Phenomenology of delirium: Assessment of 100 adult cases using  standardised measures

Background Delirium phenomenology is understudied.

Aims To investigate the relationship between cognitive and non-cognitivedelirium symptoms and test the primacy of inattention in delirium.

Method People with delirium (n=100) were assessed using the Delirium Rating Scale–Revised–98 (DRS–R98)and Cognitive Test for Delirium (CTD).

Results Sleep–wake cycle abnormalities and inattentionwere most frequent, while disorientation was the least frequentcognitive deficit. Patients with psychosis had either perceptualdisturbances or delusions but not both. Neither delusions norhallucinations were associated with cognitive impairments.Inattention was associated with severity of other cognitive disturbances but not with non-cognitive items. CTD comprehensioncorrelated most closely with non-cognitive features of delirium.

Conclusions Delirium phenomenology is consistent with broad dysfunction of higher cortical centres, characterised in particularby inattention and sleep–wake cycle disturbance. Attentionand comprehension together are the cognitive items that bestaccount for the syndrome of delirium. Psychosis in deliriumdiffers from that in functional psychoses.

INTRODUCTION

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INTRODUCTION

Although our understanding of the clinical epidemiology of deliriumhas advanced considerably over the past decade, greater phenomenologicalstudy should allow more targeted studies of underlying mechanismsand therapeutic response. Delirium involves a constellationof symptoms reflecting widespread disruption of higher corticalfunctions that characteristically occur with an acute onsetand fluctuating course. However, the interrelationship of delirium symptoms and their relevance to aetiology, treatment experienceand outcome are poorly understood. Moreover, there is a dearthof research using validated instruments designed to assessthe phenomenological breadth and complexity of this disorder(Turkel et al, 2006).

Two validated tools open the way for more detailed phenomenologicalstudy of delirium. The Cognitive Test for Delirium (CTD; Hart et al, 1996) measures five cognitive domains using standard neuropsychologicalmethods. The Delirium Rating Scale – Revised–98(DRS–R98; Trzepacz et al, 2001a,b) covers a broad rangeof delirium symptoms not measured by other delirium instruments,including language, thought process abnormalities, visuospatial ability and both short- and long-term memory. We report a 2-yearstudy of the frequency and severity of symptoms in 100 casesof delirium occuring in a palliative care setting using theDRS–R98 and the CTD. We explored the interrelationshipamong delirium symptoms and, by measuring cognition carefullyin conjunction with the DRS–R98, tested the primacy of inattention in delirium.

METHOD

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METHOD

Study design
We conducted a prospective cross-sectional study of deliriumsymptoms and cognitive performance in consecutive cases ofDSM–IV delirium referred from a palliative care in-patientservice. Patients assessed on daily ward rounds by the palliativecare team as having altered mental state were screened withthe Confusion Assessment Method (CAM; Inouye et al, 1990) –a four-item instrument based on DSM–III–R criteria. Patients were not included if they were near death or if circumstanceswere too difficult to allow assessment (in the opinion of thetreating medical team), which resulted in a small number (lessthan 10%) being excluded. During the study period there were434 new admissions to the unit, of which 100 (23%) are describedhere.

Delirium according to DSM–IV criteria (American Psychiatric Association, 1994)was confirmed by a research physician – (either the principalinvestigator (D.J.M.) or one of three specialist registrarstrained to establish acceptable interrater reliability. Eachcase was then assessed by completion of the DRS–R98 followedby the CTD. The DRS–R98 rated the preceding 24 h period,whereas the CTD measured cognition at the time of its administration.Responses to the CTD were not used to rate DRS–R98 items.Both the DRS–R98 and the CTD are well-validated instruments, highly structured and anchored for rating and scoring.

Consent
The procedures and rationale for the study were explained toall patients, but because of their delirium at entry into thestudy it was presumed that most were not capable of givinginformed written consent. Because of the non-invasive natureof the study, ethics committee approval was given to augmentpatient assent with proxy consent from next of kin (where possible)or a responsible caregiver for all participants in accordancewith the Helsinki guidelines for medical research involvinghuman subjects (World Medical Association, 2004).

