To investigate whether the inhaled anesthetic desflurane, compared with propofol, exerts cardioprotective effects and reduces the incidence of severe postoperative major cardiac events in patients undergoing coronary artery bypass graft (CABG) surgery.

Cardiac surgery is among the highest-risk surgical procedures, with a high incidence of severe postoperative complications that affect patient prognosis. It is a critical factor significantly increasing perioperative mortality and poses a major challenge to the prognosis of patients undergoing cardiac surgery. Coronary-artery bypass grafting (CABG) is the most common cardiac surgery, with over 300,000 procedures performed annually in the United States alone. The incidence of cardiac complications after cardiac surgery is as high as 50%, including approximately 35% for new-onset atrial fibrillation, 30% for acute kidney injury, 16% for respiratory failure, 5% for severe infection, and an in-hospital mortality rate of about 3.5%. Key pathogenic factors contributing to severe complications after cardiac surgery include surgical stress responses, insufficient organ perfusion during perioperative management, and tissue/organ damage or dysfunction caused by oxidative stress responses induced by the release of inflammatory factors.

Outcomes and prognosis following cardiac surgery are influenced by patient characteristics, surgical techniques, and perioperative management. Over the years, we have continuously sought to develop effective strategies to reduce the incidence of perioperative complications and mortality. Anesthesia for CABG (Coronary Artery Bypass Graft) is typically induced solely with intravenous agents (Total Intravenous Anesthesia - TIVA) or using a combination of volatile (inhaled) and intravenous agents. When administered prior to, during, or after an ischemic event, volatile anesthetics exert cytoprotective effects via multiple mechanisms. These include modulating G protein-coupled receptors, intracellular signaling pathways, gene expression, potassium channels, and mitochondrial function . Furthermore, volatile anesthetics reduce myocardial infarct size in animal models. Several randomized controlled trials (RCTs) suggest volatile anesthetics can reduce biomarkers of myocardial injury, even when administered for only a brief period before ischemia. Additionally, inhaled anesthetics , besides reducing postoperative cardiac troponin release and preserving cardiac function after cardiac surgery, may also lower the risk of myocardial infarction .

However, the impact of volatile anesthetics on postoperative complications and mortality following cardiac surgery remains inconsistent. Some meta-analyses have demonstrated reduced mortality after CABG with volatile anesthetics, a finding consistent with observations from moderate-sized randomized controlled trials. Two international consensus conferences identified volatile anesthetics as key non-surgical interventions to improve survival in patients undergoing major surgery, with potential significant clinical implications for over 300 million surgical patients annually. Guidelines from the American College of Cardiology, American Heart Association, and European Association for Cardio-Thoracic Surgery recommend applying these findings to anesthetic management in cardiac surgery patients, advocating inhalational anesthetics for maintenance in patients at cardiovascular risk to reduce postoperative complications. However, other randomized controlled trials and meta-analyses have failed to confirm such benefits. Conflicting results also exist regarding postoperative complications, including pulmonary complications, neurocognitive disorders, and renal injury.

The large-scale international multicenter Myriad trial-designed to enroll 10,600 patients undergoing isolated CABG to compare inhalational anesthetics (isoflurane, sevoflurane, or desflurane) versus intravenous propofol on postoperative mortality-the study was prematurely terminated for futility after enrolling 5,400 CABG cases. Interim analysis revealed no differences in 30-day and 1-year all-cause mortality between volatile anesthesia and total intravenous anesthesia (TIVA) groups. Another multicenter study (Br J Anaesth. 2024 Aug;133(2):296-304), involving 3,123 cardiac surgery patients across 16 Chinese centers, compared inhalational (sevoflurane/desflurane) and intravenous (propofol) anesthesia for composite outcomes including 30-day all-cause mortality and severe organ complications. No significant difference was observed: 33.8% in the inhalational group versus 33.2% in the intravenous group (adjusted OR 1.05, 95% CI 0.90-1.22; P=0.57).

Desflurane , introduced into clinical practice in 1990 as an inhaled anesthetic, is characterized by rapid induction and recovery , contributing to reduced postoperative recovery-related complications . Studies confirm that desflurane anesthesia lowers the surgical stress response , aiding in the maintenance of hemodynamic stability . Furthermore, multiple studies have found that compared to intravenous anesthesia, desflurane offers superior myocardial protection for CABG patients, reducing pulmonary complications, shortening hospital stays, lowering mortality, and improving quality of life . Its mechanisms may relate to its effects on mitochondrial permeability transition pore, mitochondrial electron transport chain, reactive oxygen species, ATP-sensitive potassium channels, G protein-coupled receptors, and protein kinase C biological functions. In non-cardiac surgery, desflurane did not reduce postoperative respiratory complications compared to sevoflurane . Although clinical evidence supporting the beneficial effects of inhaled anesthetics, particularly desflurane, in cardiac surgery patients is limited and insufficient , they do highlight its potential advantages . Research into desflurane's optimal administration method and dosage , as well as its long-term effects , is ongoing.

