Ultrasound-guided internal branch of superior laryngeal nerve block on postoperative sore throat: A randomized controlled trial.

INTRODUCTION: Ultrasound-guided internal branch of the upper laryngeal nerve block (USG-guided iSLN block) have been used to decrease the perioperative stress response of intubation. It is more likely to be successful than blindly administered superior laryngeal nerve blocks with fewer complications. Here, we evaluated the efficacy of USG-guided iSLN block to treat postoperative sore throat (postoperative sore throat, POST) after extubation.
METHODS: 100 patients, aged from 18 to 60 years old, ASA I~II who underwent general anesthesia and suffered from the moderate to severe postoperative sore throat after extubation were randomized into two groups(50 cases per group). Patients in group S received USG-guided iSLN block bilaterally (60mg of 2% lidocaine, 1.5ml each side), whereas those in group I received inhalation with 100 mg of 2% lidocaine and 1mg of budesonide suspension diluted with normal saline (oxygen flow 8 L /min, inhalation for 15 minutes). The primary outcome were VAS scores in both groups before treatment (T0), 10 min (T1), 30 min(T2), 1h(T3), 2 h(T4), 4h(T5), 8h(T6), 24h(T7), and 48h(T8) after treatment. The secondary outcome were satisfaction scores after treatment, MAP, HR, and SPO2 fromT0 to T8. The adverse reactions such as postoperative chocking or aspiration, cough, hoarseness, dyspnea were also observed in both groups.
RESULTS: Patients in group S had significantly lower VAS score than that in group I at points of T1 ~ T6 (P < 0.01). HR of group S was lower than that of group I at points of T1 ~ T2and T4 (P < 0.05), and MAP was lower than that of group I at points of T1 ~ T3 (P < 0.05). Satisfaction scores of group S were higher than that of group I (P <0.05), In group S, 2 case (4%) needed to intravenous Flurbiprofen Injection 50 mg to relieve pain; in group I, 13 cases (26%) received Flurbiprofen Injection. 2 case of group S appeared throat numbness after treatment for 3 hours; 2 patients have difficult in expectoration after treatment recovered after 3hour. No serious adverse events were observed in both groups.
CONCLUSION: Compared with inhalation, USG-guided iSLN block may effectively relieve the postoperative sore throat after extubation under general anesthesia and provided an ideal treatment for POST in clinical work.

RCT Entities:   Population Interventions Outcomes

Introduction

Postoperative sore throat (POST) is one of the common complications after extubation in patients under general anesthesia with tracheal intubation [1]. It is associated with mucosal damage and edema of the pharynx and larynx, for example, tracheal mucosa edema caused by excessive pressure of the cuff. Most POST have self-healing ability, but it could increase the discomfort of patients, prolong hospitalization time of patients [2, 3], and even affect the mortality rate [4, 5]. Many studies have been designed to find out possible approaches to reduce the occurrence of POST. Although, the occurrence of POST can be reduced by choosing a smaller type of endotracheal tube, softening tube, and using appropriate pressure of tracheal cuff, it is still an inevitable problem.

The medial branch of the superior laryngeal nerve accompanied by the superior laryngeal artery passed through the thyrohyoid membrane and divided into many small branches to the pharynx, epiglottis, and the sensory nerve of the laryngeal mucosa above the glottic fissure. Blocking the internal branch of the superior laryngeal nerve (iSLN) can achieve the anesthetic effect of the root of tongue, epiglottis, and laryngeal mucosa above glottis fissure [6]. Several studies have also shown that the blockade of the internal branch of the superior laryngeal nerve can be used during fiberoptic bronchoscopy, laryngoscopic surgery, conscious intubation of difficult airway to reduce the hemodynamic change caused by airway stimulation and provide better practical condition for operation [7-9]. Although others have reported bilateral iSLN block may reduce the severity of POST in assisted laryngoscopic surgery, we are not aware of any high quality randomized, controlled trials that have investigated the effectiveness of ultrasound guided internal branch of superior laryngeal nerve block (USG-guided iSLN block) on pcostoperative sore throat as compared with atomization inhalation, as treatment for POST.

