Comparison of Anesthetic Quality and Recovery Between Afentanil and Remifentanil: A Multicenter, Randomized, Double-Blind, Controlled, Non-Inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 990
- 主要终点
- Incidence of Intraoperative Rescue Events
研究概览
简要总结
The goal of this clinical trial is to compare two commonly used opioid pain medications-alfentanil and remifentanil-during general anesthesia for surgery, and to find out whether alfentanil is as good as (not worse than) remifentanil in keeping patients stable (steady blood pressure and heart rate) and adequately pain-free during the operation. The study will enroll adults aged 18-65 years who are in good to fair health (ASA class I-III) and are scheduled for elective non-cardiac, non-brain surgery lasting 1 to 4 hours with expected blood loss under 500 mL.
The main questions it aims to answer are:
How often do patients need extra painkillers or blood-pressure medications during surgery (a "rescue event") when receiving alfentanil compared with remifentanil?
How quickly do patients wake up, breathe on their own, and get discharged from the recovery room after the operation?
Do patients experience differences in pain levels, nausea, vomiting, or thinking/memory problems in the days after surgery?
If there is a comparison group: Researchers will compare the alfentanil group with the remifentanil group to see if the rate of rescue events with alfentanil is not more than 8% higher than with remifentanil (the non-inferiority margin). Both groups will receive the same standard anesthetic (propofol and muscle relaxants) and the same postoperative pain management; only the study opioid differs.
Participants will:
Sign an informed consent form and undergo screening tests, including blood work, physical exam, and medical history review.
Be randomly assigned (like a coin flip) to receive either alfentanil or remifentanil during their operation, with the drug given through an IV. Neither the patient nor the care team will know which drug is given until after the study is completed.
Have their blood pressure, heart rate, breathing, and brain activity (using BIS monitors to measure depth of anesthesia) continuously tracked during surgery.
After surgery, be followed for up to 3 days, during which they will be asked to rate their pain (using a simple 0-10 scale) and complete a short memory/thinking test (MMSE) at set times.
Provide small blood samples before, right after, and 24 hours after surgery to measure stress hormones and inflammation markers.
This study will involve about 990 patients across multiple hospitals and will take about 2 years to complete. The results will help doctors choose the best opioid for safer, smoother surgeries and faster recovery.
详细描述
- Background and Rationale
Total intravenous anesthesia (TIVA) with propofol is widely employed for a broad spectrum of surgical procedures due to its favorable pharmacokinetic profile, reduced environmental pollution, and lower incidence of postoperative nausea and vomiting compared to volatile anesthetics. In clinical practice, propofol-based TIVA is routinely complemented by potent, short-acting opioid analgesics to attenuate the stress response to laryngoscopy and surgical stimulation, thereby ensuring hemodynamic stability and providing adequate intraoperative antinociception.
Remifentanil, an ultrashort-acting synthetic opioid with a context-sensitive half-time independent of infusion duration, has become a dominant choice for TIVA maintenance. Its rapid metabolism by non-specific tissue and plasma esterases ensures predictable and prompt emergence from anesthesia, making it highly controllable. However, the very properties that confer its controllability also underlie its major clinical drawbacks: the abrupt cessation of its analgesic effect upon discontinuation frequently leads to severe acute postoperative pain, opioid-induced hyperalgesia, and a significant requirement for rescue analgesics during the early recovery phase. Furthermore, its use is associated with notable intraoperative bradycardia and hypotension, and its rapid offset complicates the transition to postoperative analgesia.
Alfentanil, another short-acting μ-opioid receptor agonist, presents a distinct pharmacological profile. While also rapidly acting, its analgesic potency is approximately one-quarter that of fentanyl, with an elimination half-life of 8-32 minutes. Critically, alfentanil is predominantly metabolized via hepatic CYP3A4 enzymes, resulting in a context-sensitive half-time that increases with the duration of infusion. This characteristic suggests that, during prolonged surgeries, alfentanil may provide a more gradual offset of analgesia, potentially serving as a built-in "bridge" to postoperative pain management, reducing the incidence of rebound pain and emergence agitation. Additionally, its more sustained receptor occupancy may offer superior hemodynamic stability against surgical stimuli, particularly in patients with cardiovascular comorbidities.
