Modified anterior approach versus traditional posterior approach for ultrasound-guided superior laryngeal nerve block in awake endotracheal intubation: a randomized non-inferiority clinical trial

Abstract

Study objective

This study was undertaken to compare the effect of the modified ultrasound-guided anterior superior laryngeal nerve block (SLNB) with the traditional ultrasound-guided posterior SLNB in providing intubation conditions during awake tracheal intubation (ATI) in patients without difficult airway.

Design

Randomized, assessor-blind. Registration number: ChiCTR2200058086.

Setting

West China Hospital of Sichuan University, Chengdu, China.

Patients

104 patients aged 18–65 years, of American Society of Anesthesiologists status I-III, posted for elective general surgery with general endotracheal anesthesia.

Interventions

The patients were randomized into two groups (modified group, n = 52; traditional group, n = 52). Modified anterior SLNB or traditional posterior SLNB was performed under ultrasound guidance.

Measurements

The primary outcome was the proportion of acceptable intubation condition (AIC), which was analyzed in both per-protocol (PP) and intention-to-treat (ITT) populations. The prespecified non-inferiority margin was −4.8%. Secondary outcomes included intubation success rate on the first attempt, hemodynamic parameters during ATI, time taken for airway anesthesia and intubation, recall of intubation, patient perception of comfort, and incidence and severity of postoperative complications.

Main results

In the PP population, the proportion of AIC in the modified group was 49/49 (100%) and that in the traditional group was 49/49 (100%), absolute difference 0, lower limit of 1-sided 95% CI, −0.3%. In the ITT population, the primary outcomes in the modified and traditional group were 52/52 (100%) and 51/52 (98.1%), respectively, with an absolute difference of 1.9% and a lower limit of 1-sided 95% CI of −1.2%. The non-inferiority of modified ultrasound-guided anterior SLNB was confirmed in both populations.

Conclusions

Among adults without difficult airways during videolaryngoscope-assisted ATI, the modified ultrasound-guided anterior SLNB, compared to the traditional posterior approach, showed a statistically non-inferior effect in terms of providing AIC.

Keywords:

• Airway nerve block
• awake tracheal intubation
• superior laryngeal nerve block
• intubation conditions
• randomized controlled trial

Introduction

Awake tracheal intubation (ATI) involves placing the endotracheal tube in an awake, spontaneously breathing patient [1]. ATI can provide an extra margin of safety by allowing the patient to maintain gas exchange and airway patency, reducing the risk of aspiration during the procedure. Successful ATI facilitated by minimal sedation and excellent local anesthesia can improve patient safety by reducing the risk of adverse events [2].

Airway topicalization is commonly used to facilitate ATI and can be implemented in various ways. There are reservations about performing topical anesthesia of the airway because of some unsolved drawbacks, including poor airway anesthesia quality [3] due to unreliable effects and the increased risk of exceeding the maximum dose of local anesthesia, leading to local anesthetic systemic toxicity (LAST) [4–6]. Moreover, our team has demonstrated that airway nerve blocks provide better anesthesia quality for ATI and lower overall complications than topical anesthesia [3]. Of the various airway nerve block options for anesthesia of supraglottic structures, ultrasound-guided superior laryngeal nerve block (SLNB) has demonstrated a dependable efficacy in blunting supraglottic mucosal sensation by abolishing glottic closure and gag reflex. Usually combined with SLNB, translaryngeal injection (TLI) via the cricothyroid membrane can provide additional anesthesia to the trachea and inhibit the cough reflex.

The posterior approach (bilateral injections) for ultrasound-guided SLNB has been presented earlier [7–9]. However, its clinical application is still hindered by the challenging visualization of the superior laryngeal nerve [10] and anatomical variability of the superior laryngeal artery [11]. Thereafter, some groups proposed alternative anterior approaches and validated their implementability in human cadavers [12,13]. These anterior approaches were theoretically simpler in terms of location technique (landmark-guided) and number of injections (only single injection), but they had the drawbacks of an indistinct target plane and unclear drug diffusion. Furthermore, no clinical data have substantiated the efficacy and safety of an anterior approach for SLNB to facilitate ATI in patients undergoing general endotracheal anesthesia.

