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Symptom profile of delirium in children and adolescent—does it differ from adults and elderly?
Available online at www.sciencedirect.com
General Hospital Psychiatry 34 (2012) 626 – 632
Symptom profile of delirium in children and adolescent—does it differ from adults and elderly? Sandeep Grover, M.D.⁎, Natasha Kate, M.D., Savita Malhotra, M.D., Subho Chakrabarti, M.D., F.R.C.Psych., Surendra Kumar Mattoo, M.D., Ajit Avasthi, M.D. Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India Received 8 February 2012; accepted 6 March 2012
Abstract Objective: The objective was to evaluate the phenomenology, etiology and outcome of delirium in children and adolescents (8–18 years of age) seen in a consultation–liaison psychiatric service in India. Additionally, an attempt was made to compare the phenomenology with adult and elderly patients with delirium. Method: Thirty children and adolescents (age 8–18 years) diagnosed with delirium by the consultation–liaison psychiatry team were rated on the Delirium Rating Scale-Revised-98 (DRS-R-98) and compared with DRS-R-98 data on 120 adults and 109 elderly patients. Results: The commonly observed symptoms in children and adolescents with delirium were disturbance in attention, orientation, sleep–wake cycle disturbances, fluctuation of symptoms, disturbance of short-term memory and motor agitation. The least commonly seen symptoms included delusions and motor retardation. Compared to adults, children and adolescents had lower frequency of long-term memory and visuospatial disturbances. Compared to the elderly, children and adolescents had higher frequency of lability of affect. For severity of symptoms, compared to adults, the children and adolescents had lower severity of sleep–wake disturbances, abnormality of thought, motor agitation, orientation, attention, short-term memory, long-term memory and visuospatial abilities. When compared to elderly patients, children and adolescents had higher severity of lability of affect and lower severity of language disturbances, short-term memory and visuospatial abilities. Conclusions: In general, phenomenology, of delirium in children and adolescents (age 8–18 years) is similar to that seen in adults and elderly patients. © 2012 Elsevier Inc. All rights reserved. Keywords: Delirium; Children and adolescents; Phenomenology
1. Introduction As a neuropsychiatric condition, delirium is associated with many negative consequences such as increased morbidity, mortality, prolonged hospital stay and higher health care costs in adults and elderly [1,2]. The database for delirium for adults and elderly is large, but limited for children and adolescents. A recent review noted that the latter is limited to case reports and small case series, and the total number of cases described in literature from 1980 to
⁎ Corresponding author. Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Tel.: +91 172 2756807; fax: +91 172 2744401; 2745078. E-mail address: [email protected] (S. Grover). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2012.03.003
March 2009 included 217 children and adolescents with definite [meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IVTR) criteria] delirium and 136 children and adolescents with probable delirium [3]. Following this review, studies describing the clinical characteristics of delirium in children and adolescents have included a retrospective study from India with 46 children aged ≤14 years [4]; a prospective study of 23 cases aged up to 16 years [5]; a study of 49 patients from a pediatric intensive care unit (ICU) [6]; a study of 26 patients aged up to 17 years evaluating the usefulness of the Pediatric Anesthesia Emergence Delirium Scale (PAED), the Delirium Rating Scale-88 and the Delirium Rating Scale-Revised R-98 (DRS-R-98) [7]; and a study of 68 children and adolescents for the validity and reliability of the Pediatric Confusional Assessment Method
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(pCAM) in the ICU [8]. Another report of three children suggested that refractory agitation in infants may be a marker of delirium [9]. In the previous retrospective study from our center, it was shown that the common symptoms observed in children and adolescents with delirium include sleep–wake cycle disturbance, impairment in orientation, attention, short-term memory and presence of agitation. Delusions and hallucinations were reported by only a few patients [4]. Hatherill et al. [5] observed that children and adolescents with delirium who are referred to psychiatrists usually have hyperactive delirium and are at high risk of mortality and that their delirium is often due to multiple etiologies. The existence of limited data suggests that there is a need to evaluate the various aspects of delirium in children and adolescents. Against this background, this study aimed to: (a) evaluate the symptoms of delirium in children and adolescents (aged 8–18 years) as assessed on DRS-R-98 [10] prospectively, (b) evaluate the associated etiologies and the outcome of delirium and (c) compare the symptoms with adult and elderly patients with delirium. 2. Methodology 2.1. Setting The study was carried out at a multispecialty teaching hospital in North India. The Department of Psychiatry provides round-the-clock psychiatric consultation–liaison (CL) cover for the entire hospital including all emergency and specialty services. Most common referrals received by the CL team are for the management of delirium [11]. 2.2. Ethical considerations The study was approved by the Ethics Review Committee of the Institute, and written informed consent was obtained from the primary caregivers of the patients. 2.2.1. Design The study had a prospective design. All the patients aged 8–18 years diagnosed with delirium by DSM-IV-TR criteria by the CL team and whose caregivers provided consent were eligible for the study. The lower limit was fixed at 8 years because it was felt that younger children would not be able to describe the psychotic symptoms as coherently as the older ones. The sociodemographic and clinical profiles of the eligible subjects were recorded, and the rating for symptom profile and severity of delirium was done on DRS-R-98 [10]. Additionally, information about the etiology was recorded on the Delirium Etiology Checklist (DEC). The required information was obtained from the patients, caregivers, medical staff and medical records. For comparison of symptoms with adults and elderly patients, we obtained the DRS-R-98 data from two of our previous studies [12,13]. One of these studies exclusively focused on symptom profile of 109 elderly patients (aged
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≥65 years). The other study included 151 patients aged ≥18 years; out of these 151 patients, data of 120 adult patients (aged 19–64 years) were used to form the adult group for the comparison. 2.2.2. Instruments The DRS-R-98 [10] is a 16-item scale with 13 items constituting the severity scale and 3 items being of diagnostic significance. Each item is rated from 0 to 3 to yield a total severity score ranging from 0 to 39, with a higher score indicating greater severity. A score of ≥ 1 on any item indicates the presence of that particular symptom and forms the basis for the frequency of symptom. The scale has good validity, sensitivity, interrater reliability (intraclass correlation coefficient 0.98) and specificity for distinguishing delirium from dementia, depression and schizophrenia. The DEC [14] makes etiological attribution based on all the available clinical information. The checklist covers 12 categories [drug intoxication, drug withdrawal, metabolic/endocrine disturbance, traumatic brain injury, seizures, infection (intracranial), infection (systemic), neoplasm (intracranial), neoplasm (systemic), cerebrovascular, organ insufficiency, other central nervous system (CNS) disorder, and other systemic disorder]. Presence and suspected role of each cause are rated on a 5-point scale based on the degree of attribution to the delirium episode, and range from ‘ruled out/not present/not relevant’ (score 0) to ‘definite cause’ (score 4). Additionally, each etiological factor was also noted. 