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
In brief
Ultra-low tidal volume ventilation lowers 1-year cognitive score by about 2 points
In a randomized trial of COVID-19 ARDS patients, those ventilated with 4 mL/kg tidal volumes scored roughly two points less on a 5-minute cognitive test at one year compared with 6 mL/kg ventilation, while mortality and quality-of-life measures were similar. The modest cognitive decline appears linked to higher carbon dioxide levels during ventilation, raising questions about the trade-off between lung protection and brain outcomes.
- Journal
- Critical care (London, England) (Q1)
- Published
- 14 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jean-Christophe Richard, Fatima Chorfa, Nicolas Terzi, Hodane Yonis, Florent Wallet, Claire Dupuis, et al.
- PMID
- 42449426
- DOI
- 10.1186/s13054-026-06195-3
Why clinicians should know about it
- Picked for Pulmonary and Respiratory Medicine (paper of the day, 16 July 2026).
Abstract
BACKGROUND: 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 (PaCO2). This follow-up study aimed to evaluate whether ULTV impacted long-term pre-specified secondary outcomes in the VT4COVID trial. METHODS: 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 (PaO2) over inspired oxygen fraction (FiO2) ≤ 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. RESULTS: 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 (CI95%):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 [CI95%:-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 PaCO2 during ARDS management (p < 0.01), but not with AUC or minimal PaO2. CONCLUSIONS: ULTV is associated with a small but significant decrease in cognitive status at day-365 possibly related to exposure to higher PaCO2. TRIAL REGISTRATION: The trial was prospectively registered with ClinicalTrials.gov (NCT04349618) on April 16, 2020.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.