Survivors of critical illness demonstrate skeletal muscle wasting with associated
functional impairment.
To perform a comprehensive prospective characterization of skeletal muscle wasting,
defining the pathogenic roles of altered protein synthesis and breakdown.
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.
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.
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 < .001),
even by day 3 (−8.7% [95% CI, −59.3% to 50.6%] vs −1.8% [95% CI, −12.3% to 10.5%],
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).
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.