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Patterns of Postoperative Delirium in Children*

Jochen Meyburg, MD1; Mona-Lisa Dill1; Chani Traube, MD2; Gabrielle Silver, MD3;
Rebecca von Haken, MD4

Objective: Intensive care delirium is a substantial problem in need for early screening. Our findings support the view of delirium
adults. Intensive care delirium is increasingly recognized in pedi- as a continuum of acute neurocognitive disorder. Further research
atrics in parallel with the development of specific scoring systems is needed to investigate prophylactic and treatment approaches for
for children. However, little is known about the fluctuating course intensive care delirium. (Pediatr Crit Care Med 2017; 18:128–133)
of intensive care delirium in children after surgery and possible Key Words: Cornell Assessment of Pediatric Delirium; intensive
implications on diagnostic and therapeutic strategies. care delirium; pediatric delirium; subsyndromal delirium
Design: Patients that needed treatment in the PICU following
elective surgery were screened for intensive care delirium with
the Cornell Assessment of Pediatric Delirium. When the patients

D
were awake (Richmond Agitation and Sedation Score > -3), two elirium as an acute brain dysfunction has become an
trained investigators conducted the Cornell Assessment of Pedi- important issue in adult critical care, since affected
atric Delirium twice daily for five consecutive days. patients have a higher mortality (1) and a significant
Patients: Ninety-three patients aged 0 to 17 years. risk of long-term neurocognitive impairment (2). Over the
Interventions: Eight hundred forty-five assessments completed. past years, there has been rising awareness that intensive care
Measurements and Main Results: Of the 845 scores, 230 were delirium (ICD) is not restricted to adult patients. First reports
consistent with delirium (27.2%). Sixty-one patients (65.5%) were from the 1980s and 1990s described behavioral disturbances
diagnosed with intensive care delirium. Half of these patients in children on intensive care wards but did not classify them as
(n = 30; 32.2%) had a short-lasting delirium that resolved within ICD (3, 4). A prospective pediatric study by Schieveld et al (5)
24 hours, and half (n = 31; 33.3%) had delirium of longer dura- found a very low prevalence of ICD of only 4.5% among psychiat-
tion. Delirium could be clearly distinguished from sedation by anal- ric referrals. With the adaptation of delirium scores to the special
ysis of individual test items of the Cornell Assessment of Pediatric demands in children, higher rates of delirium up to 16.9% were rec-
Delirium. Time spent delirious had a measurable effect on out- ognized (6). Recent studies using scoring systems that are suitable
come variables, including hospital length of stay. for children under 2 years old, that is, the Cornell Assessment of
Conclusion: Most postoperative PICU patients develop intensive Pediatric Delirium (CAPD) and the Preschool Confusion Assess-
care delirium. Some have a short-lasting course, which underlines the ment Method for the ICU (psCAM-ICU), yielded overall delirium
rates of 21–44% (7, 8). The true rate of ICD in children may be even
*See also p. 191. higher, since up to 82% of ventilated adult patients are affected (9).
1
Department of General Pediatrics, University Children’s Hospital, Because recognition of pediatric delirium is fairly novel, there
Heidelberg, Germany. has been little opportunity to describe the course of delirium
2
Pediatric Critical Care Medicine, Weill Cornell Medical College, New in critically ill children. One of the key features of delirium is
York, NY.
its fluctuating course, which may have significant implications
3
Department of Child and Adolescent Psychiatry, Weill Cornell Medical
College, New York, NY. on screening algorithms. Two retrospective studies (10, 11) only
4
Department of Anesthesiology, University Hospital Heidelberg, Heidel- scored their patients once. In the early prospective studies by
berg, Germany. the Dutch group, patients were also assessed once, followed by
Drs. Traube and Silver received support for travel from Weill Cornell Medi- a neuropsychologic investigation on the same day (5, 6, 12). The
cal College. Dr. Meyburg received support for travel from Heidelberg Uni-
versity Children’s Hospital. Dr. von Haken received funding from lectures
CAPD and the Pediatric Confusion Assessment Method for the
on delirium in adults, and from Orionpharma; her institution received fund- ICU (pCAM-ICU) are quick bedside tools and thus can be uti-
ing from Köhler Chemie. The remaining authors have disclosed that they lized repeatedly in individual patients. The most recent studies
do not have any potential conflicts of interest.
have scored at least some of their patients more than once, but
For information regarding this article, E-mail: jochen.meyburg@med.uni-
heidelberg.de no details on the course of the score results are given (7, 8, 13).
Copyright © 2017 by the Society of Critical Care Medicine and the World The aim of this study was to learn more about the time course
Federation of Pediatric Intensive and Critical Care Societies of ICD in children after surgery. There are two reasons why this
DOI: 10.1097/PCC.0000000000000993 is important. First, incomplete presentations of ICD are well

