East Asian Arch Psychiatry 2013;23:56-64

ORIGINAL ARTICLE

Symptoms and Aetiology of Delirium: A Comparison of Elderly and Adult Patients
谵妄的症状和病原学:老年和成年患者的比较
S Grover, M Agarwal, A Sharma, SK Mattoo, A Avasthi, S Chakrabarti, S Malhotra, P Kulhara, D Basu

Dr Sandeep Grover, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Dr Munish Agarwal, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Dr Akhilesh Sharma, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Surendra K. Mattoo, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Ajit Avasthi, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Subho Chakrabarti, MD, FRCPsych, Department of Psychiatry, Post-graduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Savita Malhotra, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Parmanand Kulhara, FRCPsych, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Prof. Debasish Basu, MD, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

Address for correspondence: Dr Sandeep Grover, Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Tel: (91-172) 2756 807; Fax: (91-172) 2744 401;email: drsandeepg2002@yahoo.com

Submitted: 3 April 2013; Accepted: 25 April 2013


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Abstract

Objective: To compare the symptoms of delirium as assessed by the Delirium Rating Scale–Revised-98 (DRS-R-98) and associated aetiologies in adult and elderly patients seen in a consultation-liaison service.

Methods: A total of 321 consecutive patients with a DSM-IV-TR diagnosis of delirium were assessed on the DRS-R-98 and a study-specific aetiology checklist.

Results: Of the 321 patients, 245 (76%) aged 18 to 64 years formed the adult group, while 76 (24%) formed the elderly group (≥ 65 years). The prevalence and severity of various symptoms of delirium as assessed using the DRS-R-98 were similar across the 2 groups, except for the adult group having statistically higher prevalence and severity scores for thought process abnormalities and lability of affect. For both groups and the whole sample, factor analysis yielded a 3-factor model for the phenomenology. In the 2 groups, the DRS-R-98 item loadings showed subtle differences across various factors. The 2 groups were similar for the mean number of aetiologies associated with delirium, the mean number being 3. However, the 2 groups differed with respect to hepatic derangement, substance intoxication, withdrawal, and postpartum causes being more common in the adult group, in contrast lung disease and cardiac abnormalities were more common in the elderly group.

Conclusion: Adult and elderly patients with delirium are similar with respect to the distribution of various symptoms, motor subtypes, and associated aetiologies.

Key words: Delirium; Syndrome

摘要

目的:以谵妄评分量表修订版(DRS-R-98)评估谵妄症状,并透过谘询会诊服务,把老年和成 年患者的谵妄症状和相关病原学作比较。

方法:以DRS-R-98和研究特定清单,对以DSM-IV-TR诊断为谵妄的321名患者作出评估。

结果:321名患者当中,245(76%)名18至64岁患者被编入成年组,其馀76(24%)名65岁 或以上患者被编入老年组。根据DRS-R-98评估,除了前者其思考过程异常和情感不稳的现患率 显著较高和较严重,2个小组在各种谵妄症状的现患率和严重性皆相若。此外,两组和整体皆分 别产生有关现象学的3因子模型。在2个小组当中,DRS-R-98因子负荷只显示各种因子有微妙 别。2个小组其谵妄相关的病原学数量皆约3个。不过,肝功能异常、物质中毒、物质戒断和产 後起因方面於成年患者中较为常见,相反较多老年患者有肺病和心脏异常。

结论:成年和老年谵妄患者的各种症状、运动亚型和相关病原学皆相若。

关键词:谵妄、症状

Introduction

Even though delirium is a common clinical entity, diagnosing and managing those affected can be extremely challenging due to its broad-based phenomenology. Thus, a clearer delineation of phenomenology can improve the diagnosis and management of delirium.

