Excerpt from Confusional States and Acute Memory Disorders

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Background

Delirium, also referred to as encephalopathy, or an acute confusional state, is defined as a transient disorder of cognition and attention accompanied by disturbances of the sleep-wake cycle and psychomotor behavior.¹ The key feature of delirium is the inability to maintain a coherent stream of thought or action, along with an impairment in attention and/or arousal. Patients cannot keep attention focused, and this attentional disorder underlies many of the other cognitive deficits. Delirious patients are distractible, may be hypersensitive to stimuli, and cannot prioritize important from irrelevant environmental sounds or sights. A mother's ability to hear only the cry of her baby and ignore the street noises, creaking floors, plumbing noises, or music from next door, is an example of the type of focused attention that is impossible in delirium.

Most patients with delirium have associated cognitive deficits such as altered perception (including hallucinations, illusions, and delusions, such as thinking that IV tubing is a snake or misinterpreting shadows on the ceiling as animals); memory loss (especially distorted memories, approximate answers, and misidentification of people or places); language deficits (especially writing); disorientation; difficulty with calculations, abstraction, insight, and judgment; and mood disorders, which can include fear, elation, anxiety, or depression. Some patients have relatively preserved orientation, language, and other cognitive function but simply cannot maintain focus on a conversation, talking about irrelevant details such as the sound of a beeper or a pattern on the wall.

Central to delirium is an alteration of consciousness, either alert and agitated, or somnolent, along with psychomotor abnormalities such as restlessness, agitation, and sleep-wake cycle disturbance. Another common set of associated symptoms in delirium are autonomic disturbances such as tachycardia, hypertension, fever, sweating, and piloerection. 

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)² defines delirium as the following:

• Disturbance of consciousness (ie, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention
• A change in cognition (such as 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.
• Evidence from the history, physical examination, or laboratory findings shows that the disturbance is caused by the direct physiological consequences of a general medical condition.

Delirium has been subdivided into 4 motoric subtypes, based on the alteration of level of consciousness.

• Hypoactive delirium with low psychomotor behavioral activity
• Hyperactive delirium with high psychomotor activity
• Mixed delirium with features of both hypo- and hyperactivity
• Delirium without psychomotor behavioral changes

Hypoactive delirium has in the past been less recognized than the hyperactive variety, but recent evidence indicates that it is much more common than the hyperactive variants, especially in intensive care patients.

Delirium is distinguished from dementia, which consists of a nonacute, usually progressive cognitive deficit usually reflecting deficits of multiple cognitive functions (negative symptoms in the Hughlings Jackson sense) and usually much less associated with the psychomotor, autonomic, and level of consciousness alterations (positive symptoms) that characterize delirium. 

Pathophysiology

Delirium is a syndrome, or a symptom complex, rather than a disease; the pathophysiology of delirium depends largely on the etiology of the syndrome. The syndrome can be attributed to numerous causes including, but not limited to, the following.

• Pulmonary disease (eg, hypoxia)
• Other abnormal systemic metabolic conditions such as hepatic or renal dysfunction
• Endocrine disorders such as thyroid or adrenal hypofunction or hyperfunction
• Ingestion of toxins or side effects of single or multiple interacting medications or withdrawal from alcohol or drugs
• Electrolyte imbalances, especially abnormalities in sodium, BUN, creatinine, glucose, calcium, magnesium, and phosphorus
• Nutritional deficiencies such as thiamine, cobalamin, or niacin
• Sepsis or systemic infections including simple urinary tract infections and CNS infections such as meningitis or encephalitis related to infection with HIV, herpes simplex, and West Nile virus
• Seizures or postictal states
• Inflammatory or autoimmune conditions such as paraneoplastic disorders, Hashimoto encephalopathy, and vasculitis
• Acute structural lesions such as cerebral infarctions or hemorrhages.

An overlap exists with acute psychiatric disorders (especially acute mania).

