Delirium
David Meagher
Paula Trzepacz
Introduction
Delirium is an acute or subacute, usually reversible syndrome of impaired higher cortical functions hallmarked by generalized cognitive disturbance and caused by one or more aetiologies. It is most common in medical-surgical patients, especially in intensive care units, and those in hospice and nursing homes. The term ‘delirium’ derives from the Latin ‘lira’ meaning literally to wander from the furrow. Prior to DSM-III (1980) such disturbances were described by a plethora of labels (acute organic brain syndrome, acute confusional state, brain failure, toxic encephalopathy, intensive care psychosis), before Lipowski advocated for the umbrella term delirium to subsume these multiple synonyms. This engendered a more scientific research effort and consistent approach to detection and management. Though delirium has been recognized for at least two millenia, it is only now beginning to receive the attention that it warrants, with increasing appreciation of the considerable impact upon outcomes and independent need for treatment as a brain disorder beyond only treating its underlying aetiological precipitants.
Inattention is the cardinal disturbance, including distractibility, reduced vigilance or concentration, and impaired environmental awareness. This contrasts with dementia, another disorder of generalized cognitive deficits, where memory deficits are cardinal. While full-blown episodes are easier to diagnose, its prodrome, subclinical presentation, and potential persistence present unresolved dilemmas regarding diagnostic boundaries of delirium. Further, comorbidity with dementia presents challenges for detection and attribution of progressive impairments in the elderly. Though delirium occurs at any age, there is a dearth of research in younger age groups such that it is unclear whether research findings from geriatric studies can be generalized to other age groups (e.g. regarding risk factors and outcomes). Studies that clarify common features such as phenomenology, neural circuitry or electrophysiology are thus critical.
Clinical features
Delirium is a complex neuropsychiatric syndrome with a broad range of cognitive and neurobehavioural symptoms which is why it can be misattributed to other psychiatric disorders by nonspecialists. Symptoms involve cognition, thought, language, sleep-wake cycle, perception, affect, and motor behaviour. The constellation of symptoms—along with the cardinal symptom of inattention and acute onset and fluctuating temporal course—are characteristic of delirium and when comorbid with dementia, delirium dominates the clinical presentation.(1) Phenomenology studies (mostly crosssectional) suggest that ‘core’ symptoms occur with greater frequency while other less consistent ‘associated’ symptoms may reflect the biochemical influence of particular aetiologies or genetic, neuronal or physiological vulnerabilities (see Table 4.1.1.1). Accumulating evidence indicates three core domains of delirium phenomenology: ‘Cognition’ comprising of inattention and other cognitive deficits; ‘Higher Level Thinking Processes’ including impaired executive function, semantic expression, and comprehension; and ‘Circadian Rhythm’ including fragmented sleep-wake cycle.(2) The underlying neural support for these domains is consistent with neuroanatomical findings in lesion and functional neuroimaging studies that implicate certain brain regions and neural circuitry.
Table 4.1.1.1 Symptoms of delirium | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Delirium occurs as a stage of consciousness in the continuum between normal awakeness/alertness and stupor or coma. During the 20th century, delirium was described as a ‘clouding of consciousness’ but this rather nebulous concept has been replaced by a better understanding of the components of phenomenology that culminate in severely impaired higher order brain functions. Specifically, a disproportionate disturbance of attentional processes, including environmental awareness difficulties, along with impaired higher level thinking reflected in irrelevant, unfocused or illogical thought processes and impaired abstraction and comprehension (i.e. executive cognition and semantic language function) typifies the delirious state. Sleep-wake cycle fragmentation belies a circadian disturbance that may contribute to the abnormal level of consciousness and alterations in motor behaviour, where hypoactivity contributes to difficulties in differential diagnosis of delirium from stupor. Delirium is distinguished from stuporose states by the presence of arousability. The majority of intensive care unit patients emerging from comatose states experience a period of diagnosable delirium.(3)
Inattention is the cardinal and required symptom to diagnose delirium and is noticeable on interview by distractibility, spatial inattention, and inability to sustain attention. More formal testing can be assessed using months of the year backwards or digit span. The Cognitive Test for Delirium (CTD)(4) allows for separate visual digit span and vigilance testing. Memory impairment—of both short and long term—can be affected by inattention but appears to be independently impaired. Visuospatial impairment can be assessed by observing patient behaviour in their immediate environment e.g. losing their way or getting lost. Constructional ability can be tested formally by copying figures; clock face drawing assesses not only proportions and details but also involves prefrontal executive functions for placing the minute hand correctly. Delirious patients have executive dysfunction affecting abstraction, initiation/ perseveration, switching mental sets, working memory, temporal sequencing and organization, insight and judgment. Poor performance on the Trailmaking Part B test distinguishes delirious from nondelirious patients and requires not only spatial attention and concentration but also switching mental sets. Though none of these cognitive deficits is specific to delirium, the array and pattern is highly suggestive.
