Sepsis is distinguished by organ dysfunction that could be life-threatening, originating from the host’s abnormal response to infection. Septic shock is essentially sepsis that is compounded by severe circulatory, metabolic, and cellular dysfunction, carrying a higher mortality risk in comparison to uncomplicated sepsis.1 A comprehensive meta-analysis conducted from 2009 to 2019 across regions such as North America, Europe, and Australia discovered that the 90-day mortality rates were 32.2% for sepsis and 38.5% for septic shock.2 Similarly, a cross-sectional study in China indicated that sepsis accounted for 20% of ICU patient diagnoses, with 90-day mortality rates observed at 35.5% for sepsis and 51.9% for septic shock.3

The methods for treating sepsis include antibiotics, infection source control, hemodynamic optimization. Anti-endotoxin antibodies have been used in clinical practice, but have not shown significant therapeutic effects.4 Scholars are continuously investigating new treatment approaches based on the pathological and physiological mechanisms of sepsis, particularly for septic shock with a high mortality rate. It is widely accepted that an excessive inflammatory response in sepsis patients can lead to organ dysfunction and early death.5 Continuous hemofiltration dialysis was first reported in 1993 by Bellomo et al.’s study as a method to clear inflammatory mediators.6 Subsequent studies have confirmed that the adsorption or filtration modes of continuous renal replacement therapy (CRRT) may effectively remove pro-inflammatory and anti-inflammatory cytokines in sepsis patients,7–11 helping to maintain a stable immune balance.12

Currently, China and several Western countries have started using the oXiris hemofilter for treating septic shock patients.4,13 The oXiris hemofilter combines the functions of CRRT, endotoxin adsorption, and cytokine adsorption, effectively suppressing the inflammatory response in septic shock patients.6 Preliminary small-scale clinical trials have indicated that oXiris can notably decrease endotoxin levels and remove inflammatory mediators in hyperendotoxemia patients.14–18 However, it remains uncertain whether oXiris hemofilter can enhance circulatory status, organ function, clinical outcomes in patients experiencing septic shock. Therefore, this study retrospectively analyzes the clinical outcomes from our center to offer additional insights into the application of oXiris hemofilter in septic shock patients.

Our study found that the oXiris hemofilters significantly reduced levels of PCT, hs-CRP, and IL-6 compared to the control group. Although the 72-h and 7-day mortality rates were lower in the oXiris group, these differences were not statistically significant. Additionally, there was no significant difference in 28-day mortality between the two groups. Furthermore, the oXiris group exhibited longer hospital stays, increased mechanical ventilation times, and higher ICU and total hospitalization costs compared to the control group; however, these differences were also not statistically significant.

Endotoxin, a lipopolysaccharide present in the cell wall of Gram-negative bacteria, is released into the bloodstream upon bacterial death in significant quantities. This release triggers the activation of the monocyte-macrophage system through endotoxin stimulation, leading to the generation of several inflammatory markers like C-reactive protein, procalcitonin, tumor necrosis factor-α (TNF-α), and IL-6. This sequence initiates an immune inflammatory cascade, promoting the binding of neutrophils to endothelial cells. At the same time, the excessive release of protease due to lysosome membrane breakdown causes damage to vascular endothelial cells, microvascular dysfunction, and irregular contractions, eventually resulting in septic shock.21 Oxidative stress can trigger molecular pathways, initiating inflammatory responses and causing tissue injury, a critical mechanism in the development of multiple organ failure in septic shock.22 Conventional CRRT membrane materials primarily provide kidney support, while adsorptive CRRT membrane materials like AN69/AN69ST/PMMA not only offer traditional CRRT functions but also have the ability to adsorb inflammatory mediators. The latest AN69 series product, the oXiris membrane material, is an advancement that not only absorbs inflammatory mediators but also endotoxins, while still providing kidney support. PMX adsorption columns target endotoxins through perfusion, and CytoSorb absorbs cytokines through hemoperfusion. Among current blood purification products, the oXiris membrane material stands out for its comprehensive functionality.23

Research conducted in laboratory settings has shown the effectiveness of the oXiris hemofilter in the elimination of inflammatory mediators and endotoxin.24 A small trial that involved random assignment of participants to different groups found that the oXiris hemofilters successfully removed inflammatory mediators including TNF- α, IL-6, IL-8, and IFN-γ.25 Additional studies have pointed out that patients with sepsis who survived exhibited a more rapid reduction in IL-6 levels post-treatment in comparison to patients who did not survive.14 The findings of this investigation indicated a substantial decrease in infection markers PCT, hs-CRP, and IL-6, with a particular focus on the significant decrease in IL-6 compared to the control group, thereby suggesting the effectiveness of the oXiris hemofilter in eliminating inflammatory mediators.