This study was therefore designed to test the hypothesis in a randomized clinical trial that the combined use of modified ultrasound-guided anterior SLNB with TLI is not inferior to the combination of traditional ultrasound-guided posterior SLNB with TLI in achieving clinically acceptable intubation conditions in patients without difficult airways in the operating room.

Methods

Study design

This study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University, China, and was registered in the Chinese Clinical Trials Register (www.chictr.org.cn); registration number: ChiCTR2200058086 (date of registration: March 29^th, 2022). This prospective, randomized, assessor-blind, non-inferiority clinical trial was conducted at West China Hospital, a tertiary teaching hospital, from August 2022 to February 2023. Patient enrollment began on August 1st, 2022. The full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmjopen.bmj.com/content/13/2/e068779.full. The CONSORT checklist was used to write our report [14].

Population

The study population comprised of patients scheduled for elective general surgery that required tracheal intubation. Patients of both sexes with an American Society of Anesthesiologists (ASA) physical status of I–III, age 18–65 years, were included. The exclusion criteria were as follows: Patients who had contraindications to SLNB (coagulopathy, infection at the needle insertion site, or allergy to local anesthetics) or were deemed to have difficult airway (Mallampati grade III–IV, inter-incisor distance < 3 cm, thyromental distance < 6.5 cm, or body mass index ≥ 26 kg/m²); having asthma or ischemic heart disease; preoperative hoarseness and sore throat; plan to transfer without extubation; and conditions that precluded adequate communication.

Randomisation and blinding

Patients were included in the study after obtaining written informed consent. The patients were randomized to either the modified group (modified ultrasound-guided anterior SLNB) or the traditional group (ultrasound-guided posterior SLNB) in a 1:1 ratio. The primary investigator of the study performed randomization using a computerized randomization table. An independent assistant opened a sealed envelope 1 h before surgery to inform the operator which nerve block technique to be performed. Because of the nature of the trial, the anesthesiologist performed intervention and all patients were not blinded to group allocation. However, the outcome assessor was blinded to the intervention.

Preparations before airway anesthesia

All patients received preoxygenation with a facemask delivering 100% oxygen to obtain an end-expiratory oxygen concentration above 90%. Intravenous administration of midazolam (0.03 mg/kg) and sufentanil (0.1 ug/kg) were performed.

Airway anesthesia procedures

All investigators were certified trained anesthetists and airway anesthesia was always performed by the same investigator. All the patients underwent ultrasound-guided SLNB and video laryngoscope-assisted ATI.

Modified ultrasound-guided anterior SLNB was administered to the patients in the modified group. Traditional ultrasound-guided posterior SLNB was administered bilaterally to patients in the traditional group. Immediately after SLNB, all participants underwent ultrasound-guided TLI, and gauze was taped to cover all the needle holes. The time taken for airway anesthesia was recorded.

Modified ultrasound-guided anterior SLNB

Patients in the modified group were placed in the supine position for the modified ultrasound-guided anterior SLNB. After cleaning and draping, a high-frequency 38 mm linear transducer was placed transversely over the TC. The probe was then moved cephalad until the thyroid incisura notch was observed (Figure 1A). Using a 22-gauge 50-mm nerve block needle, bilateral SLNB was administered by a single injection of 6 mL of 2% lidocaine via an out-of-plane approach. The injection was performed in the midline targeting the space above the thyrohyoid membrane (TH-Mb), and the needle tip was superficial to the TH-Mb [12]. The TH-Mb and pre-epiglottic spaces were pushed down after lidocaine injection (Figure 1B).

Figure 1. Transverse sonography of the modified ultrasound-guided anterior superior laryngeal nerve block (SLNB) (A,B), and parasagittal sonography of the traditional ultrasound-guided posterior SLNB (C,D). (A) midline transverse plane ultrasound image at the level of the thyroid notch. TH-Mb is identified at ultrasound as bounded anteriorly by the TC and posteriorly by the PES. (B) When performing SLNB via the modified anterior approach, lidocaine were injected targeting the space anterior to TH-Mb. Lidocaine were visualised to push the TH-Mb, and it diffused rapidly to lateral paraglottic space. (C) Right parasagittal ultrasound image when performing ultrasound-guided posterior SLNB. TH-Mb is a hyperechoic layer, marking the interface with the PES. (D) Lidocaine were injected targeting the space anterior to TH-Mb and were visualised to push the TH-Mb. Yellow dotted line: TH-Mb, white solid arrow: needle orientation, white dotted circled area: lidocaine. SM: strap muscles; TC: thyroid cartilage; Hy: hyoid bone; TH-Mb: thyrohyoid membrane; PES: pre-epiglottic space; epi: epiglottis.

