Study reference

Study characteristics

Patient characteristics

Prognostic factor(s)

Follow-up

Estimates of prognostic effect

Comments

Alvarez, 2018

Type of study: single-center prospective observational cohort study

Setting and country: pediatric cardiac intensive care unit (CICU) in USA

Funding and conflicts of interest: Pediatric Critical Care Clinical Research Program and the Heart Institute of the Children’s Hospital Colorado

Inclusion criteria: all patients from birth to 21 years old admitted over a 10-week period between June 2015 to August 2016

Exclusion criteria: admitted to CICU for less than 12 hours; admitted to pediatric CICU>24 hours prior first delirium screening; to identify only new delirium diagnoses. Neuromuscular blockade and/or therapeutic hypothermia

N= 99

Age(median):

24 months (IQR 2-72)

Sex: 53% M / 47% F

Potential confounders or effect modifiers: mechanical ventilation 57%

Describe prognostic factor(s) and method of measurement:

STS-EACTS surgical score for surgically treated patients; cardiopulmonary bypass time (15 minute increments), cross-clamp time, age (months), mechanical ventilation on admission, any mechanical ventilation, benzodiazepine use, opioid use, drug exposure prior to admission, location prior to admission (home versus inpatient) and anticholinergics.

Patient characteristics from medical record: age, sex, race/ethnicity, date of admission, date and type of surgical procedure, diagnoses. deep hypothermic circulatory arrest time, and. Type of respiratory support (both on admission and daily), use of vasopressor/inotrope, opiates, benzodiazepines, anticholinergics, steroids, Withdrawal Assessment Tool -1 scores and CAPD score.

Duration or endpoint of follow-up:

For how many participants were no complete outcome data available?

N (%): 46, these were excluded resulting in a sample size of 99 patients

Reasons for incomplete outcome data described? Missing data were excluded

Multivariable mixed logistic regression model:

STS-EACTS score >3: OR 1.08 (95% CI 0.25; 4.64) P=0.91

Cardio Pulmonary Bypass time (15 minutes): 1 (95% 0.87; 1.16) P=0.98

Age (months): 0.35 (95% CI 0.19; 0.64) P=0.0001

Mechanical ventilation: 4.1 (95% CI 1.7; 9.89) P=0.02

Benzodiazepines: 3.78 (95% CI 1.46; 9.79) P=0.01

Dervan, 2020

Type of study: Retrospective cohort study

Setting and country: tertiary care PICU, Seattle, USA

Funding and conflicts of interest:

Authors have disclosed that they do not have any potential conflicts of interest

Inclusion criteria: All children admitted to the PICU March 1, 2014, to October 1, 2016, with at least one Cornell Assessment of Pediatric Delirium score

Exclusion criteria: ND

N = 2446 (N=1538 (63%) LOS <48hr)

Age:

<2: 32%

2-5: 17%

5-12: 21%

 ³ 12: 19%

Sex: 53 % M / 47 % F

Describe prognostic factor(s) and method of measurement:

Multivariable logistic regression, including all factors that were significant at the 0.10 from univariate analyses.

Covariates were selected to retain in the multivariable models using backward stepwise selection, eliminating covariates with p value greater than 0.2 and re-entering those with p less than 0.1

Duration or endpoint of follow-up:

For how many participants were no complete outcome data available?

N (%): ?

Reasons for incomplete outcome data described? -

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Is alleen een figuur gegeven van multivariate analyses

Age under 2 yrs:

First PRISM

Baseline PCPC

Etc.

Mody, 2018

Type of study: retrospective cohort study

Setting and country: tertiary care PICU, New York, USA

Funding and conflicts of interest: funding received from pharmaceutical companies by several authors; other authors did not receive funding from these companies.

Inclusion criteria: All patients admitted consecutively to our academic, urban, tertiary care PICU from January 2015 to June 2015 were included. This group is a part of a larger cohort of children included in a 12-month dataset.

Exclusion criteria: -

N= 580

Age at admission:

<1: 25%

1-2: 20%

3-5: 20%

6-12: 17%

>12: 18%

Sex: 53% M

Potential confounders or effect modifiers:

See table 1

Describe prognostic factor(s) and method of measurement:

Cognitive status (delirium, coma or normal)

Benzodiazepine exposure

Opiate exposure

Mechanical ventilation

In marginal structural model (MSM)

Duration or endpoint of follow-up: unclear

For how many participants were no complete outcome data available?

N (%): ?

