Background/Objectives: 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. Methods: 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. Results: A U-shaped relationship was observed between PaCO₂ and mortality, with both low 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, p < 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. Conclusions: 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.

Background: Severe pneumonia is a kind of disease that develops from lung inflammation, and new drugs are still required to treat the same. Erythropoietin (EPO) is widely used to treat anemia in patients. However, there are fewer studies on the role of EPO in neutrophil extra cellular trappings (NETs) and pneumonia, and the mechanism is unclear. Objective: To investigate the possible effects of EPO on the formation of NETs and progression of pneumonia. Methods: Mice pneumonia model was induced by tracheal lipopolysaccharide (LPS) administration. Hematoxylin and eosin (H&E) staining and automatic blood cell analysis were performed in this model to confirm the effects of EPO on lung injury. Flow cytometry, enzyme-linked immunosorbent serological assay, and immunostaining assay were conducted to detect the effects of EPO on the inflammation as well as formation of NETs in mice. Immunoblot was further conducted to confirm the mechanism. Results: EPO alleviated LPS-induced lung injury. EPO reduced the release of inflammatory factors induced by LPS. In addition, EPO inhibited the formation of NETs. Mechanically, EPO inhibited tumor necrosis factor (TNF) receptor associated factor 2 (TRAF2)/nuclear factor kappa-B (NF-kappa B) activity in mouse models, and therefore suppressed the progression of pneumonia. Conclusion: EPO inhibited formation of NETs to ameliorate lung injury in a pneumonia model, and could serve as a drug of pneumonia. (c) 2023 Codon Publications. Published by Codon Publications.