2.2.3. Procedure All the referrals received by the psychiatry CL service for those aged 8–18 years during the period from January 2009 to June 2011 and diagnosed with delirium were considered for the study. Only those whose caregivers provided written informed consent were enrolled. DSM-IV-TR was used to confirm the diagnosis of delirium, followed by the recording the demographic and clinical details. Next, a qualified psychiatrist obtained the relevant information from the patients, caregivers, medical staff and medical records to record phenomenology by DRS-R-98 and the associated etiological factors by DEC. 2.2.3.1. Analysis. Data were analyzed using SPSS-14. Frequency, percentage, mean and standard deviation were calculated for the descriptive data. Student's t, χ 2 and Fisher's Exact Tests were used for comparison between the groups using two-tailed tests. Correlations between various variables were assessed by using Pearson product–moment correlation or Spearman rank correlation analysis. 3. Results During the study period, in total, 2416 calls were received for patients belonging to all age groups, of which 144 pertained to patients aged 8–18 years of age. Of the 144
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referrals for patients aged 8–18 years of age, 37 (25.7%) were diagnosed as having delirium. As three patients left the hospital prior to assessment for the study and in four cases the caregivers refused consent, 30 subjects were enrolled for the study. 3.1. Demographic profile Mean age of the sample was 14.8 years (S.D.: 3.17; range 8–18 years), and 19 (63.3%) out of 30 patients were male. Majority (90%) of the patient had a hospital emergent delirium. 3.2. Clinical profile Most of the referrals were received from medical wards (66.66%), and a minority (33.33%) of the referrals were from different surgical specialities and general surgery. Patients were assessed for their delirium after a mean duration of 3.2 days (S.D.: 4.1; range 1 day to 21 days) after the onset of the symptoms of delirium. 3.3. Etiology of delirium in children and adolescents As shown in Table 1, the most common DEC etiological category associated with delirium was that of metabolic and endocrine causes, followed by infections (either systemic or intracranial). In terms of specific etiologies, the most common etiologies were sepsis (53.3%), anemia (40%), hypoxia (43.3%) and trauma (23.3%; which included Traumatic Brain Injury and fractures due to accidents). Other less common etiological factors associated with delirium were medications (20%), seizures (20%), CNS pathology such as raised intracranial pressure (16.7%), renal
Table 1 Delirium Etiology Checklist Definite Likely Present and Present but cause cause possible apparently contributory not contributing Drug intoxication Drug withdrawal Metabolic/ endocrine Traumatic brain injury Seizures Infection (intracranial) Infection (systemic) Neoplasm (intracranial) Neoplasm (systemic) Cerebrovascular Organ insufficiency Other (CNS) Others
Ruled out/not present/not relevant
1 2 13
3 – 6
– – 1
– – –
26 28 10
1
5
–
–
24
2 4
1 –
4 1
– –
23 25
7
1
5
–
17
–
–
–
–
30
–
–
–
–
30
– –
– 7
2 3
–
28 20
1 6
1 2
– –
– –
28 22
impairment (10%), hypokalemia (6.7%), hyponatremia (6.7%), substance withdrawal (6.7%), decompensated cardiac disease (6.7%), hepatic impairment (3.3%), postoperative state (5.9%), hypernatremia (3.3%), worsening of diabetes mellitus (3.3%) and substance intoxication (3.3%). Most patients (56.6%) had three or more etiologies which could have contributed to the development of delirium, and the mean numbers of etiologies associated with delirium for the study group were 2.8 (S.D.:1.3; range 1–5). 3.4. Symptoms profile of delirium as assessed on DRS-R-98 Almost all (29 out of 30) patients fulfilled all the three DRS-R-98 diagnostic criteria (Table 2). One patient had met two out of the three diagnostic criteria. In terms of severity, the study sample had highest severity score on the item of sleep–wake cycle disturbances followed by disturbance of orientation and very closely followed by disturbance of attention. Other details are shown in Table 1. The mean DRSR98 severity score was 16.9 (S.D.: 5.2; range 9–30), and the DRS-R-98 total score was 22.3 (S.D.: 5.9; range 12–36). 3.5. Management of delirium in children and adolescents Haloperidol (N=18; 60%) was the commonest antipsychotic used, followed by olanzapine (N=5; 16.7%) and risperidone (N=2; 6.7%). Five patients were not prescribed any antipsychotic medication. All patients received supportive treatment in the form of optimal level of environmental stimulation, reducing sensory impairments, making the environment more familiar, and providing environmental cues that facilitate orientation and provide reassurance and information concerning delirium aimed to reduce fear or demoralization.
Table 2 Symptom profile of the sample (n=30) Symptoms (items)
Prevalence N (%) Score mean/standard deviation (range)
1. Sleep–wake cycle disturbances 2. Perceptual disturbance 3. Delusions 4. Lability of affect 5. Language 6. Thought process abnormality 7. Motor agitation 8. Motor retardation 9. Orientation 10. Attention 11. Short-term memory 12. Long-term memory 13. Visuospatial ability Diagnostic items of DRS-R-98 14. Temporal (acute) onset of symptoms 15. Fluctuation 16. Physical disorder DRS severity score DRS total score
29 (96.7%)
2.10 ± 0.84 (0–3)
24 (80%) 10 (33.3%) 27 (90%) 22 (73.3%) 22 (73.3%) 28 (93.3%) 10 (33.3%) 30 (100%) 30 (100%) 28 (93.3%) 16 (53.3%) 18 (60%)
1.43 ± 0.93 (0–3) 0.36 ± 0.55 (0–2) 1.50 ± 0.77 (0–2) 1.13 ± 0.86 (0–3) 1.16 ± 0.91 (0–3) 1.86 ± 0.81 (0–3) 0.46 ± 0.77 (0–3) 2.03 ± 0.55 (0–3) 1.96 ± 0.76 (1–3) 1.43 ± 0.77 (0–3) 0.70 ± 0.83 (0–3) 0.76 ± 0.77 (0–3)
30 (100%)
2.16 ± 0.69 (1–3)
29 (96.6%) 30 (100%)
1.43 ± 0.56 (0–2) 1.76 ± 0.43 (1–2) 16.93 ± 5.22 (9–30) 22.30 ± 5.98 (12–36)
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Additionally, all efforts were made to address the etiological factors responsible for development of delirium. 3.6. Outcome of delirium in children and adolescents Only 3 (10%) out of 30 subjects died during their hospital stay of 7.50 days (S.D.: 6.39; range 1–30 days), and in most of the survivors (N=24; 80%), the delirium improved significantly (but still scored 1 or more on one of the 13 DRS-R-98 items) at the time of discharge. One patient recovered completely (had none of the symptoms of delirium as per DRS-R-98), and in two cases (6.66%), delirium status worsened further by the time of discharge (left against medical advice) from the hospital. All the three patients who died were treated with antipsychotics, i.e., two were receiving olanzapine, and one was on haloperidol. Of the three patients who died, two were 18 years old, and one was 13 years old; two were admitted for severe burn injuries, and one was admitted with road traffic accident with multiple injuries, and the mean DRS-R-98 score of two out of the three patients was more than the mean for the study group (28 and 30). 3.7. Comparison of phenomenology of delirium between children and adolescents, adults and elderly patients On comparing the phenomenology across the present and the earlier studies on adults and elderly [12,13], very few significant differences emerged (Table 3). Compared to adults, children and adolescents had lower frequency of long-term memory and visuospatial disturbances. Compared to the elderly, children and adolescents had higher frequency of lability of affect. For symptom severity (Table 4), compared to adults, children and adolescents had lower severity of sleep–wake
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disturbances, motor agitation, orientation, attention, shortterm memory, long-term memory and visuospatial abilities; compared to the elderly, children and adolescents had higher severity of lability of affect and lower severity of short-term memory and visuospatial abilities.
