21: Delirium

Delirium is an acute disorder of attention and cognitive function that may arise at any point in the course of an illness. It is often the only sign of a serious underlying medical condition, especially in older persons who are frail or who have underlying dementia.

The prevalence of delirium on admission can range from 10% to 40%. During hospitalization, it may affect an additional 25% to 50%. The rates of postoperative delirium are estimated at 10% to 52%. Even higher rates (70% to 87%) are seen in ICUs. In addition, 80% of terminally ill patients become delirious before death.

Three forms of delirium have been recognized: the hyperactive, hyperalert form; the hypoactive, hypoalert, lethargic form; and the mixed form, which combines elements of both. The hypoactive form is often unrecognized but more common among older hospitalized patients; it is associated with a poorer overall prognosis.

Delirium as a geriatric syndrome is inherently multifactorial and develops as a result of interactions between predisposing risk factors and noxious insults or precipitants. Thus, it is imperative that clinicians identify and address all potential factors and observe patients closely for resolution.

The major predisposing risk factor for delirium is preexisting cognitive impairment, specifically dementia, which increases the risk of delirium 2- to 5-fold. Virtually all chronic medical illnesses can predispose older persons to delirium, as can specific neurological and metabolic disorders. A full list of risk factors is included in Table 21–1.

The foremost precipitating factor is medications, which contribute to more than 40% of cases of delirium. The medications most frequently associated with delirium are those with known psychoactive effects, such as sedative hypnotics, opiates, H₂ blockers, and anticholinergic drugs. The American Geriatrics Society published a list of potentially inappropriate medications for older adults, known as the 2012 Revised Beers Criteria, which encompasses some of these delirium-provoking medications. In addition, delirium risk increases in direct proportion to the number of medications prescribed. Herbal therapies are being increasingly recognized as causing or contributing to delirium, especially when taken concurrently with a psychoactive medication. This is particularly true for psychoactive herbs, such as St. John’s wort, kava kava, and valerian root. Table 21–1 lists other precipitating factors, including intercurrent illness, environmental, and surgery.

Table 21–2 shows targeted preventive interventions, most of which can also be nonpharmacologic treatments for delirium. Prevention of delirium by targeting vulnerable patients with predisposing risk factors or precipitating factors has been shown to be effective. In addition, proactive geriatrics consultation (daily geriatrician visits and targeted recommendations based on a structured protocol) is effective in vulnerable patients with preexisting dementia or functional impairments.

Pharmacologic prevention of delirium has demonstrated conflicting results in a number of randomized controlled trials examining joint surgeries and postoperative delirium. Olanzapine has been found to lower incidence but increase duration and severity of delirium while haloperidol decreased duration, severity, and length of stay but had no effect on incidence. In general, the use of antipsychotics prophylactically in delirium prevention is not recommended since no study successfully prevented delirium or demonstrated decreased morbidity. Sedation depth during surgery has been correlated with postoperative delirium. Light sedation has been associated with decreased rates of delirium, suggesting a role for lighter sedation in older surgical patients, to prevent delirium.

Symptoms & Signs

Initial evaluation of delirium is largely based on establishing a patient’s baseline cognitive functioning and the clinical course of any cognitive change. Thus, a detailed history from a reliable informant, such as a spouse, child, or caregiver, is most important. The history should seek to clarify the acuity of any mental status changes and seek clues to the underlying cause.

The cardinal historical features of delirium are acute onset and fluctuating course, in which symptoms tend to come and go or increase and decrease in severity over a 24-hour period. This is the major feature distinguishing delirium from dementia, which usually develops gradually and progressively over months to years.

Cognitive changes—

Usually determined through cognitive testing and, most importantly, close clinical observation of the quality of the patient’s response. For example, a person may score correctly on a particular cognitive task but during the task may demonstrate fluctuating attention, easy distractibility, rambling speech or lethargy.

Inattention—

Decreased ability to focus, maintain and shift one’s attention. For example, patients will demonstrate difficulty maintaining or following a conversation, perseverate on a previous answer, require repetition of instructions or struggle to follow instructions on cognitive tasks (simple repetition, digit span, backward recitation of months/days).