Several clinical trials have suggested that oXiris might enhance hemodynamic parameters, reduce the necessity for norepinephrine, improve lactic acid clearance, decrease the need for resuscitation fluids,26,27 and decrease the SOFA score.28–30 Our study presents results that are in contrast to prior investigations. It was noted that patients in the oXiris group, following 24 to 72 hours of treatment, did not display a decrease in demand for NE equivalents or lactate levels compared to the control group. While there was a decline in APACHEII score and SOFA score in the oXiris group in comparison to the control group, this difference did not achieve statistical significance. We attribute the aforementioned results to the severe shock experienced by the selected patients, 10 of whom (31.25%) initiated oXiris treatment within 24 hours of being diagnosed with septic shock. It is possible that these patients experienced a deterioration in their condition, necessitating higher doses of vasopressors. This study show that the 28-day mortality rates between the two groups were comparable (56.25% vs. 53.19%). This result contradicts several prior investigations.13,31 Pooling data from 14 studies with 695 patients, a meta-analysis discovered that septic patients using the oXiris hemofilter had lower 28-day mortality rates [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36–0.77, p = 0.001] and reduced ICU stays [weighted mean difference (WMD) −1.91; 95% CI −2.56 to −1.26, p < 0.001].32 However, concerns have been expressed by some researchers about the statistical techniques utilized, and most of the studies included were retrospective, with insufficient cases to definitively confirm the benefits of oXiris.33 These results prompt the inquiry as to why prognosis is not enhanced. One possible rationale is that although the oXiris hemofilter can eliminate endotoxins and inflammatory mediators, it may impact only a fraction of the inflammatory network, leaving the overall network unaffected. Another consideration is that the removal of certain cytokines and inflammatory mediators might overly suppress the immune response in sepsis patients. Emphasizing the significance of antibiotics in septic shock treatment is crucial. Not only do membranes for hemofiltration absorb endotoxins and inflammatory mediators but they also have the capability to capture antibiotics. At present, there are no set protocols for altering antibiotic levels in oXiris hemofilter CRRT, and the ideal antibiotic concentration is still unknown. It is crucial to acknowledge that utilizing blood hemofilters such as oXiris could potentially reduce the effectiveness of antibiotics, potentially accelerating the decline of the patient. This highlights the importance of ongoing clinical surveillance and evaluation.

There is currently no agreement on the use of oXiris in critically ill individuals with AKI. A recent randomized controlled trial conducted across multiple countries showed that initiating treatment with oXiris promptly can result in enhanced kidney function, reduced CRRT duration, and shortened ICU stay.34 In our study of the oXiris group, patients had high APACHEII and SOFA score, the dose of vasoactive drugs at the beginning of oXiris treatment was very large, indicating severe conditions. Further research is needed to determine if inflammatory adsorption therapy should be initiated when vasoactive drug doses reach a certain level (such as NE > 0.5 µg/kg/min or 1.0 µg/kg/min). Our study used an average of 2.5 oXiris hemofilters per patient, with an average hemofilter use time of 26.7 hours. The optimal number of hemofilters and timing for their use remains unclear, considering both clinical efficacy and economic factors. Notably, patients in the oXiris group incurred higher costs and longer hospitalization and ICU stays compared to the control group, possibly influenced by early mortality rates and limited control group cases.

The study comes with several limitations. Primarily, standardized clinical guidelines for the utilization of oXiris are lacking, including explicit directions for commencing and ceasing treatment, alongside inconsistencies in CRRT parameters and the simultaneous utilization of traditional hemofilters. Furthermore, this retrospective study was conducted at a singular center with a restricted number of cases. Even though PSM was utilized to account for differences in fundamental characteristics and disease severity, potential biases stemming from unobserved confounding variables remain plausible. The demographic of the study exhibited notable diversity, encompassing various infection locations (such as the abdominal cavity, lungs, blood, urine, skin, and soft tissue) and diverse pathogens (including gram-negative bacteria, gram-positive bacteria, and fungi). Solely IL-6 levels were recorded, with pivotal cytokines like endotoxin level, IL-1, IL-8, and TNF-α, which play vital roles in sepsis progression, not being evaluated, thereby limiting the substantiation endorsing the efficacy of oXiris in removing inflammatory mediators. Given the limited number of cases, our study did not analyze the differences between the two patient groups using conventional filters and oXiris filters.Moreover, essential hemodynamic information, such as cardiac output and vascular resistance, was not gathered, raising uncertainties regarding whether CRRT, by eradicating inflammatory mediators and enhancing vascular tone, amplified circulatory function in patients with septic shock. Furthermore, the study's follow-up duration was brief, precluding insights into the enduring effects of oXiris usage on the prognosis of septic shock patients.

The oXiris-continuous hemofiltration adsorption has shown promise in reducing inflammatory mediators in septic shock patients, yet it has not demonstrated significant improvements in organ function or patient prognosis. Further randomized controlled trials are necessary to validate its clinical efficacy.

This study was supported by the Sichuan Province Medical (Youth Innovation) Research Project (S20077).

Yuxin Yang: Formal analysis, Investigation, Data Curation, Writing the Original Draft. Qionglan Dong: Conceptualisation, Methodology, Project administration, Funding acquisition. Jianpeng Su, Hongjun Xiao, Dan Zan, Jinfeng Chen, Xue Chen, Qibing Tang, Cheng Zeng, Yanyan Yong, Investigation, Data Curation. All authors reviewed, revised, and approved the final version of the manuscript and agreed to the submission of this manuscript.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.