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

Abstract

Introduction: 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).

Materials and methods: 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 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 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.

Results: 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 StO2 baseline. StO2 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. StO2 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).

Conclusions: Treatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 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.

Figure 1

Sequential Organ Failure Assessment score before, during, and after recombinant activated protein C treatment. The Sequential Organ Failure Assessment (SOFA) score in the recombinant activated protein C (rh-aPC) group before, during, and after rh-aPC treatment, and in the control group at the same times. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c), and 96 hours (T1d)), and 6 hours (T2) after rh-aPC treatment (that is, 102 hours from T0). ANOVA, analysis of variance.

Figure 2

Mean arterial pressure before, during, and after recombinant activated protein C treatment. Mean arterial pressure (MAP) in the recombinant activated protein C (rh-aPC) group before, during, and after rh-aPC treatment, and in the control group at the same times. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c), and 96 hours (T1d)), and 6 hours (T2) after rh-aPC treatment (that is, 102 hours from T0). ANOVA, analysis of variance.

Figure 3

Base excess and blood lactate before, during, and after recombinant activated protein C treatment. (a) Arterial base excess (BE) and (b) blood lactate in the recombinant activated protein C (rh-aPC) group before, during, and after rh-aPC treatment, and in the control group at the same times. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c), and 96 hours (T1d)), and 6 hours (T2) after rh-aPC treatment (that is, 102 hours from T0). ANOVA, analysis of variance; n.s., not significant.

Figure 4

Baseline tissue oxygen saturation before, during, and after recombinant activated protein C treatment. Baseline tissue oxygen saturation (StO_{2 baseline}) in the recombinant activated protein C (rh-aPC) group before, during, and after rh-aPC treatment, and in the control group at the same times. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c), and 96 hours (T1d)), and 6 hours (T2) after rh-aPC treatment (that is, 102 hours from T0). ANOVA, analysis of variance; n.s., not significant.

Figure 5

Tissue oxygen saturation increase and decrease before, during, and after recombinant activated protein C treatment. (a) Rate of decrease in tissue oxygen saturation (StO_{2 downslope}) and (b) rate of increase in tissue oxygen saturation (StO_{2 upslope}) in the recombinant activated protein C (rh-aPC) group before, during, and after rh-aPC treatment, and in the control group at the same times. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c), and 96 hours (T1d)), and 6 hours (T2) after rh-aPC treatment (that is, 102 hours from T0). ANOVA, analysis of variance.