Evaluation of the Efficacy of Different Drugs Nebulized at the Glottis on Postoperative Sore Throat in Thyroid Surgery With Nerve Monitoring: a Randomized Controlled Trial
Phase: PHASE4
Conditions: Postoperative Pain, NEBULIZATION, Thyroid Surgery
Sponsor: Qianfoshan Hospital

Research Protocol
Attachment 1(Version No.: V6.0 Date: 2025.02.05)
Project Title：Evaluation of the efficacy of nebulization of different
drugs at the glottis on postoperative sore throat in thyroid surgery with
neural monitoring
Project Source：The First Affiliated Hospital of Shandong First Medical
University
Undertaking Department：Department of Anesthesiology and Perioperative
Medicine
Principal Investigator：Liang Guo

Investigator Statement and Protocol Signature Page
As the principal investigator of this research project, I will comply
with the ethical principles of the Measures for Ethical Review of Life
Science and Medical Research Involving Humans (2023), the Measures for
Ethical Review of Biomedical Research Involving Humans (2016), the WMA
Declaration of Helsinki (2013), the CIOMS International Ethical
Guidelines for Biomedical Research Involving Human Subjects (2002) and
GCP. Under the guidance of Good Clinical Practice, I will conduct the
research in accordance with the protocol approved by the Ethics Committee
and the requirements of this protocol to ensure the scientific nature of
the research and protect the health and rights of research participants.
Name: ________________
Signature: ___________
Date: ________________

Protocol Summary
Item
Content
Protocol Title
Evaluation of the efficacy of nebulization of different
drugs at the glottis on postoperative sore throat in
thyroid surgery with neural monitoring
Version
No./Date
V6.0/2025.02.05
Principal
Investigator
Liang Guo
Research NatureInterventional clinical study
Research
Objectives
Primary Objective: To evaluate the efficacy of
nebulization of different drugs at the glottis on
postoperative sore throat in thyroid surgery with neural
monitoring
Primary Outcome Measure: Incidence of postoperative sore
throat
Secondary Outcome Measures: Four-point scale score and
NRS score of postoperative sore throat at immediately
after extubation, 12 h and 24 h after surgery in research
participants; age, gender, weight, height, voice use
habits (whether a teacher or singer), anesthesia
duration, postoperative intubation duration, and
occurrence of adverse reactions (cough, hoarseness,
dysphagia) within 24 h after surgery in research
participants
Sample Size
98 cases
Study Subjects
Research participants scheduled for thyroid surgery with
neural monitoring under general anesthesia in The First
Affiliated Hospital of Shandong First Medical University
Research MethodRandomized, double-blind, placebo-controlled trial
Inclusion
Criteria
1. Research participants fully understand the purpose and
significance of this trial, voluntarily participate and
sign the informed consent form;
2. Undergo thyroid surgery with neural monitoring under
general anesthesia (one-time successful tracheal
intubation);
3. Aged 18–60 years, gender unlimited;

Item
Content
4. 18 kg/m² ≤BMI ≤30 kg/m²;
5. Operation time 1–4 hours;
6. ASA Class I–II;
7. No contraindications to the use of study drugs.
Exclusion
Criteria
1. Smokers or those with preoperative sore throat;
2. Recent upper or lower respiratory tract infection;
3. Patients refusing to participate in this study;
4. With significant dysfunction of liver, kidney and other
organs;
5. Pregnancy or lactation;
6. Mallampati class > 2;
7. Surgery requiring nasogastric tube;
8. Repeated thyroid surgery;
9. Preoperative use of non-steroidal drugs or analgesics;
10.Patients with chronic pharyngitis or reflux
esophagitis;
11.Tracheal intubation attempted by an experienced
anesthesiologist > 2 times;
12.Patients allergic to study drugs.
Study
Completion
Criteria
Completion of trials with valid sample size
Early
Withdrawal
Criteria
Withdrawal decided by investigators: Withdrawal of
research participants refers to the situation where
enrolled research participants are not suitable to
continue the trial during the trial, and the investigator
decides to withdraw the participant from the trial.
1) The investigator deems it necessary to terminate the
trial from the perspective of medical ethics.
2)
A serious adverse event (SAE) occurs, and the
investigator judges that the participant is not suitable
to continue the trial.
3) The investigator judges that withdrawal from the study
is most beneficial to the research participant.
4) Poor compliance of research participants, including:
a. Failure to take drugs and accept examinations as
required;

