The impact of extended bed rest on the musculoskeletal system in the critical care environment.

Prolonged immobility is harmful with rapid reductions in muscle mass, bone mineral density and impairment in other body systems evident within the first week of bed rest which is further exacerbated in individuals with critical illness. Our understanding of the aetiology and secondary consequences of prolonged immobilization in the critically ill is improving with recent and ongoing research to establish the cause, effect, and best treatment options. This review aims to describe the current literature on bed rest models for examining immobilization-induced changes in the musculoskeletal system and pathophysiology of immobilisation in critical illness including examination of intracellular signalling processes involved. Finally, the review examines the current barriers to early activity and mobilization and potential rehabilitation strategies, which are being, investigated which may reverse the effects of prolonged bed rest. Addressing the deleterious effects of immobilization is a major step in treatment and prevention of the public health issue, that is, critical illness survivorship

Acute skeletal muscle wasting in the critically ill

Introduction: Critical illness survivors demonstrate skeletal muscle wasting with associated functional impairment. I prospectively characterised this process, and defined the pathogenic roles of altered protein synthesis and degradation. Methods: Critically ill patients (n=63, 59% male, age 54.7±18.0 years, APACHE II score 23.5±6.5) were recruited <24 hours following intensive care admission. Muscle loss trajectory was determined through serial ultrasound measurement of rectus femoris cross-sectional area (RFCSA) and, in a subset, quantification of myofibre area (FibreCSA) and protein/DNA ratio. Histopathological analysis was performed. Muscle protein synthesis and breakdown rates were determined and respective signalling pathways examined. Results: RFCSA decreased significantly, (-17.7±12.1%, [p50% (20/37) of subjects. Protein synthesis was depressed to levels observed in fasted controls (0.035±0.018%/hr vs. 0.039±0.011%/hr, p=0.57), and increased by day 7 (0.076±0.066%/hr, p=0.03) to levels associated with fed controls (0.065+0.018%/hr, p=0.30,) independent of nutritional load. Protein breakdown remained elevated throughout (8.5±5.7 to 10.6±5.7mmol phe/min/IBW, p=0.4).Principal component analysis of intracellular signalling supported a programme of increased breakdown (r=-0.83, p=0.005) and depressed synthesis (r=-.69, p=0.041). Conclusions: Early rapid skeletal muscle wasting occurs in critical illness, is greatest in those with multi-organ failure, and results from suppression of protein synthesis and increases in catabolism. These effects are independent of feeding and are commonly associated with myonecrosis

Muscle Ultrasound Changes and Physical Function of Critically Ill Children: A Comparison of Rectus Femoris Cross-Sectional Area and Quadriceps Thickness Measurements.

UNLABELLED: Quadriceps thickness (QT) and rectus femoris cross-sectional area (RFCSA) are both used to evaluate muscle changes in critically ill children. However, their correlation and association with physical function has not been compared. OBJECTIVES: To compare QT with RFCSA changes, and their association with physical function in critically ill children. DESIGN SETTING AND PARTICIPANTS: Secondary analysis of a prospective cohort study of children 0-18 years old admitted to a tertiary mixed PICU between January 2015 and October 2018 with PICU stay greater than 48 hours and greater than or equal to one organ dysfunction. MAIN OUTCOMES AND MEASURES: Ultrasound QT and RFCSA were measured at PICU admission, PICU discharge, hospital discharge, and 6 months post-discharge. QT and RFCSA changes from baseline were compared with each other and with change in motor function, physical ability, and physical health-related quality of life (HRQOL). RESULTS: Two hundred thirty-seven images from 66 subjects were analyzed. RFCSA change was not significantly different from QT change at PICU (-8.07% [interquartile range (IQR), -17.11% to 4.80%] vs -4.55% [IQR, -14.32% to 4.35%]; p = 0.927) or hospital discharge (-5.62% [IQR, -15.00% to 9.42%] vs -8.81% [IQR, -18.67% to 2.39%]; p = 0.238) but was significantly greater than QT change at 6 months (32.7% [IQR, 5.74-109.76%] vs 9.66% [IQR, -8.17% to 25.70%]; p < 0.001). Motor function change at PICU discharge was significantly associated with RFCSA change (adjusted β coefficient, 0.02 [95% CI, 0.01-0.03]; p = 0.013) but not QT change (adjusted β coefficient, -0.01 [95% CI, -0.02 to 0.01]; p = 0.415). Similar results were observed for physical HRQOL changes at hospital discharge (adjusted β coefficient for RFCSA change, 0.51 [95% CI, 0.10-0.92]; p = 0.017 and adjusted β coefficient for QT change, -0.21 [-0.76 to 0.35]; p = 0.458). Physical ability was not significantly associated with RFCSA or QT changes at 6 months post-discharge. CONCLUSIONS AND RELEVANCE: Ultrasound derived RFCSA is associated with PICU motor function and hospital discharge physical HRQOL changes, unlike QT, and may be more useful for in-hospital muscle monitoring in critically ill children

