Delirium

Sidney T. Bogardus Jr.

CLINICAL PEARLS

Delirium is an acute change in attention and cognition. The acuteness of the mental status change helps differentiate delirium from dementia.
Inattention is one of the hallmarks of delirium and also helps differentiate delirium from dementia.
Delirium occurs in 10% to 65% of hospitalized older patients but is diagnosed in only 33% to 66% of cases.
Delirium represents a medical emergency and is associated with substantial in-hospital and posthospital morbidity and mortality, persistent cognitive and functional decline, institutionalization, and high economic costs.
According to the Confusion Assessment Method (CAM), delirium is present when there is an acute change and fluctuating course to the mental status, inattention, and either disorganized thinking or altered level of consciousness.
Predisposing risk factors include age, dementia, prior delirium, and visual or hearing impairment.
In-hospital or precipitating risk factors include medications, infection, congestive heart failure, metabolic derangements, restraints and catheters, immobility, and other noxious insults.
Interventions targeting known risk factors (e.g., cognitive impairment, immobility, vision impairment, hearing impairment, dehydration, and poor sleep) prevent 40% of delirium cases.
Evaluation of a patient with delirium should include a search for offending medications, infection, congestive heart failure, metabolic derangements, or another adverse clinical development.
Medications are implicated in approximately half of delirium cases.
Treatment should focus on mitigating existing risk factors and underlying illnesses, and on creating an environment that emphasizes cognitive and social engagement and mobility.
Use of antipsychotic medications, such as haloperidol, should be reserved for the patient with acute delirium who is a danger to himself/herself or to others.
Antipsychotic mediation should ideally be tapered beginning by the second day of use.
Medications used to treat delirium, including antipsychotics, can worsen delirium.

Delirium, defined as an acute change in attention and cognition, is a serious and common complication of hospitalization among older patients. Delirium is associated with a wide range of adverse consequences, including
in-hospital morbidity, cognitive and functional decline, prolonged hospital length-of-stay, institutionalization, increased costs, and substantial mortality. Many, if not most, cases of delirium go unrecognized in the hospital. However, efforts to prevent delirium by focusing on risk factors have recently proved successful and cost effective.

EPIDEMIOLOGY OF DELIRIUM

Incidence and Prevalence

Delirium is very common among hospitalized older patients. Estimates suggest that approximately 15% to 30% of older patients are delirious on arrival at the hospital and that the incidence of delirium during hospitalization is approximately 15% to 60%, depending on the setting.¹, ², ³, ⁴, ⁵, ⁶ In certain settings, such as the intensive care unit, the incidence of delirium may reach 70%.⁷ Delirium is also encountered in the emergency department (10%)⁸ and in hospice units (42%).⁹ Given that people older than 65 years account for approximately 35% of hospital stays and almost 50% of hospital days, nearly 30% of the entire older hospital population will experience delirium at some point during hospitalization.¹⁰,¹¹ However, although it is one of the most common adverse occurrences in the hospital, delirium is substantially under-recognized, with only 33% to 66% of cases diagnosed.¹² Some studies suggest that 84% to 95% of cases are not detected by attending physicians.¹³,¹⁴

Adverse Consequences

Delirium is often thought of as a temporary and reversible period of confusion associated with acute illness, and clinicians may assume that the confusion will resolve as the acute illness is treated. This is a misconception. Delirium is associated with substantial morbidity and increased mortality (see Table 18.1).¹,³,¹¹,¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹, ²², ²³, ²⁴, ²⁵, ²⁶, ²⁷ Patients with delirium have longer hospitalizations, prolonged cognitive and functional decline, greater risk of institutionalization, increased caregiver burden, and higher costs. Patients with delirium may be at risk for other adverse outcomes, including falls with injury, malnutrition, pressure sores, and infection. The cognitive symptoms of delirium can persist for months following hospitalization, with some estimates indicating that in fewer than half of the patients with delirium all symptoms attributable to the condition resolve 6 months after hospitalization.

Delirium is associated with excess mortality.³,¹¹,¹⁶,¹⁷,¹⁹, ²⁰, ²¹,²⁵,²⁷ In-hospital mortality rates range from 25% to 33%. Mortality 1 month following hospitalization is approximately 14% and 6 months following hospitalization is approximately 22%.¹⁵ Other studies have confirmed that patients with delirium in the hospital are more likely to die during the year following hospitalization than those without delirium, with one study finding a hazard ratio of 2.11 after adjusting for dementia and other confounding factors.¹⁶ In a multisite study by Inouye et al. delirium was shown to be an independent predictor of poor outcomes after controlling for health status, age, dementia, and functional status.¹¹

TABLE 18.1 ADVERSE OUTCOMES ASSOCIATED WITH DELIRIUM

Category	Example
In-hospital morbidity	Falls
	Pressure ulcers
	Incontinence
	Restraint use
	Unnecessary medication use
Health status	Cognitive decline (often persisting after hospital discharge)
	Functional decline (impairment in activities of daily living)
Health services utilization	Longer length of stay
	Rehospitalization
	Increased health care utilization
	Increased nursing home placement
Death

PATHOPHYSIOLOGY OF DELIRIUM

The pathophysiology of delirium is not well understood but appears to be complex.²⁸, ²⁹, ³⁰ The variety of clinical settings in which delirium occurs would seem to suggest common pathways, anatomic regions, or neurotransmitters that could be involved in the development of delirium. Unfortunately, neuroimaging studies, which could provide useful information, are very difficult to perform in patients with active delirium. Attention deficits, which are one of the hallmarks of delirium, are found in a range of conditions, such as strokes, in which there is damage to the brainstem, prefrontal region, and right parietal lobe.²⁸ Infarctions of the middle cerebral artery affecting the frontostriatal and basal ganglia regions can also cause deficits in selective attention and cognition.

