Delirium and Mortality in Critically Ill Children: Epidemiology and
Outcomes of Pediatric Delirium
Chani Traube, MD
*
,
Department of Pediatrics, Weill Cornell Medical College, New York, NY
Gabrielle Silver, MD
*
,
Department of Psychiatry, Weill Cornell Medical College, New York, NY
Linda M. Gerber, PhD,
Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY
Savneet Kaur, MBBS,
Department of Pediatrics, Weill Cornell Medical College, New York, NY
Elizabeth A. Mauer, MS,
Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY
Abigail Kerson, BA,
(no department – medical student), Weill Cornell Medical College, New York, NY
Christine Joyce, MD, and
Department of Pediatrics, New York Presbyterian Hospital, New York, NY
Bruce M. Greenwald, MD
Department of Pediatrics, Weill Cornell Medical College, New York, NY
Abstract
Objective—Delirium occurs frequently in adults, and is an independent predictor of mortality.
However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The
primary objectives of this study were to describe the incidence of delirium in critically ill children,
its duration, associated risk factors, and effect on in-hospital outcomes, including mortality.
Secondary objectives included determination of delirium subtype, and effect of delirium on
duration of mechanical ventilation (MV), and length of hospital stay (LOS).
Design—Prospective longitudinal cohort study.
Corresponding Author: Chani Traube, MD, Weill Cornell Medical College, 525 East 68
th
Street, M-508, New York, NY 10065, (212)
746-3056, chr9008@med.cornell.edu.
*
Drs. Traube and Silver contributed equally to this manuscript.
Name of institution where work performed: NY Presbyterian Hospital, Weill Cornell Medical College
Address for reprints: Reprints will not be ordered.
Disclosures: All authors have no relevant conflicts of interest to disclose.
Copyright form disclosure: Dr. Traube received support for article research from the National Institutes of Health. Dr. Greenwald
received funding from legal firms for expert testimony. The remaining authors have disclosed that they do not have any potential
conflicts of interest.
HHS Public Access
Author manuscript
Crit Care Med
. Author manuscript; available in PMC 2018 May 01.
Published in final edited form as:
Crit Care Med
. 2017 May ; 45(5): 891–898. doi:10.1097/CCM.0000000000002324.
Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Setting—Urban academic tertiary care pediatric intensive care unit (PICU).
Patients—All consecutive admissions from September 2014 through August 2015.
Intervention—Children were screened for delirium twice daily throughout their ICU stay.
Measurements and Main Results—Of 1547 consecutive patients, delirium was diagnosed in
267 (17%), and lasted a median of two days (IQR 1,5). Seventy-eight percent of children with
delirium developed it within the first three PICU days. Most cases of delirium were of the
hypoactive (46%) and mixed (45%) subtypes; only 8% of delirium episodes were characterized as
hyperactive delirium. In multivariable analysis, independent predictors of delirium included age ≤2
years, developmental delay, severity of illness, prior coma, mechanical ventilation, and receipt of
benzodiazepines and anticholinergics. PICU LOS was increased in children with delirium
(adjusted relative LOS 2.3, CI= 2.1, 2.5, p<0.001), as was duration of MV (median 4 vs. 1 day,
p<0.001). Delirium was a strong and independent predictor of mortality (adjusted OR 4.39, CI=
1.96–9.99, p<0.001).
Conclusions—Delirium occurs frequently in critically ill children and is independently
associated with mortality. Some in-hospital risk factors for delirium development are modifiable.
Interventional studies are needed to determine best practices to limit delirium exposure in at-risk
children.
Keywords
delirium; pediatric; mortality; epidemiology; critical care; intensive care
Introduction
Delirium is a frequent and serious complication of critical illness, and has been linked to
increased mortality, prolongation and complication of hospitalization, and long-term
disability(1,2). An extensive literature exists describing the incidence, duration, risk factors,
subtypes, and outcomes of delirium in adults, but there are few prospective longitudinal
studies in critically ill children that describe the natural history of pediatric delirium (PD)(3–
6).
In this study, we describe a cohort of children admitted to a single pediatric intensive care
unit (PICU) over a calendar year. Our objective was to screen each child for delirium daily,
from PICU admission through discharge, to determine incidence of delirium, time to onset,
duration and fluctuation of clinical manifestations, phenotype of delirium, associated risk
factors, and effect of delirium on in-hospital outcome measures (including mortality, length
of stay (LOS), and duration of mechanical ventilation (MV). This is one of several planned
analyses involving this cohort of patients, and all data described here are novel and have not
been published elsewhere. A subset of these patients were included in an analysis of the
effect of PD on hospital costs(7).