Traditional ultrasound-guided posterior SLNB

Patients in the traditional group were placed in the supine position for the traditional ultrasound-guided posterior SLNB. After cleaning and draping, a high-frequency 38 mm linear transducer was placed parasagittally over the submandibular area. The hyoid bone and thyroid cartilage were identified as hyperechoic structures on ultrasonography. The thyrohyoid and thyrohyoid membranes were located between the two structures (Figure 1C). Using a 22-gauge 50-mm nerve block needle, bilateral SLNB was given with 3 mL of 2% lidocaine on each side via an out-of-plane approach. Injection was performed bilaterally targeting the space above the TH-Mb, and the needle tip was superficial to the TH-Mb [8]. The TH-Mb and pre-epiglottic spaces were pushed down after lidocaine injection (Figure 1D).

Ultrasound-guided TLI

After SLNB, all the participants underwent ultrasound-guided TLI in the supine position. The high-frequency 38 mm linear transducer was placed in the transverse plane to obtain a high-bright-line echo between the thyroid cartilage and the cricoid cartilage, namely the cricothyroid membrane (C-T Mb). Using out-of-plane visualization, an advanced 22-gauge needle was connected to a 5 mL syringe containing 5 mL of 2% lidocaine. Once air from the tracheal lumen was freely aspirated, 5 mL of 2% lidocaine was injected at the end of the expiration.

Tracheal intubation: procedures

After pre-oxygenation with a facemask delivering 100% oxygen to obtain an end-expiratory oxygen concentration > 90%, video laryngoscope-assisted ATI was performed after evaluating the sedation status (Ramsay scale), and intubation conditions were assessed during ATI. An endotracheal tube (ETT) with an internal diameter of 7.5 mm for men and 7.0 mm for women. The cuff was inflated with air at an intracuff pressure of 20 cmH₂O after successful placement in the trachea. The first attempt, followed by three stable end-tidal carbon dioxide (EtCO₂) waves, was considered successful. The time required for intubation was also recorded. Mean arterial pressure (MAP), heart rate (HR), and pulse oxygen saturation (SpO₂) were measured at T0 (baseline), T1(immediately before intubation), T2 (immediately after intubation), and T3 (1 min after intubation). One minute after successful ATI, general anesthesia was induced at the discretion of the attending anesthetist. ‘Failed on the first attempt’ was defined when a patient was unable to cooperate due to Grade 4 of reactions or Grade 3 of reactions along with closing vocal cords. In cases of unsuccessful ATI, the investigator performed routine general anesthesia induction and the outcomes were also measured.

Intraoperative anesthesia management

General anesthesia was induced with propofol, sufentanil, and neuromuscular blocking drugs and was maintained with sevoflurane, remifentanil, and neuromuscular blocking drugs at the discretion of the attending anesthetist. During surgery, the patient’s lungs were ventilated using positive-pressure ventilation. Postoperatively, the residual neuromuscular blockade was reversed with neostigmine 50 µg/kg, and the patient’s trachea was extubated.

Postoperative follow-up

The postoperative follow-up was recorded by an independent observer. Recall intubation was conducted 30 min after transfer to the PACU. Participants’ perception of comfort during intubation was assessed 30 min after transfer to the PACU. The severity of hoarseness, sore throat [15] and injection-site pain was recorded at 4, 24, 48, and 72 h postoperatively. Perioperative complications were recorded.

