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Background: Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day)., Methods: The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m 2 , kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants., Findings: Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups., Interpretation: High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission., Funding: Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre., Competing Interests: Declaration of interests EDW receives honoraria for scientific lectures from Baxter Healthcare, Nutricia–Danone, and Nestlé. ARHvZ receives grants from AOP Pharma, Nutricia–Danone, Fresenius Kabi, PAION, and Rousselot; receives consulting fees from AOP Pharma, Medcaptain, and PAION; receives honoraria for lectures from Abbott, AOP Pharma, Baxter, Nestlé, Nutricia–Danone, Fresenius Kabi, GE Healthcare, and Dutch Medical Food; receives support for travel from Nutricia–Danone and Dutch Medical Food; is a member of the adult intensive care unit patient nutrition guideline committee of the European Society for Clinical Nutrition and Metabolism, the executive team of SepsisNet Netherlands, and the executive team of the Netherlands Society for Parenteral and Enteral Nutrition; and is the European Society of Intensive Care Medicine Section Feeding, Rehabilitation Endocrinology and Metabolism chair. ZP receives grants from Fresenius Kabi, Nestlé, and Baxter; receives consulting fees from Fresenius Kabi, Nestlé, Baxter, Faraday Pharmaceuticals, and Bioage Pharmaceuticals; and receives honoraria for lectures from Baxter, Nestlé, Fresenius Kabi, and Nutricia. MCGvdP receives grants from the Netherlands Organisation of Health Research and Development and the Belgian Health Care Knowledge Centre; receives in-kind support from Nutricia; receives consulting fees from Nutricia and Nestlé; and receives honoraria for lectures and support for travel from Nutricia. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The PRECISe trial is a pragmatic, multicenter randomized controlled trial that evaluates the effect of high versus standard enteral protein provision on functional recovery in adult, mechanically ventilated critically ill patients. The current protocol presents the rationale and analysis plan for an evaluation of the primary and secondary outcomes under the Bayesian framework, with an emphasis on clinically important effect sizes., Methods: This protocol was drafted in agreement with the ROBUST-statement, and is submitted for publication before database lock and primary data analysis. The primary outcome is health-related quality of life as measured by the EQ-5D-5L health utility score and is longitudinally assessed. Secondary outcomes comprise the 6-min walking test and handgrip strength over the entire follow-up period (longitudinal analyses), and 60-day mortality, duration of mechanical ventilation, and EQ-5D-5L health utility scores at 30, 90 and 180 days (cross-sectional). All analyses will primarily be performed under weakly informative priors. When available, informative priors elicited from contemporary literature will also be incorporated under alternative scenarios. In all other cases, objectively formulated skeptical and enthusiastic priors will be defined to assess the robustness of our results. Relevant identified subgroups were: patients with acute kidney injury, severe multi-organ failure and patients with or without sepsis. Results will be presented as absolute risk differences, mean differences, and odds ratios, with accompanying 95% credible intervals. Posterior probabilities will be estimated for clinically important benefit and harm., Discussion: The proposed secondary, pre-planned Bayesian analysis of the PRECISe trial will provide additional information on the effects of high protein on functional and clinical outcomes in critically ill patients, such as probabilistic interpretation, probabilities of clinically important effect sizes, and the integration of prior evidence. As such, it will complement the interpretation of the primary outcome as well as several secondary and subgroup analyses., Competing Interests: Declaration of competing interest MvdP received travel and speaker fees from Nutricia and research funding from Nestle Health Science and Fresenius-Kabi, not related to this research. EDW received research grants, travel and speakers fees from the Belgian Government Health, KCE (Belgian Health Care), Baxter Healthcare, Fresenius, Nestlé and Art Medical., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A recent large multicentre trial found no difference in clinical outcomes but identified a possibility of increased mortality rates in patients with acute kidney injury (AKI) receiving higher protein. These alarming findings highlighted the urgent need to conduct an updated systematic review and meta-analysis to inform clinical practice., Methods: From personal files, citation searching, and three databases searched up to 29-5-2023, we included randomized controlled trials (RCTs) of adult critically ill patients that compared higher vs lower protein delivery with similar energy delivery between groups and reported clinical and/or patient-centred outcomes. We conducted random-effect meta-analyses and subsequently trial sequential analyses (TSA) to control for type-1 and type-2 errors. The main subgroup analysis investigated studies with and without combined early physical rehabilitation intervention. A subgroup analysis of AKI vs no/not known AKI was also conducted., Results: Twenty-three