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Whether sublingual microcirculation reflects systemic preload remains unknownThirty-two preload dependent episodes were identified in 17 patientsEpisodes were accompanied by reduced arterial pressure and stroke volume, along with reduced sublingual microcirculationFluid administration improved microcirculation and stroke volume, but not blood pressureSublingual microcirculation might be an indicator of vascular volumeDynamic indices, such as pulse pressure variation, detect preload dependence and are used to predict fluid responsiveness. The behavior of sublingual microcirculation during preload dependence is unknown during major abdominal surgery. The purpose of this study was to test the hypothesis that during abdominal surgery, microvascular perfusion is impaired during preload dependence and recovers after fluid administration.This prospective observational study included patients having major abdominal surgery. Pulse pressure variation was used to identify preload dependence. A fluid challenge was performed when pulse pressure variation was greater than 13%. Macrocirculation variables (mean arterial pressure, heart rate, stroke volume index, and pulse pressure variation) and sublingual microcirculation variables (perfused vessel density, microvascular flow index, proportion of perfused vessels, and flow heterogeneity index) were recorded every 10 min.In 17 patients, who contributed 32 preload dependence episodes, the occurrence of preload dependence during major abdominal surgery was associated with a decrease in mean arterial pressure (72 ± 9 vs. 83 ± 15 mmHg [mean ± SD]; P = 0.016) and stroke volume index (36 ± 8 vs. 43 ± 8 ml/m2; P < 0.001) with a concomitant decrease in microvascular flow index (median [interquartile range], 2.33 [1.81, 2.75] vs. 2.84 [2.56, 2.88]; P = 0.009) and perfused vessel density (14.9 [12.0, 16.4] vs. 16.1 mm/mm2 [14.7, 21.4], P = 0.009), while heterogeneity index was increased from 0.2 (0.2, 0.4) to 0.5 (0.4, 0.7; P = 0.001). After fluid challenge, all microvascular parameters and the stroke volume index improved, while mean arterial pressure and heart rate remained unchanged.Preload dependence was associated with reduced sublingual microcirculation during major abdominal surgery. Fluid administration successfully restored microvascular perfusion.