The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

Abstract

BackgroundRecent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.MethodsWe conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.ResultsFifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.ConclusionPMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial registrationClinicalTrials.gov, NCT02413541. Registered on 3 March 2015. Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2077-y) contains supplementary material, which is available to authorized users.

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial

“…The biology of endotoxin in humans is characterised by movement through different compartments, which presumably could occur following LPS removal by the PMX cartridge. Srisawat et al recently demonstrated a similar finding with modulation of HLA-DR that was statistically significant in patients with septic shock treated with PMX versus sham, but again no significant difference in post-treatment EAA [ 27 ].…”

Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment

“…196 Recently, the immunomodulation effect of PMX-HP has been reported in another RCT by improvement of monocyte and neutrophil functions in patients with sepsis without a benefit in mortality or renal outcome. 197…”

Treatment of Pyonephritis Complicated by Septic Shock Using Extracorporeal Device Polymyxin B-Hemoperfusion

“…PMX-DHP increases surface antigen HLA-DR and CD16 expression on granulocytes, helping immune cells to recovery from immunoparalysis [11]. In this case report, we obtained the resolution of pathology by assembling rapidly conventional surgical therapy and hemoperfusion therapy with immobilized PMX-B cartridges, even though there was no recommendation for this treatment and there was a lack of literature.…”