Factor analysis is a tool extensively used to delineate the phenomenology of delirium.1-15 In the hope that this will help to unravel pathophysiology and indicate better treatment approaches, factor analysis has been used to determine correlations among symptoms and to cluster individual symptoms to generate symptom-based subgroups.16 The existing research in this field is limited to the elderly,1-4,14 critically ill,5,6 those with malignancies,10-12 and those seen in consultation-liaison (CL) services.12-15 Many of these research studies were compromised by their small sample sizes.2-4,9

Two types of symptoms have been delineated for delirium. One refers to the ‘core’ symptoms / disturbances of attention, memory, orientation, language, thought processes, and sleep-wake cycle. The other refers to the more variable ‘associated’ features of psychotic symptoms, affect disturbances, and different motor profiles.17,18 Western research has studied delirium mostly in geriatric population,1-4 even though some studies have covered children, adolescents, and adult populations.19-24 The data are scarce when it comes to comparative studies of the phenomenology in different age-groups. The only study that compared the phenomenology of delirium across the children, adults, and geriatric age-groups did not find any difference, except in the domain of cognitive functions.19 The limitations of this study were small sample sizes (49 adult and 70 geriatric patients) and all were seeking treatment for cancer-related medical indications.19

In contrast to the western research, studies from India suggest that delirium is quite common in adults.12,25,26 Most of the Indian research tried to characterise the phenomenology of delirium covering all age-groups, though predominantly in the adult population (aged < 65 years).12,13,15 We recently studied the phenomenology of delirium in children and adolescents, and compared the same with the previous studies by our group focusing on the symptom profile of delirium in adult and elderly patients.27 This comparison of symptom profile did not reveal significant difference between adults and the elderly, and their comparison was limited by the fact that data for the geriatric group were not prospectively collected. Moreover, previous studies from India lacked comprehensive assessment of the aetiological factors for delirium.

Delirium as such is understood to be an organic disorder with many underlying aetiologies. However, understanding the factors associated with delirium in a developing country setting has received less attention. It is important to understand the aetiological factors of delirium, because these may vary from one setting to another, and awareness about common aetiologies can help identify persons at high risk and prevent its development. Furthermore, it is important to compare the aetiological factors for delirium across different nations to better understand this disorder.

Against this background, the present study aimed to compare the symptoms of delirium as assessed by the Delirium Rating Scale–Revised-98 (DRS-R-98) in adult and elderly patients seen in a CL service. The study also assessed the aetiological factors associated with delirium.

Methods

The study was carried out at the Postgraduate Institute of Medical Education & Research, Chandigarh, a multi- specialty publicly funded teaching hospital in north India. The Department of Psychiatry runs a round-the-clock system for providing psychiatric cover for the entire hospital. The study followed a prospective design. Patients who were admitted to various medico-surgical and emergency wards and diagnosed to have delirium by the CL team were evaluated for phenomenology as well as aetiological factors. Patients were eligible for the study if they were aged ≥ 18 years, fulfilled the diagnosis of delirium as per the DSM-IV-TR criteria,28 and their caregivers provided written informed consent. This study was approved by our institute’s Ethics Committee.

Assessment Tools

Delirium Rating Scale–Revised-98

Delirium Rating Scale–Revised-98 is a 16-item scale, with each item rated on a 4-point scale of 0 to 3. The severity scale comprises 13 initial items, and the other 3 had diagnostic value. It has good inter-rater reliability, validity, sensitivity, and specificity for distinguishing delirium in mixed neuropsychiatric populations including dementia, depression, and schizophrenia.29 It has also been extensively used in previous research on delirium from India.12-14 In the present study, the scale was administered by a qualified psychiatrist.

Delirium Aetiology List

As there are no specific comprehensive instruments available to assess the aetiologies associated with delirium, we specifically constructed a list of putative aetiological factors to take note of. This specifically designed list was based on a review of the literature and covered numerous possible causes of delirium. To be considered as a putative aetiological factor, it was required to be of new onset whilst having an appropriate temporal relationship to the onset of delirium. The delirium aetiology list was drawn up by psychiatrists. The final list was reached by consensus based on the opinion of at least 2 psychiatrists. We still need to validate this instrument in future by evaluating its face validity, content validity, and inter-rater reliability.

