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

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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 ≥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.

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Acknowledgments

This study was supported by a Scientist Development Grant from the American Heart Association (0530152 N) to Dr. Trzeciak. Dr. Trzeciak is currently supported by a grant from the National Institutes of Health/National Institutes of General Medical Sciences (K23GM083211). Dr. Shapiro is supported by a grant from the National Institutes of Health/National Institutes of General Medical Sciences (1P50GM076659).

Conflict of interest statement

Dr. Trzeciak has previously received industry research support from Biosite and Eli Lilly, and currently receives research support from Novo Nordisk and INO Therapeutics. Dr. Shapiro has previously received industry research support from Biosite and Eli Lilly, and currently receives research support from Cumberland Pharmaceuticals. None of the other authors have potential financial conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Medicine, Divisions of Cardiovascular Disease and Critical Care Medicine, UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, One Cooper Plaza D363, Camden, NJ, 08103, USA

    Stephen Trzeciak, R. Phillip Dellinger, Michael Rizzuto, Joseph E. Parrillo & Steven M. Hollenberg

  2. Department of Emergency Medicine, UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, One Cooper Plaza D363, Camden, NJ, 08103, USA

    Stephen Trzeciak, Jonathan V. McCoy, Ryan C. Arnold & Nicole L. Abate

  3. Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Nathan I. Shapiro

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  1. Stephen Trzeciak
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  2. Jonathan V. McCoy
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on behalf of the Microcirculatory Alterations in Resuscitation and Shock (MARS) investigators

Corresponding author

Correspondence to Jonathan V. McCoy.

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Trzeciak, S., McCoy, J.V., Phillip Dellinger, R. et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med 34, 2210–2217 (2008). https://doi.org/10.1007/s00134-008-1193-6

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