Long Term Follow up of Children Enrolled in the REDvent Study

The Effect of Intensive Care Unit Therapies and Mechanical Ventilation Strategy on Long Term Outcome in Pediatric ARDS A Follow-up of the Real-time Effort Driven VENTilator Management Study (REDvent)

This is a prospective observational follow-up study of children enrolled in a single center randomized controlled trial (REDvent).

Nearly 50% of adult Acute Respiratory Distress Syndrome (ARDS) survivors are left with significant abnormalities in pulmonary, physical, neurocognitive function and Health Related Quality of Life (HRQL) which may persist for years.Data in pediatric ARDS (PARDS) survivors is limited. More importantly, there are no data identifying potentially modifiable factors during ICU care which are associated with long term impairments, which may include medication choices, or complications from mechanical ventilator (MV) management in the ICU including ventilator induced lung injury (VILI) or ventilator induced diaphragm dysfunction (VIDD).

The Real-time effort driven ventilator (REDvent) trial is testing a ventialtor management algorithm which may prevent VIDD and VILI. VIDD and VILI have strong biologic plausibility to affect the post-ICU health of children with likely sustained effects on lung repair and muscle strength. Moreover, common medication choices (i.e. neuromuscular blockade, corticosteroids) or other complications in the ICU (i.e. delirium) are likely to have independent effects on the long term health of these children. This proposed study will obtain serial follow-up of subjects enrolled in REDvent (intervention and control patients). The central hypothesis is that preventing VIDD, VILI and shortening time on MV will have a measureable impact on longer term function by mitigating abnormalities in pulmonary function (PFTs), neurocognitive function and emotional health, functional status and HRQL after hospital discharge for children with PARDS.

For all domains, the investigators will determine the frequency, severity and trajectory of recovery of abnormalities amongst PARDS survivors after ICU discharge, identify risk factors for their development, and determine if they are prevented by REDvent. They will leverage the detailed and study specific respiratory physiology data being obtained in REDvent, and use a variety of multi-variable models for comprehensive analysis. Completion of this study will enable the investigators to identify ICU related therapies associated with poor long term outcome, and determine whether they can be mitigated by REDvent.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Respiration Disorders; Ventilator-Induced Lung Injury; Respiratory Distress Syndrome, Adult; Neurocognitive Dysfunction
• Intervention / Treatment: Diagnostic test: Ventilation Inhomogeneity; Diagnostic test: Diaphragm Ultrasound; Diagnostic test: Respiratory Inductance Plethysmography; Diagnostic test: Spirometry; Diagnostic test: Functional Residual Capacity; Diagnostic test: MIP/MEP; Diagnostic test: 6 minute walk test; Diagnostic test: Neurocognitive Testing; Diagnostic test: Emotional Health Assessment; Diagnostic test: Health Related Quality of Life; Diagnostic test: Functional Status; Diagnostic test: Respiratory Status Questionnaire

Detailed Description

Background and Significance: Through advancements in critical care, PARDS mortality has decreased from 50% to less than 20%. Therapeutic strategies for PARDS have sought to improve survival, but have often ignored morbidity, despite extensive evidence that nearly 50% of adult ARDS survivors are left with significant abnormalities in pulmonary, physical, neurocognitive function and HRQL which may persist for years. Recent data highlight that approximately 20% of children with respiratory failure have low HRQL 6 months after ICU discharge, and 30% screen positive for post-traumatic stress (PTS). There are virtually no data regarding pulmonary and neurocognitive deficits in PARDS survivors. More importantly, there are no data identifying potentially modifiable factors during ICU care which are associated with long term impairments.

It is increasingly recognized that ARDS ventilator management is associated with VIDD and VILI, which increase length of MV and failed extubation.REDvent is currently testing whether a MV strategy which uses esophageal manometry to target physiologic levels of patient effort can prevent VIDD and shorten length of MV. In addition, the REDvent strategy results in more lung protective management of Positive End Expiratory Pressure (PEEP), Peak Inspiratory Pressure (PIP), and Delta Pressure (DP) which may prevent VILI. While the REDvent study is designed for ICU related outcomes, there is strong biologic plausibility that the REDvent strategy can improve long-term outcome. The investigators propose serial follow up of subjects enrolled in the REDvent study (intervention and control patients) which will leverage the infrastructure and data of an already enrolling clinical trial to fill crucial knowledge gaps regarding how PARDS survivors recover from critical illness. The central hypothesis is that preventing VIDD, VILI and shortening time on MV will have a measureable impact on longer term function by mitigating abnormalities in pulmonary function (PFT), neurocognitive function and emotional health, functional status and HRQL after ICU discharge for children with PARDS.

