Delirium, defined as an acute disorder of attention and global cognitive function, is a common, serious, and potentially preventable source of morbidity and mortality for hospitalized older persons. It occurs in 14% to 56% of such persons and represents the most frequent complication of hospitalization for this group. With the aging of the U.S. population, delirium has assumed heightened importance because persons aged 65 years and older presently account for more than 49% of all days of hospital care. Delirium complicates hospital stays for at least 20% of the 12.5 million patients 65 years of age or older who are hospitalized each year and increases hospital costs by $2500 per patient, so that $6.9 billion (in 2004 U.S. dollars) of Medicare hospital expenditures are attributable to delirium. Importantly, substantial additional costs linked to delirium accrue after hospital discharge because of the increased need for institutionalization, rehabilitation services, closer medical follow-up, and home health care. Delirium often initiates a cascade of events in older persons, leading to a downward spiral of functional decline, loss of independence, institutionalization, and ultimately, death. These statistics highlight the importance of delirium from both clinical and health policy perspectives. In fact, a recent consensus panel identified delirium as among the top three target conditions for quality-of-care improvement for vulnerable older adults. With its common occurrence, its frequently iatrogenic nature, and its close linkage to the processes of care, incident delirium can serve as a marker for the quality of hospital care and provides an opportunity for quality improvement.

The definition of and diagnostic criteria for delirium continue to evolve (Table 53-1). The standardized criteria for delirium that appear in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) remain the current diagnostic standard. Expert consensus was used to develop these criteria, however, and performance characteristics such as diagnostic sensitivity and specificity have not been reported for DSM-IV criteria. A standardized tool, the Confusion Assessment Method (CAM), provides a brief, validated diagnostic algorithm that is currently in widespread use for identification of delirium. The CAM algorithm relies on the presence of acute onset and fluctuating course, inattention, and either disorganized thinking or altered level of consciousness. The algorithm has a sensitivity of 94% to 100%, specificity of 90% to 95%, and high interrater reliability. Given the uncertainty of diagnostic criteria for delirium, a critical area for future investigation is to establish more definitive criteria, including epidemiologic and phenomenologic evaluations assisted by advances in functional neuroimaging and other potential diagnostic marker tests.

Most of the epidemiological studies of delirium involved hospitalized older patients, in whom the highest rates of delirium occur. Reported rates vary based upon the subgroup of patients studied and the setting of care (e.g., hospital, intensive care, surgical). Previous studies estimated the prevalence of delirium (present at the time of hospital admission) at 14% to 24% and the incidence of delirium (new cases arising during hospitalization) at 6% to 56%. The rates of delirium in high-risk hospital venues, such as the intensive care unit and posthip fracture settings, range from 70% to 87% and 15% to 53%, respectively. Delirium occurs in up to 60% of patients in nursing homes or postacute settings, and in up to 83% of all patients at the end of life. The rates of delirium in all older persons presenting to the emergency department in several studies have ranged from 10% to 30%. While less frequent in the community setting, delirium is an important presenting symptom to emergency departments and community physicians, and often heralds serious underlying disease. Delirium is often unrecognized; previous studies have documented that clinicians fail to detect up to 70% of affected patients across all of these settings. Furthermore, the presence of delirium portends a potentially poor prognosis; hospital mortality rates in patients with delirium range from 22% to 76%, as high as mortality rates associated with acute myocardial infarction or sepsis. Following hospitalization, the one-year mortality rate associated with cases of delirium is 35% to 40%.

The etiology of delirium is usually multifactorial, like many other common geriatric syndromes, such as falls, incontinence, and pressure sores. Although there may be a single cause of delirium, more commonly, delirium results from the interrelationship between patient vulnerability (i.e., predisposing factors) and the occurrence of noxious insults (i.e., precipitating factors). For example, patients who are highly vulnerable to delirium at baseline (e.g., such as patients with dementia or serious illness) can experience acute delirium after exposure to otherwise mild insults, such as a single dose of a sedative medication for sleep. On the other hand, older patients with few predisposing factors (low baseline vulnerability) would be relatively resistant, with precipitation of delirium only after exposure to multiple potentially detrimental insults, such as general anesthesia, major surgery, multiple psychoactive medications, immobilization, and infection (Figure 53-1). Moreover, based on predictive models of delirium, the effects of multiple risk factors appear to be cumulative. Clinically, the overall importance of the multifactorial nature of delirium is that removal or treatment of one risk factor alone often fails to resolve delirium. Instead, addressing many or all of the predisposing and precipitating factors for delirium is often required before the delirium improves.