4. Discussion This study attempts to expand the limited literature on delirium in children and adolescents. Most of the studies in the past have not used standardized rating scales for assessment of symptoms of delirium in children and adolescents [3]. Few studies in recent time have evaluated the symptoms of delirium on DRS-R-98 in children and adolescents [7] and on pCAM [8], but these have been limited to patients admitted to the ICU. To the best of our knowledge, this is the first prospective study that has looked at the phenomenology of delirium in noncritically ill children and adolescents aged 8–18 years from India. In our study, all patients had disturbance in attention, and most of them had disturbance in orientation, fluctuation of symptoms, sleep–wake cycle, short-term memory and motor agitation. Delusions and motor retardation were the least commonly observed symptoms. Earlier literature (Table 5) has also reported a similar profile of these symptoms in children and adolescents [4,15], even though two of the studies that used DRS and DRS-R-98 did not describe the frequency of symptoms [7,16]. A close comparison of the reported prevalence of various symptoms brings out the following differences. In contrast to Turkel and Tavare [15], the patients in our study (Table 5) more frequently had perceptual disturbance, delusions, motor agitation and disturbance in orientation, while as compared
Table 3 Comparison of symptom profile in children and adolescents, adult and elderly Symptoms (items)
Present study N=30 (1)
Grover et al., 2011 (data of only adult patients) N=120 (2)
Grover et al., 2012 (geriatric age group) N=109 (3)
Comparison of 1–2
Comparison of 1–3
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language (speech disturbance) Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal onset of symptoms Fluctuation Physical Disorder
96.7% 80% 33.3% 90% 73.3% 73.3% 93.3% 33.3% 100% 100% 93.3% 53.3% 60% 100% 96.6% 100%
100% 77.5% 30.8% 81.8% 78.3% 70% 96.7% 38.3% 100% 100% 96.7% 93.3% 96.7% 100% 95% 100%
97.2% 78.9% 35.8% 62.4% 79.8% 74.3% 89.0% 32.1% 95.4% 97.2% 91.8% 65.1% 63.3% 100% 92.7% 100%
0.02 a 0.08 (P=.76) 0.07 (P=.79) 0.67 (P=.41) 0.34 (P=.55) 0.12 (P=.71) 0.34 a 0.25 (P=.61) – – 0.34 a 30.68 (Pb.001) 22.10 b (Pb.001) – 0.15 (P=.69) b –
1.00 a 0.017 (P=.89) 0.06 (.80) 7.06 b (P=.007) 0.58 (P=.44) 0.07 (P=.79) 0.12 (P=.72) 0.016 (P=.89) 0.58 a 1.00 a 0.082 (.77) 1.40 (.23) 0.016 (.90) – 0.13 (P=.71) b –
a b
Fisher's Exact value. χ 2 value with Yates correction.
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Table 4 Comparison of severity of symptom in children and adolescents, adult and elderly Symptoms (items)
Present study
Grover et al., 2011 (Data of only adult patients, N=120)
Grover et al., 2012 Geriatric age group (N=109)
Comparison of 1–2
Comparison of 1–3
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal (acute) onset of symptoms Fluctuation Physical Disorder
2.10 ± 0.84 1.43 ± 0.93 0.36 ± 0.55 1.50 ± 0.77 1.13 ± 0.86 1.16 ± 0.91 1.86 ± 0.81 0.46 ± 0.77 2.03 ± 0.55 1.96 ± 0.76 1.43 ± 0.77 0.70 ± 0.83 0.76 ± 0.77 2.16 ± 0.69 1.43 ± 0.56 1.76 ± 0.43
2.76 ± 0.42 1.75 ± 1.16 0.58 ± 0.99 1.54 ± 0.93 1.32 ± 0.90 1.50 ± 1.16 2.30 ± 0.76 0.69 ± 0.99 2.36 ± 0.60 2.37 ± 0.55 2.50 ± 0.60 1.82 ± 0.85 2.25 ± 0.76 2.79 ± 0.44 1.56 ± 0.59 1.90 ± 0.28
2.30 ± 0.73 1.64 ± 1.08 0.54 ± 0.79 0.96 ± 0.87 1.35 ± 0.91 1.18 ± 0.88 1.88 ± 0.92 0.65 ± 1.00 2.18 ± 0.80 2.09 ± 0.73 1.78 ± 0.90 1.01 ± 0.92 1.16 ± 1.05 2.56 ± 0.62 1.56 ± 0.62 1.90 ± 0.29
6.11 (Pb.001) 1.41 (P=.15) 1.15 (P=.25) 0.22 (P=.82) 1.04 (P=.29) 1.49 (P=.13) 2.78 (P=.006) 1.15 (P=.25) 2.73 (P=.007) 3.34 (P=.001) 6.85 (Pb.001) 6.46 (Pb.001) 9.56 (Pb.001) 6.04 (Pb.001) 1.11 (P=.26) 2.15 (Pb.03)
1.28 (P=.19) 0.96 (P=.33) 1.12 (P=.26) 3.05 (P=.003) 1.20 (P=.23) 0.09 (P=.92) 0.07 (P=.94) 0.93 (P=.35) 0.95 (P=.34) 0.81 (P=.41) 1.96 (P=.05) 1.70 (P=.09) 1.92 (P=.05) 3.02 (P=.003) 1.06 (P=.28) 2.11 (P=.03)
with Grover et al. [4], the patients in our study more frequently had perceptual disturbance, lability of affect, language disturbance, thought process abnormality, motor agitation and impairment of short-term memory. The possible reasons for these differences could be the better design of the present study, i.e., while both earlier studies followed a retrospective chart review approach; the present study followed a prospective approach. The severity scores of various symptoms in the present study were broadly comparable with those reported by Leentjens et al. [16]; the
minor differences could be due to use of different scales. Comparison of the findings of the present study with earlier studies on the phenomenology of delirium in adults and elderly revealed very few significant differences. These few differences in the severity might be due to the time of assessment during the course of the illness and the sample size, and need further systematic exploration. The only comparative study using the DRS [16] has reported that, compared to adults, the children and adolescents had higher average scores for acute onset, hallucinations, delusions,
Table 5 Comparison of symptom profile of the present study with literature Symptoms (items)
Present study (1)
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal onset of symptoms Fluctuation Physical disorder Impaired alertness/clouding of consciousness Confusion Anxious mood Depressed mood
96.7% 80% 33.3% 90% 73.3% 73.3% 93.3% 33.3% 100% 100% 93.3% 53.3% 60% 100% 94.1% 100%
⁎Pb0.05; ⁎⁎⁎Pb0.001. a Fisher's Exact value. b χ 2 value with Yates correction.
