High vs Low PEEP in Patients With ARDS Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial

Background: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. Research Question: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? Study Design and Methods: Sixteen patients with PaO2/FIO2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. Results: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = −0.85, P < .001; r = −0.75, P < .001; r = −0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = −0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. Interpretation: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. Trial Registration: ClinicalTrials.gov; No.: NCT04241874; URL: www.clinicaltrials.gov