By Elaine Chen, MD
Assistant Professor,
Department of Internal Medicine,
Division of Pulmonary and Critical Care Medicine,
Section of Palliative Medicine,
Rush University Medical Center,
Chicago, IL

Dr. Chen reports no financial relationships relevant to this field of study.

SYNOPSIS: Statistical models were applied to several large trials of ARDS patients undergoing lung protective ventilation strategies and found that decreases in driving pressure, or ΔP, were strongly associated with increased survival.

SOURCE: Amato MBP, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015;372:747-755.

Lung protective ventilation strategies, such as limiting plateau pressures, lowering tidal volumes, and optimizing positive end-expiratory pressures (PEEP), have been shown through multiple large, randomized clinical trials to have significant mortality benefit in patients with acute respiratory distress syndrome (ARDS). Often, lung protective strategies may optimize one parameter at the expense of another. With a common goal of minimizing ventilator-induced lung injury, trials have not consistently shown which component of the strategies most strongly improves survival.

The authors define driving pressure (ΔP) as the ratio of tidal volume to respiratory system compliance (VT/CRS) and use this ratio as an index to indicate the “functional” size of the lung. They hypothesize that ΔP better predicts outcome than VT alone.

Survival prediction models were developed using advanced statistical techniques, including forward and backward stepwise multivariate analysis and multilevel mediation analysis, and were applied to 3562 patients from nine randomized trials of lung protective ventilation strategies. Patients showing significant ventilatory effort (such as those receiving pressure support ventilation or with respiratory rates above set rate) were excluded from the analysis. Models were first developed using four smaller early studies, and refined and retested with patients from larger, more recent trials.

In early models, ΔP was found to predict survival, as well as critical care tools such as APACHE and SAPS. In follow-up models, higher ΔP consistently predicted lower survival across trials compared with VT, plateau pressure, and PEEP. The total pooled sample was resampled to match PEEP, ΔP, and plateau pressure. Those with matched PEEP showed increasing mortality with increased plateau pressure (reflecting increasing ΔP); those with matched plateau pressure showed decreasing mortality with increased PEEP (reflecting decreasing ΔP). Those with increasing PEEP and increasing plateau pressure (matched ΔP ) had no difference in mortality.

The authors concluded that survival benefits in trials of low tidal volume ventilation and high PEEP ventilation were proportional to reductions in ΔP rather than the target variable and that ΔP was a critical mediator of the benefits conferred. ΔP served as a surrogate for cyclic lung strain on preserved lung units, and ventilator changes that led to decreases in ΔP were associated with improved survival.

COMMENTARY

In the years since the advent of low tidal volume ventilation and lung protective ventilation for ARDS, the concepts have been widely studied and nearly universally applied, with varying rates of adherence. As evidence has grown in support of lung protective ventilation, its cited benefits of improving outcomes have broadened beyond ARDS to all critically ill patients as well as surgical populations. We believe that, in general, smaller tidal volumes and decreased lung stretch are associated with less ventilator induced lung injury. However, are there patient populations for whom this does not apply?

This study immediately excludes all patients with spontaneous breathing effort, as measurements of pressure and compliance are difficult to interpret in these patients. Association does not imply causation, and the authors note this. There are no clinical practice implications as a result of this study, since ΔP as defined in this study is measured and not applied, and this study is limited to statistical analysis of pooled data from prior studies.

The results of this study may help providers assess whether ventilator changes might affect their patients’ survival. If following lung protective strategies leads to decreases in ΔP, we might surmise that we are improving our patients’ chances of survival. Overall, this study reflects that stiffer or smaller lungs belong to sicker patients who are more likely to die. This study challenges strict adherence to lung protective ventilation strategies in patients who do not respond favorably, but prospective trials are needed to further determine benefits of changes in ΔP.