Study Aims:

Specific Aim (SA1): To determine the frequency, severity and trajectory of recovery of PFT abnormalities amongst PARDS survivors within 6 months of ICU discharge, identify risk factors for their development, and determine if they are prevented by REDvent.

Specific Aim (SA2): To determine the frequency and severity of impairments in neurocognitive function and emotional health amongst PARDS survivors in the first year after ICU discharge, identify risk factors for their development, and determine if they may be improved by REDvent.

Specific Aim (SA3): To determine the frequency, severity and trajectory of recovery of respiratory and functional status and HRQL amongst PARDS survivors in the 12 months after ICU discharge, identify risk factors for their development, and determine if they may be improved by REDvent.

Study Design: This is a prospective observational follow-up study of children enrolled in a single center randomized controlled trial (REDvent; RO1 HL134666, PI: Khemani).

Study Measurements and Outcomes: Assessments will be made serially from enrollment up to 1 year after ICU discharge . Data gathered from the parent REDvent study during the original course of mechanical ventilation will also be used for analysis, to understand whether ICU specific therapies, management strategies, or severity of illness are associated with long term outcomes.

Expected Sample Size: REDvent plans to enroll 300 children over 4.5 years. 240 children are expected to survive to hospital discharge, 200 (83%) are expected to consent for follow-up, and allowing for 25% dropout, 150 will reach the primary follow-up endpoints.

A1.H1. At least 30% of PARDS survivors will have ventilation inhomogeneity (VI, primary outcome measured with Lung Clearance Index (LCI)) which will persist 6 months after discharge.

Analysis: LCI more than 7.5 will be considered abnormal for analysis, and is anticipated to will occur in at least 30% of patients. This yields a 95% confidence interval from 23 to 38% assuming 150 patients complete follow-up. Similar analysis is planned for secondary outcomes. Analyses will be stratified by baseline pulmonary status or history of previous pulmonary disease.

A1.H2. ICU management of PEEP and transpulmonary driving pressure will be independently associated with VI after controlling for baseline co-morbidities and PARDS severity.

Analysis: The primary outcome for this sub aim is abnormal LCI 6 (VI) months after discharge, as above. Analysis will compare median, mean, and extreme (min or max) transpulmonary pressure at PEEP, plateau, and driving pressure during the acute phase of ventilation (prior to the first SBT) stratified by normal or abnormal LCI. Length of exposure to these settings will be modeled by including an interaction between transpulmonary pressure and length of ventilation. All analyses will be adjusted with multivariable models, controlling for PARDS severity, co-morbidities, and other ventilator and ancillary therapy management.

A1.H3. REDvent will be independently associated with lower VI and fewer abnormalities in pulmonary function and respiratory muscle strength.

Analysis: The investigators will first analyze differences in median LCI between REDvent and control patients using a Mann-Whitney U or t-test. From preliminary data, the investigators anticipate a power >0.8 to detect > 10% improvement in LCI with the expected enrollment (150 patients). They will subsequently construct a multivariable linear regression model on LCI 6 months after ICU discharge to test whether REDvent management remains independently associated with less VI after adjusting for short term-ICU outcome variables. In addition, usual care acute phase arm (lack of REDvent exposure) will be considered as an independent risk factor for abnormal VI in the multivariable logistic regression model described in A1.H2.

A2.H1. At least 30% of previously unimpaired PARDS survivors will have impairment in neurocognitive function 3 months after ICU discharge, and 20% will persist with deficits at 1 year.

Analysis: As with the previous aim, the primary outcomes are expressed as binary variables for ease of interpretation. The investigators anticipate 100 previously unimpaired children will complete this aim. The primary outcome is neurocognitive function using Batelle-2 or WISC-5. They estimate approximately 40% of children will have impaired neurocognitive function at 3 month follow-up, resulting in a 95% confidence interval from 30% to 50%. Descriptive analysis will be provided by specific domain both as continuous data and categorized as above. Emotional health assessments and PTS analysis will mimic what is presented above for the subset with data available.

