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. 2025 Dec 8:76:154-163.
doi: 10.1016/j.hrtlng.2025.11.024. Online ahead of print.

Short-term effects of positive end-expiratory pressure titration strategies on lung clinical markers in COVID-19: A randomized controlled trial

Wagner Souza Leite  1 , Shirley Lima Campos  2 , Caio César Araújo Morais  3 , Romulo Aquino  4 , Emanuel Fernandes Ferreira da Silva Júnior  1 , Saulo Jose da Costa Feitosa  5 , Marianna De Fátima Araújo De Melo  5 , Débora Sidrônio Caetano  3 , Thayse Neves Santos Silva  5 , Marcelo Brito Passos Amato  6 , Daniella Cunha Brandão  7 , Armele Dornelas de Andrade  7
Affiliations

Short-term effects of positive end-expiratory pressure titration strategies on lung clinical markers in COVID-19: A randomized controlled trial

Wagner Souza Leite et al. Heart Lung. .

Abstract

Background: Severe acute respiratory failure from COVID-19 is associated with high mortality. Optimal positive end-expiratory pressure (PEEP) titration is essential for lung-protective ventilation; however, different strategies may elicit distinct clinical responses.

Objective: To compare the short-term effects of three PEEP titration strategies on lung injury score (LIS), changes in oxygenation, respiratory mechanics, and electrical impedance tomography (EIT) measures in mechanically ventilated patients with COVID-19.

Methods: In this randomized, parallel-group trial, 75 intubated patients were randomly assigned to EIT-guided PEEP (PEEP-EIT), driving pressure-guided PEEP (PEEP-DP), or ARDSNet-based PEEP (PEEP-ARDSNet). Primary outcome was change in lung injury score (LIS); secondary outcomes included PaO₂/FiO₂ ≥ 150 mmHg, PaO₂/FiO₂ response ≥ 20 mmHg, driving pressure reduction, compliance increase, EIT-based regional ventilation and aeration, and adverse events within a four-hour follow-up.

Results: Mean PEEP levels differed across groups: PEEP-EIT (13.3 cmH₂O), PEEP-DP (10.6 cmH₂O), and ARDSNet (12 cmH₂O). PEEP-EIT showed greater LIS reduction (ORweighted 3.7, 1.58 - 8.57; p = 0.004) and higher odds of oxygenation response vs. PEEP-DP (ORweighted 4.2, 2.15 - 8.27; p < 0.01) and PEEP-ARDSNet (ORweighted 3.6, 1.8- 7.1; p < 0.001). Both PEEP-EIT and PEEP-DP significantly improved driving pressure (PEEP-EIT: ORweighted 6.6, 2.6- 17.07; PEEP-DP: ORweighted 7.02, 2.7 - 18.2) and compliance (PEEP-EIT: ORweighted 9.5, 3.7- 24.33; PEEP-DP: ORweighted 5.94, 2.28 - 15.5) compared to PEEP-ARDSNet (p < 0.001 for both comparisons). No adverse events related to PEEP titration were reported.

Conclusion: EIT-guided PEEP titration outperformed ARDSNet and DP-guided strategies in reducing lung injury and improving compliance and oxygenation in patients with COVID-19.

Keywords: COVID-19; Electrical impedance; Mechanical ventilation; Positive end expiratory pressure; Respiratory mechanics.

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Conflict of interest statement

Declaration of competing interest This work was supported by grants from the Federal University of Pernambuco / PROPESQI/ PROPG, CAPES CODE 001, CNPq (SLC and ADA: 403341/2020-5; 421756/2021-7; 306240/2021-1; 303988/2025-8) and FACEPE (SLC and ADA: APQ-0249-4.08/20; APQ 0801-4.08/21; APQ-1020-4.08/25). DCB received grants from PROPG/UFPE (23076.018672/2020-32; 23076.015670/2021-88) and CNPQ (445567/2023-6: Call N°. 21/2023 - Track B- Original and Primary Studies). Neither funding body had any influence over study design, analysis, ormanuscript development at any stage.

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