Procedure

From 1 November 2010 to 30 June 2011, all patients diagnosed with delirium by the CL team were designated for inclusion in the study. Within 24 hours of psychiatric referral, respective responsible family carers were approached for participation in the study and its purposes and nature explained. Consenting carers were interviewed to confirm the patients’ diagnosis of delirium as per DSM- IV-TR criteria. Then, the required information was obtained from family members, treating team, patients, and treatment records. This entailed completing the clinical profile, aetiology list, and DRS-R-98 based on the information available from the observations made by the treating team and family members with regard to observations of the patients’ behaviour, their mental status evaluation, and investigation findings.

Data Analysis

The data were analysed using the Statistical Package for the Social Sciences, Windows version 14. Frequency counts, percentages, means, and standard deviations were used to describe the sample. Comparisons were performed using Chi-square, Fisher’s exact, and t tests. Factor analysis of all symptom items was carried out using principal component analysis. This included the following steps: preparing a correlation matrix; determining the number of components or factors to be considered; extracting a set of components or factors from the correlation matrix; rotating the components with varimax rotation (to increase interpretability); and interpretation of the results.30

Results

During the study period, a total of 868 CL calls were received, of which 823 patients were aged ≥ 18 years (668 aged 18-64 years and 155 aged ≥ 65 years). Among the latter, there were 352 (43%) who were diagnosed to have delirium, of whom 269 were adults and 83 were older subjects. In all, 344 of the delirious patients (262 adults and 82 older subjects) or their carers could be approached and 321 were finally enrolled in the study; 23 were excluded because the caregivers refused consent (n = 20) or the patients died before being assessed for the study (n = 3). Of these 321 patients, 245 (76%) who were aged 18 to 64 years formed the adult group while the other 76 (24%) formed the elderly group. The point prevalence of delirium among adults referred to the CL service was 40%, and in the elderly group it was 54%. The mean age of the adult and elderly groups was 41 and 73 years, respectively. The adult and elderly groups were similar with respect to gender distribution (males: 72% vs. 67%), duration of delirium prior to assessment (3.8 vs. 4.4 days), emergence of delirium (in hospital: 69% vs. 67%), and number of medications prescribed (3.9 vs. 4.2). Most of the patients in both groups were managed with antipsychotic medications. Those in the adult group were more likely to have a co- morbid psychiatric diagnosis (25% vs. 12%; χ2 = 6.10, p = 0.01) and a co-morbid diagnosis of alcohol dependence (22% vs. 11%; χ2 = 4.94, p = 0.03) [Table 1].

Phenomenology of Delirium

In terms of DRS-R-98 diagnostic items, all the patients fulfilled the criteria of ‘temporal (acute) onset of symptoms’ and ‘presence of an underlying physical disorder’. Details of associated clinical features are shown in Table 2. The adult and elderly groups were similar regarding the type of symptoms, except that the former had a higher point prevalence of thought process abnormalities (87.3% vs. 76.3%; χ2 = 5.45, p = 0.01) and lability of affect (87.8% vs. 78.9%; χ2 = 3.66, p = 0.05).

As shown in Table 2, the 2 groups were similar with respect to the severity of DRS-R-98 item scores, except that the mean scores on lability of affect (1.42 vs. 1.22; t = –1.97; p = 0.04) and thought process abnormalities (1.28 vs. 1.07; t = –2.15; p = 0.03) were statistically higher in the adult group.

