Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection

Abstract

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30–50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81–1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. Trial registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Successful treatment of direct hemoperfusion with polymyxin B-immobilized fiber for septic shock and severe acute kidney injury due to ceftriaxone-resistant Escherichia coli: a case report with literature review

“…Though the reason why the serum endotoxin was not elevated in this case is ambiguous, the positive rate of blood endotoxin is generally low [31]. Because of various reasons such as pretreatment, measurement method, contamination, and endotoxin concentration, there are no standard methods for endotoxin measurement [31,32]. Our endotoxin measurement method might be different from other cases Table 3.…”

Blood Purification Techniques for Sepsis and Septic AKI

“…Interestingly, blood purification techniques' beneficial effects, suggested by a recent meta-analysis, were primarily due to results from Japanese cohorts assessing polymyxin B hemoperfusion (47). Several retrospective Japanese cohorts triggered conflicting results on mortality (48)(49)(50). Two other propensity-matched cohorts were recently published.…”

Immune Mechanisms Underlying Susceptibility to Endotoxin Shock in Aged Hosts: Implication in Age-Augmented Generalized Shwartzman Reaction

“…Gram-negative bacteremia induce a more severe inflammatory response in septic patients than Gram-positive bacteremia [16]. Therefore, Gram-negative sepsis is prone to progress to septic shock, and the mortality due to Gram-negative septic shock is still higher than that associated with Gram-positive sepsis at approximately 30–40% [16,17,18]. Aging is also a risk factor for colonization by Gram-negative bacteria, such as the Klebsiella , Escherichia coli , and Enterobacter species, predisposing elderly patients to Gram-negative bacterial sepsis and septic shock [19].…”