Objective:To investigate the value of the venous-to-arterial CO 2 gap (Δ CO 2 gap) before and after the fluid challenge (FC) in determining the fluid responsivenessin septic shock patients. Methods:A total of 104 septic shock patients admitted to the Medical Intensive Care Unit (MICU) of Peking Union Medical College Hospital were included in the retrospective study. All patients were monitored by Swan Ganz floating catheter during the FC. Hemodynamics and blood gas indices were collected before FC (T0) and immediately (T1), 10 min (T2), 30 min (T3) and 60 min (T4) after FC. Responders were defined as patients with a > 10% increase in cardiac output (CO) after FC. Spearman correlation analysis was used to evaluate the correlation between CO 2 gap and CO. The value of ΔCO2 gap were calculated by the area under the receiver operating characteristic (AUROC) curve in the whole population. Results:Among 104 patients, the effective rates of FC at T1, T2, T3 and T4 were 59% (61/104), 72% (75/104), 73% (76/104), and 77% (80/104), respectively. CO of patients in the reactive group was lower than that in the non-reactive group at T2 [6.0 (4.7, 7.5) vs. 7.2 (6.4, 8.5) L/min, P=0.019], and there was no significant difference in CO 2 gap between the two groups before FC. Spearman correlation analysis showed that CO 2 gap was negatively correlated with CO, and the correlations between CO 2 content gap and CO was -0.34, and -0.33 of CO 2 pressure gap and CO, respectively (both P <0.05). ROC curve analysis showed that the ΔCO 2 gap at T1 could weakly judge the reactivity at T2, T3 and T4, but could not judge the reactivity at T1. The AUROC at T2 was 0.669 of ΔCO 2 content gap and 0.684 of ΔCO 2 pressure gap (both P <0.05). Conclusions:The evaluate time judging the effect of FC should be appropriately extended. The change value of CO 2 gap before and immediately after volume expansion in septic shock patients can judge the fluid responsiveness within 10 min after FC.