Sedation of Remazolam in Combination With Afentanil in Non-intubated Thoracoscopic Pulmonary Surgery: a Single-blind, Randomized, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 390
- 试验地点
- 1
- 主要终点
- the incidence of hypoxia
研究概览
简要总结
Non-intubated Thoracoscopic surgery (NITS) is a newly emerging minimally invasive surgical technique in recent years . Compared with traditional intubation general anesthesia, it has the advantages of less trauma, faster recovery and fewer complications . This surgical method allows patients to perform under local anesthesia or regional block and moderate sedation, providing a physiologic ventilation method , reducing the intervention on the respiratory system and conducive to rapid postoperative recovery.
The importance of sedative drugs in non-intubated thoracoscopic surgery Successful implementation of non-intubated thoracoscopic surgery requires sound regional block, airway management, and rational use of intravenous sedation and analgesics . In addition, sedative drugs need to have less respiratory and circulatory inhibition and fewer side effects. Propofol, as the most commonly used sedative drug, has a high incidence of adverse reactions such as injection pain and respiratory and circulatory inhibition. A large number of meta-analyses and systematic reviews have compared the sedative effects of remazolam and propofol, proving that Remazolam, as a new sedative, has advantages such as short half-life, rapid onset, rapid recovery, and light respiratory and circulatory inhibition.Compared with traditional benzodiazepines, Remazolam has a shorter half-life, which is conducive to rapid postoperative wakeup and reduces the risk of discomfort and cognitive dysfunction in patients. In addition, remazolam has little influence on the respiratory system and is relatively stable on the circulatory system ，which is an ideal sedation option for non-intubated thoracoscopic surgery that retains spontaneous respiration. Afentanil mainly acts on μ opioid receptors , and its analgesic intensity is about 15 times that of morphine, which has the advantages of rapid onset, short duration of action, rapid recovery, high safety, and few adverse reactions . Afentanil has a short half-life , mild respiratory depression, low incidence of cough, postoperative nausea and vomiting . Remazolam combined with afentanil is widely used in various surgeries or examinations that preserve spontaneous breathing, such as gastroenteroscopy, ERCP, hysteroscopy, short-term plastic surgery and fiberbronchoscopy, and has shown the advantage of light respiratory circulation inhibition . We speculate that remazolam combined with afentanil may have certain advantages in non-intubated thoracoscopic surgery that retains spontaneous breathing. At present, the application of remazolam combined with afentanil in non-intubated thoracoscopic surgery is still lacking. The purpose of this study was to observe the safety and effectiveness of remazolam combined with afentanil in non-intubated thoracoscopic surgery, and to provide a better choice of sedation drugs for non-intubated thoracoscopic surgery.
详细描述
Research object Patients aged 18 years or older undergoing non-intubated thoracoscopic lung surgery 3.2 Sample size calculation According to the study of Goyal R etal., propofo-based sedation resulted in a decrease in oxygen saturation in nearly 43% of patients. Therefore, assuming a 15% reduction in anoxic events in the remazolam group, PASS-2021 software, comparison of two independent sample rates, bilateral Z test, 80% confidence, and a significant difference level of 0.05, we estimated that the sample size in each group in this study was 156 patients, and considering the 20% shedding rate, 195 patients were required in each group. A sample size of 390 cases is required.
3.3 Scheduling Standards 3.3.1 Inclusion criteria:
- American Society of Anesthesiologists ASA Level I to III;
- 18 years old ≤ age ≤80 years old;
- Non-intubated thoracoscopic lung surgery under deep sedation;
- 18kg/m2≤BMI≤30 kg/m2;
- Voluntarily participate in the study and sign the informed consent. 3.3.2 Exclusion criteria:
(1) Pulmonary function examination showed moderate to severe ventilation or exchange impairment (FEV1< 60% of the predicted value, carbon monoxide diffusion < 60% of the predicted value); (2) Abnormal liver and kidney function (Child-Pugh grade liver function is grade B and grade C; Endogenous creatinine clearance ≤50mL/min, serum creatinine >178µmol/L or renal function test urea nitrogen >9mmol/L) (3) SpO2 < 95% before operation; (4) History of recovery from abnormal surgical anesthesia; (5) History of thoracic surgery or history of tuberculosis or systemic infection within one month; (6) Severe cardiovascular and cerebrovascular diseases (patients with severe cardiovascular and cerebrovascular diseases: high risk of hypertension, untreated coronary heart disease, valvular heart disease, previous myocardial infarction, cerebral infarction, cerebral thrombus, cerebral hemorrhage); (7) Take monoamine oxidase inhibitors or antidepressants within 15 days; (8) Chronic pain from long-term use of analgesics or psychotropic drugs, alcoholism; (9) Known drug allergy; (10) expected difficult airway; (11) Pregnant women or women giving birth; (12) Participation in other drug trials within three months or inability to communicate well with researchers.
