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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Muscle Weakness; Frailty; Volatile Organic Compounds; Isoprene
• Intervention / Treatment: Diagnostic test: Physical performance testing; Diagnostic test: Breath sampling and VOC analysis; Diagnostic test: Muscle ultrasound; Diagnostic test: Blood-based biomarker analysis

Detailed Description

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

• Study Type: Observational
• Enrollment (Estimated): 66

Contacts and Locations

• Study Contact: Name: Felix Klawitter, Dr. med.; Phone Number: +49381494146382; Email: felix.klawitter@med.uni-rostock.de

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Recruiting
      • Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center
      • Contact: Felix Klawitter, Dr. med.; Phone Number: +493814946382; Email: felix.klawitter@med.uni-rostock.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing elective cardiac surgery

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cardiac surgery; Patients undergoing elective cardiac surgery

Diagnostic test: Physical performance testing; Assessment of physical performance using established clinical tests and scoring systems; Diagnostic test: Breath sampling and VOC analysis; Sampling of exhaled breath and using Proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF) for VOC quantification.; Diagnostic test: Muscle ultrasound; Quantitative and qualitative assessment of different limb skeletal muscles using non-invasive ultrasound.; Diagnostic test: Blood-based biomarker analysis; Blood sampling and assessment of different blood-based biomarkers of muscle integrity using Enzyme-linked Immunosorbent Assay (ELISA) and Electrochemiluminescence Immunoassay (ECLIA)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Rostock
• Collaborators: Prof. Dr. Daniel A. Reuter, Head of Department, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center; Prof. Dr. Christian D. Etz, Head of Department, Department of Cardiac Surgery, Rostock University Medical Center; PD Dr. Johannes Ehler, Consultant, Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena
• Investigators: Principal Investigator: Felix Klawitter, Dr. med., Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 16, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Frailty
• Other Study ID Numbers: PREDICT (CardioDx)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No