ Potential of “unfinished business”—interpersonal, financial, or spiritual
▪ Depression (see Chapter 25)
▪ Signs of spiritual distress
▪ Potential for sensory overload or sensory deprivation
DIAGNOSTICS
The following diagnostic tests assist in identifying an underlying medical cause of delirium. The extent to which any diagnostic work-up is conducted is dependent on the treatment goals and wishes of the patient and family and as well as the status of the patient’s disease trajectory. As patients approach end-of-life, tests are appropriate only when they directly influence the treatment plan. For example, laboratory work to confirm hypercalcemia is necessary only if the patient’s quality of living will be enhanced by treating the hypercalcemia and if the diagnosis cannot be made on the basis of the underlying medical diagnosis and associated symptoms. Tests include the following:
Basic
▪ Complete blood count
▪ Blood chemistry (electrolytes, glucose, calcium, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase)
▪ Blood gases or oxygen saturation
▪ Blood, urine, or other cultures
▪ Serum drug levels (digoxin, theophylline, cyclosporine)
▪ Urine drug screen
Additional tests—as indicated by patient prognosis and clinical condition
▪ EEG
▪ Brain imaging to assess for acute or subacute structural pathology
INTERVENTION AND TREATMENT
It may be possible to reverse delirium even in advanced illness, with the exception of possibly the last 24 to 48 hours of life (Breitbart & Cohen, 2000; Casarett et al., 2001). When the potential cause of delirium is identified and it is consistent with patient and family treatment goals, the focus of intervention is on reversal of the delirium. When the cause of delirium cannot be identified or cannot be reversed, the focus of care is on comfort. Given the distressing nature of symptoms for both the patient and family, adequate management of symptoms in either case is paramount.
Manage the Underlying Causes of Delirium
▪ Treat increased intracranial pressure—dexamethasone, 16 to 40 mg/day orally, in the morning (Maity, Pruitt, Judy et al., 2004).
▪ Treat hypoxia: oxygen therapy.
▪ Treat infection: appropriate antiinfective agents.
▪ Correct metabolic abnormalities, as appropriate.
Hypercalcemia
Mild: hydrate by using oral, parenteral, or subcutaneous fluids (hypodermoclysis).
Moderate or severe: consider administering a bisphosphonate (e.g., pamidronate disodium) if it will improve the quality of living.
Hyponatremia due to syndrome of inappropriate antidiuretic hormone
Mild: encourage moderate alcohol intake (e.g., glass of sherry before meals) and dietary sodium intake (Waller & Caroline, 2000).
Moderate: demeclocycline, 300 mg orally twice daily (Waller & Caroline, 2000); fluid restriction is often not an issue in palliative care, but consider restricting to 1 L/day.
Severe: unless chronic hyponatremia is symptomatic, infusion of hypertonic saline is not warranted. The patient with acute, symptomatic hyponatremia is at risk for the development of cerebral edema, cerebral herniation, and death. Depending on the patient’s disease trajectory and patient and family goals for care, admission to an acute care facility for infusion therapy and monitoring may be appropriate (Smith, McKenna, & Thompson, 2000).
▪ Treat physical discomforts (e.g., constipation, dyspnea, pain, and pruritus).
▪ Address psychoemotional discomforts (e.g., anxiety, depression, and spiritual distress).
Be aware that patients with major depression are at greater risk of suicide when experiencing delirium (Waller & Caroline, 2000).
▪ Treat dehydration, as appropriate (see Chapter 23).
▪ Modify medication regimen.
Limit the use of anticholinergic drugs or decrease the number of drugs with anticholinergic properties (Box 24-2).
If accumulation of opioid metabolites is suspected, consider opioid rotation and hydration.
Be careful not to stop benzodiazepines abruptly.
Taper corticosteroids to lowest effective dose (do not discontinue abruptly).
▪ Treat withdrawal syndrome: resume the responsible drug and then taper slowly.
