Lung- and diaphragm-protective strategies in acute respiratory failure: an in silico trial

Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO₂R) to achieve LDP targets.

An in silico clinical trial was conducted using a previously published mathematical model of patient-ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO₂R, and using ECCO₂R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets.

After titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73-0.85). Adjunctive ECCO₂R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO₂R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO₂R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30).

In this in silico trial, many patients required ECCO₂R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO₂R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio.