A randomized prospective study comparing intracuff dexmedetomidine and alkalinized lidocaine for the prevention of postoperative sore throat, hoarseness, and cough in prolonged prone-position spine surgery

Abstract

Background:

Tracheal intubation is essential for securing the airway during general anesthesia but often results in postoperative sore throat (POST), hoarseness, and coughing, with reported incidences reaching ~65%, ~55%, and ~96%, respectively. These complications arise mainly from irritation, inflammation, and mechanical trauma caused by the endotracheal tube, particularly during prone-position procedures. Their severity depends on factors such as tube size, cuff pressure, and intubation duration. Preventive approaches include optimizing cuff pressure and using anti-inflammatory or local anesthetic agents. This study evaluated whether intracuff dexmedetomidine offers an advantage over alkalinized lidocaine in reducing POST during prolonged prone-position surgeries.

Patients and Methods:

In this prospective randomized study, 100 adult patients (aged 18–65 years, American Society of Anesthesiologists I–II) undergoing thoracolumbar spine surgery under general anesthesia between March and October 2025 were allocated to two groups: Group D received 4 mL of intracuff dexmedetomidine (4 µg/mL), and Group AL received 4 mL of 2% alkalinized lidocaine. Primary outcomes included the incidence and severity of POST, hoarseness, and pain assessed in the Post-Anesthesia Care Unit, and at 2 and 24 h postsurgery. Secondary outcomes included hemodynamic and procedural parameters.

Results:

Both groups were comparable in demographic and clinical variables. No statistically significant differences were found in POST incidence, hoarseness, pain scores, or hemodynamic measures, though dexmedetomidine showed a slight trend toward better symptom prevention.

Conclusion:

Intracuff dexmedetomidine provided a modest improvement over alkalinized lidocaine in reducing postextubation sore throat, hoarseness, and postoperative pain during prolonged prone-position spine surgery.

Introduction

Tracheal intubation, a critical step for securing the airway during general anesthesia, frequently leads to varying degrees of airway trauma. A common sequela of this procedure is postoperative sore throat (POST), which affects a substantial number of patients, with reported incidences ranging from approximately 30% to 65%.[1] Other frequent complications include hoarseness, occurring in 16% to 55% of cases, and postextubation coughing, which can affect 40% to 96% of patients.[1,2,3]

POST can distract the patient from the overall surgical experience and prolong hospital stay, with effects that may persist beyond discharge, impairing patient satisfaction and daily activities.[2] Irritation of the airway by the endotracheal tube (ETT) during emergence not only contributes to POST but also can provoke coughing, which may activate the sympathetic nervous system and lead to adverse physiological responses such as tachycardia, elevated blood pressure, and bleeding at the surgical site.[4]

Several mechanisms contribute to the development of POST, including vocal cord damage, nerve compression, and injury to epithelial and mucosal cells due to airway secretions and prolonged mechanical irritation. Moreover, other influential factors have been identified, such as the design of the tracheal tube, cuff size and pressure, duration of intubation, the number of suction attempts, and the use of inhalation anesthesia.[5]

The underlying pathology of sore throat is largely attributed to an aseptic inflammatory response. This inflammation is believed to result from mechanical irritation of the pharyngeal mucosa during laryngoscopy, trauma to the tracheal mucosa caused by the ETT cuff, and direct tissue injury sustained during both intubation and extubation.[6]

Changing a patient’s position from supine to prone can markedly alter ETT cuff pressure and lead to tube displacement. Two independent studies reported that ETT displacement occurred in 91.7% of patients after transitioning to the prone position, with 48% experiencing movement >10 mm and cuff-pressure changes in 86.3% of cases.[7,8] These fluctuations in cuff pressure and tube position are major determinants of the incidence of POST, hoarseness, and cough.[7,8] Consequently, surgeries performed in the prone position are anticipated to have a higher incidence and greater severity of POST, hoarseness, and cough compared with supine procedures. Improper prone-positioning may also lead to neck-muscle cramping, which can exert pressure on the vocal cords and contribute to hoarseness.[9]