Item
Content
b. Use of other drugs or foods affecting the efficacy
and safety trial results;
c. Other behaviors affecting trial results;
d. Loss to follow-up.
Voluntary withdrawal by research participants: According
to the informed consent form, research participants
have the right to withdraw from the trial midway, or fail
to receive medication and testing without withdrawing
informed consent (also regarded as withdrawal or
dropout). The reason for withdrawal should be
ascertained and recorded as much as possible.
Dosing Regimen
1) Control Group (Group C): Inhalation of 5 ml normal
saline by nebulization at the glottis after conventional
anesthesia induction and tracheal intubation
2) Experimental Group (Group N): Inhalation of 1 ml
budesonide + 4 ml lidocaine by nebulization at the glottis
after conventional anesthesia induction and tracheal
intubation
Primary Outcome
Measure
Incidence of sore throat
Secondary
Outcome
Measures
1) Four-point scale score and NRS score of postoperative
sore throat at immediately after extubation, 12 h and 24
h after surgery in research participants.
2) Whether the tracheal tube is bloody at extubation
3) Operation duration
4) Postoperative intubation duration
5) Number of cases with postoperative cough, hoarseness
and dysphagia
Statistical
Analysis Method
A preliminary experiment was conducted with reference to
previous literature. The incidence of postoperative sore
throat in the control group and experimental group was 47%
and 16% respectively. A two-sided α=0.05 and a power of
90% were set. The sample size was calculated according to

Item
Content
the following formula,
and n1=42 cases and n2=42 cases were obtained. Considering
1:1 randomization, 42 participants were required in both
experimental group
and control group. Taking into
account 15% loss to follow-up and refusal to visit, at
least 49 participants were finally required in each group,
with a total of 98 participants enrolled. Measurement data
conforming to normal distribution were statistically
described by mean ± standard deviation; measurement data
not conforming to normal distribution were statistically
described by median (interquartile range).
Non-parametric rank sum test was used for comparison
between two groups. Count data were statistically
described by frequency and percentage, and chi-square
test or Fisher's exact test was used for comparison
between two groups. Repeated measures analysis of
variance was used for sore throat score and NRS score at
different time points. According to the basic principle
of Intention-to-Treat (ITT) analysis, full analysis set
was used for analysis. Statistical analysis was performed
with SPSS 22.0 software, and two-sided test was adopted
for statistical tests. P<0.05 was considered
statistically significant.
Form of
Research
Achievement
Publication
Treatise
Trial Schedule Start Time: Q1 2025
End Time: Q1 2026