A recently published Meta-analysis indicated that, compared to propofol , desflurane demonstrated potential clinical benefit for surgical patients in terms of 30-day mortality, incidence of myocardial infarction, new-onset postoperative atrial fibrillation, postoperative pneumonia, and atelectasis . However, these findings stemmed from small sample sizes and underpowered studies .

Based on the available evidence, the inconsistent conclusions across current studies may stem from :

1. Differential organ-specific effects of inhalational versus intravenous anesthetics: Inhalational agents confer significant cardiovascular benefits, whereas intravenous agents offer neurological advantages. Consequently, using mortality or composite outcomes encompassing severe complications across all organ systems as primary endpoints leads to confounding of divergent effects, posing challenges for result interpretation and clinical practice guidance.
2. Heterogeneity in cardioprotective efficacy among inhalational agents: Existing studies have not restricted the type of inhalational anesthetics used. When compared to the intravenous agent propofol, commonly used inhalational anesthetics (isoflurane, desflurane, sevoflurane) exhibit heterogeneous cardioprotective effects: isoflurane shows weaker cardioprotection than propofol; sevoflurane demonstrates no significant difference; and desflurane exhibits stronger cardioprotection than propofol.
3. Impact of timing and duration of inhalational anesthetic administration: In clinical practice, the timing and duration of inhalational agent use influence their cardioprotective efficacy, representing a key source of effect heterogeneity across studies.

To date, no study has provided robust evidence supporting a preferred anesthesia regimen or agent for preventing severe complications and reducing mortality after cardiac surgery. Building upon the potential advantages of desflurane in myocardial protection and improving postoperative survival , identified in preliminary small-scale studies or exploratory analyses of other large trials , we plan to initiate a large-scale, national, multi-center randomized clinical trial (DECIDE-CABG trial) .

This trial will enroll 3,560 elective patients undergoing isolated CABG to compare the impact of desflurane-based inhaled anesthesia maintenance versus propofol-based TIVA maintenance on the incidence of major adverse cardiovascular events (MACE) and all-cause mortality at 30 days postoperatively . Through this large-scale, multi-center, randomized controlled study , we aim to definitively identify the optimal anesthesia regimen and anesthetic agents for CABG patients.

Inclusion Criteria:

1. Patients scheduled for elective coronary artery bypass grafting (CABG)
2. Age ≥ 18 years old;
3. Sign the informed consent form.

Exclusion Criteria:

1. Emergency or urgent operation
2. Concomitant valve or aortic surgery
3. History of myocardial infarction in recent 30 days
4. Current use of myocardial preconditioning-affecting medications, such as sulfonylurea (glibenclamide), allopurinol, theophylline, nicorandil(last dose < 8 hrs), etc
5. Participated in other randomized controlled clinical trials in recent 3 months
6. General anesthesia in recent 30 days
7. History of kidney and liver transplantation, or severe liver and kidney dysfunction (EGFR ≤ 20 mlgmin/1.73 m2, conventional dialysis or patients who have started dialysis; Child Pugh grade C/cirrhosis)
8. History of open heart surgery;
9. Hemodynamic instability or severe heart failure (SBP<90 mmHg or preoperative need of high-dose vasoactive drug support, placement of aortic balloon pump (IABP), ECMO or ventricular assist device, left ventricular ejection fraction<30%)
10. Adverse drug reactions to trial medications
11. History of malignant hyperthermia
12. Pregnancy or lactation

The sharing ofindividual Patient Data (lPD) will be considered at 1 year after the publication ofthe primary resultsf the project. Any request for lPD sharing Investigator (Pl), clearly outlining the intended use of the data.should be submitted as a proposal to the Pl, clearly outlining the intended use of the data

beginning 12 morths after publication of the primary results

Investigators who provide a methodologically sound proposal and whose proposed use of data has been approved by the steering committee. For instance for using lPD data for meta- analysis. Proposals sholId be submitted to principle investigator and committee the trial. To gain access, data requestors will need to sign a data access agreement