Associations of intraoperative end–tidal CO2 levels with postoperative outcome–secondary analysis of a worldwide observational study

Patients receiving intraoperative ventilation during general anesthesia often have low end–tidal CO 2 (etCO 2 ). We examined the association of intraoperative etCO 2 levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently–sized international, prospective study named ‘Local ASsessment of Ventilatory management during General Anesthesia for Surgery’ (LAS VEGAS). Patients at high risk of PPCs were categorized as ‘low etCO 2 ’ or ‘normal to high etCO 2 ’ patients, using a cut–off of 35 mmHg. The primary endpoint was a composite of previously defined PPCs; the individual PPCs served as secondary endpoints. The need for unplanned oxygen was defined as mild PPCs and severe PPCs included pneumonia, respiratory failure, acute respiratory distress syndrome, barotrauma, and new invasive ventilation. We performed propensity score matching and LOESS regression to evaluate the relationship between the lowest etCO 2 and PPCs. The analysis included 1843 (74 %) ‘low etCO 2 ’ patients and 648 (26 %) ‘normal to high etCO 2 ’ patients. There was no difference in the occurrence of PPCs between ‘low etCO 2 ’ and ‘normal to high etCO 2 ’ patients (20 % vs. 19 %; RR 1.00 [95 %–confidence interval 0.94 to 1.06]; P = 0.84). The proportion of severe PPCs among total occurring PPCs, were higher in ‘low etCO 2 ’ patients compared to ‘normal to high etCO 2 ’ patients (35 % vs. 18 %; RR 1.16 [1.08 to 1.25]; P < 0.001). Propensity score matching did not change these findings. LOESS plot showed an inverse relationship of intraoperative etCO 2 levels with the occurrence of PPCs. In this cohort of patients at high risk of PPCs, the overall occurrence of PPCs was not different between ‘low etCO 2 ’ patients and ‘normal to high etCO 2 ’ patients, but severe PPCs occurred more often in ‘low etCO 2 ’, with an inverse dose–dependent relationship between intraoperative etCO 2 levels and PPCs. This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anesthesiology and Intensive Care (ESAIC) and the Amsterdam University Medical Centers, location ‘AMC’. LAS VEGAS was registered at Clinicaltrials.gov ( NCT01601223 ), first posted on May 17, 2012. • This secondary analysis of the LAS VEGAS study, aimed to examine the association between etCO₂ levels and the occurrence of PPCs. • No significant difference was found in overall PPCs between ‘low etCO₂ (below 35 mmHg)’ and ‘normal to high etCO₂ (≥ 35 mmHg)’ patients (20 % vs. 19 %). • Severe PPCs were more common in the ‘low etCO₂’ group (35 % vs. 18 %). Propensity score matching did not alter the results, showing a robust association. • Potential mechanisms include hyperventilation causing ventilator-induced lung injury, ventilation-perfusion mismatching, or an underlying pulmonary pathology. • Future prospective studies should explore the causality between low etCO₂ and severe PPCs.