Delirium and Changes in Mental Status

Definition

Delirium is a clinical syndrome (see Table 361-3 ) that is characterized as an acute disorder of attention and cognitive function. Delirium is the most frequent complication of hospitalization for elders, is a potentially devastating problem at any age, and is often unrecognized despite sensitive methods for its detection. The Confusion Assessment Method and abbreviated versions of it (see Fig. 361-1 ) can provide quick, simple, operationalized diagnostic approaches for delirium. The Confusion Assessment Method algorithm has a sensitivity of 94%, a specificity of above 85%, and high interrater reliability. Complications of delirium may be preventable, so rapid and accurate diagnosis is critical.

Epidemiology

The prevalence of delirium varies widely by settings and age. For older adults in a general medical setting, the prevalence of delirium is estimated to be 23%, with higher rates when frequent surveillance is performed in older, surgical, and intensive care populations. For example, delirium occurs in 8 to 58% of postoperative patients, 50 to 70% of mechanically ventilated patients, and up to 82% of patients in medical intensive care units. Delirium is also noted in up to 38% of nursing home patients and in up to 88% of patients at the end of life.

The problem of delirium in hospitalized elderly patients has assumed particular prominence because patients aged 65 years and older currently account for more than 50% of all inpatient days of hospital care. Based on U.S. vital health statistics, delirium complicates hospital stays for at least 2.6 million adults age 65 and older and accounts for more than $164 billion in health care expenditures annually. For postoperative delirium, the estimated costs are $33 billion in the United States annually. Thus, delirium holds extensive economic and health policy implications.

Pathobiology

Similar to other common geriatric syndromes ( Chapter 24 ), delirium usually has multiple causes. A search for the many potential underlying contributors requires clinical astuteness and a thorough medical evaluation, especially because many of these factors are treatable but may result in substantial morbidity and mortality if left untreated. The process is made more challenging by the frequently nonspecific, atypical, or muted features of the underlying illness in older persons. Delirium is commonly the only initial sign of an underlying life-threatening illness, such as pneumonia ( Chapter 85 ), urosepsis ( Chapter 263 ), or myocardial infarction ( Chapter 58 ), in the older population.

The basic pathogenesis of delirium remains unclear. Recent evidence suggests that interacting biologic factors result in disruption of large-scale neuronal networks in the brain, thereby leading to acute cognitive disruption and delirium. Some of the leading proposed mechanisms include disruption in neurotransmitter systems, systemic inflammation, neuronal inflammation, neuronal injury, physiologic stressors, metabolic derangements, and genetic factors. Many neurotransmitter systems are potentially involved, but relative cholinergic deficiency and dopamine excess are the most frequently linked. Inflammation may play an important role, with peripheral inflammation triggering neuroinflammation and microglial activation. Whether underlying factors such as preclinical dementia impart a vulnerability for the brain to “lose” the ability to protect itself in the face of infection or trauma, with the end result being an episode of delirium, or if delirium itself causes neuronal injury and death is unknown, but both of these potential links are supported by emerging data.

The development of delirium usually involves a complex interrelationship between a vulnerable patient with pertinent predisposing factors and exposure to noxious insults or precipitating factors. Delirium may develop in vulnerable patients, such as cognitively impaired or severely ill patients, after a relatively benign insult, such as a single dose of sleeping medication. Conversely, in patients who are not vulnerable, delirium may develop only after exposure to multiple noxious insults. The effects of these risk factors may be cumulative. Recognition of this multifactorial causation is important to the clinician because the removal or treatment of one factor in isolation usually is not sufficient to resolve the delirium. The full spectrum of vulnerability and precipitating factors should be addressed.

Factors that predispose patients to delirium include preexisting cognitive impairment or dementia ( Chapter 371 ), history of delirium, functional impairment, visual ( Chapter 391 ) or hearing impairment ( Chapter 396 ), multiple comorbid conditions, severe underlying illness, depression ( Chapter 362 ), history of a stroke or transient ischemic attack ( Chapter 376 ), alcohol use disorder ( Chapter 364 ), and advanced age. Dementia is an important and consistent risk factor for delirium; persons with dementia have a two-fold to five-fold increased risk for delirium, and 30 to 50% of delirious patients have underlying dementia.

Medications, which are the most common remediable causes of delirium, contribute to delirium in 40% of cases (Chapter 361). Insufficiency or failure of any major organ system, particularly renal or hepatic failure, can precipitate delirium. Surgical procedures are leading risk factors for delirium. Hypoxemia and hypercarbia have been associated with delirium. Clinicians must be attuned to occult respiratory failure, which in the elderly often lacks the usual signs and symptoms of dyspnea and tachypnea and can be missed by the measurement of oxygen saturation alone. Acute myocardial infarction ( Chapter 58 ) or heart failure ( Chapter 45 ) can be manifested as delirium in an elderly patient without the usual symptoms of chest pain or dyspnea. Occult infection is a particularly notable cause of delirium. Older patients frequently fail to mount the febrile or leukocytotic response to infection, and clinicians must assess them carefully for signs of pneumonia ( Chapter 85 ), urinary tract infection ( Chapter 263 ), endocarditis ( Chapters 61 ), abdominal abscess ( Chapter 128 and 137 ), or infected joints ( Chapter 251 ). Studies in older adults presenting to the emergency department with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ( Chapter 336 ) found that delirium is a frequent presenting symptom, in some cases without typical SARS-CoV-2 symptoms or signs, such as fever or shortness of breath. A variety of metabolic disorders may contribute to delirium, including hypernatremia and hyponatremia ( Chapter 102 ), hypercalcemia ( Chapter 227 ), acid-base disorders ( Chapter 104 ), hypoglycemia ( Chapter 211 ) and hyperglycemia ( Chapter 210 ), and thyroid ( Chapter 207 ) or adrenal disorders ( Chapter 209 ). Immobilization and immobilizing devices (e.g., indwelling bladder catheters, physical restraints, bed alarms) are important factors in precipitating delirium. Dehydration and volume depletion and nutritional decline during hospitalization (e.g., weight loss, fall in serum albumin concentration) are well-documented factors contributing to delirium. Drug and alcohol withdrawal are important and often unsuspected causes of delirium in the elderly. Environmental factors, such as unfamiliar surroundings, sleep deprivation, deranged schedule, frequent room changes, sensory overload, and sensory deprivation, may aggravate delirium in the hospital. Psychosocial factors, such as depression, psychological stress, pain, and lack of social supports, also may precipitate delirium.