RCTs (n = 3303) with protein delivery of 1.49 ± 0.48 vs 0.92 ± 0.30 g/kg/d were included. Higher protein delivery was not associated with overall mortality (risk ratio [RR]: 0.99, 95% confidence interval [CI] 0.88-1.11; I 2  = 0%; 21 studies; low certainty) and other clinical outcomes. In 2 small studies, higher protein combined with early physical rehabilitation showed a trend towards improved self-reported quality-of-life physical function measurements at day-90 (standardized mean difference 0.40, 95% CI - 0.04 to 0.84; I 2  = 30%). In the AKI subgroup, higher protein delivery significantly increased mortality (RR 1.42, 95% CI 1.11-1.82; I 2  = 0%; 3 studies; confirmed by TSA with high certainty, and the number needed to harm is 7). Higher protein delivery also significantly increased serum urea (mean difference 2.31 mmol/L, 95% CI 1.64-2.97; I 2  = 0%; 7 studies)., Conclusion: Higher, compared with lower protein delivery, does not appear to affect clinical outcomes in general critically ill patients but may increase mortality rates in patients with AKI. Further investigation of the combined early physical rehabilitation intervention in non-AKI patients is warranted., Prospero Id: CRD42023441059., (© 2024. The Author(s).)

Background: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE., Methods: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted., Results: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high., Conclusions: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness., Trial Registration: PROSPERO (CRD42023438187). Registered 21/06/2023., (© 2023. The Author(s).)

Background: During Intensive Care Unit (ICU) admission, patients demonstrate up to 15% muscle loss per week, contributing to neuromuscular weakness, complicating recovery and delaying return to daily life. Biomarkers for muscle loss could aid in early detection of patients at risk and help guide resources to mitigate muscle loss, e.g. physical therapy and protein supplementation., Aims: To explore serum biomarkers for muscle mass and muscle loss in ICU patients using a metabolomics approach., Methods: Mechanically ventilated patients with an unplanned ICU admission between June and December 2021 were prospectively studied. The cross-sectional area of the rectus femoris muscle was assessed using ultrasound (RF csa ) and 188 serum metabolites were assessed using the Biocrates™ AbsoluteIDQ p180 kit for targeted metabolomics. Patients were eligible for analysis when a serum sample drawn within 5 days of ICU admission and at least 1 RF csa were available. In patients with sequential RF csa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RF csa measurements per patient in the first 10 days of ICU admission. Correlations between baseline metabolite concentrations and baseline muscle mass, as well as between baseline metabolite concentrations and muscle loss were assessed using Pearson's test for correlations. To correct for multiple testing, the Benjamini-Hochberg procedure was used., Results: Seventeen patients were eligible for analysis. Mean age was 62 (SD ± 9) years and the cohort was predominantly male (76%). Four metabolites correlated with baseline muscle mass: creatinine (R = 0.5, p = 0.041), glycerophospholipid PC_ae_C30_0 (R = 0.5, p = 0.034) and two acylcarnitines: C14_2 (R = 0.5, p = 0.042) and C10_2 (R = 0.5, p = 0.049). For muscle loss, significant associations were found for histidine (R = -0.8, p = 0.002) and three glycerophospholipids; PC_aa_C40_2 (R = 0.7, p = 0.015), PC_ae_C40_1 (R = 0.6, p = 0.032) and PC_aa_C42_1 (R = 0.6, p = 0.037). After correction for multiple testing, no significant associations remained., Conclusions: This exploratory analysis found certain metabolites to be associated with muscle mass and muscle loss. Future research, specifically addressing these metabolites is necessary to confirm or refute an association with muscle loss and determine their role as potential muscle loss marker., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Gastrointestinal (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 Findings: Although 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., Summary: 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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: In critically ill patients, optimal protein provision remains a challenge given the wide range in recommended protein delivery in international guidelines and the lack of robust, high quality evidence. As patients are confronted with poor functional outcomes after admission, often attributed to muscle wasting and persisting for multiple years, there is a pressing need for optimal nutritional strategies in the ICU, particularly including protein. This review will discuss the recent literature with regard to purpose, timing and mode of protein delivery., Recent Findings: Recent studies on the effect of dose and timing of protein on clinical and functional outcomes are largely observational in nature and the protein delivery considered as "high" still often only nears the lower end of current recommendations. The majority of trials observed no effect of protein supplementation on mortality, muscle strength or function, though some report attenuation of muscle volume loss, especially when combined with muscle activation. There is no strong evidence that ICU patients should receive supplementation with any specific amino acids., Summary: Though adequate protein provision is likely important, it is difficult to come to a uniform conclusion regarding dosing and timing due to