Association of Intraoperative End-Tidal CO₂, Ventilation, and Hypotension With Postoperative Mortality in Noncardiac Surgery: A Retrospective Cohort Study

BACKGROUND: Low intraoperative end-tidal carbon dioxide (ETco₂) has been associated with increased postoperative mortality in retrospective studies. However, whether this association is independent of intraoperative hypotension, a strong predictor of mortality, and minute ventilation, a primary determinant of ETco₂, remains uncertain. We hypothesized that low intraoperative ETco₂ is independently associated with postoperative mortality after adjustment for both intraoperative hypotension and minute ventilation. METHODS: We conducted a retrospective cohort study of adults undergoing noncardiac surgery under general anesthesia with mechanical ventilation between 2010 and 2020 at a tertiary care center. Primary exposures were intraoperative mean ETco₂, minute ventilation, and hypotension (severity and duration). The primary outcome was in-hospital mortality. Multivariable logistic regression estimated the independent association between ETco₂ and mortality after adjustment for predefined confounders. An interaction between ETco₂ and hypotension was tested. RESULTS: Among 185,455 patients (in-hospital mortality 0.85%), lower intraoperative ETco₂ was nonlinearly associated with increased mortality (adjusted odds ratio per 5-mmHg decrease from the median, 1.63; 95% CI, 1.36-1.86), independent of minute ventilation and hypotension. No significant interaction was observed between ETco₂ and hypotension (p=0.19). Findings were robust across sensitivity analyses. CONCLUSIONS: In this large retrospective cohort, low intraoperative ETco₂ was independently associated with increased in-hospital mortality, irrespective of intraoperative hypotension and minute ventilation. These results suggest that ETco₂ provides prognostic information beyond arterial pressure alone and may be a valuable marker for postoperative risk stratification.