Respiratory Distress Syndrome, Adult, Ventilator-Induced Lung Injury, Neurocognitive Dysfunction, Quality of Life, Respiration Disorders
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTVentilation Inhomogeneity
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.
DIAGNOSTIC_TESTDiaphragm Ultrasound
Diaphragm thickness and contractile activity measured during tidal breathing.
DIAGNOSTIC_TESTRespiratory Inductance Plethysmography
Measure of thoraco-abdominal asynchrony during tidal breathing
DIAGNOSTIC_TESTSpirometry
Measurement of Forced Expiratory Volume (FEV1), Forced Vital Capacity and other lung volumes using standard pulmonary function techniques
DIAGNOSTIC_TESTFunctional Residual Capacity
Measurement using body box plethysmography of functional residual capacity and other lung volumes using standard pulmonary function techniques
DIAGNOSTIC_TESTMIP/MEP
Measurement of maximal inspiratory and expiratory pressures during airway occlusion
DIAGNOSTIC_TEST6 minute walk test
Measurement of cardio-respiratory function and capabilities during treadmill walking for 6 minutes.
DIAGNOSTIC_TESTNeurocognitive Testing
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).
DIAGNOSTIC_TESTEmotional Health Assessment
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.
DIAGNOSTIC_TESTHealth Related Quality of Life
Standardized instruments to assess (in person, over the phone, or via mail) health related quality of life in children. Parent and child questionnaires.
DIAGNOSTIC_TESTFunctional Status
Survey of overall functional status, administrated by asking a series of questions to patient and families.
DIAGNOSTIC_TESTRespiratory Status Questionnaire
Survey of respiratory health, administrated by asking a series of questions to patient and families.
Sponsors
Children's Hospital Los Angeles
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional Status as measured by the pediatric functional status scale | 3 months after ICU discharge | 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. |
| Ventilation In-homogeneity using lung clearance index with nitrogen washout | 6 months after ICU discharge | 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. |
| Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests | 3 months after ICU discharge | 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 |
| Health Related Quality of Life as measured by PedsQL generic core scale | 3 months after ICU discharge | PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diaphragm Thickness on inspiration | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Diaphragm ultrasound measurement of thickness at end inspiration measured in zone of apposition of right hemi-diaphragm |
| Diaphragm Thickening fraction (measure of contractile activity) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| Ventilation In-homogeneity using lung clearance index with nitrogen washout | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| Forced Expiratory Volume in 1 second (FEV1) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Spirometry based measures of pulmonary function of forced expiratory volume, normalized based on age, height, and gender and reported as percent predicted. |
| Forced Vital Capacity (FVC) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Spirometry based measures of pulmonary function of forced vital capacity, normalized based on age, height, and gender and reported as percent predicted. |
| Forced expiratory flow at 25-75% (FEF 25-75) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| VT - tidal volume from spirometry during tidal breathing | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Lung volume measurements obtained during tidal breathing, normalized in ml/kg ideal body weight. |
| Total Lung Capacity- TLC measured during spirometry | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| Respiratory Muscle Strength Maximum inspiratory pressure (MIP) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Maximal inspiratory pressure measurements during airway occlusion in cm H20 |
| Respiratory Muscle Strength Maximum expiratory pressure (MEP) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Maximal expiratory pressure measurements during airway occlusion in cm H20 |
| Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests | 12 months after ICU discharge | 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. |
| Health Related Quality of Life as measured by PedsQL generic core scale | ICU discharge | PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life |
| Functional Status as measured by the pediatric functional status scale | ICU discharge | 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. |
| Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. | ICU discharge | Series of questions to detail respiratory based morbidity |
| Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress | 3 months after ICU discharge | 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. |
| Forced vital capacity- measured during spirometry | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Lung volume measurements obtained during pulmonary function tests with spirometry to calculate forced vital capacity, normalized by age, height and gender. |
| Functional Residual Capacity (Lung volume at end-expiration). | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics) | Prior to Hospital Discharge and no more than 1 month after ICU discharge | 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. |
| Diaphragm Thickness on exhalation | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Diaphragm ultrasound measurement of thickness at end exhalation measured in zone of apposition of right hemi-diaphragm |
Other
| Measure | Time frame | Description |
|---|---|---|
| 6 minute walk test | Prior to Hospital Discharge and no more than 1 month after ICU discharge | Measure of cardio-respiratory function after treadmill walking |
Countries
United States
Outcome results
None listed