A Randomized, Controlled Clinical Trial Comparing Remimazolam Besylate Combined With Alfentanil Versus Propofol Combined With Alfentanil for Anesthesia in Thoracic Surgery

Study Design:

This is a prospective, randomized, single-blind, parallel-group, controlled clinical trial. It is designed as a Phase IV study comparing the clinical profiles of two established anesthetic regimens.

Background and Rationale:

Thoracic surgery, particularly procedures requiring one-lung ventilation, poses significant challenges for anesthetic management, demanding excellent hemodynamic stability and respiratory control. Propofol, while a mainstay for total intravenous anesthesia, is associated with dose-dependent hypotension and respiratory depression. Remimazolam, a novel ultrashort-acting benzodiazepine, is metabolized by tissue esterases and may offer a more stable hemodynamic profile. Combining it with the short-acting opioid alfentanil could provide an effective and potentially safer alternative for thoracic anesthesia. This study seeks to generate high-level evidence comparing these two combinations in a surgical setting known for its physiological demands.

Intervention Protocol:

• Premedication & Induction: All patients will receive standardized premedication. Anesthesia induction will begin with alfentanil (10 μg/kg), followed by the study drug: either Remimazolam Besylate (0.3 mg/kg) or Propofol (1.5-2 mg/kg).
• Maintenance: Anesthesia will be maintained via continuous infusion of the assigned study drug (Remimazolam: 0.2-1 mg/kg/h; Propofol: 2-6 mg/kg/h) along with alfentanil (0-1 μg/kg/min), titrated to maintain a Bispectral Index (BIS) value between 40-60.
• Standardization: All patients will undergo standardized monitoring, airway management, and surgical and analgesic protocols as per institutional guidelines for thoracic surgery.

Primary Objectives:

To compare the incidence of intraoperative hypoxemia (SpO₂ < 90% for >10 seconds) and intraoperative hypotension (MAP < 65 mmHg or a decrease >20% from baseline) between the two groups.

Key Secondary Objectives:

Include comparison of: hemodynamic variables, need for rescue interventions, times to extubation and recovery, total drug consumption, incidence of postoperative nausea/vomiting (PONV), postoperative pulmonary complications, quality of recovery (QoR-15), and satisfaction scores from patients and surgeons.

Statistical Analysis:

Data will be analyzed based on the Intention-to-Treat principle. Categorical data will be compared using Chi-square or Fisher's exact test. Continuous data will be analyzed using Student's t-test or Mann-Whitney U test, as appropriate. Subgroup analyses are planned for specific patient populations.

Inclusion criteria

• Patients scheduled for elective thoracic surgery (e.g., pulmonary lobectomy, esophagectomy) under general anesthesia with preserved spontaneous respiration.
• American Society of Anesthesiologists (ASA) physical status class I-III.
• Age between 18 and 75 years.
• Provide written informed consent.

Exclusion criteria

• Severe hepatic or renal dysfunction (e.g., Child-Pugh class C, eGFR < 30 mL/min/1.73m²).
• Severe respiratory dysfunction (e.g., COPD GOLD stage 3-4, severe asthma).
• Anticipated difficult airway (e.g., Mallampati class IV, history of difficult intubation).
• Known allergy or hypersensitivity to benzodiazepines, opioids, or propofol.
• Pregnancy or lactation.
• Participation in another interventional clinical trial within the past 3 months.
• Mental illness or inability to cooperate with assessments.