Recognizing and Managing Delirium

Scott A. Irwin

Gary T. Buckholz

Rosene D. Pirrello

Jeremy M. Hirst

Frank D. Ferris

INTRODUCTION

Delirium is an important medical diagnosis defined as an acute change in mental status that may fluctuate and has underlying physiologic causes (1,2). Subtypes of delirium have been defined based on the presence (hyperactive) or absence (hypoactive) of psychomotor agitation, perceptual disturbances, and/or level of consciousness (3). Often both subtypes are present (mixed) (4,5,6,7,8,9,10,11,12).

In the context of serious illness, delirium is highly prevalent and associated with many undesirable consequences. Most physiologic disturbances can cause delirium; however, even with serious or advanced illness, causes can often be determined and reversed. Despite this, delirium is still underrecognized and under-managed. Careful history taking, assessment of symptoms, consideration of differential diagnoses, and clear communication among the team are key to making the diagnosis. Having the diagnosis of delirium and determining prognosis, functional status, and goals of the patient/family are paramount to successful management. With this information, delirium can be conceptualized as potentially reversible or irreversible, and both workup and management strategies flow from these concepts, as well as the presence or absence of the hyperactive subtype. Both pharmacologic and non-pharmacologic interventions can be employed to improve symptoms and relieve patient/family distress.

Prevalence and Consequences

Delirium is very common in the setting of advanced illness, with reported rates of up to 56% in the hospitalized elderly (13,14), 87% in intensive care units (15,16,17), and 88% of patients with advanced cancer or at the end-of-life (8,9,18,19,20,21,22). It likely occurs in nearly 100% of patients who are actively dying. Disagreement about the most common subtype exists, but hypoactive is often reported as the most prevalent (9,10) and is the one most often under-recognized (8). One study of 228 end-stage cancer patients found the prevalence of delirium to be 47%, and of those, 68% were hypoactive (8).

Delirium leads to unnecessary medical interventions, increased hospital admissions, prolonged hospitalizations (13,14,23,24), increased healthcare utilization and costs (14,25,26), increased need for higher levels of care (24,27), functional decline (27), increased mortality (2,8,20,21,24,27,28,29,30,31,32,33), and decreased life expectancy (28,34,35). It can also impair the recognition and control of other physical and psychological symptoms, such as pain (36,37,38). This all leads to a significant amount of distress for patients, families, and caregivers (39,40,41,42). One study of 101 cancer patients who recovered from delirium reported that 54% recalled the experience and that patients, spouses/caregivers, and nurses all reported moderate to severe distress from the experience, no matter the subtype (43).

Causes

The most common causes of delirium found in patients with serious and/or advanced illness are fluid and electrolyte imbalances, medications (benzodiazepines (44,45), opioids (21,45,46,47), steroids (45,46,48), and anticholinergics (49,50)), infections, hepatic or renal failure, hypoxia, and hematologic disturbances (21,51). A selected list of important causes to consider is presented in Table 40.1 (52).

Under-Recognition

Delirium is often unrecognized or misdiagnosed due to its complex and variable presentation, the inconsistent language used to describe it, preconceived notions about advanced illness and the dying process, and the difficulty of recognizing the hypoactive subtype. A retrospective study of 2,716 patients receiving hospice care found delirium was documented in only 17.8% of those in the homecare setting and 28.3% of those in an inpatient setting (53). Another study demonstrated that a palliative care team was only able to recognize delirium in 45% of all patients with an expertconfirmed delirium diagnosis, and in only 20% of those with hypoactive delirium (8).

Behaviors, Signs, and Symptoms

The diagnosis of delirium is based on a careful history that accurately captures all observed behaviors, signs, and symptoms that potentially indicate its presence, many of which are changes in mental status. To effectively communicate an evaluation, all clinicians need to know the definitions of and recognize the common behaviors, signs, and symptoms associated with delirium (Table 40.2).

