Association between the first 24 hours PaCO(2) and all-cause mortality of patients suffering from sepsis-associated encephalopathy after ICU admission: A retrospective study

OBJECTIVE: The relationship between the levels of the first 24-h PaCO(2) and the prognosis of sepsis-associated encephalopathy (SAE) remains unclear, and the first 24-h optimal target for PaCO(2) is currently inconclusive. This study was performed to investigate the correlation between PaCO(2) and all-cause mortality for SAE patients, establish a reference range of the initial 24-hour PaCO(2) for clinicians in critical care, and explain the possible pathophysiological mechanisms of abnormal PaCO(2) levels as a higher mortality risk factor for SAE. METHODS: The baseline information and clinical data of patients were extracted from the fourth edition Medical Information Mart for Intensive Care database (MIMIC-IV 2.0). Multivariate logistic regressions were performed to assess the relationship between PaCO(2) and all-cause mortality of SAE. Additionally, restricted cubic splines, Kaplan-Meier Survival analyses, propensity score matching (PSM) analyses, and subgroup analyses were conducted. RESULTS: A total of 5471 patients were included in our cohort. In the original and matched cohort, multivariate logistic regression analysis showed that normocapnia and mild hypercapnia may be associated with a more favorable prognosis of SAE patients, and survival analysis supported the findings. In addition, a U-shaped association emerged when examining the initial 24-hour PaCO(2) levels in relation to 30-day, 60-day, and 90-day mortality using restricted cubic splines, with an average cut-off value of 36.3mmHg (P for nonlinearity<0.05). Below the cut-off value, higher PaCO(2) was associated with lower all-cause mortality, while above the cut-off value, higher PaCO(2) was associated with higher all-cause mortality. Subsequent subgroup analyses revealed similar results for the subcohort of GCS≤8 compared to the original cohort. Additionally, when examining the subcohort of GCS>8, a L-shaped relationship between PaCO2 and the three clinical endpoints emerged, in contrast to the previously observed U-shaped pattern. The findings from the subcohort of GCS>8 suggested that patients experiencing hypocapnia had a more unfavorable prognosis, which aligns with the results obtained from corresponding multivariate logistic regression analyses. CONCLUSION: The retrospective study revealed the association between the first 24-h PaCO(2) and all-cause mortality risk (30-day, 60-day, and 90-day) for patients with SAE in ICU. The range (35mmHg-50mmHg) of PaCO(2) may be the optimal target for patients with SAE in clinical practice.