Factor Analysis of Delirium Rating Scale–Revised- 98

The Kaiser-Guttman Rule was used to determine the optimum number of the factors. Items were included in the analysis only if they had a loading of ≥ 0.4 on that factor. When the loading was ≥ 0.4 on more than 1 factor, the item was assigned to the factor on which it had the higher loading. Scree plots were also generated. The initial principal component analysis of the whole sample yielded 4 factors. Based on our previous experience and the literature, 3-factor models were generated for the whole sample and the 2 groups, respectively. The 3-factor model Kaiser-Meyer- Olkin (KMO) [-0.702; χ2 = 1231; p < 0.001] explained 45% of the variance for the whole sample, which was 47% for the adult group (KMO, -0.703; χ2 = 1016; p < 0.001) and 49% for the elderly group (KMO, -0.603; χ2 = 379.52; p < 0.001). Table 3 shows the distribution of various symptoms on different factors, which is being more or less similar for the whole sample and the adult group.

In the whole group, all items of the DRS-R-98 had significant loading on 1 of the 3 factors. The first factor included sleep-wake cycle disturbances, perceptual disturbances, delusions, lability of affect, motor agitation, fluctuation of symptom severity, and inverse of motor retardation; it was therefore named as the psychotic and motor symptoms factor. The second factor included language abnormalities, thought process abnormalities, disturbances in short-term memory, long-term memory, and visuospatial ability; it was named as cognitive factor. The third factor included disturbances in attention, orientation, temporal onset of symptoms, and a physical disorder; it was therefore named as the diagnostic factor. In the factor analysis for the adult group the same factor structure was retained, with similar distribution of items across all the 3 factors.

In the elderly group, the first factor included items evaluating disturbance in language, thought process abnormalities, long-term memory, and visuospatial ability along with presence of delusions; it was named as the cognitive factor. The second factor was similar to factor 1 of whole group and adult patients, except that it did not load delusions and lability of affect, and additionally loaded presence of a physical disorder as a diagnostic item. The third factor loaded the items of disturbances in attention, orientation, and short-term memory along with inverse of lability of affect.

Aetiological Factors for Delirium

In all, the patients presented with a mean of 3 aetiologies associated with delirium. More than 75% of the patients had 2 aetiologies or more, 50% had 3 or more, and 25% had 5 or more.

As shown in Table 4, the most common aetiology was the presence of metabolic disturbances (n = 192; 60%), followed by organ insufficiency (n = 155; 48%), medications (n = 128; 40%), post-surgery status (n = 74; 23%), and sepsis (n = 69; 22%). The most common metabolic abnormalities were hypoxia followed by anaemia and hyponatraemia. The 2 groups (adult and elderly) were similar for the type of aetiology associated with delirium, except that hepatic derangement (21% vs. 8%), substance intoxication (9% vs. 1%), withdrawal (16% vs. 5%), and postpartum (3% vs. 0%) were more common in the adult group, while lung disease (9% vs. 3%) and cardiac abnormalities (34% vs. 8%) were more common in the elderly group.

Discussion

Delirium forms the largest diagnostic category among the psychiatric referrals.25 The present research compared the phenomenology of delirium in adult and elderly hospital populations referred to psychiatric CL service, and used factor analysis to study the DRS-R-98–assessed phenomenology of delirium. Delirium was diagnosed as per DSM-IV-TR and its phenomenology rated by a well- validated scale. The sample size in the present study was larger than that in most previous factor analytic studies of delirium.2,3,5,8-10,12-14 No exclusion criterion was used so as to include a truly representative sample. Patients with dementia were not excluded, as evidence suggests that the clinical presentation of delirium is not significantly affected by the presence of dementia.2

The similar finding of higher point prevalence of delirium in the elderly (54%) was shown in previous studies25,31 as well as that from our centre.14,25 Thus, delirium emerges as the commonest diagnosis in psychiatric referrals. This indicates the need for the psychiatric trainees to be adequately sensitised and familiarised to diagnose and manage delirium.

In the present study, the rate of developing delirium during hospitalisation (68%) was higher than that in the previous studies from different centres / countries,32-34 but similar to that from our centre.13,31 The mean duration of delirium at the time of psychiatric evaluation was about 4 days, which suggests a considerable lag of time in the development of delirium and psychiatric referral. This emphasises that patients admitted to general medical and surgical wards should be screened for delirium from time to time to facilitate earlier diagnosis.

