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Background: During critical illness skeletal muscle wasting occurs rapidly. Although beta‐hydroxy‐beta‐methylbutyrate (HMB) is a potential treatment to attenuate this process, the plasma appearance and muscle concentration is uncertain. Methods: This was an exploratory study nested within a blinded, parallel group, randomized clinical trial in which critically ill patients after trauma received enteral HMB (3 g daily) or placebo. Plasma samples were collected at 0, 60, and 180 min after study supplement administration on day 1. Needle biopsies of the vastus lateralis muscle were collected (baseline and day 7 of the HMB treatment intervention period). An external standard curve was used to calculate HMB concentrations in plasma and muscle. Results: Data were available for 16 participants (male n = 12 (75%), median [interquartile range] age 50 [29–58] years) who received placebo and 18 participants (male n = 14 (78%), age 49 [34–55] years) who received HMB. Plasma HMB concentrations were similar at baseline but increased after HMB (T = 60 min: placebo 0.60 [0.44–1.31] µM; intervention 51.65 [22.76–64.72] µM). Paired muscle biopsies were collected from 11 participants (placebo n = 7, HMB n = 4). Muscle HMB concentrations were similar at baseline between groups (2.35 [2.17–2.95]; 2.07 [1.78–2.31] µM). For participants in the intervention group who had the repeat biopsy within 4 h of HMB administration, concentrations were greater (7.2 and 12.3 µM) than those who had the repeat biopsy >4 h after HMB (2.7 and 2.1 µM). Conclusion: In this exploratory study, enteral HMB administration increased plasma HMB availability. The small sample size limits interpretation of the muscle HMB findings. [ABSTRACT FROM AUTHOR]

Background: Beta‐hydroxy‐beta‐methylbutyrate (HMB) is a nutrition supplement that may attenuate muscle wasting from critical illness. This trial aimed to determine feasibility of administering a blinded nutrition supplement in the intensive care unit (ICU) and continuing it after ICU discharge. Methods: Single‐center, parallel‐group, blinded, placebo‐controlled, randomized feasibility trial. After traumatic injury necessitating admission to ICU, participants were randomized to receive an enteral study supplement of 3 g of HMB (intervention) or placebo daily for 28 days or until hospital discharge. Primary outcome was feasibility of administering the study supplement, quantified as protocol adherence. Secondary outcomes included change in quadriceps muscle thickness, measured weekly until day 28 or hospital discharge by using ultrasound and analyzed by using a linear mixed model. Results: Fifty randomized participants (intervention, n = 26; placebo, n = 24) showed comparable baseline characteristics. Participants received 862 (84.3%) of the 1022 prescribed supplements during hospitalization with 543 (62.8%) delivered via an enteral feeding tube. The median (IQR) number of study supplements successfully administered per participant was 19.5 (13.0–24.0) in the intervention group and 16.5 (8.5–23.5) in the placebo group. Marked loss of quadriceps muscle thickness occurred in both groups, with the point estimate favoring attenuated muscle loss with the intervention, albeit with wide CIs (mean intervention difference after 28 days, 0.26 cm [95% CI, −0.13 to 0.64]). Conclusion: A blinded, placebo‐controlled, randomized clinical trial of daily enteral HMB supplementation for up to 28 days in hospital is feasible. Any effect of HMB supplementation to attenuate muscle wasting after traumatic injury remains uncertain. [ABSTRACT FROM AUTHOR]

Author(s): Selina M. Parry [sup.1], Catherine L. Granger [sup.1] [sup.2] [sup.3], Sue Berney [sup.3] [sup.4], Jennifer Jones [sup.4], Lisa Beach [sup.2], Doa El-Ansary [sup.1], René Koopman [sup.5], Linda Denehy [sup.1] [...], Purpose To identify measures used to evaluate the broad constructs of functional impairment and limitations in the critically ill across the continuum of recovery, and to evaluate, synthesise and compare the clinimetric properties of the measures identified. Methods A systematic review of articles was carried out using the databases Medline (1950-2014), CINAHL (1982-2014), EMBASE (1980-2014), Cochrane Library (2014) and Scopus (1960-2014). Additional studies were identified by searching personal files. Eligibility criteria for selection: Search 1: studies which assessed muscle mass, strength or function using objective non-laboratory measures; Search 2: studies which evaluated a clinimetric property (reliability, measurement error, validity or responsiveness) for one of the measures identified in search one. Two independent reviewers assessed articles for inclusion and assessed risk of bias using the consensus-based standards for selection of health status measurement instruments checklist. Results Thirty-three measures were identified; however, only 20 had established clinimetric properties. Ultrasonography, dynamometry, physical function in intensive care test scored and the Chelsea critical care physical assessment tool performed the strongest for the measurement of impairment of body systems (muscle mass and strength) and activity limitations (physical function), respectively. Conclusions There is considerable variability in the type of measures utilized to measure physical impairments and limitations in survivors of critical illness. Future work should identify a core set of standardized measures, which can be utilized across the continuum of critical illness recovery embedded within the International Classification of Functioning framework. This will enable improved comparisons between future studies, which in turn will assist in identifying the most effective treatment strategies to ameliorate the devastating longer-term outcomes of a critical illness.

Sarcopenia is an age-related condition of slow, progressive loss of muscle mass and strength, which contributes to frailty, increased risk of hospitalization and mortality, and increased health care costs. The incidence of sarcopenia is predicted to increase to >200 million affected older adults worldwide over the next 40 years, highlighting the urgency for understanding biological mechanisms and developing effective interventions. An understanding of the mechanisms underlying sarcopenia remains incomplete. Iron in the muscle is important for various metabolic functions, including oxygen supply and electron transfer during energy production, yet these same chemical properties of iron may be deleterious to the muscle when either in excess or when biochemically unshackled (eg, in ferroptosis), it can promote oxidative stress and induce inflammation. This review outlines the mechanisms leading to iron overload in muscle with aging and evaluates the evidence for the iron overload hypothesis of sarcopenia. Based on current evidence, studies are needed to (a) determine the mechanisms leading to iron overload in skeletal muscle during aging; and (b) investigate whether skeletal muscles are functionally deficient in iron during aging leading to impairments in oxidative metabolism. [ABSTRACT FROM AUTHOR]