Delirium

A clinical state characterized by an acute, fluctuating change in mental status, with inattention and altered levels of consciousness.

The term delirium is used in various ways. Some health care practitioners use the terms delirium and acute confusional state synonymously. Some use delirium to describe confusion with hyperactivity. Some use delirium to describe severe confusion and use acute confusional state to describe mild disorientation. The Merck Manual of Geriatrics uses delirium as defined above.

Delirium can be classified on the basis of psychomotor activity (ie, level of arousal). In hyperactive delirium (about 25% of cases), psychomotor activity is increased and agitation is prominent; hyperactive delirium may be misdiagnosed as an anxiety state, and the patient merely sedated (ie, a serious underlying etiology may be overlooked). In hypoactive delirium (about 25% of cases), psychomotor activity is decreased; hypoactive delirium may be misdiagnosed as depression or may be undetected. In mixed delirium (about 35% of cases), psychomotor activity has hyperactive and hypoactive features. In about 15% of cases, psychomotor activity is normal.

Epidemiology and Etiology

Delirium is very common among the elderly. Of general medical patients >= 70 years admitted to the hospital, 10 to 20% are delirious at admission, and 10 to 20% become delirious during hospitalization. The incidence of postoperative delirium among patients >= 70 is 15 to 25% after elective procedures and 35 to 65% after emergency procedures (eg, hip fracture repair). The incidence in other settings (eg, nursing homes, the community) is unknown but is likely to be increasing because patients are being discharged earlier from acute care.

Risk factors include advanced old age, underlying dementia, functional impairment, and medical comorbidity and its treatments. Factors that can precipitate delirium are as follows (using the mnemonic DELIRIUM):

• Drug use (especially when the drug is introduced or the dosage is adjusted--see Table 39-1)
• Electrolyte and physiologic abnormalities (eg, hyponatremia, hypoxemia)
• Lack of drugs (withdrawal)
• Infection (especially urinary tract or respiratory infection)
• Reduced sensory input (eg, blindness, deafness, darkness, change in surroundings)
• Intracranial problems (eg, stroke, bleeding, meningitis, postictal state)
• Urinary retention and fecal impaction
• Myocardial problems (eg, myocardial infarction, arrhythmia, heart failure)

Also, almost any acute illness affecting any organ system, or an exacerbation of any chronic illness, may precipitate delirium.

Pathophysiology

The neuropathophysiology of delirium is unknown. Serum anticholinergic activity is often increased, probably due to endogenous factors or to drug therapy. The elderly are particularly vulnerable to decreased cholinergic transmission. Levels of phenylalanine and tryptophan, which are involved in neurotransmitter synthesis, may be abnormal, and levels of leukotrienes and interferons may be elevated.

Symptoms and Signs

The hallmark of delirium is acute cognitive dysfunction with impaired attentiveness, which develops suddenly or over a short time (usually hours to days). A patient with delirium has acute fluctuations in mental status, with varying levels of inattention and altered levels of consciousness. Changes in orientation, memory, and abstract thinking may occur but are not diagnostic. Psychomotor activity (level of arousal) may be variably abnormal. Hallucinations, delusions, tremor, abnormalities in the sleep-wake cycle, and other symptoms (see Table 39-2) may be present. In some frail elderly patients, delirium precedes the appearance of another illness and is the only early manifestation of that illness. Delirium may persist for many weeks or months; infrequently, it never clearly resolves, or it modulates into chronic cognitive dysfunction (dementia).

Diagnosis

Diagnosis consists of two elements: establishing the presence of delirium and establishing the underlying cause, if possible. Failure to diagnose or misdiagnosis occurs in up to 80% of cases but is less likely with interdisciplinary input (eg, from physicians, nurses, and persons who know the patient well, such as family members). The diagnostic criteria for delirium are shown in Table 39-3.

A thorough history is required to determine the frequency and duration of mental status changes and other clinical features. A drug review focuses on changes in the drug regimen (eg, additions, deletions, dose changes) that may have precipitated the delirium. Psychoactive drugs, particularly sedative-hypnotics, antidepressants, anticholinergic drugs, and opioids, are likely precipitants (see Table 39-1), but almost any drug may be implicated. Use of over-the-counter drugs and alcohol should also be reviewed.

A physical examination can be challenging in a patient with delirium. Vital signs, including pulse, blood pressure, respiratory rate, temperature, and oxygen saturation, may provide important etiologic clues. Cardiac, pulmonary, abdominal, neurologic, and mental status examinations should be performed.

The Confusion Assessment Method (CAM) may be the most useful tool for diagnosing delirium (see Table 39-4). CAM identifies the criteria necessary for diagnosis; other criteria that are not necessary for diagnosis (although common in delirium) include abnormal psychomotor activity, sleep-wake cycle disturbances, hallucinations, delusions, and tremor. CAM can detect delirium even in the presence of dementia.

