Open Access Open Badges Research article

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

Abele Donati12*, Elisa Damiani1, Laura Botticelli1, Erica Adrario1, Maria Rita Lombrano1, Roberta Domizi1, Benedetto Marini1, Jurgen WGE Van Teeffelen3, Paola Carletti1, Massimo Girardis4, Paolo Pelaia1 and Can Ince2

Author Affiliations

1 Anesthesia and Intensive Care Unit, Department of Biomedical Science and Public Health, Università Politecnica delle Marche, via Tronto 10, 60126 Torrette di Ancona, Italy

2 Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands

3 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands

4 Surgical ICU, Anesthesia and Intensive Care Department, University Hospital of Modena, Modena, Italy

For all author emails, please log on.

BMC Anesthesiology 2013, 13:25  doi:10.1186/1471-2253-13-25

Published: 26 September 2013



The 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.


Prospective 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.


In 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.


aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.

Trial registration