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.

Introducing a free-breathing MRI method to assess peri-operative myocardial oxygenation and function: A volunteer cohort study.

BACKGROUND: Induction of general anaesthesia has many potential triggers for peri-operative myocardial ischaemia including the acute disturbance of blood gases that frequently follows alterations in breathing and ventilation patterns. Free-breathing oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging may provide the opportunity to continuously quantify the impact of such triggers on myocardial oxygenation. OBJECTIVE: To investigate the impact of breathing patterns that simulate induction of general anaesthesia on myocardial oxygenation in awake healthy adults using continuous OS-CMR imaging. DESIGN: Prospective observational study. SETTING: Single-centre university hospital. Recruitment from August 2020 to January 2022. PARTICIPANTS: Thirty-two healthy volunteers younger than 45 years old were recruited. Data were analysed from n  = 29 (69% male individuals). INTERVENTION: Participants performed a simulated induction breathing manoeuvre consisting of 2.5 min paced breathing with a respiration rate of 14 breaths per minute, followed by 5 deep breaths, then apnoea for up to 60s inside a magnetic resonance imaging scanner (MRI). Cardiac images were acquired with the traditional OS-CMR sequence (OS bh-cine ), which requires apnoea for acquisition and with two free-breathing OS-CMR sequences: a high-resolution single-shot sequence (OS fb-ss ) and a real-time cine sequence (OS fb-rtcine ). MAIN OUTCOME MEASURES: Myocardial oxygenation response at the end of the paced breathing period and at the 30 s timepoint during the subsequent apnoea, reflecting the time of successful intubation in a clinical setting. RESULTS: The paced breathing followed by five deep breaths significantly reduced myocardial oxygenation, which was observed with all three techniques (OS bh-cine -6.0 ±â€Š2.6%, OS fb-ss -12.0 ±â€Š5.9%, OS fb-rtcine -5.4 ±â€Š7.0%, all P  < 0.05). The subsequent vasodilating stimulus of apnoea then significantly increased myocardial oxygenation (OS bh-cine 6.8 ±â€Š3.1%, OS fb-ss 8.4 ±â€Š5.6%, OS fb-rtcine 15.7 ±â€Š10.0%, all P  < 0.01). The free-breathing sequences were reproducible and were not inferior to the original sequence for any stage. CONCLUSION: Breathing manoeuvres simulating induction of general anaesthesia cause dynamic alterations of myocardial oxygenation in young volunteers, which can be quantified continuously with free-breathing OS-CMR. Introducing these new imaging techniques into peri-operative studies may throw new light into the mechanisms of peri-operative perturbations of myocardial tissue oxygenation and ischaemia. VISUAL ABSTRACT: http://links.lww.com/EJA/A922.

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.

Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. METHODS: In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. RESULTS: The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P < 0.001). Concomitantly, the levels of the biomarker angiopoietin-2 rose, showing a strong correlation based on the time points of measurements (r = 0.959, P = 0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of capillary leak were increased. After controlling for common risk factors of edema formation, we found that an increase of 1 ng/mL in angiopoietin-2 was associated with a 0.24L increase in extracellular water (P < 0.001). Angiopoietin-2 showed increased odds for the development of acute kidney injury (OR 1.095 [95% CI 1.032, 1.169]; P = 0.004) and was furthermore associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. Machine learning predicted postoperative complications when capillary leak was added to standard risk factors. CONCLUSIONS: Capillary leak and subsequent edema formation are relevant problems after cardiac surgery. Levels of angiopoietin-2 in combination with extracellular water show promising potential to predict postoperative complications after cardiac surgery. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS No. 00017057), Date of registration 05/04/2019, www.drks.de.

The use of minimal invasive extracorporeal circulation for rewarming after accidental hypothermia and circulatory arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation has become a recommended treatment option for patients with severe hypothermia with cardiac arrest. Minimal invasive extracorporeal circulation (MiECC) may offer advantages over the current standard extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective cohort analysis of hospital database for patients with accidental hypothermia and extracorporeal rewarming with MiECC admitted between 2010 and 2019. RESULTS: Overall, six of 17 patients survived to hospital discharge. Eleven patients suffered accidental hypothermia in an alpine and six in an urban setting. Sixteen patients arrived at the hospital under ongoing cardiopulmonary resuscitation (CPR). CPR time was 90 minutes (0-150). Four patients survived from an alpine setting and two from an urban setting with CPR duration of 90 minutes (0-150) and 85 minutes (25-100), respectively. Asphyctic patients tended to have lower survival (one of seven patients). Two patients of six with major trauma survived. CONCLUSION: MiECC for extracorporeal rewarming from severe accidental hypothermia is a feasible alternative to ECMO, with comparable survival rates.