Mechanical Ventilation Management, New or Progressive MODS, and Post-ICU Morbidity in Pediatric ARDS

PROJECT SUMMARY
Rationale: Most children with pediatric acute respiratory distress syndrome (PARDS), a severe form of lung
injury, require mechanical ventilation. In adults with ARDS, injurious mechanical ventilation practices increase
mortality, primarily attributed to the development of new or progressive multiple organ dysfunction syndrome
(NPMODS). Pediatric studies have not found similar consistent associations between mechanical ventilation
practices and mortality. NPMODS is a feasible alternative outcome to mortality, which is low in PARDS, that
has strong biological plausibility for association with injurious mechanical ventilation and may improve
identification of mechanical ventilation associated harm in children. Before adoption of the intermediary
outcome NPMODS, as most children survive PARDS, it is crucial to characterize the association between
NPMODS and post-ICU morbidity. Research: Through this career development award, Dr. Anoopindar Bhalla,
a pediatric intensivist, seeks to understand the associations between ventilator management, NPMODS, and
post-ICU morbidity in children with PARDS. The research will leverage the infrastructure and resources of a
Phase II randomized controlled trial on a lung-protective ventilation strategy enrolling 276 children with PARDS
and led by Dr. Bhalla’s co-mentor (PI: Khemani, NHLBI R01 HL134666, REDvent). The central hypothesis is
that injurious mechanical ventilation leads to NPMODS and, in turn, NPMODS is associated with post-ICU
morbidity in children with PARDS. These hypotheses will be tested through the following Specific Aims: 1)
Determine whether a lung-protective ventilation strategy prevents NPMODS in PARDS; 2) Identify physiologic
mechanisms of injurious ventilation which are associated with NPMODS in PARDS (including assessment of
transpulmonary pressures); 3) Characterize the association between NPMODS and post-ICU morbidity
(health-related quality of life, functional status, and pulmonary status) in PARDS. Career Development:
Through completion of the proposed research, additional career development training activities, and
multidisciplinary mentorship, Dr. Bhalla will learn key skills in 1) the principles of pediatric clinical trials; 2)
advanced study design and biostatistics; 3) the assessment of post-ICU outcomes in children. Acquiring these
skills is critical for Dr. Bhalla’s long-term career goal to lead well-designed clinical trials in critically ill children.
The assembled mentorship team with world-class experts in respiratory physiology, biostatistics, and long-term
outcomes as well as clinical trials, will support her in these endeavors. Impact: This research will provide
crucial information on the associations between injurious mechanical ventilation, NPMODS, and post-ICU
morbidity to guide future PARDS clinical trials. Furthermore, through the career development training and
generated data, Dr. Bhalla will be well-positioned to successfully compete for R01 funding and become an
independent investigator leading pediatric mechanical ventilation clinical trials.

Grant Number: 5K23HL153756-05
NIH Institute/Center: NIH
Principal Investigator: Anoopindar Bhalla