Materials and Methods
The Weill Cornell Medical College Institutional Review Board approved this observational,
minimal risk study with waiver of requirement for informed consent. This prospective
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longitudinal study took place in an urban, academic, tertiary care, mixed PICU. All patients
admitted to the PICU service for at least 24 hours between September 1, 2014 and August
31, 2015 were included.
Consistent with our PICU standard, each child was screened for delirium twice daily by the
bedside nurse, at 6 am and 6 pm, using the Cornell Assessment of Pediatric Delirium
(CAPD)(8). This is also consistent with the recent position paper published by the European
Society of Paediatric and Neonatal Intensive Care (ESPNIC), recommending use of CAPD
to assess for pediatric delirium (grade of recommendation = A) every 8–12 hours(9). The
CAPD is a well-validated observational 8-item tool that can reliably distinguish between
pain, agitation, residual sedation, and delirium(8,9). A CAPD score of 9 or higher represents
a positive screen; the diagnosis is then confirmed by the physician(8). Any developmentally
delayed child who screened positive for delirium on the CAPD subsequently had the
diagnosis of delirium confirmed (or refuted) by an intensivist or psychiatrist prior to being
classified as delirious. (The clinician had to establish an alteration from mental status at pre-
hospital baseline, in order to ensure that static encephalopathy – i.e.: the underlying
developmental delay – was not confused with delirium).
Each child was assigned a daily status: “comatose” (patients with a Richmond Agitation
Sedation Scale (RASS) score of −4 or −5, who are unarousable to verbal stimulation(10,11),
and therefore impossible to assess for delirium), “delirious” (CAPD score ≥9 with diagnosis
confirmed by physician), or “normal” mental status (i.e.: delirium-free and coma-free
(DFCF)). If an assessment opportunity was missed (due to noncompliance with screening
protocol), status for that day was designated as “unknown”.
All patients who were diagnosed with delirium at least once during their PICU stay were
designated “ever delirious” and compared to those patients who were never delirious. Time
to onset of delirium was defined as the number of days from PICU admission to the first
diagnosis of delirium. Duration of delirium was defined as the number of days spent
delirious during the PICU stay. Recurrent delirium (which frequently is a warning sign of
new inter-current illness) was defined as a second episode of delirium during a single
hospital admission, following a minimum of 24 hours spent with normal mental status
(DFCF).
Delirium subtype was determined by psychomotor activity and level of alertness, as assessed
by the RASS, over the 24 hour period(11, 12). The frequency of RASS assessment was
dependent on patient’s acuity level, and ranged from hourly to every 4 hours. The RASS
score ranges from −5 (unarousable), through 0 (alert and calm), to +4 (combative)(10).
Delirious children with RASS scores from 0 to −3 were designated as having hypoactive
delirium. Delirious children with RASS scores from 0 to +4 were designated as having
hyperactive delirium. Children with RASS scores crossing zero (including both negative and
positive numbers) were designated as having mixed delirium.
Demographic data, including age, sex, primary diagnosis, pre-existing medical conditions,
severity of illness (as measured by Pediatric index of Mortality-3 (PIM3) score(13), and
divided into tertiles), and developmental status were collected on admission. As
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developmentally delayed children are at increased risk for developing delirium during
critical illness, it is important to include these children in delirium research (8).
“Developmental delay” was defined as a Pediatric Cerebral Performance Category (PCPC)
of 4 (severe disability; conscious but dependent on others for daily support because of
impaired brain function) at pre-hospital baseline (14).
Individual patient data, including Pediatric Logistic Organ Dysfunction 2 (PELOD-2)
score(15) (after excluding neurologic component so as not to allow the presence of delirium
to affect daily organ dysfunction score), RASS scores(10, 12), CAPD scores(8), need for
respiratory support, and exposure to medications by categories (including narcotics,
benzodiazepines, corticosteroids, anticholinergics, vasoactive medications, and
neuroleptics), as well as other variables were collected daily. Upon discharge from hospital,
mortality, duration of MV, PICU LOS, and hospital LOS were recorded.