We conducted a randomized clinical trial involving patients with POST to evaluate the efficacy and safety of ultrasound-guided superior laryngeal nerve block on postoperative sore throat. Our primary objective was to assess the efficacy of this method to relieved the POST. Our secondary objectives included satisfaction score of patient, hemodynamic response and adverse events during treatment. We hypothesized that administration of USG guided block of the iSLN would provide greater pain relief in patients with POST as well as more blunt the hemodynamic response after treatment, than does treat with atomization inhalation alone.

Method

Study population

The study was approved by the Medical Ethics Committee of Foshan Chancheng Central Hospital, and informed consent was signed by patients and their families. The register number was ChiCTR1800015007. The ethics committee approved the study on Feburary 7, 2018. We registered this study on Feburary 28. Patients were enrolled in the study from June 12, 2018, to June 6, 2019. Participants were recruited for the study through advisement from Chancheng central hospital and the research was took place in PACU. Participants were enrolled if they fulfilled the following criteria: men or women between 18 and 60 years; ASA I or II; POST after extubation with tracheal intubation less than 4 hours; vital signs were stable after the operation in all patients. Patients with any of the following conditions were excluded: long-term smoking history; preoperative long-term throat discomfort and chronic laryngitis; patients who underwent oropharyngeal and neck surgery; patients who experienced difficult intubation and multiple intubations; patients who were unable to understand or cooperate with pain score; patients with long-term opioids, antipyretic analgesics or hormone treatment; patients who were allergic to local anesthesia. Because the syndrome is always self-healing, we follow-up the patients in 3days. All patients gave written informed consent before participation in this study. There were no important changes to methods after trial commencement.

Randomization and blinding

Participants were enrolled to the study by the administrator if they had POST and signed the consent, They were randomly assigned in a 1:1 ratio (50 cases in each group) to receive atomization inhalation (I group) or received iSLN block (S group) using a computer-generated table of random numbers by the administrator who don’t take part in the treatment. The envelope concealed the random numbers was opened by the anesthesiologist who performed the punctuation. The iSLN block was performed under the guidance of ultrasound. The allocation of participants was performed by an independent researcher at each clinical site who was not involved in outcome assessment. Patients in both groups were treated in the postanesthesia care unit and blinded to which treatment they would receive. The outcome assessors, data collectors, and statisticians were blinded to group allocations during the study ().

CONSORT diagram of participant flow.

ITT = intention to treat; PP = per protocol.

Interventions

All patients presented to operation room on the day of surgery after overnight fasting of 8 hours. After entering the operation room, the patients were given 8 ml/kg.h lactated Ringer's solution intravenously. MAP, HR, and SPO2 were monitored routinely. Sufentanil (0.35 ug/kg), Propofol (2 mg/kg), and cis-atracurium (0.2 mg/kg) were given intravenously for anesthesia induction, and then general anesthesia was performed by tracheal intubation. No.7 endotracheal tube was used for women and No. 7.5 tube for men, respectively. All patients were successfully intubated at one time. The intubation was performed by the anesthesiologists who had over three years of standardized training. Narcotrend was used to monitor the depth of intraoperative anesthesia, while inhalation of sevoflurane (2%-3%), intravenous injection of Sufentanil (0.015 μg∙kg-1∙h-1) and cis-atracurium (5 mg/h) were used to maintain a certain depth of anesthesia. Following postoperative successful resuscitation, patients were sent to the post-anesthesia care unit (PACU) after extubation.

Patients were provided with mask oxygen inhalation at a concentration of 40%, ECG, HR, MAP, SpO2 were monitored routinely. When the patient is fully awake, the visual analogue scale (VAS) was used to evaluate the degree of sore throat, and a digital scoring method (0–10) was used to describe the degree of pain (0 was painless, 10 was the most severe pain).