Predisposing Factors

Predisposing factors for delirium include preexisting cognitive impairment or dementia, advanced age, severe underlying illness and comorbidity, functional impairment, male gender, depression, chronic renal insufficiency, dehydration, malnutrition, alcohol abuse, and sensory impairments (vision or hearing) (Table 53-2). Preexisting cognitive impairment, or dementia, is a powerful and consistent risk factor for delirium demonstrated across multiple studies, and patients with dementia have a two- to fivefold increased risk for delirium. Moreover, up to half of delirious patients have an underlying dementia. Nearly any chronic medical condition can predispose to delirium, ranging from diseases involving the central nervous system (e.g. Parkinson’s disease, cerebrovascular disease, mass lesions, trauma, infection, collagen vascular disease), to diseases outside the central nervous system, including infectious, metabolic, cardiac, pulmonary, endocrine, or neoplastic etiologies. Independent predisposing risk factors for delirium at the time of hospital admission validated in a predictive model include severe underlying illness, vision impairment, baseline cognitive impairment, and high blood urea nitrogen (BUN):creatinine ratio (used as an index of dehydration). Predictive risk models that identify predisposing factors in populations such as surgical patients, cancer patients, and nursing home residents, have recently been developed and aid in the understanding of baseline patient characteristics contributing to delirium risk.

Precipitating Factors

Major precipitating factors identified in previous studies include medication use (see section on “Drug Use and Delirium”), immobilization, use of indwelling bladder catheters, use of physical restraints, dehydration, malnutrition, iatrogenic events, medical illnesses, infections, metabolic derangement, alcohol or drug intoxication or withdrawal, environmental influences, and psychosocial factors (see Table 53-2). Decreased mobility is strongly associated with delirium and concomitant functional decline. The use of medical equipment and devices (e.g., indwelling bladder catheters and physical restraints) may further contribute to immobilization. Major iatrogenic events occur in 29% to 38% of older hospitalized adults (three to five times the risk when compared with adults younger than 65 years old). Examples include complications related to diagnostic or therapeutic procedures, allergic reactions, and bleeding caused by over anticoagulation. Many of these events potentially are preventable. Disorders of any major organ system, particularly renal or hepatic failure, can precipitate delirium. Occult respiratory failure has emerged as an increasing problem in elderly patients, who often lack the typical signs and symptoms of dyspnea and tachypnea. In older adults, acute myocardial infarction and congestive heart failure may present with delirium or “failure to thrive” as the cardinal feature, and minimal or none of the usual symptoms of angina or dyspnea. Occult infection, caused by pneumonia, urinary tract infection, endocarditis, abdominal abscess, or infected joint, is a particularly noteworthy cause of delirium because older patients may not present with leukocytosis or a typical febrile response. Metabolic and endocrinologic disorders, such as hyper- or hyponatremia, hypercalcemia, acid–base disorders, hypo- and hyperglycemia, and thyroid or adrenal disorders, may also contribute to delirium. The precipitating factors for delirium in hospitalized older patients that have been validated in a predictive model include use of physical restraints, malnutrition, more than three medications added during the previous day (more than 70% of these were psychoactive drugs), indwelling bladder catheter, and any iatrogenic event. The presence of these independent factors contributes to delirium risk in a predictable and cumulative manner, yet each risk factor is potentially modifiable.

Drug Use and Delirium

In 40% or more of delirium cases, use of one or more specific medication contributes to its development. While medications often incite delirium, they are also the most common remediable cause of delirium. A broad array of medications and their metabolites can lead to delirium; the most common are those with known psychoactive effects, such as sedative hypnotics, anxiolytics, narcotics, H2-blockers, and medications with anticholinergic activity (Table 53-3). In previous studies, use of any psychoactive medication was associated with a fourfold increased risk of delirium, while use of two or more psychoactive medications was associated with a fivefold increased risk. Sedative–hypnotic drugs are associated with a 3- to 12-fold increased risk of delirium; narcotics with a threefold risk; and anticholinergic drugs with a 5- to 12-fold risk. The incidence of delirium, similar to other adverse drug events, increases in direct proportion to the number of medications prescribed, because of the effects of the medications themselves, as well as to the increased risk of drug–drug and drug–disease interactions. Recent studies provide compelling evidence that suboptimal medication management, ranging from inappropriate use to overuse of psychoactive medications, occurs commonly in older adults in the hospital and in community settings, and suggests that many cases of delirium and other related adverse drug events may be preventable. As the number of prescription and over-the-counter drugs consumed by the older population increases, review of potentially problematic medications will remain an important step in the search for predisposing factors in the patient with delirium.

