Potential survival benefit and early recovery from organ dysfunction with polymyxin B hemoperfusion: perspectives from a real-world big data analysis and the supporting mechanisms of action

Abstract

Background Endotoxin (ET) removal therapy with polymyxin B-immobilized fiber column hemoperfusion (PMX-HP) has been used for the treatment of septic shock. Some observational studies reported clinical benefits, particularly in specific subgroups of patients. However, larger randomized controlled trial results have been disappointing. Main body The four studies that revealed the survival benefit of PMX-HP were based on the Japanese Diagnosis Procedure Combination (DPC) national inpatient database (J-DPC study). Nevertheless, one J-DPC study and a randomized controlled trial (RCT) conducted in France evaluated PMX-HP in patients with abdominal septic shock and did not report a significant survival benefit. In both studies, the severity of illness was too low to find substantial significant differences in mortality. The results of the J-DPC studies further suggest that some subpopulations of patients could benefit from PMX-HP. Based on these results, this review revisited prior RCTs and other large-scale studies on PMX-HP. In addition, four J-DPC studies and one large-scale study reported a survival benefit with PMX-HP. A secondary analysis of the EUPHRATES trial, the most recent double-blinded RCT of PMX-HP conducted in North America, suggested a survival benefit in patients with high levels of endotoxemia. In the J-DPC studies and the EUPHRATES trial, ventilator-free days, vasoactive drug-free days, and renal replacement-free days were significantly improved in the PMX-HP groups. These findings suggest that PMX-HP can contribute to early recovery from organ dysfunction. The reduction of supportive care likely provides important health and economic benefits for managing patients with septic shock. Finally, the blood levels of mediators or biomarkers related to respiratory, cardiovascular, and renal dysfunction have been reported to be normalized with PMX-HP. Conclusions These results support the biological rationale for the improvement in organ dysfunction observed in the J-DPC studies and other large-scale studies, including the EUPHRATES trial. Real-world evidence from large data sets suggests an appropriate patient population that are likely to benefit from the utility of PMX-HP for septic shock.

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

“…The Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock 2 (EUPHAS 2) 12 , 13 project is a voluntary registry specifically conceived for evaluating and analyzing PMX-HA application in real clinical life. The EUPHAS2 observational, multicenter, multinational, prospective, web-based registry collects data concerning the use of PMX-HA in critically ill patients with septic shock, aiming to identify specific populations that may benefit from this therapy and provide proof of concept for future trials.…”

“…Demographic variables were collected, including age, gender, Body Mass Index (BMI), past medical and surgical history, a clinical course in the department of origin and clinical severity at ICU admission, as reported in the EUPHAS Registry 12 , 13 . Suspected or proven sources of infection were recorded as well.…”

“…Moreover, after excluding trials published before 2010, PMX-HA was associated with a high mortality risk (RR 1.23; 95% CI 1.04–1.46). Overall, the quality of evidence is judged as low 2 , 12 , 13 .…”

Activated Carbon for Sepsis Prevention and Intervention: A Modern Way of Utilizing Old Therapies

“…Different PAMPs and DAMPs (Table 1) can be removed by selective HP [14] targeting key molecules or non-selective HP by porous materials [27]. The part of PAMPs and DAMPs with the molecular weight range, of 5-60 kDa adsorbed with Hp device in sepsis and septic shock treatment, is classified as membrane-damaged substances (Table 2).…”

“…Activated carbon or activated charcoal (AC) is a well-known remedy and, today has enhanced biocompatibility and high-adsorptive capacity [12]. It can adsorb different inflammation-related PAMPs and DAMPs by non-selective (broad-range) [10,12,13], selective [14], and combined (non-selective and selective) [15][16][17][18] from biological fluids. AC is administered orally, per rectum, or via the hemoperfusion system for mitigation of different pathological states accompanied by inflammation, and has an impact on different parameters of homeostasis [19][20][21].…”