A2.H2. Duration of delirium while in the ICU will be independently associated with impaired neurocognitive function.

Analysis: The primary outcomes will be categorical, evaluated 3 months after discharge. The primary predictor variable is days with delirium (as identified by CAPD score > 9) modeled as an ordinal variable. Additional confounding variables will be considered including length of MV, illness severity, sedation doses, with selection as described in the previous aims. Secondary analysis will generate a linear regression model on the continuous outcome of normalized neurocognitive score from Batelle-2 or WISC-5, and will consider an interaction term based on the tool used for measurement.

A2.H3. Lack REDvent exposure will be independently associated with impaired neurocognitive function.

Analysis: The investigators will directly examine normalized neurocognitive score between REDvent and control groups using a t-test or MWU test. The percentage of children with abnormal values at 3 months will be compared between the groups with a Chi-Square test. In multivariable linear regression modeling they will examine the independent relationship between REDvent intervention arm and normalized neurocognitive score, using similar methods as detailed above. In addition, usual care acute phase arm (lack of REDvent exposure) will be considered as an independent risk factor in the multivariable logistic regression models described in A2.H2.

A3.H1. At least 25% of PARDS survivors will have a new respiratory requirement, and 40% will have a decline in overall functional status or a significant decrease in HRQL from baseline at 3 months after ICU discharge, and at least 20% of children will persist with a deficit in one of these domains at 12 months.

Analysis: As with the previous aims, the primary outcomes are expressed as binary variables for ease of interpretation. However, additional analysis will consider all outcomes as continuous variables. The primary outcomes under this aim consider 3 domains: 1) Functional Status decline: FSS 2 or more points above (worse than) baseline 2) HRQL decline: PEDsQL 5 points or more below (worse than) baseline 3) New respiratory requirement (oxygen, positive pressure, respiratory medications, and respiratory therapies). Based on the research presented above, they estimate 40% of children will have impaired HRQL or functional status at 3 month follow-up, with 95% CI ranging from 32% to 48%, and 25% of children will have a new respiratory requirement, with 95% CI ranging from 18.5 to 32.4%. The same analysis will be repeated at 12 month follow-up.

A3.H2. Cumulative exposure to neuromuscular blockade, corticosteroids, length of MV, and delirium will be independently associated with decline in 1) functional status 2) HRQL and 3) new respiratory requirement 3 months after ICU discharge after controlling for PARDS severity, co-morbidities, and other confounding variables.

Analysis: The primary outcomes will be categorical, as described in the section above (A3.H1), evaluated 3 months after discharge. The primary predictor variables include: days of neuromuscular blockade, days receiving corticosteroids, days with delirium (CAP-D > 9120-124) and days on MV, modeled as ordinal variables. Additional confounding variables will be considered with selection as described in the previous aims. Multiplicative interaction terms will be considered for inclusion (i.e. corticosteroids*neuromuscular blockade).

A3.H3. REDvent will be independently associated with improved recovery to baseline respiratory status, functional status, and HRQL recovery 3 months after ICU discharge.

Analysis: The investigators will directly examine PEDsQL change from baseline and FSS change from baseline at 3 month follow up in REDvent and control patients using Mann Whitney U tests. The percentage of children reaching baseline pulmonary requirement at 3 months will be compared between the previously stated groups with a Chi-Square test. In multivariable linear regression modeling the investigators will examine the independent relationship between REDvent intervention arms and change in FSS and HRQL outcomes using the methods detailed in the previous aims. In addition, usual care acute phase arm (lack of REDvent exposure) will be considered as an independent risk factor in the multivariable logistic regression models described in A3.H2 on the categorical outcomes described above.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Robinder G Khemani, MD; Phone Number: 323-361-2376; Email: rkhemani@chla.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
      • Contact: Robinder G Khemani, MD; Email: rkhemani@chla.usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a long term follow-up of children already enrolled in the RED-vent study.

