2.1

Study population

This prospective double-blinded randomized controlled clinical study was conducted at Zagazig University Hospital from July 2020 to September 2023. Approval from the institutional review board (the research ethical committee of the Faculty of Medicine, Zagazig University) with the reference number ZU-IRB#:6201//12/7/2020 was obtained, and the trial was registered with ClinicalTrials.gov (NCT04471597). The study was carried out according to the regulations and guidelines of Helsinki and in adherence to CONSORT guidelines ( http://www.consort-statement.org ).

Adult patients aged 21–60 years of both genders, with a BMI ≤ 35 kg/m2 and an ASA of I or II, were scheduled for elective thyroidectomy under general anesthesia. Patients with a history of difficult intubation, a history of laryngeal or tracheal surgery or pathology, chronic respiratory disease such as chronic obstructive pulmonary disease or asthma, recent respiratory tract infection in the last month, chronic cough, current smoking, symptomatic gastric reflux, or a history of allergy to the study drugs were excluded from this study.

2.2

Randomization and blinding

Forty-eight patients were assessed by the 3rd author a day prior to surgery and divided randomly by a computer-generated randomization table into two equal groups: group C (control group) received 5 ml of 0.9% normal saline topically 15 min before the expected end of surgery, and group B (bupivacaine group) received 5 ml of 0.5% bupivacaine topically 15 min before the expected end of surgery. The study drugs were prepared in foil covered syringes by the anesthesia nurse who was not involved in the study. All patients were anesthetized, and the study drugs were instilled by the 1st or the 2nd author who were blinded to the study drugs. The patients and the outcome assessors were blinded to the study groups.

2.3

Preoperative assessment

Preoperative evaluation for all patients included a detailed history and physical examination (special attention was given to airway assessment, vital signs, and chest and cardiac conditions to exclude contraindications). All patients were investigated by random blood glucose, complete blood count, liver and kidney function tests and coagulation profile. The goal of the study was to clarify the advantages and possible complications of this technique. Written informed consent regarding the procedure was obtained from every patient. Fasting for a minimum of 6–8 hours before the operation was confirmed. Patients were taught to quantify postoperative sore throat pain on a visual analog scale (VAS) of 0–10, where 0= no pain and 10= maximum worst pain.

2.4

Intraoperative

Upon arrival to the operating room, basic monitoring was performed (ECG, noninvasive blood pressure, pulse oximeter, and capnogram), and baseline data were recorded. The intravenous line was secured, and 0.01 mg/kg atropine, 4 mg ondansetron and 0.05 mg/kg midazolam were given as premedication.

The anesthesia protocol was standardized for all the patients. After preoxygenation (4 L/min of O2 for 5 minutes), general anesthesia was induced with intravenous fentanyl (2 µg/kg) and propofol (2–2.5 mg/kg), followed by cis-atracrium (0.15–0.2 mg/kg) to facilitate tracheal intubation. Intubation was performed using an endotracheal tube with 7.5 ID in males and 7 ID in females, and the pilot balloon was inflated to 20 cmH ₂ O and maintained at that pressure using a cuff manometer.

Isoflurane (1–1.5 MAC) was used for maintenance of anesthesia in an oxygen/air mixture, and muscle relaxation was maintained using 0.03 mg/kg cis-atracurium supplement every 30 min. The patient was mechanically ventilated with a tidal volume (6–8 ml/kg), and the respiratory rate was adjusted to keep the patient normocapnic and the ETCO ₂ level (35–40 mmHg).

