Influence of Oxygen on Perioperative Outcome in Patients Undergoing General Anaesthesia for Elective Non-cardiac Surgery (Promise-O2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Anesthesia
• Intervention / Treatment: Drug: Oxygen

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominik P Guensch, MD; Phone Number: +41 31 632 03 77; Email: dominik.guensch@insel.ch
• Study Contact Backup: Name: Jan-Oliver Friess, MD; Phone Number: +41 31 632 39 65; Email: jan-oliver.friess@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Bern University Hospital, Inselspital
    • Contact: Dominik P Guensch, MD; Phone Number: +41 31 632 03 77; Email: dominik.guensch@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normoxaemia First + Hyperoxia Procedure; Patients will undergo TEE imaging at normoxaemia (FiO2=0.3) first, and hyperoxia (FiO2=0.8) will be targeted second. After the image acquisition patients receive hyperoxic concentrations.	Drug: Oxygen; Two FIO2 settings during stable general anaesthesia resulting in normoxaemic and hyperoxic arterial oxygen partial pressures.; Other Names: Medical gas
Experimental: Normoxaemia First + Normoxia Procedure; Patients will undergo TEE imaging at normoxaemia (FiO2=0.3) first, and hyperoxia (FiO2=0.8) will be targeted second. After the image acquisition patients receive normoxic concentrations.	Drug: Oxygen; Two FIO2 settings during stable general anaesthesia resulting in normoxaemic and hyperoxic arterial oxygen partial pressures.; Other Names: Medical gas
Experimental: Hyperoxia First + Hyperoxia Procedure; Patients will undergo TEE imaging at hyperoxia (FiO2=0.8) first, and normoxaemia (FiO2=0.3) will be targeted second. After the image acquisition patients receive hyperoxic concentrations.	Drug: Oxygen; Two FIO2 settings during stable general anaesthesia resulting in normoxaemic and hyperoxic arterial oxygen partial pressures.; Other Names: Medical gas
Experimental: Hyperoxia First + Normoxaemia Procedure; Patients will undergo TEE imaging at hyperoxia (FiO2=0.8) first, and normoxaemia (FiO2=0.3) will be targeted second. After the image acquisition patients receive normoxic concentrations.	Drug: Oxygen; Two FIO2 settings during stable general anaesthesia resulting in normoxaemic and hyperoxic arterial oxygen partial pressures.; Other Names: Medical gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in hsTnT from preoperative baseline	ng/L	at 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Difference in high sensitive TnT from preoperative baseline	ng/L	at 2 hours after surgery
Differences in N-terminal pro B-type natriuretic peptide (NT-proBNP) from preoperative baseline	pg/ml	at 2 hours and 24 hours after surgery
Differences in heart type fatty acid binding protein (H-FABP) from preoperative baseline	pg/ml	at 2 hours and 24 hours after surgery
Difference in myocardial time to peak strain between oxygen levels	Milliseconds (ms)	Through study completion, within 1hour post-induction
Difference in myocardial strain rate between oxygen levels	Change in strain over time (/second)	Through study completion, within 1hour post-induction
Difference in myocardial strain rate ratio between oxygen levels	Change in E/A ratio	Through study completion, within 1hour post-induction
Difference in myocardial displacement between oxygen levels	Millimeters (mm)	Through study completion, within 1hour post-induction
Difference in myocardial time to peak displacement between oxygen levels	Milliseconds (ms)	Through study completion, within 1hour post-induction
Difference in myocardial velocities between oxygen levels	Change in displacement over time (millimeters/second)	Through study completion, within 1hour post-induction
Difference in myocardial velocity ratio between oxygen levels	Change in E/A ratio	Through study completion, within 1hour post-induction
Difference in peak twist	Degrees (°)	Through study completion, within 1hour post-induction
Difference in peak torsion	Degrees/centimeter (°/cm)	Through study completion, within 1hour post-induction
Difference in ejection fraction (EF)	Percent (%)	Through study completion, within 1hour post-induction
Difference in chamber volumes	Millilitres (ml)	Through study completion, within 1hour post-induction

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Jan-Oliver Friess, MD, Bern University Hospital, Inselspital; Principal Investigator: Dominik P Guensch, MD, Bern University Hospital, Inselspital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Anaesthesia; Hyperoxia; Strain; Transesophageal Echocardiography (TEE); Myocardial biomarkers; Normoxaemia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 2020_02560

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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