Setting the record straight: revisiting the debate on extracorporeal therapies in sepsis

Abstract

Dear editor,

We find ourselves grappling with certain aspects of Gabriella Bottari’s recent commentary, “Rethinking Caution: A critical appraisal of extracorporeal blood purification in sepsis” [1], particularly in relation to our own comment a few weeks earlier “A few word of caution on blood purification in sepsis” [2] in the journal.

We truly appreciate the encouragement of a rigorous scientific debate and would therefore like to take the chance to clarify a few concerns raised by this recent commentary.

We disagree with the list of limitations of the Wendel-Garcia [3] study by Bottari et al. [1]. First, the study is a prospective, controlled trial with very strict inclusion criteria (severe, refractory septic shock, IL-6 ≥ 1000 ng/l and a vasopressor dependency index ≥ 3, despite adequate volume resuscitation) and not a retrospective trial. With all due respect, their trial had a sophisticated propensity matched historical control group but was by no means a retrospective trial since the treatment group was recruited prospectively following a controlled protocol. To us, the fact that their findings contradicted their own initial proposed hypothesis of improved outcome with adjunctive EBP, only further underscores the significance and reliability of these findings. Furthermore, the discussion surrounding CVVH’s potential mortality effect in this trial is not only perplexing but also overlooks key details. What Bottari criticizes as missing in Wendel-Garcia’s work is, in fact, documented in the supplementary materials, including comparable rates of CVVHDF procedures in both groups.

Perhaps the most concerning issue, however, is the fundamental misinterpretation regarding survival vs. mortality in the eXchange-1 trial [4]. In fact, the results were the opposite of what our esteemed colleagues reported—plasma exchange was associated with a 10% survival benefit. Moreover, we have never claimed confidence that plasma exchange is superior; we simply pointed out that it cannot be equated with coupled plasma filtration and adsorption (CPFA), as the two techniques are fundamentally distinct and CPFA is a pure adsorption technology and thus closer to HA. Regardless of personal opinions and preferences, an objective fact remains: plasma exchange has a positive meta-analysis signal [5] whereas HA has a neutral signal [6].

Finally, we are not advocating for plasma exchange over hemoadsorption, we are advocating for the generation of robust evidence. Our critique lies in the authors suggestion of best practice for hemadsorption in sepsis, which, in our view is based on insufficient evidence. This distinction is crucial.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

   Klaus Stahl

2. Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria

   Pedro David Wendel Garcia

3. Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

   Pedro David Wendel Garcia & Sascha David

4. Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany

   Christian Bode

5. Department of Nephrology, Hannover Medical School, Hannover, Germany

   Sascha David

Authors

1. Klaus StahlView author publications

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2. Pedro David Wendel GarciaView author publications

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Contributions

KS, PDWG, CB and SD wrote the manuscript. All authors approved the final version of the manuscript. The comment has been written by all four authors.

Corresponding author

Correspondence to Sascha David.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This reply refers to the comment available online at https://doi.org/10.1186/s13054-025-05353-3.

This reply refers to the comment available online at https://doi.org/10.1186/s13054-025-05268-z.

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Stahl, K., Wendel Garcia, P.D., Bode, C. et al. Setting the record straight: revisiting the debate on extracorporeal therapies in sepsis. Crit Care 29, 243 (2025). https://doi.org/10.1186/s13054-025-05426-3

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• Received: 14 April 2025

• Accepted: 22 April 2025

• Published: 16 June 2025

• DOI: https://doi.org/10.1186/s13054-025-05426-3

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