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 Type
OBSERVATIONAL
Enrollment
176
Ventilation inhomogeneity will be measured using the Lung Clearance Index (LCI), derived from multiple breath Nitrogen washout during tidal breathing, measured by a mouthpiece or mask covering nose and mouth.
Diaphragm thickness and contractile activity measured during tidal breathing.
Measure of thoraco-abdominal asynchrony during tidal breathing
Measurement of Forced Expiratory Volume (FEV1), Forced Vital Capacity and other lung volumes using standard pulmonary function techniques
Measurement using body box plethysmography of functional residual capacity and other lung volumes using standard pulmonary function techniques
Measurement of maximal inspiratory and expiratory pressures during airway occlusion
Measurement of cardio-respiratory function and capabilities during treadmill walking for 6 minutes.
Detailed in person neuro-cognitive testing using standardized inventories using either the Battelle Developmental Inventory, second edition (Battelle-2) (age birth to 5 years 11 months) and the Wechsler Intelligence Scale for Children, fifth edition (WISC-5, for age 6 years to 19 years).
In person and written assessments of children and parents using the Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years and the UCLA PTSD Reaction Index (UCLA RI) for children ≥ 8 years.
Standardized instruments to assess (in person, over the phone, or via mail) health related quality of life in children. Parent and child questionnaires.
Survey of overall functional status, administrated by asking a series of questions to patient and families.
Survey of respiratory health, administrated by asking a series of questions to patient and families.
Children's Hospital Los Angeles
Los Angeles, California, United States
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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 3 months 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 6 months after ICU discharge
Respiratory Muscle Strength Maximum inspiratory pressure (MIP)
Maximal inspiratory pressure measurements during airway occlusion in cm H20
Time frame: 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
Time frame: 6 months after ICU discharge
Respiratory Muscle Strength Maximum expiratory pressure (MEP)
Maximal expiratory pressure measurements during airway occlusion in cm H20
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: ICU discharge
Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
Series of questions to detail respiratory based morbidity
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 12 months after ICU discharge
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