Perioperative hyperoxia- impact on myocardial biomarkers, strain and outcome in high-risk patients undergoing non-cardiac surgery: Protocol for a prospective randomized controlled trial.

BACKGROUND: Supplemental oxygen is used during every general anesthesia. However, for the maintenance phase of a general anesthesia, in most cases the longest part of anesthesia, only scarce evidence of dosing supplemental oxygen exists. Oxygen is a well-known coronary vasoconstrictor and thus may contribute to cardiovascular complications especially in vulnerable high-risk patients with coronary artery disease undergoing major non-cardiac surgery. Myocardial biomarkers are early indicators of myocardial injury. Oxygen supply demand mismatches due to coronary artery disease aggravated by hyperoxia might be displayed by changes from the biomarker's baseline-values. This study is designed to detect changes in myocardial biomarkers levels associated with perioperative hyperoxia. METHODS: This prospective randomized controlled interventional trial investigates the impact of maintaining perioperative high oxygen supplementation in high-risk patients undergoing non-cardiac vascular surgery on cardiac biomarkers, myocardial strain and outcome in 110 patients. Patients are allocated to be supplemented with either 0.3 (normal) or 0.8 (high) fraction of inspired oxygen (FiO2) perioperatively. Included is a short crossover phase during which transesophageal echocardiography is used to evaluate myocardial function at FiO2 0.3 and 0.8 by strain analysis in each patient. Patients will be followed up for complications at 30 days and 1 year. CONCLUSION: The trial is designed to evaluate perioperative changes from baseline myocardial biomarkers associated with perioperative FiO2. Furthermore, exploration and correlation of changes in biomarkers, acute early changes in myocardial function and clinical outcomes induced by different FiO2 may be possible.

Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial.

Background: There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods: Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results: There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions: Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration: NCT04424433.

Study design for a randomized crossover study investigating myocardial strain analysis in patients with coronary artery disease at hyperoxia and normoxemia prior to coronary artery bypass graft surgery (StrECHO-O2).

BACKGROUND: Supplemental oxygen (O2) is used routinely during anesthesia. In the treatment of acute myocardial infarction, it has been established that hyperoxia is to be avoided, whereas information on benefit and risk of hyperoxia in patients with stable coronary artery disease (CAD) remain scarce, especially in the setting of general anesthesia. This study will compare the immediate effects of normoxemia and hyperoxia on cardiac function, with a primary focus on changes in peak longitudinal left-ventricular strain, in anesthetized stable chronic CAD patients using peri-operative transesophageal echocardiography (TEE). METHODS: A single-center randomized cross-over clinical trial will be conducted, enrolling 106 patients undergoing elective coronary artery bypass graft surgery. After the induction of anesthesia and prior to the start of surgery, cardiac function will be assessed by 2D and 3D TEE. Images will be acquired at two different oxygen states for each patient in randomized order. The fraction of inspired oxygen (FIO2) will be titrated to a normoxemic state (oxygen saturation of 95-98%) and adjusted to a hyperoxic state (FIO2 = 0.8). TEE images will be analyzed in a blinded manner for standard cardiac function and strain parameters. CONCLUSION: By using myocardial strain assessed by TEE, early and subtle signs of biventricular systolic and diastolic dysfunction can be promptly measured intraoperatively prior to the onset of severe signs of ischemia. The results may help anesthesiologists to better understand the effects of FIO2 on cardiac function and potentially tailor oxygen therapy to patients with CAD undergoing general anesthesia.