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Author ORCID Identifier

https://orcid.org/0000-0001-9099-2389

Date Available

7-30-2028

Year of Publication

2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Health Sciences

Department/School/Program

Physical Therapy

Faculty

Kirby P. Mayer

Faculty

Esther E. Dupont-Versteegden

Abstract

Critical illness leads to profound skeletal muscle dysfunction, contributing to long-term disability in survivors. This dissertation integrates healthcare delivery, biological, and clinical approaches to identify determinants of muscle dysfunction and functional recovery. Chapter 1 contextualizes muscle wasting related to critical illness, including recommended rehabilitation approaches to minimize muscle dysfunction. Chapter 2 demonstrates that, compared with non-Hispanics, Hispanic adults with critical illness experienced reduced and delayed access to physical rehabilitation, a key modifiable factor within the recovery pathway. Chapters 3 and 4 systematically synthesize muscle biopsy literature characterizing the biological basis of muscle dysfunction, showing that both respiratory and peripheral muscles exhibit marked atrophy, contractile dysfunction, mitochondrial abnormalities, and increased proteolysis, reflecting a multifaceted biological disturbance. Meta-analyzes suggested that muscle atrophy is primarily driven by higher protein degradation rather than lower protein synthesis compared with non-ICU controls. Chapter 5 explores the contribution of diaphragm structure and function to physical performance at hospital discharge, showing that diaphragmatic ultrasound measures, particularly thickness and thickening fraction, were independently associated with 30-second sit-to-stand performance in survivors of critical illness. Our findings highlight that muscle dysfunction in critical illness is multifactorial, influenced by disparate rehabilitation delivery and complex biological mechanisms. This work integrates both biological mechanisms of peripheral and respiratory muscles and physical rehabilitation delivery to optimize recovery after critical illness.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2026.379

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Archival

Funding Information

  • Center for Health, Engagement and Transformation (CHET), University of Kentucky College of Medicine
    • Fund title/number: Center for Health, Engagement and Transformation (CHET) Research Funding (no grant number applicable)
    • Funding year(s): 2025
  • National Institutes of Health (NIH)
    • Fund title/number: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (R01AR081002)
    • Funding year(s): 2023–2028

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