Project Abstract Pediatric in-hospital cardiac arrest (IHCA) occurs in >15,000 children annually in the United States, most of whom do not survive to hospital discharge. As less than 5% of pediatric cardiopulmonary resuscitation (CPR) guideline recommendations are supported by high-quality evidence, there are significant knowledge gaps regarding optimal resuscitation techniques. Since pediatric IHCA represents a heterogenous process that results from the progression of many disease states, CPR physiology and the response to therapies also vary among patients. Therefore, our group has aimed to advance CPR beyond “one-size-fits-all” care and toward more patient-specific methods with an overarching objective of developing personalized, physiology-directed CPR strategies that account for both known patient characteristics and real-time physiology. A central component of in-hospital CPR is the administration of epinephrine, which is universally recommended during cardiac arrest to augment systemic vascular resistance, thereby increasing diastolic blood pressure (DBP) and coronary perfusion pressure to enhance the likelihood of return of spontaneous circulation (ROSC). Recent laboratory data and our 2023 clinical study identified substantial variability in the DBP response to epinephrine and found that a more robust increase in DBP after administration of the first dose of epinephrine is associated with higher rates of ROSC. As data are conflicting regarding ideal dosing strategies during pediatric IHCA, we postulate that epinephrine is beneficial during CPR in some clinical scenarios and potentially deleterious in others. Furthering our understanding of this variability in physiologic response will facilitate the development of methods of personalized, physiology-directed CPR to improve IHCA outcomes. Due to limitations in currently available datasets, a prospectively designed study is necessary to address this topic. Thus, we will leverage the existing infrastructure in 20 sites of the Pediatric Resuscitation Quality Collaborative (pediRES-Q), a network specifically designed to study IHCA, to prospectively collect extensive granular data including epinephrine dose timing and physiologic waveforms from bedside monitoring systems. In Aim 1, we will examine the physiologic response to epinephrine in greater detail and will build on exciting preliminary data to expand the applicability of this work to patients without invasive monitoring, investigating the pulse oximetry waveform as a non-invasive marker of CPR physiology and of epinephrine response in particular. In Aim 2, we will determine how the physiologic response to epinephrine impacts the relationship between epinephrine dosing strategies and outcomes. Finally, in Aim 3, through a well-established collaboration with machine learning experts, we will develop models to predict the response to epinephrine and subsequent CPR outcomes. The successful completion of these aims will expand our underst...