Hemoadsorption in cardiac surgery, limitations of low-risk patient selection and minimal cytokine levels

Dear Editor,

We read with interest the recent article by Hohn et al., addressing the efficacy of the hemoadsorption technique in managing cytokine elevation following cardiac surgery, with a particular focus on renal outcomes and the evolving role of extracorporeal blood purification. The RECCAS study on CytoSorb® and the SIRAKI02 randomized trial on oXiris® membranes represent pivotal contributions to this field. Yet, they also share limitations that must be carefully considered [1, 2].

The RECCAS study examined the use of CytoSorb® in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Baseline IL-6 levels during surgery were comparable between groups, at 13.7 pg/mL in the treatment group and 13.8 pg/mL in the control group. However, IL-6 levels measured at ICU admission were elevated in both 155.8 ± 159.6 pg/mL in the control group and 214.4 ± 328.8 pg/mL in the CytoSorb group. These levels continued to rise within the first 48 h of ICU admission, with a total peak of 8786.5 pg/mL observed (Supplemental Table 4). Despite these inflammatory markers, the intervention yielded no significant differences in primary inflammation outcomes [1].

Similarly, the SIRAKI02 trial assessed the oXiris® membrane and found no significant reduction in IL-6 levels during cardiac surgery, with baseline levels of 4.30 ± 4.01 pg/mL (extracorporeal blood purification) and 5.83 ± 8.84 pg/mL (standard care). At ICU admission, IL-6 levels were 47.0 ± 88.0 pg/mL in the treatment group and 63.8 ± 121.0 pg/mL in the control group [2].

Nevertheless, the SIRAKI02 trial demonstrated a significant reduction in AKI incidence from 39.7% in the standard care group to 28.4% in the intervention group (p = 0.03). In addition, RECCAS study showed secondary benefits, including reduced renal replacement therapies (RRT) duration (therefore, improving renal recovery) and improved hemodynamic stability. The authors reported a significantly shorter duration of renal replacement therapy in the treatment group (2.3 ± 0.6 days) compared to the control group (5.3 ± 1.2 days; p = 0.029) [1, 2]. These results collectively highlight the potential of hemoadsorption in improving renal and systemic outcomes in patients with AKI following cardiac surgery rather than solely focusing on cytokine removal, a concept demonstrated by Jansen’s experiments [3].

These outcomes (SIRAKI02 and RECCAS) highlight that renal benefits may occur independently of significant cytokine modulation, particularly when baseline IL-6 levels are as low as those observed in both groups, reflecting patients with a low risk of post-pump syndrome. This suggests that mechanisms beyond IL-6 reduction may drive these renal benefits. In addition, these results highlight the importance of patient selection and the role of IL-6 levels in AKI. The SIRAKI02 and RECCAS trials demonstrated significant elevations in IL-6 during the first hours of ICU admission. These findings justify the need for studies with prolonged or sequential therapies extending into ICU admission rather than limiting hemoadsorption interventions to intraoperative use during CPB.

The chemical-physical principles underlying adsorption highlight its potential to non-selectively target and remove cytokines and other middle-molecular-weight solutes. An essential aspect of optimizing hemoadsorption is maintaining a concentration gradient. This gradient is crucial for efficient cytokine removal, ensuring hemoadsorption remains effective throughout therapy. Emphasizing this mechanism is key to adapting therapy protocols to the dynamic inflammatory profile of patients and implementing hemoadsorption in selected high-risk cases, such as infective endocarditis, aortic surgery, heart transplantation, or emergency cardiac surgery [4].

These findings call for refinement in the application of hemoadsorption technologies. Key areas for future investigation include:

• Optimization of Dosing and Timing: Given the concentration-dependent nature of adsorption, protocols based on baseline cytokine levels may enhance efficacy. Extending hemoadsorption therapies beyond the intraoperative period and into ICU admission could provide a more sustained modulation of the inflammatory response, particularly in high-risk patients..

• Standardized Patient Stratification: Implementing patient stratification based on inflammatory profiles, such as baseline IL-6 levels, could optimize the targeted use of hemoadsorption therapies and enhance renal and systemic outcomes.

• Comparative Studies: Direct comparisons of CytoSorb® and oXiris® in similar patient populations would provide valuable insights into their respective efficacies and mechanisms.

In conclusion, while both CytoSorb® and oXiris® demonstrate promise in outcomes on AKI, the nuances of patient selection and mechanistic action are critical to optimizing outcomes. By aligning the unique capabilities of adsorption technologies with the pathophysiology of AKI, we can better address this persistent challenge in cardiac surgery.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

1. Nephrology Service, Hospital Las Higueras, 4270918, Talcahuano, Chile

   Gonzalo Ramírez-Guerrero & Cristian Pedreros-Rosales

2. Nephrology and Dialysis Unit, Carlos Van Buren Hospital, San Ignacio #725, 2340000, Valparaíso, Chile

   Gonzalo Ramírez-Guerrero

3. Departamento de Medicina Interna, Facultad de Medicina, Universidad de Concepción, 4070386, Concepción, Chile

   Cristian Pedreros-Rosales

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1. Gonzalo Ramírez-GuerreroView author publications

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Contributions

GRG and CPR designed the work, GRG and CPR collected and analyzed the data, GRG and CPR drafted the work or substantively revised it, and all authors read and approved the final manuscript.

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Correspondence to Gonzalo Ramírez-Guerrero.

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The authors report no conflicts of interest. 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 article. The authors alone are responsible for the content and writing of this article.

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Ramírez-Guerrero, G., Pedreros-Rosales, C. Hemoadsorption in cardiac surgery, limitations of low-risk patient selection and minimal cytokine levels. Crit Care 28, 437 (2024). https://doi.org/10.1186/s13054-024-05229-y

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• Received: 17 December 2024

• Accepted: 19 December 2024

• Published: 30 December 2024

• DOI: https://doi.org/10.1186/s13054-024-05229-y

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