Description

Inclusion Criteria:

1. Children > 1 month (at least 44 weeks Corrected Gestational Age) and ≤ 18 years of age AND
2. Supported on mechanical ventilation for pulmonary parenchymal disease (i.e., pneumonia, bronchiolitis, Pediatric Acute Respiratory Distress Syndrome (PARDS)) with Oxygen Saturation Index (OSI) ≥ 5 or Oxygenation Index (OI) ≥4 115 AND
3. Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution) AND
4. Enrolled in the REDvent Study

Exclusion Criteria (1-5 are REDvent exclusion):

1. Contraindications to use of an esophageal catheter (i.e. severe mucosal bleeding, nasal encephalocele, transphenoidal surgery) OR
2. Contraindications to use of RIP bands (i.e. omphalocele, chest immobilizer or cast) OR
3. Conditions precluding diaphragm ultrasound measurement (i.e. abdominal wall defects, pregnancy) OR
4. Conditions precluding conventional methods of weaning (i.e., status asthmaticus, severe lower airway obstruction, critical airway, intracranial hypertension, Extra Corporeal Life Support (ECLS), intubation for UAO, tracheostomy, DNR, severe chronic respiratory failure, spinal cord injury above lumbar region, cyanotic heart disease (unrepaired or palliated)) OR
5. Primary Attending physician refuses (will be cleared with primary attending before approaching the patient) OR
6. Death in the ICU OR
7. New DNR orders during acute illness in ICU OR
8. Primary Language not English or Spanish OR
9. Children in foster care or a ward of the state.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation In-homogeneity using lung clearance index with nitrogen washout	Measured by lung clearance index during multiple breath nitrogen washout testing reported as percent predicted based on age and height as well as a raw number typically ranging from 5-15.	6 months after ICU discharge
Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests	Standardized IQ-like score derived from Batelle-2 or WISC-5 cognitive tests based on age. Children < 6 years will receive the Batelle-2 and children >=6 will receive the WISC-5. Overall score will be use for analysis with a higher value indicating better cognitive function. The range of "average" cognitive function lies between 90-109. Both tests are scored on the same scale	3 months after ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	3 months after ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline to 3 months will be considered as a decline in functional status.	3 months after ICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Residual Capacity (Lung volume at end-expiration).	Measured by body box plethysmography and nitrogen washout techniques, normalized by age, height and gender. Values below or above normative values will be considered abnormal.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Functional Residual Capacity (Lung volume at end-expiration).	Measured by body box plethysmography and nitrogen washout techniques, normalized by age, height and gender. Values below or above normative values will be considered abnormal.	6 months after ICU discharge
Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)	Respiratory Inductance Plethysmography belts are used during tidal breathing to measure thoraco-abdominal asyncrhony. Higher values will be considered abnormal with a range from 0-180.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)	Respiratory Inductance Plethysmography belts are used during tidal breathing to measure thoraco-abdominal asyncrhony. Higher values will be considered abnormal with a range from 0-180.	6 Months after ICU Discharge
Diaphragm Thickness on exhalation	Diaphragm ultrasound measurement of thickness at end exhalation measured in zone of apposition of right hemi-diaphragm	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Diaphragm Thickness on exhalation	Diaphragm ultrasound measurement of thickness at end exhalation measured in zone of apposition of right hemi-diaphragm	6 months after ICU discharge
Diaphragm Thickness on inspiration	Diaphragm ultrasound measurement of thickness at end inspiration measured in zone of apposition of right hemi-diaphragm	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Diaphragm Thickness on inspiration	Diaphragm ultrasound measurement of thickness at end inspiration measured in zone of apposition of right hemi-diaphragm	6 months after ICU discharge
Diaphragm Thickening fraction (measure of contractile activity)	Diaphragm ultrasound measurement calculated as (thickness at end inspiration-thickness at end expiration)/(thickness at end expiration) measured in zone of apposition of right hemi-diaphragm.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Diaphragm Thickening fraction (measure of contractile activity)	Diaphragm ultrasound measurement calculated as (thickness at end inspiration-thickness at end expiration)/(thickness at end expiration) measured in zone of apposition of right hemi-diaphragm.	6 months after ICU discharge
Ventilation In-homogeneity using lung clearance index with nitrogen washout	Measured by lung clearance index during multiple breath nitrogen washout testing reported as percent predicted based on age and height as well as a raw number typically ranging from 5-15.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Forced Expiratory Volume in 1 second (FEV1)	Spirometry based measures of pulmonary function of forced expiratory volume, normalized based on age, height, and gender and reported as percent predicted.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Forced Expiratory Volume in 1 second (FEV1)	Spirometry based measures of pulmonary function of forced expiratory volume, normalized based on age, height, and gender and reported as percent predicted.	6 months after ICU discharge