conflicting results in mostly observational studies as well as different cut-off values for high, moderate and low protein intake. This topic is currently subject to large clinical trials., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 (iAUC 60 , -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., (© 2021 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Objectives: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative outcome prediction in elderly is based on preoperative physical status but its predictive value is uncertain. The goal was to evaluate the value of risk assessment performed perioperatively in predicting outcome in case of admission to an intensive care unit (ICU)., Methods: A total of 108 postsurgical patients were retrospectively selected from a prospectively recorded database of 144 elderly septic patients (>70 years) admitted to the ICU department after elective or emergency abdominal surgery between 2012 and 2017. Perioperative risk assessment scores including Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality (P-POSSUM) and American Society of Anaesthesiologists Physical Status classification (ASA) were determined. Acute Physiology and Chronic Health Evaluation IV (APACHE IV) was obtained at ICU admission., Results: In-hospital mortality was 48.9% in elderly requiring ICU admission after elective surgery (n = 45), compared to 49.2% after emergency surgery (n = 63). APACHE IV significantly predicted in-hospital mortality after complicated elective surgery [area under the curve 0.935 (p < 0.001)] where outpatient ASA physical status and P-POSSUM did not. In contrast, P-POSSUM and APACHE IV significantly predicted in-hospital mortality when based on current physical state in elderly requiring emergency surgery (AUC 0.769 (p = 0.002) and 0.736 (p = 0.006), respectively)., Conclusions: Perioperative risk assessment reflecting premorbid physical status of elderly loses its value when complications occur requiring unplanned ICU admission. Risks in elderly should be re-assessed based on current clinical condition prior to ICU admission, because outcome prediction is more reliable then.

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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Monitoring the microcirculation may be helpful in guiding resuscitation in patients with circulatory shock. Sublingual side-stream dark field imaging cameras allow for noninvasive, bedside evaluation of the microcirculation, although their use in clinical practice has not yet been validated. The GlycoCheck system automatically analyzes images to determine glycocalyx thickness, red blood cell filling percentage, and vessel density. Although GlycoCheck has been used to study microcirculation in critically ill patients, little is known about the reproducibility of measurements in this population., Materials and Methods: A total of 60 critically ill patients were studied. Three consecutive microcirculation measurements were performed with the GlycoCheck system in 40 of these patients by one of two experienced observers. Twenty patients were assessed by both observers. Intra- and interobserver variability were assessed using intraclass correlation coefficients (ICCs)., Results: ICCs of single measurements were poor for glycocalyx thickness and good for filling percentage and vessel density. Reproducibility could be substantially increased for all parameters when three consecutive measurements were performed and averaged., Discussion: GlycoCheck can be used to study microcirculation. However, to obtain reliable results three consecutive measurements should be performed and averaged. The variation of the measurements currently hampers the clinical application in individual patients.

Background: 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., Methods: 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., Results: 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., Conclusion: In critically ill patients with abdominal sepsis, muscle wasting associated co-morbidities rather than sarcopenia were risk factors for hospital mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Skeletal muscle wasting during critical illness is the result of disturbed metabolism. No proven effective interventions targeting skeletal muscle mass and function during critical illness currently exist. This review summarizes recent advances regarding the complexity of metabolic factors involved and the challenge of establishing the clinical effects of metabolic interventions targeting the muscle., Recent Findings: Although the catabolic state is limited to the acute phase of critical illness, its subsequent impact on muscle mass and function persists long after ICU discharge. Immobilization, inflammation and disturbed muscle energy and nutrient metabolism are key drivers of muscle protein loss. Current research focuses on the effects of enhanced protein provision, specific substrate delivery and physical exercise. Whilst some interventions have been successful at improving muscle mass, these effects do not always carry over into muscle function or strength., Summary: Increased understanding of metabolic derangements during critical illness provides new potential targets for treatment. The potential of dietary protein to attenuate the muscle protein catabolic state has yet to be established in clinical trials. Basic research should focus on ways to further improve the anabolic potential of nutrition by unravelling mechanisms that regulate anabolic and catabolic pathways and energy metabolism.