Effects of Low-dose Esmolol on Myocardial Injury After Non-cardiac Surgery in Elderly Frail Patients

Effects of Low-dose Esmolol on Myocardial Injury After Non-cardiac Surgery in Elderly Frail Patients:A Multicenter, Prospective, Double-blind, Randomized Controlled Study

This topic will focus on the following questions: Part one: To clarify the relationship between preoperative frailty and myocardial injury (cTnT ≥0.03) after non-cardiac surgery in elderly patients; To further explore the predictive factors of myocardial injury after non-cardiac surgery （MINS） in elderly frail patients before operation. Part Two: To explore the effect of low-dose esmolol on myocardial injury after non-cardiac surgery in frail elderly patients.

Esmol is a short-acting selective β-adrenergic receptor blocker, which is often used in patients with cardiovascular diseases or hypertension. It is also used to reduce stress response, control heart rate and reduce myocardial oxygen consumption during perioperative period to effectively protect cardiac function. However, the safety and efficacy of perioperative β-blockers are still controversial due to their possible effects on renal function. Several recent studies have shown that β-blockers reduce perioperative myocardial ischemia and may reduce the risk of perioperative myocardial infarction (PMI) and cardiovascular death in high-risk patients . The 2021 American College of Cardiology /American Heart Association (ACC/AHA )guidelines for coronary revascularization suggest that dose adjustment can optimize the clinical effects of β-blockers, thereby reducing adverse effects during treatment . In addition, several studies have found that continuous intraoperative infusion of low-dose esmolol (5-10μg/kg/min) can reduce intraoperative stress response and maintain hemodynamic stability. The meta-analysis of esmolol by Ollila A et al. found that esmolol has a promising application in the prevention of perioperative myocardial ischemia and serious complications associated with long-term ischemia. Does perioperative Esmolol reduce the incidence of myocardial injury after non-cardiac surgery （MINS）? The safety, outcome and benefit of perioperative esmolol in frail patients are still unclear. Therefore, this study intends to apply the appropriate dose of esmolol to prevent cardiovascular events in elderly frailty patients undergoing non-cardiac surgery, and explore the effect of low-dose esmolol on MINS in elderly frail patients, so as to provide feasible clinical measures for the safe outcome and rehabilitation of frail patients during perioperative period.

The treatment group was given esmolol 0.5mg/kg load, 10μg /kg/min continuous pump; Patient-controlled analgesia pump (sufentanil 2 μg/kg, 2 mL/h, for 48h) was used as the postoperative analgesia regimen in the two groups. If the VAS score was >3, analgesic adjuvant drugs were given intravenously and recorded. If repeated treatment is ineffective, the study will be excluded.

The control group received the same volume of 0.9% normal saline, which was continuously pumped until the end of the operation before extubation.Patient-controlled analgesia pump (sufentanil 2 μg/kg, 2 mL/h, for 48h) was used as the postoperative analgesia regimen in the two groups. If the VAS score was >3, analgesic adjuvant drugs were given intravenously and recorded. If repeated treatment is ineffective, the study will be excluded.

The control group received the same volume of 0.9% normal saline, which was continuously pumped until the end of the operation before extubation.Patient-controlled analgesia pump (sufentanil 2 μg/kg, 2 mL/h, for 48h) was used as the postoperative analgesia regimen in the two groups. If the VAS score was >3, analgesic adjuvant drugs were given intravenously and recorded. If repeated treatment is ineffective, the study will be excluded.

incidence of Postoperative myocardial injury after non-cardiac surgery（MINS）, blood samples were collected at 1 day before surgery and 1, 2, and 3 days after surgery. MINS diagnostic criteria: Blood samples were collected before surgery, 1d, 2d and 3d after surgery for Roche fourth-generation Elecsys hs-TnT detection, cardiac troponin（cTnT） ≥ 0.03 ng/mL, and MINS can be diagnosed.

the results of 30 days after surge, demographic characteristics of patients, preoperative disease complications, the treatments number of intraoperative hemodynamic instability , hospital stays, any complications occurring within 30 days after surgery, and readmitted to hospital were recorded. Perioperative MAP < 65 mmHg or bradycardia (HR) < 50 times /min in both groups, and no spontaneous remission was found 5 minutes after the operation was stopped, that is, intervention measures were given, including ephedrine, atropine, dopamine and other treatments., demographic characteristics of patients, preoperative disease complications, the number of intraoperative hemodynamic instability treatments, length of stay, any complications occurring within 30 days after surgery, and readmitted to hospital were recorded.

Inclusion Criteria: Age ≥ 65 years; ASA: ⅰ-ⅳ; Modified frailty index (mFI) ≥ 0.21; Patients undergoing non-cardiac surgery. Exclusion Criteria: Refuse to participate; Expected hospital stay <3 days; Preoperative β-blocker therapy; History of myocardial infarction or coronary artery disease; Preoperative bradycardia (heart rate [HR] < 50 bpm) or arrhythmia; Significant cardiac insufficiency (i.e., pulmonary artery pressure >18 mm Hg, cardiac index ≤ 2.2 L/min/m 2); Severe valvular heart disease; Severe lung disease (e.g. asthma or chronic obstructive pulmonary disease); Patients with perioperative troponin elevation due to nonischemic causes (e.g., sepsis, pulmonary embolism, arrhythmia); The same patient can only be included once, regardless of whether the reason for the second operation is related to the first cause. -