This study was registered prior to patient enrollment in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, identifier: ChiCTR1800017166). The study was approved by the ethics committee of Henan Cancer Hospital. All patients were informed of the intent to use this monitoring system to potentially aid surgeons in the localization and identification of the recurrent laryngeal nerves and for the assessment of their function during operation and written informed consent was obtained from each patient. We recruited 80 consecutive adult patients (including 40 men and 40 women; age range, 22-45 years) scheduled to receive a thyroid operation with intra-operative neuromonitoring. Inclusion criteria included ASAⅠ～Ⅱ, BMI between 18.5 and 27 kg/m2, Exclusion criteria were intolerance to the medications employed in the study, Mallampati classification grade III/IV or ones who were expected difficulties during intubation, regular medication which may interfere with muscle relaxants, neurological or neuromuscular disease, and hepatic or renal insufficiency. Using a sealed envelope method, Patients were allocated to a sevoflurane (S) or propofol group (P) by table of random numbers.
Anesthesia technique and measurements
Midazolam (0.05 mg/kg) and penehyclidine hydrochloride (0.01mg/kg) were injected intravenous 30 minutes prior to the induction of anesthesia. After arrival in the operating room, the patients were monitored using an electrocardiograph, non-invasive blood pressure monitor, and pulse oximeter. A BIS sensor (BIS Complete Monitoring System, Covidien IIc, USA) was attached and measurements were taken when the signal quality index was above 95. Muscle relaxation was monitored using an electrical stimulator (Veryark-TOF, VERYARK Co., Ltd) by applying train of four (TOF) on the wrist’s ulnar nerve and measuring the contraction of the adductor pollicis muscle. The TOF were calibrated above 95%. Body temperature was maintained by a heating blanket (Type SIIWT-B, Haiming Co., Ltd, Tianjin, China). Skin temperature was measured under thenar eminence and maintained above 35.5 °C.
After preoxygenation, anesthesia was induced with 2.0 mg/kg propofol, 0.3～0.5 μg/kg sufentanil and 0.3 mg/kg rocuronium was administrated to facilitate electromyographic endotracheal tube (Medtronic Xomed, Inc., Jacksonville, FL, U.S.A.) insertion when we confirmed the loss of consciousness after administration of propofol by checking the eyelash reflex and BIS under 60. If the patients would be still awake at 2 min after administration of propofol, additional propofol 0.5 mg/kg would be given. Tracheal intubation was performed using visual laryngoscopy at 180s after administration of rocuronium. Immediately after intubation, the assistant checked the intra-operative neuromonitoring signal assure the electromyographic endotracheal tube were placed in the right depth and location. Anesthesia were maintained by 1.5～3.0 vol.% sevoflurane or 4.0～6.0 mg/kg/h propofol associated with 0.1 μg/kg/min remifentanil, respectively.
Neuromuscular function was assessed using acceleromyography of the adductor pollicis muscle (Veryark-TOF, VERYARK Co., Ltd) according to the guidelines of manufacture. After loss of consciousness (BIS value < 60), neuromuscular monitoring began immediately with TOF stimulation (0.2 ms duration, frequency 2 Hz, 2s duration with supramaximal current, repeated every 20s), record the time between rocuronium administrated and the TOF decreased to 75 %(T1), 50 %(T2)and 0(T3). The time required for the TOF reappearance to counts of 4(T4), TOF ratio to recover to 50 %(T5) and 75%(T6) also recorded.
All patients were treated by the same surgeon team and the NIM-Response 3.0 machine (Medtronic Xomed, Inc., Jacksonville, Florida, U.S.A.) was used for intermittent RLN monitoring in all patients. Sinus bradycardia and tachycardia were treated with atropine and esmolo, respectively. Hypertension and hypotension were corrected by symptomatic treatment. If swallow or body movement happened, additional intravenous anesthetics propofol (0.5 mg/kg) is used to prevent further patient movement. All the adverse responses were recorded. Record the time form operation start (incision) and intubation to the time recurrent laryngeal nerve neuromonitoring. All patients were delivery to postanesthesia care unit with electromyographic endotracheal tube. Record the respiratory complication and delayed recovery.
SigmaPlot 12.5 software (Systat Software, Inc., Point Richmond, CA) was used for sample size calculation and statistical analyses. Sample size was calculated to achieve a power of 0.9 for the first time TOF recovery profile T4. The minimum sample size turned out to be 37 in 0.1μg/kg/min remifentanil treatment base on a pilot study so the study was done using 40 subjects in each group. The Shapiro-Wilk test was used for testing data for normality. We report data as means and standard deviations (SD) or median and interquartile range (IQR, 25th to 75th percentile) and depict data as line plots on data distribution. Quantitative variables were compared by t-test/Mann–Whitney test (for nonparametric data). Comparisons of frequency distributions were performed using the Chi-squared test/ Fisher's exact test. P < 0.05 was defined as statistically significant.