Anticholinergic drugs are often associated with delirium³¹, ³², ³³ that can be reversed by the cholinesterase inhibitor physostigmine. Furthermore, elevated serum anticholinergic activity has been correlated with delirium. These findings have led to a cholinergic hypothesis of delirium. Dopaminergic drugs can also lead to delirium. Hypoxia, which can precipitate delirium, increases extracellular dopamine concentration and reduces acetylcholine release. Dopamine also exists in a balance with acetylcholine. Serotonin, which impacts mood, wakefulness, and cognition, is increased in hepatic encephalopathy and septic delirium. Other suspect neurotransmitters include γ-aminobutyric acid (GABA), glutamate, endorphins, and cortisol.

Under the “final common pathway” theory, many different illnesses or causes lead to the same ultimate defect in brain chemistry, resulting in a set of core symptoms (e.g., disorientation, cognitive deficits, sleep-wake cycle disturbances, disorganized thinking, and language abnormalities). The exact nature of the final defect remains to be firmly identified. Other investigators suggest that delirium is more likely to be a “final common symptom,” or set of symptoms, caused by a variety of different brain defects. Cognitive function is a high-order function and may be especially likely to fail in the face of mounting stresses on the equilibrium of a frail or vulnerable patient.

CLINICAL FEATURES OF DELIRIUM

Definition

Delirium is broadly defined as an acute decline in attention and cognition. Numerous other terms are often used interchangeably with delirium, including acute confusional state, acute confusional episode, toxic-metabolic encephalopathy, acute brain syndrome, acute brain failure, intensive care unit (ICU) psychosis, and others. The American Psychiatric Association’s Diagnostic and Statistical Manual, Fourth edition (DSM-IV)³⁴ lists four central features of delirium (see Table 18.2).

Symptoms and Signs

Patients with delirium are usually sick. Many are frail to begin with, having multiple chronic illnesses. However, it is also possible that delirium may be the only sign of new or worsening illness in a hospitalized patient. For example, a patient with impending sepsis may not present with fever or a localizing symptom or sign, and delirium may be the only clue to the presence of infection. Likewise, a patient with myocardial infarction or congestive heart failure may develop delirium without other conventional localizing symptoms. In older patients with dementia, delirium may be the only sign suggesting the presence of new acute illness. Consequently, any patient with new delirium should be evaluated medically for new or worsening illness.

TABLE 18.2 DIAGNOSTIC AND STATISTICAL MANUAL, FOURTH EDITION, (DSM-IV) FEATURES OF DELIRIUM

Disturbance of consciousness (e.g., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention
A change in cognition (e.g., memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia
The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day
There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition
(alternative) There is evidence from the history, physical examination, or laboratory findings that the delirium has more than one etiology (e.g., more than one etiologic general medical condition) or a general medical condition plus substance intoxication or medication side effect

American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. text revision. Washington, DC: American Psychiatric Association; 2000.

The development of delirium is relatively rapid over a period of hours to days but it then persists for days or even months, even after the patient’s acute illness or illnesses has/have resolved. The course of delirium for an individual patient tends to fluctuate during the course of the day. Many patients have worse symptoms in the evening or at night, with lucid periods in the morning or during the day. If a patient is seen only during a lucid period, delirium may be missed; history from family or nursing staff who have been with the patient at other times may provide the clues to the diagnosis by documenting the presence of mental status change.

Inattention is one of the hallmarks of delirium. Patients with delirium have difficulty focusing, sustaining or shifting attention. Distractibility can be noticed in casual conversation but may be easier to miss than more prominent findings of tangentiality, disorganization, or frank confusion. Lack of attention can sometimes be subtle and may be attributed to illness or fatigue or dementia.

Patients with delirium generally have altered levels of consciousness. At one end of the spectrum, perhaps a third of patients have a reduced level of consciousness and may be drowsy, or even lethargic and difficult to arouse. At the other end of the spectrum, approximately a third of patients may be hypervigilant. The remaining patients may have periods of a reduced level of consciousness alternating with periods of a heightened level of consciousness. A common picture of the patient with delirium is of a hyperactive person who is agitated and confused, often vocalizing inappropriately, and with behavioral problems complicating patient care (e.g., pulling out intravenous lines). The diagnosis of delirium in these patients is usually straightforward because the behavioral problems are brought to the attention of treating clinicians. However, the patients who have hypoactive delirium with a slightly reduced level of consciousness may not be recognized as delirious precisely because the lack of agitation may not cause any overt problems in their day-to-day care. If the patient’s level of consciousness is reduced enough, it may make it difficult to discern the problems in cognition that are another common feature of delirium.

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