Delirium is such a common event in patients with serious illness that it makes the assessment of pain and symptoms difficult and is a major cause of distress among patients, family members, and health-care providers. Approximately 50% of delirium episodes are reversible (Fig. 5.1). Diagnosis of delirium is commonly missed, and its early symptoms, such as anxiety, insomnia, and mood changes, may be treated with anxiolytics and antidepressants, which may worsen the delirium [3, 4].

5.1 CLINICAL FEATURES OF DELIRIUM

The symptoms of delirium tend to fluctuate during the day and develop acutely, usually from hours to days. Its main diagnostic criteria, based on DSM-IV-TR criteria, are:

• Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention
  
• A change in cognition (such as deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia [1]

Three clinical subtypes of delirium have been described based on the type of arousal disturbance. Hyperactive delirium is characterized by confusion, agitation, hallucinations, delusions, myoclonus, and/or hyperalgesia. Hyperactive delirium is commonly mistaken as anxiety or extrapyramidal symptom. Hypoactive delirium is characterized by confusion, somnolence, and/or withdrawal, which might simulate depression. Mixed delirium presents as alternating symptoms of both hyperactive and hypoactive delirium [3–5].

Terminal delirium is the term used for the approximately 80% of patients who develop delirium in the last hours to days of life. Bruera et al. have shown in a study of 52 hospitalized patients that 88% of patients died with delirium and 83% with cognitive failure, occurring on average 16 days before death [6]. In the last 24–48 h of life, the delirium is most likely not reversible. This is due to the irreversibility of the common process that occurs at final hours of life, like multiorgan failure [6].

5.2 DIFFERENTIAL DIAGNOSIS OF DELIRIUM

The symptoms of delirium can also been associated with other psychiatric disorders like depression, anxiety, mania, psychosis, and dementia. Patients with hypoactive delirium are frequently diagnosed with depression or even overlooked completely. However, while delirium is common in palliative care patients at the advance stage of their disease, depression occurs less frequently. On the other hand, patients with mild delirium often have depressive symptoms. To differentiate between delirium and depression, the important factors to consider are the following: the abrupt onset, severity of cognitive symptoms, and characteristic fluctuating arousal or consciousness, which is the most predominant symptom of delirium [7]. Another confounding diagnosis to be considered is dementia, as it shares some clinical features with delirium, but differs in that there is little or no clouding of consciousness and has an insidious onset. Patients with dementia may also develop superimposed delirium, acutely exacerbating their usual symptoms [8] (please see Table 5.1 for clinical features of delirium, dementia, psychosis, and depression).

5.3 CAUSES FOR DELIRIUM

The pathophysiology of delirium is still not fully understood, but many neurotransmitters are thought to play a role on it. The most important hypothesized mediators are an excess of dopamine and a deficiency of acetylcholine. Circulating cytokines and other neurotransmitters have also been implicated [8].

The etiology of delirium is often multifactorial [9, 10]. Inouye et al. describe the interaction between predisposing or vulnerability factors and precipitating or incident factors [11, 12]. Patients with baseline cognitive impairment, poor functional status, advanced age, as well as increased severity of illness and multiple comorbidities are at higher risk of developing delirium (Table 5.2). Precipitating factors include medications, acute illness, underlying neurologic disease, surgery sleep deprivation, and certain environmental conditions [11–13]. Delirium in the palliative care setting is almost always multifactorial and in most cases a specific cause often remains unidentified. However, this should not deter the health-care professional from investigating for underlying causes as some of them might be reversible if treated adequately.

Delirium is a common complication near the end of life. Symptoms and signs of delirium—including confusion, restlessness, agitation, and/or day–night reversal—occurring in the last days of life are referred to as terminal delirium. It is not reversible and usually is accompanied by other clinical signs of the dying process like increased pharyngeal secretions, moaning, groaning, and grimacing that, in combination with agitation and restlessness, may be misinterpreted as physical pain. A hypoactive form of delirium may occur with less psychomotor activity. Delirium can be distressing to family members and interpreted as an “uncontrolled pain or traumatic death” unless it is recognized and treated appropriately [14–16].

5.4 DELIRIUM ASSESSMENT

Delirium is frequently missed but more often misdiagnosed, because the symptoms might mimic other entities. A detailed history and physical exam, including listening to the observations of caregivers, are key to the early diagnosis of delirium. All the possible reversible causes should be investigated since the treatment will depend on correction of the cause. All medications should be revised, particularly opioids, benzodiazepines, antiemetics, and steroids, as they are frequent causes of delirium.

The health provider should maintain a high index of suspicion and use a scale or instrument to rapidly screen for delirium.

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