Early hemoperfusion with an immobilized polymyxin B fiber column eliminates humoral mediators and improves pulmonary oxygenation

Abstract

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.

Method: Thirty-six patients with sepsis were included. In each patient a thermodilution catheter was inserted, and the oxygen delivery index and oxygen consumption index were measured. DHP-PMX was performed in patients with a normal oxygen delivery index and oxygen consumption index (> 500 ml/minute per m2 and > 120 ml/minute per m2, respectively). The Acute Physiology and Chronic Health Evaluation II score was used as an index of the severity of sepsis, and survival was assessed after 1 month. The humoral mediators measured were the chemokine IL-8, plasminogen activator inhibitor-1, and neutrophil elastase (NE). These mediators were measured before DHP-PMX treatment, and at 24, 48, and 78 hours after the start of treatment. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) ratio was measured before DHP-PMX treatment and at 24, 48, 72, 92, and 120 hours after the start of treatment.

Results: All patients remained alive after 1 month. Before DHP-PMX treatment, the Acute Physiology and Chronic Health Evaluation II score was 24 +/- 2.0, the IL-8 level was 54 +/- 15.8 pg/ml, plasminogen activator inhibitor-1 was 133 +/- 28.1 ng/ml, and NE was 418 +/- 72.1 mug/l. These three humoral mediators began to decrease from 24 hours after DHP-PMX treatment, and the decline became significant from 48 hours onward. The PaO2/FiO2 ratio was 244 +/- 26.3 before DHP-PMX treatment but improved significantly from 96 hours onward. There were significant negative correlations between the PaO2/FiO2 ratio and blood levels of NE and IL-8.

Conclusion: The mechanism of action of DHP-PMX is still not fully understood, but we report the following findings. The mean blood levels of plasminogen activator inhibitor-1, NE, and IL-8 were significantly decreased from 48 hours after DHP-PMX treatment. The mean PaO2/FiO2 ratio was significantly improved from 96 hours after DHP-PMX treatment. Improvement in the PaO2/FiO2 ratio appeared to be related to the decreases in blood NE and IL-8 levels.

Figure 1

Changes in PAI-1. The plasminogen activator inhibitor (PAI)-1 level was 1,138 ± 26.3 ng/ml before direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX), but it was 67 ± 17.4 ng/ml at 24 hours after the start of treatment, 54 ± 13.6 ng/ml at 48 hours, and 52 ± 9.8 ng/ml at 72 hours, with statistically significant decreases from 48 hours onward compared with baseline (P < 0.05).

Figure 2

Changes in NE. The neutrophil elastase (NE) level was 443 ± 68.2 μg/l before direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX), but it was 366 ± 74.0 μg/l at 24 hours after the start of treatment, 274 ± 42.5 μg/l at 48 hours, and 249 ± 41.3 μg/l at 72 hours, with statistically significant decreases from 48 hours onward compared with baseline (P < 0.05).

Figure 3

Changes in IL-8. The IL-8 level was 54 ± 14.6 pg/ml before direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX), but it was 27 ± 7.5 pg/ml at 24 hours after the start of treatment, 19 ± 4.3 pg/ml at 48 hours after, and 20 ± 4.5 pg/ml at 72 hours after, with a statistically significant decrease from 48 hours onward compared with baseline (P < 0.05).

Figure 4

Changes in PaO₂/FiO₂ ratio. The arterial oxygen tension (PaO₂)/fractional inspired oxygen (FiO₂) ratio was 244 ± 26.3 before direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX). It increased to 274 ± 28.6 at 24 hours after the start of treatment, 289 ± 26.2 at 48 hours, 348 ± 46.0 at 72 hours, 322 ± 22.1 at 96 hours, and 352 ± 25.4 at 120 hours, with statistically significant improvement from 96 hours onward compared with baseline (P < 0.05).

Figure 5

Relationship between the PaO₂/FiO₂ ratio and NE. There was an inverse relationship between the arterial oxygen tension (PaO₂)/fractional inspired oxygen (FiO₂) ratio (P/F ratio) and peripheral blood neutrophil elastase (NE) level. The correlation coefficient between the log-transformed PaO₂/FiO₂ ratio and log-transformed NE value was -0.337 (P = 0.0198).

Figure 6

Relationship between the PaO₂/FiO₂ ratio and IL-8. There was an inverse relationship between the arterial oxygen tension (PaO₂)/fractional inspired oxygen (FiO₂) ratio (P/F ratio) and peripheral blood IL-8 level. The correlation coefficient between the log-transformed PaO₂/FiO₂ ratio and log-transformed IL-8 value was -0.417 (P = 0.0032).