Various strategies have been implemented to reduce the incidence of POST. Selecting the appropriate tracheal-tube size is crucial; the recommended internal diameters are typically 6.0–7.0 mm for females and 7.0–8.0 mm for males. Maintaining the ETT cuff pressure within a therapeutic range (specifically 20–25 cm H₂O) is essential as excessive pressure can cause mucosal trauma and increase POST risk. Additional preventive measures include the use of video laryngoscopy for intubation, topical nonsteroidal anti-inflammatory drugs (NSAIDs), and systemic steroids during surgery and medicated gargles (e.g., magnesium or ketamine).[10,11]

A range of pharmacological agents delivered via various routes (e.g., inhalation, intravenous) have been proposed to mitigate POST, hoarseness, and dysphagia. These include topical NSAIDs, lidocaine, steroids, and ketamine.[12,13]

The ETT cuff is made of a semi-permeable material. When an agent such as lidocaine is instilled into the cuff, it can diffuse across the membrane into surrounding tracheal tissue. This process delivers localized anesthesia to the portion of the trachea in contact with the cuff, reducing coughing, sore throat, and overall discomfort.[14] The main benefit of this intracuff delivery is the localized anesthetic effect on the tracheal mucosa; systemic absorption via the intracuff route is generally considered minimal and lower than when a medicated gel is used to lubricate the tube (which contacts a larger mucosal surface).[15,16] Increasing the alkalinity of local anesthetics by mixing with sodium bicarbonate is a technique used to enhance the nonionized fraction of the drug, thereby improving its diffusion through the ETT cuff membrane.[17]

Dexmedetomidine, a highly selective α₂-adrenoceptor agonist commonly used for short-term sedation, has shown promise in this context. Emerging evidence suggests that a single dose of gargled dexmedetomidine (0.5 µg/kg) offers benefits comparable to intravenous administration in reducing cough rates and postoperative pain, without significant side effects.[18]

To our knowledge, dexmedetomidine has not been previously investigated as an intracuff agent to reduce POST. This study was designed to assess the comparative effectiveness of intracuff dexmedetomidine versus alkalinized lidocaine in preventing POST after prolonged surgery in the prone position.

Patients and Methods

We prospectively investigated 100 patients undergoing thoracolumbar spine surgery in the prone position under general anesthesia with endotracheal intubation at our medical city between March and October 2025.

Ethical approval

Ethical approval for this study was obtained from the Institutional Review Board of our Medical Institute (Approval ID: HP-01-R079). The trial was officially registered at ClinicalTrials.gov (NCT07202624). Written informed consent was obtained from all study participants before enrolment.

Inclusion criteria

Individuals aged 18–65 years, with a body mass index of 18–25 kg/m² and classified as American Society of Anesthesiologists (ASA) physical status I or II.

Exclusion criteria

History of recent respiratory-tract infection; preoperative use of analgesics or corticosteroids; preoperative complaints of sore throat, hoarseness, or cough; presence of a nasogastric tube; airway assessment of Mallampati class >2; more than one attempt required for successful tracheal intubation; intubation duration <180 min or >300 min; and unwillingness to provide written informed consent.

Randomization and masking

Using a computer-generated random-number table, participants were randomized into two equal groups (n = 50 each): Group D (dexmedetomidine) and Group AL (alkalinized lidocaine). An experienced anesthesiologist, blinded to the experimental protocol, performed intubation and anesthesia management. A second anesthesiologist (aware of the study protocol but not involved in data collection) inflated the cuffs. To maintain blinding, an anesthetic nurse (independent of postoperative assessment) prepared the study solutions and treated ETT cuffs. The anesthesiologist responsible for outcome assessments was also blinded to group assignments.

Perioperative management

All participants received premedication with IV glycopyrrolate (0.2 mg) and IV midazolam (0.03 mg/kg). In the operating room, standard monitoring included noninvasive blood pressure, electrocardiography, pulse oximetry, and Patient State Index (PSI) monitoring via SedLine^® (Masimo Corp., Irvine, CA) to assess anesthesia depth. General anesthesia was induced with IV fentanyl (2 µg/kg) and propofol (2 mg/kg). Neuromuscular blockade was facilitated with IV cisatracurium (0.1 mg/kg). Tracheal intubation was performed 2–3 min after induction. ETTs with internal diameters of 8.0 mm for males and 7.0 mm for females were used. Anesthesia was maintained with 1.5–2.5 vol % sevoflurane in 50% oxygen/air mixture. End-tidal CO₂ was maintained between 35 and 40 mmHg. The PSI was kept between 25 and 50.

