“Established” Respiratory Treatment in Acute Respiratory Distress Syndrome: Scientific Rigor or a Square Peg in a Round Hole?

To the Editor:

Dr. Hardin, in his editorial (1), surmises that there is nothing new under the sun, particularly that established ventilatory approaches should also be applied to coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS) (C-ARDS). We know of only two trials in unselected (“average”) ARDS that provide significant results: one establishing that 6 ml/kg is better than 12 ml/kg and the other establishing that positive end-expiratory pressure (PEEP) higher than 15 cm H₂O increases mortality. Further advances in ARDS treatment were only proved or suggested in subgroups: prone position if Pa_O2/Fi_O2 ratio is below 150 mm Hg and higher PEEP in hyperinflammatory phenotypes. Therefore, subgroups deviate from the average ARDS behavior and require modification of standard management.

Like many, we are not so certain that all patients benefit from 6 ml/kg predicted body weight Vt—or tolerate the suggested entries of a PEEP–Fi_O2 table. Outcomes from intermediate Vt may be, on average, equivalent to a lower Vt (2). Many clinicians seem to have already figured this out; Vt in all groups of the Panwar study (3) was set in the 7–8 ml/kg range, which is similar to those in the quoted article by Hager and colleagues (4).

Lung protection is linked to repetitive excessive “strain;” consequently, Vt is ideally set individually in relation to gas volume or compliance (i.e., driving pressure) rather than predicted body weight. In patients with relatively preserved lung gas volumes (e.g., many with early-stage COVID-19), very low Vts may lead to dyspnea or asynchronies, adversely affecting the outcome. Conversely, even Vt of 6 ml/kg may be excessive for some patients with very severe ARDS. In this context, it does not seem a paradox that in LUNG-SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure), patients with better compliance had a larger Vt, and we do not think it reasonable to presume that these patients would have necessarily benefited from lower Vt (1).

Just as one Vt does not translate into the same strain, a higher PEEP may improve oxygenation and outcome (i.e., if there is extensive recruitable lung tissue), or overstretch compliant airspaces.

That some small minority of patients with broadly defined ARDS might be found that resemble some stage of the evolving C-ARDS physiology is hardly surprising. What is different, however, is that unexpectedly high gas volumes and compliance occur routinely despite infiltrates and impressive hypoxemia in the early stages of C-ARDS (5). Therefore, why infer that considering respiratory mechanics and recruitability when choosing Vt and PEEP is somehow heretical, advocating a strategy “the same as it ever was”? Patients with C-ARDS are not your “average” ARDS.