Association of Intraoperative End-tidal Carbon Dioxide, Ventilation, and Hypotension with Postoperative Mortality in Noncardiac Surgery: A Retrospective Cohort Study

BACKGROUND: Low intraoperative end-tidal carbon dioxide (ET co2 ) 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 ET co2 , remains uncertain. The authors hypothesized that low intraoperative ET co2 is independently associated with postoperative mortality after adjustment for both intraoperative hypotension and minute ventilation. METHODS: The authors conducted a retrospective cohort study of adults undergoing noncardiac surgery during general anesthesia with mechanical ventilation between 2010 and 2020 at a tertiary care center. Primary exposures were intraoperative mean ET co2 , minute ventilation, and hypotension (severity and duration). The primary outcome was in-hospital mortality. Multivariable logistic regression estimated the independent association between ET co2 and mortality after adjustment for predefined confounders. An interaction between ET co2 and hypotension was tested. RESULTS: Among 185,455 patients (in-hospital mortality, 0.85%), lower intraoperative ET co2 was nonlinearly associated with increased mortality (adjusted odds ratio per 5-mmHg decrease from the median, 1.63; 95% CI, 1.36 to 1.86) independent of minute ventilation and hypotension. No significant interaction was observed between ET co2 and hypotension ( P = 0.19). Findings were robust across sensitivity analyses. CONCLUSIONS: In this large retrospective cohort, low intraoperative ET co2 was independently associated with increased in-hospital mortality, irrespective of intraoperative hypotension and minute ventilation. These results suggest that ET co2 provides prognostic information beyond arterial pressure alone and may be a valuable marker for postoperative risk stratification.