Fifteen min before the anticipated time of end of surgery, the oropharyngeal cavity was gently suctioned using a catheter then the pilot balloon was deflated then, direct laryngoscopy with appropriate size MacIntosh blade was introduced until visualization of ETT within the vocal cords, the study drugs were administered in a 5ml syringe using a 22 gauge needle truncated near the needle hub according to the aforementioned randomization; in group (C): 5 ml of normal saline 0.9% and in group (B): 5 ml of bupivacaine 0.5% were topically applied around the ETT as follows: 2 ml were instilled anteriorly and 2 ml posteriorly to ETT and the remaining 1 ml was instilled on both sides of the ETT within the laryngeal inlet. After that, the patients in both groups underwent manual ventilation with a double tidal volume of 6–8 times or more to distribute air bubbles throughout the upper airway, anesthetizing the oropharynx and spreading around the ETT to the surrounding mucosal structures (laryngopharynx, larynx, and upper part of the trachea). Following this, the cuff was inflated to the premedication pressure, and the patient received mechanical ventilation as usual.

At the end of surgery, the isoflurane was turned off, and with the first attempt at spontaneous respiration, the muscle relaxant was reversed using 0.05 mg/kg neostigmine and 0.02 mg/kg atropine after gentle suctioning of the oropharynx. I.V. paracetamol (1 g) and 75 mg diclofenac sodium I.M. were given to all the patients as postoperative analgesia.

On emergence, the anesthesiologist responsible for data collection, who was not aware of the applied technique, assessed bucking and grade and counted the number of coughs before awake extubation and recorded the hemodynamic data. All patients were allowed to undergo awake extubation; extubation of the ETT while the patient could breathe spontaneously, follow verbal commands, and maintain a sustained head lift for more than 5 seconds.

Finally, all patients were transferred to the postanaesthesia care unit (PACU), where they were monitored for one hour for hemodynamic and SpO2 changes.

2.5

Parameter evaluation

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  Patient characteristics: Age, sex, BMI, and ASA physical status.

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  Operative time (min) .

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  The primary outcome:

  • –

    The incidence and grade of coughing ^, were assessed as follows:

    Grade 0: no cough.

    Grade 1: single cough with mild severity.

    Grade 2: cough lasting less than 5 s with moderate severity.

    Grade 3: sustained bouts of persistent cough for more than 5 s.

• ■

  The secondary outcomes:

  • –

    Hemodynamics (HR and MAP) and oxygen saturation (SpO2) were recorded at baseline, after administration of the study drug, before extubation, and then at 1, 2, 5, and 10 min immediately following extubation.

  • –

    The extubation time was defined as the time from the end of anesthesia (discontinuation of isoflurane) to the time at which the endotracheal tube was removed.

  • –

    The incidence and degree of postoperative sore throat (POST) were assessed by the VAS at 1, 2, 4, 6 and 12 h postoperatively.

  • –

    Residual effects of topical anesthesia included numbness in the throat, hoarseness (change in voice may range from mild hoarseness noted by the patient to complete aphonia), and voice tone down at 6 and 12 h postoperatively.

2.6

Sample size calculation

Assuming that the percentage of patients having no cough was 65% in the topical ropivacaine group versus 23% in the control group, so the sample size was calculated to be 44 cases divided into two groups, with 22 in each group, calculated using open Epi program with confidence interval of 95% and power of test 80%, taking in consideration that 10% was added for dropout, so the total sample size was 48 patients (24 in each group).

2.7

Statistical analysis

Data was analyzed using SPSS (Statistical Package for the Social Sciences) version 26 (IBM Corp., 2019). IBM SPSS Statistics for Windows, Version 26.0 (Armonk, NY: IBM Corp.). If appropriate, categorical variables were defined using absolute frequencies and compared using the chi-square test or Fisher’s exact test. The chi-square trend test was performed to compare ordinal data between the two groups. The Shapiro-Wilk test was developed to validate assumptions for parametric tests. Quantitative variables were described using means and standard deviations, or medians and quartile ranges, depending on the type of data. To compare quantitative data between the two groups, we utilized independent sample t -tests (for normally distributed data) and Mann-Whitney tests (for nonnormally distributed data). The level of statistical significance was set at P < 0.05. A highly significant difference was indicated by p ≤ 0.001.