Patients with preexisting dementia can deteriorate into delirium with seemingly minor stressors such as urinary tract infections, traumatic injuries, or even environmental change. Focal CNS disorders in strategic locations can also cause delirium. Strokes are frequent causes of delirium. Lesion loci associated with acute confusional states include the basal forebrain (eg, infarction as complication of surgery to repair an anterior communicating artery aneurysm), the caudate nucleus, and thalamic lesions that affect Papez circuit (anterior nucleus, fornix, mammillothalamic tract), and hippocampal lesions, such as acute posterior cerebral artery territory strokes or herpes simplex encephalitis.

In addition, Wernicke aphasia and mirror-image lesions of the Wernicke area affecting the right hemisphere can also present with acute confusion or agitation, as can some thalamic lesions causing aphasia. Strokes are more likely to be associated with delirium when they occur in elderly patients with preexisting cerebral atrophy and also when they are accompanied by seizures. Multifocal strokes in embolic conditions, vasculitis, or hypoxic-ischemic encephalopathy are also frequent causes of delirium.

Frequency

United States

• Delirium is an extremely common condition. 
• Acute encephalopathies develop in 30-50% of hospitalized patients older than age 70; since nearly half of hospital populations are elderly, a conservative estimate is that approximately 10% of hospitalized patients on medical or surgical units have delirium at any given time. In addition, delirium often follows surgical procedures.
• Delirium has been associated with longer hospital stays, increased mortality, and also a risk of nearly 50% of permanent neurocognitive impairment in survivors.
• Delirium is estimated to affect more than 2 million persons in the United States each year, and the excess hospital cost associated with delirium exceeds $4 billion.

As the population of older Americans increases, the frequency and cost of delirium are likely to increase. Several studies have investigated risk factors for the development of delirium during hospitalization. Perhaps the easiest to use is provided by Inouye and colleagues for patients older than age 70.³ Five independent risk factors were preexisting dementia or cognitive impairment, vision impairment, functional impairment, high comorbidity, and use of physical restraints. Rates for low risk (0-1 factors), intermediate risk (2-3 factors), and high risk (4-5 factors) were 4%, 18%, and 63%, respectively. Other studies have found the presence of fractures, infections, and use of sedative or narcotic analgesic drugs to be predictors of delirium.

International

Delirium is common throughout the world. A review by Brown and Boyle in the British Medical Journal estimated that a fourth of hospitalized patients older than age 65 develop delirium during hospitalization.⁴

Mortality/Morbidity

Delirium is associated with high rates of mortality and morbidity, especially if undiagnosed. Inouye estimated in-hospital mortality of more than 20%, and mortality within a year of 35-40%.⁵ Ely and colleagues also found that delirium was an independent predictor of both mortality and longer hospital stays.⁶ The morbidity and mortality rates depend heavily on the patient's reason for admission and associated medical illnesses.

Race

Available studies on risk factors for delirium have not identified race as a specific predictor of delirium. 

Sex

A recent study of delirium in older patients admitted to a general internal medicine service found male gender to be an independent risk factor for delirium, along with several other factors.⁷ Most studies of delirium have not reported gender as a major predictor.

Age

• Virtually all studies of delirium have found age to be a predictor of acute confusional states. Aging changes in the brain, and especially preexisting cognitive deficits or strokes, render the nervous system more sensitive to toxic or metabolic insults, such as medication side effects, electrolyte imbalances, endocrine disorders and renal or hepatic failure, and infections, among many other conditions.
• Elderly patients may have exaggerated responses to over-the-counter and prescription medications with anticholinergic activity. These include diphenhydramine (Benadryl, Tylenol PM), bladder antispasmodics such as oxybutynin, and atropine sulfate (eg, Lomotil). Thioridazine (Mellaril), a prescription antipsychotic medication, and tricyclic antidepressants such as amitriptyline (Elavil) also have anticholinergic activity. These drugs may cause exaggerated adverse effects, including sundowning. Other medications implicated in delirium are narcotic analgesics, benzodiazepines, theophylline, and antiparkinson medications.

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