Reasons for incomplete outcome data described? -

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Multivariate mixed effects model:

Cognitive status day prior:

Coma 0.85 (95%CI 0.51 – 1.41)

Delirium 8.16 (95%CI 5.67 – 11.74)

Benzodiazepine exposure day prior 2.02 (95%CI 1.39 – 2.93)

Opiate exposure day prior 1.09 (95% CI 0.75 – 1.59)

Mechanical ventilation 3. 92 (2.59 – 5.92)

Patel, 2017

Type of study: prospective cohort study

Setting and country: pediatric cardiac intensive care unit (PCICU), USA

Funding and conflicts of interest: all authors have disclosed no conflict of interest; funding not reported

Inclusion criteria: PCICU admission following on-pump cardiac surgery age ≤ 21 years

Exclusion criteria: ND

N = 194

Age:

0-2: 42%

3-5: 25%

6-13: 15%

>13: 19%

Sex: 59 % M / 41 % F

Potential confounders or effect modifiers: 37% mechanically ventilated

Describe prognostic factor(s) and method of measurement:

Multivariable logistic regression, including all factors that were significant at the 0.10 alpha level in bivariate analyses, was performed to predict development of delirium. Bi-directional stepwise selection based on Akaike information criterion produced the final model

Duration or endpoint of follow-up:

For how many participants were no complete outcome data available?

N (%):

Reasons for incomplete outcome data described? Days with missing delirium assessment were excluded (1,4% of days)

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Age

0-2 reference

>2-5 0.30 (0.12 – 0,70)

>5-13 0.30 (0.10 – 0.87)

>13 0.06 (0.02 – 0.22)

Baseline albumin

≤ 3 mg/dL reference

>3 mg/dL 0.19 (0.04 0.84)

Developmental delay

No delay: reference

Delay: 3.38 (1.18 – 9.66)

RACHS score

Rachs score 1-2: reference

Rachs score 3-4: 2.93 (1.32 – 6.50)

Cyanotic heart disease

No: reference

Yes: 2.43 (1.16 – 5.09)

Ramirez, 2019

Type of study: cross-sectional study

Setting and country: Colombia

Funding and conflicts of interest: Dirección de Investigación e Innovación (CIDI) of the Universidad Pontificia Bolivariana (project: 434B-08/15-45). The CIDI did not participate in the design of the study or in data compilation, analysis or decision to submit the manuscript

Inclusion criteria:

 patients between 5 and 14 years of age consecutively admitted to the PICU of Hospital Pablo Tobón Uribe --- a high complexity university hospital

Exclusion criteria: patients with stupor or in coma, with communication problems precluding evaluation, receiving deep sedation throughout admission, and those cases in which informed consent could not be obtained

N= 156

Median age:

Delirium: 10.0

Without delirium: 11.0

Sex: 62% M /38 % F with delirium; 50% M/50% F, without delirium

Potential confounders or effect modifiers: Mechanical ventilation 31% with delirium; 5% without delirium

Describe prognostic factor(s) and method of measurement:

Independent variables were: age in years, gender, educational level, administration of deep sedation upon admission (yes/no, depending on whether the RASS score was ≤3), PRISM score, history of intellectual disability, epilepsy, vision problems or hearing problems, and each of the 6 most frequent main diagnoses upon admission according to the DEC.

2) following characteristics had been recorded in the case history during the last 24---72 h: postoperative condition, mechanical ventilation, respiratory failure, ineffective clearing of the airway, altered heart rate or blood pressure (tachycardia, bradycardia, hypertension or hypotension according to the criteria of the American Heart Association), hyperthermia (temperature ≥ 38.0 ◦C), hypothermia (temperature ≤ 36.0 ◦C), hypoxemia (PaO2 < 60 mmHg), pain scored from 0 to 10 based on a visual analog scale (VAS), acidosis, electrolytic alterations, anemia, nutritional imbalances, neurologic

al diseases of any kind, seizures, intoxication, heart, kidney or liver failure, metabolic disorders (e.g., blood glucose or thyroid alterations), infection, loss of skin integrity, constipation and restricted mobility.

3) Drug groups: (administered in the last 72 h): analgesics, corticosteroids, opioids, antibiotics, anticholinergic agents, benzodiazepines, antipsychotics and --- as a single variable --- other psychotropic agents.

Duration or endpoint of follow-up:

For how many participants were no complete outcome data available?

N (%):

Reasons for incomplete outcome data described?

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value^1: chi-kwadraat 10.567, p=0.103

Characteristic (OR (95%CI))

History of intellectual disability 17.54 (3.23---95.19)

Mechanical ventilation 18.80 (4.29---82.28)

Liver failure 54.88 (4.27---705.33)

Neurological disease 4.41 (1.23---15.83)

Use of anticholinergic drugs 3.23 (1.02---10.26)

Use of other psychotropic agents 4.88 (1.42---16.73)

Tachycardia 4.74 (1.21---18.51)

o

Silver, 2015

Type of study: prospective cohort study

Setting and country: PICU, New York, USA

Funding and conflicts of interest: Supported, in part, by grant UL1-TR000457-06 from the National Center for Advancing Translational Sciences

Inclusion criteria: prospective observational study, conducted over 10 weeks in an urban academic tertiary care PICU. All patients were eligible for inclusion, regardless of age or diagnosis

Exclusion criteria: deeply sedated patients: unarousable to verbal stimulation

N= 99

Age:

0-2: 34%

2-5: 19%

5-13: 21%

>13: 25%

Sex: 60% M

Potential confounders or effect modifiers: Mechanical ventilation 25%

Describe prognostic factor(s) and method of measurement:

Any bivariate association that achieved a p value of less than 0.2 was entered into the multivariate model.