TABLE 40.1 Selected common causes of delirium

System	Causes
Brain	Stroke, seizure, head trauma, brain mass or metastases, normal pressure hydrocephalus, infection
Heart, lungs, circulation	Cardiac or pulmonary disease (anything that causes hypoxia), carotid disease, anemia, infection
Digestive, urinary	Hepatic or renal failure, peritonitis, bowel obstruction, fecal impaction, constipation, urinary retention, urinary tract infection
Endocrine	Thyroid, parathyroid, adrenal
Metabolic	Acid-base or electrolyte disturbances, abnormal glucose, dehydration
Toxicity and/or withdrawal	Drugs of abuse, opioids, steroids, benzodiazepines, anticholinergics, immunosuppressants, interferon, histamine-2 blockers (cimetidine and ranitidine)

ASSESSMENT

Routine screening can help identify patients at risk for delirium who can then be assessed more thoroughly. Once delirium is suspected, a careful assessment is necessary to optimally manage patients with delirium, including the following:

TABLE 40.2 Behaviors/symptoms/signs often associated with delirium

Behaviors/Symptoms/Signs	Definition
Acute onset	Rapid onset of symptoms over minutes to days, even if began or occurred in the past
Agitation	Unintentional, excessive, and purposeless cognitive and/or motor activity
Altered level of consciousness	Clinically differentiable degrees of awareness and alertness, that is, hypervigilant, alert, lethargic, cloudy, stuporous, and comatose
Confusion	Not oriented to person, place, time, or situation
Delusion	A fixed and false belief or wrong judgment that opposing evidence does not change. Can be paranoid, grandiose, somatic, and persecutory
Disinhibition	Unable to control immediate impulsive response to a situation
Disorganized thinking	Thoughts are confusing, vague, and/or do not logically flow; they are loosely or not connected
Fluctuation or waxing/waning	Intensity changes rapidly; symptoms may come and go
Hallucination	Perception of an object or event that does not exist. May be visual, auditory, olfactory, gustatory, or tactile
Inattention	Inability to focus or direct thinking
Irritable	Prone to excessive impatience, annoyance, or anger to get needs met
Labile affect	Rapidly changing and out of context mood symptoms
Psychosis	Loss of contact with reality
Restlessness	See agitation

Careful description of the observed behaviors, signs, and symptoms
Differentiation of delirium from other related diagnoses
An understanding of the underlying context of the patient, that is, the primary diagnosis, associated comorbidities, functional status, and prognosis
The goals of care for the patient and family

Screening

Multiple tools have been developed to facilitate routine screening for delirium and tracking of symptom severity (52,54). The Confusion Assessment Method (CAM) is a brief, nine-item screening tool that looks at change over time (temporal profile), attention, thought processes, and levels of consciousness (55,56). It can be easily administered by non-psychiatrically trained personnel and has been validated in many populations, including patients with advanced illnesses (57). A shorter, four-question version of the CAM, which can be administered quickly, has accuracy similar to the full nine-question version (25). It has a sensitivity of 94% to 100% and specificity of 90% to 95% (55), but this can vary by setting and the administrator’s clinical discipline.

Gold Standard Assessment

The gold standard for assessing delirium is a thorough history, a complete mental status and physical examination, and comparison with the DSM-IV TR criteria for delirium (2,58,59). As delirious patients are often not good historians, the gathering of collateral information is key. Caregivers, including family members and support staff, can identify and describe the behaviors, signs, and symptoms they see using simple, clear, and common language (see Table 40.2). This will help make the diagnosis of delirium and differentiate it from other diagnoses with similar presentations (see Table 40.3). Each observed behavior, sign, and symptom should be described by change over time (temporal profile), severity, and response (positive or negative) to previous therapeutic interventions (60).

A careful medication history, which documents all changes in medications and dosages over recent days, weeks, or even months, especially those leading up to the mental status changes, should be included. The types and severity of all allergic and adverse reactions need to be noted and confirmed. A careful drug and alcohol history is important; of particular interest are drugs that cause withdrawal syndromes, for example, alcohol, opioids, benzodiazepines, and muscle relaxants.

Diagnostic and Severity Rating Tools

The Delirium Rating Scale Revised-98 and the Memorial Delirium Assessment Scale are diagnostic and severity rating tools that can be used to confirm the diagnosis of delirium and to monitor changes over time (61). Both tools require that the rater have familiarity with basic psychiatric concepts.

TABLE 40.3 Differential diagnoses

	Delirium	Dementia	Psychotic Disorders	Depression	Anxiety
Onset	Hours to days	Gradual	Varies	Varies	Varies
Changes in alertness	Yes	Late	No	No	No
Frequent fluctuation	Yes	No	No	No	Varies

The Delirium Rating Scale Revised-98 includes 3 specific diagnostic items and a 13-item severity rating scale (61,62). When compared with expert psychiatric diagnosis with DSM criteria, it has a sensitivity of 91% to 100% and a specificity of 85% to 100%. It has been shown to differentiate delirium from disorders with similar presentations, including depression, dementia, and schizophrenia. Its predecessor, the Delirium Rating Scale, has been used to evaluate delirium in children and adolescents (63).