Turkel & Tavare, 2003 N=84 (2) 98% 43% 0 79%
69% 77% 52%
Grover et al., 2009 N=38 (3)
Comparison of 1–2
Comparison of 1–3
100% 39.5% 23.7% 60.5% 23.7% 21.1% 68.4% 31.6% 100% 89.5% 84.2% 7.9%
1.00 a 12.23 (Pb.001)⁎⁎⁎ 26.66 (Pb.001)⁎⁎⁎ 1.23 b (P=.26) – – 5.78 b (P=0.016)⁎
0.44 a 11.25 (Pb.001)⁎⁎⁎ 0.77 (P=.37) 6.04 (0.013) b⁎ 16.66 (Pb.001)⁎⁎⁎ 18.56 (Pb.001)⁎⁎⁎ 4.93 (Pb.02)⁎ 0.02 (0.87) – 0.12 a 0.28 (0.59) 15.00 b (Pb.001)⁎⁎⁎
100% 95% 96% 61% 0%
100%
6.59 b (Pb.010)⁎⁎⁎
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psychomotor symptom and lability of mood but lower scores for cognitive deficits, fluctuation and sleep–wake disturbance, while compared to the elderly, the children and adolescents had higher average scores for acute onset, hallucinations, delusions, psychomotor symptoms and lability of mood but lower scores for cognitive deficits, fluctuation and sleep–wake disturbance [16]. A comparison of the findings of the present study with earlier research [16] on comparative findings of phenomenology of delirium vis-a-vis the adults and elderly subjects demonstrates more similarities and a few differences, and indicates a need to explore these findings further. In a recent study, Janssen et al. [7] evaluated the utility of PAED, DRS and DRS-R-98 in children and adolescents aged 1–17 years and reported that PAED could be completed for most of the patients (93.5%) under evaluation, followed by DRS (66.9%), and DRS-R-98 was completed for the least number of patients (46.8%) under evaluation. For DRS-R98, the mean age of patients who could be rated was 9.6 years, and that of those who could not be rated was 4.3 years. The authors reported specificity of 100% and sensitivity of 75% for DRS-R-98. The authors also pointed out that many of items of cognition on DRS-R-98 were difficult to rate, especially in younger children. For most of the children, visuospatial ability, short-term memory and long-term memory were either scored as being normal or unrateable (due to sedation, severity of illness and young age). Although, in the present study, we did not evaluate the validity of DRS-R-98, in general, it can be concluded that children 8 years or above can be evaluated on DRS-R-98. The possible reason for the lack of difficulty in the present study, in contrast to that reported by Janssen et al. [7], could be due to the fact that patients included in our study were not as critically ill as could be and that, in the present study, most of patients were admitted to general medical and surgical wards and were not as young as 1 year of age, which was the lower age limit in the study by Janssen et al. [7]. In their review of literature, Hatherill and Flisher [3] pointed out that male gender may be a predisposing factor for development of delirium in children and adolescents. Even though, in our study, majority of the patients were males, it would be wrong to conclude that male gender is a predisposing factor. This overrepresentation of males in the hospital attending sample may simply be a reflection of treatment-seeking behavior in India. In general, health of the male gender is given more importance, and more males seek treatment compared to females. We reported a similar pattern in an earlier study on delirium in children and adolescents from our center [4]. Existing literature suggests that preexisting emotional and behavioral problems, progressive cognitive impairment and mental retardation act as predisposing factor for the development of delirium. In contrast, none of our subjects had any psychiatric comorbidity. However, this could have been influenced by the service pattern of the hospital; further studies are required with relevant control groups and detailed
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assessment to provide conclusive evidence for these predisposing factors. The finding of the present study suggests that the most commonly associated etiological factor was sepsis and that it was closely followed by anemia, hypoxia and trauma. However, with respect to anemia, it must be noted that we did not evaluate separately anemia due to acute blood loss or chronic anemia. As a group, metabolic and endocrinological disorders were the commonest group of underlying causes, and medications and recent seizures were associated with the development of delirium in about one fourth of the cases. Similar findings have been reported across other studies on the etiology of delirium [3,4,15]. The metabolic and endocrinological disorders formed the largest group because it included the entire electrolyte imbalance group, acidosis and alkalosis, uremia and various endocrinological abnormalities. The mortality rate of 10% in our study, slightly lower than the rate of 12.5% to 29% reported by earlier research [5,15,17,18], could be due to differences in treatment setting; Schieveld et al. [17] reported on ICU subjects, while DiMario and Packer [18] focused on subjects with cancers. It is well known that patients who are admitted to the ICU in general have more severe physical illnesses compared to those admitted in general wards. Similarly, in those who have cancer, mortality may be related to the primary disease per se. Another important fact with respect to mortality was that all the three patients who died were treated with antipsychotics, i.e., two were receiving olanzapine, and one was on haloperidol. However, it must be noted that these patients had severe physical illnesses and that cause of death was due to the primary illness per se rather than the use of psychotropic medication. Like the previous research reporting the usefulness of various antipsychotics, especially haloperidol in the management of delirium [4,19–21], the present study also reported the predominant use of haloperidol, in addition to the environmental management. The results of the present study must be seen within its limitations. The present study had the following limitations: small sample size, cross-sectional design, CL-based sample predominantly from the medical wards (could have influenced etiologies associated with delirium), inclusion of etiologically heterogenous group of patients (could have influenced the phenomenology), no control group (for predisposing factors and outcome) and lack of evaluation of motoric subtypes of delirium. Future studies should include larger sample from diverse medical and surgical backgrounds, and assess the patients longitudinally to study the course and outcome, including the response to different treatment modalities. Within these limitations, the present study suggests that children and adolescents with delirium commonly have disturbance in attention, orientation, sleep–wake cycle disturbances, fluctuation of symptoms, disturbance of short-term memory and motor agitation. The least commonly seen symptoms included delusions and motor retardation.
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This symptomatology does not differ significantly from that of adults and elderly patients. This suggests that delirium manifests similarly across all age groups. Delirium in children and adolescents are commonly associated with sepsis and/or endocrine–metabolic disturbances. Hence, all patients with sepsis and/or endocrine–metabolic disturbances should be monitored for delirium so as to detect the same as early as possible. Delirium-related phenomenology and mortality in children and adolescents (aged 8–18 years) appear to be similar to those in adults and elderly patients. References [1] Trzepacz PT, Meagher DJ. Delirium. In: Levenson JL, editor. Textbook of psychosomatic medicine. Washington DC: American Psychiatric Association; 2005, pp. 91–130. [2] Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical inpatients: a systematic literature review. Age Ageing 2006;35:350–64. [3] Hatherill S, Flisher AJ. Delirium in children and adolescents: a systematic review of the literature. J Psychosom Res 2010;68: 337–44. [4] Grover S, Malhotra S, Bharadwaj R, Bn S, Kumar S. Delirium in children and adolescents. Int J Psychiatry Med 2009;39:179–87. [5] Hatherill S, Flisher AJ, Nassen R. Delirium among children and adolescents in an urban sub-Saharan African setting. J Psychosom Res 2010;69:187–92. [6] Smeets IA, Tan EY, Vossen HG, Leroy PL, Lousberg RH, van Os J, Schieveld JN. Prolonged stay at the paediatric intensive care unit associated with paediatric delirium. Eur Child Adolesc Psychiatry 2010; 19:389–93. [7] Janssen NJ, Tan EY, Staal M, Janssen EP, Leroy PL, Lousberg R, van Os J, Schieveld JN. On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98. Intensive Care Med 2011;37: 1331–7. [8] Smith HA, Boyd J, Fuchs DC, Melvin K, Berry P, Shintani A, Eden SK, Terrell MK, Boswell T, Wolfram K, Sopfe J, Barr FE, Pandharipande PP, Ely EW. Diagnosing delirium in critically ill children: validity and reliability of the Pediatric Confusion
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Assessment Method for the Intensive Care Unit. Crit Care Med 2011;39:150–7. Schieveld JN, Staal M, Voogd L, Fincken J, Vos G, van Os J. Refractory agitation as a marker for pediatric delirium in very young infants at a pediatric intensive care unit. Intensive Care Med 2010;36:1982–3. Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-Revised-98: comparison with the Delirium Rating Scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci 2001;13:229–42. Grover S, Subodh BN, Avasthi A, Chakrabarti S, Kumar S, Sharan P, Malhotra S, Kulhara P, Mattoo SK, Basu D. Prevalence and clinical profile of delirium: a study from a tertiary care hospital in north India. Gen Hosp Psychiatry 2009;31:25–9. Grover S, Chakrabarti S, Shah R, Kumar V. A factor analytic study of the Delirium Rating Scale-Revised-98 in untreated patients with delirium. J Psychosom Res 2011;70:473–8. Grover S, Kate N, Aggarwal M, Mattoo SK, Avasthi A, Malhotra S, Kulhara P, Chakrabarti S, Basu D. Delirium in elderly: a study from a psychiatric liaison service in North India. Int Psychogeriatr 2012;24: 117–27. Trzepacz PT, Meagher DJ, Leonard M. Delirium. In: Levenson J, editor. American Psychiatric Publishing textbook of psychosomatic medicine. . Washington, DC: American Psychiatric Publishing; 2011. Turkel SB, Tavare CJ. Delirium in children and adolescents. J Neuropsychiatry Clin Neurosci 2003;15:431–5. Leentjens A, Schieveld J, Leonard M, Lousberg R, Verhey F, Meagher D. A comparison of pediatric, adult and geriatric delirium. J Psychosom Res 2008;64:219–23. Schieveld J, Leroy P, van Os J, Nicolai J, Vos G, Leentjens A. Pediatric delirium in critical illness: phenomenology, clinical correlates and treatment response in 40 cases in the pediatric intensive care unit. Intensive Care Med 2007;33:1033–40. DiMario F, Packer R. Acute mental status changes in children with systemic cancer. Paediatrics 1990;85:353–60. Schieveld J, Leentjens A. Delirium in severely ill young children in the pediatric intensive care unit (PICU). J Am Acad Child Adolesc Psychiatry 2005;44:392–4. Brown R, Henke A, Greenhalgh D, Warden G. The use of haloperidol in the agitated, critically ill pediatric patient with burns. J Burn Care Rehabil 1996;17:34–8. Harrison A, Lugo R, Lee W, Appachi E, Bourdakos D, Davis S, et al. The use of haloperidol in agitated critically ill children. Clin Pediatr 2002;41:51–4.
