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The phenomenon of desorption: What are the best adsorber exchange intervals?
Critical Care volume 28, Article number: 178 (2024)
Comment
To the Editor,
With great interest we read the recent article in the Journal by Jansen et al. providing a proof-of-principle that treatment with CytoSorb® hemoperfusion (HP) reduces plasma concentration of circulating cytokines in a model of systemic inflammation and that this reduction of circulating cytokines does not negatively affect the induction of endotoxin tolerance [1]. In this study, twenty-four healthy volunteers received an intravenous LPS challenge twice, half of which underwent HP during the first challenge and the cytokine response, as well as the degree of endotoxin tolerance were analyzed. The authors need to be congratulated for performing this study, providing important data that HP might be of clinical value for patients with hyperinflammation without having a late impact on immunological phenotypes.
One aspect that has been shown with this data set, is the declining clearance rates over time, which most likely reflects individual saturation points of the adsorber. Furthermore, for Interleukin 8 (Il-8) and Macrophage Inflammatory Protein-1 Alpha (MIP-1α) the study described a situation during the longitudinal HP treatment, in which concentrations became higher after the adsorber, representing a negative clearance or in other words a so-called desorption phenomenon. This means that cytokines were released back into the circulation by the saturated adsorber. This phenomenon has been described before for certain antibiotics [2] and MDMA [3]. In line with these observations, we found a declining and finally negative clearance rate for bilirubin in a patient with severe hyperbilirubinemia after 6 h of HP. The 28-year-old woman presented with a hemolytic crisis in Evans syndrome triggered by parainfluenza type 3 infection and developed progressive encephalopathy due to excessively elevated bilirubin. As she already received intermittent renal replacement therapy, the decision was made to add a CytoSorb® adsorber to aggressively treat the hyperbilirubinemia. The clearance of bilirubin was measured longitudinally. The initial clearance of 14.9 ml/min fell rapidly over few hours and was even negative within less than 6 h (Fig. 1).
The recently published data of an ESICM survey demonstrated, that CytoSorb is the most commonly used extracorporeal blood purification technique by European intensivists [4]. Nevertheless data on how to decide on adsorber exchange intervals is scarce so far and different approaches have been described. Some suggest changing adsorbers regarding to clinical response [5]. One proposed method by Schultz et al. suggests, that the dosing of adsorption efficacy should be calculated with the amount of blood purified, but the formula does not account for adsorber changes and may be too complex for bedside application [6]. A best practice consensus from 2023 concludes, that adsorber changes should be considered every 8 to 12 h [7]. Importantly, none of the mentioned approaches considers the desorption effect and suggested time spans are longer than for the observed occurrence of a negative clearance by Jansen et al. and our observation. This is especially relevant, as Matson et al. discuss in their work hypothetical mechanisms of HP’s toxicity, one of which suggests, that the gradual desorption of cytokines may promote an inflammatory response contrary to the therapeutic intention [8].
In summary, according to the study’s data and our findings, we suggest, that adsorber change intervals should be individually evaluated. The decision could be based on the initial serum level of the substance(s) one seeks to adsorb; meaning the higher it initially is, the shorter the exchange interval should be, due to faster saturation. Ideally, measurement of serial clearance rates during course of a treatment could predict the time of adsorber saturation and indicate adsorber change. Overall desorption from extracorporeal adsorbers should be subject to further investigations.
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Abbreviations
- HP:
-
Hemoperfusion
- LPS:
-
Bacterial lipopolysaccharide
- Il-8:
-
Interleukin 8
- MIP-1α:
-
Macrophage Inflammatory Protein-1 Alpha
- MDMA:
-
3,4-Methylendioxy-N-methylamphetamin
References
Jansen A, et al. CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo. Crit Care. 2023;27(1):117.
Schneider AG, et al. Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption. Sci Rep. 2021;11(1):10493.
Lang CN, et al. Use of the CytoSorb adsorption device in MDMA intoxication: a first-in-man application and in vitro study. Intensive Care Med Exp. 2020;8(1):1–8.
Stahl K, et al. Current clinical practice in using adjunctive extracorporeal blood purification in sepsis and septic shock: results from the ESICM “EXPLORATION” survey. Intensive Care Med Exp. 2024;12(1):5.
Friesecke S, et al. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017;20(3):252–9.
Schultz P, et al. High-dose CytoSorb hemoadsorption is associated with improved survival in patients with septic shock: a retrospective cohort study. J Crit Care. 2021;64:184–92.
Mitzner S, et al. Adjunctive hemoadsorption therapy with CytoSorb in patients with septic/vasoplegic shock: a best practice consensus statement. J Clin Med. 2023;12(23):7199.
Matson J, et al. Adverse outcomes with extracorporeal adsorbent blood treatments in toxic systemic inflammation: a perspective on possible mechanisms. Ann Intensive Care. 2022;12(1):105.
Acknowledgements
Members of the BonHanZA (Bonn-Hannover-Zurich-ARDS) study group are: Eva-Maria Kleinert1, Rolf Erlebach1, Rea Andermatt1, Daniel Andrea Hofmaenner1, Mattia Mueller1, Reto Schuepbach, Pedro David Wendel-Garcia1, Christoph Camille Ganter1, Klaus Stahl2, Tobias Welte2, Thorben Pape2, Ann-Kathrin Rath2, Bahar Nalbant2, Jannik Ruwisch2, Christian Bode3, Benjamin Seeliger3, Christian Putensen3, Konrad Peukert3, Andrea Sauer3, Lennart Wild3. 1University Hospital Zurich, Zurich, Switzerland. 2Hannover Medical School, Hannover, Germany. 3University Hospital Bonn, Bonn, Germany.
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The authors declare that they received no funding in any form related to this project.
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AB and SD are responsible for the conception and design of the work; AB acquired the data, which was analyzed by SD and AB. AB, RE, MM and SD made substantial contributions to the interpretation of data. AB, RE, MM and SD have drafted the work and substantially revised it. All authors have approved the submitted version and agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
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Sascha David is supported by an unrestricted research Grant from Cytosorbents for a RCT to test CytoSorb in CRS (CYTORELEASE-Ex).
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Buhlmann, A., Erlebach, R., Müller, M. et al. The phenomenon of desorption: What are the best adsorber exchange intervals?. Crit Care 28, 178 (2024). https://doi.org/10.1186/s13054-024-04968-2
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DOI: https://doi.org/10.1186/s13054-024-04968-2