Ingestion of free amino acids compared with an equivalent amount of intact protein results in more rapid amino acid absorption and greater postprandial plasma amino acid availability without affecting muscle protein synthesis rates in young adults in a double-blind randomized trial

Background The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. Objective 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. Methods 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. Results 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). Conclusions 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

Protein metabolism in critical illness

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

Protein metabolism in critical illness

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

Nutritional strategies during gastrointestinal dysfunction

Purpose of reviewGastrointestinal (GI) dysfunction is common among critically ill patients and is associated with poor outcomes. In particular, nutrient delivery can be impaired in patients with GI dysfunction and pose a significant challenge to clinicians in daily clinical practice. This review aims to summarize the impact of GI dysfunction on nutrition therapy during critical illness and provide an update on recent advances in nutritional strategies during gastrointestinal dysfunction.Recent findingsAlthough prognostic gastrointestinal dysfunction scoring systems exist, a lack of clear, uniform definitions of GI dysfunction limits diagnosis and subsequent adequate treatment. Recent studies have further investigated separate components of GI dysfunction in ICU patients, including the role of altered GI motility, nutrient digestion and absorption and the metabolic consequences of gut dysfunction. Various strategies to improve nutrient delivery are discussed. However, the evidence supporting their routine use is sometimes lacking.GI dysfunction frequently occurs during critical illness and negatively affects nutrition therapy. Strategies to improve nutrient delivery during GI dysfunction are available, though more research into the diagnosis and pathophysiology of GI dysfunction will likely further improve patient outcomes

Pulmonary pathophysiology development of COVID-19 assessed by serial Electrical Impedance Tomography in the MaastrICCht cohort

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 PaO2/FiO2-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) cmH2O vs. 11.3 (SD 3.4) cmH2O, (p = 0.475), for ICU survivors and non-survivors. At day 1-3, compliance was ~ 55 mL/cmH2O vs. ~ 45 mL/cmH2O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12-13 cmH2O. At day 4-6 compliance changed to ~ 50 mL/cmH2O vs. ~ 38 mL/cmH2O. At day 7 and beyond, compliance was ~ 38 mL/cmH2O with the intersection at a PEEP of ~ 9 cmH2O vs. ~ 25 mL/cmH2O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH2O. 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

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients

Abstract Background Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets. Methods The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models. Discussion The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04633421 . Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course:design of the Maastricht Intensive Care COVID cohort (MaastrICCht)

Introduction The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection.Methods and analysis Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht.Ethics and dissemination Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early.Trial registration number The Netherlands Trial Register (NL8613)