Combined assessment of end-tidal CO₂ and pulse pressure variability during passive leg raising for non-invasive prediction of preload responsiveness in septic shock.

backgroundTraditional assessment of preload responsiveness during passive leg raising (PLR) relies on invasive cardiac output monitoring. We hypothesized that the physiological coupling between cardiac output, end-tidal carbon dioxide (EtCO2), and pulse pressure variability (PPV) could provide a reliable non-invasive alternative for predicting preload responsiveness.

methodsWe conducted a prospective observational study in 71 mechanically ventilated septic shock patients. Pulse index Contour Cardiac Output (PiCCO), arterial pressure, and EtCO₂ were monitored during standardized PLR maneuvers. Cardiac index (CI), arterial pressure, stroke volume variability (SVV), PPV, and EtCO₂ were measured before and after PLR. Patients with a PLR-induced CI increase ≥ 15% were classified as preload responders. Linear regression analysis and Pearson correlation coefficients were calculated to assess the relationships between PLR-induced changes in CI and other parameters. We evaluated the predictive performance of individual parameters and their combination using receiver operating characteristic (ROC) analysis, with the DeLong test used to compare the performance of the combined model to individual predictors.

resultsAmong 71 patients, 37 (52.11%) were preload responders. The absolute change in EtCO₂ (∆EtCO₂), relative change in EtCO₂ (∆EtCO₂%), and PPV were all significantly higher in responders compared to non-responders. A positive correlation was observed between PLR-induced changes in CI and both EtCO₂ (r = 0.538, p < 0.001) and PPV (r = 0.584, p < 0.001). The area under the ROC curve (AUC) for ∆EtCO₂% was 0.88 (95% CI: 0.79–0.95) with an optimal cutoff value of > 5.88% (sensitivity 91.89%, specificity 76.47%). The AUC for PPV was 0.85 (95% CI: 0.75–0.93) with a cutoff value of > 10% (sensitivity 81.1%, specificity 79.41%). Importantly, a novel logistic regression-derived combined PPV-∆EtCO₂% score demonstrated improved predictive performance (AUC 0.94, 95% CI: 0.86–0.98) with a cutoff value of > 0.67 (sensitivity 83.8%, specificity 94.1%).

conclusionThe combination of PPV and ∆EtCO₂% during PLR provides a promising non-invasive method for predicting preload responsiveness in mechanically ventilated septic shock patients, outperforming either parameter alone. This approach offers a promising alternative to invasive cardiac output monitoring in guiding fluid therapy decisions.

trial registrationThe study was registered on December 26th, 2019, at the Chinese Clinical Trial Registry (ChiCTR1900028210). URL of trial registry record： https://www.chictr.org.cn/bin/project/edit?pid=46568 .