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Symptom profile of delirium in children and adolescent—does it differ from adults and elderly? Sandeep Grover, M.D.⁎, Natasha Kate, M.D., Savita Malhotra, M.D., Subho Chakrabarti, M.D., F.R.C.Psych., Surendra Kumar Mattoo, M.D., Ajit Avasthi, M.D. Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India Received 8 February 2012; accepted 6 March 2012
Abstract Objective: The objective was to evaluate the phenomenology, etiology and outcome of delirium in children and adolescents (8–18 years of age) seen in a consultation–liaison psychiatric service in India. Additionally, an attempt was made to compare the phenomenology with adult and elderly patients with delirium. Method: Thirty children and adolescents (age 8–18 years) diagnosed with delirium by the consultation–liaison psychiatry team were rated on the Delirium Rating Scale-Revised-98 (DRS-R-98) and compared with DRS-R-98 data on 120 adults and 109 elderly patients. Results: The commonly observed symptoms in children and adolescents with delirium were disturbance in attention, orientation, sleep–wake cycle disturbances, fluctuation of symptoms, disturbance of short-term memory and motor agitation. The least commonly seen symptoms included delusions and motor retardation. Compared to adults, children and adolescents had lower frequency of long-term memory and visuospatial disturbances. Compared to the elderly, children and adolescents had higher frequency of lability of affect. For severity of symptoms, compared to adults, the children and adolescents had lower severity of sleep–wake disturbances, abnormality of thought, motor agitation, orientation, attention, short-term memory, long-term memory and visuospatial abilities. When compared to elderly patients, children and adolescents had higher severity of lability of affect and lower severity of language disturbances, short-term memory and visuospatial abilities. Conclusions: In general, phenomenology, of delirium in children and adolescents (age 8–18 years) is similar to that seen in adults and elderly patients. © 2012 Elsevier Inc. All rights reserved. Keywords: Delirium; Children and adolescents; Phenomenology
1. Introduction As a neuropsychiatric condition, delirium is associated with many negative consequences such as increased morbidity, mortality, prolonged hospital stay and higher health care costs in adults and elderly [1,2]. The database for delirium for adults and elderly is large, but limited for children and adolescents. A recent review noted that the latter is limited to case reports and small case series, and the total number of cases described in literature from 1980 to
⁎ Corresponding author. Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Tel.: +91 172 2756807; fax: +91 172 2744401; 2745078. E-mail address: [email protected] (S. Grover). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2012.03.003
March 2009 included 217 children and adolescents with definite [meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IVTR) criteria] delirium and 136 children and adolescents with probable delirium [3]. Following this review, studies describing the clinical characteristics of delirium in children and adolescents have included a retrospective study from India with 46 children aged ≤14 years [4]; a prospective study of 23 cases aged up to 16 years [5]; a study of 49 patients from a pediatric intensive care unit (ICU) [6]; a study of 26 patients aged up to 17 years evaluating the usefulness of the Pediatric Anesthesia Emergence Delirium Scale (PAED), the Delirium Rating Scale-88 and the Delirium Rating Scale-Revised R-98 (DRS-R-98) [7]; and a study of 68 children and adolescents for the validity and reliability of the Pediatric Confusional Assessment Method
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(pCAM) in the ICU [8]. Another report of three children suggested that refractory agitation in infants may be a marker of delirium [9]. In the previous retrospective study from our center, it was shown that the common symptoms observed in children and adolescents with delirium include sleep–wake cycle disturbance, impairment in orientation, attention, short-term memory and presence of agitation. Delusions and hallucinations were reported by only a few patients [4]. Hatherill et al. [5] observed that children and adolescents with delirium who are referred to psychiatrists usually have hyperactive delirium and are at high risk of mortality and that their delirium is often due to multiple etiologies. The existence of limited data suggests that there is a need to evaluate the various aspects of delirium in children and adolescents. Against this background, this study aimed to: (a) evaluate the symptoms of delirium in children and adolescents (aged 8–18 years) as assessed on DRS-R-98 [10] prospectively, (b) evaluate the associated etiologies and the outcome of delirium and (c) compare the symptoms with adult and elderly patients with delirium. 2. Methodology 2.1. Setting The study was carried out at a multispecialty teaching hospital in North India. The Department of Psychiatry provides round-the-clock psychiatric consultation–liaison (CL) cover for the entire hospital including all emergency and specialty services. Most common referrals received by the CL team are for the management of delirium [11]. 2.2. Ethical considerations The study was approved by the Ethics Review Committee of the Institute, and written informed consent was obtained from the primary caregivers of the patients. 2.2.1. Design The study had a prospective design. All the patients aged 8–18 years diagnosed with delirium by DSM-IV-TR criteria by the CL team and whose caregivers provided consent were eligible for the study. The lower limit was fixed at 8 years because it was felt that younger children would not be able to describe the psychotic symptoms as coherently as the older ones. The sociodemographic and clinical profiles of the eligible subjects were recorded, and the rating for symptom profile and severity of delirium was done on DRS-R-98 [10]. Additionally, information about the etiology was recorded on the Delirium Etiology Checklist (DEC). The required information was obtained from the patients, caregivers, medical staff and medical records. For comparison of symptoms with adults and elderly patients, we obtained the DRS-R-98 data from two of our previous studies [12,13]. One of these studies exclusively focused on symptom profile of 109 elderly patients (aged
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≥65 years). The other study included 151 patients aged ≥18 years; out of these 151 patients, data of 120 adult patients (aged 19–64 years) were used to form the adult group for the comparison. 2.2.2. Instruments The DRS-R-98 [10] is a 16-item scale with 13 items constituting the severity scale and 3 items being of diagnostic significance. Each item is rated from 0 to 3 to yield a total severity score ranging from 0 to 39, with a higher score indicating greater severity. A score of ≥ 1 on any item indicates the presence of that particular symptom and forms the basis for the frequency of symptom. The scale has good validity, sensitivity, interrater reliability (intraclass correlation coefficient 0.98) and specificity for distinguishing delirium from dementia, depression and schizophrenia. The DEC [14] makes etiological attribution based on all the available clinical information. The checklist covers 12 categories [drug intoxication, drug withdrawal, metabolic/endocrine disturbance, traumatic brain injury, seizures, infection (intracranial), infection (systemic), neoplasm (intracranial), neoplasm (systemic), cerebrovascular, organ insufficiency, other central nervous system (CNS) disorder, and other systemic disorder]. Presence and suspected role of each cause are rated on a 5-point scale based on the degree of attribution to the delirium episode, and range from ‘ruled out/not present/not relevant’ (score 0) to ‘definite cause’ (score 4). Additionally, each etiological factor was also noted. 