USG guided block of the iSLN: For performing the block, patients were positioned supine, with the neck extended. A high-frequency (6–13MHz) ultrasound probe (Sonosite, USA) was placed over the submandibular area with a longitudinal orientation (). The greater horn of the hyoid bone and thyroid cartilage were identified, which are hyperechoic signals on sonography. The thyrohyoid muscle and thyrohyoid membrane between these two structures and there was a hyperechoic mass between the detected two structures, which was the internal branch of superior laryngeal nerve (). The block was performed using a 24gauge 1 inch needle with a 5 ml syringe that was filled with lidocaine 2%. An out-of-plane method was used to inject 2% lidocaine (1.5 ml each side) bilaterally, followed by local compression and observation for 5 minutes.

Ultrasound image of iSLN block.

(A) Hyoid bone and thyroid cartilage were marked in the ultrasound image. (B) The red dotted line and yellow circle represented thyrohyoid membrane and superior laryngeal nerve respectively. (C) The white arrow represented the needle path.

Patients in Group I were treatment with 2% lidocaine (100 mg) + Budesonide suspension (1 mg) diluted with normal saline to 10 ml (oxygen flow of 8 L/min). and mouthing-containing aerosol inhalation for 15 minutes. They inhale atomized gas with a nebulizer for 15minutes. Patients didn’t know other people’s treatment method because they were separated into independent space by curtains.

Patients were sent to the ward of hospital after treatment, the anesthetists who was blinded to the treatment were assigned to follow-up and collect the results of treatment.

Measures

The primary outcome were VAS scores in both groups before treatment (T0), 10 min (T1), 30 min(T2), 1h(T3), 2 h(T4), 4h(T5), 8h(T6), 24h(T7), and 48h(T8) after treatment

The VAS scores were recorded because that they are directly relative to POST. After 30 minutes of treatment, 50 mg of Flurbiprofen ester was given via intravenous injection to the patients with VAS≥4 points to relieve pain, and the total dosage was recorded within 48 hours.

MAP, HR and, SPO 2 were recorded from T0 to T8, and adverse reactions were observed at the same time as the secondary outcome. Meanwhile, patients' satisfaction scores with treatment were also recorded 48 h after treatment. Two hours after the treatment of sore throat, patients were instructed to drink 20 ml of water to observe the occurrence of choking, aspiration and regurgitation, newly onset of hoarseness, and dyspnea.

Statistical analysis

A detailed statistical analysis plan was made before the study was completed and any analyses were performed. An independent statistician who was unaware of the group assignments performed all the analyses. The software named IBM SPSS statistics 24.0 was used for the analysis. For VAS scores 2 hours after treatment according to previous study [10], a minimal clinically important difference of 10 is recommended and commonly used.

We calculated that a sample size of 49 patients in each group would give the study 80% power to detect a 20-point greater improvement in VAS scores in the S group than in the I group at a two-sided significance level of 0.05. The calculation was operated on the website http://powerandsamplesize.com.

Age, BMI, intubation time, patient satisfaction score, VAS score of sore throat, blood pressure, and heart rate were continuous quantitative normally distributed data expressed as means and standard deviations (SD). Quantitative discrete data were expressed as median and range. Qualitative nominal data e.g. incidence of complications were expressed as percentage. Among them, age, BMI, intubation time, and patient satisfaction score were analyzed using Student’s t-test, while inter-group comparison of VAS score of sore throat, blood pressure and heart rate was performed by repeated measures ANOVA. Greenhouse-Geisser's correction was applied when the Mauchly's test of sphericity was not followed, and multivariate analysis of variance was used to compare Group I and Group S at each time points. Chi-square or Fisher’s exact tests were used as appropriate to compare qualitative data. A P-value<0.05 was considered statistically significant.

Results

General data

125 patients were interest to the research from January to August in 2019, 5 patients declined and 20 patients were excluded. The trial was stopped when enough patients were included to the study. 100 patients with moderate to severe sore throat after extubation under general anesthesia were enrolled in the study. There was no significant difference in gender, age, weight, height, BMI, and intubation time before treatment between the two groups (Table 1).

Table 1

Demographic details of patients.

