It is an incredible privilege to take care of children at their most critical juncture. As pediatric critical care practitioners we must be able to provide timely and evidenced based care for these children, and support families with the knowledge that one's chosen treatment is based upon evidence and experience. However, as a specialty we can only create evidence based standards through rigorous clinical research. Committed to a career in intensive care medicine, it is my duty to provide my patients with the highest, evidence based care, and help our specialty grow by conducting studies to gather evidence for the best practices. To do this, I must learn the necessary skills to foster my development into a thorough and rigorous clinical researcher. While I have undergraduate and graduate level experience in statistics and clinical investigation, with the """"""""rarity"""""""" of pediatric disease, multi-ite studies are needed to draw meaningful conclusions about critically ill children. This is particularly important for mechanically ventilated children-the most common yet most variable intervention in pediatric critical care. Seeking to conduct multi-center mechanical ventilation trials, I must equip myself with knowledge and skills about the design and implementation of such trials, and also gain expertise on evaluating potential objective outcomes for trials on ventilated children. The specific research project detailed in this application is the first step fr me to develop these skills. Using an animal model to validate a minimally invasive measure of upper airway obstruction and subsequently applying this measure to mechanically ventilated children at a single site, I hope to master skills related to the evaluation of pulmonary function, particularly upper airway obstruction. Upper airway obstruction is a complicating factor in ventilation trials because it prolongs length of mechanical ventilation. It is a bigger problem in children (compared to adults) as it is estimated on clinical grounds that 1/3 of all pediatric extubation failures result from upper airway obstruction. However, risk factors for and therapies targeting post-extubation airway obstruction are inconsistent, likely because clinical acumen to measure upper airway obstruction is lacking. Therefore, this project describes validating a minimally invasive technique to measure upper airway obstruction, initially in Rhesus Monkeys. It will then be applied in children to evaluate the accuracy of clinical stridor scales, and determine whether commonly applied therapeutics or supportive care impact resolution of airway obstruction, by demonstrating improvement in the objective, non-invasive measures. While this study will equip me with important skills to conduct clinical trials, I will get specifi experience with the nuances of multi-institutional trials through a series of meetings and activities with the NICHD Collaborative Pediatric Critical Care Research Network (CPCCRN) and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. These networks have undertaken many multi-center trials in critically ill children, and will help me learn the necessary skills to take a multi-center trial from an idea to reality.

Public Health Relevance

This career development award concentrates on acquiring the knowledge, skills, and preliminary data to conduct a large scale multi-center trial on upper airway obstruction after mechanical ventilation in children. The activities during the award period will involve specific training to validate novel minimally invasive pulmonary function tests for upper airway obstruction in children, provide preliminary data regarding the reliability of outcome measures for studies on upper airway obstruction, and afford the opportunity for specific training in the nuances of conducting multi-center pediatric mechanical ventilation trials.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-X (O1))
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Maholmes, Valerie
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Children's Hospital of Los Angeles
Los Angeles
United States
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Yehya, Nadir; Thomas, Neal J; Khemani, Robinder G (2018) Risk Stratification Using Oxygenation in the First 24 Hours of Pediatric Acute Respiratory Distress Syndrome. Crit Care Med 46:619-624
Khemani, Robinder G; Smith, Lincoln (2017) The Conflicting Paradigm of Ventilator-Associated Conditions. Pediatr Crit Care Med 18:1078-1079
Kamerkar, Asavari; Hotz, Justin; Morzov, Rica et al. (2017) Comparison of Effort of Breathing for Infants on Nasal Modes of Respiratory Support. J Pediatr 185:26-32.e3
Khemani, Robinder G; Newth, Christopher J L (2017) CPAP alone best estimates post-extubation effort during spontaneous breathing trials in children. Intensive Care Med 43:150-151
Khemani, Robinder G; Sekayan, Tro; Hotz, Justin et al. (2017) Risk Factors for Pediatric Extubation Failure: The Importance of Respiratory Muscle Strength. Crit Care Med 45:e798-e805
Khemani, Robinder G; Ross, Patrick A; Typpo, Katri (2017) The authors reply. Crit Care Med 45:e1304-e1305
Khemani, Robinder G; Hotz, Justin; Morzov, Rica et al. (2016) Evaluating Risk Factors for Pediatric Post-extubation Upper Airway Obstruction Using a Physiology-based Tool. Am J Respir Crit Care Med 193:198-209
Markovitz, Barry P; Kukuyeva, Irina; Soto-Campos, Gerardo et al. (2016) PICU Volume and Outcome: A Severity-Adjusted Analysis. Pediatr Crit Care Med 17:483-9
Khemani, Robinder G; Flink, Rutger; Hotz, Justin et al. (2015) Respiratory inductance plethysmography calibration for pediatric upper airway obstruction: an animal model. Pediatr Res 77:75-83
Khemani, Robinder G; Smith, Lincoln (2015) Are we ready to accept the Berlin definition of acute respiratory distress syndrome for use in children? Crit Care Med 43:1132-4

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