Neurochemical Hypothesis

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Cholinergic transmission in the CNS has a major role in cognition and attention, and an acute cholinergic deficit exists in delirium. Dopaminergic transmission is increased in delirium, and this or the imbalance between cholinergic and dopaminergic systems may be etiologic. Disturbances in other neurotransmitters are hypothesized, perhaps explaining subtypes or variations in presentations of delirium. Serotonin may be increased in delirium associated with serotonin syndrome and in hepatic encephalopathy, but decreased in delirium from other causes. Glutamate and y-aminobutyric acid (GABA) are believed to be increased in alcohol withdrawal and hepatic encephalopathy. Melatonin may be increased or decreased in delirium, which may explain hypo-active and hyperactive subtypes. Norepinephrine may be increased in delirium associated with anoxia and in hepatic encephalopathy. Inflammation may also play a role in causing delirium, either by a direct neurotoxic effect or by causing disturbances in the neurotransmitters. Figure 48-1 depicts a theoretic explanation for the etiology of delirium.

• Tools for diagnosing and managing delirium include Confusion Assessment Method and Memorial Delirium Assessment Scale.

Dementia is the strongest risk factor for development of delirium.

• Diagnostic testing needs to be informed by a thorough history and careful physical examination.

Diagnostic criteria for delirium are adapted from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM IV-TR, 2000) (Box 48-1). Given the high prevalence of delirium in certain health care settings and clinical circumstances, diagnosis should not depend solely on a high index of suspicion. Formal evaluation of mental status to detect delirium or dementia should become part of routine assessment of elderly patients presenting with a change of condition. This not only fosters appropriate preventive and therapeutic interventions, but also alerts the interdisciplinary team (IDT) to plan care to ensure patient and staff safety, specific patient and family education, carefully considering cognition and function at discharge planning.

*More vulnerable in immature or already impaired brain.

Figure 48-1 Theoretic etiologic hypothesis for delirium.

*More vulnerable in immature or already impaired brain.

Figure 48-1 Theoretic etiologic hypothesis for delirium.

Box 48-1 Diagnostic Criteria for Delirium (DSM IV-TR)

A. Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention.

B. A change in cognition (e.g., memory deficits, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia.

C. The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.

D. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a general medical condition, a substance intoxication, or a substance withdrawal;

is the result of multiple etiologies; is caused by an etiology other than these (e.g., sensory deprivation); or cannot be determined.

Modified from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.

Several standardized instruments have been developed to assess for delirium and monitor severity. The Confusion Assessment Method (CAM) is based on DSM IV-R criteria and has 94% to 100% sensitivity and 90% to 95% specificity, with good interrater reliability when used with formal cognitive testing and administered by trained interviewers (Inyoue et al., 1990). Once diagnosed, the 10-item Memorial Delirium Assessment Scale is useful to monitor severity (Breibart et al., 1997). Other scales are used in specific settings (e.g., ICU). Given the fluctuating course of delirium, it is essential to perform monitoring frequently.

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