Thought process abnormalities in delirium range from circumstantiality and tangentiality to frank loose associations in more severe cases. Naming impairment is common though more severe cases can mimic fluent dysphasia with semantic deficits being characteristic such that communication is wrought with deficits of meaningfulness. Interestingly, the dysphasia can be mistaken for Wernicke’s aphasia and possible stroke but is reversible when the delirium clears. Careful assessment can usually distinguish between semantic deficits (language impairment) and loose associations (thought process disorder) except with word salad.
Disruption of sleep-wake cycle is essentially ubiquitous in delirium except in the briefest episodes (e.g. concussion) and often predates the appearance of a full-blown episode. Minor disturbances with insomnia or excessive daytime somnolence may be hard to
distinguish from other medically ill patients without delirium, but more substantial alterations involve sleep fragmentation or even complete sleep-wake cycle reversal that reflect disturbed circadian rhythm regulation. The relationship of circadian disturbances to the characteristic fluctuating severity of delirium symptoms over a 24 hr period or to motor disturbance is unknown.
distinguish from other medically ill patients without delirium, but more substantial alterations involve sleep fragmentation or even complete sleep-wake cycle reversal that reflect disturbed circadian rhythm regulation. The relationship of circadian disturbances to the characteristic fluctuating severity of delirium symptoms over a 24 hr period or to motor disturbance is unknown.
Motor activity alterations are very common in delirium. They have been used to define clinical subtypes (hypoactive, hyperactive, mixed) though studies are inconsistent as to the prevalence of these subtypes and often include nonmotor symptoms in descriptions. Cognitive impairments and EEG slowing are comparable in hyperactive and hypoactive patients though other symptoms may vary. Psychotic symptoms occur in both although the prevailing stereotype suggests that they only occur in hyperactive cases. Hypoactive cases are prone to non detection or misdiagnosis as depression. A range of studies suggest that motor subtypes differ regarding underlying pathophysiology, treatment needs, and prognosis for function and mortality though inconsistent subtype definitions and delayed/poorer detection of hypoactives impacts interpretation of these findings.
Psychotic symptoms occur in up to 50 per cent of patients with delirium. Thought content abnormalities include suspiciousness, overvalued ideation and frank delusions. Delusions are typically poorly-formed and less stereotyped than in schizophrenia or Alzheimer’s disease. They usually relate to persecutory themes of impending danger or threat in the immediate environment (e.g. being poisoned by nurses), and less commonly to grandiose themes. Misperceptions include depersonalization, delusional misidentifications, illusions and hallucinations. Hallucinations and illusions are primarily visual though they can be tactile and auditory whereas auditory modalities tend to dominate in psychosis in mood and primary psychotic disorders. Formications suggest dopamine or anticholinergic toxicity.
Delirium may be abrupt as with concussion, drug intoxication or stroke, or can be preceded by a prodromal period characterized by anxiety, sleep disturbance, cognitive impairments and increased levels of perceived distress. Symptom profile appears similar across age groups(5) but delirium is understudied in pediatric patients. The propensity for particular aetiologies to shape clinical presentation is also understudied. Unfortunately, delirium tremens (with florid psychosis and agitation) is the dominant clinical stereotype even though many cases present with relative hypoactivity especially in the elderly, those with concomitant dementia, or where delirium is related to metabolic causes or organ failure. This misleading stereotype is one of the reasons for the poor recognition of delirium where typically 50 per cent of cases are missed in routine clinical practice.
Diagnosis and differential diagnosis
ICD-10 and DSM-IV share key features used to diagnose delirium (i.e. acute onset, fluctuating course, inattention, and disorganized thinking) although the ICD-10 description gives better account of the breadth of symptoms that can occur (e.g. disturbances of sleep and motor activity). DSM IV is more inclusive and preferred in research studies, though may be less rigorous than ICD-10 when used by less skilled clinicians. DSM-IV classifies cases according to presumed aetiological cause, though a single aetiology occurs in less than half of cases and no aetiology is identified in around 10 per cent. Delirium is also subclassified according to its relationship to dementia.
