Project Summary Mechanically ventilated children often have patient-ventilator asynchrony (PVA) although this is incompletely characterized in the literature and infrequently recognized at the bedside. When a ventilated patient has spontaneous effort, the ventilator attempts to synchronize with the patient, but PVA represents a mismatch between what the patient wants and what the ventilator delivers. PVA is common in ventilated adults and is associated with longer duration of ventilation, increased risk of infection, lung injury, diaphragm dysfunction, and adverse neurocognitive effects. While there are many types of PVA, they are not equally harmful or prevalent. Therapeutic strategies should focus on the most harmful forms of PVA. Although we still don’t know which PVA subtypes are truly most harmful, Double Cycled (DC) breaths (where a second breath is delivered before the first breath is complete) have the strongest biological plausibility for harm, because DC induces lung stress, strain, ventilator induced lung injury and eccentric contraction of the diaphragm. PVA is understudied in children, even though it may be more common and goes largely unrecognized even by highly trained clinicians. Moreover, existing pediatric studies have failed to identify a clear relationship between PVA and worse clinical outcomes, although these studies have not focused on the highest risk patients (such as those with Acute Respiratory Distress Syndrome (ARDS)), have used different definitions for PVA and its subtypes, and have been inadequately powered to evaluate the relationship between PVA subtypes and outcome. This proposal will set the stage for therapeutic strategies to manage PVA in children and will fill crucial knowledge and implementation gaps including: (1) harmonizing how PVA is measured and defined, (2) identifying the most harmful PVA subtypes and the patients at risk, and (3) using innovative and accurate bedside tools to improve the recognition of PVA. We will leverage the expertise and preliminary data from three premier pediatric research groups who have the expertise to use precise methods to capture the patient’s neural respiratory effort, which is crucial to correctly identify PVA subtypes. This proposal will include prospective, multi-center collection of ventilator waveforms from 200 ventilated children using precise techniques to capture neural respiratory effort, in addition to detailed secondary analysis of existing waveforms and clinical data from over 350 children. We will use causal inference and mediation approaches to evaluate the relationship between PVA subtypes and clinical and mechanistic outcomes by leveraging data from a randomized controlled trial (REDVent, R01HL124666) where PVA rates and subtypes likely differ between intervention and control groups. This trial is prescribing a mechanical ventilation strategy promoting more spontaneous breathing to achieve lung and diaphragm protective ventilation, compared to usual care.

Project Narrative This project will focus on Patient-Ventilator Asynchrony (PVA) in children through a prospective observational study in 3 pediatric ICUs, in addition to detailed analysis of existing data and data being gathered as part of an ongoing clinical trial which is testing a novel ventilator strategy. We will characterize the frequency and risk factors for common PVA subtypes in children, identify if PVA is independently associated with poor clinical outcomes and characterize the physiologic pathways which may be involved, and develop automated tools to improve the clinical recognition of PVA in children.