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Original Investigation
Caring for the Critically Ill Patient
October 16, 2013

Acute Skeletal Muscle Wasting in Critical Illness

Author Affiliations
  • 1Institute of Health and Human Performance, University College London, London, England
  • 2Imperial College London St Mary’s Hospital NHS Trust, London, England
  • 3NIHR Comprehensive Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, England
  • 4Centre of Human and Aerospace Physiological Sciences, King’s College London, London, England
  • 5Royal Brompton Hospital, Imperial College London, London, England
  • 6Division of Neuropathology, National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, England
  • 7King’s College Hospital NHS Trust, London, England
  • 8Department of Clinical Physiology, University of Nottingham, Nottingham, England
  • 9Lane Fox Clinical Respiratory Physiology Research Unit, St Thomas’ Hospital, Guy’s & St Thomas’ NHS Foundation Trust, London, England
  • 10Division of Asthma, Allergy and Lung Biology, King’s College London, London, England
JAMA. 2013;310(15):1591-1600. doi:10.1001/jama.2013.278481
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 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 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076% [95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] μmol of phenylalanine/min/ideal body weight × 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = −0.83, P = .005) and decreased synthesis (n = 9, r = −0.69, P = .04).

Conclusions and Relevance  Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness.

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