Laryngoscopy and endotracheal intubation are fundamental components of general anaesthesia; however, these procedures are associated with a transient but significant cardiovascular stress response. Mechanical stimulation of the highly innervated structures of the larynx and tracheobronchial tree activates somatovisceral reflex pathways and the sympathoadrenal system, resulting in increased catecholamine release. This physiological response manifests as elevations in heart rate, systolic and diastolic blood pressure, and mean arterial pressure (MAP). The magnitude of this response is influenced by factors such as the duration of laryngoscopy, the intensity of airway stimulation and the force applied during intubation [1,2]. The haemodynamic response generally begins within 5–10 seconds of airway instrumentation, reaches its maximum intensity within 1–2 minutes and gradually returns towards baseline levels over approximately 5 minutes. Although the increase in systolic blood pressure is usually around 25–30 mmHg and is well tolerated by healthy individuals, it may be clinically significant in patients with pre-existing cardiovascular or cerebrovascular disorders. Excessive sympathetic stimulation can increase myocardial oxygen demand and potentially precipitate myocardial ischaemia, cerebrovascular events and acute pulmonary oedema, particularly in susceptible individuals [2–4]. Consequently, preventing excessive haemodynamic fluctuations during airway manipulation is an important objective of balanced anaesthetic management. Several pharmacological approaches have been investigated to attenuate this response, including opioids, beta-adrenergic blockers, alpha-2 adrenergic agonists and local anaesthetic agents. These drugs act through different mechanisms to suppress sympathetic activation or reduce sensory transmission from the airway. Both systemic and topical routes of administration have been explored, with topical airway anaesthesia offering the advantage of directly reducing afferent stimulation during airway instrumentation [5]. Ropivacaine is a long-acting amide local anaesthetic that produces reversible blockade of voltage-gated sodium channels, thereby inhibiting the initiation and propagation of nerve impulses. Its favourable sensory blockade profile and relatively prolonged duration of action have established its role in regional anaesthesia and postoperative analgesia. More recently, topical administration of ropivacaine through nebulization and other airway delivery techniques has attracted interest for attenuating cardiovascular responses during intubation and airway irritation during extubation. Its longer duration of action compared with lignocaine may provide sustained suppression of airway reflexes and potentially reduce coughing during emergence from general anaesthesia [6]. Dexmedetomidine, a highly selective alpha-2 adrenergic agonist, has demonstrated efficacy in attenuating the sympathoadrenal response to laryngoscopy and endotracheal intubation. Its central sympatholytic action reduces norepinephrine release and sympathetic outflow, thereby limiting increases in heart rate and blood pressure. Although intravenous administration is well established, its use may be associated with dose-dependent adverse effects, particularly bradycardia and hypotension. Nebulization represents an alternative route of administration that may provide local airway effects along with systemic absorption. Previous investigations have explored nebulized dexmedetomidine as a means of reducing haemodynamic responses during airway manipulation [7–9]. Lignocaine is another commonly employed local anaesthetic for topical airway anaesthesia. By inhibiting sodium channel-mediated nerve conduction, it reduces sensory input arising from the upper airway and attenuates reflex responses to airway instrumentation. Nebulized lignocaine has been used for airway anaesthetization, particularly as an adjunct during awake fibre-optic intubation, and has also been investigated for reducing haemodynamic responses associated with laryngoscopy and intubation [10]. Recent comparative investigations have further explored the potential benefits of nebulized local anaesthetic agents and alpha-2 agonists. Saxena et al. evaluated nebulized 0.75% ropivacaine against nebulized dexmedetomidine for attenuation of the haemodynamic response to intubation, highlighting the potential of topical airway drug administration as an alternative approach to conventional intravenous pharmacological interventions [11]. Similarly, Misra et al. investigated preoperative dexmedetomidine nebulization and its influence on cardiovascular responses during laryngoscopy and endotracheal intubation [12]. These studies provide a rationale for further evaluating different nebulized agents with distinct pharmacological mechanisms. Despite the established use of lignocaine for topical airway anaesthesia and the emerging evidence supporting nebulized ropivacaine and dexmedetomidine, comparative evidence regarding their relative efficacy in controlling haemodynamic responses during both intubation and extubation remains limited. Furthermore, their effects on postoperative airway-related complications, including cough, sore throat and hoarseness of voice, warrant further evaluation. Therefore, the present study was undertaken to compare the efficacy of nebulized 0.75% ropivacaine, dexmedetomidine (1 µg/kg) and 4% lignocaine in attenuating haemodynamic responses during laryngoscopy and endotracheal intubation. The study also evaluated their effects on haemodynamic changes during extubation, cough response and the incidence of postoperative sore throat and hoarseness of voice.