Outcomes

The primary outcome was the proportion of acceptable intubation conditions (AIC). As shown in Supplementary Table 1, the evaluation of the intubation condition was based on the Cormack-Lehane classification [16], vocal cord movement [17], 5-point reaction scale [18], and severity of coughing [17]. Clinically, AIC was defined when each part was scaled to Grade 1 or Grade 2 [17]. The proportion of AIC = number of participants with AIC/number of participants who received ATI in each group. Secondary outcomes included intubation success rate on the first attempt, MAP, HR, and SpO₂ during the peri-intubation period, time taken for airway anesthesia (time elapsed from beginning the block procedure (after prepping and draping) until withdrawal of the needle after TLI), time taken for intubation (the time elapsed from insertion of the blade between the teeth to the time the first EtCO₂ wave was collected), recall of intubation (no recall; indistinct memories; completely able to recall the whole intubation process), patient perception of comfort (0–10 scale, with 0 being worst discomfort and 10 being no discomfort), severity of hoarseness, sore throat, injection-site pain (according to Supplementary Table 2), and other perioperative complications including airway hemorrhage (observation of bleeding of the laryngeal mucosa via videolaryngoscope or observation of bloody secretions via coughing or suction), superior laryngeal nerve damage, LAST, and laryngospasm (grading of laryngospasm was shown in Supplementary Table 2).

Sample size calculation and statistical analysis

In our protocol, the non-inferiority margin was defined as −4.8% [19]. Based on our pilot study, the proportion of AIC in the modified and traditional groups was 100% and 93.75 respectively (unpublished data). The required sample size per group was calculated to be 44 using a one-sided Farrington-Manning test with a margin equal to −4.8%, a statistical power of 80%, and a 1-sided type 1 error rate of 5%. Accounting for at least 10% of dropouts, the total sample size was inflated to 100 participants (n = 50 per group).

Following international principles for reporting non-inferiority trials [20,21] the primary outcome analysis was performed in the intention-to-treat (ITT) population, and analysis of the per-protocol (PP) dataset was considered of equal importance to reach a robust interpretation. For the primary outcome, the difference between the two study groups (with a lower limit of the 1-sided 95% confidence interval (95% CI)) was estimated for the absolute proportion of AIC (modified group – traditional group). If the lower limit did not exceed −4.8%, non-inferiority was declared.

For secondary outcomes, all analyses were performed with superiority testing with a 2-sided α = 0.05. We used Pearson’s chi-square test (or Fisher’s exact test) for qualitative variables and Student’s t-test for quantitative variables. The Whitney-Mann U test was used to compare the ordinal variables.

Non-inferiority analyses were conducted using SAS version 9.4 (SAS Institute, Inc.). SPSS 25.0 was used for the other statistical analyses. p < .05.

Results

Trial population

Between August 2022 and February 2023, 178 patients were enrolled, and 104 patients (intention-to-treat population) were randomly allocated to groups (52 patients in the modified group and 52 patients in the traditional group). Among the 104 randomized patients, 6 (5.8%) were excluded from the per-protocol analyses: five patients did not receive the completely allocated treatment, and one patient had a protocol violation. 98 patients (49 in the modified group and 49 in the traditional group) met the per-protocol principle (per-protocol population) (Figure 2). The baseline patient characteristics are presented in Table 1. The median age was 51 years, 49% of the patients were male, and colorectal surgery was the most frequent surgery type.

Figure 2. Flow diagram of patient data distribution. SLNB: superior laryngeal nerve block; TLI: translaryngeal injection; PP: per-protocol; ITT: intention-to-treat.

Table 1. Baseline participant characteristics.

