DELIRIUM: Advances in Diagnosis, Pathophysiology, and Treatment

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Delirium is an acute confusional state with an average prevalence of about 20% in general hospital populations, based on both referral and consecutive admission study designs. It involves alterations in cognition, mood, perception, thinking, and sleep. Symptoms tend to fluctuate in intensity over a 24-hour period, with periods of relative lucidity interspersed with periods of more severe impairment. The features of delirium are as follows:

  • Diffuse cognitive impairment

  • Perceptual disturbances and hallucinations (especially visual)

  • Delusions (usually persecutory)

  • Abnormalities of thought process

  • Language alterations (especially semantic content of writing)

  • Sleep–wake cycle disturbances

  • Altered or labile affect

  • Acute or abrupt onset of symptoms

  • Fluctuation of symptom severity

  • Identifiable (or presumed) physical cause

Levels of consciousness and awareness may also fluctuate, though not reaching the degree of impairment of stupor or coma. Because the sleep-wake cycle in delirium is fragmented over a 24-hour period, fluctuations in level of awareness or consciousness might be affected by alterations in sleep physiology, including ultradian rhythms.

Several studies suggest that delirium as a comorbid condition increases length of stay during general medical hospitalizations,30, 37, 128 even when diagnosis related group (DRG)-adjusted. This has economic as well as personal suffering implications.

Elderly populations experiencing an episode of delirium have an especially poor prognosis. They have longer lengths of stay,36, 56, 92 even when adjusted for DRG or illness severity,30, 92 and increased in-hospital mortality.30, 92 Delirium during an index admission is associated with postdischarge functional decline in activities of daily living,36, 52, 63, 83 persistent or progressive cognitive impairment 6 months later,29, 56 and loss of independent community living compared with prior-to-the-index admission.29, 56 Mortality postdischarge of delirious elderly is increased compared with nondelirious elderly: at 6 months after the index admission 20%,36 26%,56 and 27%52 had died, and at 1 year 37%52 and 39%29 had died. Francis et al30 found that medical illness severity predicted 6-month mortality in delirious elderly patients. In many of these reports, delirium was comorbid with dementia, as high as 81% in a study by Koponen et al.52 Cognitive deficits that appear to persist following delirium might suggest residual delirium effects,56 but more likely these deficits are related to an underlying dementia that progressed51 and that had previously increased the vulnerability to delirium on the basis of “diminished brain reserve” during the early yet undiagnosed period of dementia.30

Across a broad age range, there is significant morbidity and mortality associated with experiencing a delirium episode, even for a wide variety of underlying causes. Mortality is high: during the index admission it was 11%,92 17%,37 23%,96 and 26%140; at 3 months after admission it was 11%92 and 30%144; at 6 months it was 17%136; at 1 year it was 38%96; and at 5 years it was 51%.140 Mortality rates are significantly higher for delirious than for nondelirious cases. At 5-year follow-up, however, mortality risk was more related to the underlying medical prognosis than to the previous episode of delirium.140

Section snippets

RISK FACTORS

Several studies have sought to identify risk factors associated with delirium. At any age, polypharmacy, substance intoxication, and multiple medical problems are common risk factors for delirium.37, 136

Thiamine deficiency often goes unnoticed in nonalcoholic patients and is an underappreciated cause or risk factor for delirium.85 Low serum albumin is an important risk factor at any age because of its role in transporting many drugs through the bloodstream. More unbound drug becomes available

DIAGNOSIS AND ASSESSMENT

Diagnostic criteria for delirium were first published in the Diagnostic and Statistical Manual III (DSM-III). Differentiation of delirium from other so-called organic mental disorders was not possible before DSM-III. DSM, published in 1952,17 described acute and chronic brain syndromes, which were considered disorders caused by or associated with impairment of brain-tissue function. They were “characterized by a basic syndrome consisting of (1) impairment of orientation, (2) impairment of

