Driving Pressure—The Emperor’s New Clothes*
Although there is a strong physiologic rationale to support the importance of ΔP in mechanically ventilated patients with ARDS, randomized controlled trials designed to manipulate or optimize these variables based on physiologic rationale in the critically ill have been disappointing—high-frequency oscillatory ventilation is a recent example in patients with ARDS (8). Observational studies of interventions are inherently biased by confounding by indication—the promising results in these studies are frequently not replicated in clinical trials. Furthermore, the studies by Villar et al (6) and Amato et al (3) are not observational studies of interventions, but observational studies of physiologic targets. Along with confounding by indication, these types of studies have at least two other major concerns. First, the observation of a physiologic profile in survivors does not mean that an intervention targeted at achieving that profile will reduce mortality. There are numerous examples of observational studies in the critically ill that have identified independent predictors of mortality, such as hypoalbuminemia, anemia, and oxygen delivery, that demonstrated no benefit (or even harm) when manipulated in subsequent randomized controlled trials. Explanations for these results may include: 1) the target is not in the causal pathway or 2) the intervention itself causes harm.
Second, physiologic variables (e.g., VT, Pplat, and PEEP) are interrelated in more complex ways than simple confounding associations—examples of this include mathematical coupling and physiologic coupling. Mathematical coupling occurs because variables are actually derived from each other—ΔP is a linear combination of Pplat and PEEP. Physiologic coupling occurs because the three primary variables (VT, Pplat, and PEEP) modify each other when changed in complicated ways that are unpredictable—and their association itself may be associated with mortality. For instance, a recruitable patient will have experience a reduction in Pplat for a given VT, and that “recruitability” may be what is associated with lower mortality, regardless of how they are managed.
Further refinements to the concept of ΔP, such as transpulmonary ΔP (i.e., the difference between transalveolar pressure at end inspiration and end expiration), may represent a better surrogate for lung stress, as it would exclude any contribution from the chest wall (4, 9).