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known in adult patients as subsyndromal delirium (SSD). SSD respectively. Chi-square test was used for discrete variables. Delir-
can progress to full-blown ICD, and it is discussed whether such ium scores were analyzed by the total CAPD score, and by indi-
deterioration can be prevented by early recognition and treat- vidual test-item scores. Subgroup analysis of patients with delirium
ment. Little if anything is known about partial or subsyndromal was analyzed by analysis of variance. Analysis of covariance was
ICD in children. Second, there are no generally accepted guide- used to assess the effect of delirium on hospital length of stay (LOS)
lines for the treatment of pediatric ICD. Given the potential harm after adjusting for disease severity and time to first assessment. p
caused by psychotropic medications (14), it is imperative that we values of less than 0.05 were regarded as statistically significant. All
learn more about the duration and resolution of symptoms in analyses were performed in SPSS 20 (IBM, Armonk, NY).
affected patients. A better understanding of the distinct features
of pediatric delirium, and how they emerge and evolve, may help
in better defining severity and impact of ICD.
RESULTS
Demographic Data
Demographic data are given in Table 1. A total of 93 children
METHODS
were included in the study, of which 61 (65.6%) were delirious
Study Design in at least one assessment (CAPD, ≥ 9). The sex ratio was equal in
This study was conducted in a 22-bed general PICU in a tertiary- the two groups of patients with (male:female, 31:30) and with-
care academic medical center over a 6-month period from May out delirium (16:16), respectively. Patients with delirium were
2014 to October 2014. All patients admitted to the PICU follow- significantly younger compared to the control group (2.0 ± 3.2 vs
ing elective surgery were included. The only exclusion criterion 6.4 ± 5.7 yr; p < 0.001). It was not possible to analyze subgroups
was refusal by the parents to provide informed consent prior to
the operation. When appropriate, assent was obtained from the Demographic Details and
Table 1.
child as well. Demographic and clinical data were collected for all Admission Diagnoses of Subjects
study subjects. The study was approved by the Institutional Review
Board of the University Hospital Heidelberg. Characteristic n (%)

Patients included 93
Assessment of Postoperative Delirium, Severity of
Male 47
Illness, and Level of Care
The authorized German version of the CAPD (15) was used for Female 46
the assessment of postoperative delirium. The CAPD is an obser- Patient age, yr, n (%)
vational screen with eight individual test items that correlate with
 0–1 44 (47.3)
the Diagnostic and Statistical Manual-V diagnostic criteria for
delirium (16). Each item is scored 0–4. A total score of greater than  1–6 30 (32.3)
or equal to 9 is consistent with a diagnosis of delirium. Screen-  6–12 9 (9.7)
ing was started when the Richmond Agitation and Sedation
Score (RASS) was greater than –3, that is, the child would briefly  12–18 10 (10.8)
awaken to voice, open his eyes, and make short eye contact (17). Diagnoses
All assessments were done by the same two trained investigators   Congenital heart disease 58
together with the nurse in charge of the patient. Scoring was done
twice daily in the middle of the nurses’ morning and at the end of   CNS tumor or malformation 7
the evening shifts, respectively. Over a period of five consecutive   Urologic malformation 5
days, a total of 10 assessments per patient were made. Scoring   Tethered cord 5
was continued in the step-down unit if a patient was transferred
from the PICU before the end of the assessment period. To  Craniosynostosis 5
determine severity of illness, the revised version of the Pediatric   Chronic renal failure requiring 5
Index of Mortality 2 (PIM2) was calculated at the timepoint of transplantation
the first assessment (18). The level of care was determined using   Airway malformations 3
the Intensive Nursing and Performance System classification, a
 Meningomyelocele 2
validated system that is used in several German ICUs. Based on a
detailed scoring system, patients are assigned once daily to differ-   Biliary atresia 2
ent categories from 1 (intermediate care patient, spontaneously   Oesophageal atresia 1
breathing) to 6 (patient with multiple organ failure requiring
more than one extracorporeal support system) (19). Mechanical ventilation on the PICU, n (%)
 None 23 (24.7)
Statistical Analysis   < 24 hr 42 (45.2)
After testing for normal distribution, Student t test was used to
  ≥ 24 hr 28 (30.1)
compare the two groups of patients with and without delirium,

