Acute skeletal muscle wasting in critical illness

Abstract

IMPORTANCE: Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment. OBJECTIVE: To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND PARTICIPANTS: Sixty-three critically ill patients (59%male; mean age: 54.7 years [95%CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95%CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay. MAIN OUTCOMES AND MEASURES: Muscle losswas determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized. RESULTS: There were significant reductions in the rectus femoris CSA observed at day 10 (-17.7%[95%CI, -25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3%(95%CI, 6.1% to 14.5%), the fiber CSA by 17.5%(95%CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5%(95%CI, 13.4%to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (-15.7%; 95%CI, -27.7%to 11.4%) compared with single organ failure (-3.0%; 95%CI, -5.3%to 2.1%) (P