The present study showed that the symptom profile of adult and elderly patients with delirium was mostly similar, except that lability of affect and thought process abnormalities were statistically more common and more severe in the adult group. The lack of significant differences in most symptoms among adults and the elderly is consistent with a western study comparing similar age- groups.19 However, the latter evaluated the symptom profile using DRS, which has only 1 item to evaluate the cognitive dysfunction, whereas the present study entailed the DRS-R-98 which evaluates the cognitive domain of delirium by recourse to specific evaluations for attention, orientation, short-term memory, long-term memory, and visuospatial ability. In our previous study,27 we did not find a significant difference in the symptom profile of children and adolescents with delirium compared to adults and the elderly, except for very few items. Taken together, it can be concluded that the symptom profile of delirium is mostly similar across different age-groups. From the clinical perspective, these findings can have important implications in terms of developing or using screening instruments for the assessment of delirium across different age-groups.

Existing research suggests 2 types of symptoms in delirium. The ‘core’ features that are almost invariably present include disturbances of attention, memory, orientation, language, thought processes, and sleep-wake cycle, while the ‘associated’ features are more variable in their presentation including psychotic symptoms, affect disturbances, and different motor profiles.17,18 Findings of the present study are consistent with this assumption, as disturbances in sleep-wake cycle, attention and orientation; fluctuation of symptom severity; and short-term memory impairments were present in more than 90% of the sample. Motor agitation present in about 90% of our patients may reflect referral bias as overt behavioural symptoms prompt referral more often. However, this profile is similar to the findings noted in previous studies12,13 from our centre, which also included patients with delirium evaluated by our CL services. Disturbances of language or thought process, indicating disturbance of higher order thinking, were present in more than 80% of our patients. This concurs with recent studies in other populations in which such disturbances were reported as key elements of delirium, with recommendations to include them in the diagnostic criteria.11,17,35 Such consistent expression of thought process abnormalities suggests that the de-emphasis of disorganised thinking as a diagnostic criterion between DSM-III-R and DSM-IV may warrant re-examination during development of criteria for delirium in DSM-V and / or ICD-11.36 However, any re-introduction of disorganised thinking as a key criterion requires that more reliable ways of assessment for non-psychiatrists be devised, as this was a key reason for its removal after DSM-III-R.37

The 3-factor structure of DRS-R-98 in the present study explained 45 to 49% of the variance, depending on the study group. Existing factor-analytic studies of the original DRS and the DRS-R-98 have also yielded 2 or 3 factors, which can explain 44 to 64% of the variance.2,3,5,8-15 Almost all the earlier factor analyses have yielded one or more cognitive and behavioural factors.2,3,5,8-15 Thus, despite differences in study populations and assessment instruments, considerable consistency of results is evident across different studies, including ours. In most of the previous studies (including from our centre),12-15 the first factor was a composite cognitive factor that accounted for most of the variance. It consisted of what would be considered as the ‘core’ symptoms, such as inattention, reduced awareness, memory impairments, and other cognitive abnormalities. In previous reports, moreover, 1 or more neurobehavioural factors consisting of ‘associated’ symptoms such as delusions, hallucinations, and motor abnormalities accounted for the rest of the variance. In the present study, in 2 of the 3-factor analyses (whole sample and adult group), the first factor comprised psychotic and motor symptoms while the second factor comprised cognitive symptoms, although the eigenvalue and percentage explained by each of these factors were nearly equal. This was at variance with the literature. The third factor more or less indicated the diagnostic features of the DSM-IV. Motor and psychotic symptoms explaining the maximum variance in the symptoms could be due to the fact that the study was limited to the referred patients.

