Acute Skeletal Muscle Wasting in Critical Illness

Abstract

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 loss was 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, −20.9% to −4.8%]; 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 compared with single organ failure by day 7 (−15.7% [95% CI, −19.1% to −12.4%] vs −3.0% [95% CI, −10.5% to 4.6%], P < .001), even by day 3 (−8.7% [95% CI, −13.7% to −3.6%] vs −1.8% [95% CI, −7.3% to 3.8%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1

Titin‐based mechanosensing modulates muscle hypertrophy

“…Finally, from a clinical perspective, passive muscle stretch might prove an applicable therapeutic strategy during conditions associated with rapid decrease of muscle mass. For example, to combat ICU‐acquired muscle weakness which develops in critically ill patients following long periods of muscle inactivity 52. Indeed, studies in large animal models suggest that passive muscle stretch spares muscle mass during inactivity 53…”

Pathophysiology of heart failure and frailty: a common inflammatory origin?

“…More than half of the patients admitted with ADHF were found to be frail. This state is promoted by chronic underlying skeletal muscle changes from long‐standing heart failure, but an acute myopathic process can also develop during hospitalization and be compounded by immobility (Puthucheary et al ., 2013; Kitzman et al ., 2014). Our lack of understanding of the etiology and the implications of frailty are due to our poor comprehension of the pathophysiology of this condition.…”

Perioperative catabolism

“…9,10 Protein catabolism Typical features of protein catabolism are stimulated rates of protein breakdown and amino acid oxidation which lead to a net loss of body protein. [11][12][13] Metabolically healthy patients lose 40-80 g of nitrogen after elective abdominal surgery, equivalent to 1.2-2.4 kg of wet skeletal muscle. 14 Patients with burns or sepsis experience daily losses of up to 800 g of muscle mass.…”

“…15 Muscle wasting occurs early and rapidly during the first week of critical illness and is more severe among patients with multi-organ failure. 12 Significant muscle weakness and physical disability can persist for more than five years after injury and critical illness. 16,17 There is no evidence to suggest that the magnitude of catabolic changes in elderly patients differs from those in younger adults.…”