Abstract
Intensive care unit-acquired weakness (ICU-AW) impairs hospital outcomes and causes a long-term physical disability among ICU survivors. No treatment has yet been identified. Repetitive vascular occlusion stimulus (RVOS) induces brief repeated ischaemia and reperfusion cycles using a cuff and could be a novel intervention to prevent ICU-AW. RVOS limits disuse muscle atrophy and weakness in both healthy controls and bed-bound orthopaedic patients improves vascular function and induces systemic anti-inflammatory effects.
This thesis investigated the feasibility and efficacy of RVOS application to ICU patients and examined the underlying mechanisms of its reported protective effects in healthy controls. Methodologies utilised included: ultrasonography to assess the skeletal muscle size and vascular function, strength and physical function tests to assess functionality, immunoassays on plasma and muscle biopsies to assess blood biomarkers and signalling pathway, NIRS to assess microcirculation, and flow cytometry to assess inflammatory markers on circulatory leukocytes.
Recruitment of ICU patients was low due to high ineligibility and low consent rates. RVOS application appears safe and acceptable and indicated a positive effect against target organ failure (lower AKI incidence and greater SOFA score reduction) (Chapter 3). No effectiveness against muscle wasting and vascular dysfunction were detected, however, an increase in growth factor IGF-1 and reduction in vascular dysfunction and inflammatory markers syndecan-1, IL-4, and TNF-RII were observed (Chapter 4). In healthy controls, no upregulation in the Akt/mTOR protein synthesis signalling pathway was observed in local muscle tissue, despite inducing significant ischemic and reactive hyperaemic stimulus. No remote effects on vessel and microcirculation of skeletal muscle were observed (Chapter 5). Downregulation of CD11b, Hsp70, NF-κBp65, and p38MAPK levels in activated NK and monocytes and upregulation in p38MAPK were observed in activated neutrophils, suggesting subset specific effect (Chapter 6).
RVOS application to ICU patients was not feasible, however, the observed effects on target organs, biomarkers, and leukocyte subsets warrant further investigation.