Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

The purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5).

Patients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO₂) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO₂ (StO_{2 baseline}), rate of decrease in StO₂ during VOT (StO_{2 downslope}), and rate of increase in StO₂ during the reperfusion phase were (StO_{2 upslope}) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated.

The mean ± standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 ± 6.6 and 28.6 ± 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 ± 1.3 vs. 1.9 ± 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 ± 2.2 vs. 12.2 ± 3.2; P < 0.05). There were no differences between groups in StO_{2 baseline}. StO_{2 downslope} in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 ± 11.8 vs. -8.1 ± 2.4%/minute) was significantly steeper than in the control group. StO_{2 upslope} increased and was higher than in the control group at T1c, T1d and T2 (101.1 ± 62.1 vs. 54.5 ± 23.8%/minute) (P < 0.05).

Treatment with rh-aPC may improve muscle oxygenation (StO_{2 baseline}) and reperfusion (StO_{2 upslope}) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO_{2 downslope}). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patients.