4 research outputs found
Skeletal muscle metabolism in critically ill patients
The loss of skeletal muscle mass is of importance for the length of the
hospital stay and recovery in critically ill patients admitted to the
intensive care unit (ICU). In the acute illness, the export of amino
acids from skeletal muscle provides substrates for vital functions and
thus enhances survival. As there is no inactive store of protein in the
body, the protein being depleted represents functional tissue. Eventually
the role of muscle tissue as an exporter of substrates as well as the
functional proprerties of muscle may become impaired. Hence, in long term
ICU patients the muscle depletion may become a limiting factor for
survival. The aims of this project were to evaluate efforts to limit
skeletal muscle wasting in ICU patients staying for a prolonged time in
the unit and also to develop a protocol for interventional studies on
this group of patients. These aims were approached by characterising the
biochemical markers of muscle protein depletion and then investigating
the effects of interventions.
The changes in the biochemical markers for muscle protein catabolism were
established early on in the course of the critical illness and there was
a characteristic pattern of changes in relation to the length of stay for
several markers. Despite the heterogeneity of the acute clinical
appearance of the patients, muscle biochemistry shows similarities in the
long-term critically ill patients. Furthermore the scatters of several of
the markers do not differ from the scatter in a reference population. The
results made it possible to design a protocol to be used in ICU patients,
as well as in healthy volunteers to evaluate interventions. The protein
content was lower in patients sampled on day 5 or later of the ICU stay
in comparison with the patients sampled earlier. In paired samples, the
decrease over time was found to be 10 % per 5 days. Muscle protein
synthesis was not different in ICU patients compared to an age matched
reference group, however, the scatter was large with outliers in the high
as well as the low range. The persisting catabolism leading to loss of
muscle tissue is presumably of great importance for the prognosis of the
disease and for the length of hospital stay and recovery. The free
glutamine concentration in muscle decreased down to 25% of reference
levels, with all values outside the 95% confidence interval of the
reference group. The decrease was established already in the biopsies
taken at the earliest time point of ICU stay, and there was no further
change detected in relation to length of stay. Branced chain and aromatic
amino acids concentrations in muscle were high compared to the reference
group, but no further increase over time was observed. In the total
patient series the concentrations remained at the same level and no
further increase over time was observed. The total muscle water content
was elevated in the ICU patients due to doubling of the extracellular
water. In addition the intracellular water content decreased between the
paired biopsies. Growth hormone treatment was shown to increase the
intracellular water by 6 %. Among the energy-rich phosphates the ATP and
phosphorylated creatine concentrations were low as compared to the levels
in the reference group with no relation to length of stay demonstrated.
The effect of treatment with growth hormone, 0.3 U /kg/day, was marginal
on protein content but increased muscle protein synthesis by 33 % (p<
0.01) and the free glutamine concentration by 100% (p< 0.05).
Supplementation with glutamine or [alpha] -ketoglutarate (0.28g/ kg bw/24
h) on the other hand, was not shown not affect protein content and showed
a marginal effect on muscle protein synthesis and the free glutamine
concentration. The statistical correlation between the free glutamine and
muscle protein synthesis was very weak but attained statistical
significance, r 2 = 0.09 (p< 0.05). Immobilization by unloading of one
leg for 10 days in healthy volunteers resulted in a decrease of the RNA
concentration and an increase in the concentration of branched chain
amino acids indicative of muscle protein catabolism.
In summary changes in biochemical markers for muscle protein catabolism
are established early in the course of critical illness and there is a
characteristic pattern of changes with a relation to the length of stay
for several markers. Despite the heterogeneity of the acute clinical
appearance of the patients, muscle biochemistry show similarities in
long-term patients in the ICU. Growth hormone was shown to affect muscle
metabolism with an increase in protein synthesis rate and glutamine
concentration and in addition a decrease of intracellular water content.
Supplementation with glutamine or [alpha] -ketoglutarate was shown to
increase protein synthesis rate and glutamine concentration only
marginally. These results indicate a potential to save muscle proteins in
long term ICU patients
An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers
Abstract Background There is extensive documentation on skeletal muscle protein depletion during the initial phase of critical illness. However, for intensive care unit (ICU) long-stayers, objective data are very limited. In this study, we examined skeletal muscle protein and amino acid turnover in patients with a prolonged ICU stay. Methods Patients (n = 20) were studied serially every 8–12 days between days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg muscle protein turnover was assessed by measurements of phenylalanine kinetics, for which we employed a stable isotope-labeled phenylalanine together with two-pool and three-pool models for calculations, and results were expressed per 100 ml of leg volume. In addition, leg muscle amino acid flux was studied. Results The negative leg muscle protein net balance seen on days 10–20 of the ICU stay disappeared by days 30–40 (p = 0.012). This was attributable mainly to an increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by an attenuated efflux of free amino acids from the leg. Leg muscle protein breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3-methylhistidine. The arterial plasma concentrations of free amino acids did not change over the course of the study. Conclusions In critically ill patients with sustained organ failure and in need of a prolonged ICU stay, the initial high rate of skeletal muscle protein depletion was attenuated over time. The distinction between the acute phase and a more prolonged and more stable phase concerning skeletal muscle protein turnover must be considered in study protocols as well as in clinical practice. Trial registration Australian New Zealand Trial Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016
Additional file 1: of An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers
Table S1. Individual patients characteristics. Table S2. Patient characteristics at the two measurement points. Figure S1. Longitudinal presentation of plasma flow. Figure S2. Longitudinal presentation of phenylalanine turnover using the two-pool model. Figure S3. Longitudinal presentation of SOFA scores and nutrition. Figure S4. Longitudinal presentation of all amino acid fluxes. Figure S5. Amino acid concentrations. (PDF 185 kb