Assessments
Demographic data, psychotropic drug exposure and the possibilityof underlying dementia (suggested by history or investigation)were collected. Nursing staff were interviewed to assist ratingof symptoms over the previous 24 h.

Delirium Rating Scale – Revised–98
The original Delirium Rating Scale (Trzepacz et al, 1988)is widely used to measure symptom severity in delirium, but has the limitations of grouping cognitive disturbances intoa single item, not distinguishing motoric disturbances andnot assessing thought process or language disorder. It hastherefore been substantially revised to allow broad phenomenologicalassessment and serial ratings. The DRS–R98 is a 16-item scale with 13 severity items and 3 diagnostic items and ithas high interrater reliability, sensitivity and specificityfor detecting delirium in mixed neuropsychiatric and otherhospital populations (Trzepacz et al, 2001a). It was validatedboth as a total scale (16 items) and a severity scale (13 items)for repeated measures. Each item is rated 0 (absent/normal)to 3 (severe impairment), with descriptions anchoring each severitylevel. Severity scale scores range from 0 to 39, with higherscores indicating more severe delirium. Delirium typicallyinvolves scores above 15 points (severity scale) or 18 points(total scale). For determination of item frequencies in thisstudy, any item scoring at least 1 was considered present.

Cognitive Test for Delirium
The CTD (Hart et al, 1996) was specifically designed to assesspatients with delirium – in particular those who areintubated or unable to speak or write. It assesses 5 neuropsychologicaldomains (orientation, attention, memory, comprehension andvigilance), emphasising non-verbal (visual and auditory) modalities.Each individual domain is scored 0–6 in 2-point increments, except for comprehension which is scored in single-point increments.Total scores range between 0 and 30, with higher scores indicatingbetter cognitive function. This measure reliably differentiatesdelirium from other neuropsychiatric conditions including dementia,schizophrenia and depression (Hart et al, 1997).

Performance on individual neuropsychological sub-tests (e.g.attention) can be scored on a 4-point scale (6 normal, 4 mildinattention, 2 moderate inattention, 0 severe inattention).Item severities were used to compare the relationship betweenindividual items of the DRS–R98 to assess the relationshipbetween cognitive and non-cognitive elements of delirium.

Aetiology
Attribution of aetiology based on all available clinical informationwas made by the palliative care physician according to a standardiseddelirium aetiology checklist (further information availablefrom the authors upon request) with 12 categories: drug intoxication,drug withdrawal, metabolic/endocrine disturbance, traumaticbrain injury, seizures, infection (intracranial), infection(systemic), neoplasm (intracranial), neoplasm (systemic), cerebrovascular,organ insufficiency, other central nervous system disorderand other systemic disorder. The presence and suspected roleof multiple potential causes were documented for each caseof delirium, rated on a 5-point scale for degree of attributionto the delirium episode, ranging from ‘ruled out/notpresent/not relevant’ (0) to ‘definite cause’(4).

Statistical analyses
Statistical analysis was conducted using the Statistical Packagefor the Social Sciences version 10.1. Demographic and ratingscale data were expressed as means plus standard deviation.Continuous variables were compared by one-way analysis of variance(ANOVA). The severity of categorical and/or quasi-continuousvariables such as the individual items of the DRS–R98 and CTD was compared with chi-squared analyses. Pearson correlationswere performed between some individual items and between scaletotal scores. Level of significance was determined with a cut-offof 0.05, except where multiple comparisons were made when aBonferroni correction (P<0.001) was applied.

RESULTS

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RESULTS

Half of the 100 patients in the study were men, and the meanage of the group was 70.1 years (s.d.=11.5). A mean of 3.5(s.d.=1.3) aetiological categories were noted per case, withneoplasm (67%), systemic infection (63%), metabolic–endocrinedisorder (45%), organ failure (32%), drug intoxication (27%)and central nervous system lesions (26%) being the most commoncontributing causes. Patients had a mean DRS–R98 totalscore of 21.1 (s.d.=5.5) and severity score of 16.6 (s.d.=5.5),and a mean CTD score of 14.5 (s.d.=8.1). The characteristicsof patients with delirium only are compared with those of patientswith comorbid dementia in Table 1.

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Table 1 Characteristics of patients with delirium v. patients with comorbid delirium and dementia

Table 2 summarises the cognitive and non-cognitive disturbancesassessed with the DRS–R98. Inattention (diagnostic criterionA of DSM–IV) was present in 97% of patients; other cognitivedeficits were also common (76–89%), disorientation beingthe least frequent. Among the non-cognitive items, sleep disturbance(97%) and motoric disturbance (62% each for hypoactive and hyperactiveitems, with 31 patients having evidence of both) were common,such that 94 patients had evidence of at least some degreeof motoric disturbance (items 7 and 8 of DRS–R98). Languageand thought process abnormalities were each present in overhalf the group but were less common than cognitive symptoms.Even when only more severe degrees of impairment were considered, attention and sleep–wake cycle deficits remained themost common, each at 73%.

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Table 2 Frequency of delirium symptoms rated with the Dementia Rating Score–Revised–98 and recorded if present at different levels of severity (n=100)

Forty-nine patients had evidence of psychosis, as defined bya score of $≥$ 2 on item 2 (perceptual disturbances), item 3 (delusions)or item 6 (thought disturbance) on the DRS–R98. Eighteenof these patients scored 3 on one of these three items, indicatingflorid psychosis. The 49 patients with psychosis were not significantlydifferent from the other 51 patients regarding motoric profile(DRS–R98 items 7 and 8) and overall severity of cognitivedisturbance (measured by the CTD). They were younger (t=1.9,P=0.05) with higher total DRS–R98 scores (t=–3.8;P<0.001) and more severe affective lability ( ${chi}$ ²=16.1, d.f.=2,P<0.001).

Patients with psychosis tended to have disturbance of a singlepsychotic component, with only 6 of these 49 patients scoring $≥$ 2 on more than one item. For the whole cohort, DRS–R98items 2 (perceptual disturbance) and 3 (delusions) were notsignificantly correlated (r=0.16); item 6 (thought disturbance)was not significantly correlated with item 2 (r=0.15) or item3 (r=0.01). Moreover, when the analysis was restricted to patientswith psychosis (n=49), thought disturbance and perceptual disturbanceswere inversely correlated (r–0.49, P=0.001) and bothdelusions (r=0.59, P=0.001) and thought disturbance (r=0.35,P=0.01) correlated positively with affective lability, whereasperceptual disturbance was negatively correlated with affectivelability (r=–0.41, P=0.003).

Although neither delusions nor perceptual disturbances correlated significantly with any of the cognitive items of DRS–R98or CTD, thought process disturbance correlated with impairmentsof attention (r=–0.46, P=0.001), memory (r–0.40, P<0.01), orientation (r=–0.30, P=0.03) and comprehension(r=–0.28, P=0.05) items on the CTD, and with attention(r=0.59, P<0.001), orientation (r=0.33, P=0.03) and long-termmemory (r=0.34, P=0.03) items – but not short-term memoryor visuospatial function items – on the DRS–R98.

Cognitive dysfunction rated with the CTD is shown in Table 3.This shows wide-spread impairment of neuropsychological function,with the most frequent (94%) and severest impairments in attentionand vigilance. This parallels the DRS–R98 impairments,of which attention was most often impaired and orientationleast impaired, even though these scales were rated independently of one another and for different time frames – DRS–R98for the previous 24 h and CTD for current performance. TheDRS–R98 attention item includes distractibility and thereforeencompasses both attention and vigilance as assessed in theCTD. Corresponding items on the CTD and the DRS–R98 correlatedhighly: DRS–R98 orientation and CTD orientation (r=–0.75),DRS–R98 attention and CTD attention (r=–0.73),DRS–R98 attention and CTD vigilance (r=–0.60),and CTD memory with DRS–R98 short-term memory (r=–0.47)and long-term memory (r=–0.61). Interestingly, CTD comprehensioncorrelated with the DRS–R98 item for language (r=–0.42,P=0.001) but not with thought process abnormalities (r–0.09).

