Recently, direct hemoperfusion with a polymyxin B-coated fiber column (DHP-PMX) has been increasingly used for the treatment of sepsis, and an improvement in outcomes has been reported. However, the mechanism of the method is not known in detail. In the present study, we examined whether the performance of DHP-PMX improved tissue oxygen metabolism in patients with sepsis. Twenty-two patients with sepsis, satisfying the following criteria, were enrolled in the study: (i) signs of systemic inflammatory response syndrome caused by infection; and (ii) mean arterial blood pressure > or =60 mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for appropriate intravenous infusion, and the DHP-PMX was carried out twice within 24 h (for 3 h each time). Then, the gastric mucosal-arterial PCO(2) difference (PCO(2) gap) was calculated as the gastric mucosal PCO(2) minus arterial PCO(2). A PCO(2) gap > or =8 mm Hg was used to define abnormal tissue oxygen metabolism. PCO(2) gap was measured before PMX-DHP, as well as 24, 48, and 72 h afterward. PCO(2) gap was 20 +/- 4.9 mm Hg before DHP-PMX vs. 16 +/- 2.7 mm Hg (P = 0.189) at 24 h, 12 +/- 2.8 mm Hg (P = 0.046) at 48 h, and 11 +/- 2.2 mm Hg (P = 0.045) at 72 h afterward, showing a significant decrease from 48 h onward compared with before treatment. These findings suggest that DHP-PMX improves tissue oxygen metabolism.

Introduction The objective of this study was to clarify the efficacy and mechanism of action of direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) in patients with acute lung injury or acute respiratory distress syndrome caused by sepsis.

Background: We investigated whether direct hemoperfusion with an immobilized polymyxin B column (DHP with PMX) could reduce the blood level of neutrophil elastase. Methods: 20 sepsis patients were enrolled in the study. DHP with PMX was performed twice within a 24-hour period. Neutrophil elastase was measured 7 times. Results: Neutrophil elastase was 468 ± 75.1 µg/l, while it was 1,531 ± 201.7 µg/l immediately after the first session, declined to 351 ± 73.9 µg/l before the second session of DHP with PMX, and increased again to 599.3 ± 112.7 µg/l immediately after the second session, 328 ± 73.7 µg/l at 24 h, 264 ± 39.3 µg/l at 48 h, and 230 ± 36.1 µg/l at 72 h after DHP with PMX. The levels from 48 h onwards were significantly lower compared with that before treatment. Conclusion: DHP with PMX has an overall effect that reduces circulating neutrophil elastase levels.

Involvement of the activation of neutrophils and vascular endothelial cells in the pathology of sepsis has recently been reported. We therefore investigated whether direct hemoperfusion (DHP) with a polymyxin B immobilized fiber column (PMX) could reduce the level of plasminogen activator inhibitor-1 (PAI-1), an index of vascular endothelial cell activation. Twelve sepsis patients satisfying the following criteria were enrolled in the study: (i) stable global oxygen metabolism (oxygen delivery index>500 mL/min/m2 and oxygen consumption index>120 mL/min/m2); (ii) abnormal tissue oxygen metabolism (PCO2 gap: gastric mucosal PCO2 minus arterial PCO2 difference>8 mm Hg); and (iii) mean blood pressure>or=60 mm Hg. Direct hemoperfusion with PMX was performed twice (for 3 h each time) within 24 h. Plasminogen activator inhibitor-1 was measured a total of 5 times: before PMX-DHP, immediately after the first DHP with PMX session (3 h after the start), and 24, 48, and 72 h afterward. The PAI-1 value was 150+/-30.0 ng/mL before DHP with PMX, 178+/-60.0 ng/mL immediately after DHP with PMX, 90+/-22.1 ng/mL at 24 h after, 65+/-21.0 ng/mL at 48 h after, and 64+/-18.3 ng/mL 72 h after. The values were significantly lower from 48 h onward compared with baseline. These data suggest that DHP with PMX inhibits vascular endothelial cell activation.

In the present study, we examined whether the performance of hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) reduces circulating interleukin-8 concentration in patients with sepsis. Fifteen patients with sepsis satisfying the following criteria were enrolled in the study: (i) signs of systemic inflammatory response syndrome caused by infection; and (ii) mean arterial blood pressure > or =60 mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for appropriate intravenous infusion, and the DHP-PMX was carried out twice at 24 h intervals (for 3 h each time). Circulating interleukin-8 concentration was measured seven times. The sequential organ failure assessment (SOFA) score was calculated twice. Circulating interleukin-8 concentration was 55 +/- 15.7 pg/mL before DHP-PMX, while it was 101 +/- 58.8 pg/mL immediately after the first session of treatment. It was 24 +/- 9.0 pg/mL before the second session of DHP-PMX, and it was 28 +/- 8.0 pg/mL immediately after the second session. The IL-8 level was 17 +/- 4.3 pg/mL at 48 h afterward, and 18 +/- 4.3 pg/mL at 72 h afterward, showing a significant decrease from 48 h onwards, compared with before treatment (P < 0.05). The SOFA score was 9 +/- 1.5 and the APACHE II score was 19 +/- 2.0 before DHP-PMX, while the SOFA score was 7.0 +/- 0.9 at 72 h afterward, showing a significant decrease compared with before treatment (P < 0.05). The present findings indicate that DHP-PMX indirectly reduces circulating interleukin-8 concentration and improves SOFA score.

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