Laboratory evaluation is guided by the history, drug review, and physical examination. CBC, serum electrolytes, urinalysis, and cultures are the most useful laboratory tests. CT of the head, cerebrospinal fluid analysis, and electroencephalography are less useful but are frequently performed. Patients may have to be sedated during these tests, and the risk of sedation may outweigh the benefit of diagnostic yield. Thus, these tests are probably best reserved for patients at particularly high risk (eg, those who have had head trauma and are taking anticoagulants), those with new focal neurologic abnormalities, or those for whom the history, drug review, and physical examination have not confirmed an etiology. An ECG and a chest x-ray can be obtained if an underlying cardiac or pulmonary disorder is suspected.

Differential diagnosis: The primary differential diagnoses are depression and dementia, both of which may co-exist with delirium (see Table 39-2). Hypoactive delirium must be differentiated from depression. In one study, one third of hospitalized patients referred for evaluation of depression had hypoactive delirium.

Differentiation between delirium and dementia is not always clear, and the features of the two syndromes sometimes overlap. Onset of delirium is rapid; dementia usually develops slowly, although that caused by a stroke or anoxia may occur acutely. In delirium, the ability to attend is primarily affected. In early stages of dementia, memory rather than attention is affected, although in late stages, attention may be severely impaired. Because delirium is often caused by toxic or metabolic factors that impair brain cell function and because dementia is usually caused by damage or loss of brain cells, delirium is often regarded as potentially reversible and dementia as permanent. Therefore, the duration of cognitive decline is probably the clearest way to differentiate these disorders. Although most persons with delirium recover fully, some never do. In addition, a few persons have dementia due to a reversible cause and may recover. The diagnosis of dementia should not be applied until all appropriate treatments have been tried and several months have passed to allow for recovery.

Complications

Patients with delirium are particularly vulnerable to iatrogenic problems, especially those due to physical or chemical (ie, drug) restraints. Bladder and bowel incontinence or retention is common and can directly contribute to delirium. Bedridden patients with delirium are prone to atelectasis, deconditioning, and pressure sores. Acute malnutrition, related to an inability to attend to eating, may occur.

Prognosis and Treatment

Hospitalized patients with delirium have up to a 10-fold higher risk of medical complications (including death), longer hospitalization, higher hospital costs, and increased need for postacute placement at discharge.

Management of delirium includes treatment of underlying disorders, removal of contributing factors, behavioral control, avoidance of iatrogenic complications, and support of the patient and family. A geriatric interdisciplinary team, involving family and friends, can provide the best care. Failure to provide sufficient care may lead to life-threatening (and costly) complications and long-term loss of function.

Behavioral control may be necessary to ensure patient comfort and to promote safety. Usually, social restraint is preferred to physical or chemical restraints. Placement of delirious patients in rooms near the nursing station is recommended, and family members are encouraged to stay with patients. Items that help orient patients (eg, clocks, calendars) should be provided, and patients who need glasses and hearing aids should be encouraged to wear them.

Discontinuation of drugs or treatments known to precipitate delirium is recommended. Less commonly, drugs can be used to treat delirium directly; for example, delirium caused by alcohol withdrawal can be treated with benzodiazepines, and anticholinergic drug toxicity, if severe, can be treated with physostigmine.

Psychoactive drug treatment may be required to treat agitation rather than the delirium itself. If psychoactive drug treatment is required, documentation and assessment of the target symptoms and the response to treatment are necessary. For most patients, low doses of high-potency antipsychotics (eg, haloperidol 0.25 to 1 mg po, IM, or IV) are preferred. Use of risperidone (0.25 to 1 mg) has recently been suggested to treat the agitation of hyperactive delirium. Risperidone may have slightly less extrapyramidal effects than does haloperidol at low doses. Benzodiazepines (eg, lorazepam 0.25 to 1 mg po, IM, or IV) are the treatment of choice for patients with delirium due to alcohol or sedative withdrawal or for patients with parkinsonism who cannot tolerate the extrapyramidal effects of an antipsychotic. All drugs used to treat agitation can produce oversedation, and their use sometimes prolongs delirium and increases the risk of complications.

Risk of atelectasis, deconditioning, and pressure sores can be reduced by mobilization; ie, the patient sits in a chair or ambulates rather than remains bedridden. Close attention to nutritional intake and, sometimes, manual assistance with eating are necessary to avoid malnutrition.

Family and staff members should be informed that delirium is usually reversible but that cognitive deficits often take weeks or months to abate after resolution of the acute illness. Patient support and safety are paramount.