Variable		I group	S group	X2or t	aP
Female sex	(male/female)	14/36	18/32	0.735	0.391
Age (y)	(mean±SD)	36.1±7.8	37.9±6.9	-1.18	0.963
Height		162.8±7.2	162.2±6.2	0.466	0.266
Weight		59.5±8.0	59.2±7.3	0.532	0.17
BMI	(kg/m2)	22.4±2.8	22.5±2.7	-0.126	0.676
ASA grade		6/44	5/45	0	1
Intubation time	(min)	96.8±18.9	102.6±24.3	0.102	0.739

Abbreviations: BMI, body mass index(calculated as weight in kilograms divided by height in meters squared);ASA, American Society of Anesthesiologists

aP values were calculated using chi-square test or t test.

VAS score at different time points between the two groups

VAS score of sore throat at T1~T6 in Group S was lower than that in Group I, with a significant difference between the two groups, but there was no significant difference between the two groups at T7~T8. The analgesic effect of sore throat in Group S was significantly better than that in Group L at T1-T6, whereas there was no significant difference between the two groups at the rest of time points (Table 2).

Table 2

VAS scores of both group.

	I group	S group	t	P
T0	6.1±0.7	6.2±0.7	-0.576	0.566
T1	4.4±1.0	2.0±0.8a	13.186	0
T2	2.8±0.8	0.9±0.8a	11.907	0
T3	2.2±0.8	0.8±0.7a	9.27	0
T4	1.5±0.9	0.6±0.8a	5.379	0
T5	1.0±0.7	0.4±0.5a	4.729	0
T6	0.6±0.5	0.3±0.5a	2.671	0.009
T7	0.3±0.4	0.2±0.4	0.907	0.367
T8	0.3±0.4	0.2±0.4	0.464	0.644

Abbreviations: Compared with group L, a represented P < 0.05; group I: inhalation group; group S: medial branch block of superior laryngeal nerve group; T0: immediately before treatment; T1: 10 minutes after treatment; T2: 30 minutes after treatment; T3: 1 hour after treatment; T4: 2 hours after treatment; T5: 4 hours after treatment; T6: 8 hours after treatment; T7: 24 hours after treatment; T8: 48 hours after treatment. P values were calculated using t test.

Besides, the results of repeated measures ANOVA indicated a significant trend in VAS through the study (F = 44.603, P< 0.05) and the two groups had significantly different trends (F = 68.566. P < 0.05).

Hemodynamics at different time points between the two groups

The MAP of Group S was lower than that of Group I at T1-T3 (Table 3), HR was lower than that of Group L at T1, T2, and T4 (Table 4), and higher than that of Group I at T4. However, there was no significant difference between the two groups at the remaining time points. Repeated measures ANOVA indicated a significant trend in MAP and HR through the study (F = 49.516, P = 0.000; F = 50.427, P = 0.000) but the Group L didn’t have significantly different trends compared with Group I through the study (F = 2.231, P = 0.138; F = 0.882, P = 0.350).

Table 3

Comparison of MAP at different time points after operation between the two groups [(x±s), mmHg, n = 50].

	I group	S group	t	P
T0	88.6±4.7	90.0±8.4	-0.992	0.325
T1	84.1±3.8	79.3±8.9 a	3.495	0.001
T2	87.7±4.6	79.4±7.3a	6.826	0
T3	84.9±4.1	77.6±6.4a	6.895	0
T4	75.5±4.1	77.7±7.5	-1.78	0.078
T5	75.8±3.8	77.1±5.6	-1.264	0.209
T6	77.0±4.1	78.4±4.19	-1.59	0.115
T7	76.3±3.6	77.3±3.5	-1.445	0.152
T8	76.6±3.8	77.9±4.2	-1.673	0.097

Note: Compared with group L, aP < 0.05; group L: aerosol inhalation group; group S: medial branch block of superior laryngeal nerve group; T0: immediately before treatment; T1: 10 minutes after treatment; T2: 30 minutes after treatment; T3: 1 hour after treatment; T4: 2 hours after treatment; T5: 4 hours after treatment; T6: 8 hours after treatment; T7: 24 hours after treatment.

P values were calculated using t test.

