Assessment of Sarcopenia in the Intensive Care Unit and 1-Year Mortality in Survivors of Critical Illness

Skeletal muscle wasting in the intensive care unit (ICU) has been associated with mortality, but it is unclear whether sarcopenia, defined by skeletal muscle mass and function, is useful for detailed risk stratification after ICU discharge. In this cohort study, 72 critically ill patients with an ICU stay of ≥48 h were identified. Skeletal muscle mass was assessed from the muscle thickness (MT) of the patients’ quadriceps using ultrasound images before ICU discharge. Skeletal muscle function was assessed from the patients’ muscle strength (MS) before ICU discharge according to the Medical Research Council sum score. A diagnosis of sarcopenia in the ICU was made in patients with low MT and low MS. The study endpoint was 1-year mortality. Sarcopenia in the ICU was diagnosed in 26/72 patients (36%). After adjusting for covariates in the Cox regression, sarcopenia in the ICU was significantly associated with 1-year mortality (hazard ratio 3.82; 95% confidence interval, 1.40–10.42). Sarcopenia in the ICU, defined by low skeletal muscle mass and function, was associated with 1-year mortality in survivors of critical illness. Skeletal muscle mass and function assessed at the bedside could be used to identify higher-risk patients in the ICU.

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Skeletal Muscle Mass Regulation in Critical Illness

10.1093/med/9780199653461.003.0035 ◽

2014 ◽

Author(s):

Zudin Puthucheary ◽

Hugh Montgomery ◽

Nicholas Hart ◽

Stephen Harridge

Keyword(s):

Skeletal Muscle ◽

Critical Illness ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Bed Rest ◽

Protein Homeostasis ◽

Highly Sensitive ◽

And Function ◽

Inadequate Nutrition

Muscle is a dynamic, plastic, and malleable tissue that is highly sensitive to mechanical and metabolic signals. Muscle mass is regulated by protein homeostasis, with protein being continually turned over, reflecting a balance between synthesis and breakdown. This chapter discusses the effect of critical illness on skeletal muscle mass, protein homeostasis, and the intracellular signalling driving anabolism and catabolism. The focus will be on the unique challenges to which the skeletal muscle are exposed, such as inflammation, sepsis, sedation, and inadequate nutrition, which, in combination with the disuse signals of immobilization and bed rest, engender dramatic changes in muscle structure and function. The mechanisms regulating muscle loss during critical illness are being unravelled, but many questions remain unanswered. Detailed understanding of these mechanisms will help drive strategies to minimize or prevent intensive care-acquired muscle weakness and the long-term consequences experienced by ICU survivors.

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Sex Differences in the Associations between L-Arginine Pathway Metabolites, Skeletal Muscle Mass and Function, and their Responses to Resistance Exercise, in Old Age

The journal of nutrition health & aging ◽

10.1007/s12603-017-0964-6 ◽

2017 ◽

Vol 22 (4) ◽

pp. 534-540 ◽

Cited By ~ 5

Author(s):

M. da Boit ◽

S. Tommasi ◽

D. Elliot ◽

A. Zinellu ◽

S. Sotgia ◽

...

Keyword(s):

Skeletal Muscle ◽

Sex Differences ◽

Resistance Exercise ◽

Old Age ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

And Function

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Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function

Experimental Gerontology ◽

10.1016/j.exger.2021.111668 ◽

2021 ◽

pp. 111668

Author(s):

Hui Gong ◽

Yang Liu ◽

Xing Lyu ◽

Lini Dong ◽

Xiangyu Zhang

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Lipoprotein Subfractions ◽

And Function

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Myopathy and Neuropathy Acquired in the Intensive Care Unit

Mayo Clinic Critical and Neurocritical Care Board Review ◽

10.1093/med/9780190862923.003.0097 ◽

2019 ◽

pp. 677-684

Author(s):

Priya S. Dhawan ◽

Jennifer A. Tracy

Keyword(s):

Skeletal Muscle ◽

Intensive Care Unit ◽

At Risk ◽

Intensive Care ◽

Peripheral Neuropathy ◽

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Critical Illness Polyneuropathy ◽

Muscle Disorder

Acquired weakness in critically ill patients is common, affecting between one-third to one-half of patients in the intensive care unit (ICU). Exposure to simultaneous stressors such as metabolic derangements, fluid and electrolyte shifts, infection, catabolic stress, and medications put patients in the ICU at risk for damage to both nerve and skeletal muscle with substantial and often lasting morbidity. Critical illness polyneuropathy is a length-dependent, axonal peripheral neuropathy occurring in patients in the ICU and unrelated to the primary illness. Critical illness myopathy is an ICU-associated muscle disorder occurring independently of denervation and uniquely identified by electrophysiologic and histologic characteristics.

