Chapter 14

Sean P. Heffernan1, Esther Oh2, Constantine Lyketsos3, and Karin Neufeld4

1 Schweizer Fellow in Affective Disorders, Johns Hopkins Hospital, Baltimore, Maryland, U.S.

2 Assistant Professor, Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Associate Director, the Johns Hopkins Memory and Alzheimer’s Treatment Center, Baltimore, Maryland, U.S.

3 Elizabeth Plank Althouse Professor and Chair of Psychiatry, Johns Hopkins Bayview Professor of Psychiatry and Behavioral Sciences, Baltimore, Maryland, U.S.

4 Clinical Director of Psychiatry, Johns Hopkins Bayview Associate Professor of Psychiatry and Behavioral Science, Baltimore, Maryland, U.S.


Delirium is defined as disturbances of consciousness, attention, perception, thinking, memory, psychomotor behavior, emotion, and the sleep-wake schedule. The duration is variable, but the cognitive change is abrupt in onset, usually over the course of hours to days, and ranging in severity from mild to very severe [1]. Delirium is a clinical syndrome indicating underlying pathology; it is not a disease unto itself.

One of the earliest described medical syndromes in ancient writings, delirium is referred to by many names; acute or toxic confusional state, intensive care unit (ICU) psychosis, acute brain failure, and altered mental status are some of the synonyms [2]. Despite its numerous names, it is common and prevalent in all hospital settings. Ten to 42 percent of patients admitted to a general hospital develop delirium during their course [3–5], and 60–85 percent of mechanically ventilated patients admitted to an ICU will have delirium during their stay [6]. Prevalence is high in frail elderly patients; nearly 10 percent of those presenting to the emergency department and 60 percent of those admitted are delirious [7–9]. Prevalence is also high on oncology wards and AIDS services, where rates are 18 percent and 46 percent respectively [10, 11], suggesting that severity of medical illness increases delirium risk.

Delirium is associated with adverse outcomes, most notably with an increased risk of death in the months to years following the episode [12–17]. Delirium is also associated with increased length of hospital stay [17–21], prolonged duration of mechanical ventilation [12], longer ICU stays [17, 18], longer inpatient stays [22, 23], and higher rate of transition to long-term care [24] including nursing homes [25]. Associated poor long-term outcomes following an episode of delirium include decreased functional abilities [26] and persistent cognitive impairment [27, 28]. The effects of delirium are not limited to the patient, as an episode of delirium has been shown to cause severe distress in care providers and family alike [29] and is estimated to cost the United States healthcare system between $38 billion and $152 billion annually [30].

One might conclude that the basic ICD-10 description combined with high incidence would make detection easy. Retrospective analyses indicated that delirium is missed in 65 percent of cases in the emergency department and 72 percent of cases on the inpatient medicine ward [7, 31]. Delirium is a difficult diagnosis to make due in large part to its heterogeneous phenomenology, which can masquerade as other conditions.


The diagnosis of delirium is based on the presence of an abrupt change in the level of consciousness and ability to focus attention. The presentation fluctuates, frequently described as “waxing and waning,” and can have associated changes in cognition, perception, affect, motoric capacity, and prominent sleep-wake cycle disturbances including insomnia, nocturnal exacerbation of symptoms, and disturbing dreams [32]. The phenomenology can include symptoms that are evident in other primary psychiatric illnesses.

Delirium is a disorder of sustained attention and as such can affect a patient’s thinking in a number of ways. Attentional deficits result in difficulty with learning and retaining new information and can result in short-term and intermediate recall deficits, inability to perform sequential tasks, and difficulty with orientation to time, place, and person. Given these deficits, delirium can mimic an amnestic syndrome. Attention and memory problems may result in disrupted logical thought formation, tangentiality, or loosening of associations, mimicking psychotic disorders such as schizophrenia or dementing illnesses of Alzheimer’s or vascular etiology.

Perceptual disturbances, such as hallucinations and illusions, can be present in delirium. Hallucinations, or perceptions without a stimulus, can be present in all sensory modalities in delirium but are most frequently visual. Illusions, or misperceptions of actual stimuli, such as seeing people in shadows, are also reported in delirium. Patients may also develop delusions, or fixed, false, idiosyncratic beliefs. The content of delusions may vary and can be paranoid, persecutory, or somatic. For example, delirious patients may believe their care providers or family members are conspiring against them. The presence of perceptual disturbances and delusions often drive consultation of a psychiatrist since such experiences are often associated with psychotic disorders such as schizophrenia or severe depression and bipolar disorder.

Affective lability, or quick-changing emotional expression, can be seen in delirium. The patient may present with rapid shifts of emotion, with associated anxiety, irritability, or uncontrollable crying. This instability of mood often prompts the team caring for the patient to seek a psychiatric consultation for assessment of a mood disorder. A small study found that 37 percent of general hospital inpatients over the age of 50 years, diagnosed by the non-psychiatric house officers as having major depression at time of consultation, were found to have hypoactive delirium [33].

