The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates.
We sought to compare ...protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids.
Twenty-four healthy, young participants (mean ± SD age: 22 ± 3 y and BMI 23 ± 2 kg/m2; sex: 12 male and 12 female participants) received a primed continuous infusion of l-ring-2H5-phenylalanine and l-ring-3,5–2H2-tyrosine, after which they ingested either 30 g intrinsically l-1–13C-phenylalanine–labeled milk protein or an equivalent amount of free amino acids labeled with l-1–13C-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period.
Postprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time × treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 ± 9%) than with milk protein treatment (59 ± 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 ± 0.015%/h to 0.053 ± 0.014%/h and 0.039 ± 0.016%/h to 0.051 ± 0.010%/h, respectively; P-time × treatment = 0.629).
Ingestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised.
The majority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the Intensive Care Unit (ICU) for mechanical ventilation. The role of multi-organ ...failure during ICU admission as driver for outcome remains to be investigated yet.
Prospective cohort of mechanically ventilated critically ill with SARS-CoV-2 infection.
94 participants of the MaastrICCht cohort (21% women) had a median length of stay of 16 days (maximum of 77). After division into survivors (n = 59) and non-survivors (n = 35), we analysed 1555 serial SOFA scores using linear mixed-effects models.
Survivors improved one SOFA score point more per 5 days (95% CI: 4–8) than non-survivors. Adjustment for age, sex, and chronic lung, renal and liver disease, body-mass index, diabetes mellitus, cardiovascular risk factors, and Acute Physiology and Chronic Health Evaluation II score did not change this result. This association was stronger for women than men (P-interaction = 0.043).
The decrease in SOFA score associated with survival suggests multi-organ failure involvement during mechanical ventilation in patients with SARS-CoV-2. Surviving women appeared to improve faster than surviving men. Serial SOFA scores may unravel an unfavourable trajectory and guide decisions in mechanically ventilated patients with SARS-CoV-2.
We performed a comprehensive health assessment in mechanically ventilated coronavirus disease 2019 survivors to assess the impact of respiratory and skeletal muscle injury sustained during ICU stay ...on physical performance at 3 months following hospital discharge.
Preregistered prospective observational cohort study.
University hospital ICU.
All mechanically ventilated coronavirus disease 2019 patients admitted to our ICU during the first European pandemic wave.
At 3 months after hospital discharge, 46 survivors underwent a comprehensive physical assessment (6-min walking distance, Medical Research Council sum score and handgrip strength), a full pulmonary function test, and a chest CT scan which was used to analyze skeletal muscle architecture. In addition, patient-reported outcomes measures were collected. Physical performance assessed by 6-minute walking distance was below 80% of predicted in 48% of patients. Patients with impaired physical performance had more muscle weakness (Medical Research Council sum score 53 51-56 vs 59 56-60; p < 0.001), lower lung diffusing capacity (54% 44-66% vs 68% of predicted 61-72% of predicted; p = 0.002), and higher intermuscular adipose tissue area (p = 0.037). Reduced lung diffusing capacity and increased intermuscular adipose tissue were independently associated with physical performance.
Physical disability is common at 3 months in severe coronavirus disease 2019 survivors. Lung diffusing capacity and intermuscular adipose tissue assessed on CT were independently associated with walking distance, suggesting a key role for pulmonary function and muscle quality in functional disability.
Abstract
Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different ...pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1–3 after intubation, 66 from day 4–6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO
2
/FiO
2
-ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (
p
= 0.017) and PEEP was 11.8 (SD 2.8) cmH
2
O vs. 11.3 (SD 3.4) cmH
2
O, (
p
= 0.475), for ICU survivors and non-survivors. At day 1–3, compliance was ~ 55 mL/cmH
2
O vs. ~ 45 mL/cmH
2
O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12–13 cmH
2
O. At day 4–6 compliance changed to ~ 50 mL/cmH
2
O vs. ~ 38 mL/cmH
2
O. At day 7 and beyond, compliance was ~ 38 mL/cmH
2
O with the intersection at a PEEP of ~ 9 cmH
2
O vs. ~ 25 mL/cmH
2
O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH
2
O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.
Low skeletal muscle mass on intensive care unit admission is related to increased mortality. It is however unknown whether this association is influenced by co-morbidities that are associated with ...skeletal muscle loss. The aim of this study was to investigate whether sarcopenia is an independent risk factor for hospital mortality in critical illness in the presence of co-morbidities associated with muscle wasting.
Data of 155 patients with abdominal sepsis were retrospectively analyzed. Skeletal muscle area was assessed using CT-scans at the level of vertebra L3. Demographic and clinical data were retrieved from electronic patient files. Sarcopenia was defined as a muscle area index below the 5th percentile of the general population. Uni- and multivariable analyses were performed to assess the association between sarcopenia and hospital mortality, correcting for age and comorbidities.
The prevalence of sarcopenia was higher in patients that did not survive until hospital discharge. However, it appeared that this relation was confounded by the presence of chronic renal insufficiency and cancer. These were independent risk factors for hospital mortality, whereas sarcopenia was not.
In critically ill patients with abdominal sepsis, muscle wasting associated co-morbidities rather than sarcopenia were risk factors for hospital mortality.
•The prevalence of sarcopenia is higher in non-surviving critically ill patients.•Sarcopenia is not an independent risk factor for mortality in critical illness.•The association between sarcopenia and increased mortality in critically ill is mediated by chronic co-morbidities.