Forced Vital Capacity (FVC)	Spirometry based measures of pulmonary function of forced vital capacity, normalized based on age, height, and gender and reported as percent predicted.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Forced Vital Capacity (FVC)	Spirometry based measures of pulmonary function of forced vital capacity, normalized based on age, height, and gender and reported as percent predicted.	6 months after ICU discharge
Forced expiratory flow at 25-75% (FEF 25-75)	Spirometry based measures of pulmonary function of forced expiratory flow at 25-75% of breath, normalized based on age, height, and gender and reported as percent predicted.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Forced expiratory flow at 25-75% (FEF 25-75)	Spirometry based measures of pulmonary function of forced expiratory flow at 25-75% of breath, normalized based on age, height, and gender and reported as percent predicted.	6 months post ICU discharge
VT - tidal volume from spirometry during tidal breathing	Lung volume measurements obtained during tidal breathing, normalized in ml/kg ideal body weight.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
VT - tidal volume from spirometry during tidal breathing	Lung volume measurements obtained during tidal breathing, normalized in ml/kg ideal body weight.	6 months after ICU discharge
Total Lung Capacity- TLC measured during spirometry	Lung volume measurements obtained during pulmonary function tests with spirometry and body box plethysmography to calculate total lung capacity, normalized by age, height and gender.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Total Lung Capacity- TLC measured during spirometry	Lung volume measurements obtained during pulmonary function tests with spirometry and body box plethysmography to calculate total lung capacity, normalized by age, height and gender.	6 months after ICU discharge
Forced vital capacity- measured during spirometry	Lung volume measurements obtained during pulmonary function tests with spirometry to calculate forced vital capacity, normalized by age, height and gender.	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Forced vital capacity- measured during spirometry	Lung volume measurements obtained during pulmonary function tests with spirometry to calculate forced vital capacity, normalized by age, height and gender.	6 months after ICU discharge
Respiratory Muscle Strength Maximum inspiratory pressure (MIP)	Maximal inspiratory pressure measurements during airway occlusion in cm H20	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Respiratory Muscle Strength Maximum inspiratory pressure (MIP)	Maximal inspiratory pressure measurements during airway occlusion in cm H20	6 months after ICU discharge
Respiratory Muscle Strength Maximum expiratory pressure (MEP)	Maximal expiratory pressure measurements during airway occlusion in cm H20	Prior to Hospital Discharge and no more than 1 month after ICU discharge
Respiratory Muscle Strength Maximum expiratory pressure (MEP)	Maximal expiratory pressure measurements during airway occlusion in cm H20	6 months after ICU discharge
Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests	Standardized IQ-like score derived from Batelle-2 or WISC-5 cognitive tests. Overall score will be use for analysis with a higher value indicating better cognitive function. The range of "average" cognitive function lies between 90-109.	12 months after ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	1 month after ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	2 months after ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	6 months after ICU discharge
Health Related Quality of Life as measured by PedsQL generic core scale	PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life	12 months after ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.	ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.	1 month after ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.	2 months after ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.	6 months after ICU discharge
Functional Status as measured by the pediatric functional status scale	Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.	12 months after ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	1 month after ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	2 months after ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	3 months after ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	6 months after ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.	Series of questions to detail respiratory based morbidity	12 months after ICU discharge
Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress	The Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years will be used to assess for emotional and behavioral abnormalities as a survey tool. The UCLA PTSD Reaction Index (UCLA RI) will be used for children ≥ 8 years. The UCLA RI is a semi-structured interview assessing for exposure to traumatic events and PTS in children.	3 months after ICU discharge
Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress	The Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years will be used to assess for emotional and behavioral abnormalities as a survey tool. The UCLA PTSD Reaction Index (UCLA RI) will be used for children ≥ 8 years. The UCLA RI is a semi-structured interview assessing for exposure to traumatic events and PTS in children.	12 months after ICU discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minute walk test	Measure of cardio-respiratory function after treadmill walking	Prior to Hospital Discharge and no more than 1 month after ICU discharge
6 minute walk test	Measure of cardio-respiratory function after treadmill walking	6 months after ICU discharge

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Neurocognitive Disorders; Infant, Newborn, Diseases; Cognition Disorders; Infant, Premature, Diseases; Thoracic Injuries; Cognitive Dysfunction; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Respiration Disorders; Ventilator-Induced Lung Injury
• Other Study ID Numbers: CHLA-18-00354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No