Effectiveness of Low Volume and Low Pressure in Severe Hypoxemic Patients

Condition(s) studied

Investigational drug(s) / intervention(s)

low tidal volume: Patients ventilated with assist/control modes of mechanical ventilation with tidal volume between 6.0 ml/kg PBW and 8.0 ml/kg PBW with PPLAT ≤ 30 cmH2O, until weaning criteria are met: P/F ratio \> 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 \< 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.

high tidal volume: Patients ventilated with assist/control modes of mechanical ventilation with tidal volume between 8.0 ml/Kg PBW and 10.0 ml/kg PBW with PPLAT ≤ 30 cmH2O, until weaning criteria are met: P/F ratio \> 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 \< 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.

low driving pressure: Patients ventilated with assist/control modes of mechanical ventilation with driving pressure between 7.0 cmH2O and 12.0 cmH2O with VT ≤ 10 ml/kg PBW, until weaning criteria are met: P/F ratio \> 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 \< 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.

high driving pressure: Patients ventilated with assist/control modes of mechanical ventilation with driving pressure between 12.0 cmH2O and 18.0 cmH2O with VT ≤ 10 ml/kg PBW, until weaning criteria are met: P/F ratio \> 250 mmHg; PEEP ≤ 8 cmH2O and lower than the previous day; FiO2 \< 0.5 and lower than the previous day; systolic arterial pressure ≥ 85 mmHg.

Study summary

The present study set up to answer two questions: (a) "how low tidal volume must be to provide protective ventilatory settings able to minimize the risk of death due to Ventilator-Induced Lung Injury (VILI)?"; (b) "if protection from VILI is better achieved by targeting the driving pressure instead of the tidal volume, what is the optimal target for the driving pressure?". Solving these questions is pivotal for clinicians to personalized and precise mechanical ventilation practices to reduce the risk of VILI and avoid unnecessary risks associated to protective ventilatory settings.

Two multicenter emulated target trials will be performed using data collected with the Electronic Health Record MargheritaTre, to investigate the effect of low tidal volumes (6.0 to 8.0 ml/kg PBW vs 8.0 to 10.0 ml/kg PBW) and low driving pressures (7.0-12.0 cmH2O vs 12.0-18.0 cmH2O), respectively. Data will be used to obtain the dose-response curve of lower VT and lower ∆P in mechanically ventilated patients with acute severe hypoxemia.

Eligibility

Primary outcome measure(s)

• ICU all-cause mortality — 14 days from assignment to intervention arm
  All patients will be classified as either alive if "alive at ICU discharge" or dead if "dead at ICU discharge"

Trial sites (1)

Other trials for the same condition