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NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

Journal of Frailty & Aging ◽

10.14283/jfa.2018.35 ◽

2018 ◽

pp. 1-3

Author(s):

B.C. Clark

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

The Past ◽

Conceptual Definition ◽

Age Related ◽

Per Se ◽

Definition Of ◽

And Function

Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.

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Sarcopenia in women with hip fracture: A comparison of hormonal biomarkers and their relationship to skeletal muscle mass and function

Osteoporosis and Sarcopenia ◽

10.1016/j.afos.2020.06.001 ◽

2020 ◽

Vol 6 (3) ◽

pp. 139-145

Author(s):

Ming Li Yee ◽

Raphael Hau ◽

Alison Taylor ◽

Mark Guerra ◽

Peter Guerra ◽

...

Keyword(s):

Skeletal Muscle ◽

Hip Fracture ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

And Function

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Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments

Journal of Gastroenterology ◽

10.1007/s00535-020-01711-w ◽

2020 ◽

Vol 55 (10) ◽

pp. 927-943 ◽

Cited By ~ 2

Author(s):

Giovanni Marasco ◽

Matteo Serenari ◽

Matteo Renzulli ◽

Luigina Vanessa Alemanni ◽

Benedetta Rossini ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Appropriate Treatment ◽

Risk Of Mortality ◽

Short And Long Term ◽

Poor Outcomes ◽

And Function

Abstract Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

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The gut microbiota influences skeletal muscle mass and function in mice

Science Translational Medicine ◽

10.1126/scitranslmed.aan5662 ◽

2019 ◽

Vol 11 (502) ◽

pp. eaan5662 ◽

Cited By ~ 37

Author(s):

Shawon Lahiri ◽

Hyejin Kim ◽

Isabel Garcia-Perez ◽

Musarrat Maisha Reza ◽

Katherine A. Martin ◽

...

Keyword(s):

Skeletal Muscle ◽

Neuromuscular Junction ◽

Gut Microbiota ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Neuromuscular Junctions ◽

Short Chain Fatty Acids ◽

Germ Free ◽

Mouse Skeletal Muscle ◽

And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

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Growth differentiation factor 15 (GDF-15) inhibition to increase muscle mass and function in cancer cachexia.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15633 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15633-e15633

Author(s):

Matthew Peloquin ◽

Brianna LaCarubba ◽

Stephanie Joaqium ◽

Gregory Weber ◽

John Stansfield ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

Cancer Cachexia ◽

Tumor Model ◽

Growth Differentiation Factor 15 ◽

Myostatin Inhibition ◽

And Function

e15633 Background: Almost half of cancer deaths are attributed to cancers most frequently associated with cachexia. Cachexia is a complex metabolic disease characterized by anorexia and unintentional weight loss. Skeletal muscle depletion has been recognized as a key feature of the disease, however muscle anabolic therapies have not been successful, suggesting that treatments that target multiple aspects of the disease will be most effective. Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia and weight loss and is associated with cachexia in cancer patients. In preclinical cancer cachexia models, GDF-15 inhibition is sufficient to normalize food intake and body weight, including skeletal muscle mass. However, it remains to be determined whether the increased skeletal muscle mass also results in restoration of muscle function. Therefore, we examined the effect of GDF-15 inhibition on muscle mass and function in mouse models of cancer cachexia in comparison with myostatin inhibition, an established muscle anabolic pathway. Methods: Cachectic mouse tumor models were established with subcutaneous implantation of tumor cell lines reported to be GDF-15-dependent; mouse renal cell carcinoma (RENCA) and human ovarian cancer (TOV-21G) cell lines. Mice were treated with anti-GDF-15 (mAB2) or anti-myostatin (RK35) monoclonal antibodies and skeletal muscle function was assessed in vivo via maximum force, maximum rate of contraction and half relax time. In the RENCA tumor model, GDF-15 inhibition fully restored body weight and skeletal muscle mass whereas myostatin inhibition showed only a modest effect. Results: Consistent with the muscle mass improvement, GDF-15 inhibition dramatically increased functional muscle endpoints compared to the partial effect of myostatin inhibition. Interestingly, in the TOV-21G tumor model GDF-15 inhibition only partially restored body weight, however skeletal muscle mass and muscle function were completely normalized. Consistent with the functional assessment, GDF-15 inhibition in the RENCA tumor model decreased the expression of several catabolic genes (i.e. Trim63, Fbxo32, Myh7 and Myh2). The GDF-15 effect is likely to be secondary to the reversal of anorexia since wildtype mice pair-fed to Fc-GDF-15-treated mice demonstrated equivalent muscle mass loss. Conclusions: Taken together these data suggest that GDF-15 inhibition holds potential as an effective therapeutic approach to alleviate multiple aspects of cachexia.

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