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


METHODS
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.


RESULTS
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.


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


BACKGROUND
NCT01806428.
Anesthesia and Intensive Care Unit, Department of Biomedical Science and Public Health, Università Politecnica delle Marche, via Tronto 10, 60126 Torrette di Ancona, Italy. a.donati@univpm.it.
Abele
A
Donati
Elisa
E
Damiani
Laura
L
Botticelli
Erica
E
Adrario
Maria Rita
MR
Lombrano
Roberta
R
Domizi
Benedetto
B
Marini
Jurgen Wge
JW
Van Teeffelen
Paola
P
Carletti
Massimo
M
Girardis
Paolo
P
Pelaia
Can
C
Ince