Influence of weaning methods on the diaphragm after mechanical ventilation

Introduction: Diaphragm weakness occurs after mechanical ventilation (MV), termed ventilator-induced diaphragmatic dysfunction. Weaning must balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of an injured diaphragm. The trial investigated which weaning method allows more efficient restoration of diaphragm homeostasis. Methods: Rats (n=32) received 12h of MV followed by either 12h of pressure support ventilation (PSV) or intermittent spontaneous breathing trails (SBT) or rats were directly euthanized after 12h MV (CMV). Acutely euthanized rats served as controls (CON). Diaphragm force generation, activity of calpain-1, caspase-3 (proteolysis), oxidative modification in proteins (oxyblot) and lipids (4-HNE) (all Western blot) were detected. Normally distributed data were analyzed by 2-way or 1-way ANOVA. Results: MV resulted in a reduction of diaphragmatic force compared to CON (p=0.034). PSV and SBT further decreased contractility compared to CMV and CON (both p Discussion: MV resulted in a loss of diaphragmatic contractility, which was aggravated in SBT and PSV. This could indicate muscle overload during weaning. We could detect a reduction of oxidized proteins in SBT, while in PSV we found a reduction in caplain-1 and oxidized lipids and proteins. This might indicate a more efficient recovery by PSV compared to SBT.