High vs. low PEEP in ARDS patients exhibiting intense inspiratory effort during assisted ventilation: a randomized cross-over trial

BackgroundPEEP can potentially modulate inspiratory effort (ΔPes), which is the major determinant of selfinflicted lung injury. Research questionDoes high PEEP reduce ΔPes in moderate-to-severe ARDS patients on assisted ventilation? Study Design and MethodsSixteen patients with PaO2/FiO2≤200 mmHg and ΔPes≥10 cmH2O underwent a randomized sequence of four ventilator settings: PEEP=5 cmH2O or PEEP=15 cmH2O + synchronous (pressure support ventilation, PSV) or asynchronous (pressure-controlled intermittent mandatory ventilation, PC-IMV) inspiratory assistance.ΔPes, 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. ResultsΔPes was not systematically different at high vs. low PEEP (PSV: median 20 [15-24] cmH2O vs. 15[13-23], p=0.24;PC-IMV: 20 [18-23] vs. 19 [17-25], p=0.67).Similarly, respiratory system and transpulmonary driving pressure, 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 and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance, respectively (r=-0.85,p<0.001; r=-0.75, p<0.001; r=-0.80,p<0.001, 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=0.006).High PEEP caused variable recruitment and systematic redistribution of tidal volume towards dorsal lung regions, thereby reducing dynamic strain in ventral areas (PSV: 0.49 [0.37-0.83] vs. 0.96 [0.62-1.56],p=0.003;PC-IMV: 0.65 [0.42-1.31] vs. 1.14 [0.79-1.52],p=0.002).All results were consistent during synchronous and asynchronous inspiratory assistance. InterpretationThe impact of high PEEP on ΔPes and lung stress is inter-individually variable according to different effects on 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.