Delirium is poorly detected in clinical practice by nonpsychiatrists with more than 50 per cent of cases missed, misdiagnosed, or diagnosed late. This is due to multiple factors: the complex and fluctuating nature of delirium symptoms, inadequate education and interview skills of nonpsychiatrists, underappreciation of the prognostic significance of delirium, and inadequate routine cognitive screening in real world practice. Delirium can be the first indicator of serious physical morbidity (e.g. stroke) and represents a medical emergency. It is not surprising therefore that nondetection is associated with poorer outcomes that include elevated mortality.(6) Poor outcomes in hypoactive patients may be in part due to nondetection.
The course of delirium is highly variable reflecting the heterogeneity of aetiology and patient populations in which delirium occurs, with recent studies emphasizing that it is frequently not the benign and transient condition that was previously thought. While in many cases, delirium is brief (hours to days), represents a transitional state from unconsciousness or is a benign reaction to treatment exposures, in other cases it can be more prolonged (e.g. after traumatic brain injury) or associated with serious complications and persistent cognitive difficulties where differentiation from dementia becomes difficult. Rudberg et al.(7) studied elderly medical-surgical inpatients with delirium and found that episode duration was 24 hrs or less in over two-thirds of patients. Conversely, Sylvestre et al.(8) studied elderly medical admissions over two-month follow-up and identified five separate patterns of recovery, with fast improvement in only 11 per cent of patients. Greater clarity regarding the factors that shape these varying courses is needed.
Delirium diagnosis is complicated by comorbidity where over 50 per cent of cases are superimposed on dementia or other preexisting cognitive impairments. Distinguishing delirium from the neuropsychiatric symptoms of dementia can be challenging but acute onset, fluctuating course, temporal relationship to an identifiable physical precipitant, prominent inattention and altered level of consciousness usually allow differentiation. Third party informants and previous medical charts can be crucial in clarifying the trajectory of cognitive impairment. Studies comparing symptoms of delirium and dementia indicate that where they coexist, delirium symptoms dominate the clinical picture. Given the poor prognostic implications of delirium, a management hierarchy applies with delirium taking diagnostic precedence over other neuropsychiatric disorders so that any acute alteration in mental state is presumed to be delirium until otherwise established.
Some symptoms of delirium also overlap with primary psychiatric disorders. Major depressive disorder can be misdiagnosed in hypoactive presentations or when affective lability includes tearfulness and sad mood. Agitated depression or severe mania (‘Bell’s mania’) can mimic hyperactive delirium but the affective lability and incongruent moods of delirium contrast with more sustained alterations in mood and effect in major mood disorders. The character of psychotic symptoms in delirium differs from primary psychotic illness (see above). Acute schizophrenic psychosis involves disorganized thoughts with delusions and hallucinations but inattention is less prominent. Acute schizophrenia can include marked cognitive impairment with perplexity that can mask or be mistaken for comorbid delirium and in such cases the EEG can be helpful. Table 4.1.1.2 describes key clinical features for differentiating delirium from other neuropsychiatric conditions.
Table 4.1.1.2 Differential diagnosis of delirium vs other common neuropsychiatric conditions | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Nondetection of delirium is particularly common in older patients with comorbid dementia, multiple medical problems and hypoactive motor presentations. Chronic subsyndromal delirium in the elderly is commonly related to low grade infections or medication adverse effects, where adjusting medications can significantly improve cognition. Monitoring for any acute deterioration from baseline function coupled with regular formal assessment with simple cognitive tests such as the digit span, months of year backwards, serial sevens or clock drawing enables delirium detection. Unfortunately, overreliance on orientation as a measure of cognition precludes more accurate detection. The emphasis on orientation, inconsistent administration, and ceiling effects limit the usefulness of the (MMSE) in measuring delirium. The Cognitive Test for Delirium was designed specifically for delirium and emphasizes attention, semantic comprehension, and nonverbal, right hemisphere cognitive functions. It is particularly useful in critically medically ill persons.
The Confusion Assessment Method (CAM)(9) is a screening tool to assess the presence or absence of four items from DSM-III-R delirium criteria to make a provisional diagnosis of delirium. It is especially suited to epidemiological studies and screening in high risk populations where neuropsychiatric differential diagnosis or broad phenomenological measurements are not needed. Its accuracy is enhanced if ratings are anchored by formal testing as in the CAM-ICU(10) but is substantially reduced when used by nurses because they frequently miss inattention when it is present.
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