Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Background: Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. Methods: We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. Results: There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. Conclusion: In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. Clinical Trail Registration: https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Effect of Supplemental Oxygen on von Willebrand Factor Activity and Ristocetin Cofactor Activity in Patients at Risk for Cardiovascular Complications Undergoing Moderate-to High-Risk Major Noncardiac Surgery-A Secondary Analysis of a Randomized Trial.

Increased von Willebrand Factor (vWF) activity mediates platelet adhesion and might be a contributor to the development of thrombotic complications after surgery. Although in vitro studies have shown that hyperoxia induces endovascular damage, the effect of perioperative supplemental oxygen as a possible trigger for increased vWF activity has not been investigated yet. We tested our primary hypothesis that the perioperative administration of 80% oxygen concentration increases postoperative vWF activity as compared to 30% oxygen concentration in patients at risk of cardiovascular complications undergoing major noncardiac surgery. A total of 260 patients were randomly assigned to receive 80% versus 30% oxygen throughout surgery and for two hours postoperatively. We assessed vWF activity and Ristocetin cofactor activity in all patients shortly before the induction of anesthesia, within two hours after surgery and on the first and third postoperative day. Patient characteristics were similar in both groups. We found no significant difference in vWF activity in the overall perioperative time course between both randomization groups. We observed significantly increased vWF activity in the overall study population throughout the postoperative time course. Perioperative supplemental oxygen showed no significant effect on postoperative vWF and Ristocetin cofactor activity in cardiac risk patients undergoing major noncardiac surgery. In conclusion, we found no significant influence of supplemental oxygen in patients undergoing major non-cardiac surgery on postoperative vWF activity and Ristocetin cofactor activity.

Perioperative Supplemental Oxygen and Postoperative Copeptin Concentrations in Cardiac-Risk Patients Undergoing Major Abdominal Surgery-A Secondary Analysis of a Randomized Clinical Trial.

Noncardiac surgery is associated with hemodynamic perturbations, fluid shifts and hypoxic events, causing stress responses. Copeptin is used to assess endogenous stress and predict myocardial injury. Myocardial injury is common after noncardiac surgery, and is often caused by myocardial oxygen demand-and-supply mismatch. In this secondary analysis, we included 173 patients at risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients were randomly assigned to receive 80% or 30% oxygen throughout surgery and the first two postoperative hours. We evaluated the effect of supplemental oxygen on postoperative Copeptin concentrations. Copeptin concentrations were measured preoperatively, within two hours after surgery, on the first and third postoperative days. In total, 85 patients received 0.8 FiO2, and 88 patients received 0.3 FiO2. There was no significant difference in postoperative Copeptin concentrations between both study groups (p = 0.446). Copeptin increased significantly within two hours after surgery, compared with baseline in the overall study population (estimated effect: −241.7 pmol·L−1; 95% CI −264.4, −219.1; p < 0.001). Supplemental oxygen did not significantly attenuate postoperative Copeptin release. Copeptin concentrations showed a more immediate postoperative increase compared with previously established biomarkers. Nevertheless, Copeptin concentrations did not surpass Troponin T in early determination of patients at risk for developing myocardial injury after noncardiac surgery.

Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial.

Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: -41.5 ng·L-1, 95%CI -134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L-1, 95%CI -7.6, 30.1; p = 0.24), and dopamine (effect estimated: -1.61 ng·L-1, 95%CI -7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.

Effect of perioperative levosimendan administration on postoperative N-terminal pro-B-type natriuretic peptide concentration in patients with increased cardiovascular risk factors undergoing non-cardiac surgery: protocol for the double-blind, randomised, placebo-controlled IMPROVE trial.

INTRODUCTION: Elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) after non-cardiac surgery is a strong predictor for cardiovascular complications and reflects increased myocardial strain. NT-pro-BNP concentrations significantly rise after non-cardiac surgery within the first 3 days. Levosimendan is a potent inotropic drug that increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days. Thus, we will test the effect of a pre-emptive perioperative administration of levosimendan on postoperative NT-pro-BNP concentration as compared with the administration of a placebo in patients undergoing moderate-risk to high-risk major abdominal surgery. METHODS AND ANALYSIS: We will conduct a double-blinded prospective randomised trial at the Medical University of Vienna, Vienna, Austria (and potentially a second centre in Germany), including 230 patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients will be randomly assigned to receive a single dose of 12.5 mg levosimendan versus placebo after induction of anaesthesia. The primary outcome will be the postoperative maximum NT-pro-BNP concentration between both group within the first three postoperative days. Our secondary outcomes will be the incidence of myocardial ischaemia, myocardial injury after non-cardiac surgery and a composite of myocardial infarction and death within 30 days and 1 year after surgery between both groups. Our further secondary outcome will be stratification of NT-pro-BNP values according to previously thresholds to predict mortality of myocardial infarction after surgery. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Medical University of Vienna on 14 July 2020 (EK 2187/2019). Written informed consent will be obtained from all patients a day before surgery. Results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04329624.

Perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery - A subanalysis of randomized clinical trial.

STUDY OBJECTIVE: Oxidative stress plays a pivotal role in the development and aggravation of cardiovascular diseases. The influence of intraoperative inspired oxygen concentrations on oxidative stress is still not entirely known. Therefore, we evaluated in this sub-study if supplemental oxygen affects the oxidation-reduction potential in patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. DESIGN: Sub-study of a prospective parallel-arm double-blinded single-center superiority randomized trial. SETTING: Operating room and postoperative recovery area. INTERVENTION: Administration of 0.8 FiO2 versus 0.3 FiO2 throughout surgery and for the first two postoperative hours. MEASUREMENTS: The primary outcome was the static oxidation-reduction potential (sORP) and the oxidation-reduction potential capacity (cORP) between both groups. The secondary outcome was the trend of sORP and cORP in the overall study population. We assessed sORP and cORP before induction of anesthesia, 2 h after induction of anesthesia, within 2 h after surgery and on the first and third postoperative day. MAIN RESULTS: 258 patients were analyzed. 128 patients were randomly assigned to the 80% oxygen group and 130 patients were randomly assigned to the 30% oxygen group. Postoperative sORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -1.162 mV,95% CI: -2.584 to 0.260; p = 0.109). On average, we observed a change in sORP of 5.288 mV (95% CI:4.633 to 5.913, p < 0.001) per day. cORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -0.015µC, (95%CI: -0.062 to 0.032; p = 0.524). On average, we observed a change in cORP values of -0.170µC (95%CI: -0.194 to -0.147, p < 0.001) per day. CONCLUSION: In contrast to previous reports, we could not find any evidence of an association between intraoperative supplemental oxygen and perioperative oxidative stress assessed by sORP and cORP. TRIAL REGISTRATION: clinicaltrials.gov: NCT03366857https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Perioperative supplemental oxygen and NT-proBNP concentrations after major abdominal surgery - A prospective randomized clinical trial.

STUDY OBJECTIVE: Supplemental oxygen is a simple method to improve arterial oxygen saturation and might therefore improve myocardial oxygenation. Thus, we tested whether intraoperative supplemental oxygen reduces the risk of impaired cardiac function diagnosed with NT-proBNP and myocardial injury after noncardiac surgery (MINS) diagnosed with high-sensitivity Troponin T. DESIGN: Parallel-arm double-blinded single-centre superiority randomized trial. SETTING: Operating room and postoperative recovery area. PATIENTS: 260 patients over the age of 45 years at-risk for cardiovascular complications undergoing major abdominal surgery. INTERVENTION: Administration of 80% versus 30% oxygen throughout surgery and for the first two postoperative hours. MEASUREMENTS: The primary outcome was the postoperative maximum NT-proBNP concentration in both groups, which was assessed within 2 h after surgery, and on the first and third postoperative day. The secondary outcome was the incidence of MINS in both groups. MAIN RESULTS: 128 patients received 80% oxygen and 130 received 30% oxygen throughout surgery and for the first two postoperative hours. There was no significant difference in the median postoperative maximum NT-proBNP concentration between the 80% and the 30% oxygen group (989 pg.mL-1 [IQR 499; 2005] and 810 pg.mL-1 [IQR 409; 2386], effect estimate: 159 pg.mL-1, 95%CI -123, 431, p = 0.704). There was no difference in the incidence of MINS between both groups. (p = 0.703). CONCLUSIONS: There was no beneficial effect of perioperative supplemental oxygen administration on postoperative NT-proBNP concentration and MINS. It seems likely that supplemental oxygen has no effect on the release of NT-proBNP in patients at-risk for cardiovascular complications undergoing major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03366857. https://clinicaltrials.gov/ct2/results?cond=NCT+03366857&term=&cntry=&state=&city=&dist=.