1. Research Objectives
To evaluate the efficacy of nebulization of different drugs at the
glottis on postoperative sore throat in thyroid surgery with neural
monitoring.
Primary Outcome Measure
Incidence of postoperative sore throat in research participants.
Secondary Outcome Measures
1)Four-point scale score and visual analogue scale score of postoperative sore
throat at immediately after extubation, 12 h and 24 h after surgery; 2) Whether
the tracheal tube is bloody at extubation; 3) Anesthesia duration; 4)
Postoperative intubation duration; 5) Number of cases with postoperative cough,
hoarseness and dysphagia.
2. Research Background
Postoperative sore throat (POST) is one of the common complications
after general anesthesia with endotracheal intubation, with an incidence
rate of 30%–70% reported in the literature (Mchard F E, Chung F.
Postoperative sore throat: cause, prevention and treatment[J].
Anaesthesia. 1999,54(5):444-453.). Severe POST accompanied by cough,
hoarseness, dysphagia, etc., seriously reduces patients' postoperative
comfort and satisfaction, and is not conducive to rapid postoperative
recovery. Thyroid surgery is performed in a special position with shoulder
elevation and head hyperextension, which aggravates the stimulation of
the glottis by tracheal intubation. In addition, the thyroid gland is
surrounded by abundant blood vessels and nerves, and surgical stimulation
can induce the release of a large number of inflammatory factors, thereby
aggravating pharyngeal pain (CAI H D, LIN C Z, YU C X, et al. Bilateral
superficial cervical plexus block reduces postoperative nausea and
vomiting and early postoperative pain after thyroidectomy[J]. J Int Med
Res,2012,40(4):1390-1398.). The neural monitoring tracheal tube has a
larger diameter than ordinary tracheal tubes. Electrical stimulation is
periodically emitted through neural probes to collect feedback signals
with minimal or no use of muscle relaxants. Muscle tension at the glottis
and continuous electrical stimulation also aggravate pharyngeal pain.

As a non-invasive clinical method, nebulized inhalation atomizes
drugs and water into mist to enter the oral cavity, pharynx and respiratory
tract through a nebulizer, which can rapidly relieve inflammatory
congestive edema of the pharynx, exert anti-inflammatory, expectorant and
even antitussive effects, and also has a certain damp-heat moistening
effect. When drugs act directly on damaged mucosa, they can effectively
increase the local drug concentration in the respiratory tract, thereby
relieving respiratory spasm and eliminating respiratory inflammation.
Nebulized inhalation therapy can rapidly alleviate pharyngeal
complications and avoid side effects caused by systemic administration
to a certain extent, with remarkable clinical effects (Farkas A, Balashazy
I, Szoes K. Characterization of Regional and local deposition of inhaled
aerosol drugs in The respiratory system by computational fluid and
Particle dynamics methods[J]. J Aerosol Med,2006,19(3):329-343.
Kleinstreuer C, Zhang Z, Donohue J F. Targeted drug aerosol delivery in
the human respiratory system[J]. Annu Rev Biomed
Eng,2008,10(8):195-220.).
Budesonide is a type of glucocorticoid, which can significantly
inhibit leukocyte infiltration and phagocytosis, reduce the release of
local inflammatory mediators. At the same time, nebulized inhalation of
glucocorticoids can improve vascular tension, reduce capillary
permeability and congestion, thereby reducing the occurrence of
pharyngeal inflammation and edema and relieving postoperative sore throat
(Cheng Zhe, Zheng Wanlai, Zhan Shilong, et al. Efficacy analysis of
budesonide suspension for nebulized inhalation in the treatment of
postoperative sore throat after general anesthesia for oral surgery[J].
Journal of Stomatology,2016,36(1):61-63.). Lidocaine is an amide local
anesthetic with strong tissue diffusivity and mucosal penetrability and
rapid onset. It inhibits the excitation of airway C sensory fibers by
blocking ion flow required for the generation and conduction of nerve
impulses, stabilizes nerve cell membranes, reduces central sensitivity,
and alleviates pharyngeal pain (Moustafa M A. Nebulized lidocaine alone
or combined with fentanyl as a premedication to general anesthesia in
spontaneously breathing pediatric patients undergoing rigid
bronchoscopy[J]. Paediatr Anaesth,2013,23(5):429-434. Zhou Yaru, Zha
Jiaming, Jing Zhixin, et al. Determination of related substances in
lidocaine aerosol by HPLC[J]. Chinese Journal of Pharmaceutical
Analysis,2018,38(3):469-476. Wang Yuhong, Qiu Bo, Jiang Jiandong, et al.