2.2.3. Procedure All the referrals received by the psychiatry CL service for those aged 8–18 years during the period from January 2009 to June 2011 and diagnosed with delirium were considered for the study. Only those whose caregivers provided written informed consent were enrolled. DSM-IV-TR was used to confirm the diagnosis of delirium, followed by the recording the demographic and clinical details. Next, a qualified psychiatrist obtained the relevant information from the patients, caregivers, medical staff and medical records to record phenomenology by DRS-R-98 and the associated etiological factors by DEC. 2.2.3.1. Analysis. Data were analyzed using SPSS-14. Frequency, percentage, mean and standard deviation were calculated for the descriptive data. Student's t, χ 2 and Fisher's Exact Tests were used for comparison between the groups using two-tailed tests. Correlations between various variables were assessed by using Pearson product–moment correlation or Spearman rank correlation analysis. 3. Results During the study period, in total, 2416 calls were received for patients belonging to all age groups, of which 144 pertained to patients aged 8–18 years of age. Of the 144
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referrals for patients aged 8–18 years of age, 37 (25.7%) were diagnosed as having delirium. As three patients left the hospital prior to assessment for the study and in four cases the caregivers refused consent, 30 subjects were enrolled for the study. 3.1. Demographic profile Mean age of the sample was 14.8 years (S.D.: 3.17; range 8–18 years), and 19 (63.3%) out of 30 patients were male. Majority (90%) of the patient had a hospital emergent delirium. 3.2. Clinical profile Most of the referrals were received from medical wards (66.66%), and a minority (33.33%) of the referrals were from different surgical specialities and general surgery. Patients were assessed for their delirium after a mean duration of 3.2 days (S.D.: 4.1; range 1 day to 21 days) after the onset of the symptoms of delirium. 3.3. Etiology of delirium in children and adolescents As shown in Table 1, the most common DEC etiological category associated with delirium was that of metabolic and endocrine causes, followed by infections (either systemic or intracranial). In terms of specific etiologies, the most common etiologies were sepsis (53.3%), anemia (40%), hypoxia (43.3%) and trauma (23.3%; which included Traumatic Brain Injury and fractures due to accidents). Other less common etiological factors associated with delirium were medications (20%), seizures (20%), CNS pathology such as raised intracranial pressure (16.7%), renal
Table 1 Delirium Etiology Checklist Definite Likely Present and Present but cause cause possible apparently contributory not contributing Drug intoxication Drug withdrawal Metabolic/ endocrine Traumatic brain injury Seizures Infection (intracranial) Infection (systemic) Neoplasm (intracranial) Neoplasm (systemic) Cerebrovascular Organ insufficiency Other (CNS) Others
Ruled out/not present/not relevant
1 2 13
3 – 6
– – 1
– – –
26 28 10
1
5
–
–
24
2 4
1 –
4 1
– –
23 25
7
1
5
–
17
–
–
–
–
30
–
–
–
–
30
– –
– 7
2 3
–
28 20
1 6
1 2
– –
– –
28 22
impairment (10%), hypokalemia (6.7%), hyponatremia (6.7%), substance withdrawal (6.7%), decompensated cardiac disease (6.7%), hepatic impairment (3.3%), postoperative state (5.9%), hypernatremia (3.3%), worsening of diabetes mellitus (3.3%) and substance intoxication (3.3%). Most patients (56.6%) had three or more etiologies which could have contributed to the development of delirium, and the mean numbers of etiologies associated with delirium for the study group were 2.8 (S.D.:1.3; range 1–5). 3.4. Symptoms profile of delirium as assessed on DRS-R-98 Almost all (29 out of 30) patients fulfilled all the three DRS-R-98 diagnostic criteria (Table 2). One patient had met two out of the three diagnostic criteria. In terms of severity, the study sample had highest severity score on the item of sleep–wake cycle disturbances followed by disturbance of orientation and very closely followed by disturbance of attention. Other details are shown in Table 1. The mean DRSR98 severity score was 16.9 (S.D.: 5.2; range 9–30), and the DRS-R-98 total score was 22.3 (S.D.: 5.9; range 12–36). 3.5. Management of delirium in children and adolescents Haloperidol (N=18; 60%) was the commonest antipsychotic used, followed by olanzapine (N=5; 16.7%) and risperidone (N=2; 6.7%). Five patients were not prescribed any antipsychotic medication. All patients received supportive treatment in the form of optimal level of environmental stimulation, reducing sensory impairments, making the environment more familiar, and providing environmental cues that facilitate orientation and provide reassurance and information concerning delirium aimed to reduce fear or demoralization.
Table 2 Symptom profile of the sample (n=30) Symptoms (items)
Prevalence N (%) Score mean/standard deviation (range)
1. Sleep–wake cycle disturbances 2. Perceptual disturbance 3. Delusions 4. Lability of affect 5. Language 6. Thought process abnormality 7. Motor agitation 8. Motor retardation 9. Orientation 10. Attention 11. Short-term memory 12. Long-term memory 13. Visuospatial ability Diagnostic items of DRS-R-98 14. Temporal (acute) onset of symptoms 15. Fluctuation 16. Physical disorder DRS severity score DRS total score
29 (96.7%)
2.10 ± 0.84 (0–3)
24 (80%) 10 (33.3%) 27 (90%) 22 (73.3%) 22 (73.3%) 28 (93.3%) 10 (33.3%) 30 (100%) 30 (100%) 28 (93.3%) 16 (53.3%) 18 (60%)
1.43 ± 0.93 (0–3) 0.36 ± 0.55 (0–2) 1.50 ± 0.77 (0–2) 1.13 ± 0.86 (0–3) 1.16 ± 0.91 (0–3) 1.86 ± 0.81 (0–3) 0.46 ± 0.77 (0–3) 2.03 ± 0.55 (0–3) 1.96 ± 0.76 (1–3) 1.43 ± 0.77 (0–3) 0.70 ± 0.83 (0–3) 0.76 ± 0.77 (0–3)
30 (100%)
2.16 ± 0.69 (1–3)
29 (96.6%) 30 (100%)
1.43 ± 0.56 (0–2) 1.76 ± 0.43 (1–2) 16.93 ± 5.22 (9–30) 22.30 ± 5.98 (12–36)
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Additionally, all efforts were made to address the etiological factors responsible for development of delirium. 3.6. Outcome of delirium in children and adolescents Only 3 (10%) out of 30 subjects died during their hospital stay of 7.50 days (S.D.: 6.39; range 1–30 days), and in most of the survivors (N=24; 80%), the delirium improved significantly (but still scored 1 or more on one of the 13 DRS-R-98 items) at the time of discharge. One patient recovered completely (had none of the symptoms of delirium as per DRS-R-98), and in two cases (6.66%), delirium status worsened further by the time of discharge (left against medical advice) from the hospital. All the three patients who died were treated with antipsychotics, i.e., two were receiving olanzapine, and one was on haloperidol. Of the three patients who died, two were 18 years old, and one was 13 years old; two were admitted for severe burn injuries, and one was admitted with road traffic accident with multiple injuries, and the mean DRS-R-98 score of two out of the three patients was more than the mean for the study group (28 and 30). 3.7. Comparison of phenomenology of delirium between children and adolescents, adults and elderly patients On comparing the phenomenology across the present and the earlier studies on adults and elderly [12,13], very few significant differences emerged (Table 3). Compared to adults, children and adolescents had lower frequency of long-term memory and visuospatial disturbances. Compared to the elderly, children and adolescents had higher frequency of lability of affect. For symptom severity (Table 4), compared to adults, children and adolescents had lower severity of sleep–wake
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disturbances, motor agitation, orientation, attention, shortterm memory, long-term memory and visuospatial abilities; compared to the elderly, children and adolescents had higher severity of lability of affect and lower severity of short-term memory and visuospatial abilities.