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Table 3 Frequency of different severity levels of cognitive dysfunction and mean item scores assessed with the Cognitive Test for Delirium (n=100)

In view of the central role given to disturbed attention incurrent delirium descriptions, patients were divided into threecategories according to the severity of attentional deficitmeasured using the CTD: score 4–6, (n=32), score 2 (n=34)and score 0 (n=34). These groups differed for many items (Table 4);however, when significance levels were corrected for multiplecomparisons, the degree of inattention was associated withthe level of impairment of other cognitive disturbances (ratedon both CTD and DRS–R98) but not the non-cognitive DRS–R98items, except for language ( ${chi}$ ²=19.5, d.f.=6, P=0.001).

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Table 4 Item scores for the two delirium scales according to degree of inattention on the Cognitive Test for Delirium

We further examined whether impairment on the other CTD itemsrelated to scores on DRS–R98 items as strongly as didCTD attention, to ascertain whether attention had a uniquerole. After corrections for multiple comparisons, the severityof vigilance impairment was closely related to all other aspectsof cognition but not to non-cognitive items (except for language)and thus mirrored the findings with the CTD attention item. Orientation, memory and comprehension were less strongly associatedwith DRS–R98 cognitive items (Table 5). In contrastto attention, severity of comprehension disturbance was associatedwith the most non-cognitive DRS–R98 symptoms, includingsleep–wake cycle disturbance, psychomotor retardationand language difficulties. These patterns suggest two differentdomains of delirium symptoms.

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Table 5 Significance values for relationship between DRS—R98 items and severity levels for individual CTD items (other than attention)

Seventeen patients had documented evidence of pre-existing cognitive deficits, suggesting their delirium co-occurred with chroniccognitive impairment. These patients were significantly older,had a greater aetiological burden of underlying diseases, andhad more severe disturbances on the DRS–R98 and CTD thanpatients with delirium only (see Table 1). This differencein severity of DRS–R98 scores was accounted for by greaterdisturbance on the five DRS–R98 cognitive items (t=–2.8, P<0.01) rather than the eight DRS–R98 neuropsychiatricand behavioural items.

Out of concern that the inclusion of patients (n=17) with comorbid pre-existing cognitive impairment might have influenced findings,analyses were repeated for the study population with deliriumonly (n=83). The findings regarding DRS–R98 item frequencies,patterns of psychosis and interrelationship of cognitive itemson CTD and DRS–R98 phenomenology were essentially unaltered.

DISCUSSION

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DISCUSSION

This work investigates a more comprehensive range and specificityof symptoms than previous studies of delirium. We assessed100 consecutive cases of DSM–IV delirium using valid,sensitive and standardised instruments designed for detailedphenomenological and neuropsychological evaluation of delirium.We confirmed that delirium is a complex neuropsychiatric syndrome that includes a combination of cognitive, behavioural and psychopathological features. We assessed the frequency and severity of less studiedsymptoms including visuospatial impairment, disorganised thinking,language impairment and different components of attention,memory, and motoric presentations, as well as more detailedevaluation of characteristics of sleep–wake cycle abnormality,perceptual disturbances and thought process abnormality. Previous phenomenological work has generally classed symptoms as presentor absent without proportioning severity. This can result inmore minor disturbances (e.g. of sleep) that are common inall hospitalised patients being rated as equivalent to moresignificant major disturbances (e.g. sleep–wake cycle reversal) that occur in delirium.

Our findings support the concept of delirium as primarily adisorder of cognition with prominent disturbance of attentionconsistent with DSM–IV, but also highlight the frequencyof non-cognitive disturbances. Notably, the frequency of sleepand motoric disturbances were higher than previously describedusing the original Delirium Rating Scale (Meagher & Trzepacz, 1998).This may be related to sampling bias in the current study inthe hospice setting or to methodological differences betweenthe original scale and its revised version, or both.