Disorganized thinking—

Manifested as rambling and, at its extreme, incoherent speech. Problems with memory, disorientation, or language are frequent.

Altered level of consciousness—

Ranges from agitated, vigilant states to lethargic or stuporous states.

Other features—

Not essential for diagnosis but commonly seen are psychomotor agitation or retardation, perceptual disturbances (eg, hallucinations, illusions), paranoid delusions, emotional lability, and sleep-wake cycle disturbances.

Laboratory Findings and Imaging

The algorithm in Figure 21–1 provides a systematic approach to the diagnosis and evaluation of delirium in the older person. No specific laboratory tests exist that positively identify delirium. Current research has focused on specific biomarkers that have been promising, but all require further investigation: S-100 beta, insulin-like growth factor-1, neuron specific enolase and inflammatory markers including cytokines interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, procalcitonin, and cortisol.

Laboratory tests in the evaluation of delirious patients should include complete blood count, electrolytes (including calcium), kidney and liver function, glucose, and oxygen saturation. Furthermore, in searching for occult infection, blood cultures, urinalysis/urine culture, chest x-ray may be considered. Other laboratory tests may be pursued if specific contributing factors have not been identified in a particular patient. These include thyroid function tests, arterial blood gas, vitamin B₁₂ levels, drug levels, toxicology screens, cortisol levels, and evaluation of the cerebrospinal fluid.

Brain imaging with CT or MRI are indicated by a history or signs of recent fall or head trauma, fever of unknown origin, new focal neurologic symptoms, or no obvious cause has been identified. An electroencephalogram may be indicated to evaluate for occult seizure activity. It can also be used in differentiating delirium from nonorganic psychiatric disorders.

Physical Examination

Detailed physical examination is essential for evaluation of delirium. Delirium may often be the initial manifestation of serious underlying disease in an older person; thus, astute attention to early localizing signs on physical examination may allow early diagnosis of a precipitating insult. A careful search for evidence of occult infections should be performed, including signs of pneumonia, urinary tract infection, acute abdominal processes, joint infections, or new cardiac murmur. A detailed neurologic examination with attention to focal or lateralizing signs is also crucial.

Special Tests

Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-5)—

The American Psychiatric Association DSM-5 guidelines were developed based on expert opinion and remain the current standard for definition and diagnostic criteria for delirium.

Confusion Assessment Method—

Simple, validated tool currently in widespread use (Table 21–3). It has sensitivity of 94% to 100%, specificity of 90% to 100%, and negative predictive value of 90% to 100% for delirium. It has also been validated in patients with dementia. In the intensive care setting, it is feasible to perform cognitive evaluation and screen for delirium using the CAM-ICU, a modification of the CAM for use in mechanically ventilated, restrained, or nonverbal patients. CAM-ICU has not, however, been found to perform as well, with sensitivity of 64% to 73% and negative predictive value of 83%; among verbal patients, the sensitivity drops to <50%.

Other instruments—

Instruments developed and validated for use in identification of delirium include the Nursing Delirium Screening Scale (NuDesc), Delirium Symptom Interview, NEECHAM Confusion Scale, Delirium Observation Screening Scale, and Intensive Care Delirium Screening Checklist. Instruments developed and validated for use in determining severity of delirium, once it is identified, include the Memorial Delirium Assessment Scale, Clinical Global Impression Scale, and Delirium Severity Index. Other instruments that both diagnose and determine severity of delirium include the Delirium Rating Scale-98 and Cognitive Test for Delirium.

The main diagnostic dilemma facing the clinician is differentiating delirium from dementia. This is especially difficult when knowledge of baseline cognitive function is missing or when there are known cognitive deficits and one must determine whether the current condition is caused by underlying chronic cognitive impairment or to delirium. Thus, it is crucial to obtain a reliable history about baseline status from an informant. Inattention and altered level of consciousness are usually not features of mild to moderate dementia, and their presence supports the diagnosis of delirium. In patients with known dementia, a history that includes worsening confusion over and above the baseline cognitive impairment also suggests delirium.

