Effects of Protective Ventilation with Lung Expansion versus Permissive Atelectasis on Pulmonary Inflammation and Mechanical Power of Ventilation in an Experimental Model of Acute Lung Injury

Background: The energy transferred from the mechanical ventilator to the respiratory system over time, so-called mechanical power, may cause lung injury even with protective ventilation. We hypothesized that protective ventilation aiming at moderate lung expansion results in less mechanical power and lung injury than aiming at permissive atelectasis or maximum lung expansion. Methods: Twenty-four anesthetized pigs with acute lung injury induced by saline lung lavage were randomly assigned to ventilation according to either Acute Respiratory Distress Syndrome Clinical Network´s low positive end-expiratory pressure (PEEP) table (LowPEEP), or high PEEP table (HighPEEP), or Open Lung Approach with PEEP titrated to the highest respiratory system compliance and periodic recruitment maneuvers (OLA) (n=8/group). Mechanical power was calculated from pressure-volume curves, and physiological variables were measured. We assessed pulmonary inflammation as the tissue-normalized uptake rate of 2-deoxy-2-18Ffluoro-D-glucose measured by positron-emission computed tomography (K iS ) and determined the gradient between randomization and 24h thereafter (∆K iS ). Results: The median (IQR) PEEP was 5(0.1), 12(0.2), and 12(0.2) cmH 2 O during LowPEEP, HighPEEP, and OLA, respectively. ΔK iS was higher in LowPEEP than OLA (0.0183±0.0109 vs. 0.0049±0.0088 min -1 ; P=0.024; d=0.47), but did not differ significantly from HighPEEP (0.0080±0.0073 min -1 ; P=0.104; d=0.85). ΔK iS also did not differ between HighPEEP and OLA (P=0.876; d=0.60). The median (IQR) mechanical power in LowPEEP 9.5(1.5) J/min was higher than in HighPEEP 7.5(2.3) J/min; P=0.008; d=4.28 and OLA 6.8(2.1) J/min; P=0.002; d=4.69, but did not statistically differ between HighPEEP and OLA (P=0.886; d=0.199). Mechanical power correlated positively with ΔK iS across groups (ρ=0.425, P=0.038). Conclusions: In this porcine model of acute lung injury, protective ventilation with individualized higher PEEP aiming at lung expansion resulted in less pulmonary inflammation and lower mechanical power compared to protective ventilation with permissive atelectasis. A strategy with higher PEEP but without individualization did not differ significantly from the other two strategies regarding inflammation.