Effects of salbutamol on the kinetics of sevoflurane and the occurrence of early PPC in patients with mild to moderate COPD: a randomized controlled study v1
Authors: not provided jiangzhejiang 
Published: March 2021

3. Research protocol 3.1 Types of research Prospective, randomized, controlled, clinical studies Primary outcome Ratio of inhaled sevoflurane concentration (Insevo) to end-expiratory sevoflurane concentration (Etsevo )，namely the FA/FI fraction. Secondary endpoints (1) The time of opening eyes, extubation and oral birthday of patients in anesthesia recovery room. (2) Number and incidence of pulmonary complications within 7 days after operation. 3.2Research methodology 3.2.1 Research site Shaoxing People's Hospital 3.2.2 Research participants patients with mild to moderate COPD were recruited in the study. (1)Inclusion criteria: ASA Ⅰ~ II grade ;65~75 years old; long-term smoking history or previous confirmed chronic bronchitis, emphysema ; Pulmonary function test was performed before surgery and the severity of classification was obtained (mild to moderate COPD); Body mass index18~30 kg/m2; No upper respiratory infection within 2 weeks before surgery; Stable COPD patients (2) Exclusion criteria: Allergic to β2 receptor agonists, alcohol and freon; pulmonary arterial hypertension (PAP ﹥50 mmHg at rest); cardiac insufficiency or heart failure; patients refused to cooperate; renal insufficiency (BUN﹥10 mmol/L,Cr﹥1.5mg/dl）。 (3) Exclusion criteria: patient withdrawal; incomplete data; loss of follow-up ; adverse events 3.2.3 Main research methods Salbutamol (40 vial) and its similar in appearance placebo (40 vial, normal saline) were used in this study. The computer-generated random sequence numbers were stored in an opaque envelope. The investigators who were responsible for assessing the primary endpoints, as well as the anesthesiologists, postoperative care unit nursing staff, and variable assessors, were blinded to study group assignment. Before operation, signed informed consent was obtained, no preoperative medication was administered , no food for 10 h and 4 h for drinking before operation. Pre-anesthesia preparation: Routine monitoring was initiated, the peripheral vein was cannulated, and sodium lactate Ringer's solution 500 mL for volume expansion; Radial artery catheterization was performed to monitor invasive blood pressure; Give salbutamol reagent oral spray 200 μg (2 spray) and record reagent number; No drugs (antibiotics, hormones, etc.) were given before induction, and no test dose was injected if epidural catheter was retained. BIS monitoring: Clean the skin repeatedly with alcohol cotton balls and use BIS after dryingXPDedicated four-conductor electrode (BIS-sensor) chipXP), Electrode 1 is facing the eyebrow (about 5 cm from the nose root), Electrode 2 is located between 1 and 4 above the brow, The lower edge of electrode 4 is aligned with the right eyebrow arch, Electrode 3 is aligned with the center of the eye. Anesthesia induction: Salbutamol aerosol spray or placebo was administered through inhalation 30 min before anesthesia induction. Oxygen flow rate was set to 8 L/min before oxygenation. Fentanyl 3.0 μg/kgwas injected intravenously slowly, Propofol 1.5~2.0 mg/kg rocurium 0.9 mg/kg；Tracheal tube was fixed after successful tracheal intubation (female ID 7.0, male ID 8.0), then mechanical control ventilation was initiated, adjusting tidal volume 8~10 ml/kgrespiratory rate 10 bpm, I/E ratio 1:2, to keep EtCO2 within30 to 45 mmHg .When the hemodynamics is stable for 4~5 min, the sevoflurane volatile vaporizer was opened (2% sevoflurane was used to prime the respiration circuit to ensure the uniform filling of the circuit), the inhalation concentration was 2% and the oxygen flow rate was 2 L·min-1. The concentration of sevoflurane was collected at one end of the Y interface of the endotracheal tube through sidestremline method. During the wash -out period, the oxygen flow rate was 4 L/min . Anaesthesia maintenance: No exogenous stimulation (including changing the position) and no anesthetic drugs were added during observation. Ephedrine 5~10 were injected intravenously (MAP ﹤50 mmHg) during observation. Atropine 0.25~0.5 mg was givenwhen the heart rate (﹤45 times/min) .Salbutamol 200 or placebo was given through the respiratory circuit 30 min before the completion of surgery, The vaporizer was closed 30 minutes before the last skin suture was placed, with fresh gas flow set at 4L/min. Following this, end-tidal samples were collected from first breaths at 1, 2, 3, 4, 5, 7, 10 and 15 min after discontinuation of its administration. Observation variables End-tidal samples were collected from first breaths at 1, 2, 3, 4, 5, 7, 10 and 15 min, and then the surgery began. The hemodynamic parameters and airway pressure data in the corresponding time points. End-tidal samples were collected from first breaths at 1, 2, 3, 4, 5, 7, 10 and 15 min after discontinuation of its administration. The hemodynamic parameters and airway pressure data in the corresponding time points. Arterial blood samples were extracted from the patients before induction (0 min), then at 30 min and 60 min after initiation of the operation. Observe the occurrence of pulmonary complications in all patients within 7 days after operation. Statistical analysis After all the tests, according to the random number, the subjects were divided into salbutamol group and control group for statistical analysis. Stata7.0 software package for statistical analysis, The mean ± standard deviation (mean±SD) are used for all measurements, A complete randomized t test was used to test the differences between groups, Analysis of variance (ANOVA,) within groups S-N-K methods), Comparison of counting data using chi-square test or Fisher exact probability calculation. P ﹤0.05, the difference was statistically significant.