Urine analysis and cultureChest radiographElectrocardiogramFurther evaluation guided by initial evaluationBrain imaging with magnetic resonance with contrast (preferred) or computed tomographySerum ammoniaErythrocyte sedimentation rateBlood culturesLumbar puncture (if suspicion of meningitis, should be performed initially)Electroencephalography (if high suspicion of status epilepticus, should be performed initially)Autoimmune, paraneoplastic, and infectious serologies

There are no clear data as to the yield of brain imaging in delirious patients. Most clinicians will proceed to imaging quickly if the initial laboratory work-up is unrevealing. A non-contrast head CT can exclude intracerebral hemorrhage and many large space-occupying lesions. Magnetic resonance imaging (MRI) of the brain with gadolinium can definitively exclude most cases of acute stroke and allow for assessment of structural changes consistent with neurodegenerative disease, toxic exposures, and encephalitis. Therefore, MRI is likely the test of choice if brain imaging is to be performed on patients with delirium, but this technique may be limited by the patient’s inability to remain still for long periods of time, contraindications such as many types of cardiac pacemakers, as well as cost.

Management of delirium

Management of the patient with delirium involves both addressing symptoms of the disorder and identifying and treating the underlying etiology. Tapering or discontinuing likely offending medications is often the first step in management of a delirious patient, given the high incidence of medication-induced or medication-exacerbated delirium.

The first-line treatment for delirium involves non-pharmacologic environmental and structural interventions that can be extremely effective [4]. Inouye and colleagues [45] published a study of a multicomponent intervention designed to reduce and treat delirium in over 850 patients 70 years and older admitted to a general medical ward. These patients were matched (not randomized) to either an intervention unit or a standard care unit in the hospital. A variety of nursing methods were used to assess and treat various factors that may contribute to delirium, including cognitive impairment (through increasing orientation reminders and cognitive stimulation), sleep deprivation (by instituting unit-wide noise reduction and environmental improvement at night), immobility (through early and frequent mobilization), visual impairment (by making available visual aids and adaptive equipment), hearing impairment (through providing amplifying devices and communication techniques), and dehydration (by instituting aggressive volume repletion). The study demonstrated good adherence to this regimen in the intervention group. The patients in the intervention group demonstrated a decreased incidence of delirium as well as a decreased number of days with delirium. Elements of this protocol are inexpensive and quite easy to employ in most hospital or nursing home settings. Other studies have shown a decreased incidence of delirium with staff education programs or through early involvement of geriatrics or psychiatry consultations [46, 47].

Many of these same strategies have also been used for primary prevention of delirium. Hospitals and other health care facilities are increasingly taking a proactive approach to identifying at-risk individuals and initiating these non-pharmacologic strategies in order to reduce the incidence of delirium, beginning at the time of admission or early in the postoperative period.

Medications, usually antipsychotic drugs or benzodiazepines, are often administered to treat agitation, behavioral problems or insomnia in patients with delirium. However, multiple studies have examined this approach and have failed to show that these medications are effective. In some trials, these drugs have been shown to reduce the incidence of delirium without convincing impact on clinical outcomes and, in others, these medications have either demonstrated no effect on delirium or led to clinical worsening. As a result, medications are not typically recommended for the treatment or prevention of delirium [4, 48].

Pharmacologic therapy should be reserved for patients who are posing a direct harm to themselves or to staff, and even in this context, it should be recognized that no convincing evidence supports their effectiveness. Benzodiazepines are clearly the proper choice in cases of alcohol or sedative withdrawal. Antipsychotics should be used in all other cases of delirium in the lowest dose possible with careful attention to cardiac issues including QT prolongation. Use of these agents must be judicious, not only due to lack of effectiveness, but in the context of US Food and Drug Administration (FDA) warnings regarding an apparent increased mortality in elderly individuals exposed to these antipsychotic drugs [49].

Future directions

The field of delirium remains, some 2,500 years after its initial description, largely understudied compared with diseases with much lower prevalence. The opportunities for future research in this area are enormous and have been mentioned throughout the course of this chapter.

Detailed clinical descriptions of delirium using careful modern cognitive techniques and neuropsychological testing are needed in order to fully define the spectrum of this disease and distinguish it from other cognitive disorders, including the neurodegenerative diseases. Imaging data including MRI as well as functional and perfusion studies are sorely lacking in patients with a history of delirium and in those who are actively delirious. These imaging data may provide important information towards elucidating the pathophysiology of delirium and defining neural networks which are disrupted.

Genetic data involving patients with delirium are also lacking; many of the differential responses to medication that can cause a delirium may be a result of polymorphisms in drug metabolism pathways. In addition, inflammatory pathways and alterations in the brain’s neurotransmitter milieu that are triggered during an episode of delirium need to be more fully defined in order to develop novel therapeutic approaches, which must be tested in double-blind, randomized controlled trials. It is only through these types of research approaches that this very common and costly medical problem can eventually be adequately addressed.

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