Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis

Objective: Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy. Design: Prospective observational study. Setting: Emergency Department and Intensive Care Unit. Participants: Septic patients with systolic blood pressure < 90 mmHg despite intravenous fluids or lactate >= 4.0 mM/L treated with early goal-directed therapy (EGDT). Measurements and results: We performed Sidestream Dark Field (SDF) videomicroscopy of the sublingual microcirculation < 3 h from EGDT initiation and again within a 3-6 h time window after initial. We imaged five sites and determined the mean microcirculatory flow index (MFI) (0 no flow to 3 normal) blinded to all clinical data. We calculated the Sequential Organ Failure Assessment (SOFA) score at 0 and 24 h, and defined improved SOFA a priori as a decrease >= 2 points. Of 33 subjects; 48% improved SOFA over 0-24 h. Age, APACHE II, and global hemodynamics did not differ significantly between organ failure groups. Among SOFA improvers, 88% increased MFI during EGDT, compared to 47% for non-improvers (P = 0.03). Median change in MFI was 0.23 for SOFA improvers versus -0.05 for non-improvers (P = 0.04). Conclusions: Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics. These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.