Table 4

HR comparison of two groups at different time points after operation [(x±s), times/min, n = 50].

	I group	S group	t	P
T0	89.6±7.0	89.6±8.9	0.05	0.96
T1	85.6±6.0	78.3±6.5a	5.823	0
T2	83.6±5.9	78.7±6.3a	4.008	0
T3	79.5±5.8	77.6±5.7	1.655	0.101
T4	81.2±5.3	78.3±6.4a	2.56	0.014
T5	77.3±5.6	79.0±5.8	-1.531	0.129
T6	74.5±6.5	76.6±5.1	-1.787	0.077
T7	74.2±5.9	76.3±6.3	-1.734	0.086
T8	74.3±6.3	76.3±6.0	-1.698	0.093

Note: Compared with group L, aP < 0.05; group L: aerosol inhalation group; group S: medial branch block of superior laryngeal nerve group; T0: immediately before treatment; T1: 10 minutes after treatment; T2: 30 minutes after treatment; T3: 1 hour after treatment; T4: 2 hours after treatment; T5: 4 hours after treatment; T6: 8 hours after treatment; T7: 24 hours after treatment.

P values were calculated using t test.

Satisfaction and adverse reactions

The satisfaction score of Group S (3.4±0.7) was higher than that of Group I (3.0±0.7), and the difference was statistically significant (t = -3.070, P = 0.003). 2 cases (4%)intravenous injection of Flurbiprofen Axetil (50 mg) was needed in this group. While 13 patients (26%) still needed 50 mg of Flurbiprofen Axetil intravenously to relieve pain after treatment (χ2 = 9.490, P = 0.002). Furthermore, in Group S, there were 2 case with throat numbness and discomfort for 2 hours after block, and 2 case with expectoration weakness. There were no chocking, aspiration and regurgitation, newly onset of hoarseness, dyspnea in both groups.

Discussion

Sore throat after extubation is one of the most common complications during the recovery of anesthesia. Previous studies have shown that the incidence of sore throat after extubation was 24%-70% in general anesthesia patients [2]. It is mainly related to injury of tracheal mucosa, mucosal inflammation and ischemia caused by endotracheal intubation [4]. Besides, intubation without the neuromuscular block agent, intubation with double-lumen endotracheal tube, or excessive pressure of the cuff may also increase the risk of POST [11]. Some POST patients may recover by themselves, but some patients could be affected by POST for a long time, which seriously decreases the satisfaction of patients with anesthesia. We have taken some treatment measures, such as lidocaine (intravenous injection, external use of gel and atomization inhalation), steroids (intravenous injection and atomization inhalation), non-steroidal anti-inflammatory drugs, intravenous injection of N-methyl-D-aspartate (NMDA) receptor antagonists (magnesium, ketamine) [12]. However, there is still no satisfactory treatment for those patients with the severe sore throat.

In this study, we provide evidence that ultrasound guided superior laryngeal nerve block could provide greater pain relief in patient, more blunt the hemodynamic response and higher satisfaction scores after treatment than does treated with atomization inhalation alone. We founded that VAS score of sore throat at T1~T6 in Group S was significantly lower than that in Group I. As expected, ultrasound guided superior laryngeal nerve block could alleviated the POST syndrome in patient. We also founded that the MAP and HR rate of Group S was more stable than that of Group I; the satisfaction score of Group S (3.4±0.7) was higher than that of Group I. (3.0±0.7), which indicated that this method could improve hemodynamic parameters and the satisfaction of patients.

Previous studies indicated that USG guided block of the iSLN before intubation can reduce the incidence of sore throat after extubation under general anesthesia [13]. However, these approaches reported in prior studies were carried out before intubation for prevention. The difference of our study is that approaches were applied for pain treatment instead of prevention. In our study, the internal branch of the superior laryngeal nerve was blocked under the guidance of ultrasound, the VAS score decreased significantly, the analgesic effect was faster, than that of atomization inhalation with hormone combined with local anesthetics.

