Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study

Deniel G, Dhelft F, Lancelot S, Orkisz M, Roux E, Mouton W, Benzerdjeb N, Richard J-C and Bitker L (2024) Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study. Front. Med. 11:1338602. doi: 10.3389/fmed.2024.1338602

Summary:

In this study, the effects of ultra-protective ventilation (UPV) in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) on lung inflammation were compared to conventional protective ventilation (PV) in an experimental swine model of acute respiratory distress syndrome (ARDS). The hypothesis was that UPV, characterized by very low tidal volumes (VT < 4 mL/kg), would reduce lung inflammation more effectively than PV. The main outcome was assessed using positron emission tomography (PET) with [11C](R)-PK11195 to measure lung inflammation.

Methods:

ARDS was induced in anesthetized and mechanically ventilated pigs by tracheal instillation of chlorhydric acid. The pigs were then randomized to receive either UPV (VT 1 mL/kg, PEEP 20-25 cmH2O, RR 5/min) under VV-ECMO or PV (VT 6 mL/kg, PEEP 28-30 cmH2O, RR 25/min) for 4 hours. PET with [11C](R)-PK11195 and CT imaging were performed to assess lung inflammation and respiratory mechanics.

Results:

1. Experimental ARDS Induction:

ARDS was confirmed by a PaO2/FiO2 ratio < 150 mmHg. The severity of ARDS was similar between groups, but the UPV group exhibited lower plateau pressures and lung elastance.

2. Respiratory Mechanics and CT Parameters:

UPV resulted in significantly lower VT, dynamic strain, mechanical power, and non-aerated lung volume in the posterior regions, with higher total PEEP and end-expiratory lung volume (EELV) compared to PV. UPV also showed less regional non-aerated lung and increased hyperinflation in anterior lung regions.

3. PET Findings:

The primary outcome, regional [11C](R)-PK11195 uptake (BPND), was significantly lower in the UPV group (0.35 [0.20–0.59]) compared to the PV group (1.01 [0.75–1.59], p = 0.01), indicating reduced lung inflammation. This reduction was consistent across all lung regions.

4. Multivariate Analysis:

Regional [11C](R)-PK11195 BPND was independently associated with the interaction of regional tidal hyperinflation and lung compliance, suggesting that lung inflammation is influenced by these factors.

5. mRNA and Pathology Analysis:

The UPV group showed a trend towards lower TSPO mRNA expression in posterior lung regions and significant interaction in IL10 expression, indicating possible M2 macrophage phenotype expression. However, no significant differences were found in other markers or acute lung injury scores.

Conclusion:

In this experimental ARDS model, UPV combined with VV-ECMO significantly decreased regional lung inflammation compared to PV. The findings suggest that ARDS patients treated with VV-ECMO could benefit from UPV strategies to reduce ventilator-induced lung inflammation. Further research is needed to explore the clinical applicability of these findings and the potential for similar benefits in human patients.

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Discussion Questions:

1. What are the potential benefits and drawbacks of implementing UPV strategies in clinical settings for ARDS patients undergoing VV-ECMO, and how can we optimize these protocols to balance lung protection and overall patient outcomes?

2. How can we effectively monitor and manage the potential for hyperinflation and regional lung strain in patients receiving UPV, and what tools or techniques could be developed to enhance bedside assessment of these factors?

3. Given the findings of reduced lung inflammation with UPV in this experimental model, what additional studies or clinical trials are necessary to validate these results in human patients, and what key parameters should be measured to ensure comprehensive evaluation of UPV's effectiveness?

Javier Amador-Castañeda, BHS, RRT, FCCM, CEO

Interprofessional Critical Care Network (ICCN)

Copyright © 2024 Deniel, Dhelft, Lancelot, Orkisz, Roux, Mouton, Benzerdjeb, Richard and Bitker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.