Influence of Oxygen on Perioperative Outcome in Patients Undergoing General Anaesthesia for Elective Non-cardiac Surgery

Coronary Artery Disease Clinical Trial

— Promise-O2  

Official title:

Influence of Different Inspired Oxygen Fractions on Perioperative Myocardial Biomarkers, Myocardial Strain and Outcome in Patients Undergoing General Anaesthesia for Elective Non-cardiac Surgery: A Prospective Randomized Open-label Single Centre Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04808401
• Other study ID #: 2020_02560
• Status: Recruiting
• Phase: N/A
• Start date: May 7, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Dominik P Guensch, MD
• Phone: +41 31 632 03 77
• Email: dominik.guensch[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the impact of supraphysiologic oxygen (hyperoxia) on myocardial function in anaesthetized patients undergoing non-cardiac vascular surgery.

Description:

Up to 110 patients with either proven coronary artery disease (CAD) or two or more risk factors for CAD undergoing elective or non-emergent non-cardiac vascular surgery will be recruited. Three blood samples for levels of myocardial biomarkers will be obtained at different perioperative time points (before anaesthesia induction, 2 hours after skin closure and 24 hours after the end of the surgery). The three myocardial biomarkers investigated are high-sensitive Troponin T (hsTnT), N-terminal (NT)-pro hormone BNP (NT-proBNP) and heart-type fatty acid binding protein (H-FABP). In the timeframe shortly after the induction of anaesthesia and prior to the start of surgery, myocardial strain as a marker of cardiac function will be measured by transesophageal echocardiography (TEE). Echocardiography measurements will be acquired at two different oxygen states for each patient.The fraction of inspired oxygen (FiO2) will be adjusted to reach a normoxaemic state (FiO2=0.3) and a hyperoxic state (FiO2=0.8). Patients will be randomized to which oxygen level is investigated first. Thereafter, the patients are again randomly assigned to either the normoxaemic or the hyperoxic state for the remainder of the perioperative treatment until 2 hours after skin closure. Surgery will be performed as planned by the treating team. Differences in the perioperative levels of myocardial biomarkers at the different time points and their dynamics will be assessed. Echocardiography images will be analyzed in a blinded manner for cardiac function and systolic and diastolic strain parameters. The results will help anaesthesiologists to better weigh risks and benefits when selecting an inspired oxygen fraction in such patients, and will help to evaluate hyperoxia as a risk factor for myocardial injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent

• Patients eligible for the study should be scheduled for elective or non-emergent non-cardiac vascular surgery under general anaesthesia with endotracheal intubation, and have either

• proven CAD and will undergo high- or intermediate surgical risk procedure according to European (European Society of Cardiology, ESC / European Society of Anaesthesiology and Intensive Care, ESAIC) guidelines on non-cardiac surgery.

or

• two or more risk factors for CAD and will undergo high- or intermediate surgical risk procedures according to European ESC/ESAIC guidelines on non-cardiac surgery.

Exclusion Criteria:

• Acute coronary event 30 days before surgery

• Acute congestive heart failure

• Hemodynamic instability before induction of aneasthesia (vasopressor or inotrope infusion since hospitalization for index surgery)

• Atrial fibrillation or other severe arrhythmia

• Severe pulmonary disease (dependent on oxygen therapy or the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 or severe carbon monoxide diffusion impairment or severe pulmonary hypertension)

• Preoperative oxygen saturation (SpO2) below 90% on room air

• Increased risk of oxygen toxicity (e.g., chemotherapy for malignancy within 3 months, bleomycin treatment, airway laser surgery)

• Scheduled surgery in the thoracic cavity

• ICU admission for respirator weaning and delayed extubation

• Pre-existing surgical site infection (SSI)

• Current active signs of systemic inflammatory response syndrome (SIRS) or sepsis according The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

• Pregnancy

• Emergency surgery (to be performed within less than 12 hours of scheduling)

• Ambulatory surgery

• Baseline hs-TnT level elevated above 65ng/L

Related Conditions & MeSH terms

• Anesthesia
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Oxygen
Two FIO2 settings during stable general anaesthesia resulting in normoxaemic and hyperoxic arterial oxygen partial pressures.

Locations

Country	Name	City	State
Switzerland	Bern University Hospital, Inselspital	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

Devereaux PJ, Szczeklik W. Myocardial injury after non-cardiac surgery: diagnosis and management. Eur Heart J. 2020 May 1;41(32):3083-3091. doi: 10.1093/eurheartj/ehz301. — View Citation

Friess JO, Mikasi J, Baumann R, Ranjan R, Fischer K, Levis A, Terbeck S, Hirschi T, Gerber D, Erdoes G, Schoenhoff FS, Carrel TP, Madhkour R, Eberle B, Guensch DP. Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial. BJA Open. 2023 Apr 27;6:100135. doi: 10.1016/j.bjao.2023.100135. eCollection 2023 Jun. — View Citation

Guensch DP, Fischer K, Yamaji K, Luescher S, Ueki Y, Jung B, Erdoes G, Grani C, von Tengg-Kobligk H, Raber L, Eberle B. Effect of Hyperoxia on Myocardial Oxygenation and Function in Patients With Stable Multivessel Coronary Artery Disease. J Am Heart Assoc. 2020 Mar 3;9(5):e014739. doi: 10.1161/JAHA.119.014739. Epub 2020 Feb 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in hsTnT from preoperative baseline	ng/L	at 24 hours after surgery
Secondary	Incidence of myocardial injury in non-cardiac surgery (MINS)	MINS is defined as an absolute change of hsTnT levels of at least 5ng/L from preoperative baseline or an hs-TnT level of at least 65ng/L	at 24 hours after surgery
Secondary	Difference in high sensitive TnT from preoperative baseline	ng/L	at 2 hours after surgery
Secondary	Differences in N-terminal pro B-type natriuretic peptide (NT-proBNP) from preoperative baseline	pg/ml	at 2 hours and 24 hours after surgery
Secondary	Differences in heart type fatty acid binding protein (H-FABP) from preoperative baseline	pg/ml	at 2 hours and 24 hours after surgery
Secondary	Difference in myocardial time to peak strain between oxygen levels	Milliseconds (ms)	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial strain rate between oxygen levels	Change in strain over time (/second)	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial strain rate ratio between oxygen levels	Change in E/A ratio	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial displacement between oxygen levels	Millimeters (mm)	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial time to peak displacement between oxygen levels	Milliseconds (ms)	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial velocities between oxygen levels	Change in displacement over time (millimeters/second)	Through study completion, within 1hour post-induction
Secondary	Difference in myocardial velocity ratio between oxygen levels	Change in E/A ratio	Through study completion, within 1hour post-induction
Secondary	Difference in peak twist	Degrees (°)	Through study completion, within 1hour post-induction
Secondary	Difference in peak torsion	Degrees/centimeter (°/cm)	Through study completion, within 1hour post-induction
Secondary	Difference in ejection fraction (EF)	Percent (%)	Through study completion, within 1hour post-induction
Secondary	Difference in chamber volumes	Millilitres (ml)	Through study completion, within 1hour post-induction