This study was registered in the Chinese Clinical Trial Registry (ChiCTR1800015537). The Institutional Review Board (Shanghai Eye, Ear, Nose, and Throat Hospital affiliated with Fudan University) approved the study procedures, and each enrolled patient provided written informed consent.
Adult patients with American Society of Anesthesiologists physical status I and II scheduled for middle ear surgery due to cholesteatoma otitis media were consecutively recruited. Patients were randomly assigned to the propofol/remifentanil (PR) or desflurane/remifentanil (DR) group by computer-generated allocation. Patients were excluded if they were receiving cardiovascularly active drugs or drugs related to coagulation (e.g., warferin, heparin, enoxiparin, NSAID or aspirin).
Upon arriving to the operating room, non-invasive monitoring of arterial blood pressure, pulse oximetry, electrocardiography, and bispectral index (BIS) monitoring (BIS VISTA Monitoring System; Aspect Medical Systems, Inc., Norwood, MA, USA) was established. Anesthesia was induced by intravenous 2 mg/kg propofol (Fresenius Kabi, Beijing, China), 0.3 μg/kg remifentanil (Yichang Renfu Pharmaceutical, Yichang, China), and 0.6 mg/kg rocuronium (Hameln Pharmaceuticals GmbH, Hameln, Germany). After flexible laryngeal mask insertion, anesthesia was maintained with propofol/remifentanil (PR) or desflurane/remifentanil (DR). Patients in the PR group received an effect site target-controlled infusion of propofol based on Schnider’s pharmacokinetic model [10] and remifentanil based on Minto’s model [11], delivered using a commercial pump (Orchestraw Base Primea, Fresenius Vial, Brezins, France). Effect site concentration was 2–6 μg/ml for propofol. For patients in the DR group, anesthesia was maintained with 4–8% desflurane. The effect site concentration of remifentanil was 1–8 ng/ml for both groups. Mean blood pressure was maintained within ±30% change of the pre-induction value. Ephedrine was needed for any decrease in mean blood pressure lower than 30% from the patient’s pre-induction value.
Patients received mechanical ventilation in pressure-controlled mode with a tidal volume of 8 ml/kg at a rate of 10 breaths per min to provide an end-tidal CO2 concentration of 35–45 mmHg. The carrier gas flow for both groups consisted of oxygen and air (FiO2 0.5) during anesthesia maintenance. Intravenous 1 mg/kg parecoxib (Pfizer Pharmaceuticals, Beijing, China), and 0.01 mg/kg hydromorphone hydrochloride (Yichang Renfu Pharmaceutical) were given at the end of surgery for postoperative analgesia, and 0.15 mg/kg ondansetron hydrochloride and 0.1 mg/kg dexamethasone were given to prevent postoperative nausea and vomiting.
Surgery was performed by one of three surgeons with subspecialty training in otology using a similar stepwise technique. The surgeons were blinded to the anesthesia type by shielding the vaporizer and propofol and remifentanil syrings. Patients’ heads were positioned 15° higher than their bodies for the entire procedure. Attending surgeons who were blind to treatment group rated surgical field visibility from 0 to 5 according to the Boezaart grading scale where 0 denotes the best and 5 the worst visibility [12]. Surgical field visibility was recorded at four time points: skin incision, bone drilling, clearance of cholesteatoma, and laying of fascia. Hemodynamic profile was recorded at the following time points: arrival to the operating room, 10 min after skin incision, completion of drilling, completion of clearance of cholesteatoma, completion of laying of fascia, extubation, 10 min after extubation, and post-anesthesia care unit (PACU) discharge.
Anesthesia time was defined as the time from anesthesia induction to anesthetic discontinuation. After surgery, patients were transferred to the PACU for monitoring and management by an attending anesthesiologist who was blinded to the group assignment. This anesthesiologist was blinded to the study, as was the research assistant who recorded extubation time (time from the end of surgery to extubation), PACU time (time between extubation and achieving a modified Aldrete score [13] > 9), postoperative pain (visual analogue scale (VAS) from 0 to 10 with 0 = no pain and 10 = worst pain imaginable), and postoperative nausea and vomiting (PONV) episodes. If VAS score was > 4, a rescue analgesic (intravenous 0.01 mg/kg hydromorphone hydrochloride) was given. Intravenous (10 mg) metoclopramide was given when needed as an antiemetic.
The primary outcome was surgical field visibility. Secondary outcomes were requirement for remifentanil, hemodynamic profile, and recovery time. Based on a pilot study of 10 adult patients receiving DR anesthesia, mean surgical field visibility was 2 (standard deviation, 1) during clearance of the focal lesion during middle ear microsurgery. Based on an estimate of 40% improvement in surgical field visibility, we calculated that 40 patients in each group were needed to provide statistical power of 80% at a 5% significance level. Remifentanil usage is expressed as the median (first/third quartiles) and was analyzed using a Mann-Whitney rank sum test. Other continuous variables are expressed as mean ± standard deviation (SD) and were analyzed using Student’s t-tests. Categorical data were analyzed using χ2 tests or Fisher’s exact tests. Repeated measures ANOVA was used to analyze changes in hemodynamic profiles (heart rate and mean blood pressure) over time. Statistical significance was set at P < 0.05.