• Eleni Papoutsi, Konstantinos Gkirgkiris, Vasiliki Tsolaki, Ioannis Andrianopoulos, Konstantinos Pontikis, Katerina Vaporidi, Spyridon Gkoufas, Magdalini Kyriakopoulou, Anna Kyriakoudi, Elisabeth Paramythiotou, Evangelos Kaimakamis, Clementine Bostantzoglou, Militsa Bitzani, Mary Daganou, Vasilios Koulouras, Eumorfia Kondili, Antonia Koutsoukou, Ioanna Dimopoulou, Anastasia Kotanidou, Ilias I Siempos, and Greek REsearch on Treatment of Acute illness (GRETA) Collaborators.
• National and Kapodistrian University of Athens, First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, Athens, Attica, Greece.
• Am. J. Respir. Crit. Care Med. 2024 Oct 10.

RationaleDue to effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age.ObjectiveWe endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (≥80 years), patients.MethodsWe performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor, and 90-day mortality as the dependent variable.FindingsBased on data from 4567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (p=0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and non-survivors significantly changed across the adult lifespan (p<0.01). In both cohorts, a driving pressure threshold of 11 cmH2O was associated with mortality in very old patients.InterpretationData from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.

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