Relationship between Delirium and Dementia

While delirium and dementia are highly interrelated, the nature of their relationship remains poorly examined. The contribution of delirium itself to permanent cognitive impairment or dementia remains controversial; however, previous studies document that at least some patients postdelirium never recover their baseline level of cognitive function. Thus, delirium and dementia may represent two ends along a spectrum of cognitive impairment with “chronic delirium” and “reversible dementia” falling along this continuum. Dementia is the leading risk factor for delirium, and fully two-thirds of cases of delirium occur in patients with dementia. Moreover, studies have shown that delirium and dementia are both associated with decreased cerebral metabolism, cholinergic deficiency, and inflammation, reflecting their overlapping clinical, metabolic, and cellular mechanisms. Delirium can alter the course of an underlying dementia, with dramatic worsening of the trajectory of cognitive decline, resulting in more rapid progression of functional losses and worse long-term outcomes. In follow-up studies, patients with dementia in whom delirium develops have worse outcomes than those with dementia alone, including worsened cognitive function and increased rates of hospitalization, institutionalization, and death.

The fundamental pathophysiological mechanisms of delirium remain unclear. Delirium is thought to represent a functional rather than structural lesion, with characteristic electroencephalographic (EEG) findings demonstrating global functional derangements and generalized slowing of cortical background (alpha) activity. The leading current hypotheses view delirium as the final common pathway of many different pathogenic mechanisms, resulting from dysfunction of multiple brain regions and neurotransmitter systems. Evidence from EEG, evoked-potential studies, and neuroimaging studies suggest predominantly right-sided abnormalities in delirium localized to the prefrontal cortex, thalamus, basal ganglia, temporoparietal cortex, fusiform, and lingual gyri. Studies using x-ray computed tomography (CT) or magnetic resonance imaging (MRI) have found lesions or structural abnormalities in the brains of patients with delirium. Several studies of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) found that delirium is mostly associated with decreased blood flow. However, results from previous studies have been highly variable. Associated neurotransmitter abnormalities involve elevated brain dopaminergic function, reduced cholinergic function, or a relative imbalance of these systems. Serotonergic activity may interact to regulate or alter activity of these other two systems, and serotonin levels may be either increased or decreased. Extensive evidence supports the role of cholinergic deficiency. Acetylcholine plays a key role in consciousness and attentional process. Given that delirium is manifested by an acute confusional state often with alterations of consciousness, it is likely to have a cholinergic basis. Anticholinergic drugs can induce delirium in humans and animals, and serum anticholinergic activity is increased in patients with delirium. Physostigmine reverses delirium associated with anticholinergic drugs, and cholinesterase inhibitors appear to have some benefit even in cases of delirium that are not induced by drugs. The stress response associated with severe medical illness or surgery involves sympathetic and immune system activation, including increased activity of the hypothalamic–pituitary–adrenal axis with hypercortisolism, release of cerebral cytokines that alter neurotransmitter systems, alterations in the thyroid axis, and modification of blood–brain barrier permeability. Age-related changes in central neurotransmission, stress management, hormonal regulation, and immune response may contribute to the increased vulnerability of older persons to delirium. The description of delirium as “acute brain failure”—involving multiple neural circuits, neurotransmitters, and brain regions—suggests that understanding delirium may help to elucidate the essential underlying mechanisms of brain functioning.

Cardinal Features

Acute onset and inattention are the central features of delirium. Determining the acuity of onset requires accurate knowledge of the patient’s prior cognitive status. Pinpointing the origin and time course of changes in mental status often entails obtaining historical information from another close observer, such as a family member, caregiver, or nurse. Typically with delirium, the mental status changes occur over hours to days, in contrast to the changes that occur with dementia, which present insidiously over weeks to months. Another key feature is the fluctuating course of delirium, with symptoms tending to wax and wane in severity over a 24-hour period. Lucid intervals are characteristic, and the reversibility of symptoms within a short time can deceive even an experienced clinician. Inattention is manifested as difficulty focusing, maintaining, and shifting attention or concentration. With simple cognitive assessment, patients may display difficulty with straightforward repetition tasks, digit spans, or recitation of the months of the year backward. Delirious patients appear easily distracted, experience difficulty with multistep commands, cannot follow the flow of a conversation, and often perseverate with an answer to a previous question. Additional major features include a disorganization of thought and altered level of consciousness. Disorganized thoughts are a manifestation of underlying cognitive or perceptual disturbances, and can be recognized by disjointed and incoherent speech, or an unclear or illogical progression of ideas. Clouding of consciousness is typically manifested by lethargy, with a reduced awareness of the environment that may show diurnal variation. Although not cardinal elements, other frequently associated features include disorientation (more commonly to time and place than to self), cognitive impairments (e.g., memory and problem-solving deficits, dysnomia), psychomotor agitation or retardation, perceptual disturbances (e.g., hallucinations, misperceptions, illusions), paranoid delusions, emotional lability, and sleep–wake cycle disruption.

Tools for Evaluation of Delirium

Table 53-4

Related posts:

Community-Based Long-Term Care and Home Care Inflammation and Aging Malnutrition and Enteral/Parenteral Alimentation Management of Agitation in Dementia Non-Hodgkin’s and Hodgkin’s Lymphomas and Myeloma Upper Gastrointestinal Disorders

Stay updated, free articles. Join our Telegram channel

Join