[Lancet Respir Med发表述评]：采用超小潮气量通气进行肺保护：时机尚早

Since 2000, following the publication of the ARMA study,¹ low tidal volume (V_T) ventilation (LTV) has been the standard of care for patients with acute respiratory distress syndrome (ARDS). LTV often refers to ventilation with V_T of 6·0 mL/kg predicted bodyweight, based on what was compared in the landmark ARMA study (ventilation with V_T of 6·0 mL/kg vs 12·0 mL/kg predicted bodyweight resulting in a mortality rate of 31% vs 40%). Several—mostly observational—studies have since confirmed the benefits of ventilation with V_T of 6·0 mL/kg predicted bodyweight, including in invasively ventilated patients with COVID-19.²

Should V_T always be as low as 6·0 mL/kg predicted bodyweight? In medicine, there is never a strategy that is applicable to all patients, and this rule also applies to V_T. Notably, in the ARMA study, ventilation with a V_T up to 8·0 mL/kg predicted bodyweight was allowed with LTV. Additionally, most patients in this study were deeply sedated and paralysed, which is important for two reasons. First, maintaining V_T as low as 6·0 mL/kg predicted bodyweight in spontaneously breathing patients is difficult, if not impossible. Second, passive patients might benefit from ventilation with low V_T more than active patients because an inactive diaphragm leads to further atelectasis, which reduces end-expiratory lung volume and consequently increases the risk of volutrauma.

In the past 10 years, it became clear that V_T should be titrated to the functioning size of the lung. Several observational studies have shown that low driving pressure, the resultant of applied V_T and the functioning size of lung, has a strong association with outcome even when periods of high driving pressure are short.³ A post-hoc analysis of the Xtravent study⁴ suggested a benefit of a reduction of V_T to 3·0 mL/kg predicted bodyweight in patients with severe ARDS, albeit this strategy required extracorporeal CO₂ removal to prevent severe respiratory acidosis.

In The Lancet Respiratory Medicine, Jean-Christophe Richard and colleagues⁵ report on a randomised trial that compared ultra-low V_T ventilation ([ULTV] 4·0 mL/kg predicted bodyweight; without extracorporeal CO₂ removal) with LTV (6·0 mL/kg predicted bodyweight) in patients with COVID-19-related ARDS.⁵ ULTV resulted in a significant reduction in marginal mean V_T (4·9 mL/kg predicted bodyweight [SE 0·1] vs 6·2 mL/kg predicted bodyweight [0·1]; p<0·0001) and driving pressure (9·7 cm H₂O [SE 0·3] vs 11·4 cm H₂O [0·3]; p<0·0001). However, there was no difference in the primary outcome (win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38), a composite of death at day 90 and ventilator-free days at day 60. The rate of severe respiratory acidosis was higher in patients receiving ULTV (absolute difference 20% [95% CI 9 to 31]; p=0·0004).

Should Richard and colleagues conclude that ULTV is not beneficial? Is a V_T of 6·0 mL/kg predicted bodyweight sufficiently low or was driving pressure in this study already sufficiently low, and a reduction of less than 6·0 mL/kg predicted bodyweight had no added value? Does ULTV not improve outcomes in patients with COVID-19, even if it is questionable whether this type of ARDS differs from other types of ARDS?⁶

Not so fast; maybe ULTV improves outcomes, but we should take more care of the respiratory rate. Studies from 2018 and 2020 have shown associations of mechanical power with outcome.^3,  7 Mechanical power is mostly driven by V_T, driving pressure, and respiratory rate. One study published in 2021 even suggested that with use of a low V_T, mechanical power is only dependent on driving pressure and respiratory rate.⁸ In the study by Richard and colleagues, mechanical power was slightly, but non-significantly, lower with ultra-low V_T ventilation than with LTV (21·9 J/min vs 23·8 J/min), probably because clinicians chose a higher respiratory rate to compensate for the reduction in minute ventilation (29 breaths per min vs 25 breaths per min). Could the higher respiratory rate have nulified the potential benefit of ultra-low V_T?

Here, we want to cite a randomised trial published in 1998, 2 years before the ARMA study.⁹ In this study, a so-called protective ventilation strategy consisting of ventilation with a V_T 6·0 mL/kg predicted bodyweight, titrated positive-end expiratory pressure (PEEP) with driving pressure less than 20 cm H₂O, and permissive hypercapnia compared with a conventional strategy consisting of ventilation with a V_T 12·0 of mL/kg predicted bodyweight, the lowest PEEP for acceptable oxygenation, and normal arterial CO₂concentration resulted in markedly reduced mortality, improved liberation of ventilation, and less barotrauma. The impressive outcome benefit of this protective strategy might not be explained by higher PEEP,¹⁰ but the combination of a lower V_T and permissive hypercapnia resulting in a lower respiratory rate.

However, Richard and colleagues showed that ULTV resulted in higher CO₂ levels (55·7 Torr vs 46·0 Torr), so they used permissive hypercapnia? However, arterial pH was not different between the groups and higher CO₂ concentrations were maybe required. Additionally, ventilation with low V_T combined with high respiratory rate might only be beneficial in patients with ARDS and a very low compliance (ie, when a higher V_T greatly increases the driving pressure).⁸ Whereas in patients with a relative normal compliance, ventilation with low V_T combined with high respiratory rate could be harmful, because it greatly increases the mechanical power.

In conclusion, ventilation is a complex intervention and in the right context, personalised titrations of V_T and respiratory rate are crucial (figure). New studies are needed with the best combination of V_T and respiratory rate, maybe by using driving pressure and mechanical power as targets. As a start, clinicians could consider accepting a higher arterial CO₂ or low pH level more often.