Delirium symptoms can be divided into ‘core’ featuresthat are almost invariably present (disturbances of attention,memory, orientation, language, thought processes and sleep–wakecycle) and ‘associated’ features that are morevariable in presentation (e.g. psychotic symptoms, affectivedisturbances, different motoric profiles) (American Psychiatric Association, 1999;Trzepacz, 1999). Disturbance of attention is a cardinal symptomof delirium and in our analysis associated strongly with allother cognitive deficits and language, but not with most ofthe non-cognitive features. Some neurologists have viewed deliriumas a disorder of attention. However, the frequency of non-cognitivesymptoms and their lack of association with the severity of objectively measured attentional impairment strongly supportthe view of delirium being a broader neuropsychiatric disorder.Unfortunately, DSM–IV criteria do not adequately reflectthe importance of these other symptoms, for example, sleep–wakecycle disturbance, altered motoric behaviours, and thoughtcontent and process abnormalities. Sleep–wake cycle disturbancemay underlie the fluctuating nature of delirium severity overa 24 h period (Balan et al, 2003).

Pattern of cognitive disruption in delirium
This study confirms delirium as a disorder of global cognition characterised by a prominent disturbance of attention and vigilance. Disorientation was the least frequent cognitive symptom, eventhough many non-psychiatric physicians rely on bedside testsof orientation to time, place and person as their principalmental status evaluation. Almost a quarter of our deliriouspatients had no evidence of disorientation on the DRS–R98 and only 52% had evidence of greater than mild disturbanceof orientation on the CTD. The use of disorientation as a keyindicator of delirium is thus fraught with the likelihood ofmissed cases, and the use of other, more consistent symptoms(such as inattention) would be a more reliable way of screeningfor suspected delirium. The use of instruments such as the Mini-MentalState Examination (Folstein et al, 1975), which are heavilyweighted towards orientation, to detect or monitor deliriumis therefore not supported by these findings.

The cognitive impairment of delirium may represent a singleconstruct or a constellation of elements with differing under-pinnings.Poor performance on CTD attention and vigilance items was significantlyrelated to the degree of disturbance on all other cognitiveitems on both the CTD and DRS–R98, but much less so fornon-cognitive items. Because intact attention is required torecall new information, it is unclear whether the short-termmemory deficits measured on the DRS–R98 (tested in verbalmodality) and the visual memory deficits measured on the CTDare truly primary memory dysfunctions or secondary to attentionaldeficits. The DRS–R98 long-term memory impairments maybe more related to retrieval problems and perhaps less affectedby inattention than short-term memory for new material.

Performance on CTD orientation, memory and comprehension itemswas significantly related to fewer cognitive items comparedwith CTD attention. The CTD comprehension item (comprisinga combination of language and executive function) was associatedwith more non-cognitive DRS–R98 items than the otherCTD items and may denote a different domain of delirium symptomsthan does attention. The combination of disturbed attentionand comprehension may best represent the underlying disturbancescentral to overall delirium phenomenology.

Visuospatial abnormalities are not usually measured in deliriumassessments even though they may underlie problems of wanderingand poor environmental interactions. Mean visuospatial abilityscores were almost as impaired as attention, and CTD attentionis measured in a visuospatial modality. This overlap may reflectthe shared role of the non-dominant posterior parietal cortexin both attention and visuospatial functions (Trzepacz, 1999).

Despite an enduring emphasis on the characteristic fluctuatingnature of delirium, this has not been directly studied. Ratingsof equivalent cognitive items on the DRS–R98 and CTDwere highly correlated (inversely as expected), despite onebeing a symptom rating scale evaluating a 24 h period and theother a cognitive test measuring current status. This suggeststhat certain delirium symptoms – cognition and language– are not as fluctuant as previously described, althoughthis requires further scrutiny with serial measurement overrelatively short periods.