Demographic and clinical data were collected upon enrollment, including age, gender, diagnosis, severity-of-illness score using Pediatric Index of Mortality II (PIM2), and history of prematurity. Severe impairment in the child’s ability to communicate with caregiver at baseline was used as a proxy for severe developmental delay. Clinical data were collected daily, including need for oxygen and mechanical ventilation. Hospital length of stay (LOS) was calculated from day of hospital admission to day of hospital discharge

Duration or endpoint of follow-up:

For how many participants were no complete outcome data available?

N (%): 12 and these were excluded

Reasons for incomplete outcome data described? 12 subjects were unavailable for assessment: nine subjects were either off the unit (in surgical or radiologic suites) or involved in clinical care that could not be interrupted at the time the psychiatrist was available; three subjects were transferred out of the PICU prior to the psychiatrist’s availability)

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Age

0-2 3.43 (0.70 – 16.78)

2-5 8.80 (1.82 – 42.53)

5-13 2.99 (0.58 – 15.41)

>13 Reference

Developmental delay

Yes 3.45 (1.54 – 7.76)

No Reference

Mechanical ventilation

Yes 3.86 (1.81 – 8.24)

No Reference

Traube, April 2017, Critical Care Medicine

Type of study: multicentre cross-sectional study

Setting and country: 25 PICU’s in United States, the Netherlands, New Zealand, Australia and Saudi Arabia

Funding and conflicts of interest: Supported, in part, by Weill Cornell Medical College Clinical and Translational Science Center (CTSC Grant UL1 TR000457) for REDCap; several authors received personal funding for other projects, mostly non-commercial

Inclusion criteria: On designated study days, every child physically admitted to the pediatric critical care unit at 8 AM local time was included in analysis

Exclusion criteria: developmental delay; unknown delirium status

N=994

Age:

0-2: 49%

2-5: 15%

5-13: 20%

>13: 17%

Sex: 54% M /46 % F

Potential confounders or effect modifiers: Mechanical ventilation: 36%

Describe prognostic factor(s) and method of measurement:

Medical records were examined for demographics (age, sex, race, and ethnicity), reason for admission, presence of physical restraints, respiratory support, and exposure to specific medications on the study day.

Duration or endpoint of follow-up: cross-sectional study

For how many participants were no complete outcome data available?

N (%): Age: 1 missing, race: 5 missing and ethnicity: 17 missing

Reasons for incomplete outcome data described? -

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:?

Multivariate log reg model:

Age >2 yr: 0.7 (0.5 – 1.0)

Physical restraints: 4.0 (2.0 7.7)

Mechanical ventilation: 1.7 (1.1 – 2.7)

Narcotics: 2.3 (1.5 – 3.5)

Benzodiazepines: 2.2 (1.5 – 3.3)

Antiepileptics: 2.9 (1.8 4.8)

General anesthesia: 0.4 (0.3 – 0.8)

Vasopressors: 2.4 (1.5 – 3.8)

Traube, 2017, JPEDS

Type of study: retrospective cohort study

Setting and country: Cancer PICU, New York, USA

Funding and conflicts of interest: unknown

Inclusion criteria: all consecutive admissions between the ages of 0-21 years during the 3 month study period

Exclusion criteria: -

N=188, 319 admissions

Age:

0-2: 10%

2-5: 24%

5-13: 25%

>13: 41%

Sex: 50% M / 50% F

Potential confounders or effect modifiers:-

Describe prognostic factor(s) and method of measurement:

Clinical information was collected via review of the electronic medical record. Demographic data included sex, age, primary oncologic diagnosis, primary reason for admission, history of stem cell transplant and presence of metastatic central nervous system disease. Data on medication administered, laboratory values, need for supplemental oxygen, provision of total parenteral nutrition and do not-resuscitate status was also collected.

Duration or endpoint of follow-up: cross-sectional

For how many participants were no complete outcome data available?

N (%): not reported

Reasons for incomplete outcome data described? Not reported

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:?