Nonpharmacological Treatment
Nonpharmacological strategies that may be instituted by the clinician are based on known risk factors for delirium (Inouye, Bogardus, Charpentier et al., 1999; Inouye, Bogardus, Williams et al., 2003; Lundstrom, Edlund, Karlsson et al., 2005; Weber, Coverdale, & Kunik, 2004). These interventions can be initiated in any setting and are particularly valuable in allowing families to take an active role in maintaining patient comfort (Casarett et al., 2001).
▪ Provide orientation clues.
Orient frequently to time and place.
Encourage familiar persons to be present and keep familiar objects close by.
Keep a calendar and clock visible; open shades during the day and darken the room at night but use a night-light.
Provide cognitively stimulating activity several times a day (discuss current events, structured reminiscence).
If the patient is experiencing illusions or hallucinations, gently correct misconceptions while reassuring the patient that he or she is safe.
▪ Use strategies to promote sleep and rest (see Chapter 8).
▪ Avoid too little or too much environmental stimulation.
Encourage use of patient’s visual and hearing aids.
Keep a calm environment (noise reduction).
Provide adequate lighting during the day and only minimal lighting at night.
▪ Reduce immobility.
Avoid use of restraints. Keep the patient safe through supervision.
Provide for mobility during the day (ambulation, time out of bed, or, for critically ill patients—range of motion).
Pharmacological Management
Antipsychotic Agents
▪ First line (except in cases of alcohol or benzodiazepine withdrawal)—haloperidol as follows (Cook, 2004; Kuebler, Varga, & Davis, 2005; Michaud, Burnand, & Stiefel, 2004):
Mild symptoms: 0.5 to 5 mg orally twice or three times daily.
Moderate to severe symptoms (especially severe agitation): 0.5 to 5 mg intravenously or subcutaneously; repeat every 1 to 4 hours until symptoms are controlled, using the more frequent interval for most severe agitation. When calmed, the patient can be maintained with oral or subcutaneous doses. Doses generally do not exceed 20 mg per 24 hours.
▪ Second line: atypical agents as follows (Schwartz & Masand, 2002):
Olanzapine 2.5 to 5 mg orally at bedtime. May be increased to 20 mg/day if symptoms persist.
Rispiradone 0.25 to 0.5 mg orally twice daily. May be increased to 4 mg/day if symptoms persist (0.25 to 0.5 mg orally every 4 hours).
Quetiapine 25 to 50 mg orally twice daily. May be titrated up every 1 to 2 days to 100 mg orally twice daily. For agitation or refractory symptoms, 25 to 50 mg orally every 4 hours may be given.
These agents (especially quetiapine) should be considered first line in delirious patients with dopamine deficiency: Lewy body dementia, Parkinson’s disease, and other movement disorders (Samuels & Neugroschl, 2005).
Benzodiazepines
▪ Benzodiazepines used as an adjunct to antipsychotics:
The use of benzodiazepines for treatment of delirium is controversial. The general consensus is that they should be avoided with the exception of delirium due to alcohol or sedative withdrawal or in presence of seizures (Cook, 2004; Meagher, 2001). However, in cases where symptoms, particularly agitation, are refractive to neuroleptic therapy, judicious addition of a short-acting benzodiazepine to therapy is warranted.
Lorazepam (1 to 2 mg intravenously or subcutaneously every 1 to 4 hours) is the drug of choice due to its short half-life and lack of active metabolites (APA, 1999b).
▪ Benzodiazepines used for delirium associated with withdrawal:
In palliative care populations, short-acting agents are preferred (Mayo-Smith, Beecher, Fischer et al., 2004).
Lorazepam, 1 to 4 mg intravenously every 5 to 15 minutes, or lorazepam, 1 to 4 mg intramuscularly every 30 to 60 minutes, until calm, and then every hour can be used as needed to control agitation.
Once symptoms are controlled, maintain lorazepam at 1 to 2 mg orally twice to four times daily until delirium clears. Be aware that symptoms may persist for 6 to 12 months after the withdrawal of alcohol (Mayo-Smith et al., 2004).
Terminal Sedation
Sedation may be required for agitation unresponsive to the preceding interventions (Vena, Kuebler, & Schrader, 2005). Depending on the severity and response of the patient to treatment, therapy may be intermittent or continuous.
