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The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome

  • Donati, Abele1, 2
  • Damiani, Elisa1
  • Botticelli, Laura1
  • Adrario, Erica1
  • Lombrano, Maria Rita1
  • Domizi, Roberta1
  • Marini, Benedetto1
  • Van Teeffelen, Jurgen WGE3
  • Carletti, Paola1
  • Girardis, Massimo4
  • Pelaia, Paolo1
  • Ince, Can2
  • 1 Università Politecnica delle Marche, Anesthesia and Intensive Care Unit, Department of Biomedical Science and Public Health, via Tronto 10, Torrette di Ancona, 60126, Italy , Torrette di Ancona (Italy)
  • 2 University of Amsterdam, Department of Translational Physiology, Academic Medical Center, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands , Amsterdam (Netherlands)
  • 3 Cardiovascular Research Institute Maastricht, Maastricht University, Department of Physiology, Maastricht, MD, 6200, The Netherlands , Maastricht (Netherlands)
  • 4 University Hospital of Modena, Surgical ICU, Anesthesia and Intensive Care Department, Modena, Italy , Modena (Italy)
Published Article
BMC Anesthesiology
Springer (Biomed Central Ltd.)
Publication Date
Sep 26, 2013
DOI: 10.1186/1471-2253-13-25
Springer Nature


BackgroundThe role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.MethodsProspective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.ResultsIn the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p < 0.05 in all cases), while the PBR did not change. No-aPC patients (n = 9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.ConclusionsaPC significantly improves the microcirculation in patients with severe sepsis/septic shock.Trial registrationNCT01806428

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