Muscle recovery following Aortic Surgery induced ICUAW
Research type
Research Study
Full title
Prospective observational Study into Muscle Recovery following Aortic Surgery induced Intensive Care Unit Acquired Weakness (VARIANCE)
IRAS ID
245046
Contact name
Mark Griffiths
Contact email
Sponsor organisation
Barts Health
Duration of Study in the UK
2 years, 9 months, 2 days
Research summary
Research Summary
Survivors of critical illness and complicated surgery now face a new challenge in recovering from the deleterious psychological and physiological effects experienced within critical care. Hence survivors have a decreased health-related quality of life and physical function. Muscle weakness, in this context called Intensive Care Unit, Acquired Weakness (ICUAW) probably plays a significant role. ICUAW can lead to a substantial increase in mortality, morbidity, hospital-acquired infections and pressure ulcers. Risk factors for ICUAW include neuromuscular blocking agents(paralysis drugs), hyperglycaemia (high blood glucose), inactivity and sepsis.
We have investigated patients undergoing aortic surgery as a model of ICUAW because half of the patients having uncomplicated surgery suffer at least 10% loss of thigh muscle bulk within a weak of surgery. The mechanisms accounting for the recovery from muscle wasting have not been investigated in this model, and the correlation between ICUAW and patient-centred outcomes during recovery such as functional ability and health-related quality of life (HRQoL) has been little studied. The purpose of this study is to fill the gap in the literature and to identify markers that identify patients as being susceptible to ICUAW and a poor recovery from there.Summary of Results
The overarching aim of this work was to explore muscle recovery in patients with intensive care unit acquired weakness (ICUAW), associated with major cardiac surgery. The principle aims and objectives to meet this were to firstly characterise the effects of aortic surgery and critical illness on muscle mass, strength, function and health related quality of life (HRQoL). The effects on muscle homeostasis were split into three parts; the acute initial muscle loss, the recovery period up to follow up and the overall trajectory. Secondly, to understand how the indices of muscle mass and strength correlate with other parameters, including muscle responses between the dominant and non-dominant limbs. Finally, this work aimed to investigate the profiles of circulating, potential biomarkers and modulators of muscle homeostasis and correlate these with clinical outcomes.
The data presented are broadly similar to previous studies, where using a similar model, approximately 50% of patients experience acute muscle wasting in the first week following cardiac surgery. However, where this work differed is that it also assessed the cohorts up until follow up, finding that contrary to the hypothesis, patients continued to waste, unlike strength, function and HRQoL which recovered well. Therefore, these data validate major cardiac surgery as a model of acute muscle wasting, aiding a greater understanding in underlying pathophysiology.
An additional difference from previous research, is that in the cohort the dominant and non-dominant limbs were assessed independently. Both limbs correlated extremely well with one another and responded similarly, post- surgery, suggesting that future research could only measure either the dominant or non-dominant limb, or take an average of both if both are available.
Certain biomolecular mediators were assayed and compared with clinical outcomes. Circulating growth differentiation factor (GDF-15) was elevated acutely returning to baseline by follow up. Circulating insulin like growth factor (IGF-1) concentrations were higher in the ‘wasters’ group than the ‘non- wasters’ group which was contrary to the expected relationship with IGF-1 being an important mediator of muscle growth. Furthermore IGF-1 at day seven correlated well with muscle size, reaffirming the previous point that IGF-1 has a role as an anabolic agent in muscle recovery or the prevention of further atrophy. With regards to novel biomarkers of muscle homeostasis, a short-lived response to injury was found in resistin, Stanniocalcin (STC-1) and Neutrophil gelatinise associated lipocalin (NGAL), consistent with their known biology as inflammatory mediators. Furthermore, when dividing into non-wasters and wasters, the group had significantly elevated results. With regards to mitochondrial peptides, MOTS-c and MT-RNR2, measured post AVR surgery, a trend decreasing up to day three and returning to normal by day seven was observed.REC name
London - Brent Research Ethics Committee
REC reference
18/LO/1618
Date of REC Opinion
28 Nov 2018
REC opinion
Further Information Favourable Opinion