Psychotic symptoms
The significance of psychotic symptoms in delirium remains unclear.It is not known whether patients develop these features dueto specific physiological causes, cognitive impairment withmisunderstanding of the external environment, misperceptions,as part of mood disturbances, or through some other aspectof individual patient vulnerability (Francis, 1992). We foundthat thought process abnormalities – but not delusionsor perceptual disturbances – correlated with overallcognitive impairment. Both delusions and thought disorder correlatedwith affective lability, although perceptual disturbance wasinversely correlated to both thought disorder and affectivelability. Previous work comparing the psychosis of deliriumwith that of schizophrenia found that in delirium thought contentdisturbances tended to involve themes from the immediate environmentand circumstances, hallucinations were frequently visual ratherthan auditory, and formal thought disorder typically comprisedpoverty of thinking and illogicality (Cutting, 1987). We found little relationship among the three elements of psychosis indelirium, as suggested by previous work (Trzepacz & Dew, 1995).This contrasts with functional psychotic illness, in whichcloser relationships have been identified (O’Leary et al, 2000;Meagher et al, 2004). The psychosis of delirium also differsfrom dementia, in which psychotic symptoms are less commondespite the shared generalised nature of brain impairment,and psychosis is associated with degree and rate of declinein cognition (Levy et al, 1996; Aalten et al, 2005). Thesedifferences may have important implications for delirium neuropathophysiology.

Psychotic symptoms are considered particularly common in hyperactive delirium, such as delirium tremens, but also occur in hypoactive presentations. We did not find a relationship between psychosisand motoric items, highlighting the fact that patients withquieter presentations also experience disturbing psychoticsymptoms.

Advancing the concept of delirium
The concept of delirium has evolved considerably over the past25 years. This is reflected in recent studies comparing diagnosticfrequency when DSM–III, DSM–III–R, DSM–IVand ICD–10 criteria are applied to single populations(Laurila et al, 2003; Cole et al, 2003). Future descriptionswill allow further refinement of the syndrome in keeping withemerging evidence and need to account for key phenomenologicalissues, including the following:

delirium detection and diagnosis are confounded by inadequateappreciation of variations in presentation and breadth of symptoms;
core features used to define delirium should be readily detectableand occur with consistency; over-reliance on less common symptomscontributes to non-detection, which in turn hampers clinicaland research efforts;
core defining features should differentiatedelirium from other neuropsychiatric disorders, especiallydementia.

Study limitations
Studies with cross-sectional designs do not examine symptomevolution or whether domains of symptoms vary as overall severitychanges. Longitudinal studies suggest that early delirium ischaracterised by psychomotor disturbances and a disrupted sleep–wakecycle (Fann et al, 2005), and that orientation difficulties,inattention, poor memory, emotional lability and sleep disturbancesare more persistent symptoms (Levkoff et al, 1994; McCusker et al, 2003).

Second, the inclusion of patients with dementia might affectthe clinical profile but there was little discernible effectwhen our study analyses were repeated for the pure-deliriumstudy population. It appears that delirium phenomenology isaltered little by the presence of dementia (Trzepacz et al, 1998),such that delirium symptoms tend to overshadow dementia whenthey co-exist although these symptoms do occur in the contextof greater overall cognitive impairment. Equally, it shouldbe recognised that in order to be truly representative of delirium,studies need to include patients who also have dementia, inrecognition of the substantial comorbidity between the twoconditions.

This study describes delirium phenomenology in a palliativecare population, which may restrict its generalisability toother groups with this condition. Delirium is considered aunitary syndrome with a stereotyped constellation of symptomsthought to reflect disturbance of a final common neural pathway(Trzepacz, 1999). Moreover, the term has subsumed the manysynonyms that have been used to denote acute generalised cognitivedisturbances in various settings but were not based on scientificevidence. Nonetheless, clinical profile may be influenced byfactors that characterise different aetiological or treatmentsettings, but single studies have not compared symptom profiles across patient groups. Delirium occurring in cancer patientstends to be particularly multifactorial in causation, withhypoactive motoric presentations especially common (Morita et al, 2001;Centeno et al, 2004; Spiller & Keen, 2006). Our sampleincluded patients with a broad range of relevant aetiologiesand medications, many with significant psychotropic effectsthat could alter clinical presentation. Further studies areneeded to explore the impact of aetiological, treatment andother individual patient factors on the clinical presentationof delirium.

REFERENCES

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