What links ventilator driving pressure with survival in the acute respiratory distress syndrome? A computational study

BACKGROUND: Recent analyses of patient data in acute respiratory distress syndrome (ARDS) showed that a lower ventilator driving pressure was associated with reduced relative risk of mortality. These findings await full validation in prospective clinical trials. METHODS: To investigate the association between driving pressures and ventilator induced lung injury (VILI), we calibrated a high fidelity computational simulator of cardiopulmonary pathophysiology against a clinical dataset, capturing the responses to changes in mechanical ventilation of 25 adult ARDS patients. Each of these in silico patients was subjected to the same range of values of driving pressure and positive end expiratory pressure (PEEP) used in the previous analyses of clinical trial data. The resulting effects on several physiological variables and proposed indices of VILI were computed and compared with data relating ventilator settings with relative risk of death. RESULTS: Three VILI indices: dynamic strain, mechanical power and tidal recruitment, showed a strong correlation with the reported relative risk of death across all ranges of driving pressures and PEEP. Other variables, such as alveolar pressure, oxygen delivery and lung compliance, correlated poorly with the data on relative risk of death. CONCLUSIONS: Our results suggest a credible mechanistic explanation for the proposed association between driving pressure and relative risk of death. While dynamic strain and tidal recruitment are difficult to measure routinely in patients, the easily computed VILI indicator known as mechanical power also showed a strong correlation with mortality risk, highlighting its potential usefulness in designing more protective ventilation strategies for this patient group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-0990-5) contains supplementary material, which is available to authorized users.