	Modified group (n = 52)	Traditional group (n = 52)	p-value^a^,^b
Mean age (SD) in years	50.0 (10.9)	52.8 (11.6)	.20
Sex, n (%)			.33
Male	29 (55.8)	24 (46.2)
Female	23 (44.2)	28 (53.8)
Education, n (%)			.86
Illiterate	6 (11.5)	2 (3.8)
Elementary	2 (3.8)	6 (11.5)
Middle	14 (26.9)	15 (28.8)
High	12 (23.1)	13 (25.0)
College	18 (34.6)	16 (30.8)
Mean weight (SD) in kg.	60.6 (9.5)	58.1 (9.0)	.97
Mean height (SD) in cm.	162.3 (7.5)	162.3 (7.2)	.40
Mean BMI (SD) in kg/m^2	22.9% (2.6%)	22.0% (2.4%)	.97
ASA status, n (%)			.57
I	0	0
II	46 (88.5)	44 (84.6)
III	6 (11.5)	8 (15.4)
Mallampatti class, n (%)			.55
I	23 (44.2)	20 (38.5)
II	29 (55.8)	32 (61.5)
Mean thyromental distance (SD) in cm.	7.7 (0.8)	7.5 (0.7)	.29
Surgery types, n (%)			.98
Gastrointestinal	8 (15.4)	13 (25.0)
Pancreas	2 (3.8)	6 (11.5)
Liver	5 (9.6)	4 (7.7)
Biliary	14 (26.9)	10 (19.2)
Colorectal	21 (40.4)	14 (26.9)
Other surgical procedure	2 (3.8)	5 (9.6)
Ramsay score, n (%)			.67
2	48 (92.3)	50 (96.2)
3	4 (7.7)	2 (3.8)
Mean anesthesia time (SD) in minutes	227.0 (107.9)	226.6 (121.8)	.99
Mean surgery time (SD) in minutes	154.2 (90.1)	153.6 (105.7)	.98

SD: standard deviation; BMI: body mass index; ASA: American Society of Anesthesiologists.

^ap-value comparing the modified SLNB + TLI versus the traditional SLNB + TLI.

^bt-test used to compare means and chi-square test used to compare proportions; the Whitney-Mann U test was used for comparison of ordinal variables.

Primary outcome

In the PP population, the primary outcome AIC occurred in 49 patients (100%) in the modified group and 49 patients (100%) in the traditional group (100% vs. 100%; absolute difference:0; lower limit of the one-sided 95% CI: −0.3%). In the ITT population, AIC occurred in 52 patients (100%) in the modified group and 51 patients (98.1%) in the traditional group (100% vs. 98.1%; absolute difference: 1.9%; lower limit of the one-sided 95% CI: −1.2%) (Table 2). The lower limits in both populations (−0.3% and −1.2%, respectively) did not exceed the non-inferiority margin of −4.8%, thus demonstrating non-inferiority. Exploratory post hoc analyses found no significant statistical difference for intergroup differences in intubation conditions by applying nonparametric tests. The proportion of excellent intubation conditions was also comparable between the groups (PP population: 61.2% vs. 54.0%; absolute difference: 7.2%; 2-sided 95% CI: −12.3% to 26.7%; ITT population: 57.7% vs. 51.9%; absolute difference: 5.8%; 2-sided 95% CI: −13.3% to 24.9%).

Table 2. Outcomes in the intention-to-treat and per-protocol population.

	Intention-to-treat population			Per-protocol population
Outcomes	Modified group (n = 52)	Traditional group (n = 52)	p-valuea^,^b	Modified group (n = 49)	Traditional group (n = 49)	p-value^a^,^b
Primary outcome
Clinically acceptable, n (%)(excellent + good)	52 (100)	51 (98.1)	<.05 for non-inferiority	49 (100)	49 (100)	<.05 for non-inferiority
Components of the primary outcome
Intubation condition, n (%)			.50			.47
Excellent	30 (57.7)	27 (51.9)		30 (61.2)	26 (54.0)
Good	22 (42.3)	24 (46.2)		19 (38.8)	23 (46.0)
Poor	0	1(1.9)		0	0
Cormack-Lehane classification, n (%)			.84			.72
I	34 (65.4)	33 (63.5)		34 (69.4)	32 (65.3)
II	18 (34.6)	19 (36.5)		15 (30.6)	17 (34.7)
Vocal cord position, n (%)			.25			.72
Open	43 (82.7)	47 (90.4)		43 (87.8)	44 (89.9)
Moving	9 (17.3)	5 (9.6)		6 (12.2)	5 (10.2)
Reaction, n (%)			.42			.45
No reaction	38 (73.1)	42 (80.8)		38 (77.6)	41 (83.7)
Slight grimacing and/or gagging	14 (26.9)	8 (15.4)		11 (22.4)	7 (14.3)
Heavy grimacing and/or gagging	0	1 (1.9)		0	1 (2.0)
Verbal objection	0	1 (1.9)		0	0
Unexpected coughing, n (%)			.59			.74
None	43 (82.7)	45 (86.5)		42 (85.7)	43 (87.8)
	9 (17.3)	7 (13.5)		7 (14.3)	6 (12.2)
Secondary outcomes
First attempt, n (%)			1.00			1.00
Succussed	49 (94.2)	50 (96.2)		49 (100)	49 (100)
Failed	3 (5.8)	2 (3.8)
Recall of intubation, n (%)			.55			.46
No recall	36 (69.2)	38 (73.1)		34 (69.4)	36 (73.5)
Indistinct memories	5 (9.6)	7 (13.5)		4 (8.2)	7 (14.3)
Completely able to recall	11 (21.2)	7 (13.5)		11 (22.4)	6 (12.2)
Mean airway anesthesia time (SD) in seconds	194.4 (66.5)	233.7 (105.2)	.03	197.4 (66.8)	237.7 (107.1)	.04
Mean intubation time (SD) in seconds	74.0 (56.5)	69.8 (53.1)	.65	74.9 (58.1)	66.8 (47.1)	.24
Mean NRS (SD) for comfort (0–10 scale)	9.1 (1.7)	8.9 (1.6)	.78	9.2 (1.7)	9.2 (1.7)	.97