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of patients based on their ethnicity, since the families originated more severely affected children remained delirious throughout
from a total of 25 countries. As a substitute with regard to pos- the 5-day study period.
sible sociocultural differences, we grouped patients as having a To test whether the mildly elevated scores in group 1 were
migrant background or not, as defined by German authorities. sedation falsely classified as delirium, further analyses were
However, no significant differences were found between the two made. Each item in the CAPD was analyzed separately. The
clinical groups. There were no significant differences in disease analysis of the individual test items is shown in Figure 2. Each
severity (PIM2) between delirious children and children who of the eight items of the CAPD can be rated with 0–4 points. In
never developed clinical symptoms of delirium. Type of surgery, the children who did not develop delirium (group 0; Fig 2A),
use of cardiac bypass, or the extent of hyperthermia or blood mean values for all test items were close to zero. In children
loss did not have an impact on the development of delirium. with delirium greater than 24 hours (group 2; Fig 2B), mean
values were significantly higher, with markedly elevated values
Delirium Patterns for items 2, 5, and 8. In children with short-lasting delirium
Interestingly, two different patterns of ICD were found in our (group 1), normal and pathologic scores were analyzed sepa-
postoperative patients. Half of the delirious patients (30/61, rately. We found that during asymptomatic periods (Fig 2C),
group 1) had an early short-lasting delirium (24 hr), and the values were almost identical to unaffected children (Fig
the other half (31/61, group 2) had delirium of longer dura- 2A). In contrast, during the short periods of delirium (Fig 2D),
tion, with higher scores (12.5 ± 4.0 vs 15.8 ± 5.0 [mean ± sd]; the pattern of the test items closely resembled the distribution
p < 0.001) throughout the study period (Fig. 1). Eleven of these in the severely affected group 2 patients (pattern B). Table 2

Figure 1. Cornell Assessment of Pediatric Delirium (CAPD) scores (mean and sd) in children without delirium (white bars), with mild delirium (gray bars),
and severe delirium (black bars). Patients were investigated twice daily for five consecutive days (investigations 1–10) starting at a Richmond Agitation and
Sedation Score greater than –3. Compared to patients without delirium: **p < 0.01 and *p < 0.05. Compared to patients with mild delirium: #p < 0.01.

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A B the three groups. Compared to


patients who were never deliri-
ous, patients with longer lasting
delirium required longer periods
of mechanical ventilation, took
longer to emerge from sedation,
had longer length of hospital
stay, and a higher resource utili-
zation as measured by INPULS.
Patients with short-lasting delir-
ium had intermediate values as
compared to patients who were
never delirious. Even after con-
trolling for severity of illness,
time to first assessment, and
duration of mechanical ventila-
tion, delirium remained an inde-
pendent predictor of increased
hospital LOS (p = 0.043).