The Memorial Delirium Assessment Scale is another diagnostic and severity rating scale designed for serial measurements in clinical intervention trials. It is a 10-item rating scale that can be used as frequently as every 4 hours to track the course of delirium (64). It has a sensitivity of 97% and a specificity of 95%, when compared with expert psychiatric diagnosis using DSM criteria. Other tools have been designed for use in the intensive care unit (16,65,66,67), with children (63,66), and by non-psychiatrically trained staff (68,69).

Several tools are often used inappropriately to screen for and assess delirium. Both the Mini-Mental State Exam and the Clock Drawing task are measures of global cognitive function, and the Mini-Mental State Exam can be used as a screen for Alzheimer’s dementia. Neither of these are specific to nor should be used to assess delirium (70,71,72).

ALTERNATIVE DIAGNOSES TO CONSIDER

Many of the signs, symptoms, and behaviors associated with delirium can be associated with other diagnoses. As the underlying causes and management vary greatly, it is important to differentiate delirium from dementia, depression, anxiety, bipolar disorder, psychotic disorders (e.g., schizophrenia), personality disorders, developmental disorder, and adverse effects of medications (e.g., akathisia) (2), among other things. Table 40.3 lists differences in onset, changes in alertness, and frequency of fluctuation that help clinicians to make accurate diagnoses. When in doubt, assume the patient is experiencing delirium until proven otherwise, as delirium is the most common of these related diagnoses in patients with advanced illnesses. It should not be assumed that agitation is driven by pain; careful assessment of pain and consideration of other causes of agitation are important.
For complex clinical situations, mental health professionals can be consulted to quickly help minimize suffering for the patient, family, and caregivers (73).

TABLE 40.4 Objective signs of active dying

Categories	Signs
Cardiac dysfunction	Tachycardia Decreased cardiac output Decreased intravascular volume Peripheral cooling Peripheral and central cyanosis Mottling of the skin (livedo reticularis) Venous pooling
Respiratory dysfunction	Tachypnea with progressive slowing and decreasing tidal volume Abnormal breathing patterns, for example, apnea, Cheyne-Stokes, agonal
Renal dysfunction	Oliguria progressing to anuria Darkening of urine
Neurologic dysfunction	Loss of swallow Loss of gag reflex Buildup of oral and tracheal secretions Loss of sphincter control Altered level of consciousness Seizures

Delirium itself goes by many synonyms, including acute confusional state, ICU psychosis, encephalopathy, acute brain failure, and syndrome of cerebral insufficiency. It is important to recognize that these all refer to the same diagnosis. To ensure effective management and avoid confusion, it is best to diagnose these as “delirium.”

Underlying Diagnoses and Prognosis

Delirium in patients with advanced illnesses may or may not be reversible. To establish the potential reversibility of delirium, it is important to know each patient’s goals of care, principal underlying diagnosis and comorbidities, their functional status, and overall prognosis (74,75,76,77,78). If an underlying abnormal physiologic process is suspected, with appropriate investigation and therapies, the condition could be potentially reversible, even in the context of advanced illness, if consistent with patient/family goals.

Several studies have demonstrated the ability to find and reverse causes of delirium in the context of serious or advanced illness. One study of 213 hospice inpatients with cancer and delirium found a cause of the delirium in 93 (61%) of the 153 patients who chose to have a workup. The causes were found to be multifactorial in 52% of the cases, and a complete remission occurred in 20% (51). Another study of 104 inpatients with advanced cancer who were receiving palliative care found reversible causes in 50% of the 71 who developed delirium (21). Other studies have found reversible causes in up to 68% of cases (21,34,79).

Delirium becomes irreversible (1) if workup or reversal fail, (2) in the context of a known irreversible processes (e.g., active dying or end-stage liver failure), or (3) if workup or reversal are inconsistent with patient/family goals of care. Most patients who are actively dying (exhibiting objective signs of the dying process (74,80,81), (Table 40.4) experience either a hyperactive or a hypoactive delirium (74,80). As dying is an irreversible process of multi-system organ failure, this delirium is irreversible. Management of irreversible deliria focuses on settling and supporting the patient, the family, and caregivers.

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