SD: standard deviation.

^ap-value comparing the modified SLNB + TLI versus the traditional SLNB + TLI.

^bt-test used to compare means and chi-square test used to compare proportions; the Whitney-Mann U test was used for comparison of ordinal variables.

Secondary outcomes

The secondary outcomes in the intention-to-treat and per-protocol populations are shown in Table 2. Before intubation, the time taken for modified ultrasound-guided anterior SLNB and TLI was significantly shorter than that for traditional ultrasound-guided posterior SLNB and TLI (ITT population: 194.4 ± 66.5s vs. 233.7 ± 105.2s; p = .03). During ATI, with similar Ramsay sedation levels, no significant differences were found for the Cormack-Lehane classification, vocal cord position, reaction, and unexpected coughing during the process between the two groups (Table 2). No significant differences were found in the intubation success rate between the two groups on the first attempt (ITT population: 49/52, 94.2% vs. 50/52, 96.2%; p = 1). The time taken for intubation was comparable between the two groups (ITT population: 74.0 ± 56.5 vs. 69.8 ± 53.1s; p = .65).

Table 3 and Supplemental Figure 1 show no significant differences in HR, MAP, and SpO₂ during ATI in the modified group compared to the corresponding baseline values (p > .05); in contrast, significant cardiovascular responses were observed in the traditional group. In the ITT population, a significant increase in HR of the traditional group was observed immediately after intubation procedures, compared with baseline values (82.6 ± 18.4 vs. 79.3 ± 15.2; p < .05). Significant increases in MAP were observed immediately before (98.5 ± 12.6 mmHg vs. 95.4 ± 12.9 mmHg; p < .05) and after intubation (98.6 ± 14.5 mmHg vs. 95.4 ± 12.9 mmHg; p < .01) compared with baseline values. In the PP population, significant increases in MAP were also observed immediately before (98.0 ± 12.7 mmHg vs. 94.8 ± 12.9 mmHg; p < .01) and after intubation (98.5 ± 14.8 mmHg vs. 94.8 ± 12.9 mmHg; p < .01) compared after baseline values.

Table 3. Comparison of hemodynamic parameters at different time points.

