Open lung approach associated with high-frequency oscillatory or low tidal volume mechanical ventilation improves respiratory function and minimizes lung injury in healthy and injured rats.
BACKGROUND
To test the hypothesis that open lung (OL) ventilatory strategies using high-frequency oscillatory ventilation (HFOV) or controlled mechanical ventilation (CMV) compared to CMV with lower positive end-expiratory pressure (PEEP) improve respiratory function while minimizing lung injury as well as systemic inflammation, a prospective randomized study was performed at a university animal laboratory using three different lung conditions.


METHODS
Seventy-eight adult male Wistar rats were randomly assigned to three groups: (1) uninjured (UI), (2) saline washout (SW), and (3) intraperitoneal/intravenous Escherichia coli lipopolysaccharide (LPS)-induced lung injury. Within each group, animals were further randomized to (1) OL with HFOV, (2) OL with CMV with "best" PEEP set according to the minimal static elastance of the respiratory system (BP-CMV), and (3) CMV with low PEEP (LP-CMV). They were then ventilated for 6 hours. HFOV was set with mean airway pressure (PmeanHFOV) at 2 cm H2O above the mean airway pressure recorded at BP-CMV (PmeanBP-CMV) following a recruitment manoeuvre. Six animals served as unventilated controls (C). Gas-exchange, respiratory system mechanics, lung histology, plasma cytokines, as well as cytokines and types I and III procollagen (PCI and PCIII) mRNA expression in lung tissue were measured.


RESULTS
We found that (1) in both SW and LPS, HFOV and BP-CMV improved gas exchange and mechanics with lower lung injury compared to LP-CMV, (2) in SW; HFOV yielded better oxygenation than BP-CMV; (3) in SW, interleukin (IL)-6 mRNA expression was lower during BP-CMV and HFOV compared to LP-CMV, while in LPS inflammatory response was independent of the ventilatory mode; and (4) PCIII mRNA expression decreased in all groups and ventilatory modes, with the decrease being highest in LPS.


CONCLUSIONS
Open lung ventilatory strategies associated with HFOV or BP-CMV improved respiratory function and minimized lung injury compared to LP-CMV. Therefore, HFOV with PmeanHFOV set 2 cm H2O above the PmeanBP-CMV following a recruitment manoeuvre is as beneficial as BP-CMV.
Krebs
Joerg
J
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer, 1-3, 68165 Mannheim, Germany. joerg.krebs@umm.de
Pelosi
Paolo
P
Tsagogiorgas
Charalambos
C
Zoeller
Liesa
L
Rocco
Patricia R M
PR
Yard
Benito
B
Luecke
Thomas
T
D000818:Animals; D006612:High-Frequency Ventilation / Q000379:methods*; D008168:Lung / Q000502:physiology*; D055370:Lung Injury / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D011175:Positive-Pressure Respiration / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000379:methods; D015656:Respiratory Mechanics / Q000502:physiology*; D013990:Tidal Volume / Q000502:physiology