Chapter 026. Confusion and Delirium (Part 2) potx

Chapter 026. Confusion and Delirium
(Part 2)

Epidemiology
Delirium is a common disease, but its reported incidence has varied widely
based on the criteria used to define the disorder. Estimates of delirium in
hospitalized patients range from 14 to 56%, with higher rates reported for elderly
patients and patients undergoing hip surgery. Older patients in the ICU have
especially high rates of delirium ranging from 70 to 87%. The condition is not
recognized in up to one-third of delirious inpatients, and the diagnosis is especially
problematic in the ICU environment where cognitive dysfunction is often difficult
to appreciate in the setting of serious systemic illness and sedation. Delirium in the
ICU should be viewed as an important manifestation of organ dysfunction not
unlike liver, kidney, or heart failure. Outside of the acute hospital setting, delirium
occurs in nearly two-thirds of patients in nursing homes and in over 80% of those
at the end of life. These estimates emphasize the remarkably high frequency of this
cognitive syndrome in older patients, a population expected to grow in the
upcoming decade with the aging of the "baby boom" generation.
In previous decades an episode of delirium was viewed as a transient
condition that carried a benign prognosis. Delirium has now been clearly
associated with substantial morbidity and increased mortality, and is increasingly
recognized as a sign of serious underlying illness. Recent estimates of in-hospital
mortality among delirious patients have ranged from 25 to 33%, a rate that is
similar to patients with sepsis. Patients with an in-hospital episode of delirium
have a higher mortality in the months and years following their illness compared
with age-matched nondelirious hospitalized patients. Delirious hospitalized
patients have a longer length of stay, are more likely to be discharged to a nursing
home, and are more likely to experience subsequent episodes of delirium; as a
result, this condition has enormous economic implications.

Pathogenesis

The pathogenesis and anatomy of delirium are incompletely understood.
The attentional deficit that serves as the neuropsychological hallmark of delirium
appears to have a diffuse localization with the brainstem, thalamus, prefrontal
cortex, thalamus, and parietal lobes. Rarely, focal lesions such as ischemic strokes
have led to delirium in otherwise healthy persons; right parietal and medial dorsal
thalamic lesions have been reported most commonly, stressing the relevance of
these areas to delirium pathogenesis. In most cases, delirium results from
widespread disturbances in cortical and subcortical regions, rather than a focal
neuroanatomic cause. Electroencephalogram (EEG) data in persons with delirium
usually show symmetric slowing, a nonspecific finding supporting diffuse cerebral
dysfunction.
Deficiency of acetylcholine often plays a key role in delirium pathogenesis.
Medications with anticholinergic properties can precipitate delirium in susceptible
individuals, and therapies designed to boost cholinergic tone such as
cholinesterase inhibitors have, in small trials, been shown to relieve symptoms of
delirium. Dementia patients are susceptible to episodes of delirium, and those with
Alzheimer's pathology are known to have a chronic cholinergic deficiency state
due to degeneration of acetylcholine-producing neurons in the basal forebrain.
Another common dementia associated with decreased acetylcholine levels,
dementia with Lewy bodies, clinically mimics delirium in some patients. Other
neurotransmitters are also likely involved in this diffuse cerebral disorder. For
example, increases in dopamine can also lead to delirium. Patients with
Parkinson's disease treated with dopaminergic medications can develop a
delirious-like state that features visual hallucinations, fluctuations, and confusion.
In contrast, reducing dopaminergic tone with dopamine antagonists such as typical
and atypical antipsychotic medications has long been recognized as effective
symptomatic treatment in patients with delirium.
Not all individuals exposed to the same insult will develop signs of
delirium. A low dose of an anticholinergic medication may have no cognitive
effects on a healthy young adult but may produce a florid delirium in an elderly

person with known underlying dementia.
However, an extremely high dose of the same anticholinergic medication
may lead to delirium even in healthy young persons. This concept of delirium
developing as the result of an insult in predisposed individuals is currently the
most widely accepted pathogenic construct.
Therefore, if a previously healthy individual with no known history of
cognitive illness develops delirium in the setting of a relatively minor insult such
as elective surgery or hospitalization, then an unrecognized underlying neurologic
illness such as a neurodegenerative disease, multiple previous strokes, or another
diffuse cerebral cause should be considered.
In this context, delirium can be viewed as the symptom resulting from a
"stress test for the brain" induced by the insult. Exposure to known inciting factors
such as systemic infection or offending drugs can unmask a decreased cerebral
reserve and herald a serious underlying and potentially treatable illness.