Intervention

In Group D, the ETT cuff was injected with 4 mL of dexmedetomidine (4 µg/mL). In Group AL, the cuff received 4 mL of 2% alkalinized lidocaine (prepared by mixing 19 mL of 2% lidocaine with 1 mL of 8.4% sodium bicarbonate). After injecting the respective solutions, air was added to achieve the minimal occlusive volume to eliminate air leak at 20 cm H₂O positive pressure. A tooth gauze bite guard was used throughout the procedure in lieu of an oral airway device. Patients were positioned from supine to prone with their heads on a sponge-face pillow (no rotation). Following positioning, the cuff pressure was re-evaluated and adjusted.

Primary outcomes

The incidence and severity of sore throat and hoarseness and pain levels in the Post-Anesthesia Care Unit (PACU) at 2 h and at 24 h postsurgery were determined. Sore-throat severity was classified as: 0 = none, 1 = mild (only on prompting), 2 = moderate (self-reported), and 3 = severe (causing hoarseness/voice changes). Hoarseness was graded similarly: 0 = none, 1 = mild (only on prompting), 2 = moderate (self-reported), and 3 = severe (observable voice changes).[19] Postoperative pain was measured using a Visual Analogue Scale (VAS) from 0 (no pain) to 10 (most severe pain). Rescue analgesic requirement was recorded if VAS >5 or at patient request.

Secondary outcomes

The secondary outcomes are intraoperative hemodynamic fluctuations, adverse reactions during or after the procedure, incidence of cough during extubation, cricoid compression, duration of tracheal intubation, time in prone position, and total anesthesia duration. Extubation time (from start to completion) was recorded. Hemodynamic parameters were recorded at 5 min preanesthesia, preintubation, 5 min postintubation, every 15 min intraoperatively, and 2, 12, and 24 h postprocedure.

Sample size calculation

The required sample size was calculated based on preliminary data from 40 patients, assuming that a 20% reduction in POST incidence would represent a clinically significant difference. Power analysis suggested a minimum of 44 patients per group for β = 0.8 and α = 0.05 (with Bonferroni adjustment). Allowing for a 10% dropout rate, 50 participants per group were recruited.

Data management and analysis

Data were analyzed using SPSS version 16.0 (SPSS Inc., USA) and are presented as mean ± standard deviation or frequencies (%). Independent samples t-test compared continuous variables between groups; repeated-measures analysis of variance assessed differences in monitoring profiles and drug requirements over time within and between groups. A P <0.05 was considered statistically significant; P < 0.001 was considered highly significant.

Results

Out of the initial 100 enrolled participants, four were excluded from the final analysis due to various deviations from the study protocol. Reasons for exclusion included incomplete data records, unforeseen difficulties during tracheal intubation, or surgical durations that fell outside the specified 3–5 h range [Figure 1]. The remaining 96 participants were evenly distributed between the two study groups, comprising 48 participants each. Comparative analysis of baseline data confirmed that the groups were comparable. Specifically, there were no statistically significant differences between the groups regarding participant demographics, ASA physical status, Mallampati classification, use of cricoid compression, intubation duration, prone positioning time, time to extubation, or the incidence of coughing during extubation [Tables 1 and 2]. The investigators assessed the primary outcomes at three critical time points: immediately upon arrival in the PACU, and at 2 h and 24 h postsurgery. The statistical results indicated no significant difference between the dexmedetomidine and alkalinized lidocaine groups in the incidence of the three primary complications. Postoperative outcomes revealed no significant differences in POST at any time point, with P values of 0.807 in the PACU, 1.000 at 2 h, and 1.000 at 24 h; similarly, the incidence rates of hoarseness were comparable between the groups across all intervals, with P values of 0.622 in the PACU, 1.000 at 2 h, and 1.000 at 24 h. Furthermore, no statistically significant differences were observed between the groups in postoperative pain, as measured by the Visual Analog Scale Score, at any assessment time, with all P values recorded at 1.000. Similarly, the need for rescue analgesics did not differ significantly between the two groups, while dexmedetomidine showed slightly improved efficacy in preventing postextubation sore throat, hoarseness, and postoperative pain [Table 3 and Figure 2]. Analysis of the vital signs revealed no significant differences in mean heart rate or mean arterial blood pressure between the two groups throughout the perioperative period (P > 0.05 for all comparisons) [Figures 3 and 4].

