Effects of pre-membrane acidification on extracorporeal CO2 removal compared with conventional ECCO2R in mechanically ventilated animal models: a preclinical systematic review protocol

To systematically evaluate the effect of pre-membrane blood acidification, compared with conventional extracorporeal carbon dioxide removal without acidification, on extracorporeal - carbon dioxide elimination in large animal models undergoing mechanical ventilation.

This protocol is prospectively registered in PROSPERO and will be conducted in accordance with PRISMA-P guidelines. We will include preclinical experimental studies in large animals (e.g., swine, sheep, goats, cattle, or dogs) evaluating pre-membrane acidification associated with extracorporeal carbon dioxide removal. We will conduct electronic searches in PubMed®, Web of Science, Scopus, Embase, and Google Scholar from database inception to December 2025, without language restrictions. Two independent reviewers will conduct study selection, data extraction, and risk-of-bias assessment using the SYRCLE tool. The primary outcome will be extracorporeal carbon dioxide elimination. When appropriate, we will conduct meta-analyses using random-effects models. We will standardize carbon dioxide elimination values by body weight (mL/kg/minute) to improve comparability across species.

This review will provide a structured synthesis of preclinical evidence regarding the magnitude and consistency of the effect of pre-membrane acidification on carbon dioxide elimination, ventilatory parameters, and adverse events.

By systematically evaluating available experimental data, this review aims to clarify the potential role of pre-membrane acidification as an adjunctive strategy to extracorporeal carbon dioxide removal and to identify knowledge gaps relevant for future translational and clinical research.