Impact of ultra-low tidal volume ventilation on 1-year functional outcome in COVID-19 ARDS patients. A long-term follow-up analysis of a randomized controlled trial
Abstract
Ultra-low tidal volume ventilation (ULTV) aims to minimize ventilator-induced lung injury in acute respiratory distress syndrome (ARDS), but is associated with an increase in arterial carbon dioxide (PaCO 2 ). This follow-up study aimed to evaluate whether ULTV impacted long-term pre-specified secondary outcomes in the VT4COVID trial. VT4COVID was an open-label multicenter randomized controlled superiority trial performed in ten French intensive care units. Eligible patients were COVID-19 ARDS patients with arterial oxygen pressure (PaO 2 ) over inspired oxygen fraction (FiO 2 ) ≤ 150 mmHg, randomized to ULTV with tidal volume (VT) 4 mL.kg − 1 predicted body weight (PBW), or low VT ventilation (LTV) with VT 6 mL.kg − 1 PBW. Participants, investigators, and outcome assessors were unblinded to group assignment. The following prespecified secondary outcomes were assessed at day-365: MoCA 5-minute, SF-36 and IES-R scores; mortality at day-365 was added a posteriori as an outcome. Scores were compared between arms with the Mann-Whitney test, and mortality was compared between groups with a Cox proportional-hazard model. All analyses (except mortality at day-365) were conducted according to a modified intention-to-treat principle. Two hundred and fifteen patients were randomized to ULTV ( n = 106) or LTV ( n = 109) between April,2020 and April,2021. Seven patients were lost to follow-up and 34 surviving patients had missing data for at least one score. Mortality at day-365 was not significantly different between ULTV and LTV arms (47/102 [46%] vs. 44/106 [42%], hazard ratio 1.19 (95% confidence interval (CI 95% ):0.79–1.80)). The other secondary outcomes were evaluated in 39/55 [71%] and 44/62 [71%] patients in the ULTV and LTV arm, respectively. The MoCA 5-minute score was significantly lower in the ULTV arm (median difference: -2 [CI 95% :-4–0] points, p < 0.05). There was no significant difference in SF-36 and IES-R scores between groups. In a post-hoc analysis, MoCA 5-minute score was significantly associated with area under curve (AUC) or maximal PaCO 2 during ARDS management ( p < 0.01), but not with AUC or minimal PaO 2 . ULTV is associated with a small but significant decrease in cognitive status at day-365 possibly related to exposure to higher PaCO 2 . The trial was prospectively registered with ClinicalTrials.gov (NCT04349618) on April 16, 2020.
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BibTeX
@article{richard2026impact,
title = {{Impact of ultra-low tidal volume ventilation on 1-year functional outcome in COVID-19 ARDS patients. A long-term follow-up analysis of a randomized controlled trial}},
author = {Jean-Christophe Richard and Fatima Chorfa and Nicolas Terzi and Hodane Yonis and Florent Wallet and Claire Dupuis and Laurent Argaud and Bertrand Delannoy and Guillaume Thiery and Gaël Bourdin and Thomas Rimmele and Michel Muller and Florian Sigaud and Guillaume Rigault and Emilie Joffredo and Mehdi Mezidi and Bertrand Souweine and Loredana Baboi and Hassan Serrier and Muriel Rabilloud and Laurent Bitker},
journal = {Critical Care},
year = {2026},
month = jul,
doi = {10.1186/s13054-026-06195-3},
url = {https://hal.science/hal-05751757v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Impact of ultra-low tidal volume ventilation on 1-year functional outcome in COVID-19 ARDS patients. A long-term follow-up analysis of a randomized controlled trial
AU - Jean-Christophe Richard
AU - Fatima Chorfa
AU - Nicolas Terzi
AU - Hodane Yonis
AU - Florent Wallet
AU - Claire Dupuis
AU - Laurent Argaud
AU - Bertrand Delannoy
AU - Guillaume Thiery
AU - Gaël Bourdin
AU - Thomas Rimmele
AU - Michel Muller
AU - Florian Sigaud
AU - Guillaume Rigault
AU - Emilie Joffredo
AU - Mehdi Mezidi
AU - Bertrand Souweine
AU - Loredana Baboi
AU - Hassan Serrier
AU - Muriel Rabilloud
AU - Laurent Bitker
PY - 2026
DA - 2026/07/14
JO - Critical Care
DO - 10.1186/s13054-026-06195-3
UR - https://hal.science/hal-05751757v1
AB - Ultra-low tidal volume ventilation (ULTV) aims to minimize ventilator-induced lung injury in acute respiratory distress syndrome (ARDS), but is associated with an increase in arterial carbon dioxide (PaCO 2 ). This follow-up study aimed to evaluate whether ULTV impacted long-term pre-specified secondary outcomes in the VT4COVID trial. VT4COVID was an open-label multicenter randomized controlled superiority trial performed in ten French intensive care units. Eligible patients were COVID-19 ARDS patients with arterial oxygen pressure (PaO 2 ) over inspired oxygen fraction (FiO 2 ) ≤ 150 mmHg, randomized to ULTV with tidal volume (VT) 4 mL.kg − 1 predicted body weight (PBW), or low VT ventilation (LTV) with VT 6 mL.kg − 1 PBW. Participants, investigators, and outcome assessors were unblinded to group assignment. The following prespecified secondary outcomes were assessed at day-365: MoCA 5-minute, SF-36 and IES-R scores; mortality at day-365 was added a posteriori as an outcome. Scores were compared between arms with the Mann-Whitney test, and mortality was compared between groups with a Cox proportional-hazard model. All analyses (except mortality at day-365) were conducted according to a modified intention-to-treat principle. Two hundred and fifteen patients were randomized to ULTV ( n = 106) or LTV ( n = 109) between April,2020 and April,2021. Seven patients were lost to follow-up and 34 surviving patients had missing data for at least one score. Mortality at day-365 was not significantly different between ULTV and LTV arms (47/102 [46%] vs. 44/106 [42%], hazard ratio 1.19 (95% confidence interval (CI 95% ):0.79–1.80)). The other secondary outcomes were evaluated in 39/55 [71%] and 44/62 [71%] patients in the ULTV and LTV arm, respectively. The MoCA 5-minute score was significantly lower in the ULTV arm (median difference: -2 [CI 95% :-4–0] points, p < 0.05). There was no significant difference in SF-36 and IES-R scores between groups. In a post-hoc analysis, MoCA 5-minute score was significantly associated with area under curve (AUC) or maximal PaCO 2 during ARDS management ( p < 0.01), but not with AUC or minimal PaO 2 . ULTV is associated with a small but significant decrease in cognitive status at day-365 possibly related to exposure to higher PaCO 2 . The trial was prospectively registered with ClinicalTrials.gov (NCT04349618) on April 16, 2020.
SN - 1364-8535
SN - 1466-609X
ER -