Adsorptive Hemofiltration for Sepsis Management: Expert Recommendations Based on the Asia Pacific Experience
Sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, often leading to organ dysfunction and high mortality rates. Central to the pathophysiology of sepsis is the release of bacterial endotoxins, which trigger an exaggerated inflammatory response known as the “cytokine storm.” This uncontrolled release of inflammatory mediators, including cytokines, contributes to the development of acute kidney injury (AKI) and other organ dysfunctions. Continuous renal replacement therapy (CRRT) is a cornerstone in the management of sepsis, particularly in patients with AKI. However, conventional CRRT filters have limited capacity to remove endotoxins and cytokines, which are key drivers of sepsis-induced organ damage. In recent years, the use of adsorptive hemofiltration filters, such as Oxiris, has gained attention for their ability to simultaneously adsorb endotoxins and inflammatory mediators while providing renal support. This article provides a comprehensive overview of expert recommendations for the use of Oxiris in sepsis management, based on clinical experience in the Asia Pacific (APAC) region.
The Role of Endotoxins and Cytokines in Sepsis
Endotoxins, which are components of the outer membrane of gram-negative bacteria, play a pivotal role in the pathogenesis of sepsis. They activate the immune system, leading to the release of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). This cytokine storm results in widespread inflammation, endothelial damage, and microcirculatory dysfunction, ultimately leading to organ failure. AKI is a common complication of sepsis, and its development is closely linked to the presence of endotoxins and cytokines in the circulation. Removing these harmful substances from the bloodstream can help restore chemotactic gradients, localize the immune response to the site of infection, and re-establish a regulated immune response. This forms the rationale for using adsorptive hemofiltration filters like Oxiris in sepsis management.
Oxiris: A Unique CRRT Filter
Oxiris is the only CRRT filter currently available that combines the ability to adsorb endotoxins and inflammatory mediators with the provision of renal support. Its unique properties make it particularly suited for the management of sepsis, where both endotoxin and cytokine removal are critical. The use of Oxiris has been increasing in the APAC region, approaching the levels seen in Europe. However, existing recommendations for its clinical application are primarily based on European experience and do not address specific considerations relevant to the APAC region, such as the socioeconomic diversity and variations in clinical practice. To address this gap, a panel of 14 critical care experts from the APAC region developed consensus recommendations for the use of Oxiris in sepsis, using a standardized, three-step, modified Delphi-based process.
Consensus Recommendations for Oxiris Use in Sepsis
The expert panel developed a set of recommendations to guide the use of Oxiris in sepsis, focusing on patient selection, clinical and laboratory criteria for initiation, timing of therapy, frequency of filter changes, and indicators of treatment success. These recommendations are summarized below.
Patient Population and Indications
Oxiris is primarily recommended for critically ill patients with both septic shock and AKI requiring CRRT. However, it may also be considered in patients with sepsis or septic shock before they meet the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 AKI criteria, based on clinical indicators such as marked disturbances in hemodynamic stability, microcirculatory function, and organ function. The decision to initiate CRRT with Oxiris should be driven by clinical judgment, taking into account a combination of clinical and laboratory parameters.
Clinical Criteria for Initiation
Key clinical criteria for initiating CRRT with Oxiris include marked disturbances in hemodynamic stability (e.g., fluid balance, mean arterial pressure, vasopressor dose), microcirculatory function (e.g., partial pressure of carbon dioxide gap), and organ function (e.g., high Sequential Organ Failure Assessment (SOFA) score). These criteria help identify patients who are likely to benefit from the additional therapeutic effects of Oxiris beyond conventional CRRT.
Laboratory Criteria for Initiation
Laboratory parameters that can guide the decision to initiate CRRT with Oxiris include indicators of infection severity (e.g., elevated levels of procalcitonin and IL-6), sepsis severity (e.g., lactate levels), kidney function (e.g., urine output), and metabolic function (e.g., life-threatening electrolyte imbalances). Although endotoxin removal is a key reason for using Oxiris, it may not always be feasible to measure endotoxin levels due to limitations in the availability and reliability of endotoxin assays. In such cases, more accessible parameters like procalcitonin and IL-6 can be used to assess the severity of infection and bacteremia.
Timing of Therapy Initiation
Once the decision to initiate CRRT with Oxiris is made, therapy should be started as soon as possible. Early intervention is critical to maximize the therapeutic benefits of endotoxin and cytokine removal, particularly in patients with septic shock and AKI.
Frequency of Filter Changes
The Oxiris filter should be changed at 12 to 24 hours if high cytokine levels persist, high filter transmembrane pressures are observed, or imminent circuit clotting is anticipated. However, the frequency of filter changes can be extended up to 72 hours if the patient’s overall condition and biomarkers continue to improve. The duration of Oxiris use should be determined on a case-by-case basis, with close monitoring and clinical judgment.
Indicators of Treatment Success and Discontinuation
Treatment success should be evaluated based on a combination of clinical observations and improvements in laboratory markers within the first 24 hours of Oxiris initiation. Key indicators of success include improvements in hemodynamic stability, organ function, and immune response, as well as evidence of microbial clearance and stabilization of metabolic function. The relative improvement in these parameters is more important than specific defined values or cut-offs.
Special Populations and Contraindications
Oxiris should be used with caution in certain populations, including patients with compromised or exhausted vascular access points, pediatric patients with body weight less than 30 kg, and those receiving palliative care. The use of Oxiris is contraindicated in patients with heparin-induced thrombocytopenia.
Practical Considerations for Oxiris Administration
The parameters for administering the Oxiris filter are similar to those used for CRRT with conventional dialysis filters. Regional citrate or systemic heparin should be used as an anticoagulant for CRRT with Oxiris. The dosing should target an effluent dose of 20 to 35 mL per kilogram per hour, with a blood flow rate of 150 to 200 mL per minute, depending on the patient’s hemodynamic stability.
Challenges and Future Directions
Despite the potential benefits of Oxiris in sepsis management, its use in the APAC region is hindered by several challenges. These include the limited availability and reliability of endotoxin tests, restricted access to Oxiris, and the perception among some clinicians that conventional CRRT filters are an acceptable compromise. Additionally, there is a lack of large clinical studies demonstrating the benefits of CRRT with Oxiris. Randomized controlled trials (RCTs) would provide the most valuable evidence to guide its use, but designing and conducting such trials is challenging due to the heterogeneous nature of sepsis patients.
To address these challenges, the establishment of a regional registry for Oxiris in the APAC region has been proposed. Such a registry would record important measures for informing clinical decisions and could guide future trial design. In the meantime, expert recommendations based on clinical experience in the APAC region provide valuable guidance for clinicians using Oxiris in sepsis management.
Conclusion
Oxiris represents a significant advancement in the management of sepsis, offering the unique ability to simultaneously adsorb endotoxins and inflammatory mediators while providing renal support. The expert recommendations developed by the APAC panel provide a comprehensive framework for the use of Oxiris in sepsis, addressing key considerations such as patient selection, clinical and laboratory criteria for initiation, timing of therapy, frequency of filter changes, and indicators of treatment success. While challenges remain, the increasing use of Oxiris in the APAC region and the ongoing efforts to gather more clinical evidence hold promise for improving outcomes in sepsis patients.
doi.org/10.1097/CM9.0000000000001671
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