This single-blinded, parallel, controlled trial with equal randomization was approved by the Institutional Review Board of Peking Union Medical College Hospital (PUMCH) (IRB No. S-631) and registered in Chinese Clinical Trial Registry (ChiCTR-IOR-15006602) on May 23th, 2015. Informed consent was obtained from all individual participants included in the study. The study protocol adhered to CONSORT guidelines.
Nighty-six patients with American Society of Anesthesiology Physical Status Classification (ASA)Ⅰ-Ⅱ, aged 20-80 years, scheduled for elective radical thyroidectomy under general anesthesia from May 26th 2015 to April 2016 were enrolled. Exclusion criteria were: preoperative sore throat, hoarseness, dysphagia, high risk of regurgitation or aspiration, obesity (body mass index, BMI>30 kg/m2), symptoms of upper respiratory infection within 2 weeks before surgery, previous surgeries of the oral cavity or pharynx, and estimated surgery time >4h. All the patients scheduled for thyroid surgery received laryngofiberscope preoperatively to evaluate the function of vocal cord. Cases without definitive identification of recurrent laryngeal nerve or with mechanical or thermal injury of recurrent laryngeal nerve during surgery were also excluded.
The admitted patients were randomly assigned to ETT group (ETT group, n=48) or flexible reinforced LMA group (LMA group, n=48) by a computer-generated table of random numbers immediately prior to surgery. No restriction was used for randomization. The random numbers for assignment were sealed in opaque envelopes, which could only be opened by the anesthesia providers.
The study was conducted in the operating rooms in Peking Union Medical College Hospital in Beijing, China. In ETT group, patients were intubated with a high-volume, low-pressure-cuff plain endotracheal tube (Covidien, Mexico). In order to control the possible bias, smaller sized ETTs (size 7.0 for female patients and 7.5 for male) were chosen for our patients, which were reported to be associated with a lower incidence of sore throat . The cuff of ETT was inflated with room air, and cuff pressure was strictly adjusted to 25cmH2O with a handheld aneroid manometer (VBM, Einsteinstr, Germany). In LMA group, a flexible reinforced LMA (LMA FlexibleTM, Laryngeal Mask Company Limited, Seychelles, Singapore) was used according to the patient’s body weight (BW) (size 3 (BW<50 kg), 4 (BW 50–70 kg), or 5 (BW>70 kg)). The cuff of flexible reinforced LMA was fully deflated before insertion. After lubrication of the posterior surface with water-based jelly, FLMA was inserted with digital intraoral manipulation. Cuff pressure of FLMA was adjusted to 40cmH2O with manometer. Proper position was confirmed by a visualization of more than half vocal cords through bronchoscopy.
The patients, data collectors and outcome assessors were blinded to the group assignment. In order to ensure patients’ safety, the anesthesiologist in charge of the anesthesia was not blinded to the group assignment. ETT and FLMA were placed by two experienced anesthesiologists who had successfully inserted ETT for over 300 times in thyroid surgeries and ETT for over 300 times in other surgeries. All the surgeries were carried out by one surgical team.
On arrival at the operating room, all the patients received midazolam 0.03 mg·kg-1 as a premedication. Intraoperative monitoring included electrocardiography, noninvasive blood pressure, pulse oximetry (SpO2), capnograpy (EtCO2), gas analysis, tidal volume, airway pressure and bispectral index (BIS). Anesthesia was induced with target-controlled infusion of propofol (at effect-site concentration of 3-3.5μg/ml) and bolus injection of fentanyl 2μg/kg and rocuronium 0.6mg/kg.
During the operation, anesthesia was maintained with intermittent bolus injection of fentanyl and target controlled infusions (TCI) of propofol using Graseby 3500 Anaesthesia Syringe Pump - Diprifusor (Smiths-medical, UK). The systolic blood pressure fluctuation was maintained within 15% of baseline and BIS value between 40–60 (Aspect XP, space Lab, USA). Propofol infusion was discontinued around 10 minutes before the end of surgery and neostigmine 6mg was given to antagonize the residual muscle relaxant. FLMA/ETT was extracted when the patient could follow voice commands and EtCO2 was bellow 45mmHg on spontaneous respiration. None of the patients received additional analgesics in PACU or wards during postoperative 48 hours.
The primary end point was the incidence and severity of postoperative sore throat. Secondary end points were: (1) the incidence and severity of buckling during extubation, (2) postoperative numbness and hoarseness, (3) hemodynamic profiles. Laryngopharyngeal symptoms were evaluated at 1, 24, and 48 h after surgery by three anesthesiologists who were blinded to the treatment group of the patient. Sore throat was assessed using a visual analog scale (VAS, 0 = none, 10 = most severe). Numbness was evaluated according to patients’ self-report. Hoarseness was assessed based on whether there were changes of the voice to harsh or strained. The scale used to evaluate the severity of buckling during extubation was a three-graded scale: 0=None, 1=Mild buckling (once/twice cough without head lifting-off the bed and lasting less than 15 seconds), 2=Severe buckling (cough more than twice with head lifting-off the bed or lasting longer than 15 seconds). In addition, the diastolic blood pressure (DBP), systolic blood pressure (SBP) and heart rate (HR)  were recorded the time before, at 1minute, 3 minutes and 5 minutes after endotracheal intubation/insertion of LMA.
Previous study showed that the incidence of sore throat at 6 h after thyroid surgery was 84% for the control group . If a 30 % decrease in the incidence of sore throat was considered clinically significant, power analysis program (G* power 3.1) calculated that 35 patients per group were needed for a power of 80 % and an error of 0.05. Considering a 10 % dropout rate, 38 patients for each group were necessary. SPSS software (version 13.0; SPSS, Inc., Chicago, IL, USA) was used for data analysis. Continuous normally and non-normally distributed data was described as mean ± standard deviation and median , respectively. Between-group demographic data with normal distribution was analyzed with unpaired t-test or Chi Square test, if appropriate. Hemodynamic data at each time point was compared by one-way ANOVA. The incidences of sore throat, hoarseness, numbness and buckling were analyzed using Fisher’s exact test. The Mann–Whitney U test was used to compare the severity of sore throat. A two-sided p-value <0.05 was considered statistically significant.