Groups/parameters	Baseline values (T0)	Endotracheal intubation
		Immediately before (T1)	Immediately after (T2)	1 min after (T3)
Intention-to-treat population
Traditional group (n = 52)
Mean SpO2 (SD)	98.7 (1.7)	99.3 (1.1)*	98.5 (2.3)	99.6 (1.0)*
Mean HR (SD) in beats per minute	79.3 (15.2)	79.5 (15.3)	82.6 (18.4)*	78.3 (14.8)
Mean MAP (SD) in mmHg	95.4 (12.9)	98.5 (12.6)*	98.6 (14.5)**	96.1 (13.5)
Modified group (n = 52)
Mean SpO2 (SD)	99.4 (3.4)	99.4 (1.4)	98.9 (1.8)	99.6 (1.1)
Mean HR (SD) in beats per minute	76.6 (15.6)	76.7 (15.5)	78.8 (17.5)	75.7 (17.3)
Mean MAP (SD) in mmHg	95.0 (16.8)	96.1 (11.4)	96.3 (12.7)	94.2 (13.4)
Per-protocol population
Traditional group (n = 49)
Mean SpO2 (SD)	98.6 (1.7)	99.3 (1.1)*	98.6 (2.3)	99.6 (1.0)**
Mean HR (SD) in beats per minute	78.9 (15.4)	79.2 (15.4)	81.9 (18.3)	77.9 (15.0)
Mean MAP (SD) in mmHg	94.8 (12.9)	98.0 (12.7)**	98.5 (14.8)**	95.9 (13.7)
Modified group (n = 49)
Mean SpO2 (SD)	99.4 (3.5)	99.4 (1.4)	99.0 (1.7)	99.6 (1.2)
Mean HR (SD) in beats per minute	76.9 (15.6)	77.5 (15.7)	78.8 (18.0)	75.8 (17.7)
Mean MAP (SD) in mmHg	95.9 (16.8)	96.7 (11.5)	96.6 (12.9)	94.5 (13.6)

SD: standard deviation; SpO₂: pulse oxygen saturation; MAP: arterial pressure; HR: heart rate.

* p<.05 compared with the baseline values.

** p<.01, compared with the baseline values.

After surgery, no significant difference was found for the recall of intubation (p > .05) (Table 2) and participant perception of comfort during ATI in the modified group compared with the traditional group (ITT population: 9.1 ± 1.7 vs. 8.9 ± 1.6; p = .49) (Table 2). Neither ITT nor PP analyses revealed significant differences in postoperative sore throat, hoarseness, or injection-site pain at 0.5 h, 4 h, 24 h, 48 h and 72 h between the two groups (p > .05) (Supplement Tables 3–5). None of these patients reported sustained hoarseness, sore throat, or injection-site pain at 72 h, except for one patient in the traditional group who reported sustained hoarseness over 72 h. Upon follow-up, the hoarseness disappeared on postoperative day 7.

In this study, airway hemorrhage occurred in six patients in the modified group and four patients in the traditional group. None of the patients experienced complications such as LAST, laryngospasm, or superior laryngeal nerve injury.

Discussion

In this randomized clinical trial that involved patients without a difficult airway, the modified anterior approach for ultrasound-guided SLNB, compared to the traditional approach, met the criterion for non-inferiority with regard to the proportion of AIC.

We selected a target plane situated directly above the TH-Mb and verified its efficacy through left and right parasagittal scans following the anterior injection of lidocaine [19]. Our results demonstrated that the space above the TH-Mb represents an optimal target plane for ultrasound-guided posterior SLNB [8] as well as our modified SLNB technique. To our knowledge, there are no clinically validated SLNB techniques that can provide excellent airway conditions with minimal trauma by using only a single injection. Compared with the landmark-guided approaches described by Fowler et al. [13], our ultrasound-guided technique offers distinct advantages.

In this study, a protocol consisting of modified ultrasound-guided anterior SLNB and TLI was performed in an average of 194.4 s, with the glottis open in over 80% of the patients. Preparation before ATI is often time-consuming, with previous studies reporting that it can take approximately 3–20 min, challenging a patient’s patience and comfort level [22–25]. We believe that this modified technique may improve patient comfort and provide more time for patients with difficult airways in future research.

In our study, tracheal intubation was performed by experienced anesthetists. To minimize the potential harm of ATI procedures, ATI attempts were stopped and defined as ‘failed on the first attempt’ when a patient was unable to cooperate due to Grade 4 reactions or Grade 3 reactions along with closing vocal cords. Routine anesthesia induction and videolaryngoscope-assisted intubation were performed once the first attempt failed. Five cases of ATI failed on the first attempt at laryngeal exposure, and four of them experienced severe gagging that that hinder intubation. This finding suggests that the anesthetic effects of these two protocols (anterior or posterior SLNB combined with TLI) on the oropharynx might be incomplete. Future research could consider adding glossopharyngeal topical anesthesia to our protocol to blunt the gag reflex. However, video laryngoscopy usually demands a higher quality of upper-glottic anesthesia than awake fiberoptic intubation (AFOI). If our technique is applied in AFOI protocols, the incidence of severe gagging may decrease because of less stimulation of the upper glottic structures. Additionally, unexpected mild coughing occurred in 17.3% of the patients in the modified group and in 13.5% of the patients in the traditional group. Topical anesthesia with a higher concentration of lidocaine may reduce the incidence of coughing [25]. Whether TLI with 4% lidocaine provides a more stable and lasting effect than that with 2% lidocaine requires further investigation.

