Beyond 6 ml/kg: can we personalize lung-protective ventilation?

Hot off the press: “Effect of Lowering Tidal Volume on Mortality in ARDS Varies with Respiratory System Elastance” by Goligher, Costa, and colleagues. 

The 30,000 foot view:

• This work is predicated on the driving pressure hypothesis, popularized by the landmark paper by Amato and colleagues. In that analysis, driving pressure was the ventilation parameter that best stratified mortality risk, at a cutoff of 15 cm H2O.
  • • As a reminder, driving pressure is defined as Plateau minus PEEP.
• The authors sought to determine if the mortality benefit of low tidal volume ventilation (LTVV) differs based on respiratory system elastance.
  • • As a reminder, elastance is calculated as (Plateau pressure – PEEP)/Tidal volume; it could also be written as Driving Pressure/Tidal Volume. It is the inverse of compliance. 
    • If you need a brush-up on these concepts prior to reading on, check out the Equation of Motion Part 1 and 2.
    • In this study, elastance was normalized to the predicted body weight (PBW). Healthy patients typically have a normalized elastance < 1 cm H2O/(ml/kg).
• This work is a secondary analysis of five ARDS trials that tested high vs low tidal volume strategies. In total, data on over 1,000 patients was analyzed.
• Using Bayesian multivariable logistic regression, the posterior probability that 60-day mortality benefit from LTVV varies with elastance was 93%. 
  • • This model was adjusted for P:F ratio, severity of illness scores, and the mortality rate of the control group of each original study.
    • The posterior probability of absolute risk reduction in mortality at least 5% rose with increasing elastance, from 29% in the “low” elastance (<2 cmH2O/(ml/kg)) group, compared to 82% in the high (>3 cmH2O/(ml/kg)) group.
    • Notably, the mortality benefit of LTVV did not vary with P:F ratio!
• Important limitations of this study include the age of the trials (over 20 years old at this point) and the post-hoc design. 

Putting it into context

What does this mean for 6 ml/kg tidal volumes in ARDS?

• There is consistent (observational) data about the prognostic value of driving pressure. What has been less clear, though, is if it is a reasonable therapeutic target.
• The design of this study suggests a potential causal relationship of LTVV on mortality, dependent on elastance. The easiest way to conceptualize this at the bedside is observing the driving pressure at the current set tidal volume, and making adjustments accordingly.
• Blanket application of a set tidal volume for all ARDS patients, regardless of underlying physiology, probably never made sense. We are overdistending some lungs, and probably being too restrictive in others.
• For some patients, 6 ml/kg may still not be “lung protective” if the delivered tidal volume exceeds the amount of lung available for ventilation. This analysis suggested that a driving pressure > 15 cm H2O (a high elastance situation) should make one consider lowering the tidal volume below 6 ml/kg PBW. 
  • • See the figures below for illustration of this concept. The excess tidal volume delivered would likely cause tidal hyperinflation of the aerated lung, more than any potential recruitment of the atelectatic/flooded alveoli.
• Conversely, a patient with low elastance and driving pressure < 15 may be able to tolerate careful increases in tidal volume. Potential benefits could include decreased dyssynchrony and decreased need for sedation and neuromuscular blockade. 
  • • The authors suggest (and I agree) that as long as the driving pressure is in a safe range, this strategy is supportable, and physiologically rational.

It’s worth emphasizing again that the P:F ratio did not predict response to LTVV. Future intervention trials may be better served by stratifying patients based on driving pressure than P:F ratio.