Effects of Different Ventilation Rates on Resuscitation in a Porcine Ventricular Fibrillation Cardiac Arrest Model

Objective: We tested the a priori hypothesis that a ventilation rate of 20 breaths per minute (bpm) is non-inferior to 10 bpm and 5 bpm with respect to resuscitation outcomes and physiology following advanced airway placement in a porcine ventricular fibrillation (VF) cardiac arrest model. Methods: Twenty-four pigs underwent 4 min of untreated VF and 4 min of chest compressions without ventilation. Animals were randomized to 5, 10, or 20 bpm (n = 8 per group) for 4 min of asynchronous CPR followed by defibrillation. The primary endpoint was achieving ROSC; secondary endpoints included 24-h survival, neurological scores (Cerebral Performance Category, CPC), hemodynamic parameters, and respiratory/acid-base physiological parameters. Results: For the primary endpoint, ROSC rates were comparable across groups: 6/8 (75%) in the 5 bpm group, 7/8 (87.5%) in the 10 bpm group, and 6/8 (75%) in the 20 bpm group ( P = 0.837). All animals that achieved ROSC survived for 24 hours with favorable neurological function (CPC 1-2). Notably, this high survival rate reflects the controlled experimental model (short no-flow time and healthy subjects) rather than direct human clinical outcomes. During CPR, intrathoracic pressure (ITP) and hemodynamics were comparable across groups (all P > 0.05). During the ventilation stage, the 20 bpm group showed significantly better CO₂ clearance, with lower PaCO₂ than the 5 bpm group (mean difference: ﹣12.88 mmHg, 38.50 ± 8.26 vs 51.38 ± 15.41 mmHg, P = 0.022) and higher arterial pH than the 5 bpm group (mean difference: 0.15, 7.29 ± 0.12 vs 7.14 ± 0.12, P = 0.001). At 1 h post-ROSC, the 20 bpm group exhibited significantly higher diastolic blood pressure (DBP, mean difference: 26.26 mmHg, 97.83 ± 15.09 vs 71.57 ± 14.86 mmHg, P = 0.002) and coronary perfusion pressure (CPP, mean difference: 27.96 mmHg, 90.67 ± 13.76 vs 62.71 ± 18.84 mmHg, P = 0.001), as well as higher arterial pH (mean difference: 0.10, 7.37 ± 0.04 vs 7.27 ± 0.04, P = 0.029) and smaller base deficit (BE, mean difference: 6.77 mEq/L, ﹣2.83 ± 2.32 vs ﹣9.60 ± 2.20 mEq/L, P = 0.001) compared with the 10 bpm group. Although peak airway pressure (P peak ) was higher in the 20 bpm group compared to the 5 bpm group (mean difference: 4.75 cmH 2 O, 32.63 ± 3.16 cmH 2 O vs. 27.88 ± 1.81 cmH 2 O, P = 0.010), mean airway pressure (P mean ) did not differ significantly among groups ( P = 0.473). Conclusion: Ventilation at 20 bpm did not compromise ROSC, hemodynamics, or ITP compared with lower rates in the porcine VF model. Furthermore, 20 bpm facilitated superior acid-base balance and post-resuscitation stability, providing a physiological basis for further investigation of moderate increases in the ventilation rate in specific controlled clinical settings to optimize metabolic clearance.