The reasons of iSLN block to alleviate sore throat were as follows. Firstly The internal branch of superior laryngeal nerve innervates most of the mucosal sensory in the laryngopharynx above the glottic fissure, and involves branches of the sympathetic trunk and superior cervical ganglion. iSLN block can not only block noxious stimulation but also produce sympathetic nerve block (In this study, it was also found that MAP and HR in the early stage of ultrasound-guided bilateral iSLN block were significantly lower than those in the atomization inhalation group, which may be related to the alleviation of pain and block of sympathetic nerve resulting in expansion of throat blood vessels and reduction of edema. Secondly, local anesthetics may provide an analgesic effect, improve local blood supply and produce anesthetic effect on local tissues. In this study, a short-acting local anesthetic of lidocaine was selected for the experiment and proved as an efficient medicine.

The ultrasound-guided technique was used to block the internal branch of superior laryngeal nerve in this study. A vertical puncture can be achieved between the region when touching the greater horn of hyoid bone and the upper horn of thyroid cartilage. After breaking through the thyroid hyoid ligament, local anesthetics can be injected carefully. Previous study has demonstrated that ultrasound-guided localization was superior than application of anatomical localization, with shorter duration of intubation, better tolerance and hemodynamic stability, and higher degree of comfort intubation using fiberoptic bronchoscope in patients with difficult airway in patients during the operation. Anatomical localization required deep palpation of the hyoid bone, which can make patients uncomfortable, and the failure rate of block would be higher for patients with shorter or thicker necks. Manikandan S. et al. [14] applied ultrasound-guided iSLN block for awake tracheal intubation in patients with cervical posterior fixation. The authors placed the ultrasound probe in front of the cervical vertebra and used intraplanar puncture technique. The upper laryngeal artery was identified as a marker, and local injection was made near the superior laryngeal artery after the blood was withdrawn. Awake intubation was then carried out without the discovery of any complications after iSLN by injecting local anesthetics near the superior laryngeal artery. Furthermore, prior evidence has shown that iSLN can be identified and located accurately under the guidance of ultrasound [15, 16]. Many reports revealed that iSLN was difficult to visualize under ultrasound [17, 18]. It was found that ibSLN could not always be displayed under ultrasound scanning, but thyrohyoid membrane and the superior laryngeal artery penetrating through the thyrohyoid membrane with internal branch of superior laryngeal nerve could be easily visualized [19]; besides, when local anesthetics were injected into the surface of thyrohyoid membrane and the "space" in the medial region of the superior laryngeal artery, satisfactory anesthetic effects were also achieved [16, 17]. In our study, the high-resolution ultrasound imaging system was used to confirm the visibility of ultrasound-guided iSLN image. When iSLN can not be clearly imaged, the spatial structure around the superior laryngeal nerve was selected as a substitute marker. The greater horn of hyoid bone and thyroid cartilage were identified as markers by the longitudinal location of ultrasound. Extra-planar puncture or transverse location of the thyrohyoid membrane were used to track the intra-planar puncture of the superior laryngeal artery. It was a reliable and repeatable method to use the peripheral structure of superior laryngeal nerve as a localization marker, which was consistent with the spatial anatomical structure of superior laryngeal nerve and indicated a high success rate of the blockade [16].

In this study, there was 1 case of throat numbness and discomfort for 2 hours after nerve block. There were no adverse reactions such as choking when drinking, aspiration and regurgitation, newly onset of hoarseness, dyspnea, nausea and vomiting in both groups. iSLN block is a peripheral nerve block method, and its blocking effect will lead to abnormal throat sensation, weakened protective reflex, and possible inhalation of gastric contents. The puncturing process damages adjacent blood vessels or tissues at times, causing hematoma or peripheral tissue injury. Vasovagal reactions caused by excessive neck operation can lead to hypotension and bradycardia [19]. Blockade of the external branch of the superior laryngeal nerve may lead to low voice and blockade of unilateral recurrent laryngeal nerve may result in hoarseness. It has been reported that hoarseness occurs in part after ultrasound-guided bilateral ibSLN block, and aphasia and dyspnea after bilateral recurrent laryngeal nerve block [20]. The introduction of ultrasound-guided technology can greatly reduce the occurrence of such complications. To reduce the possibility of nerve injury or blocking other nerves, it is suggested that operators should be trained strictly to improve puncture technique and be skilled in basic knowledge of anatomy and ultrasonography to avoid the occurrence of adverse reactions in operation Meanwhile, short-acting local anesthetics could increase block safety, and visualization of local anesthetic diffusion guided by ultrasound could reduce the injection volume and avoid blocking other nerves [21, 22].

