Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial

Crit Care Med. 2022 Feb 1;50(2):192-203. doi: 10.1097/CCM.0000000000005395.


Objectives: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation.

Design: Randomized clinical trial.

Setting: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands.

Patients: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode.

Interventions: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care.

Measurements and main results: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively.

Conclusions: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Diaphragm / metabolism*
  • Diaphragm / physiopathology
  • Female
  • Humans
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Lung / metabolism*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Respiration, Artificial / methods
  • Respiration, Artificial / standards*
  • Respiration, Artificial / statistics & numerical data
  • Respiratory Insufficiency / epidemiology
  • Respiratory Insufficiency / prevention & control
  • Respiratory Insufficiency / therapy
  • Work of Breathing / drug effects
  • Work of Breathing / physiology*