PHENOMENOLOGY

The phenomenology of delirium has been characterized inadequately. The more knowledge we have about the incidence and interrelationships of various delirium symptoms, the greater the accuracy we can expect from future DSM versions and the more information we can elucidate about underlying neuropathogenesis and syndrome subtypes. Different symptom profiles might predict outcomes. For example, Wada and Yamaguchi143 reported more cognitive impairment, sleep-wake cycle disturbance, and mood

DELIRIUM ASSESSMENT METHODS

Several assessment instruments for delirium have been developed during the past decade and were recently reviewed.132 Some were developed without regard to any gold standard (i.e., DSM criteria). The validation of some methods was confounded by comorbid dementia in the populations evaluated. Some screening instruments are not specific enough or sufficiently detailed to assess the breadth of delirium symptoms, and false-positive cases may be identified. Nonetheless, the existence of efforts to

NEUROPATHOPHYSIOLOGY

Lesion studies and functional brain imaging may offer clues about which brain regions are affected during delirium. Prefrontal cortex; right cerebral hemisphere (especially parietal); and subcortical nuclei (especially right-sided thalamus and caudate) are important areas.131 For example, strokes in the anteromedial thalamus10, 31, 110 and posterior parietal cortex11, 50, 75, 94 present with severe delirium as the main clinical manifestation. In depressed patients, caudate lesions27, 66 and

NEUROTRANSMISSION IN DELIRIUM

Alterations in neurotransmission underlying delirium include cholinergic, dopaminergic, serotonergic, and GABA-ergic systems, with noradrenergic, glutamatergic, opiatergic, and histaminergic systems possibly also involved. Many of these neurotransmitters play an important role in the neurologic pathways delineated as possibly underlying delirium (see previous section). The cholinergic and dopaminergic systems have received the most attention, with decreased acetylcholine and increased dopamine

TREATMENT

Standard management and treatment of delirium begins with a careful search for underlying causes that might be reversed. Environmental manipulations, such as the use of calendars, night lights, family photos, and reorientation by staff, are also implemented. Treatment of the delirium itself needs to occur simultaneously with these measures and is largely pharmacologic, most often using haloperidol. Interestingly, haloperidol lowers glucose use during PET scans of humans in frontal and anterior

References (149)

  • J.L. Levenson

    High-dose intravenous haloperidol for agitated delirium following lung transplantation

    Psychosomatics

    (1995)
  • P.J. Manos

    Letter to Editor

    Psychosomatics

    (1995)
  • M. Marzanatti et al.

    Effects of nonsedating histamine H-1 antagonists on EEG activity and behavior in the cat

    Pharmacol Biochem Behav

    (1989)
  • J.M. Monti

    Involvement of histamine in the control of the waking state

    Life Sciences

    (1993)
  • E. Ongini et al.

    Stimulation of dopamine D-1 receptors by SKF 38393 induces EEG desynchronization and behavioral arousal

    Life Sciences

    (1985)
  • F. Ovsiew

    Letter to editor

    Psychosomatics

    (1995)
  • D. Picotte-Prillmayer et al.

    H-2 blocker delirium

    Psychosomatics

    (1995)
  • F. Adams

    Emergency intravenous sedation of the delirious medically ill patient

    J Clin Psychiatry

    (1988)
  • F. Adams

    Neuropsychiatric evaluation and treatment of delirium in the critically ill cancer patient

    The Cancer Bulletin

    (1984)
  • N. Akaike et al.

    Quinolone and fenbufen interact with GABA-A receptors in dissociated hippocampal cells of rats

    J Neurophysiol

    (1991)
  • M.S. Albert et al.

    The Delirium Symptom Interview: An interview for the detection of delirium symptoms in hospitalized patients

    J Geriatr Psychiatry Neurol

    (1992)
  • D. Ames et al.

    Organic mental disorders associated with buproprion in three patients

    J Clin Psychiatry

    (1992)
  • D.H. Armstrong et al.

