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. . Chapter 026. Confusion and Delirium (Part 2) Epidemiology Delirium is a common disease, but its reported incidence has varied. 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. 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