OBJECTIVES:In septic patients with acute circulatory failure, reliable predictors of fluid responsiveness are needed at the bedside. We hypothesized that the respiratory change in pre-ejection period (ΔPEP) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. DESIGN:Prospective clinical investigation. SETTING:A ten-bed hospital intensive care unit. PATIENTS:Patients admitted after septic shock equipped with an arterial catheter. INTERVENTIONS:Pre-ejection period (PEP)—defined as the time interval between the beginning of the R wave on the electrocardiogram and the upstroke of the radial arterial pressure curve (PEPKT) or the pulse plethysmographic waveforms (PEPPLET)—and cardiac index (transthoracic echocardiography-Doppler) were determined before and after volume infusion of colloid (8 mL·kg). ΔPEP (%) was defined as the difference between expiratory and inspiratory PEP divided by the mean of expiratory and inspiratory values. Respiratory changes in pulse pressure (ΔPP) was also measured. MEASUREMENTS AND MAIN RESULTS:Twenty-two volume challenges were done in 20 deeply sedated patients. ΔPEPKT, ΔPEPPLET, and ΔPP (measured in all patients) before volume expansion were correlated with cardiac index change after fluid challenge (r = .73, r = .67, and r = .70, respectively, p < .0001). Patients with a cardiac index increase induced by volume expansion ≥15% and <15% were classified as responders and nonresponders, respectively. Receiver operating characteristic curves showed that the threshold ΔPP value of 17% allowed discrimination between responder/nonresponder patients with a sensitivity of 85% and a specificity of 100%. For both ΔPEPKT and ΔPEPPLET, the best threshold value was 4% with a sensitivity-specificity of 92%–89% and 100%–67%, respectively. CONCLUSIONS:The present study found ΔPEPKT and ΔPEPPLET to be as accurate as ΔPP in the prediction of fluid responsiveness in mechanically ventilated septic patients.