Characterising biological mechanisms underlying ethnicity-associated outcomes in COVID-19 through biomarker trajectories: a multicentre registry analysis.

BACKGROUND: Differences in routinely collected biomarkers between ethnic groups could reflect dysregulated host responses to disease and to treatments, and be associated with excess morbidity and mortality in COVID-19. METHODS: A multicentre registry analysis from patients aged ≥16 yr with SARS-CoV-2 infection and emergency admission to Barts Health NHS Trust hospitals during January 1, 2020 to May 13, 2020 (wave 1) and September 1, 2020 to February 17, 2021 (wave 2) was subjected to unsupervised longitudinal clustering techniques to identify distinct phenotypic patient clusters based on trajectories of routine blood results over the first 15 days of hospital admission. Distribution of trajectory clusters across ethnic categories was determined, and associations between ethnicity, trajectory clusters, and 30-day survival were assessed using multivariable Cox proportional hazards modelling. Secondary outcomes were ICU admission, survival to hospital discharge, and long-term survival to 640 days. RESULTS: We included 3237 patients with hospital length of stay ≥7 days. In patients who died, there was greater representation of Black and Asian ethnicity in trajectory clusters for C-reactive protein and urea-to-creatinine ratio associated with increased risk of death. Inclusion of trajectory clusters in survival analyses attenuated or abrogated the higher risk of death in Asian and Black patients. Inclusion of C-reactive protein went from hazard ratio (HR) 1.36 [0.95-1.94] to HR 0.97 [0.59-1.59] (wave 1), and from HR 1.42 [1.15-1.75]) to HR 1.04 [0.78-1.39] (wave 2) in Asian patients. Trajectory clusters associated with reduced 30-day survival were similarly associated with worse secondary outcomes. CONCLUSIONS: Clinical biochemical monitoring of COVID-19 and progression and treatment response in SARS-CoV-2 infection should be interpreted in the context of ethnic background

Can the critically ill patient generate sufficient energy to facilitate exercise in the ICU?

S.M.P. is supported by a National Health and Medical Research Council Early Career Fellowship (#1111640) and was a recipient of a short-term European Respiratory Society Fellowship in 2016

Emerging outcome measures for nutrition trials in the critically ill

This is a pre-copyedited, author-produced version of an article accepted for publication in Current Opinion in Clinical Nutrition and Metabolic Care following peer review. The version of record Bear, D. E., et al. (2018). "Emerging outcome measures for nutrition trials in the critically ill." Current Opinion in Clinical Nutrition and Metabolic Care 21(6): 417-422. is available online at: doi: 10.1097/MCO.000000000000050

Functional Outcomes and Physical Impairments in Pediatric Critical Care Survivors: A Scoping Review

This is a pre-copyedited, author-produced version of an article accepted for publication in Pediatric Critical Care Medicine following peer review. The version of record is available online at: DOI: 10.1097/PCC.0000000000000706.Ms. Ong is currently receiving a grant (KKHHEF/2014/05) from “KK Women’s and Children’s Hospital Health Endowment Fund” and is supported by a graduate research scholarship from the National University of Singapore. She received funding from the National University of Singapore Graduate Research Grant. Dr. Lee received funding from the KK Women's and Children's Hospital

Designing nutrition-based interventional trials for the future: addressing the known knowns

Abstract The consistent decline in critical illness mortality has a significant effect on trial design, whereby either an improbable effect sizes or large number of patients are required. The signal-to-noise ratio is of particular interest for the critically ill. When considering the potential signal, interventions need to match outcomes in regard to biological plausibility. Provision of nutrition is a complex decision with many underappreciated aspects of noise. However, a fundamental interaction is often not accounted for time. Working as a community to evolve trial design will be our challenge for nutrition interventions in the critically ill for the future

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial

Background Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. Methods This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. Discussion If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients.</p