Glycemic Variability and Autonomic Nervous System in Cardiac Surgery Patients (CAESAR)

Perioperative Blood Glucose Variability and Autonomic Nervous System Activity in On-pump Cardiac Surgery Patients: Study Protocol of a Single-center Observational Study.

On-pump coronary artery bypass graft (CABG) and valve replacement surgeries are high-risk procedures. Among the risk factors for postoperative complications, perioperative hyperglycemia and blood glucose variability have been reported to be associated with increased morbidity and mortality. The treatment of hyperglycemia using intravenous insulin infusion improves the prognosis in cardiac surgery patients. However, the determinants of postoperative blood glucose variability and the mechanisms leading to its deleterious impact are unknown. Thus, to date, there is no therapeutic intervention that could effectively prevent and treat the deleterious impact of glycemic variability on postoperative outcome. The purpose of the study is to evaluate whether perioperative alteration of the autonomic nervous system and preoperative blood glucose variability could be related to perioperative glycemic variability.

Study Overview

• Status: Completed
• Conditions: Autonomic Nervous System; Cardiac Surgical Procedures; Blood Glucose Variability
• Intervention / Treatment: Procedure: coronary artery bypass surgery; Procedure: aortic valve replacement surgery

Detailed Description

The main objective is to describe the relationship between preoperative glycemic variability and glycemic variability during the first 48 postoperative hours.

The secondary objectives are :

1. to describe the relationship between preoperative glycemic variability and glycemic variability during the first 48 hours postoperative according to:

   • diabetic and non-diabetic status
   • the type of surgical intervention

2. to describe the relationship between the parameters evaluating the preoperative activity of the autonomic nervous system and:

   • preoperative glycemic variability
   • glycemic variability during the first 48 postoperative hours

3. to describe the relationship between glycemic variability during the first 48 postoperative hours and:

   • parameters evaluating the activity of the autonomic nervous system during the first 48 postoperative hours
   • diabetes phenotype
   • markers of inflammation
   • markers of endothelial dysfunction
4. to describe the morbidity and mortality within 30 days after surgery.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • Post operative intensive care unit of the cardiac surgery department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Diabetic and non-diabetic adult patients undergoing planned on-pump cardiac surgery

Description

Inclusion Criteria:

• Planned cardiac surgery
• Age ≥ 18 years old and < 80 years old
• Group 1: patients with known insulin-requiring type 2 diabetes mellitus undergoing planned on-pump coronary artery bypass surgery
• Group 2: patients with known non-insulin-requiring type 2 diabetes mellitus undergoing planned on-pump coronary artery bypass surgery
• Group 3: non-diabetic patients undergoing planned aortic valve replacement surgery
• Group 4: non-diabetic patients undergoing planned on-pump coronary artery bypass surgery

Exclusion Criteria:

• Emergent surgery (less than 48 hours between anesthestetic consultation and surgery)
• Combined surgery (coronary artery bypass graft associated with valve surgery, multiple valve replacement, surgery of the ascending aorta)
• Extreme weight: body mass index (BMI) > 35 kg.m-2 or < 18 kg.m-2.
• Off-pump coronary artery bypass graft surgery
• Type 1 diabetes mellitus
• Patient unable to consent
• Pregnant and/or breastfeeding woman
• Permanent preoperative chronic heart rhythm disorder
• Pacemaker
• Unstable patient condition in preoperative period
• Expected life expectancy less than 48 hours.
• Subject unlikely to cooperate in the study and/or low cooperation anticipated by the investigator.
• Duration of continuous preoperative glycemic recording of less than 48 hours.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; patients with known insulin-requiring type 2 diabetes mellitus undergoing planned on-pump coronary artery bypass graft surgery	Procedure: coronary artery bypass surgery; coronary artery bypass surgery
Group 2; patients with known non-insulin-requiring type 2 diabetes mellitus undergoing planned on-pump coronary artery bypass surgery	Procedure: coronary artery bypass surgery; coronary artery bypass surgery
Group 3; non-diabetic patients undergoing planned aortic valve replacement surgery	Procedure: aortic valve replacement surgery; aortic valve replacement surgery
Group 4; non-diabetic patients undergoing planned on-pump coronary artery bypass graft surgery	Procedure: coronary artery bypass surgery; coronary artery bypass surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability, measured by subcutaneous blood glucose continuous monitoring sensor, calculated by the coefficient of glycemic variability	Continuous blood glucose monitoring using a subcutaneous blood glucose continuous monitoring sensor (FreeStyle Libre Pro)	From 14 days before surgery (at least 48 hours before surgery) to 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autonomic nervous system activity, measured by non-invasive continuous heart rate monitoring, calculated by measuring the R-R interval	Continuous non-invasive continuous heart rate monitoring using the MooKy HR memory device will allow the continuous measurement of the R-R interval and the R-R interval variability to quantify the activity of the autonomic nervous system.	From the day before surgery (at admission in the cardiac surgery department the day before surgery) to Day 3 after surgery
Vasopressine blood level	Vasopressine blood level will be measured from blood samples to assess the relationship between blood glucose variability and endothelial dysfunction.	The day before surgery, at admission in the postoperative intensive care unit, at day 1 and at day 2 after surgery
Autonomic nervous system activity	Compass 31 scale: the Compass 31 scale is a validated clinical scale that allows to identify the degree au autonomic nervous system dysfunction.	The day before surgery.
Endocan blood level	Endocan blood level will be measured from blood samples to assess the relationship between blood glucose variability and endothelial dysfunction.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.
8-iso PGF2a urinary level	8-iso PGF2a urinary level will be measured from urinary samples to assess the relationship between blood glucose variability and oxidative stress.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.
IL-6 blood level	IL-6 blood level will be measured from blood samples to assess the relationship between blood glucose variability and systemic inflammation.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.
IL-10 blood level	IL-10 blood level will be measured from blood samples to assess the relationship between blood glucose variability and systemic inflammation.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.
TNF-alpha blood level	TNF-alpha blood level will be measured from blood samples to assess the relationship between blood glucose variability and systemic inflammation.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.
Angiotensine blood level	Angiotensine blood level will be measured from blood samples to assess the relationship between blood glucose variability and endothelial dysfunction.	The day before surgery, and at admission in the postoperative intensive care unit, and at day 1 and at day 2 after surgery.

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Guillaume BESCH, MD, PhD, CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2021/616

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No