Acute respiratory and skeletal muscle wasting in critical illness
File(s)
Author(s)
Patel, Sunil
Type
Thesis
Abstract
Acute skeletal muscle wasting in critical illness is common and contributes to ICU acquired weakness, which negatively impacts quality of life in survivors. There is no gold-standard for describing muscle wasting and longitudinal descriptions in multiple muscle groups are lacking. Understanding the pathophysiology of myonecrosis, a common histological description during critical illness, also requires exploration.
At ICU admission, 27% of ICU patients had a low muscle mass state and lost 10% of muscle bulk on a second CT study (12 days (IQR 6-19). Furthermore, muscle quality significantly declined in parallel and was associated with underlying inflammation. Prospective assessment of peripheral and respiratory muscle in the first 14 days of critical illness showed significant loss in diaphragm, parasternal and rectus femoris muscle bulk as early as day 3. Severity of wasting between respiratory and non-respiratory muscle was not significantly different. Severe COVID-19 infection did not significantly affect the extent of wasting, High rates of wasting were associated with inflammation, but distinct phenotypes were not identified on cytokine analysis. Non-invasive assessment of parasternal muscle strain was reliable and reproducible and longitudinal modelling showed association with mechanical ventilation strategy and increased muscle atrophy.
Protein and immunohistochemical analysis of necrotic skeletal muscle showed an upregulation of pMLKL, and co-localisation and translocation with RIPK3 at day 7-10 – providing the first description of necroptosis activation in skeletal muscle during critical illness.
Ultrasound reliably described longitudinal quantitative and qualitative changes in skeletal muscle. When compared to CT imaging, the extent of loss in peripheral and respiratory muscle was similar. Muscle atrophy in COVID-19 patients was not significantly different to other aetiologies of ARDS. Parasternal muscle strain assessment may serve as a useful non-invasive measure of respiratory muscle loading. Finally, the evidence to support activation of programmed necrosis warrant further investigation.
At ICU admission, 27% of ICU patients had a low muscle mass state and lost 10% of muscle bulk on a second CT study (12 days (IQR 6-19). Furthermore, muscle quality significantly declined in parallel and was associated with underlying inflammation. Prospective assessment of peripheral and respiratory muscle in the first 14 days of critical illness showed significant loss in diaphragm, parasternal and rectus femoris muscle bulk as early as day 3. Severity of wasting between respiratory and non-respiratory muscle was not significantly different. Severe COVID-19 infection did not significantly affect the extent of wasting, High rates of wasting were associated with inflammation, but distinct phenotypes were not identified on cytokine analysis. Non-invasive assessment of parasternal muscle strain was reliable and reproducible and longitudinal modelling showed association with mechanical ventilation strategy and increased muscle atrophy.
Protein and immunohistochemical analysis of necrotic skeletal muscle showed an upregulation of pMLKL, and co-localisation and translocation with RIPK3 at day 7-10 – providing the first description of necroptosis activation in skeletal muscle during critical illness.
Ultrasound reliably described longitudinal quantitative and qualitative changes in skeletal muscle. When compared to CT imaging, the extent of loss in peripheral and respiratory muscle was similar. Muscle atrophy in COVID-19 patients was not significantly different to other aetiologies of ARDS. Parasternal muscle strain assessment may serve as a useful non-invasive measure of respiratory muscle loading. Finally, the evidence to support activation of programmed necrosis warrant further investigation.
Version
Open Access
Date Issued
2023-07-03
Date Awarded
01/01/2024
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Patel, Brijesh
Singh, Suveer
Takata, Masao
Sponsor
Healthcare Corporation of America (HCA) UK Intensive Care Research Fellowship
Publisher Department
Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)