Sedation of Remazolam Combined With Afentanil in Non-intubated Thoracoscopic Pulmonary Surgery

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:

1. American Society of Anesthesiologists ASA Level I to III;
2. 18 years old ≤ age ≤80 years old;
3. Non-intubated thoracoscopic lung surgery under deep sedation;
4. 18kg/m2≤BMI≤30 kg/m2;
5. 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.

3.4 Randomization and blind method Block randomization was employed. The randomization scheme was generated by the researchers using the website (www.random.org). Random number in a light-tight sealed envelope. In this study, patients meeting the inclusion/exclusion criteria will be randomized into the trial group (remazolam, group R) and the control group (propofol, group P) in a 1:1 ratio. Since propofol is colored and remazolam is colorless, the anesthesiologist performing the anesthesia is non-blind. Follow-up personnel and statisticians, patients and chest doctors were blind.

3.5 Specific research content BIS, electrocardiogram, SpO2, blood pressure, heart rate, open venous access, nasal catheter oxygen inhalation (3L/min) were monitored. Under the guidance of local anesthesia ultrasound, three paravertebral T4-5-6 points were blocked successively, and 0.25% ropivacaine 15ml was administered. After disinfection, the anesthetic plane was tested to be effective before cutting the skin, then intravenous medication was started. If the patient is in pain before the incision, the surgeon gives additional local anesthesia and then starts intravenous medication. Two anesthesiologists are in charge of the patient throughout the procedure. Afentanil (dose 10μg/kg, Yichang Renfu Pharmaceutical Co., LTD.), 3 minutes before sedative administration. Then, in the remazolam group, 0.3mg/kg remazolam (Yichang Renfu Pharmaceutical Co., LTD.) was administered for > 60 seconds. Sedation was maintained by continuous infusion of remazolam 0.2 to 1mg/kg/h and afentanil 0 to 1μg/kg/min. The propofol group 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. For example, if the MOAA/ S is higher than 2 and the patient is still overreacting and cannot tolerate surgery, use 0.1mg/kg remazolam push or 0.5mg/kg propofol, respectively, as additional sedation. In addition, both groups were given 5μg/kg of afentanil for additional analgesia. After surgery, patients were transferred to the recovery room, where their HR, SpO2, NIBP, and MOAA/S were monitored. A modified Aldrete score was used to assess recovery. Patients are only allowed to return to the room if their Aldrete score is at least 9 and there are no obvious side effects such as nausea or dizziness.

Hypotension was defined as MAP<65 mmHg or a 20% decrease from baseline, while hypertension was defined as MAP>105 mmHg or a 20% increase from baseline. According to the American Heart Association, when hypotension or hypertension occurs, we take two blood pressure readings immediately to provide a more accurate blood pressure. Patients with hypotension and accelerated heart rate received a 4ug norepinephrine push injection, then titrated to BP and heart rate. In contrast, patients with hypotension and HR < 60 bpm received a push dose of 10 mg ephedrine, which was then titrated to blood pressure and heart rate. In hypertensive patients, 5 mg urapidil was administered and titrated to BP. If the heart rate drops to <45 bpm, atropine 0.25mg is injected intravenously and titrated to the heart rate. If heart rate >110 bpm, Esmolol (10 mg) is administered intravenously and titrated to heart rate.