•The assessment of muscle loss during critical illness using computed tomography scans is hampered by the formation of edema.•Edema in critical illness leads to overestimation of muscle area ...measurements.•Edema formation and decreased muscle quality were associated with a higher disease severity.•Muscle radiation attenuation cannot be used as an indicator for formation of edema.•In critical illness, researchers must be careful with the interpretation of muscle area measurements.
Changes in muscle mass and quality are important targets for nutritional intervention in critical illness. Effects of such interventions may be assessed using sequential computed tomography (CT) scans. However, fluid and lipid infiltration potentially affects muscle area measurements. The aim of this study was to evaluate changes in muscle mass and quality in critical illness with special emphasis on the influence of edema on this assessment.
Changes in skeletal muscle area index (SMI) and radiation attenuation (RA) at the level of vertebra L3 were analyzed using sequential CT scans of 77 patients with abdominal sepsis. Additionally, the relation between these changes and disease severity using the maximum Sequential Organ Failure Assessment (SOFA) score and change in edema were studied.
SMI declined on average 0.35%/d (±1.22%; P = 0.013). However, SMI increased in 41.6% of the study population. Increasing edema formation was significantly associated with increased SMI and with a higher SOFA score. Muscle RA decreased during critical illness, but was not significantly associated with changes in SMI or changes in edema.
In critically ill patients, edema affects skeletal muscle area measurements, which leads to an overestimation of skeletal muscle area. A higher SOFA score was associated with edema formation. Because both edema and fat infiltration may affect muscle RA, the separate effects of these on muscle quality are difficult to distinguish. When using abdominal CT scans to changes in muscle mass and quality in critically ill patients, researchers must be aware and careful with the interpretation of the results.
Reply to Vijayakumar and Shah van Gassel, Rob J. J.; Bels, Julia L. M.; Gietema, Hester A. ...
American journal of respiratory and critical care medicine,
06/2021, Letnik:
203, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Van Gassel et al. thank Vijayakumar and Shah for their letter regarding their report on the high prevalence of pulmonary sequelae at 3 months in mechanically ventilated survivors of coronavirus ...disease (COVID-19) assessed by pulmonary function testing and high-resolution computed tomography (HRCT). They acknowledge that their remarks highlight two key challenges that remain to be addressed in future work: 1) the long-term follow-up of these respiratory sequelae and their evolution/persistence over time and 2) unraveling the role of (micro)thrombosis in the respiratory sequelae as observed in survivors of COVID-19.
Protein metabolism in critical illness Chapple, Lee-anne S.; van Gassel, Rob J.J.; Rooyackers, Olav
Current opinion in critical care,
08/2022, Letnik:
28, Številka:
4
Journal Article
Purpose of review
Critically ill patients experience skeletal muscle wasting that may contribute to the profound functional deficits in those that survive the initial injury. Augmented protein ...delivery has the potential to attenuate muscle loss, yet the ability for dietary protein to improve patient outcomes is reliant on effective protein metabolism. This review will discuss the recent literature on protein delivery and digestion, amino acid absorption, and muscle protein synthesis (MPS) in critically ill adults.
Recent findings
Critically ill patients are prescribed protein doses similar to international recommendations, yet actual delivery remains inadequate. The majority of trials that have achieved higher protein doses have observed no effect on muscle mass, strength or function. Critically ill patients have been observed to have minimal deficits in protein digestion and amino acid absorption when delivery bypasses the stomach, yet postprandial MPS is impaired. However, the literature is limited due to the complexities in the direct measurement of protein handling.
Summary
Postprandial MPS is impaired in critically ill patients and may exacerbate muscle wasting experienced by these patients. Studies in critically ill patients require assessment not only of protein delivery, but also utilization prior to implementation of augmented protein doses.
Background
Postprandial rise of plasma essential amino acids (EAAs) determines the anabolic effect of dietary protein. Disturbed gastrointestinal function could impair the anabolic response in ...critically ill patients. Aim was to investigate the postprandial EAA response in critically ill patients and its relation to small‐intestinal function.
Methods
Twenty‐one mechanically ventilated patients and 9 healthy controls received a bolus containing 100 ml of a formula feed (Ensure) and 2 g of 3‐O‐Methyl‐d‐glucose (3‐OMG) via postpyloric feeding tube. Fasting and postprandial plasma concentrations of EAAs, 3‐OMG, total bile salts, and the gut‐released hormone fibroblast growth factor 19 (FGF19) were measured over a 4‐hour period. Changes over time and between groups were assessed with linear mixed‐effects analysis. Early (0–60 minutes) and total postprandial responses are summarized as the incremental area under the curve (iAUC).
Results
At baseline, fasting EAA levels were similar in both groups: 1181 (1055–1276) vs 1150 (1065–1334) μmol·L−1, P = .87. The early postprandial rise in EAA was not apparent in critically ill patients compared with healthy controls (iAUC60, −4858 −6859 to 2886 vs 5406 3099–16,853 µmol·L−1·60 minutes; P = .039). Impaired EAA response did not correlate with impaired 3‐OMG response (Spearman ρ 0.32, P = .09). There was a limited increase in total bile salts but no relevant FGF19 response in either group.
Conclusion
Postprandial rise of EAA is blunted in critically ill patients and unrelated to glucose absorption measured with 3‐OMG. Future studies should aim to delineate governing mechanisms of macronutrient malabsorption.
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