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Optimizing positive end-expiratory pressure in asymmetric acute lung injury in a porcine model: the role of transpulmonary pressure

Acute hypoxemic respiratory failure is a critical challenge in intensive care. A substantial proportion of patients present with asymmetric acute lung injury (ALI), complicating management due to heterogeneous lung involvement. While lung-protective mechanical ventilation represents the standard of...

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Main Authors: Mutschler, Claudine (Author) , Seybold, Benjamin (Author) , Aschauer, Stefan (Author) , Englert, Nils (Author) , Weis, Cleo-Aron Thias (Author) , Poth, Tanja (Author) , Cetiner, Defne (Author) , Wielpütz, Mark Oliver (Author) , Kehr, Dorothea (Author) , Weigand, Markus A. (Author) , Kalenka, Armin (Author) , Fiedler-Kalenka, Mascha (Author)
Format: Article (Journal)
Language:English
Published: 14 October 2025
In: International journal of molecular sciences
Year: 2025, Volume: 26, Issue: 20, Pages: 1-29
ISSN:1422-0067
DOI:10.3390/ijms26209985
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms26209985
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/26/20/9985
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Author Notes:Claudine H. Mutschler, Benjamin Seybold, Stefan Aschauer, Nils Englert, Cleo-Aron Weis, Tanja Poth, Defne Cetiner, Mark O. Wielpütz, Dorothea Kehr, Markus A. Weigand, Armin Kalenka and Mascha O. Fiedler-Kalenka
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Summary:Acute hypoxemic respiratory failure is a critical challenge in intensive care. A substantial proportion of patients present with asymmetric acute lung injury (ALI), complicating management due to heterogeneous lung involvement. While lung-protective mechanical ventilation represents the standard of care, the optimal approach to positive end-expiratory pressure (PEEP) titration remains unclear. This study investigated the effects of transpulmonary pressure (TPP)-guided PEEP titration vs. a fixed PEEP strategy in a porcine model of unilateral ALI. A total of 14 pigs underwent ALI induction via unilateral surfactant depletion and were randomized to receive either a fixed PEEP of 5 cmH2O or a PEEP targeting a slightly positive TPP at end-expiration. Over six hours, respiratory mechanics, high-resolution computed tomography (HRCT), histological lung injury scores (LIS), and plasma protein biomarkers were assessed. TPP-guided PEEP titration significantly lowered driving pressure and improved compliance compared to fixed low PEEP, suggesting more homogeneous tidal volume distribution. HRCT revealed less collateral injury in the initially non-injured lung in the TPP-guided group. However, histopathological LIS did not differ between groups. Exploratory cytokine profiling showed systemic inflammatory activation - including pro- and anti-inflammatory responses - only in the TPP-guided group. These findings indicate that TPP-guided PEEP titration may optimize ventilation by balancing alveolar recruitment and overdistension in asymmetric ALI, with clear effects on physiological and imaging parameters, but without parallel effects on cytokine responses. Further research is needed to assess its long-term impact and clinical relevance.
Item Description:Veröffentlicht: 14. Oktober 2025
Gesehen am 03.12.2025
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms26209985

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