Skeletal Muscle Dysfunction in Critical Illness Current and Emerging Ultrasound Applications for Diaphragm and Peripheral Muscle Assessment

Abstract

Skeletal muscle dysfunction is a frequent and early complication of critical illness, affecting both respiratory and locomotor muscles and contributing to weaning failure of mechanical ventilation, prolonged intensive care unit (ICU) stay, and long-term disability. The diaphragm, as the primary respiratory muscle, is particularly impacted by sepsis and mechanical ventilation, while peripheral muscles undergo rapid atrophy due to systemic catabolism and immobility. Ultrasound has emerged as a bedside tool for monitoring muscle structure and function, providing non-invasive, reproducible assessments independent of patient cooperation. Beyond techniques focused on muscle quantity, advanced ultrasound methods are introducing new dimensions of assessment, including tissue quality, mechanical properties, and perfusion, thereby expanding the horizons of muscle evaluation in critical illness. The overarching aim of this dissertation was to advance the understanding and clinical application of classical and innovative ultrasound techniques for detecting and monitoring diaphragm and peripheral muscle dysfunction in septic shock patients. Specifically, it sought to (i) synthesise evidence on advanced diaphragm ultrasound modalities; (ii) design a prospective protocol for combined diaphragm and locomotor muscle assessment; (iii) evaluate concomitant changes in diaphragm thickness and estimated stiffness during septic shock under invasive mechanical ventilation; (iv) explore the temporal evolution of rectus femoris cross-sectional area and estimated stiffness using shear-wave elastography (SWE); and (v) illustrate the clinical utility of ultrasound through a complex case of immune-mediated necrotizing myopathy. The present work, structured according to the Scandinavian model, is composed of one integrative review, one research protocol, and three original studies. The review mapped seven innovative ultrasound techniques, highlighting their complementary contributions to multidimensional diaphragm assessment across motion, contractility, tissue quality, and perfusion. The prospective monocentric MUSiShock protocol established a methodological framework for simultaneous diaphragm and peripheral muscle monitoring in septic shock. The diaphragm study identified heterogeneous thickness trajectories but a more consistent increase in estimated stiffness, independently associated with ventilatory settings and fluid balance, suggesting SWE-derived shear modulus reflects both structural and functional determinants of diaphragm activity. The longitudinal study on rectus femoris confirmed early and marked wasting and explored the new concept of anisotropy-related changes in estimated stiffness not captured by size alone. Finally, the case report illustrated the added value of SWE in a complex weaning failure scenario. Overall, this doctoral research underscores the potential of ultrasound, particularly SWE, as a multidimensional non-invasive bedside tool for assessing skeletal muscle dysfunction in critically ill patients. By integrating structural and mechanical markers across respiratory and locomotor domains, these studies contribute to a more comprehensive understanding of muscle pathophysiology in sepsis and mechanical ventilation.