Limitation

This study still has some limitations that are described as follows. Firstly, we used a single concentration and a single dose of local anesthetics in this study, with further study required concerning the optimal concentration and dose of local anesthetics. Secondly, some patients with throat and neck surgeries and multiple intubations were excluded from this study, which remains to be explored in the future to the therapeutic effect of these special patients.

Conclusion

Ultrasound-guided bilateral ibSLN block with local anesthetic of lidocaine has a faster onset and better analgesic effect than traditional atomization inhalation of hormone combined with local anesthetics for the treatment of POST. Besides, its analgesic effect does not fade with the effect regression of local anesthetics, associated with higher patients' satisfaction and fewer complications, which provides an alternative safe and effective method for clinical treatment of POST.

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21 Aug 2020

PONE-D-20-15831

Ultrasound-guided internal branch of superior laryngeal nerve block on postoperative sore throat

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We will update your Data Availability statement on your behalf to reflect the information you provide.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: No

Reviewer #3: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Why the comparison was between US guided versus non US guided internal branch of superior laryngeal nerve block

Cost of the technique and experiences and instruments needed is required to discuss

Please compare between both groups as regards length and type of the surgery done as it may affect results

Was aspiration score was done

Clarify or how long period the internal branch of superior laryngeal nerve block work

Reviewer #2: The objective of this study is to conduct a two-arm RCT to evaluate the comparative effectiveness of the USG-guided iSLN block (group S), versus the inhalation (group I) to treat POST. While the study objectives sound interesting, some shotcomings were observed, in regards to abiding by the CONSORT guidelines for conducting and reporting results of high-quality RCTs. A model paper to follow abiding by the CONSORT guidelines is below:

https://www.sciencedirect.com/science/article/pii/S0889540619300010

The study, however, is registered within the Chinese CT Registry, and is accessible via a ChiCTR number.

Methods:

An orderly manner for Methods reporting is suggested, following CONSORT guidelines, without repeating information, such as Trial Design, Participant Eligibility Crtieria and settings, Interventions, Outcomes, sample size/power considerations, Interim analysis and stopping rules, Randomization (details on random number generation, allocation concealment, implementation), Blinding issues, etc. The authors are advised to create separate subsections for each of the possible topics (whichever necessary), and that way produce a very clear writeup. Please find some particular comments:

(a) Randomization: For instance, the steps of sequence generation (methods used to generate random allocation sequence), allocation concealment (methods to implement random allocation sequences) and blinding should be made very clear. Note, allocation concealment and blinding are not the same thing, and should be reported separately. The trial staff recruiting patients should not have the randomization list. Randomization should be prepared by the trial statistician, and he/she would not participate in the recruiting. Also, was a (block) randomization performed? If block, then what's the block size? Those details are necessary. How was the allocation sequence generated?

(b) Sample size/Power: A statement on sample size/power in the manuscript is presented, but it is not clear what (statistical) test was used, the effect size, etc. Those need to be clearly stated.

(c) Study Design & Statistical Analysis: The study has a relatively short duration; I wonder how meaningful it is to evaluate the effects via the repeated measures ANOVA? Also, the statistical analysis entirely relied on Gaussian assumptions of the responses; was it guaranteed? Also after conducting ANOVA, how was multiplicity testing adjusted to compare between various time-points?

In general, what is the perspective of this study once the 48 hours has passed?

Reviewer #3: Li and colleagues present in this paper results of a formally correct study to test the efficacy of ultrasound-guided internal branch of superior laryngeal nerve block on postoperative sore throat. Although, the following considerations should be considered to strenghten the paper:

1. The population sample is calculated on the basis of VAS score at 2h (T4): only T4 should be considered as primary outcome for sample size calculation, the other timepoints should be considered as secondary outcomes.