In the current study, the most common postprocedural complication was airway hemorrhage. Among all 104 participants, only one exhibited mucosal bleeding (spotting) in the larynx before blade placement; six cases of bloody discharge were observed through the suction tube prior to extubation; three cases of coughing up bloody discharge were reported and disappeared on the same day. None of the patients developed airway hemorrhage, which necessitated additional treatment during the follow-up period. Tracheal or laryngeal mucosal bleeding is common following landmark-guided TLI, and has been reported to occur in 30–76% of patients [26]. It has been speculated that the correct location of the midline with the use of ultrasound may decrease the risk of subsequent airway hemorrhage [27]. Future studies could use fiberoptic-guided spraying or laryngo-tracheal atomization devices to replace TLI and reduce the risk of bleeding associated with invasive airway anesthesia techniques.

In this study, no patient was diagnosed with superior laryngeal nerve injury, which was a potential and theoretical disadvantage of traditional SLNB techniques with double lateral injections. In contrast, the modified technique we developed minimized the risk of superior laryngeal nerve neuropraxia, not only by choosing a route with little or no nerve crossing but also by performing a single injection. Although we lack data to compare the SLN neuropraxia rate of our modified technique with other airway nerve block techniques, future studies on awake intubation can be designed to compare the risk of nerve injury between topical anesthesia and a variety of nerve block techniques.

This study had some limitations. First, this trial was open label. It was inappropriate to blind the procedure because an extra saline injection would be required. Second, we excluded patients with difficult airways from the design of this study, as the safety of this first proposed modified SLNB technique has yet to be clinically proven. It is also unethical to place a patient with a difficult airway at such a potential risk, although this may improve the generalization of our conclusion. Third, topical anesthesia for videolaryngoscopy-assisted ATI may require larger doses of local anesthetic, which may carry a higher risk of LAST [4–6]. Additionally, a meta-analysis by our team also demonstrated that airway nerve blocks provide better airway anesthesia quality for ATI than topical anesthesia [3], especially in providing open vocal cords [28]. Therefore, we do not consider it reasonable to include a group of subjects who underwent surface anesthesia techniques. In addition, videolaryngoscopy-assisted ATI was performed rather than AFOI, which also limits the generalization of the results. Fourth, based on previous findings [8,13] and our clinical experience, we determined a dose of 6 ml 2% lidocaine, and the space above the TH-Mb was validated as the final target plane. However, we did not measure plasma lidocaine concentrations, thus the optimal dosage of lidocaine and time window of intubation in our protocol remained unclear. A dose-response study may be required for ultrasound-guided SLNB using different approaches.

Conclusion

Among adults without difficult airways during videolaryngoscope-assisted ATI, the modified ultrasound-guided anterior SLNB, compared with the traditional posterior approach, showed a statistically non-inferior effect with regard to providing AIC. This modified technique is less time-consuming and may increase the safety of ATI by attenuating cardiovascular stress responses.

Authors contributions

Qiyuan Huang conceptualization and design of the study; investigation; analyses and interpretation of the data; original draft preparation; final approval of the version to be published; and agreement to be accountable for all aspects of the work.

Yusi Hua design and methodology; manuscript review and editing; pilot study implementation; final approval of the version to be published; agreement to be accountable for all aspects of the work.

Ruihao Zhou original draft preparation, final approval of the version to be published, agreement to be accountable for all aspects of the work.

Guo Chen conceptualization, resources, supervision, manuscript review and editing, final approval of the version to be published, agreement to be accountable for all aspects of the work.

Tao Zhu conceptualization, supervision, manuscript review and editing, final approval of the version to be published, agreement to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data relevant to the study are included in the article or are uploaded as Supplementary Information. The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [grant number 2018YFC2001800] to TZ and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences [grant number 2019-I2M-5-011] to TZ.