Effect of lidocaine on hERG potassium channel[J]. Acta Pharmaceutica
Sinica,2016,51(11):1698-1703.).
3. Research Basis
1. Mchard F E, Chung F. Postoperative sore throat: cause, prevention and
treatment[J]. Anaesthesia. 1999,54(5):444-453.
2. CAI H D, LIN C Z, YU C X, et al. Bilateral superficial cervical plexus block
reduces postoperative nausea and vomiting and early postoperative pain after
thyroidectomy[J]. J Int Med Res,2012,40(4):1390-1398.
3. Farkas A, Balashazy I, Szoes K. Characterization of Regional and local
deposition of inhaled aerosol drugs in The respiratory system by computational fluid
and Particle dynamics methods[J]. J Aerosol Med,2006,19(3):329-343.
4. Kleinstreuer C, Zhang Z, Donohue J F. Targeted drug aerosol delivery in the
human respiratory system[J]. Annu Rev Biomed Eng,2008,10(8):195-220.
5. Cheng Zhe, Zheng Wanlai, Zhan Shilong, et al. Efficacy analysis of budesonide
suspension for nebulized inhalation in the treatment of postoperative sore throat
after general anesthesia for oral surgery[J]. Journal of Stomatology,2016,36(1):61-63.
6. Moustafa M A. Nebulized lidocaine alone or combined with fentanyl as a
premedication to general anesthesia in spontaneously breathing pediatric patients
undergoing rigid bronchoscopy[J]. Paediatr Anaesth,2013,23(5):429-434.
7. Zhou Yaru, Zha Jiaming, Jing Zhixin, et al. Determination of related substances
in lidocaine aerosol by HPLC[J]. Chinese Journal of Pharmaceutical
Analysis,2018,38(3):469-476.
8. Wang Yuhong, Qiu Bo, Jiang Jiandong, et al. Effect of lidocaine on hERG
potassium channel[J]. Acta Pharmaceutica Sinica,2016,51(11):1698-1703.
4. Research Content
1. Study Population
Research participants scheduled for thyroid surgery with neural
monitoring under general anesthesia in The First Affiliated Hospital of
Shandong First Medical University.
Sample Size Calculation
A preliminary experiment was conducted with reference to previous
literature. The incidence of postoperative sore throat in the control
group and experimental group was 47% and 16% respectively. A two-sided
α=0.05 and a power of 90% were set. The sample size was calculated

according to the formula,
and n1=42
cases and n2=42 cases were obtained. Considering 1:1 randomization, 42
participants were required in both experimental group 1 and control group.
Taking into account 15% loss to follow-up and refusal to visit, at least
49 participants were finally required in each group, with a total of 98
participants enrolled.
5. Research Method
1. Inclusion Criteria
1. Research participants fully understand the purpose and significance of this
trial, voluntarily participate and sign the informed consent form;
2. Undergo thyroid surgery with neural monitoring under general anesthesia
(one-time successful tracheal intubation);
3. Aged 18–60 years, gender unlimited;
4. 18 kg/m² ≤BMI ≤30 kg/m²;
5. Operation time 1–4 hours;
6. ASA Class I–II;
7. No contraindications to the use of study drugs.
2. Exclusion Criteria
1. Smokers or those with preoperative sore throat;
2. Recent upper or lower respiratory tract infection;
3. Patients refusing to participate in this study;
4. With significant dysfunction of liver, kidney and other organs;
5. Pregnancy or lactation;
6. Mallampati class > 2;
7. Surgery requiring nasogastric tube;
8. Repeated thyroid surgery;
9. Preoperative use of non-steroidal drugs or analgesics;
10. Patients with chronic pharyngitis or reflux esophagitis;
11. Tracheal intubation attempted by an experienced anesthesiologist > 2 times;
12. Patients allergic to study drugs.
3. Recruitment of Research Participants
After obtaining ethical approval, recruitment will be conducted in
the thyroid surgery ward by researchers specially responsible for

recruitment, targeting patients meeting the inclusion and exclusion
criteria who need thyroid surgery with neural monitoring.
4. Grouping of Research Participants
Eligible research participants will be randomly assigned to the
control group and experimental group at a ratio of 1:1.

