Association of Arterial PaCO2 with the Survival of Mechanically Ventilated Patients with Acute Respiratory Failure: A Multicenter Retrospective Cohort Study

<b>Background/Objectives</b>: Acute respiratory failure (ARF) is associated with a high mortality. This study aimed to explore the association of arterial partial pressure of carbon dioxide (PaCO₂) in relation to survival outcomes in mechanically ventilated patients with ARF. <b>Methods</b>: This multicenter retrospective cohort study integrated the data from the eICU Collaborative Research Database (eICU-CRD; n = 10,946), the Medical Information Mart for Intensive Care IV (MIMIC-IV; n = 6683), and clinical records from two university-affiliated intensive care units in China (n = 410). The patients were categorized into low, normal, and high PaCO₂ groups using a restricted cubic spline model to explore the relationship between PaCO₂ and mortality. The 28-day survival distributions among the three groups were compared using Kaplan-Meier curves, with statistical significance assessed via the log-rank test. A multivariable Cox proportional hazards model was constructed to evaluate the independent prognostic value of PaCO₂ for multiple complications. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the low and high PaCO₂ groups relative to the normal PaCO₂ group. <b>Results</b>: A U-shaped relationship was observed between PaCO₂ and mortality, with both low PaCO₂ (<36.4 mmHg) and high PaCO₂ (>57.9 mmHg) associated with an increased mortality risk. Kaplan-Meier survival analysis demonstrated that patients in the intermediate PaCO₂ range (36.4-57.9 mmHg) exhibited the highest survival rate (65.2%), whereas those in the low and high PaCO₂ groups had significantly lower survival rates (60.0% and 63.2%) (log-rank test, <i>p</i> < 0.001). Adjusted survival analyses further revealed that complications such as sepsis and chronic kidney disease significantly influenced the mortality across PaCO₂ strata. Compared with the intermediate PaCO₂ group, the hazard of death increased by 25.5% in the low PaCO₂ group and by 18.9% in the high PaCO₂ group. <b>Conclusions</b>: This retrospective analysis indicates that arterial PaCO₂ levels within the optimal range are associated with improved survival in patients with acute respiratory failure (ARF) on mechanical ventilation, but prospective studies are needed to establish causality and consider potential confounding factors.