ARDSに対する肺保護換気は一般的になっており、日本のARDS診療ガイドライン2021でも一回換気量を4〜8 mL/kgに制限することが推奨されています。ただ4 mL/kgの超低容量換気では呼吸性アシドーシスが問題となり、呼吸数を増やして対応するもののmechanical powerの変化が気になっていました。個人的には6〜8 mL/kg程度で管理することが多いです。
今回は、COVID-19関連ARDSに対する超低容量換気（ULTV）の効果をみた、フランスの多施設共同オープンラベルRCT（VT4COVID）の結果です。
Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial
Richard JC, Terzi N, Yonis H, et al. published online ahead of print, 2023 Jul 12. Lancet Respir Med. 2023;S2213-2600(23)00221-7.
Background: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS.
Methods: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618.
Findings: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004).
Interpretation: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS.
PMID: 37453445
6 mL/kgの対照群と比較してULTVでは主要アウトカム（90日死亡と60日VFDの複合アウトカム）に有意差はありませんでした。そして予想通り、重症の呼吸性アシドーシス（pH <7.15かつPaCO2 >45 mmHg）と呼吸数はULTVで多い結果でした。ΔPはULTVで小さいものの、呼吸数の増加で相殺されてmechanical powerには差がないようです。
mechanical powerを下げつつ呼吸性アシドーシスに対応するとなるとECO2RによるCO2除去が合理的のように思われますが、RESTの結果（JAMA 2021、Thorax 2022）から考えるとCOVID-19でも大きな効果は期待できないかもしれません。