Despite these theoretical advantages, high-level comparative evidence remains sparse. Existing studies are predominantly limited by small sample sizes, single-center designs, and an overreliance on "extubation time" as the primary metric, while neglecting comprehensive, patient-centered outcomes such as pain trajectories, cognitive recovery, inflammatory stress responses, and overall perioperative morbidity. Furthermore, there is a notable paucity of data applying rigorous non-inferiority methodology to determine whether alfentanil can match remifentanil's established intraoperative performance while potentially offering superior recovery characteristics. 2. Study Objectives and Hypotheses
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Age between 18 and 65 years, with no gender restriction; (2) BMI ≥ 18 kg/m²; (3) ASA classification I-III; (4) Elective surgeries that are not related to the chest or brain, with an anticipated duration of 60-240 minutes; (5) Anticipated blood loss < 500 mL; (6) Voluntary consent to sign the Informed Consent Form.
排除标准
- •(1) Abuse or long-term use of opioid medications; (2) Severe hepatic and renal dysfunction (ALT/AST > 2×ULN, Cr > 176 μmol/L); (3) Serious cardiovascular diseases, including but not limited to: Severe cardiac arrhythmias or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, or uncontrolled atrial fibrillation; a history of acute myocardial infarction, unstable angina pectoris within the past 6 months, or having undergone coronary stenting or coronary artery bypass surgery.
- •Congestive heart failure classified as NYHA Class II or above, or left ventricular ejection fraction (LVEF) < 50%.
- •(4) A history of cerebrovascular accidents (including ischemic and hemorrhagic strokes) or transient ischemic attacks within the past 6 months; (5) Uncontrolled severe hypertension: resting systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg (confirmed by repeated measurements); (6) Symptomatic aortic dissection, or lower limb arterial occlusion requiring treatment.(4) Severe blood system disorders, including but not limited to severe anemia, aplastic anemia, acute leukemia, thrombotic thrombocytopenic purpura, etc.
- •(5) Difficulty in predicting airway management; (6) Pregnancy or lactation; (7) Allergy to opioids/propropofol/eggs/soybeans; (8) Participation in other clinical trials within the past 3 months.
研究组 & 干预措施
Alfentanil group
patients receive alfentanil during surgery
干预措施: alfentanil (Drug)
Remifentanil group
Patients receive remifentanil during surgery
干预措施: Remifentanil (Drug)
结局指标
主要结局
Incidence of Intraoperative Rescue Events
时间窗: From induction of anesthesia until the end of surgery (skin closure).
A composite endpoint defined as the need for rescue analgesia (administration of sufentanil \>5 μg intravenously) or rescue vasoactive medication (ephedrine, phenylephrine, norepinephrine, or esmolol) at any time during the surgical procedure, to manage inadequate analgesia or hemodynamic instability.
次要结局
- Recovery Times(From the end of drug infusion until occurrence of each event (measured in the immediate post-anesthesia period).)
- Postoperative Hyperalgesia(Assessed during the postoperative period, up to 24 hours after surgery.)
- Postoperative Pain Intensity (VAS)(At 0.5, 2, 6, 12, and 24 hours after surgery.)
- Incidence of Adverse Reactions within 24 Hours(Within the first 24 hours following surgery.)
- Total Propofol Consumption(From induction of anesthesia until the end of surgery (skin closure).)
- Perioperative Stress and Inflammatory Biomarkers(At three time points: preoperatively (baseline, Day -1), immediately at the end of surgery (Day 1), and 24 hours postoperatively (Day 2).)
- Early Postoperative Cognitive Function(Baseline (preoperative, Day -1), and on postoperative Day 1, Day 2, and Day 3.)
研究者
Jianbo Wu
Chief Physician,Director of Department of Anesthesiology
Qianfoshan Hospital