Intensive Care Medicine

, Volume 34, Issue 12, pp 2210–2217 | Cite as

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

  • Stephen Trzeciak
  • Jonathan V. McCoyEmail author
  • R. Phillip Dellinger
  • Ryan C. Arnold
  • Michael Rizzuto
  • Nicole L. Abate
  • Nathan I. Shapiro
  • Joseph E. Parrillo
  • Steven M. Hollenberg
  • on behalf of the Microcirculatory Alterations in Resuscitation and Shock (MARS) investigators



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.


Prospective observational study.


Emergency Department and Intensive Care Unit.


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).


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.


Microcirculation Resuscitation Sepsis Severe sepsis Septic shock Organ failure 



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.

Supplementary material

134_2008_1193_MOESM1_ESM.doc (377 kb)
MOESM1 [ESM] (DOC 377 kb)


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Stephen Trzeciak
    • 1
    • 2
  • Jonathan V. McCoy
    • 2
    Email author
  • R. Phillip Dellinger
    • 1
  • Ryan C. Arnold
    • 2
  • Michael Rizzuto
    • 1
  • Nicole L. Abate
    • 2
  • Nathan I. Shapiro
    • 3
  • Joseph E. Parrillo
    • 1
  • Steven M. Hollenberg
    • 1
  • on behalf of the Microcirculatory Alterations in Resuscitation and Shock (MARS) investigators
  1. 1.Department of Medicine, Divisions of Cardiovascular Disease and Critical Care MedicineUMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University HospitalCamdenUSA
  2. 2.Department of Emergency MedicineUMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University HospitalCamdenUSA
  3. 3.Department of Emergency MedicineBeth Israel Deaconess Medical CenterBostonUSA

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