American Journal of Respiratory and Critical Care Medicine

To the Editor:

We read with interest the manuscript by Costa and colleagues (1) showing that the combination of driving pressure and respiratory rate is significantly associated with mortality in patients with acute respiratory distress syndrome. Their analysis suggests that a simplified composite variable (driving pressure multiplied by four plus respiratory rate [4DPRR]) is as informative as the more comprehensive equation of mechanical power. Although we are delighted to see that respiratory rate, long neglected, has finally been considered (better late than never) as an essential determinant of ventilator-induced lung injury (VILI), we believe that some conceptual and methodological considerations need to be highlighted.

First, it is essential to make a clear distinction between a parsimonious epidemiological model that includes ventilatory variables associated with mortality and the more VILI-relevant physical concept of total energy transferred during mechanical ventilation—expressed as mechanical power (2). Regarding the latter, all elements of the ventilator’s settings, including positive end-expiratory pressure (PEEP), should be included because all contribute to the total mechanical energy (3). Mechanical power is not intended to be the “unifying theoretical explanation” of VILI, but it is a more physiological way to summarize the physical contributions of the ventilator settings expressed in meaningful and understandable physical units (J/min) (2).

Although 4DPRR may help estimate the average trade-off between driving pressure and respiratory rate under purely theoretical isocapnic conditions, it is a population-associated statistical measure based entirely on the effect size derived from a mediation analysis; it does not describe a physical quantity or encapsulate total mechanical energy. Indeed, its 4:1 ratio may not apply under all conditions (e.g., when PEEP achieves lung recruitment, increases lung homogeneity, or alters dead space). The mechanical effects of PEEP on mortality hazard may be more complex. Indeed, although PEEP’s effect on total lung stress and strain will depend on multiple factors (e.g., baseline compliance, recruitability, and lung homogeneity), its amount is not indifferent to the outcome because PEEP can influence driving pressure (for a given Vt) and dead space (and can indirectly influence the respiratory rate) as well as acting independently as a key component of the total mechanical energy delivered.

The relevance of PEEP in determining total stress and strain of the respiratory system is, in one sense, intuitive: omitting PEEP from a calculation of energy would imply that applying 30 cm H2O of PEEP to an individual patient adds no risk of VILI or other adverse outcomes. On the contrary, it is clear from the univariate, population-based models presented by Costa and colleagues (1) that PEEP, the static elastic component of mechanical power and of total power, impacts mortality with an effect size of similar magnitude as respiratory rate and driving pressure. There are not sufficient data available to fully elucidate the effect of PEEP on outcome, but there is already evidence—some from the same authors—that mechanical power is associated to outcome in the same populations (4).

Second, the simplicity of the bedside calculation of 4DPRR is not superior to the simplicity of the bedside calculation of mechanical power through simplified formulas (5). In addition, the 4DPRR formulation obscures the conceptual understanding of the delivered mechanical energy. Therefore, we argue that moving from the physical and physiological model of mechanical power to a contrived expression based on statistical models devoid of direct physical meaning may be a retrograde step.

1. Costa ELV, Slutsky AS, Brochard LJ, Brower R, Serpa-Neto A, Cavalcanti AB, et al. Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2021;204:303311.
2. Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, et al. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med 2016;42:15671575.
3. Collino F, Rapetti F, Vasques F, Maiolo G, Tonetti T, Romitti F, et al. Positive end-expiratory pressure and mechanical power. Anesthesiology 2019;130:119130.
4. Serpa Neto A, Deliberato RO, Johnson AEW, Bos LD, Amorim P, Pereira SM, et al.; PROVE Network Investigators. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med 2018;44:19141922.
5. Chiumello D, Gotti M, Guanziroli M, Formenti P, Umbrello M, Pasticci I, et al. Bedside calculation of mechanical power during volume- and pressure-controlled mechanical ventilation. Crit Care 2020;24:417.
*Corresponding author (e-mail: ).

Originally Published in Press as DOI: 10.1164/rccm.202104-0923LE on June 3, 2021

Author disclosures are available with the text of this letter at


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American Journal of Respiratory and Critical Care Medicine

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