▪ Intermittent: chlorpromazine suppository, 12.5 to 50 mg orally, per rectum, intramuscularly, or intravenously, every 4 to 12 hours. Titrate to 600 mg/day as necessary. This phenothiazine neuroleptic may assist in clearing the sensorium and is very sedating. One advantage of chlorpromazine is its ease of administration in the home care environment.
▪ Continuous
Midazolam intravenously or subcutaneously, initial bolus of 0.5 to 2 mg, followed by 0.5 to 6 mg/hr. Titrate to 15 to 20 mg/hr.
Phenobarbital intravenously or subcutaneously, initial bolus of 100 to 200 mg, followed by 600 to 1200 mg/day with a maximum dosage of 2500 mg/day. Consider the drug’s long half-life, interindividual variability in pharmacokinetics, and high potential for drug interaction when prescribing and titrating (Cheng, Roemer-Becuwe, & Pereira, 2002; Stirling, Kurowska, & Tookman, 1999). Monitor carefully for respiratory depression.
Propofol intravenously, 2.5 to 5 mcg/kg/min (approximately 10 mg/hr). Titrate to effect by increments of 10 mg every 10 to 20 minutes. Maximum dosage is 200 mg/hr. Propofol should not be infused for longer than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc loss.
PATIENT AND FAMILY EDUCATION
The experience of delirium is frightening to both the patient and the family. Both need reassurance that the delirium may be reversible and that the symptoms can be managed. Because caregiving itself is stressful, information may need to be given in small doses and at repeated intervals.
Several examples of educational handouts are readily available for those caregivers who might benefit from written information (APA, 1999a; Gagnon et al., 2002; Torpy, Lynm, & Glass, 2004).
Explain the causes of delirium and the interventions being initiated to reverse it.
▪ Teach the family the following interventions.
Report changes in the patient’s mental status or complaints of feeling confused or unable to concentrate.
Gently correct patient illusions or hallucinations and reassure that the environment is safe (e.g., there are no spiders on the walls).
Provide orientation clues.
Refer to the time of day often (e.g., “It looks like we’re going to have a lovely fall day”).
Keep the environment familiar. If the patient is unable to be at home, take familiar objects to the inpatient facility.
Have familiar persons at the bedside.
Have a visible clock and calendar and mark off days on the calendar.
▪ Keep a calm, yet pleasantly stimulating environment:
Provide calm music that is pleasing to the patient.
Use soft lighting. Provide daily sunlight exposure when possible.
Minimize disturbances.
Encourage people to talk with the patient.
▪ Teach appropriate administration of all medications (e.g., neuroleptics, benzodiazepines, or barbiturates for delirium symptoms).
▪ Teach the importance of maintaining the pain regimen even if the patient is not able to ask for medications or to communicate pain.
If sedation is required to manage the patient’s agitation, discuss the pros and cons of this intervention with the family. In the presence of terminal agitation, the time before sedation may be the last time the family sees the patient awake. Encourage the family to say their good-byes and to address unfinished business while the patient can potentially respond. Reinforce with the family that the patient can likely hear even when sedated and that it is important to continue to share supportive thoughts and feelings and to share good-byes even when the patient cannot respond.
EVALUATION AND PLAN FOR FOLLOW-UP
Patient status is monitored for improvement or decline in the symptoms of delirium. One of the delirium severity rating scales will be helpful for assessing and documenting these changes. When delirium cannot be reversed, the goal is comfort. The patient is monitored to ensure that distressing symptoms, such as illusions, hallucinations, restlessness, and agitation, are optimally managed.
After the treatment of delirium related to medication side effects, the clinician needs to use caution in the selection of medications for control of other symptoms that may emerge over time. The offending class of medication should not be used in the future, if possible. If that class of medication is required for comfort, the medication should be started at a low dose and the patient monitored frequently for early signs of delirium.