Psychomotor activity can vary widely and is the distinguishing feature when describing the subtypes of delirium, which include hyperactive, hypoactive, and mixed type [34]. Psychomotor agitation is a constellation of both intentional and unintentional motions, including pacing around a room, wringing or flapping of hands and limbs, and physical aggression. In severe cases, this activity can be harmful to the patient or others due to violence or removal of indwelling catheters and lines. The hyperactive subtype of delirium is associated with psychomotor agitation and aggression; patients are restless, combative, and can be aroused and vocal. While these patients appear alert, their attention is impaired. The psychomotor agitated delirious patient is the most easily recognized by providers but may be mislabeled as a primary psychiatric disturbance such as schizophrenia or mania due to bipolar disorder [35].

Psychomotor slowing is marked by retardation of thought and activity, reduced physical movement and speech, and abulia, a lack of initiative or motivation. The hypoactive delirium subtype is characterized by somnolence along with psychomotor slowing and is often confused with depression. Affected patients may appear uninterested or apathetic and often have difficulty maintaining attention and arousal. Patients with hypoactive delirium can be difficult for clinical staff to identify; unlike those with psychomotor agitation, they are quiet and do not demand attention from the staff. Maintaining a high index of suspicion and diligent direct examination are the best means to identify patients with these phenomena. The mixed subtype of delirium includes alternating states of agitation and hypoactivity [34]. Mixed delirium is most common (54.9 percent of cases), followed by the hypoactive subtype (43.5 percent), and pure hyperactive delirium (1.6 percent) [36]. Mixed delirium is more likely to feature agitation than other subgroups and may be misinterpreted as psychotic illness [32].

These specific symptoms can lead physicians to mistake delirium for other psychiatric illnesses. Because delirium can mimic almost any other psychiatric disorder, it is imperative that providers are careful not to base the premise of a new diagnosis on a delirious presentation. A thorough history with the use of a collateral informant is very important to assess baseline function; a lack of past psychiatric history with abrupt onset of attentional and other cognitive symptoms in the setting of medical illness is highly suggestive of delirium. Physicians must be cautious not to attribute symptoms of delirium to a patient’s known chronic illness.


Delirium is a direct physiological consequence of general medical illness that can be conceptualized as the brain’s involvement in multi-organ system failure [12, 17, 34, 35, 37, 38]. Current hypotheses invoke excess dopamine transmission in the hyperactive subtype and insufficient cholinergic neurotransmission in the hypoactive subtype [39–41]. Further details are beyond the intended scope of this chapter; Fricchione’s 2008 article in the American Journal of Psychiatry details proposed pathways [40]. While the pathophysiology is not yet clear, there are established etiologies that are illustrated in the mnemonic I WATCH DEATH in Table 14.1 [42].

Table 14.1 Etiology of delirium: I WATCH DEATH.

Disorder Clinical examples
Infection Systemic, sepsis, ARDS, CNS infection
Withdrawal From alcohol or sedative/hypnotics such as benzodiazepines or barbiturates
Acute metabolic derangements Acidosis; electrolyte abnormalities including hypercalcemia, hyponatremia; acute renal or hepatic failure
Trauma To brain, or severe burns, hip fracture, or operations
Central nervous system Infections, ischemic or hemorrhagic stroke, hematoma, tumor, seizure, vasculitis, hydrocephalus, paraneoplastic limbic encephalitis, meningeal carcinomatosis
Hypoxia Anemia, hypotension, heart failure, respiratory failure
Deficiency Vitamins such as B12, thiamine
Endocrinopathy Hyper- or hypoglycemia, hyperparathyroidism, hypothyroidism, cortisol dysregulation
Acute vascular accident Hypertensive encephalopathy, arrhythmia, shock
Toxins Medications (esp. anticholinergic, GABA-ergic), organophosphates, solvents, illicit drug or alcohol, vitamin toxicity, carbon monoxide
Heavy metal Lead, mercury

Adapted from Wise [42].

There are a number of risk factors that make a patient more likely to become delirious (see Table 14.2). Some factors are intrinsic to the patient, such as age, preexisting cognitive disorders, visual, hearing and functional impairment, smoking, and alcoholism or other substance use disorders. There are a number of factors that are associated with illness or are iatrogenic that can contribute to precipitation of delirium, including use of physical restraints, bladder catheters and intravenous catheter complications, immobilization, and malnutrition. The use of multiple psychoactive medications or the addition of three or more new medicines also present risk factors for delirium. Many medications are implicated in causing or worsening delirium, including anticholinergics, opioids, benzodiazepines, beta-blockers, antiemetics, antipsychotics, anticonvulsants, and other psychotropics [34, 43–46]. In delirious patients, especially those with pre-existing cognitive impairment, it is important to minimize exposure to medicines, particularly psychotropics and anticholinergics.

Table 14.2 Risk factors for delirium.

Host character Illnesses associated and iatrogenic causes
Cognitive disorders Physical restraints
Age Bladder catheter or multiple IVs and central lines
Severe multisystem illness Immobilization
Psychiatric illness Malnutrition (can also be etiology)
Alcoholism Two or more psychoactive medications
Hypertension Three or more medications added during course
Smoking Prolonged pain
Traumatic brain injury Sleep disturbances (also a symptom)
ApoE4 polymorphisms
Visual or hearing impaired

Ely [43], Inouye and Charpentier [44], Inouye et al. [45], Morandi et al. [34], Van Rompaey et al. [46].

Approach to diagnosis

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May 29, 2017 | Posted by in PSYCHIATRY | Comments Off on Delirium
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