In contrast, in our elderly group, the first factor was cognitive symptoms, which included long-term memory disturbances and higher order cognitive disturbances, i.e. disturbance of language and thought process. Motor and psychotic symptoms formed the second factor and the third factor included another aspect of cognitive symptoms including disturbances of attention, orientation, and short- term memory. On a closer look into the adult group and the whole sample, this factor structure appears to be clearer in that motor and psychotic symptoms load onto 1 factor, higher-order cognitive symptoms load onto another, and the diagnostic items load onto the third. In the elderly group, however, the distribution of each symptom was slightly different and each did not load clearly to a symptom group as that in the adult group. This subtle difference in factor structures reflects differences in the phenomenology of delirium in adults and the elderly. Notably, however, the sample size of the adult group was almost 3.5 times that of the elderly group, which could have influenced the findings.

In the present study, the mean number of aetiologies was 3, which was similar to that reported in the existing literature,38-40 including a study from our centre.15 The most common aetiologies in our study were metabolic disturbances, organ insufficiency, medications and sepsis, which was also in keeping with the existing literature.25,31,32 These findings suggest that in severely ill medical or surgical patients, it is important to treating subtle metabolic disturbances to reduce proneness to delirium. Similar efforts should be made to the treatment of organ insufficiency and infections, as well as to reduce medication loads. Apart from clinical perspective, it is important that the family members of these patients be provided information about delirium and re-orientation cues, so as to facilitate early diagnosis and the institution of early non-pharmacological preventive measures. It is also important for primary treating teams to appreciate that management of these underlying physical abnormalities may be sufficient to treat delirium.

Only few significant differences with regard to different types of aetiologies associated with delirium were found across different age-groups, one of which compared the aetiological factors or associated medical-surgical conditions in adults with the elderly.19 In this study, however, only cancer patients were included; by contrast, patients from different medical-surgical setups were included and the findings suggested that in the elderly, pulmonary and cardiac insufficiency were more commonly associated with delirium. Hence, in a setup like ours, if services for screening of patients with delirium are to be started, we need to specifically focus on cardiac and pulmonary diseases in such patients. Whereas for adults, the screening for delirium should focus on substance abuse, substance intoxication or withdrawal states, especially if associated with hepatic decompensation.

In conclusion, the present study suggests that delirium forms the largest diagnostic category in CL referrals from various medical and surgical wards across all age-groups, with a significantly higher percentage pertaining to the elderly than adults. The most common symptoms of delirium noted across adult and elderly patients include disturbances of sleep-wake cycle, attention, orientation, short-term memory, motor agitation, and fluctuation of symptom severity. The types of symptoms seen in adult and elderly patients are similar, except that the former had a significantly higher prevalence of thought process abnormalities and lability of affect. The present study also provides further support for a 3-factor structure of symptoms of delirium, and endorses the traditional distinction between ‘core’ and ‘associated’ symptoms of the condition. The findings of the factor analyses suggest that there were minor differences in variance explained by different symptoms, as well as similar aetiologies associated with delirium in both age-groups. The exceptions were that hepatic derangement, substance intoxication and withdrawal, and being postpartum were more common in adults, while more elderly had lung disease and cardiac abnormalities.

One limitation of our study was that cross-sectional assessments and an aetiologically heterogeneous sample limit definitive conclusions. Accordingly, future studies should include longitudinal investigations of aetiologically homogenous populations and concurrent investigations of underlying neurobiology. Such improvements might be more helpful in unravelling this complex condition. The effect of treatment and management of underlying causes on delirium outcomes warrant further study. A second limitation was that only patients referred to the psychiatry CL team enrolled in our delirium study, and can only be generalised to such referrals. Future studies should screen all admitted inpatients to improve generalisation of the findings. Thirdly, the delirium aetiology list we used needed to be validated. Finally, the risk factors for delirium were not studied, and that identifying them may also help in instituting preventive strategies.

Declaration

The authors declared no conflict of interest in this manuscript.

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