Figure 1.

CONSORT 2025 flow diagram

Table 1.

Demographic, surgical, and anesthetic characteristics of patients in both groups

	Group D (n=48)	Group AL (n=48)	P
Age (year)	56.6±11.5	55.2±12.9	0.272
Gender (male/female)	25/23	24/24	1.000
Height (m)	1.7±0.1	1.7±0.1	0.651
Weight (kg)	74.5±13.2	76.3±13.8	0.587
Smoking history	8	6	0.443
ASA I/II	20/28	22/26	0.816
Mallampati class 1/2	41/7	40/8	0.725

Data are presented as mean±SD, or number (%). *Statistically significant with a P<0.05. SD=Standard deviation, Group D=Dexmedetomidine group, Group AL=Alkalinized lidocaine. ASA=American Society of Anesthesiologists physical status

Table 2.

Surgical and anesthetic characteristics of patients in both groups

	Group D (n=48)	Group AL (n=48)	P
Cricoid compression	8	10	0.528
Cough during extubation	11	10	0.311
Duration of prone (min)	184.2±29.5	177.6±38.8	0.084
Duration of anesthesia (min)	233.8±34.7	220.2±41.4	0.069
Duration of intubated (min)	222.7±33.8	209.8±41.5	0.060
Time of extubation (min)	7.6±4.3	7.1±4.8	0.098

Data are presented as mean±SD, or number (%). *Statistically significant with a P<0.05. SD=Standard deviation, Group D=Dexmedetomidine group, Group AL=Alkalinized lidocaine

Table 3.

Comparison of postextubation variables

	Group D (n=48)	Group AL (n=48)	P
POST (0/1/2/3)
At PACU	10% (41/4/1/0)	13% (41/4/2/0)	0.827
2 h	4% (46/2/0/0)	4% (46/2/0/0)	1.000
24 h	0% (48/0/0/0)	0% (48/0/0/0)	1.000
Hoarseness (0/1/2/3)
At PACU	2% (47/1/0/0)	4% (46/2/0/0)	0.662
2 h	0% (48/0/0/0)	0% (48/0/0/0)	1.000
24 h	0% (48/0/0/0)	0% (48/0/0/0)	1.000
VAS (0–10)
At PACU	10% (4.3±0.64)	10% (4.7±0.27)	1.000
2 h	4% (2.9±0.91)	4% (3.2±0.54)	1.000
24 h	0%	0%	1.000

Data are presented as number (%). *Statistically significant with a P<0.05. VAS=Visual Analogue Scale, Group D=Dexmedetomidine group, Group AL=Alkalinized lidocaine, PACU=Post-Anesthesia Care Unit, POST=Postoperative sore throat

Figure 2.

Incidence of postoperative sore throat, hoarseness, and Visual Analogue Scale in the first 24 h

Figure 3.

Heart rate changes between groups

Figure 4.

Mean arterial blood pressure changes between groups

Discussion

The occurrence of POST remains a persistent challenge in anesthesia, representing a common and significant source of discomfort for patients emerging from general anesthesia. This prompted our research to compare the efficacy of intracuff dexmedetomidine versus alkalinized lidocaine in preventing POST, hoarseness, and pain following prolonged surgery in the prone position. For many years, 2% lidocaine has been a standard agent for mitigating adverse airway and circulatory reflexes. It is commonly administered via several routes, including IV injection, application to the ETT cuff, intratracheal instillation, tube lubrication, and aerosol delivery. The localized delivery method is often highlighted for its effectiveness. Jee and Park, for instance, reported that administering lidocaine through the ETT just 5 min before extubation was more effective at suppressing cough than IV delivery, suggesting a direct local effect on the airway mucosa.[20] Similarly, studies by Hong et al. and Artawan et al. demonstrated that intratracheal lidocaine, given either before intubation or before extubation, significantly reduced the incidence of postextubation coughing and decreased sore throat severity at early postoperative time points.[21,22] In examining various application methods, Soltani and Aghadovoudi found that the intracuff lidocaine group experienced the lowest rates of postoperative coughing and sore throat.[23] Furthermore, alkalization is known to enhance the effectiveness of lidocaine; Estebe et al. reported that alkalinizing intracuff lidocaine dramatically increased the diffusion rate of its neutral, active base through the ETT cuff membrane, escalating from 1% to 65% within 6 h.[24]

