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)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Ventilation In-homogeneity using lung clearance index with nitrogen washout
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children > 1 month (at least 44 weeks Corrected Gestational Age) and ≤ 18 years of age AND
- •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
- •Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution) AND
- •Enrolled in the REDvent Study
- •Exclusion Criteria (1-5 are REDvent exclusion):
- •Contraindications to use of an esophageal catheter (i.e. severe mucosal bleeding, nasal encephalocele, transphenoidal surgery) OR
- •Contraindications to use of RIP bands (i.e. omphalocele, chest immobilizer or cast) OR
- •Conditions precluding diaphragm ultrasound measurement (i.e. abdominal wall defects, pregnancy) OR
- •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
- •Primary Attending physician refuses (will be cleared with primary attending before approaching the patient) OR
- •Death in the ICU OR
- •New DNR orders during acute illness in ICU OR
- •Primary Language not English or Spanish OR
- •Children in foster care or a ward of the state.
排除标准
- 未提供
结局指标
主要结局
Ventilation In-homogeneity using lung clearance index with nitrogen washout
时间窗: 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
时间窗: 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
时间窗: 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
Functional Status as measured by the pediatric functional status scale
时间窗: 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.
次要结局
- Diaphragm Thickness on exhalation(6 months after ICU discharge)
- Diaphragm Thickness on inspiration(6 months after ICU discharge)
- Diaphragm Thickening fraction (measure of contractile activity)(6 months after ICU discharge)
- Forced Expiratory Volume in 1 second (FEV1)(6 months after ICU discharge)
- Total Lung Capacity- TLC measured during spirometry(6 months after ICU discharge)
- Ventilation In-homogeneity using lung clearance index with nitrogen washout(Prior to Hospital Discharge and no more than 1 month after ICU discharge)
- Forced Vital Capacity (FVC)(6 months after ICU discharge)
- Forced expiratory flow at 25-75% (FEF 25-75)(6 months post ICU discharge)
- Forced vital capacity- measured during spirometry(6 months after ICU discharge)
- VT - tidal volume from spirometry during tidal breathing(6 months after ICU discharge)
- Functional Residual Capacity (Lung volume at end-expiration).(6 months after ICU discharge)
- Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)(6 Months after ICU Discharge)
- Respiratory Muscle Strength Maximum inspiratory pressure (MIP)(6 months after ICU discharge)
- Respiratory Muscle Strength Maximum expiratory pressure (MEP)(6 months after ICU discharge)
- Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests(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(12 months after ICU discharge)
- Health Related Quality of Life as measured by PedsQL generic core scale(12 months after ICU discharge)
- Functional Status as measured by the pediatric functional status scale(12 months after ICU discharge)
- Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.(12 months after ICU discharge)
研究者
Robinder Khemani
Principal Investigator
Children's Hospital Los Angeles