Control Group (Group C):
Drug Name: 0.9% Sodium Chloride Injection
Storage Condition: Store at room temperature;
Administration Method: Conventional anesthesia induction,
inhalation of 5 ml normal saline by nebulization at the glottis after
tracheal intubation

Experimental Group (Group N):
Drug Name: Budesonide Suspension for Inhalation
Specification: 2mL; 1mg;
Storage Condition: Store at 8–30℃, do not refrigerate;
Drug Name: Lidocaine Hydrochloride Injection
Specification: 5mL; 0.1g;
Storage Condition: Sealed storage;
Administration Method: Conventional anesthesia induction,
inhalation of 1 ml budesonide + 4 ml lidocaine by nebulization at the
glottis after tracheal intubation
5. Grouping and Blinding
5.1 Block Randomization Grouping
Patients were grouped by block randomization, and the sequence was
concealed in opaque sealed envelopes. Drug blinding was performed by
specialized personnel not directly involved in the clinical trial. Block
randomization grouping was adopted (random number table generated by
statistical software (SAS)), coded sequentially as 1,2,3,4…243, and
divided into 2 groups according to block randomization.
5.2 Blinding
This trial is designed as double-blind, with research participants
unaware of group allocation and investigators unaware of the drugs used.(1)
The total random table is kept by specialized personnel responsible for
statistics;(2) Pumped drugs are prepared by specialized nurses not
directly involved in the clinical trial according to the total random
table.

5.3 Unblinding
Overall Unblinding: Unblinding will be performed after the completion of
case report form entry and statistical analysis.
Emergency Unblinding: Performed when a research participant experiences a
serious adverse event and the investigator believes that knowing the drug used by
the participant is necessary to take effective measures.
6. Rescue Medication and Supportive Treatment
For patients with severe postoperative sore throat, nebulization
therapy will be continued.
7. Criteria for Early Withdrawal/Termination of Trial by Research
Participants
7.1 Withdrawal Decided by Investigators
Withdrawal of research participants refers to the situation where
enrolled research participants are not suitable to continue the trial
during the trial, and the investigator decides to withdraw the participant
from the trial.
1. The investigator deems it necessary to terminate the trial from the
perspective of medical ethics.
2. A serious adverse event (SAE) occurs, and the investigator judges that the
participant is not suitable to continue the trial.
3. The investigator judges that withdrawal from the study is most beneficial to
the research participant.
4. Poor compliance of research participants, including:a. Failure to take drugs
and accept examinations as required;b. Use of other drugs affecting the efficacy trial
results, such as analgesics, non-steroidal anti-inflammatory drugs, etc.;c. Other
behaviors affecting trial results;d. Loss to follow-up.
7.2 Voluntary Withdrawal by Research Participants
According to the informed consent form, research participants have
the right to withdraw from the trial midway, or fail to receive medication
and testing without withdrawing informed consent (also regarded as
withdrawal or dropout). The reason for withdrawal should be ascertained
and recorded as much as possible.
8. Adverse Events
Definition of Serious Adverse Event (SAE)
SAE refers to any adverse medical event meeting any of the following
criteria (a–f):a. Resulting in death;b. Life-threatening (in the
definition, life-threatening refers to an immediate risk of death for a
critically ill patient, not hypothetical death in the future if the

