Delirium is an acute, fluctuating change in mental status, with inattention, disorganized thinking, and altered levels of consciousness.  It is a potentially life-threatening disorder characterized by high morbidity and mortality. Guidelines address recognition, risk factors, and treatment for delirium.  
Mortality for those diagnosed with delirium in the hospital is twice that of patients with similar medical conditions without delirium and rises as high as 14% within 1 month of diagnosis.  Delirium occurs in >20% of hospitalizations annually and is the most common hospital-related complication in the US.  Delirium is common in the intensive care unit especially among mechanically ventilated patients. In critically ill patients it is associated with an increased length of stay and increased mortality.  Studies have demonstrated a 12% prevalence of delirium in older emergency department patients.  Despite its frequency, delirium is frequently under-recognized given the fluctuating nature of symptoms and an overall underappreciation of its significance by healthcare providers. Moreover, delirium has also been associated with elevated risks for functional and cognitive decline, poor rehabilitation potential, institutionalization, and rehospitalization.      While delirium is generally considered reversible, studies suggest that delirium symptoms can last for weeks to months following onset.  Persistent delirium has been found to be frequent in older hospitalized patients, and associated with adverse outcomes. 
The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) notes that in order to be diagnosed with delirium, a patient must show all 4 of the following features. 
A disturbance in attention (i.e., reduced clarity of awareness of the environment) is evident, with reduced ability to focus, sustain, or shift attention. This disturbance in consciousness might be subtle, initially presenting solely as lethargy or distractibility, and might be frequently dismissed by clinicians and/or family members as being related to the primary illness.
A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance not better accounted for by a pre-existing or evolving dementia.
The disturbance develops over a short period of time (usually hours to days), represents an acute change from baseline, and tends to fluctuate during the course of the day.
There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition, substance intoxication, or substance withdrawal. The changes in attention and cognition must not occur in the context of a severely reduced level of arousal, such as coma.
Hyperactive delirium - a condition where a patient might have heightened arousal, with restlessness, agitation, hallucinations, and inappropriate behavior
Hypoactive delirium - a condition where a patient might display lethargy, reduced motor activity, incoherent speech, and lack of interest
Mixed delirium - a combination of hyperactive and hypoactive signs and symptoms.
The term subsyndromal delirium has also been used to define partially resolved or incomplete forms of delirium.
The prevalence of delirium in the community is believed to be 1% to 2%, a figure that increases to 14% for patients age >85 years.  Among hospitalized patients, the prevalence of delirium ranges from 14% to 24% in the ER, to 15% to 53% for postoperative patients, and 70% to 87% for intensive care patients.   
The pathophysiology of delirium remains relatively unclear. In general, neuroimaging studies reveal disruptions in higher cortical functioning in multiple disparate areas of the brain, including the prefrontal cortex, subcortical structures, thalamus, basal ganglia, lingual gyri, and frontal, fusiform and temporoparietal cortex.  
Electroencephalographic (EEG) studies also show diffuse slowing of cortical activity.
Theories on the pathogenesis of delirium point to the role of neurotransmitters, inflammation, and chronic stress on the brain. For example, the role of cholinergic deficiency in inducing delirium is strengthened by the clear association of anticholinergic drug use with increased incidence.  Studies in surgical patients have demonstrated a dysfunctional interaction between the cholinergic and immune systems in patients who developed postoperative delirium. 
Dopaminergic excess is also believed to contribute, as evident by the protective role of dopamine antagonists, such as antipsychotic medications. Other neurotransmitters have also been implicated including norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, and melatonin.
Evidence also points to the role of cytokines such as interleukins 1 and 2 and TNF-alpha and interferon in contributing to delirium. 
Finally, chronic hypercortisolism, as induced by chronic stress secondary to illness or trauma, may also contribute to delirium initiation. 
Yale University School of Medicine
MP is on the writing committee for the American Board of Internal Medicine Critical Care exams. MP has lectured at American Thoracic Society and American College of Chest Physicians meetings.
Dr Margaret Pisani would like to gratefully acknowledge David M. Dosa, a previous contributor to this monograph. DMD declares that he has no competing interests.
Professor and Associate Dean for Nursing Science Studies
College of Nursing
University of Illinois at Chicago
MF declares that he has no competing interests.
Associate Medical Director
Consultant Emergency Medicine
Guy's and St Thomas' NHS Foundation Trust
Clinical Lead and Consultant
Accident Emergency Medicine
St Thomas' Hospital
AP declares that he has no competing interests.
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