To the Editor

Electrical impedance tomography (EIT) is increasingly utilized for tailoring positive end-expiratory pressure (PEEP). By non-invasively assessing lung collapse and over-distention [1], EIT helps adjust PEEP to minimize both conditions, assuming they are equally harmful. The EIT-guided PEEP selection approach may potentially provide more lung protection by reducing mechanical power [2].

Although the balance between over-distension and collapse may help individualize PEEP titration, the requirement for specialized EIT equipment limits its widespread application. Furthermore, EIT focuses on morphology without considering PEEP's impact on hemodynamics and ventilation-perfusion matching. Alternatively, PEEP can be titrated by calculating intrapulmonary shunt (Qs/Qt) and dead space (Vd/Vt) using blood gases [3]. High alveolar pressure can cause both lung over-distension (high stress and strain) and pulmonary capillary collapse and subsequently impaired CO₂ elimination (namely functional over-distension). However, whether the calculated Vd/Vt and Qs/Qt are consistent with EIT-derived over-distension and collapse is unclear. In this pilot study, we attempted to compare these PEEP selection approaches.

The experiment protocol was approved by the Animal Care Committee of Fujian Provincial Hospital. The animals were treated in compliance with the hospital's guidelines for the care and utilization of laboratory animals.

Preparation and measurements

Eight male Bama miniatured pigs (weight 40.1 to 58.0 kg) were anesthetized with 10 mg·kg^–1·h^–1 pentobarbital. Rocuronium bromide boluses of 0.5 mg·kg^–1 were administered as needed to suppress spontaneous breathing. After tracheotomy, mechanical ventilation was initiated. A catheter in the right carotid artery enabled blood pressure monitoring and gas sampling. A Swan-Ganz catheter, inserted via the internal jugular vein, facilitated mixed venous blood sampling and hemodynamic measurements. Mixed expired CO₂ (PeCO₂) was measured via a mainstream PeCO₂ module. Vital signs and cardiac output (via thermodilution) were monitored. Collapse and over-distension were determined using EIT (PulmoVista 500, Dräger, Germany) at the 4th–5th intercostal space, with thresholds previously reported [1].

Experiment protocol

Lung injury was induced using a 'two-hits' model: surfactant depletion and injurious ventilation [4]. Saline lung lavage (30 ml·kg-1) was repeated until PaO₂/FiO₂ < 100 mmHg for 10 min at PEEP 5 cmH₂O, followed by injurious ventilation for 60 min, with driving pressure/PEEP adjusted every 15 min [4].

After lung recruitment, a decremental PEEP trial (20 to 4 cmH₂O, 2 cmH₂O steps) was conducted. Static compliance, cardiac output, and blood gases were measured at each PEEP level. EIT data were continuously recorded for offline analysis. Pigs were euthanized post-experiment with pentobarbital overdose. Qs/Qt and Vd/Vt were calculated using established formulas (5). 'Optimal' PEEPs were determined by three methods: minimal sum of Vd/Vt and Qs/Qt, maximal compliance, and minimal sum of EIT-measured over-distension and collapse. The lower PEEP was selected in case of a tie.

As PEEP decreased, collapse and Qs/Qt increased in parallel. PaO₂ exhibited a non-linear relationship with PEEP changes and did not correlate strongly with collapse (Fig. 1A). As PEEP was reduced, over-distension decreased, while Vd/Vt increased (Fig. 1B). Lung compliance peaked at PEEP of 16 cmH₂O, while the sum of collapse and over-distension was minimized at PEEP of 18 cmH₂O (Fig. 1C). Blood pressure and cardiac output increased following the decrement of PEEP (Fig. 1D). At the individual level, 'Optimal' PEEP values varied among the three approaches. The EIT-guided approach and Vd/Vt + Qs/Qt method based on blood gas analysis showed discrepancies in PEEP values for all animals. However, when comparing the EIT-guided approach with the best compliance method, two animals exhibited identical PEEP values, while differences remained in others (Fig. 1E). End-of-experiment lung pathology showed no differences among animals (Fig. 1F).

