The sick and the weak: Neuropathies/ myopathies in the critically ill

Friedrich O, Reid M, van den Berghe G, Vanhorebeek I, Hermans G, Rich MM, Larsson L (2015)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Review article

Publication year: 2015

Journal

Physiological Reviews

Book Volume: 95

Pages Range: 1025-1109

Article Number: A09

Journal Issue: 3

DOI: 10.1152/physrev.00028.2014

Abstract

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca(2+) dysregulation is present through altered Ca(2+) homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

Authors with CRIS profile

Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie

Related research project(s)

PPP USA - Muscle Biotechnology and altered Myo-Kinesiology in Sepsis Jan. 1, 2015 - Dec. 31, 2016

Involved external institutions

Karolinska Institute SE Sweden (SE) University of Florida US United States (USA) (US) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE)

How to cite

APA:

Friedrich, O., Reid, M., van den Berghe, G., Vanhorebeek, I., Hermans, G., Rich, M.M., & Larsson, L. (2015). The sick and the weak: Neuropathies/ myopathies in the critically ill. Physiological Reviews, 95(3), 1025-1109. https://doi.org/10.1152/physrev.00028.2014

MLA:

Friedrich, Oliver, et al. "The sick and the weak: Neuropathies/ myopathies in the critically ill." Physiological Reviews 95.3 (2015): 1025-1109.

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