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

Abstract

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 >or=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 >or=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.

Figure 1

Timeline of study activities. Time zero was the time of early goal-directed therapy (EGDT) initiation, defined as the time of insertion of a central venous catheter for invasive monitoring for protocol-directed resuscitation. Sequential organ failure assessment (SOFA) scores were calculated at 0 and 24 hours. We performed initial SDF videomicroscopy as soon as possible after EGDT initiation, within 3 hours of catheter insertion in all cases (Visit 1), and we repeated SDF (Visit 2) as soon as possible within a 3–6 hour window after initial the SDF study.

Figure 2

Parallel univariate plots of the change in microcirculatory flow index (ΔMFI) between early time points (Visit 1 and 2) in both organ failure groups. The horizontal lines to the right of each plot represent median values for ΔMFI for each organ failure group. The median ΔMFI for organ failure improvers was a rise of 0.23, and for non-improvers was −0.05 (p=0.04). The proportion of subjects that increased MFI was higher in SOFA improvers compared to non-improvers (88% vs. 47%, p=0.03). [SOFA = Sequential Organ Failure Assessment score]

Figure 3

Mean values for percent change in microcirculatory flow index (MFI) stratified by quartile of raw values for change in organ function (ΔSOFA). [Quartile I = improved organ function; Quartile IV = worsening organ function]