2. The VAS score was calculated only considering throat pain or postoperative pain can interfere in the evaluation?

3. The kind of surgeries should be specified in the results.

4. The paper needs editing by a proficient English speaker for orthography, language and punctuation.

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Reviewer #1: Yes: Mohammad Waheed El-Anwar

Reviewer #2: No

Reviewer #3: No

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15 Oct 2020

1) Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Dear, Editor，We have change the style of article and file name to meet PLOS ONE's style requirements. You can see the details in the revised article. We also change the file name about the article.

2) Thank you for submitting your clinical trial to PLOS ONE and for providing the name of the registry and the registration number. The information in the registry entry suggests that your trial was registered after patient recruitment began. PLOS ONE strongly encourages authors to register all trials before recruiting the first participant in a study.

As per the journal’s editorial policy, please include in the Methods section of your paper:

(a) your reasons for your delay in registering this study (after enrolment of participants started);

In fact , we register on Feburary 28，2018,and recruited patients from June 12, 2018, to June 6, 2019. You can find the details on http://www.chictr.org.cn/searchproj.aspx by searching ChiCTR1800015007.1

In our protocol ，the time schedule is different because the preliminary experiment was made to make sure the technique is safe and useful, we apply to registered this study after that.

The authors confirm that all ongoing and related trials for this study are registered.

Please also ensure you report the date at which the ethics committee approved the study as well as the complete date range for patient recruitment and follow-up in the Methods section of your manuscript."

The details has been added in the article. We report the date at which the ethics committee approved the study as well as the complete date range for patient recruitment and follow-up in the Methods section. The ethics committee approved the study on Feburary 7，2018.

Because the syndrome is always self-healing， we follow-up the patients in 3days.

3) Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians.

The details has been added in the article. All patients gave written informed consent before participation in this study.

4) In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) a description of how participants were recruited, and b) descriptions of where participants were recruited and where the research took place.

Participants were recruited for the study through advisement from Chancheng central hospital and the research was took place in PACU.

5) Please provide a sample size and power calculation in the Methods, or discuss the reasons for not performing one before study initiation.

We calculated that a sample size of 49 patients in each group would give the study 80% power to detect a 20-point greater improvement in VAS scores in the S group than in the I group at a two-sided significance level of 0.05.The calculation was operated on the website http://powerandsamplesize.com.The previous study has found that 90% of patients recovered after ultrasound guided injection of Isln,and 67.7% patients recovered after inhalation，so the proportion was used to calculated the sample size. http://powerandsamplesize.com/Calculators/Compare-2-Proportions/2-Sample-Equality?

6) To comply with PLOS ONE submission guidelines, in your Methods section, please provide additional information regarding your statistical analyses, including the name and version of the specific statistical software used for the analysis. For more information on PLOS ONE's expectations for statistical reporting, please see https://journals.plos.org/plosone/s/submission-guidelines.#loc-statistical-reporting.

The software named IBM SPSS statistics 24.0 was used for the analysis.

7) Please amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical.

We have changed the file names to make sure they are identical.

8) Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

The supporting information files has been added to the bottom of the article, we have tried to revised the article follow the guideline.

9) We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

The de-identified data sets has been uploaded this time following the guideline. Telephone number of ethics committee was 0757-827788715

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository 仓库知识库and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We uploaded de-identified data sets as supplyment materials this time following the guideline.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

22 Oct 2020

Ultrasound-guided Internal Branch of Superior Laryngeal Nerve Block on Postoperative Sore Throat: A Randomized Controlled Trial

PONE-D-20-15831R1

Dear Dr.Zhang Jinfang

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Ehab Farag, MD FRCA FASA

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

27 Oct 2020

PONE-D-20-15831R1

Ultrasound-guided Internal Branch of Superior Laryngeal Nerve Block on Postoperative Sore Throat: A Randomized Controlled Trial

Dear Dr. Jinfang:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

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Academic Editor

PLOS ONE