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Positive end-expiratory pressure (PEEP) has been interwoven with acute respiratory distress syndrome (ARDS) since its first description by Ashbaugh et al. [1].Thereafter, the potentially competing effects of PEEP on lung volume, gas-exchange, and hemodynamics were quickly recognized, prompting the first proposals for methods to optimize PEEP in the clinical setting.Eight years after the term ARDS was minted, a seminal study by Suter et al. [2] defined "optimal PEEP" as the value associated with best respiratory compliance.That level was associated with the best oxygen delivery and dead space reduction, even though PaO 2 continued to increase at PEEP levels higher than the compliance-defined optimum.This thoughtful approach was based not only on arterial "oxygenation", but also on hemodynamics and respiratory mechanics.Subsequent research regarding "best PEEP" has resembled the search for the "Holy Grail", and has developed sequentially along three main lines: oxygenation, lung mechanics, and clinical trials (Fig. 1).

In search of the Holy Grail: identifying the best PEEP in ventilated patients