Endotoxin activity trend and multi‐organ dysfunction in critically ill patients with septic shock, who received Polymyxin‐B hemadsorption: A multicenter, prospective, observational study

Abstract

BackgroundThe baseline endotoxin activity (EAT0) may predict the outcome of critically ill septic patients who receive Polymyxin‐B hemadsorption (PMX‐HA), however, the clinical implications of specific EA trends remain unknown.MethodsSubgroup analysis of the prospective, multicenter, observational study EUPHAS2. We included 50 critically ill patients with septic shock and EAT0 ≥ 0.6, who received PMX‐HA. The primary outcome of the study was the EA and SOFA score progression from T0 to 120 h afterwards (T120). Secondary outcomes included the EA and SOFA score progression in whom had EA at 48 h (EAT48) < 0.6 (EA responders, EA‐R) versus who had not (EA non‐responders, EA‐NR).ResultsSeptic shock was mainly caused by 27 abdominal (54%) and 17 pulmonary (34%) infections, predominantly due to Gram negative bacteria (39 patients, 78%). The SAPS II score was 67.5 [52.8–82.3] and predicted a mortality rate of 75%. Between T0 and T120, the EA decreased (p < 0.001), while the SOFA score and the Inotropic Score (IS) improved (p < 0.001). In comparison with EA‐NR (18 patients, 47%), the EA‐R group (23 patients, 53%) showed faster IS improvement and lower requirement of continuous renal replacement therapy (CRRT) during the ICU stay. Overall hospital mortality occurred in 18 patients (36%).ConclusionsIn critically ill patients with septic shock and EAT0 ≥ 0.6 who received PMX‐HA, EA decreased and SOFA score improved over 120 h. In whom high EA resolved within 48 h, IS improvement was faster and CRRT requirement was lower compared with patients with EAT48 ≥ 0.6.

Which Patient Phenotype Is the Ideal Candidate for Hemoadsorption in Acute and Chronic Kidney Disease?

“…Polymyxin-B-coated polystyrene fibers have been included in a special adsorption cartridge (Toraymyxin, Toray, Japan) and are capable of removal of circulating endotoxin up to approximately 20 μg in a two-hour treatment. [31][32][33] The controversial results achieved so far in studies involving extracorporeal hemoadsorption with Toraymyxin [34,35] could be attributable to the remarkable heterogeneity of the treated populations in different studies. [30,36] Analyses have demonstrated that positive results are more likely in patients with significant organ failure and in patients with endotoxin activity between 0.6 and 0.9.…”

Clinical implications of endotoxin activity and Polymyxin‐B hemoperfusion in critically ill patients with septic cardiomyopathy: A single‐center, retrospective, observational study

“…Among 60 patients (45.9%) with SCM, who received dobutamine as inotropic agent, median ejection fraction was 40% [30][31][32][33][34][35][36][37][38][39][40], and systolic dysfunction was frequent (n = 53, 88.3%) and coexisted with other cardiac function alterations in most of the cases (n = 32, 53.3%) (Table S1). These patients were characterized by higher median values of CCI (0.002), SAPS II score (0.003), SOFA score (0.001), and NT pro-BNP (p = 0.002).…”

“…[12][13][14] Nonetheless, we found that extracorporeal endotoxin removal by PMX-HP was independently associated with R-SCM, and this result was in accordance with Vincent et al, 37 who demonstrated cardiac function improvement after this therapy in 17 (47.2%) critically ill patients with abdominal sepsis. The pathophysiology of this finding may be explained by the potential removal of endotoxin, 38,39 endogenous cannabinoids 40 (that are cofactors for the inducible nitric oxide synthetase), proapoptotic mediators, 41 and monocytes 42 that are upregulated in sepsis and play a role in the pathophysiology of SCM. 12,43,44 In line with the findings of the EUPHAS2 registry, 19,20,38,39 our results confirm the feasibility of PMX-HP in daily clinical practice for the complementary management of sepsis as well as it provides some insights for the application of this therapy aiming to reverse SCM, thus potentially improving patient clinical outcome.…”

“…The pathophysiology of this finding may be explained by the potential removal of endotoxin, 38,39 endogenous cannabinoids 40 (that are cofactors for the inducible nitric oxide synthetase), proapoptotic mediators, 41 and monocytes 42 that are upregulated in sepsis and play a role in the pathophysiology of SCM. 12,43,44 In line with the findings of the EUPHAS2 registry, 19,20,38,39 our results confirm the feasibility of PMX-HP in daily clinical practice for the complementary management of sepsis as well as it provides some insights for the application of this therapy aiming to reverse SCM, thus potentially improving patient clinical outcome. Our study showed that SCM was directly associated with pulmonary infection.…”

Endotoxin removal therapy with Polymyxin B immobilized fiber column: a single center experience from EUPHAS2 registry

“…A clinically significant increase in circulating endotoxin levels might be observed during bactericidal antimicrobial therapy due to bacterial lysis, resulting in even further activation of inflammatory response 6 . Based on some recent evidence, patients with unresponsive septic shock may benefit from extracorporeal adsorption of circulating endotoxins as an adjunctive treatment 7 , 8 , especially those with a measured endotoxin activity assay 9 (EAA) ranging from 0.6 to 0.9 10 , 11 .…”