4. Discussion This study attempts to expand the limited literature on delirium in children and adolescents. Most of the studies in the past have not used standardized rating scales for assessment of symptoms of delirium in children and adolescents [3]. Few studies in recent time have evaluated the symptoms of delirium on DRS-R-98 in children and adolescents [7] and on pCAM [8], but these have been limited to patients admitted to the ICU. To the best of our knowledge, this is the first prospective study that has looked at the phenomenology of delirium in noncritically ill children and adolescents aged 8–18 years from India. In our study, all patients had disturbance in attention, and most of them had disturbance in orientation, fluctuation of symptoms, sleep–wake cycle, short-term memory and motor agitation. Delusions and motor retardation were the least commonly observed symptoms. Earlier literature (Table 5) has also reported a similar profile of these symptoms in children and adolescents [4,15], even though two of the studies that used DRS and DRS-R-98 did not describe the frequency of symptoms [7,16]. A close comparison of the reported prevalence of various symptoms brings out the following differences. In contrast to Turkel and Tavare [15], the patients in our study (Table 5) more frequently had perceptual disturbance, delusions, motor agitation and disturbance in orientation, while as compared
Table 3 Comparison of symptom profile in children and adolescents, adult and elderly Symptoms (items)
Present study N=30 (1)
Grover et al., 2011 (data of only adult patients) N=120 (2)
Grover et al., 2012 (geriatric age group) N=109 (3)
Comparison of 1–2
Comparison of 1–3
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language (speech disturbance) Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal onset of symptoms Fluctuation Physical Disorder
96.7% 80% 33.3% 90% 73.3% 73.3% 93.3% 33.3% 100% 100% 93.3% 53.3% 60% 100% 96.6% 100%
100% 77.5% 30.8% 81.8% 78.3% 70% 96.7% 38.3% 100% 100% 96.7% 93.3% 96.7% 100% 95% 100%
97.2% 78.9% 35.8% 62.4% 79.8% 74.3% 89.0% 32.1% 95.4% 97.2% 91.8% 65.1% 63.3% 100% 92.7% 100%
0.02 a 0.08 (P=.76) 0.07 (P=.79) 0.67 (P=.41) 0.34 (P=.55) 0.12 (P=.71) 0.34 a 0.25 (P=.61) – – 0.34 a 30.68 (Pb.001) 22.10 b (Pb.001) – 0.15 (P=.69) b –
1.00 a 0.017 (P=.89) 0.06 (.80) 7.06 b (P=.007) 0.58 (P=.44) 0.07 (P=.79) 0.12 (P=.72) 0.016 (P=.89) 0.58 a 1.00 a 0.082 (.77) 1.40 (.23) 0.016 (.90) – 0.13 (P=.71) b –
a b
Fisher's Exact value. χ 2 value with Yates correction.
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Table 4 Comparison of severity of symptom in children and adolescents, adult and elderly Symptoms (items)
Present study
Grover et al., 2011 (Data of only adult patients, N=120)
Grover et al., 2012 Geriatric age group (N=109)
Comparison of 1–2
Comparison of 1–3
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal (acute) onset of symptoms Fluctuation Physical Disorder
2.10 ± 0.84 1.43 ± 0.93 0.36 ± 0.55 1.50 ± 0.77 1.13 ± 0.86 1.16 ± 0.91 1.86 ± 0.81 0.46 ± 0.77 2.03 ± 0.55 1.96 ± 0.76 1.43 ± 0.77 0.70 ± 0.83 0.76 ± 0.77 2.16 ± 0.69 1.43 ± 0.56 1.76 ± 0.43
2.76 ± 0.42 1.75 ± 1.16 0.58 ± 0.99 1.54 ± 0.93 1.32 ± 0.90 1.50 ± 1.16 2.30 ± 0.76 0.69 ± 0.99 2.36 ± 0.60 2.37 ± 0.55 2.50 ± 0.60 1.82 ± 0.85 2.25 ± 0.76 2.79 ± 0.44 1.56 ± 0.59 1.90 ± 0.28
2.30 ± 0.73 1.64 ± 1.08 0.54 ± 0.79 0.96 ± 0.87 1.35 ± 0.91 1.18 ± 0.88 1.88 ± 0.92 0.65 ± 1.00 2.18 ± 0.80 2.09 ± 0.73 1.78 ± 0.90 1.01 ± 0.92 1.16 ± 1.05 2.56 ± 0.62 1.56 ± 0.62 1.90 ± 0.29
6.11 (Pb.001) 1.41 (P=.15) 1.15 (P=.25) 0.22 (P=.82) 1.04 (P=.29) 1.49 (P=.13) 2.78 (P=.006) 1.15 (P=.25) 2.73 (P=.007) 3.34 (P=.001) 6.85 (Pb.001) 6.46 (Pb.001) 9.56 (Pb.001) 6.04 (Pb.001) 1.11 (P=.26) 2.15 (Pb.03)
1.28 (P=.19) 0.96 (P=.33) 1.12 (P=.26) 3.05 (P=.003) 1.20 (P=.23) 0.09 (P=.92) 0.07 (P=.94) 0.93 (P=.35) 0.95 (P=.34) 0.81 (P=.41) 1.96 (P=.05) 1.70 (P=.09) 1.92 (P=.05) 3.02 (P=.003) 1.06 (P=.28) 2.11 (P=.03)
with Grover et al. [4], the patients in our study more frequently had perceptual disturbance, lability of affect, language disturbance, thought process abnormality, motor agitation and impairment of short-term memory. The possible reasons for these differences could be the better design of the present study, i.e., while both earlier studies followed a retrospective chart review approach; the present study followed a prospective approach. The severity scores of various symptoms in the present study were broadly comparable with those reported by Leentjens et al. [16]; the
minor differences could be due to use of different scales. Comparison of the findings of the present study with earlier studies on the phenomenology of delirium in adults and elderly revealed very few significant differences. These few differences in the severity might be due to the time of assessment during the course of the illness and the sample size, and need further systematic exploration. The only comparative study using the DRS [16] has reported that, compared to adults, the children and adolescents had higher average scores for acute onset, hallucinations, delusions,
Table 5 Comparison of symptom profile of the present study with literature Symptoms (items)
Present study (1)
Sleep–wake cycle disturbances Perceptual disturbance Delusions Lability of affect Language Thought process abnormality Motor agitation Motor retardation Orientation Attention Short-term memory Long-term memory Visuospatial ability Temporal onset of symptoms Fluctuation Physical disorder Impaired alertness/clouding of consciousness Confusion Anxious mood Depressed mood
96.7% 80% 33.3% 90% 73.3% 73.3% 93.3% 33.3% 100% 100% 93.3% 53.3% 60% 100% 94.1% 100%
⁎Pb0.05; ⁎⁎⁎Pb0.001. a Fisher's Exact value. b χ 2 value with Yates correction.