Mr. J. is a 69-year-old man with renal cell cancer status post right nephrectomy and radiotherapy. Two years after initial treatment, metastatic lesions were found in his right lung, right pelvis, and femur. He completed radiotherapy for the bone metastases but was not considered a candidate for biologic therapy. He has elected palliative care at home under the direction of a home care hospice team. He is cared for at home by his daughter. Mr. J.’s main problems include pain and occasional anxiety. His current medications include sustained-release morphine 60 mg twice daily with immediate-release morphine 15 mg orally for breakthrough pain; ibuprofen 400 mg orally four times daily, Senokot-S 2 tablets twice daily, and lorazepam 0.5 mg orally as needed.
During the regular interdisciplinary team conference, Mr. J.’s nurse reports that he has become increasingly withdrawn over the past 3 days and is sleeping most of the time. Mr. J. was responsive to verbal stimuli, able to take fluids and oral medications, and did not appear to be in discomfort. However, the presence of noisy, rattling respirations was distressing to his daughter. Because the nurse considered the patient to be near death, hyoscyamine (Levsin) 0.125 mg was ordered sublingually every 4 hours to control excessive secretions. The following morning, Mr. J.’s daughter calls the hospice distraught over her father’s poor night. She reports that he has been constantly trying to get out of the bed, talking incoherently and, contrary to his usual demeanor, is aggressive and belligerent. She reports administering lorazepam three times during the night without any calming effect.
The team’s clinician makes a visit to assess the situation. Upon arrival at the home, Mr. J. is resting quietly in the bed. His daughter is fatigued and frustrated. “I can’t believe he is so quiet now. Last night was a nightmare.” Upon assessment, the clinician finds that Mr. J. is lethargic but responds to verbal stimuli. He tends to “fall asleep” during her questions. His Mini-Mental State Examination score is 10/30. His skin is hot and dry, with poor skin turgor. His oral mucosa is dry and crusted with purulent sputum. His daughter reports that he “caught a cold” a few days ago, apparently from his grandson, who visited last week. His symptoms included a sore throat, nasal congestion, productive cough (yellow-green sputum), upper chest discomfort, general malaise, and mild shortness of breath. Mr. J.’s oral temperature is 101.4° F, blood pressure 130/84 mm Hg, pulse 104, and respirations 24. His pulse oximetry reading is 91%. Auscultation of the lungs reveals upper airway congestion, but bases are clear. His abdomen is soft, and bowel sounds are hypoactive. The daughter reports that he had a bowel movement yesterday. He is voiding without difficulty, but fluid intake has been low in the last 2 days, and his urine is dark amber.
The clinician concludes that Mr. J.’s clinical picture and symptom presentation indicate delirium. Mr. J.’s underlying vulnerability for development of delirium include his age and advanced metastatic disease. In this case, the clinician believes that the acute onset of bronchitis, dehydration, and the addition of an anticholinergic medication were precipitating factors. The clinician discusses treatment options with the daughter, including the possibility that this episode of delirium could possibly be reversed with treatment of the bronchitis, hydration, and change in medications. In the event that the decision is made not to treat the bronchitis or the treatment is not effective, measures are available to control the agitation. Mr. J.’s daughter elects a treatment plan that will seek to correct the underlying causes. The plan includes the following:
Bronchitis: azithromycin 500 mg orally ASAP followed by 250 mg orally for 4 days; acetaminophen 650 mg orally every 4 hours as needed for fever; guiafenesin 200 mg orally every 4 hours while awake, once able to take oral fluids.
Dehydration: 1000 ml of 5% dextrose in normal saline subcutaneously over next 24 hours as tolerated. Increase oral hydration to at least 1.5 liters per day as sensorium improves.
Delirium: Discontinue hyoscyamine and lorazepam. Begin haloperidol 0.5 mg orally three times daily. Call if patient exhibits agitation or restlessness.
The following afternoon, the clinician returns to reassess Mr. J. His daughter reports that he slept peacefully during the night. Mr. J. is lethargic but less somnolent; his Mini-Mental State Examination score is 23/30. He is afebrile and skin turgor has improved. He has a congested cough but is able to clear his airway. Sputum remains purulent. He is taking fluids well by mouth, and his urine is clear yellow. He denies having pain.
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