condition worsens);c. Resulting in hospitalization or prolongation of
hospital stay;Hospitalization or prolongation of hospital stay shall not
be reported as SAE if meeting at least one of the following criteria:
Hospital stay <12 hours after admission;
Pre-planned admission (e.g., elective or scheduled surgery arranged before
the first administration of study drugs; or admission is part of the study procedure);
Hospitalization unrelated to adverse events (e.g., admission to social welfare
institutions for temporary care). However, it should be emphasized that invasive
treatment received during hospitalization may meet the criteria of "important
medical event" and thus should be reported as SAE based on clinical judgment.d.
Resulting in significant or permanent disability/functional impairment (disability
refers to substantial damage to an individual's ability to perform normal life functions;
functional loss does not include events of relatively minor medical importance, such
as headache, nausea, vomiting, diarrhea, influenza and accidental trauma (e.g., ankle
sprain)).e. Resulting in congenital malformation or birth defect: congenital
malformation or birth defect in a newborn (fetus) born (or aborted) to a female
research participant exposed to drugs or the female partner of a male research
participant exposed to drugs.f. Other important medical events: events that may not
immediately result in death, life-threatening conditions or
hospitalization/prolongation of hospital stay, but according to medical judgment,
may harm research participants or require medical intervention to prevent one of the
above situations.
6. Trial Procedure
1. Screening Period
Sign informed consent form, collect general data: past medical
history or medication history, personal history, physical examination,
vital signs;
Randomization:Research participants are randomly divided into two
groups: Control Group (Group C), Budesonide + Lidocaine Group (Gtoup N).
Block randomization grouping is adopted, with 49 people in each group.
Nebulization:A research nurse is responsible for allocating and
preparing intraoperative nebulization drugs. After conventional
anesthesia induction and tracheal intubation, a sterile suction tube for
nebulization is connected to the tracheal tube and fixed at the upper end
of the test electrode of the neural monitoring tracheal tube. After the
tracheal tube is fixed, the nebulization tube is located at the glottis.
The anesthesiologist connects the wall-mounted nebulization device and
performs nebulization at an oxygen flow rate of 2 L/min for 1 hour.

2. Observation Period
Anesthesia:After entering the operating room, research participants
receive routine monitoring of ECG, SPO2, NIBP, skin temperature and BIS
anesthesia depth monitoring. The anesthesia method is the same in all
groups. Anesthesia induction is performed with midazolam 0.03 mg/kg,
sufentanil 0.4 ug/kg, etomidate 0.4 mg/kg and atracurium 0.6 mg/kg. Mask
oxygenation and denitrogenation are performed before intubation,
followed by connection to the anesthesia machine. Anesthesia machine
parameters: VT 6–8 ml/kg, RR 10–12 times/min, inspiratory-expiratory
ratio 1:2, oxygen concentration 60%, fresh gas flow 2 L/min, maintaining
end-tidal partial pressure of carbon dioxide at 35–45 mmHg.
Intraoperative Management:Tracheal cuff pressure is monitored every
15 minutes with a cuff manometer, maintaining pressure at 25–30 cmH₂O.
Anesthesia maintenance is performed with target-controlled infusion of
propofol 0.5–2 ug/ml, remifentanil 0.2–0.3 ug/kg/min, and additional
atracurium 0.15 mg/kg and sufentanil 0.2 ug/kg as needed, maintaining BIS
value at 40–60. A warming blanket is used intraoperatively to keep the
body temperature of research participants not lower than 36℃. After
surgery, patients are sent to PACU for resuscitation. No hormonal drugs
or non-steroidal anti-inflammatory drugs are used in all research
participants during the perioperative period.
3. Postoperative Follow-up
Research participants are interviewed face-to-face by a professional
anesthesiologist unaware of group allocation. The follow-up endpoint is
24 h after surgery, and follow-up time points are immediately after
surgery, 12 h and 24 h; follow-up contents include four-point scale score
and visual analogue scale score of postoperative sore throat at each time
point, whether the tracheal tube is bloody at extubation, and occurrence
of postoperative cough, hoarseness and dysphagia. If the NRS score ≥4
at 24 h after surgery, the investigator will track and observe the research
participant and provide symptomatic treatment until the NRS score <4.
4. Rescue and Supportive Treatment
Record the four-point scale score and NRS score of pharyngeal pain
at any follow-up time point. Terbutaline nebulization is given if the
four-point scale score > grade 2 and NRS score >4.
5. Data Collection
Record age, gender, weight, height, BMI index, whether a teacher or
singer of research participants; record anesthesia duration,