Turkel & Tavare, 2003 N=84 (2) 98% 43% 0 79%
69% 77% 52%
Grover et al., 2009 N=38 (3)
Comparison of 1–2
Comparison of 1–3
100% 39.5% 23.7% 60.5% 23.7% 21.1% 68.4% 31.6% 100% 89.5% 84.2% 7.9%
1.00 a 12.23 (Pb.001)⁎⁎⁎ 26.66 (Pb.001)⁎⁎⁎ 1.23 b (P=.26) – – 5.78 b (P=0.016)⁎
0.44 a 11.25 (Pb.001)⁎⁎⁎ 0.77 (P=.37) 6.04 (0.013) b⁎ 16.66 (Pb.001)⁎⁎⁎ 18.56 (Pb.001)⁎⁎⁎ 4.93 (Pb.02)⁎ 0.02 (0.87) – 0.12 a 0.28 (0.59) 15.00 b (Pb.001)⁎⁎⁎
100% 95% 96% 61% 0%
100%
6.59 b (Pb.010)⁎⁎⁎
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psychomotor symptom and lability of mood but lower scores for cognitive deficits, fluctuation and sleep–wake disturbance, while compared to the elderly, the children and adolescents had higher average scores for acute onset, hallucinations, delusions, psychomotor symptoms and lability of mood but lower scores for cognitive deficits, fluctuation and sleep–wake disturbance [16]. A comparison of the findings of the present study with earlier research [16] on comparative findings of phenomenology of delirium vis-a-vis the adults and elderly subjects demonstrates more similarities and a few differences, and indicates a need to explore these findings further. In a recent study, Janssen et al. [7] evaluated the utility of PAED, DRS and DRS-R-98 in children and adolescents aged 1–17 years and reported that PAED could be completed for most of the patients (93.5%) under evaluation, followed by DRS (66.9%), and DRS-R-98 was completed for the least number of patients (46.8%) under evaluation. For DRS-R98, the mean age of patients who could be rated was 9.6 years, and that of those who could not be rated was 4.3 years. The authors reported specificity of 100% and sensitivity of 75% for DRS-R-98. The authors also pointed out that many of items of cognition on DRS-R-98 were difficult to rate, especially in younger children. For most of the children, visuospatial ability, short-term memory and long-term memory were either scored as being normal or unrateable (due to sedation, severity of illness and young age). Although, in the present study, we did not evaluate the validity of DRS-R-98, in general, it can be concluded that children 8 years or above can be evaluated on DRS-R-98. The possible reason for the lack of difficulty in the present study, in contrast to that reported by Janssen et al. [7], could be due to the fact that patients included in our study were not as critically ill as could be and that, in the present study, most of patients were admitted to general medical and surgical wards and were not as young as 1 year of age, which was the lower age limit in the study by Janssen et al. [7]. In their review of literature, Hatherill and Flisher [3] pointed out that male gender may be a predisposing factor for development of delirium in children and adolescents. Even though, in our study, majority of the patients were males, it would be wrong to conclude that male gender is a predisposing factor. This overrepresentation of males in the hospital attending sample may simply be a reflection of treatment-seeking behavior in India. In general, health of the male gender is given more importance, and more males seek treatment compared to females. We reported a similar pattern in an earlier study on delirium in children and adolescents from our center [4]. Existing literature suggests that preexisting emotional and behavioral problems, progressive cognitive impairment and mental retardation act as predisposing factor for the development of delirium. In contrast, none of our subjects had any psychiatric comorbidity. However, this could have been influenced by the service pattern of the hospital; further studies are required with relevant control groups and detailed
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assessment to provide conclusive evidence for these predisposing factors. The finding of the present study suggests that the most commonly associated etiological factor was sepsis and that it was closely followed by anemia, hypoxia and trauma. However, with respect to anemia, it must be noted that we did not evaluate separately anemia due to acute blood loss or chronic anemia. As a group, metabolic and endocrinological disorders were the commonest group of underlying causes, and medications and recent seizures were associated with the development of delirium in about one fourth of the cases. Similar findings have been reported across other studies on the etiology of delirium [3,4,15]. The metabolic and endocrinological disorders formed the largest group because it included the entire electrolyte imbalance group, acidosis and alkalosis, uremia and various endocrinological abnormalities. The mortality rate of 10% in our study, slightly lower than the rate of 12.5% to 29% reported by earlier research [5,15,17,18], could be due to differences in treatment setting; Schieveld et al. [17] reported on ICU subjects, while DiMario and Packer [18] focused on subjects with cancers. It is well known that patients who are admitted to the ICU in general have more severe physical illnesses compared to those admitted in general wards. Similarly, in those who have cancer, mortality may be related to the primary disease per se. Another important fact with respect to mortality was that all the three patients who died were treated with antipsychotics, i.e., two were receiving olanzapine, and one was on haloperidol. However, it must be noted that these patients had severe physical illnesses and that cause of death was due to the primary illness per se rather than the use of psychotropic medication. Like the previous research reporting the usefulness of various antipsychotics, especially haloperidol in the management of delirium [4,19–21], the present study also reported the predominant use of haloperidol, in addition to the environmental management. The results of the present study must be seen within its limitations. The present study had the following limitations: small sample size, cross-sectional design, CL-based sample predominantly from the medical wards (could have influenced etiologies associated with delirium), inclusion of etiologically heterogenous group of patients (could have influenced the phenomenology), no control group (for predisposing factors and outcome) and lack of evaluation of motoric subtypes of delirium. Future studies should include larger sample from diverse medical and surgical backgrounds, and assess the patients longitudinally to study the course and outcome, including the response to different treatment modalities. Within these limitations, the present study suggests that children and adolescents with delirium commonly have disturbance in attention, orientation, sleep–wake cycle disturbances, fluctuation of symptoms, disturbance of short-term memory and motor agitation. The least commonly seen symptoms included delusions and motor retardation.
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This symptomatology does not differ significantly from that of adults and elderly patients. This suggests that delirium manifests similarly across all age groups. Delirium in children and adolescents are commonly associated with sepsis and/or endocrine–metabolic disturbances. Hence, all patients with sepsis and/or endocrine–metabolic disturbances should be monitored for delirium so as to detect the same as early as possible. Delirium-related phenomenology and mortality in children and adolescents (aged 8–18 years) appear to be similar to those in adults and elderly patients. References [1] Trzepacz PT, Meagher DJ. Delirium. In: Levenson JL, editor. Textbook of psychosomatic medicine. Washington DC: American Psychiatric Association; 2005, pp. 91–130. [2] Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical inpatients: a systematic literature review. Age Ageing 2006;35:350–64. [3] Hatherill S, Flisher AJ. Delirium in children and adolescents: a systematic review of the literature. J Psychosom Res 2010;68: 337–44. [4] Grover S, Malhotra S, Bharadwaj R, Bn S, Kumar S. Delirium in children and adolescents. Int J Psychiatry Med 2009;39:179–87. [5] Hatherill S, Flisher AJ, Nassen R. Delirium among children and adolescents in an urban sub-Saharan African setting. J Psychosom Res 2010;69:187–92. [6] Smeets IA, Tan EY, Vossen HG, Leroy PL, Lousberg RH, van Os J, Schieveld JN. Prolonged stay at the paediatric intensive care unit associated with paediatric delirium. Eur Child Adolesc Psychiatry 2010; 19:389–93. [7] Janssen NJ, Tan EY, Staal M, Janssen EP, Leroy PL, Lousberg R, van Os J, Schieveld JN. On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98. Intensive Care Med 2011;37: 1331–7. [8] Smith HA, Boyd J, Fuchs DC, Melvin K, Berry P, Shintani A, Eden SK, Terrell MK, Boswell T, Wolfram K, Sopfe J, Barr FE, Pandharipande PP, Ely EW. Diagnosing delirium in critically ill children: validity and reliability of the Pediatric Confusion
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