Prognostic Value of Exhaled Isoprene Levels for Morbidity and Functional Outcome in Cardiosurgical Patients

Study Overview
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Brief Summary
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The perioperative preservation of functionality and quality of life plays an increasingly important role in older physically limited and frail patients undergoing cardiac surgery. Hereby, impairments of the skeletal muscle system integrity often contributes to a reduced physical performance. Early identification of these high-risk patients could help to initiate appropriate preventive and therapeutic measures. Volatile organic compounds (VOC) represent a non-invasive and real-time measurable approach for recording physiological and pathophysiological processes. Isoprene (2-methyl-1,3-butadiene) is one of the most abundantly exhaled VOCs and has recently been shown to originate from skeletal muscle metabolism. However, the prognostic value of isoprene as a volatile biomarker for skeletal muscle integrity, physical performance and functional outcome in patients undergoing cardiac surgery has not been evaluated before.

Detailed Description
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This is a single center prospective observational study evaluating exhaled isoprene as a perioperative volatile biomarker of skeletal muscle integrity, physical performance and functional outcome in cardiosurgical patients. All study participants will be assessed by comprehensive clinical examinations, laboratory testing, breath analysis and skeletal muscle ultrasound before, during as well as five and thirty days after surgery. Clinical assessments will be performed using established clinical scores and scales (e.g. the Short Physical Performance Battery and the Fried Frailty Index). Laboratory testing comprises a broad panel of blood-based biomarkers of skeletal muscle integrity and metabolism. The investigators hypothesize that: perioperative exhaled isoprene levels correlate with postoperative measures of physical performance, functional outcome and morbidity perioperative exhaled isoprene levels differ between patients with and without physical frailty perioperative exhaled isoprene levels correlate with sonographic and laboratory parameters of skeletal muscle integrity

Official Title
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Prognostic Value of Exhaled Isoprene Levels for Morbidity and Functional Outcome in Cardiosurgical Patients - A Single Center Prospective Observational Cohort Study

Conditions
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Frailty, Muscle Weakness, Volatile Organic Compounds, Isoprene

Intervention / Treatment
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* Diagnostic Test: Physical performance testing
* Diagnostic Test: Breath sampling and VOC analysis
* Diagnostic Test: Muscle ultrasound
* Diagnostic Test: Blood-based biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 65 years planned cardiac surgery operation duration >60 min Exclusion Criteria: refusal of study participation emergency / urgent surgery acute myocardial infarction acute or chronic infection Pre-existing illness with permanent restriction of mobility Pre-existing neuromuscular disease current malignant disease terminal renal insufficiency severe liver cirrhosis severe obstructive pulmonary disease

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac surgery<br>Patients undergoing elective cardiac surgery | Diagnostic Test: Physical performance testing<br>* Assessment of physical performance using established clinical tests and scoring systems<br>Diagnostic Test: Breath sampling and VOC analysis<br>* Sampling of exhaled breath and using Proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF) for VOC quantification.<br>Diagnostic Test: Muscle ultrasound<br>* Quantitative and qualitative assessment of different limb skeletal muscles using non-invasive ultrasound.<br>Diagnostic Test: Blood-based biomarker analysis<br>* Blood sampling and assessment of different blood-based biomarkers of muscle integrity using Enzyme-linked Immunosorbent Assay (ELISA) and Electrochemiluminescence Immunoassay (ECLIA)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Physical Performance Battery | Assessment of patient's physical performance using the Short Physical Performance Battery (SPPB, Score, scales 0-12), whereby a higher SPPB corresponds to a better physical performance. | day 5 after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated Ambulation Score | Assessment of functional patient outcome using the Cumulated Ambulation Score (CAS, Score, scales 0-6), whereby a higher CAS corresponds to a better functional outcome. | days 5 and 30 after surgery | 
| Morbidity | Assessment of the cumulative number of postoperative complications after surgery. | day 30 after surgery | 
| Isoprene concentration in patients with and without frailty | Comparison of exhaled isoprene levels (concentrations, part per billion volume - ppbV) measured by PTR-TOF between patients with and without physical frailty. | day 5 after surgery | 
| Medical Research Council Sum Score | Assessment of general muscle strength of study participants using the Medical Research Council Sum Score (MRCSS, Score, scales 0-60), whereby a higher MRCSS corresponds to a higher muscle strength. | day 5 after surgery | 
| Muscle thickness | Assessment of muscle thickness (mm) using muscle ultrasound in eight different limb skeletal muscles. | day 5 after surgery | 
| Concentrations of blood-based biomarkers | Assessment of blood-based biomarker concentrations (pmol/l) of skeletal muscle integrity and metabolism. | day 5 after surgery |