C D
DISCUSSION
Increasing incidence of ICD
reported in recent pediatric
studies may be understood
two-fold. First, without wide-
spread screening, the diagno-
sis of hypoactive delirium can
be missed easily even though
hypoactive symptoms may be
the most common presentation
of ICD (20). Pediatric delirium
tools such as the CAPD have
been specifically developed to
include symptoms of hypo-
active delirium. Second, the
majority of patients in the PICU
are younger than 2 years (5), a
group that was difficult to assess
in the past. With the develop-
Figure 2. Individual items of the Cornell Assessment of Pediatric Delirium (mean and sd) in children with no ment of suitable delirium tools
delirium (A) (white bars) and with severe delirium (B) (black bars). For children with mild delirium (gray bars), for all ages, significantly higher
two different diagrams are shown for asymptomatic (C) and symptomatic (D) periods, respectively. *Compared to
patients without delirium (A): p < 0.001. rates of ICD have been found
in younger children (7, 8).
Delirium in adults is predomi-
shows how the individual items of the CAPD reflect the DSM nantly found in the elderly, and it can be speculated that the
domains for the diagnosis of delirium. Items 2, 5, and 8 that developing as well as the ageing brain are especially sensitive
are affected in both group 1 and group 2 patients are mostly to noxious stimulation (21). In our collective, 57% of the chil-
related to cognition, orientation, affect, and psychomotor dren were younger than 2 years, 48% younger than 1 year, and
activity. Hence, the pattern found in group 1 can be distin- 34% younger than 6 months. In addition, most of our patients
guished from sedation and should be regarded as a mild or (75.3%) were ventilated during their PICU stay. The overall
short-lasting delirium. incidence of ICD in our study of 66% is the highest reported
so far for pediatric patients. It is in the range of the highest risk
Severity of Illness and Outcome Measures group in adults, that is, ventilated patients (9).
Clinical outcome of the study patients is given in Table 3. No sig- Studies in nongeriatric adult patients requiring intensive care
nificant difference in disease severity (PIM2) was found between show that the average duration of ICD is relatively short, typically

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Table 2. Items of the Cornell Assessment of Pediatric Delirium and Their Correspondence
to DSM Domains
Cornell Assessment of Pediatric Delirium Item Diagnostic and Statistical Manual Delirium Domains

Does the child make eye contact with the caregiver? Consciousness
Are the child’s actions purposeful? Cognition
Is the child aware of his/her surroundings? Consciousness
Orientation
Does the child communicate needs and wants? Consciousness
Psychomotor activity
Is the child restless? Orientation
Cognition
Affect/distress
Is the child inconsolable? Orientation
Cognition
Affect/distress
Is the child underactive—very little movement while awake? Orientation
Affect/distress
Does it take the child a long time to respond to interactions? Consciousness
Psychomotor activity

Table 3. Severity of Illness and Outcome Measures of Patients Without Delirium, With
Mild Delirium (< 24 Hr), and With Severe Delirium (> 24 hr)
No Delirium Mild Delirium Severe Delirium
Outcome Parameter (Group 0) (Group 1) (Group 2) p

n (%) 32 (34.4) 30 (32.3) 31 (33.3)


Pediatric Index of Mortality 2 1.21 ± 1.06 1.27 ± 0.84 1.41 ± 0.68 Not significant
Mechanical ventilation on the PICU (hr) 9.0 ± 18.7 29.7 ± 39.8 69.0 ± 74.5 < 0.001
Time to first analysis (d)
a
1.0 ± 1.0 2.0 ± 1.9 3.7 ± 3.2 < 0.001
Length of stay (d)
b
10.6 ± 7.3 13.5 ± 7.1 21.8 ± 19.7 0.043
Level of care (INPULS) 3.0 ± 0.3 2.9 ± 0.3 3.3 ± 0.4 < 0.001
Delirium screening commenced when Richmond Agitation and Sedation Score > –3.
a

Controlled for Pediatric Index of Mortality 2, duration of mechanical ventilation, and time to first assessment.
b

Values are expressed as mean ± sds.

ranging from 1 to 5 days (22, 23). If this is also the case in the disorder. Unlike the pCAM-ICU/psCAM-ICU that yield brief, in
PICU, then screening for delirium should be initiated as early the moment assessments, the CAPD specifically takes the fluctu-
as possible in the postoperative course. In fact, Smith et al (24) ating course of delirium into account. Nevertheless, Traube et al
noted that ICD had probably already resolved in a considerable (7) state that two of three of their few false negatives would have
number of electable study patients due to the consenting process been detected by performing the screening twice daily. This is
that could have taken several days. In the present study, consent exactly what was done in the present study.
was obtained prior to elective surgery, so assessment of delirium By frequent assessments at close intervals, we could dis-
could be started immediately once the RASS was greater than tinguish two different patterns of ICD in our patients. Group
–3. However, delirium may be missed not only in the beginning 2 had full-blown delirium with permanently elevated CAPD
but also in the later course due to the typical fluctuation of the scores over several days. In a third of these children, the

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