postoperative intubation duration (from the end of surgery to extubation
of tracheal tube), whether the tracheal tube is bloody at extubation;
record four-point scale score and visual analogue scale score of
pharyngeal pain at immediately after surgery, 12 h and 24 h after surgery,
and the number of cases with postoperative cough, hoarseness and dysphagia
in research participants.
6. Data Management
Electronic information entry is performed by two data entry
administrators, and all information required by the research protocol
must be provided. Investigators must keep the original documents of each
participant in the trial, and all data must be derived from the original
documents. Cases with missing data or illogical data will be deleted
during data processing.
7. Compliance with Ethical Principles and Relevant Regulations
7.1 Ethics Committee Review
This protocol, written informed consent form, case report form and
materials directly related to research participants must be submitted to
the Ethics Committee, and the study can be officially carried out only
after obtaining written approval from the Ethics Committee. The
investigator shall notify the Ethics Committee in writing when the study
is suspended and/or completed; the investigator shall promptly report all
changes occurring in the research work (such as revisions of the protocol
and/or informed consent form) to the Ethics Committee, and shall not
implement these changes without obtaining approval from the Ethics
Committee, unless the changes are made to eliminate obvious and immediate
risks to research participants. In such cases, the Ethics Committee will
be notified.
7.2 Procedure for Obtaining Informed Consent
The investigator provides the research participant or his legal
representative with an easy-to-understand informed consent form approved
by the Ethics Committee, and gives sufficient time for the research
participant or his legal representative to consider the study. No research
participant shall be enrolled before obtaining the signed written
informed consent form from the research participant. During the
participation of research participants, all updated versions of the
informed consent form and written information will be provided to them.
The informed consent form shall be kept as an important document of the
clinical trial for future reference.

8. Statistical Analysis Plan
Sample Size Calculation
A preliminary experiment was conducted with reference to previous
literature. The incidence of postoperative sore throat in the control
group and experimental group was 47% and 16% respectively. A two-sided
α=0.05 and a power of 90% were set. The sample size was calculated
according to the formula,
and n1=42
cases and n2=42 cases were obtained. Considering 1:1 randomization, 42
participants were required in both experimental group 1 and control group.
Taking into account 15% loss to follow-up and refusal to visit, at least
49 participants were finally required in each group, with a total of 98
participants enrolled.
Statistical Analysis
Measurement data conforming to normal distribution were
statistically described by mean ± standard deviation; measurement data
not conforming to normal distribution were statistically described by
median (interquartile range). Non-parametric rank sum test was used for
comparison between two groups. Count data were statistically described
by frequency and percentage, and chi-square test or Fisher's exact test
was used for comparison between two groups. Repeated measures analysis
of variance was used for sore throat score and NRS score at different time
points.
According to the basic principle of Intention-to-Treat (ITT) analysis,
full analysis set was used for analysis. Statistical analysis was
performed with SPSS 22.0 software, and two-sided test was adopted for
statistical tests. P<0.05 was considered statistically significant.
9. Quality Control
The principal investigator shall train the personnel participating
in the research. Investigators shall strictly follow the trial protocol
and adopt corresponding standard operating procedures to ensure the
implementation of the quality control and quality assurance system of the
clinical trial.
10. Form of Research Achievement Publication
Treatise.

11. Trial Schedule
Start Time: Q1 2025
End Time: Q1 2026
12. Appendices
NRS Score
0: No pain1–3: Mild pain (pain does not affect sleep)4–6: Moderate
pain (pain affects sleep)7–9: Severe pain (unable to fall asleep,
awakened by pain during sleep or unable to sleep)10: Excruciating
pain
Four-point Scale Score Classification for Postoperative Sore Throat
Grade 1: No sore throat.
Grade 2: Mild sore throat (complains of sore throat only when asked).
Grade 3: Moderate sore throat (complains of sore throat repeatedly).
Grade 4: Severe sore throat (hoarseness or voice change caused by sore
throat).