Clinical trial NCT03714399: Muscle Recovery Following Aortic Surgery Induced ICUAW.
Official title: A Prospective Observational Study Into Muscle Recovery Following Aortic Surgery Induced Intensive Care Unit-acquired Weakness (VARIANCE).
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Diseases
Intensive Care Unit Syndrome
Intensive Care Neuropathy
Intensive Care (ICU) Myopathy
Critical Illness Myopathy
Surgery
Keywords: Intensive Care Unit Acquired Weakness (ICUAW)
Critical Illness Polyneuromyopathy (CIPM)
Health Related Quality of Life (HRQoL)
Ultrasound (US)
Cardiac Surgery
Rectus Femoris Cross Sectional Area (RFcsa)
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
Collaborators: name: Queen Mary University of London
First posted: 2018-10-22
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inclusion criteria include any consenting adult receiving elective aortic surgery at Bartshealth NHS trust with no evidence of pre-hospital neuromuscular conditions.

Brief summary: To identify determinants of 'good and bad recovery' from ICUAW and build knowledge around the timing of these processes. Also, the investigators want to discover the effects of ICUAW on physical function and HRQoL following aortic surgery.

Detailed description: The aim is to identify determinants of recovery from intensive care unit-acquired weakness (ICUAW) and to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after critical illness. This phenomenon has become more evident over recent years and still requires extensive research.

ICUAW is an umbrella term for more specifically, polyneuropathy and myopathy. Recent research has found that 50% of patients undergoing elective cardiac surgery lose significant muscle mass (9.6% in the wasters group) within the first seven days. These patients are receiving relatively uncomplicated surgery yet still suffering from muscle breakdown, which cannot be described by inactivity alone. ICUAW can lead to a significant increase in mortality, morbidity, hospital-acquired infections and pressure ulcers. Risk factors for ICUAW include neuromuscular blocking agents, hyperglycaemia, inactivity and sepsis. The correlation between a relatively homogenous (cardiac surgical) group and patient-centred outcomes during recovery such as functional ability and health-related quality of life (HRQoL) has been little studied.

Patients undergoing elective aortic valvular surgery at St Bartholomew's Hospital London will be recruited for the study. We have chosen the cardiac surgical model due to being a homogenous cohort where the time of insult from surgery from the cardiac bypass, can be measured in correlation with ICUAW. Due to the clamped aorta within the operation, prolonged periods of reduced blood flow to the body occurs, and therefore an element of ischaemia and reperfusion can lead to muscle wasting. Rectus Femoris cross-sectional area (RFcsa) will be measured at pre-determined intervals and the images then greyscaled and muscle quality assessed. To assess and quantify 'good and bad recovery,' we will correlate these tests with functional capacity and HRQoL. Additionally, Blood and urine samples will be taken at pre-defined intervals to observe for markers of oxidative stress, organ injury and molecular profiles. Muscle biopsies will be taken during surgery and observed for histological and fibre profiles.

The primary objective is to identify determinants of recovery from ICUAW and to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after aortic valvular surgery. Specifically, to observe the cross-sectional area of the Rectus Femoris (RFcsa) and correlate this with muscle strength and HRQoL during the recovery phase. The RFcsa, hand-held dynamometry, knee straightening dynamometry, Free Fat Mass Index, standing and lying vital capacity and the short physical performance battery (SPPB) will be observed. Also, HRQoL will be measured using the reintegration to normal living index (RNLI), hospital and anxiety depression score (HADS), EQ-5D-5L (EuroQol research foundation). The primary endpoint will be once all these data are gathered and analysed.

The secondary aim is to understand the molecular and genomic profile of blood samples and the histology of the muscle biopsies. The secondary objective will be supported with additional data from urine analysis (Albumin-creatinine ratio, ACR). The secondary endpoint will be once these data are gathered and analysed.

Eligibility criteria: Inclusion Criteria:

* Above the age of 18
* Receiving elective aortic valvular surgery at Barts Health NHS Trust

Exclusion Criteria:

* Previous Stroke
* Neuromuscular disease
* Malignancy
* Underlying neuromuscular disease
* Paediatrics
* Non-consenting adults

Primary outcomes:
measure: To observe the change in cross sectional area of the Rectus Femoris (RFcsa) during critical illness and recovery.
timeFrame: Pre-operatively, day 7/Hospital Discharge and 6-15week follow up clinic.
measure: To Observe a change in Hand Held Dynamometry strength (grip strength) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Pre-operatively, Day 7/Hospital Discharge and 6-15 week follow up clinic.
measure: To observe a change in Knee straightening dynamometry, strength and joint moment (torque) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Pre-operatively, Day 7/Hospital Discharge and 6-15 week follow up clinic.
measure: To observe a change in Short Physical Performance Battery (SPPB) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Pre-operatively, Day 7/Hospital Discharge and 6-15 week follow up clinic.
measure: Lying and Standing Vital Capacity (FVC - forced vital capacity) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Pre-operatively, Day 7/Hospital Discharge and 6-15 week follow up clinic.
measure: To measure Free Fat Mass Index (FFMI) and correlate this with RFcsa, function and HRQoL during critical illness and recovery.
timeFrame: Pre-operatively, Day 7/Hospital Discharge and 6-15 week follow up clinic.
measure: To measure the EQ-5D-5L (Euroscore) to assess general health and correlate this with the primary objective (RFcsa).
timeFrame: Pre operatively, Day 7/Hospital discharge and 6-15 week follow up.
measure: Hospital anxiety and depression score (HADS) to assess HRQoL and correlate this with the overall primary objective (RFcsa).
timeFrame: Pre-operatively, Day 7/Hospital discharge and 6-15 week follow up.
measure: Reintegration to normal living index (RNLI) to assess HRQoL and correlate this with the overall primary objective (RFcsa).
timeFrame: Pre-operatively and 6-15 week follow up clinic.
Secondary outcomes:
measure: The secondary aim is to understand the molecular profile (bloods).
timeFrame: Pre-operatively, Day 1, Day 3, Day 7/hospital discharge and 6-15 week follow up.
measure: Urine Analysis
timeFrame: pre-operatively, Day 1, Day 3, Day 7/hospital discharge and 6-15 week follow up.
measure: Muscle Biopsy
timeFrame: Intra-operatively
measure: Cardiac post operative morbidity score (C-POMS) will be used to calculate morbidity risk.
timeFrame: Day 3, day 5, day 8 and day 15 post cardiac surgery.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Bartholomew's hospital (Barts NHS trust)
Study officials:
affiliation: Substantive Employee and primary supervisor to PhD student
name: Mark Grffiths, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Director of research and supervisor to PhD student
name: Julie Sanders, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Substantive employee and PhD student
name: Ashley Thomas, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bloch SA, Donaldson AV, Lewis A, Banya WA, Polkey MI, Griffiths MJ, Kemp PR. MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery. Crit Care. 2015 Apr 7;19(1):147. doi: 10.1186/s13054-015-0853-5.