Definition and Epidemiology

Delirium is a serious and significant health problem for older adults and others and one that requires prompt recognition and treatment. Delirium is often the first and only indicator in older adults of underlying physical illness, such as infection, myocardial infarction, or drug toxicity, and it is the leading complication of hospitalization for older adults. Delirium persists in up to 25% of patients and is associated with worse clinical outcomes including higher in-hospital and postdischarge mortality, longer lengths of stay, greater probability of placement in a nursing facility, and the possibility of permanent cognitive impairment.¹

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), delirium can develop from a general medical condition, substance intoxication or withdrawal, medications, or multiple causes (Box 192-1).² It is characterized by a disturbance in attention, consciousness, and cognition. The hallmark of delirium is a clouding of consciousness, with an inability to focus, sustain, or shift attention, as well as a change in cognition, including impairment in short-term memory, disorientation, and perceptual disturbances.² This syndrome can occur in elders at any point across the care continuum, from community and long-term care to acute care settings. Once thought to be transient, delirium symptoms can last weeks to months. Persistent delirium has been associated with worse long-term cognitive and functional outcomes than delirium that has resolved.³

The incidence estimates for delirium in hospitalized patients range widely, from 11% to 82%, because of both sampling and diagnostic criteria.¹ Patients who have undergone hip fracture repair are particularly prone to delirium, with incidence rates ranging from 35% to 65%.⁴ Delirium has also been described in patients at the end of life, particularly in patients with advanced cancer, and is very common in intensive care unit (ICU) patients. Delirium is also a common problem in long-term and subacute settings. It has been suggested that many patients who become delirious are never recognized as such and may be incorrectly labeled as having dementia, a psychiatric disorder, or unmanageable behavior.¹ Patients with an underlying dementia are at even greater risk for development of delirium in the setting of acute illness, which is known as delirium superimposed on dementia (DSD).⁵

The prevalence of DSD ranges from 22% to 89% in hospitalized individuals 65 years and older and warrants careful monitoring of patients at risk who enter the health care setting with an acute problem.⁵ Eight percent to 17% of all older adults seen in the emergency room are delirious. This number rises to 40% for nursing home residents who come to the emergency room.¹

Physician consultation is indicated for patients with delirium.

Pathophysiology

The exact cause of delirium remains a topic of disagreement. Several mechanisms have been proposed that might explain the physiologic precipitant underlying the development of delirium^6–8: (1) an insufficiency of cerebral metabolism as demonstrated by diffuse slowing on an electroencephalogram in a patient with delirium; (2) a central abnormality caused by an imbalance of central cholinergic and adrenergic metabolism; (3) the activation of cytokines; (4) a stress reaction as evidenced by abnormally high circulating corticosteroid levels and an abnormality in brain network connectivity and changes in inhibitory tone. All of these can contribute to the disruption of neurotransmission.

Despite the continuing disagreement as to the exact mechanism, the acetylcholine theory has drawn more attention of late. Patients with Alzheimer dementia have decreased acetylcholine because of loss of cholinergic neurons and are at high risk of delirium. Anticholinergic drugs are known to precipitate delirium, and certain metabolic abnormalities may decrease acetylcholine synthesis in the central nervous system and contribute to the development of delirium. There is also some evidence that even drugs used commonly in the elderly, such as digoxin, furosemide, prednisone, and theophylline, may have anticholinergic activity.⁹ Increased levels of anticholinergic activity have been shown to correlate with the severity of delirium in some hospitalized elderly patients.

It is likely that several physiologic, psychological, and environmental variables, in combination with the known effects of the normal aging process, contribute to the development of delirium.

Clinical Presentation

Delirium occurs acutely during hours to days and is characterized by fluctuations in mental status during the course of the day. This fluctuating presentation is problematic because patients may have periods of lucidity interspersed with inattention and high distractibility, motor restlessness, speech that is difficult to follow, and perceptual disturbances that range from misinterpretations of the environment to frank visual halluci­nations. Memory, particularly in relation to recent events, is often impaired, and disorientation, most commonly to time (day of the week or time of the year) or place, is usually present. Patients may also exhibit affective signs of fear, anxiety, or anger. They may have a history of a fragmented and disordered sleep-wake cycle. Symptoms may be worse in the late afternoon or evening, which is labeled sundowning; however, it is not clear whether sundowning is a component of delirium or a separate clinical condition.¹⁰ Patients with a history of dementia are at greatest risk for sundowning.

Clinical subtypes of delirium that have been identified include hyperactive, hypoactive, and mixed variants.¹¹ The hyperactive subtype, manifesting with agitation and restlessness, is often thought of as the typical presentation of delirium. Surprisingly, these cases account for less than 25% of all cases but have the worst outcomes, including nursing home placement or death within 1 month.¹² The hypoactive subtype includes patients who have decreased alertness, sparse or slow speech, lethargy, slowed movements, and apathy. These patients may be somnolent or stuporous. Because these patients are quiet and do not present increased demands for care or surveillance from family or nursing staff, the chance that these patients will not be identified as delirious is high. However, in one study of hip fracture patients that looked at both delirium severity and psychomotor types, patients with pure hypoactive delirium had better outcomes than did patients with hyperactive delirium, even after adjustment for severity.¹² The mixed variant subtype includes symptoms of both hyperactive and hypoactive delirium, with patients cycling between the two; this accounts for more than 50% of cases. These patients often are not identified as being delirious until they become agitated and confused with more symptoms of the hyperactive state.

Because the diagnosis of delirium is based on history, physical examination, or laboratory evidence of an underlying medical condition, careful attention to other symptoms and conditions is necessary. A careful history from family or caregivers is imperative, especially in community-dwelling older adults.

In long-term care, the nursing staff can provide invaluable information as to subtle changes in behavior, appetite, or functional status that may be the warning signs of an underlying problem. Urinary tract infection and pneumonia in the frail nursing home patient often manifest with an altered mental status as the only indicator of an underlying problem.

Polypharmacy and biologic vulnerability for adverse effects make the older person more prone to medication-induced delirium, and a thorough review of all medications, including prescription and over-the-counter preparations, is an essential part of the assessment process.¹³ Anticholinergic medications have long been implicated as a risk factor for delirium, and although research results have been mixed as to the strength of the association and the relationship to severity of symptoms, these medications need to be discontinued whenever possible.¹⁴ The patient’s use of alcohol and other substances also needs to be evaluated and validated with family members when possible.

It is also important to assess psychosocial and sociocultural factors to better understand the patient’s baseline personality and psychological functioning. For patients admitted to the hospital, information from family members or long-term care facilities can be critical in understanding premorbid behavior and function.