The Ethics Committee of the Anqing Affiliated Hospital of Anhui Medical University approved the study. This study was registered in the Chinese Clinical Trial Registry (ChiCTR1800017482). Initial registration date was 01/08/2018. Each patient signed an informed consent before surgery. The study took place at the Anqing Affiliated Hospital of Anhui Medical University.
One hundred and-eighty patients were enrolled from August 2018 to November 2018. All of the patients in this study were classified as either American Society of Anesthesiologists (ASA) class I or II, were aged between 18-and 65-years-old from both sexes and were scheduled to undergo thyroid surgery. The exclusion criteria in this study included incidences of asthma, chronic cough, perioperative upper respiratory infection symptoms, a current smoking status, medication involving angiotensin-converting-enzyme inhibitors (ACE-I), bronchodilators or steroid medications, bradycardia or an atrioventricular conduction block, hepatic insufficiency, renal insufficiency, local anesthetic allergy, platelet abnormality, coagulation abnormalities, anticoagulation and a refusal to participate in the study.
Subjects were randomised to the LIDO group, the DEX group and the CON Group with a 1:1:1 allocation using computer-generated random number. Group assignments were kept in sealed envelopes, and only the nurse responsible for preparing the anesthetics was allowed to open the envelope and the assigned drug. The assigned drugs according to group assignments in syringes which has no difference in appearance. The patients, data collectors (anesthesiologist) did not know the drugs used for intravenous administration. All of the patients were NPO since approximately 6 h before surgery.
All surgeries were performed by three experienced surgeons. All patients received intramuscular hyoscine (0.3 mg) 30 min before the induction of anesthesia. Mean arterial blood pressure (MAP), heart rate (HR), electrocardiogram (ECG) and peripheral pulse oximeter (SPO2) values were monitored by using a multiparameter monitor (Philips MIX500, Boeblingen, Germany). In the LIDO group, the patients were given an IV bolus infusion of lidocaine (2%)1.5 mg/kg made to 20 ml with normal saline and 20 ml normal saline respectively, over 10 min before induction of anesthesia, followed by a continuous IV infusion of lidocaine 1.5 mg/kg made up to 20 ml and 20 ml normal saline every hour until 30 min before the end of surgery, respectively. In the DEX group, patients were given IV bolus infusion of dexmedetomidine 0.5 μg/kg made to 20 ml with normal saline and 20 ml normal saline respectively, over 10 min before induction of anesthesia, followed by a continuous IV infusion of dexmedetomidine 0.4 μg/kg made up to 20 ml and 20 ml normal saline every hour until 30 min before the end of surgery, respectively. In the CON group, the patients were given an 20 ml normal saline and 20 ml normal saline respectively, over 10 min before induction of anesthesia, followed by a continuous IV infusion 20 ml normal saline and 20 ml normal saline every hour until 30 min before the end of surgery, respectively. General anesthesia was induced with midazolam (0.05 mg/kg), propofol (2 mg/kg), sufentanil (0.5 μg/kg) and vecuronium (0.1 mg/kg), and anesthesia was maintained with propofol (50–80 μg/kg/min) and remifentanil (0.15–0.2 μg/kg/min). Tracheal intubation was performed after adequate muscle relaxation. All of the patients were ventilated with an Aspire view anesthetic machine (GE Healthcare, Madison, WI, USA). In the three groups, the tidal volume (VT) was maintained at 8 ml/kg, the respiratory rate (RR) was fixed at 12 breaths/min, the inspiratory to expiratory time ratio (I: E) was 1:2 and the inspired oxygen fraction (FiO2) was 0.5 (balanced with air) throughout the anesthesia period. To maintain a controlled ventilation, vecuronium was intermittently used for muscle relaxation. The depth of anesthesia was maintained with an infusion rate of propofol and remifentanil, according to the Bispectral Index values (BIS) and the hemodynamic parameters within 20% of the baseline. To prevent the occurrence of intraoperative awareness, the BIS values were kept between 45 and 60 in the three groups during surgery. Neuromuscular blocks were reversed with atropine (0.5 mg) and neostigmine (1 mg) before the tracheal extubation. Experienced surgeons preserved the anatomical integrity of motor nerves by visual identification and exposure both of the external branch of the superior laryngeal nerve and the recurrent laryngeal nerve, and the recurrent laryngeal nerve was prevented injury by intraoperative neuromonitoring during thyroid surgery. After the tracheal extubation, all of the patients were transferred to the post anesthesia care unit (PACU).
Demographic and clinical characteristics, including age, height, weight, ASA grade, gender, PLT (platelet), APTT (activated partial thromboplastin time), PT (prothrombin time), TT (thrombin time), Fib (fibrinogen) were recorded. Intraoperative fluid input, intraoperative blood loss and intraoperative urine output were recorded. The incidence and severity of cough within 5 min during the extubation was recorded: 0 = no cough, 1 = minimal (single) cough, 2 = moderate (≤5 s) cough and 3 = severe (> 5 s) cough (bucking) . The MAP and HR were measured and recorded before induction, during tracheal extubation and 5 min after tracheal extubation. The time to awareness, the postoperative length of hospital and any adverse events including local anesthetic toxicity, supraventricular or ventricular arrhythmias, bradycardia (HR < 60beat/min), hypotension (systolic blood pressure < 90 mmHg), need for vasopressors and prolonged respiratory support were recorded. Volume of drainage within the first and second 24 h after surgery, cervical hematoma, need for surgical revision, need for transfusion and time to removal of drainage were recorded. Patients were assessed in surgical ward for pain intensity using a 10 cm visual analogue scale (VAS: 0 = no pain, 10 = the most imaginable pain).
Calculation of sample size was based on the incidence of cough. In the pilot study, the two treatments infusion reduced the incidence of cough by 35%, and incidence of cough in the CON group was 62% and an α of 0.05, 55 patients would be required in each group (assuming a power of 0.80). Anticipating a study drop-out rate of 10%, we included 60 patients per group.
Data analysis was performed by using SPSS for Windows V.16.0 (SPSS Inc., Chicago, IL). Data were expressed as numbers, percentages or means±standard deviations. The quantitative variables were performed by using a one-way ANOVA with post hoc analysis. Repeated measurements were analysed using linear mixed model with a Bonferroni correction. Intergroup differences of the parameters at each time point were determined by using a one-way ANOVA with a post hoc analysis. The qualitative data were presented as numbers/percentages, and analysed by using a χ2 test. P values of less than 0.05 were considered to be statistically significant.