Other important diagnoses that must be differentiated from delirium are depression, mania, and other nonorganic psychotic disorders, such as schizophrenia. These diseases do not typically arise in the context of a medical illness. Again, the history and clinical course can assist in providing important clues in differentiating these syndromes. Altered level of consciousness is not prominent in these other diseases. At times, the differential diagnosis can be quite difficult as a result of subtle symptoms or an uncooperative patient. Because of the potential life-threatening nature of delirium, one should err on the side of treating the patient as delirious until further information is available.

Delirium is associated with adverse hospital outcomes, including increased morbidity, mortality, functional decline, and immobility and its attendant complications (aspiration pneumonia, pressure ulcers, deep venous thrombosis, pulmonary emboli, urinary tract infections). Moreover, delirium is associated with complications related to its underlying causes. All of these factors contribute to the poor long-term prognosis for delirium in older patients. Delirium is also independently associated with long-term problems, such as poor long-term functioning, mortality, increased length of stay, need for formal home health care rehabilitation services, new institutionalization, and increased costs of care.

Three concurrent approaches are involved in the treatment of delirium (see Figure 21–1): (a) identification and treatment of the underlying medical cause; (b) eradication or minimization of contributing factors of delirium; and (c) management of delirium symptoms.

Complete review of the medication history (including prescription, over-the-counter, as needed, and herbal medications) is needed to identify potentially contributing medications. Drug interactions should be evaluated. Current kidney and liver function status should be assessed and medication dosage/frequency adjusted accordingly. A complete history and physical (including neurological) examination should be performed, along with selected laboratory and radiologic screening tests. Occult infection should be evaluated.

If no identifiable cause or contributor is identified, further testing should be pursued, as shown in Figure 21–1.

Nonpharmacologic Strategies

In general, nonpharmacologic strategies should be used in all delirious patients. Table 21–2 details a number of the strategies utilized to prevent or treat delirium, including reorientation, environment optimization, sensory deficit correction, avoiding restraints, mobility/self-care, and sleep hygiene.

Pharmacologic Strategies

Pharmacologic therapy for delirium should be reserved for severely agitated individuals whose behavior threatens medically necessary care (such as mechanical ventilation) or poses a safety hazard. All medications used in the treatment of delirium can also cause or worsen confusion; thus, a general principle is to use the lowest dose possible for the shortest period of time. The end point should be an awake and manageable patient, not a sedated patient. All too often, a medication is started for management of agitated delirium but continued indefinitely, obscuring the ability to follow mental status on serial evaluation and putting the patient at significant risk for adverse drug reactions.

Acetylcholine deficiency has been recognized as a contributing factor in the etiology of delirium. Cholinesterase inhibitors, however, have not been beneficial in the management of delirium, despite previous hopes. Small trials of donepezil and rivastigmine did not demonstrate benefits in delirium and in one trial, may have been associated with increased mortality. Table 21–2 covers the classes of medications currently recommended for the treatment and management of delirious patients.

Delirium has traditionally been described as a reversible syndrome, implying that patients invariably return to their baseline cognitive and functional state. Clinically, however, delirium is not always transient, and can result in long-term cognitive and functional deficits. After delirium, some patients develop subjective memory complaints, and demonstrate reduced performance on cognitive tests. These research findings suggest that the pathologic processes associated with delirium may be associated with direct and persistent neurologic damage.

Furthermore, patients who develop delirium have been found more likely to be diagnosed with dementia at a later date. It appears that delirium increases the risk of developing dementia and may accelerate the rate of progression to dementia. Thus, delirium can in fact alter the trajectory of cognitive decline for older persons.

American Psychiatric Association guidelines. http://psychiatryonline.org/guidelines.aspx

Hospital Elder Life Program. http://www.hospitalelderlifeprogram.org/public/public-main.php

National Institute for Health and Clinical Excellence (NICE) guidelines for delirium. http://guidance.nice.org.uk/cg103

Systematic Reviews of delirium studies by Martin Cole and colleagues in the Cochrane Library, Database of Abstracts of Reviews of Effectiveness. http://www.cochranelibrary.com

Veteran Affairs guidelines for delirium. http://www.hsrd.research.va.gov/publications/esp/delirium.cfm