Statistical Analysis
Demographic and clinical data were reported as N (%) and median (IQR) for categorical and
continuous variables, respectively. Bivariate relationships between relevant variables and
delirium development (ever vs. never delirious) were analyzed by Chi-Square/Fisher’s Exact
tests, as appropriate. A conservative approach was taken towards unknown days, presuming
them to be non-delirious, in order to avoid overestimating delirium presence. Multivariable
logistic regression, modeling delirium development (ever/never), was constructed from bi-
directional stepwise selection based on Akaike information criterion (AIC) of all factors
from bivariate analyses that reached significance of 0.1. A multivariable linear regression
was constructed to model PICU LOS, using same approach of the following relevant risk
factors: delirium development, mechanical ventilation, probability of mortality, age,
developmental delay, and pre-existing medical condition. Because LOS was skewed, LOS
was log-transformed prior to modeling. A final multivariable logistic regression was
constructed to assess the independent effect of delirium development on in-hospital
mortality after controlling for severity of illness on admission. Statistical tests were two-
sided with significance evaluated at 0.05 alpha level. Analyses were performed with R
version 3.2.4 for Windows 64-bit.
Results
Descriptives of Patient Population
Our cohort included 1,547 unique admissions, and 7,591 study days. Demographic and
clinical patient information is presented in Table 1. Fifty-seven percent of patients were
male, 59% were under age five, and 21% were developmentally delayed. Forty-six percent
were admitted with a primary diagnosis of respiratory failure, and 31% were admitted for
post-operative care. Forty-two percent of patients were mechanically ventilated during their
PICU stay. Forty-three percent were prescribed narcotics, 29% benzodiazepines, and 41%
corticosteroids during their PICU course. Only seven percent of patients were on vasoactive
medications. The average probability of mortality (POM) as calculated by PIM3 was 2%,
with a median of 1%. Median PICU LOS was three days.
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Delirium Incidence and Associated Risk Factors
Delirium was diagnosed in 267 patients, for an incidence of 17.3%. Of the 7,591 patient
study days, 1,259 were days with delirium, for a prevalence of 16.6% in this cohort. 566
patient days (7.5%) were classified as days with coma (almost always medication-induced),
and 5671 patient days (74.7%) as days with normal mental status (DFCF). Only 95 patient
days (<2%) were classified as unknown, due to missed opportunities for delirium screening.
In bivariate analyses(Table 1), pre-existing factors associated with diagnosis of delirium
included age ≤2 years, developmental delay, pre-existing medical condition, and severity of
illness. PICU-related factors linked to the development of delirium included mechanical
ventilation (MV), coma, and receipt of benzodiazepines, narcotics, corticosteroids,
anticholinergics, and vasoactive medications.
In multivariable modeling, independent predictors of delirium included age ≤2 years,
developmental delay, severity of illness, mechanical ventilation, ever coma, and
administration of benzodiazepines and anticholinergics(Table 2). After step-wise selection,
narcotics fell out of the final model. The adjusted odds for delirium diagnosis were more
than five times greater in patients who ever received benzodiazepines, as compared to those
who never received benzodiazepines (adjusted OR=5.2, CI=3.7,7.5, p<0.001)(Table 2).
Description of Delirium
In the 267 patients who were delirious, duration of delirium ranged from one to 52 days,
with an interquartile range of 1–5 days, and a median of two days(Figure 1a). Of those who
were ever delirious, 77.5% were diagnosed with delirium within the first three PICU days,
and 65.5% within the first 48 hours of admission(Figure 1b). Twenty-seven percent
experienced recurrent delirium, with 71 patients experiencing at least 2 discrete episodes of
delirium (range 2–14 delirium episodes in patients with recurrent delirium).
When assessed by phenotype, only eight percent (8.4%) of patient days with delirium were
hyperactive. Forty-six percent (46.4%) of patient days with delirium were hypoactive, and
45.2% were mixed-type.
PELOD Scores (even after discounting neurologic component) were significantly higher on
days with delirium, as compared to PELOD scores on days without delirium (mean 3.9 vs
2.2, p<0.001).
Effect on In-Hospital Outcomes
PICU and hospital LOS were both increased in children with delirium (median 7 vs. 3 days,
p<0.001, and 8 vs. 3 days, p<0.001, respectively). After controlling for relevant confounders,
including probability of mortality and mechanical ventilation, children with delirium
demonstrated a more than two-times longer PICU LOS (adjusted relative LOS=2.3,
CI=2.1,2.5, p<0.001)(Table 3). Duration of MV was associated with delirium status as well
(median 4 vs. 1 day(s) for those ever delirious as compared to MV children who were never
delirious(p<0.001)(Table 1). In-hospital mortality was significantly greater for children with
delirium (5.24% vs. 0.94%, p<0.001), even after controlling for POM on admission, with
adjusted OR for mortality of 4.39 (CI=1.96,9.99) for those ever delirious(p<0.001).
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