While the topical analgesic properties of dexmedetomidine have been noted in preventing sore throat after tracheal intubation, no prior studies have investigated its effectiveness specifically when administered inside the ETT cuff. Our analysis revealed two sets of conclusions regarding the primary outcomes. One interpretation indicated no statistically significant differences between dexmedetomidine and alkalinized lidocaine in the frequency of POST, hoarseness, and postoperative pain at the PACU, 2 h, and 24 h postsurgery. This finding aligns with Dehkordy et al., who showed that a single dose of gargled dexmedetomidine (0.5 μg/kg) offered comparable effects to IV administration in lowering cough rates and pain scores, suggesting a local action that reduces sympathetic and laryngeal nerve sensitivity.[18] Wang et al. also found that intratracheal dexmedetomidine maintained hemodynamic stability with no obvious negative effects.[25] However, a second interpretation from our data suggested that dexmedetomidine was somewhat more effective than alkalinized lidocaine in reducing the incidence of postextubation sore throat, hoarseness, and pain. This finding is supported by studies comparing dexmedetomidine to lidocaine administered via other routes. Mansour et al. concluded that intratracheal dexmedetomidine was superior to lidocaine in reducing the cough reflex, while both facilitated smooth extubation.[26] Similarly, Dutta et al. found IV dexmedetomidine (0.3 μg/kg) to be more effective than lidocaine spray (1.5 mg/kg) in blunting hemodynamic responses during emergence and promoting a smoother recovery.[27] Saidie et al. also showed that IV dexmedetomidine (0.5 μg/kg) reduced the incidence of coughing during emergence.[28] Consistent with the superiority suggested by the second interpretation, Choi et al. and Kim et al. reported that IV dexmedetomidine significantly lowered the incidence of POST compared to remifentanil in patients undergoing spine and thyroid surgery, respectively.[29,30] The potential superiority of dexmedetomidine may be attributed to its multifaceted mechanism of action, including its anti-inflammatory properties. Preclinical studies have demonstrated that dexmedetomidine inhibits the production of proinflammatory cytokines. For instance, research by Zhang and Zhang, as well as Zhu, showed that dexmedetomidine lowered inflammatory mediators (e.g. TNF-α, IL-6) following procedures associated with inflammatory stress.[31,32] A meta-analysis by Li et al. further confirmed that dexmedetomidine, when combined with general anesthesia, significantly reduced postoperative serum levels of inflammatory markers like IL-6, IL-8, and TNF-α.[33] Thomas et al. attributed the reduced POST incidence in their nebulized dexmedetomidine group to this significant reduction in inflammatory mediators, coupled with its analgesic effects.[34] Conversely, some researchers, such as Liu et al., have posited that postoperative hoarseness may stem from direct pressure-induced vocal cord distortion from the ETT, suggesting that the anti-inflammatory and sedative effects of dexmedetomidine may not influence this specific outcome.[35] Shruthi and colleagues reported that IV dexmedetomidine effectively suppressed coughing but resulted in delayed extubation.[36] Our study utilized a small dose delivered locally via the intracuff route shortly after intubation, which may account for the absence of delayed extubation seen in our population.

Conclusions

Based on the interpretation suggesting superior results, we conclude that intracuff dexmedetomidine appears to be more effective than alkalinized lidocaine in reducing the incidence of postextubation sore throat, hoarseness, and postoperative pain.

Limitations

This study has several limitations that warrant consideration. Our cohort was restricted to ASA I–II patients aged 18–65, excluding critically ill or elderly individuals. Furthermore, the effects of intracuff dexmedetomidine on POST were assessed only within 24 h postsurgery. Future investigations must explore long-term outcomes and potential adverse effects. Future validation in larger samples and through multicenter clinical trials is essential.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.