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

Abstract

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.

Figure 1.

Analysis of the physiologic signals. Flow, volume, airway opening pressure (Pao), esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), and transpulmonary pressure (PL,dyn) during the first 30 s of an hour of recordings. An end-expiratory occlusion was administered at the arrow to confirm adequate positioning and filling of the catheter. The asterisks mark the maximal volume, Pdi, and P_L identified by the script in each breath, respectively, whereas the circles mark the minimal values. The delta in each breath was calculated as maximum–minimum (dynamic pressures).

Figure 2.

Titration algorithm. An increase in tidal volume greater than 2 mL/kg predicted bodyweight compared with a subject’s own baseline was also considered a breach of lung-protective ventilation. Pdi = transdiaphragmatic pressure, Pplat = plateau airway pressure, RR = respiratory rate, Vt = tidal volume.

Figure 3.

Proportion of breaths in diaphragm-protective range, defined as 3–12 cm H₂O per breath, in each group. Dots represent the mean; bars represent the se of the mean; asterisks represent the hours with a significant difference between the groups in the post hoc analysis. Shaded area represents the 95% CI obtained with Loess regression.

Figure 4.

Tidal volume (A), dynamic transpulmonary pressures (B)‚ and transpulmonary driving pressures (C) over time. Dots represent the mean; bars represent the sem. None of the hours differed significantly between both groups in the post hoc analysis.