    Effect of haloperidol on dopamine-induced increase in renal blood flow

    Drug Intell Clin Pharm

    (1986)
  • E.J. Bartlett et al.

    Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects

    Am J Psychiatry

    (1994)
  • D. Berggren et al.

    Postoperative confusion following anesthesia in elderly patients treated for femoral neck fractures

    Anesth Analg

    (1987)
  • J. Bogousslavsky et al.

    Manic delirium and frontal-like syndrome with paramedian infarction of the right thalamus

    J Neurol Neurosurg Psychiatry

    (1988)
  • J. Boiten et al.

    An unusual sequela of a frequently occurring neurologic disorder: Delirium caused by brain infarct

    Ned Tijdschr Geneeskd

    (1989)
  • Breitbart W, Marotta R, Platt M, et al: A randomized double-blind trial of haloperidol, chlorpromazine, and lorazepam...
  • P.A. Broderick et al.

    Dopamine and serotonin in rat striatum during in vivo hypoxic-hypoxia

    Metab Brain Dis

    (1989)
  • M.T. Champagne et al.

    The NEECHAM Confusion Scale: Assessing confusion in the hospitalized and nursing home elderly

    Gerontologist

    (1987)
  • J.A. Coffman et al.

    Cholinergic mechanisms in delirium

    Am J Psychiatry

    (1988)
  • J. Cutting

    The phenomenology of acute organic psychosis: Comparison with acute schizophrenia

    Br J Psychiatry

    (1987)
  • Diagnostic and Statistical Manual, Mental Disorders

    (1952)
  • Diagnostic and Statistical Manual-II

    (1968)
  • Diagnostic and Statistical Manual-III

    (1980)
  • Diagnostic and Statistical Manual-III-R, revised

    (1987)
  • Diagnostic and Statistical Manual-IV

    (1994)
  • D.M. Feeney et al.

    Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury

    Science

    (1982)
  • F. Fernandez et al.

    Treatment of severe, refractory agitation with a haloperidol drip

    J Clin Psychiatry

    (1988)
  • F. Fernandez et al.

    Management of delirium in terminally ill AIDS patients

    Int J Psychiatry Med

    (1989)
  • G.S. Figiel et al.

    ECT-induced delirium in depressed patients with Parkinson's disease

    J Neuropsychiatry Clin Neurosci

    (1991)
  • G.S. Figiel et al.

    Radiologic correlates of antidepressant-induced delirium: The possible significance of basal ganglia lesions

    J Neuropsychiatry Clin Neurosci

    (1989)
  • M.D. Foreman

    Confusion in the hospitalized elderly: Incidence, onset, and associated features

    Res Nurs Health

    (1989)
  • J. Francis et al.

    Prognosis after hospital discharge of older medical patients with delirium

    J Am Geriatr Soc

    (1992)
  • J. Francis et al.

    A prospective study of delirium in hospitalized elderly

    JAMA

    (1990)
  • J.H. Friedman

    Syndrome of diffuse encephalopathy due to nondominant thalamic infarction

    Neurology

    (1985)
  • S.B. Gelfand et al.

    Using intravenous haloperidol to control delirium

    Hosp Comm Psychiatry

    (1992)
  • G.E. Gibson et al.

    Decreased synthesis of acetylcholine accompanying impaired oxidation of pyruvate in rat brain slices

    Biochem J

    (1975)
  • Y. Gustafson et al.

    Acute confusional states in elderly patients treated for femoral neck fracture

    J Am Geriatr Soc

    (1988)
  • R.E. Hales et al.

    An evaluation of patients who received an organic mental disorder diagnosis on a psychiatric consultation-liaison service

    Gen Hosp Psychiatry

    (1988)
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    Address reprint requests to Paula T. Trzepacz, MD, WPIC, 3811 O'Hara Street, Pittsburgh, PA 15213

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    From the Neuropsychiatry Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

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