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Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood.Objectives: We hypothesized that diaphragm muscle fibers of mechanically ventilated critically ill patients display atrophy and contractile weakness, and that the ubiquitin-proteasome pathway is activated in the diaphragm.Methods: We obtained diaphragm muscle biopsies from 22 critically ill patients who received mechanical ventilation before surgery and compared these with biopsies obtained from patients during thoracic surgery for resection of a suspected early lung malignancy (control subjects). In a proof-of-concept study in a muscle-specific ring finger protein-1 (MuRF-1) knockout mouse model, we evaluated the role of the ubiquitin-proteasome pathway in the development of contractile weakness during mechanical ventilation.Measurements and Main Results: Both slow-and fast-twitch diaphragm muscle fibers of critically ill patients had approximately 25% smaller cross-sectional area, and had contractile force reduced by half or more. Markers of the ubiquitin-proteasome pathway were significantly up-regulated in the diaphragm of critically ill patients. Finally, MuRF-1 knockout mice were protected against the development of diaphragm contractile weakness during mechanical ventilation.Conclusions: These findings show that diaphragm muscle fibers of critically ill patients display atrophy and severe contractile weakness, and in the diaphragm of critically ill patients the ubiquitin-proteasome pathway is activated. This study provides rationale for the development of treatment strategies that target the contractility of diaphragm fibers to facilitate weaning.

In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not.

Introduction This narrative review summarizes current knowledge on the physiology and pathophysiology of expiratory muscle function in ICU patients, as shared by academic professionals from multidisciplinary, multinational backgrounds, who include clinicians, clinical physiologists and basic physiologists. Results The expiratory muscles, which include the abdominal wall muscles and some of the rib cage muscles, are an important component of the respiratory muscle pump and are recruited in the presence of high respiratory load or low inspiratory muscle capacity. Recruitment of the expiratory muscles may have beneficial effects, including reduction in end-expiratory lung volume, reduction in transpulmonary pressure and increased inspiratory muscle capacity. However, severe weakness of the expiratory muscles may develop in ICU patients and is associated with worse outcomes, including difficult ventilator weaning and impaired airway clearance. Several techniques are available to assess expiratory muscle function in the critically ill patient, including gastric pressure and ultrasound. Conclusion The expiratory muscles are the "neglected component" of the respiratory muscle pump. Expiratory muscles are frequently recruited in critically ill ventilated patients, but a fundamental understanding of expiratory muscle function is still lacking in these patients.