Multivariate log reg model (OR (95% CI)):

Age ≤ 5 yr: 2.61 (1.12 – 6.08)

Primary diagnosis of brain tumor: 4.72 (1.20 – 18.57)

Postoperative status: 3.27 (1.27 – 8.42)

Receipt of benzodiazepines: 3.71 (1.79 – 7.71)

Receipt of narcotics: 1.80 (0.74 – 4.35)

Children with cancer

Traube 2017, Critical Care Medicine, May 2017

Type of study: prospective longitudinal cohort study

Setting and country: PICU, New York, USA

Funding and conflicts of interest: Supported by the Empire Clinical Research Investigator Program, and the Clinical Translational Science Center, grant number UL1-TR000457-06. Authors declared not to have relevant conflicts of interest

Inclusion criteria: All patients admitted to the PICU service for at least 24 hours between September 1, 2014 and August 31, 2015 were included.

Exclusion criteria: -

N = 1547

Age:

0-2: 38%

>2-5: 20%

>5-13: 22%

>13: 19%

Sex: 57 % M /43 % F

Potential confounders or effect modifiers: Ever mechanically ventilated: 42%; 21% developmentally delayed

Describe prognostic factor(s) and method of measurement:

Demographic data, including age, sex, primary diagnosis, pre-existing medical conditions, severity of illness (as measured by Pediatric index of Mortality-3 (PIM3) score, and divided into tertiles), and developmental status were collected on admission.

Individual patient data, including Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score (after excluding neurologic component so as not to allow the presence of delirium to affect daily organ dysfunction score), RASS scores, CAPD scores, 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.

Duration or endpoint of follow-up: 7591 patient study days

For how many participants were no complete outcome data available?

N (%):-

Reasons for incomplete outcome data described? <2% unknown days, due to missed opportunities for delirium screening

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Age

0-2: reference

>2-5: 0.61 (0.39 – 0.94)

>5-13: 0.41 (0.26 – 0.65)

>13: 0.40 (0.24 – 0.64)

Probability mortality:

<= 0,80% reference

>0.80% & <= 1.4%: 1.274 (0.83 – 1.98)

>1.4%: 1.531 (1.016 – 2.318)

Developmental delay: 3.314 (2.328 – 4.724)

Ever mechanically ventilated: 1.634 (1.155 – 2.314)

Ever in coma: 4.244 (2.684 – 6.783)

Benzodiazepines: 5.245 (3.710 – 7.455)

Anti-cholinergics: 2.169 (1.412 – 3.416)

Winsnes, 2019

Type of study: prospective cohort study

Setting and country: PICU, Oregon, USA

Funding and conflicts of interest: Oregon Health and Science University

Inclusion criteria: all patients treated within the Doernbecher Blood and Cancer Program, ages 0 to 21 years, who were admitted to the 21-bed PHO unit or the 20-bed PICU during the study period

Exclusion criteria: Any patient who deemed too sedate to be screened for delirium

N = 807 admissions in 223 unique patients

Mean age ± SD: not described (0-21 years)

Sex: 56% M /44 % F

Potential confounders or effect modifiers:

Describe prognostic factor(s) and method of measurement:

Duration or endpoint of follow-up: one year

For how many participants were no complete outcome data available?

N (%):

Reasons for incomplete outcome data described?

(Adjusted) Factor-outcome associations (include SEs or 95%CI and p-value if available):

Incremental predictive value¹:

Multiple correspondence analysis and stepwise logistic regression modelling revealed the following variables to be associated with a positive delirium screen: younger age at admission, LOS > 5 days, patient location (PICU versus PHO unit), administration of benzodiazepines, opioids, or anticholinergics (graphically represented in figure 2)

Study reference

(first author, year of publication)

Study participation¹

Study sample represents the population of interest on key characteristics?

(high/moderate/low risk of selection bias)

Study Attrition²

Loss to follow-up not associated with key characteristics (i.e., the study data adequately represent the sample)?

(high/moderate/low risk of attrition bias)

Prognostic factor measurement³

Was the PF of interest defined and adequately measured?

(high/moderate/low risk of measurement bias related to PF)

Outcome measurement³

Was the outcome of interest defined and adequately measured?

(high/moderate/low risk of measurement bias related to outcome)

Study confounding⁴

Important potential confounders are appropriately accounted for?

(high/moderate/low risk of bias due to confounding)

Statistical Analysis and Reporting⁵

Statistical analysis appropriate for the design of the study?

(high/moderate/low risk of bias due to statistical analysis)

Alvarez 2018

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Dervan 2020

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Mody, 2018

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Patel, 2017

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Ramirez, 2019

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Silver, 2015

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Traube 2017

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Traube 2017

Moderate risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Traube 2017

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis

Winsnes, 2019

Low risk of selection bias

Low risk of Bias

Low risk of measurement bias

Moderate risk of measurement bias

Unclear

Low risk of bias due to statistical analysis