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Research
Marlies Ostermann
Guy’s & St Thomas’ Hospital, NHS Foundation Trust
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9500-9080
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Background: The EMiC2 membrane is a medium cutoff hemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous hemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.
Methods: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-ƴ, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 hours after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.
Results: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 hours (p<0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-ƴ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-hour period.
Conclusion: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.
Keywords
EMiC2 filter, middle cutoff, high cutoff, extracorporeal blood purification, sepsis, removal, acute kidney injury, CRRT, kidney replacement therapy
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The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
- RevisionAdditionalfiles.docx
Additional file 1 Sites of sampling from the CVVHD circuit Additional file 2 Reduction ratio of cytokine concentrations at t = 1 (n=12), 6 (n=12), 24 (n=11), and 48 (n=7) hours compared with baseline pre-filter concentrations (%) Additional file 3 Clearance rates (mL/min) of cytokines by adsorption (pink bars) and effluent (blue bars) over time visualized as box and whisker plots (horizontal bars indicate median values) Additional file 4 Spearman's correlation between serum levels and clearances by adsorption and effluent Additional file 5 Mass balances for all cytokines (pg/min): Mass removal rate by adsorption (Mad), mass removal rate by dialysis (Mdf), and total mass removal rate (Mt) Additional file 6 Cytokine half-lives as reported in literature
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CURRENT STATUS: Published
View the published article at Critical Care.
Version 2
Posted 26 Jan, 2021
No community comments so far
Editorial decision: Accept
On 17 Jan, 2021
Editor assigned
On 13 Jan, 2021
Submission checks complete
On 13 Jan, 2021
Editor invited
On 13 Jan, 2021
No comments provided
Editorial decision: Minor revision
On 12 Dec, 2020
Review #2 received
Received 09 Dec, 2020
Review #1 received
Received 05 Dec, 2020
Reviewer #2 agreed
On 28 Nov, 2020
Reviewers invited
Invitations sent on 27 Nov, 2020
Reviewer #1 agreed
On 27 Nov, 2020
Editor assigned
On 18 Nov, 2020
Editor invited
On 18 Nov, 2020
Submission checks complete
On 18 Nov, 2020
First submitted
On 15 Nov, 2020
Metrics
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PDF Downloads: ...
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Subject Areas
Critical Care & Emergency Medicine
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A new preprint design is coming!
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See the published version of this preprint at Critical Care.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Marlies Ostermann
Guy’s & St Thomas’ Hospital, NHS Foundation Trust
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9500-9080
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Critical Care.
Version 2
Posted 26 Jan, 2021
No community comments so far
Editorial decision: Accept
On 17 Jan, 2021
Editor assigned
On 13 Jan, 2021
Submission checks complete
On 13 Jan, 2021
Editor invited
On 13 Jan, 2021
No comments provided
Editorial decision: Minor revision
On 12 Dec, 2020
Review #2 received
Received 09 Dec, 2020
Review #1 received
Received 05 Dec, 2020
Reviewer #2 agreed
On 28 Nov, 2020
Reviewers invited
Invitations sent on 27 Nov, 2020
Reviewer #1 agreed
On 27 Nov, 2020
Editor assigned
On 18 Nov, 2020
Editor invited
On 18 Nov, 2020
Submission checks complete
On 18 Nov, 2020
First submitted
On 15 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Critical Care.
Background: The EMiC2 membrane is a medium cutoff hemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous hemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.
Methods: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-ƴ, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 hours after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.
Results: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 hours (p<0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-ƴ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-hour period.
Conclusion: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.
Figure 1
Figure 2
The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
- RevisionAdditionalfiles.docx
Additional file 1 Sites of sampling from the CVVHD circuit Additional file 2 Reduction ratio of cytokine concentrations at t = 1 (n=12), 6 (n=12), 24 (n=11), and 48 (n=7) hours compared with baseline pre-filter concentrations (%) Additional file 3 Clearance rates (mL/min) of cytokines by adsorption (pink bars) and effluent (blue bars) over time visualized as box and whisker plots (horizontal bars indicate median values) Additional file 4 Spearman's correlation between serum levels and clearances by adsorption and effluent Additional file 5 Mass balances for all cytokines (pg/min): Mass removal rate by adsorption (Mad), mass removal rate by dialysis (Mdf), and total mass removal rate (Mt) Additional file 6 Cytokine half-lives as reported in literature
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