Panel A: Showing the change of intrapulmonary shunt (Qs/Qt), PaO₂, and collapse (CL) in response to the decrement of positive end-expiratory pressure (PEEP). Intrapulmonary shunt (Qs/Qt) and collapse (CL) were displayed on the left y-axis, while PaO₂ was displayed on the right y-axis. The trend indicates an increase in both Qs/Qt and CL with the decrement of PEEP, and the trend correlated well between Qs/Qt and CL. PaO₂ demonstrated a biphasic response, initially ascending, followed by a subsequent decline. Panel B: Showing the change of arterial CO₂ partial pressure (PaCO₂), mixed expired CO₂ partial pressure (PeCO₂), dead space (Vd/Vt), over-distension (OD) in response to the decrement of PEEP. Vd/Vt and OD were displayed on the left y-axis, while PaCO₂ and PeCO₂ were displayed on the right y-axis. As PEEP decreased, the gap between PaCO₂ and PeCO₂ increased, resulting in an increasing Vd/Vt. In contrast, OD decreased following the decrement of PEEP. Panel C: CL and OD were plotted on the same graph, both displayed on the left y-axis, to illustrate the trend of their sum, which exhibited a U-shaped trend. Additionally, Qs/Qt and Vd/Vt were also plotted on the left y-axis. The right y-axis shows the changes in compliance (Crs), which demonstrated an inverse U-shaped trend. Panel D: Cardiac output (CO) and mean arterial pressure (MAP) gradually increased as PEEP decreased. Panel E: 'Optimal' PEEP selected by EIT (minimal sum of CL and OD, circle), minimal Vd/Vt + Qs/Qt (square), and the best Crs (diamond). The selected PEEP levels by the three approaches exhibited notable discrepancies. Panel F: Showing the lung injury scores at the end of the experiment for each animal. For each animal, six non-overlapping fields were collected and averaged. Briefly, hematoxylin and eosin–stained sections were analyzed for neutrophil infiltration, airway epithelial cell damage, interstitial edema, hyaline membrane formation, hemorrhage, and the total lung injury score as the sum of these criteria. Each criterion was scored on a scale of 0–4, where 0 = normal, 1 = minimal change, 2 = mild change, 3 = moderate change, and 4 = severe change. There were no significant differences in lung injury scores among the animals (p = 0.378)

Full size image

In this pilot experiment, we compared blood-gas-based PEEP titration with EIT to balance over-distension and collapse. Qs/Qt effectively evaluated collapsed tissue without EIT. In contrast, dead space was not effective in detecting over-distension. A notable discrepancy existed between PEEP titration approaches.

Pulmonary gas exchange depends not only on ventilation but also on matching the blood flow. High PEEP affects hemodynamics, lung perfusion, and ventilation-perfusion matching. Blood-gas-analysis-derived over-distension results from both "true" and "functional" over-distension (5). We found that Qs/Qt + Vd/Vt derived PEEP was occasionally higher than EIT-derived PEEP, contrary to expectations. While individual animals showed variable optimal PEEP values across methods, averaged data indicated a consistent range of 16–18 cmH₂O. This highlights individual heterogeneity, suggesting that averaged data may mask crucial individual differences. These findings underscore the importance of considering multiple parameters and personalizing PEEP settings.

This study has some limitations. It's a small, non-randomized pilot study. Second, we used the Enghoff formula to calculate dead space, which includes the shunt effect. PEEP can simultaneously affect true dead space and shunt oppositely, while we assumed minimal shunt effect at high PEEP. Additionally, we didn't compare injury degree (histological, biomarkers) from different PEEP approaches.

In conclusion, morphology-based and blood gas-based approaches yielded different optimal PEEP levels. The impact of these varying approaches on lung injury warrants further study.

No datasets were generated or analysed during the current study.

CL:

Collapse

CO:

Cardiac output

CO₂ :

Carbon dioxide

Crs:

Compliance of respiratory system

EIT:

Electrical impedance tomography

FiO₂ :

Fraction of inspired oxygen

MAP:

Mean arterial pressure

OD:

Over-distension

PaCO₂ :

Arterial CO₂ partial pressure

PaO₂ :

Partial pressure of arterial oxygen

PeCO₂ :

Mixed expired CO₂ partial pressure

PEEP:

Positive end-expiratory pressure

Qs/Qt:

Intrapulmonary shunt

Vd/Vt:

Dead space

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HC is supported by the Youth Top Talent Project of Fujian Provincial Foal Eagle Program. The funding bodies had no role in the study design, data collection, analysis, interpretation, or manuscript writing.

Authors and Affiliations

1. Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital Affiliated to Fuzhou University, Fujian Provincial Center for Critical Care Medicine, Fujian Provincial Key Laboratory of Critical Care Medicine, Dongjie 134, Gulou District, Fuzhou, Fujian, China

   Han Chen

2. Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Japan

   Takeshi Yoshida

3. Beijing Shijitan Hospital, Capital Medical University, Beijing, China

   Jian-Xin Zhou

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Contributions

HC, TY, and JXZ conceived and designed the study. HC performed the experiments and data collection. HC and TY performed data analysis and interpretation. HC prepared the initial draft of the manuscript. All authors reviewed, contributed to, and approved the article’s final version. The corresponding author ultimately submitted the manuscript for publication.

Corresponding author

Correspondence to Han Chen.

Ethics approval and consent to participate

The experiment protocol was approved by the Animal Care Committee of Fujian Provincial Hospital. The animals were treated in compliance with the hospital's guidelines for the care and utilization of laboratory animals.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Chen, H., Yoshida, T. & Zhou, JX. Comparison of electrical impedance tomography, blood gas analysis, and respiratory mechanics for positive end-expiratory pressure titration. Crit Care 28, 341 (2024). https://doi.org/10.1186/s13054-024-05137-1

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• Received: 09 September 2024

• Accepted: 18 October 2024

• Published: 22 October 2024

• DOI: https://doi.org/10.1186/s13054-024-05137-1

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