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Introduction: Severe hypoxemic respiratory failure is a leading cause of pediatric cardiac (CA) arrest. Evidence guiding optimal ventilation strategies to achieve favorable neurological outcome is limited. This pilot study evaluated the effects of two mechanical ventilation modes compared to manual bag-mask ventilation (BV) on gas exchange and short-term survival in a pediatric CA swine model. We hypothesized that mechanical ventilation would maintain open lungs recruitment and provide more effective gas exchange. Methods: Eight-week-old mechanically ventilated Juvenile Yorkshire swine (n=8) were subjected to 5 minutes (min) asphyxia followed by 1 min induced ventricular fibrillation. CPR was initiated per PALS guidelines. Animals were randomized into three groups: volume control (VC) (n=4), pressure control (PC) (n=2), or BV (n=2). Invasive systemic and pulmonary hemodynamics and EtCO2 were continuously monitored. Arterial blood gases were sampled at pre asphyxia, CPR initiation, and 5 min into CPR. Animals achieving sustained ROSC were survived for 72 hrs. Animals failing to achieve ROSC by 15 min were euthanized. Statistical analysis included one-way ANOVA and Kruskal-Wallis tests. Results: ROSC was achieved in 6/8 swine (VC: 3/4, PC: 2/2, MBMV: 1/2), and 4 survived to 72 hrs (VC: 1/4, PC: 2/2, MBMV: 1/2). Overall mean (SD) time to ROSC was 9.1 (5.2) min. Median arterial pH, pO2, pCO2, and lactate values did not differ significantly among groups at any point. Pre-arrest EtCO2 were 42.8 (11.2), 39.3 (5.1), and 50.4 (6.4) mmHg for VC, PC, and BV respectively (p < 0.001). EtCO2 at 1-min post-CPR initiation showed no significant differences (p = 0.31). However, EtCO2 at 5 minutes into CPR was significantly different across groups: 39.4 (12.1), 42.7 (11.1), and 56.7 (12.0) mmHg for VC, PC, and BV respectively (p < 0.001). Conclusions: This pilot swine model study presents preliminary data on the use of mechanical ventilation during pediatric CPR. While arterial gas exchange was comparable across ventilation modes, EtCO2 levels varied significantly. We will expand our cohort to validate these findings and explore EtCO2 thresholds and waveform patterns that correlates with open lungs recruitment and are associated with ROSC and favorable neurological outcomes.