Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: A randomized crossover double-blind study

Abstract

Background Endotoxin induces an inflammatory response, with secondary release of cytokines, which can progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using a modified membrane (oXiris) capable of adsorption could reduce endotoxin and cytokine levels in septic patients. Methods Sixteen patients requiring CRRT for septic shock-associated acute renal failure and who had endotoxin levels >0.03 EU/ml were prospectively randomized in a crossover double-blind design to receive CRRT with an oXiris filter or with a standard filter. Endotoxin and cytokine levels were measured at baseline and 1, 3, 8, 16 and 24 hours after the start of CRRT. Norepinephrine infusion rate and blood lactate levels were monitored. Results During the first filter treatment period, endotoxin levels decreased in 7 of 9 (77.8%) oXiris filter patients, but in only 1 of 6 (16.7%) standard filter patients ( P = 0.02). Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and interferon (IFN)γ decreased more with the oXiris filter than with the standard filter. Lactate concentration decreased with oXiris (-1.3[-2.2 to -1.1] mmol/l, P = 0.02), but not with the standard filter (+0.15[-0.95 to 0.6]). The norepinephrine infusion rate was reduced during oXiris CRRT, but not during standard filter CRRT. In the second filter treatment period, there was no significant reduction in endotoxin or cytokine levels in either group. Conclusions CRRT with the oXiris filter seemed to allow effective removal of endotoxin and TNF-α, IL-6, IL-8 and IFNγ in patients with septic shock-associated acute renal failure. This may be associated with beneficial hemodynamic effects.

Evaluation of the Effectiveness of Continuous Venovenous Hemodiafiltration Appli̇ed With Oxiris and AN69 Membranes in Patients With Septic Shock-Related Acute Kidney Injury

“…It is thought that the use of semi-permeable membranes that can provide endotoxin and cytokine elimination is a valuable treatment option in septic shock due to gram-negative bacterial infection (30). Endotoxin may also be present in the circulation due to translocation from the ischemic gut in gram-positive infections (4). Therefore, the use of oxiris in gram-positive sepsis or septic shock may be beneficial (14).…”

“…This study was conducted in accordance with the 2008 Declaration of Helsinki and written informed consent was obtained from all patients or their relatives. G-Power version 3.1.9.4 (Universität Kiel, Germany) was used to calculate the sample size with reference to the proportions specified in a previous study (4). The minimum number of patients to be included in the study was 42 with a two-tailed alpha error of 0.05, a power of 0.80, an allocation ratio of N2 / N1 = 1 and an effect size of 0.8.…”

“…Large molecules and liquid are extravasated into the interstitium (3). As a result, organ dysfunction develops (4). One of the organ dysfunctions that may develop in sepsis is Acute Kidney Injury (AKI).…”

Prescription of CRRT: a pathway to optimize therapy

“…Similar findings were recently documented in a prospective, randomized crossover, double-blind study of 16 patients, conducted between February 2016 and February 2018. These patients required CRRT for documented or suspected Gram-negative septic shock (blood endotoxin levels > 0.03 EU/mL) and KDIGO stage 3 AKI [97]. The patients received a total of 48 h of pre-dilution CVVHDF, 24 h each with the oXiris filter, and an AN69ST filter in random order.…”

Gut lymph purification regulates monocyte activity in rats with ischemia-reperfusion injury-induced sepsis

“…OXiris, an adsorbed hemofiltration membrane, is a substitute product based on the hydrogel structure of a propylene and sodium mesylate polymer (AN69), which has been widely applied in recent years to treat sepsis and septic shock. [18,19] However, its clinical efficacy in GLP remains unclear. This study was conducted to confirm that GLP therapy based on oXiris facilitates monocyte function by targeting ITSs in the GLF of IRI-induced rats.…”