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Am Fam Physician. 2023;108(3):278-287

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Delirium is an acute disturbance in attention, cognition, and awareness that fluctuates over time. Delirium is characterized by three subtypes: hyperactive, hypoactive, and mixed. It occurs in 11% to 25% of older adults in inpatient settings and is associated with a significant financial burden. Older age, multiple comorbidities, recent surgery, and polypharmacy are independent risk factors for delirium. The diagnosis is clinical but can be challenging due to overlapping symptoms with dementia and depression. The Confusion Assessment Method is a screening tool that is 94% to 100% sensitive and 90% to 95% specific for delirium. There is no evidence to support medication use for delirium prevention. Nonpharmacologic interventions, such as sufficient hydration and nutrition, early mobilization, infection control, and frequent orientation, can prevent and treat delirium. Physical restraints should be avoided, but if needed in patients at significant risk of injury to themselves or others, their use should be reassessed at least every 24 hours. No medications are approved by the U.S. Food and Drug Administration for the treatment of delirium. If pharmacologic therapy is indicated, second-generation antipsychotics such as olanzapine, risperidone, and quetiapine are preferred over haloperidol because of their faster onset of action and fewer adverse effects. Patients hospitalized with prolonged delirium have approximately three times the chance of dying in the following year compared with patients with a quick resolution of delirium or no symptoms; therefore, prevention and early detection should be emphasized.

Delirium is a syndrome characterized by an acute disturbance in attention, cognition, and awareness that develops within hours to days and fluctuates in severity over time. There are three subtypes of psychomotor disturbances of delirium: hyperactive, hypoactive, and mixed.1 Hyperactive delirium is marked by agitation and restlessness and can be misdiagnosed as primary psychosis or dementia. Hypoactive delirium is characterized by lethargy and psychomotor impairment and can be mistaken for depression. Mixed delirium has hyperactive and hypoactive features.1 Historically, the terms delirium, acute encephalopathy, acute confusional state, acute brain dysfunction, acute brain failure, and altered mental status have been used interchangeably and imprecisely. Delirium and acute encephalopathy are the most accepted terms and refer to a deviation from the patient's baseline cognition.2 An accurate diagnosis of delirium is essential to prevent inappropriate treatments, prolonged hospitalization, cognitive decline, and increased mortality and morbidity.3,4

RecommendationSponsoring organization
Do not use benzodiazepines or other sedative-hypnotics in older adults as the first choice for treating insomnia, agitation, or delirium.American Geriatrics Society
Do not administer as-needed sedative, antipsychotic, or hypnotic medications to prevent or treat delirium without first assessing for, removing, and treating the underlying causes of delirium and using nonpharmacologic delirium prevention and treatment approaches.American Academy of Nursing
Do not use physical restraints to manage behavioral symptoms of hospitalized older adults with delirium.American Geriatrics Society

Epidemiology

Delirium is among the most common complications in hospitalized adults 65 years and older.5 It is the most common surgical complication in older adults and is associated with a significant financial burden.6 National health care costs related to postoperative delirium are an estimated $32.9 billion per year, with most costs from the lengthening of the initial hospitalization, subsequent hospitalizations, and acute rehabilitation.7 Overall costs attributable to delirium are significantly higher, ranging from $143 billion to $152 billion per year, which includes factors such as prolonged hospitalizations, outpatient visits, and nursing home stays.3

The prevalence of delirium in the community is relatively low at 1% to 2% but increases to approximately 11% to 25% with hospital admission. This dramatic difference in prevalence may be due to the symptoms of delirium prompting evaluation of the patient in a more acute setting such as the emergency department.5,8 The incidence of delirium differs significantly depending on the health care setting and the patient's associated risk factors (Table 1).3,5,9,10 The prevalence and incidence of delirium are likely underestimated because patients with baseline cognitive impairment or dementia are often excluded from studies.5

SettingIncidence (%)
Intensive care19 to 82
Medical service11 to 29
Nursing home20 to 22
Palliative care (inpatient)3 to 45
Postoperative11 to 51

Pathophysiology and Risk Factors

The pathophysiologic cause of delirium is not well understood.1 Older age, multiple comorbidities, polypharmacy, poor baseline functional status, and recent surgery are all independent risk factors for developing delirium (Table 2).8,1115 Predisposing factors are the patient's background characteristics, whereas precipitating factors are acute or subacute events preceding onset of delirium.16 Patients with delirium are typically affected by more than one risk factor and often have predisposing and precipitating elements.17 It is unlikely that only one mechanism is responsible for the cause of delirium because of the variation in risk factors.13,16 The range of potential etiologies poses a complex challenge in identifying precipitating factors but is important because delirium is reversible in 25% to 68% of patients.18

Predisposing factorsPrecipitating factorsDelirium-inducing medications
Patient characteristics
Age 65 years and older
Hospitalized
Multiple comorbidities
Polypharmacy
Poor functional status
Sensory deprivation (e.g., vision, hearing)
Terminally ill
Medical conditions
Chronic heart, kidney, liver, or lung disease
Dementias/degenerative disorders
Dialysis-dependent
Malnutrition
Psychiatric conditions
Substance use disorder
Burns
Dehydration
Hypoxia
Infection
Ischemia (e.g., cerebral, cardiac)
Malnutrition
Medication adverse effects (e.g., serotonin syndrome)
Metabolic disturbances
Seizures
Severe illness
Shock
Sleep deprivation
Surgery/anesthesia
Tethers (e.g., urinary catheter, physical restraints)
Trauma (e.g., fractures, head injury)
Uncontrolled pain
Urinary or stool retention
Withdrawal from alcohol, illicit drugs, or benzodiazepines
Analgesics (e.g., nonsteroidal anti-inflammatory drugs, opioids)
Antiarrhythmics
Antibiotics (e.g., fluoroquinolones, macrolides)
Anticholinergics
Anticonvulsants
Antidepressants (e.g., selective serotonin reuptake inhibitors, tricyclics)
Antihistamines
Antihypertensives (e.g., beta blockers, clonidine, diuretics)
Antipsychotics
Antivirals (e.g., acyclovir)
Corticosteroids (oral and parenteral)
Dopamine agonists
Gastrointestinal agents (e.g., antiemetics, antispasmodics)
Herbal supplements
Hypnotics and sedatives (e.g., barbiturates, benzodiazepines)
Hypoglycemic agents
Muscle relaxants

Diagnosis

Patients with suspected delirium should have a comprehensive history and physical examination for possible contributing medical conditions. Delirium can be precipitated by medications, adverse medication effects, uncontrolled pain, infections, severe organ damage, drug or alcohol withdrawal, dehydration, and constipation (Table 319,20). Timely identification of the etiology of symptoms is important.14,21

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