3.3.3 Shedding cases After signing informed consent and screening qualified for clinical trial, the patients did not complete the full clinical trial visit. Such as adverse events, patient loss of follow-up, patients who were converted to general anesthesia during the operation for reasons other than severe hypoxia, patients who could not complete the evaluation after surgery, patients voluntarily withdrew informed consent, and emergency blinding was initiated.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •American Society of Anesthesiologists ASA Level I to III;
- •18 years-80 years old;
- •Non-intubated thoracoscopic lung surgery under deep sedation;
- •18 kg/m2≤BMI≤30 kg/m2;
- •Voluntarily participate in the study and sign the informed consent.
排除标准
- •Pulmonary function tests showed moderate to severe ventilation or exchange disorders (FEV1< 60% of the predicted value, carbon monoxide diffusion < 60% of the predicted value);
- •Abnormal liver and kidney function (Child-Pugh grade liver function is grade B and grade C; Endogenous creatinine clearance ≤50mL/min, serum creatinine >178µmol/L or urea nitrogen >9mmol/L by renal function test);
- •SpO2 < 95% before operation;
- •History of recovery from abnormal surgical anesthesia;
- •History of thoracic surgery or history of tuberculosis or systemic infection within one month;
- •Severe cardiovascular and cerebrovascular diseases (patients with severe cardiovascular and cerebrovascular diseases:
- •High risk of hypertension, untreated coronary heart disease, valvular heart disease, previous myocardial infarction, cerebral infarction, cerebral thrombus, cerebral hemorrhage);
- •Take monoamine oxidase inhibitors or antidepressants within 15 days;
- •Chronic pain from long-term use of analgesics or psychotropic drugs, alcoholism;
- •Known drug allergy;
- •Expected difficult airway;
- •Pregnant women or women giving birth;
- •Participation in other drug trials within three months or inability to communicate well with researchers
研究组 & 干预措施
Group-R
Afentanil (dose 10 μg/kg, Yichang Renfu Pharmaceutical Co., LTD.), 3 minutes before sedative administration. Then, in the remazolam group (group R), 0.3mg/kg remazolam (Yichang Renfu Pharmaceutical Co., LTD.) > 60 seconds. Sedation was maintained by continuous infusion of remazolam 0.2 to 1 mg/kg/h and afentanil 0 to 1μg/kg/min.
干预措施: Remazolam combined with afentanil for non-intubated thoracoscopic surgery (Drug)
Group-P
Propofol group (Group P) was given 1.5 to 2mg/kg propofol, continued infusion of propofol 2 to 6 mg/kg/h and afentanil 0 to 1μg/kg/min to maintain sedation. The anesthesiologist maintained sedation at the target level, maintaining the Modified Observer Alertness/Sedation Scale (MOAA/S) between 1-2.
干预措施: Propofol combined with afentanil in non-intubated thoracoscopic surgery (Drug)
结局指标
主要结局
the incidence of hypoxia
时间窗: during the surgery
The primary indicator was the incidence of hypoxia, defined as SpO2 \< 90%,T\>10s.Record whether and how often patients experienced pulse oxygen saturation below 90%.
次要结局
- MAP at different time points(preinduction（T0） ,1minute （T1）、 3 minutes after induction（T2） ， At the beginning of the operation (T3)， 5 、10、15minutes after the operation began (T4、T5、T6) ，5minutes after withdrawal of anesthesia (T7))
- Frequency of intraoperative hypoxemia(during the surgery)
- the number of minor airway operations required and remedial measures(during the surgery)
- The minimum SpO2 were recorded(during the surgery)
- HR at different time points(preinduction（T0） ,1minute （T1）、 3 minutes after induction（T2） ， At the beginning of the operation (T3)， 5 、10、15minutes after the operation began (T4、T5、T6) ，5minutes after withdrawal of anesthesia (T7))
- SpO2 at different time points(preinduction（T0） ,1minute （T1）、 3 minutes after induction（T2） ， At the beginning of the operation (T3)， 5 、10、15minutes after the operation began (T4、T5、T6) ，5minutes after withdrawal of anesthesia (T7))
- BIS at different time points(preinduction（T0） ,1minute （T1）、 3 minutes after induction（T2） ， At the beginning of the operation (T3)， 5 、10、15minutes after the operation began (T4、T5、T6) ，5minutes after withdrawal of anesthesia (T7))
- Quality of Recovery Questionnaire (QOR-15)(The first day after surgery)
研究者
Jianbo Wu
chief physician
Qianfoshan Hospital