Questioning the classification of “high blood flow” versus “low blood flow” ECCO₂R in ultra-low tidal volume ventilation studies: a call for functional classification

Abstract

We read with great interest the recent study by Monet et al. [1] investigating the feasibility and safety of ultra-low tidal volume ventilation (≤ 3 mL/kg) combined with ECCO₂R in acute respiratory failure. While the study provides valuable insights into lung-protective strategies, we wish to highlight a critical point in the authors' classification of ECCO₂R devices into “high blood flow” (HBF) and “low blood flow” (LBF) groups, which may undermine the validity of their conclusions.

The study defines HBF as “blood flow ≥ 1000 mL/min” and LBF as “blood flow < 500 mL/min” without citing standardized criteria. This dichotomy ignores two key issues:

Threshold variability: existing literature uses conflicting cutoffs (e.g., HBF as > 800 mL/min in SUPERNOVA study [2]).

Functional disconnection: blood flow alone poorly predicts CO₂ clearance. For example, the Prismalung + ®(classified as LBF in the study) achieves 90 mL/min above CO₂ removal at 400–450 mL/min blood flow [3], surpassing some “HBF” devices at 500 mL/min with smaller membrane surfaces.

By prioritizing blood flow over CO₂ extraction rate (mL/min) and membrane efficiency (CO₂ clearance per L blood flow), the authors risk misclassifying device performance. A device with 500 mL/min above flow but low membrane efficiency may be functionally inferior to a 400 mL/min device with optimized design, yet both would be grouped differently in this analysis.

The HBF/LBF grouping aggregates fundamentally distinct technologies: HBF group includes pumpless arteriovenous devices (e.g., iLA Activve®) while LBF group combines with roller pump system (e.g., PrismaLung +®) and centrifugal pump system (e.g., Hemolung Respiratory Assist System®), ignoring their divergent hemodynamic impacts [4].

This heterogeneity introduces unmeasured confounding. For instance, the reported “no significant safety difference” between groups could mask device-specific risks (e.g., hemolysis in centrifugal pumps vs. thrombosis in pumpless systems).

The study’s primary endpoint—feasibility of ultra-low tidal volume ventilation—depends on precise CO₂ control, which is determined by ECCO₂R efficiency (CO₂ clearance/mL blood flow), not absolute flow rates. A functional classification based on CO₂ extraction capacity would possibly better predict the ability to maintain pH and PaCO₂ targets.

Therefore, to advance future ECCO₂R research, we propose:

Standardized functional metrics: report CO₂ extraction rate (mL/min) normalized to blood flow (mL/min) and membrane surface area (m²).

Device-specific subgroup analyses: compare outcomes by technology type (e.g., centrifugal vs. roller pump systems) rather than arbitrary flow categories.

Dynamic performance assessment: incorporate real-time CO₂ clearance data during dose titration, as static flow thresholds cannot capture device responsiveness to metabolic demands.

While Monet et al. [1] contribute importantly to the field, re-evaluating ECCO₂R classification strategies is essential to avoid misleading conclusions and guide evidence-based device selection.

No datasets were generated or analysed during the current study.

ECCO₂R:

Extracorporeal carbon dioxide removal

HBF:

High blood flow

LBF:

Low blood flow

1. Monet C, Renault T, Aarab Y, et al. Feasibility and safety of ultra-low volume ventilation (≤ 3 ml/kg) combined with extra corporeal carbon dioxide removal (ECCO2R) in acute respiratory failure patients. Crit Care. 2024;28:433. https://doi.org/10.1186/s13054-024-05168-8.

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Authors and Affiliations

1. Medical Affairs, Vantive Health LLC, Shanghai, China

   Minmin Wang & Qiang Yao

2. Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

   Mingli Zhu

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Contributions

MW designed and wrote the manuscript. QY & MZ reviewed it.

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Correspondence to Minmin Wang.

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MW&QY declare to have competing interests. MZ declare to have no competing interests. This article is not supported by any company or funding.

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Wang, M., Yao, Q. & Zhu, M. Questioning the classification of “high blood flow” versus “low blood flow” ECCO₂R in ultra-low tidal volume ventilation studies: a call for functional classification. Crit Care 29, 121 (2025). https://doi.org/10.1186/s13054-025-05352-4

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• Received: 28 February 2025

• Accepted: 03 March 2025

• Published: 19 March 2025

• DOI: https://doi.org/10.1186/s13054-025-05352-4

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Keywords

• Extracorporeal carbon dioxide removal
• ECCO2R
• Acute respiratory distress syndrome
• Intensive care
• Ventilator-induced lung injury