Following approval from the Institutional Ethics Committee (IEC no. BJGMCIEC/ Pharmac /ND-0624251-251, dated 23.08.2024) this prospective, randomized, double-blind, comparative interventional study was conducted in the Department of Anaesthesiology at a tertiary care teaching hospital over a period of six months. A total of 105 adult patients aged 18–60 years, belonging to American Society of Anesthesiologists (ASA) physical status I and II, scheduled for elective surgical procedures under general anaesthesia with an anticipated duration of 2–4 hours, were enrolled. Patients were randomly allocated into three groups of 35 each using a computer-generated randomization sequence. The study was conducted using a double-blinding technique, wherein both the patients and the investigator responsible for perioperative assessment and data collection were blinded to the group allocation. Patients with obesity, hypertension, ASA physical status III or above, known allergy to any of the study drugs, anticipated difficult airway, or refusal to participate were excluded. Patients undergoing emergency or day-care surgical procedures and those requiring laryngoscopy exceeding 15 seconds were also excluded. All patients underwent detailed pre-anaesthetic evaluation, including history-taking, clinical examination, airway assessment and relevant investigations. Fasting status of at least six hours was confirmed, and written informed consent was obtained. Patients were assigned to one of three groups according to the nebulized drug administered. Group R received 5 ml of 0.75% ropivacaine, Group D received dexmedetomidine 1 µg/kg diluted with normal saline to a total volume of 5 ml, and Group L received 5 ml of 4% lignocaine. Nebulization was performed using an ultrasonic nebulizer generating a fine aerosol mist and continued until complete dispersion of the solution, requiring approximately 10 minutes. Patients were monitored throughout nebulization for adverse events, including bradycardia, excessive sedation and coughing. In the operating theatre, standard ASA monitoring was established, including electrocardiography, pulse oximetry, non-invasive blood pressure, temperature and end-tidal carbon dioxide monitoring. Baseline heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), oxygen saturation (SpO₂) and end-tidal carbon dioxide (EtCO₂) were recorded. Intravenous access was secured, and intravenous fluids were administered at 10 ml/kg/hour. All patients received ondansetron (0.08 mg/kg), glycopyrrolate (5 µg/kg), midazolam (0.03 mg/kg) and dexamethasone (0.1 mg/kg) intravenously three minutes before induction. Following completion of nebulization, patients were preoxygenated with 100% oxygen for three minutes. Anaesthesia was induced with intravenous propofol (2–2.5 mg/kg), titrated until loss of the eyelash reflex, and neuromuscular blockade was achieved with vecuronium (0.08 mg/kg). Direct laryngoscopy and endotracheal intubation were performed using a cuffed endotracheal tube of 7.5 mm internal diameter for females and 8.5 mm for males. Laryngoscopy and intubation were completed within 15 seconds. Correct tube placement was confirmed by bilateral air entry and capnography. Anaesthesia was maintained using a nitrous oxide and oxygen mixture in a 2:1 ratio, supplemented with isoflurane and intermittent doses of vecuronium as required. At the completion of surgery, intravenous paracetamol (15 mg/kg) and ondansetron (0.08 mg/kg) were administered. Isoflurane was discontinued, and neuromuscular blockade was reversed using neostigmine (0.05 mg/kg) and glycopyrrolate (0.01 mg/kg). Extubation was performed after adequate recovery of consciousness and spontaneous ventilation. Patients were subsequently transferred to the post-anaesthesia care unit and monitored for three hours before transfer to the ward. Haemodynamic parameters, including HR, SBP, DBP and MAP, were recorded at baseline before nebulization, 10 minutes after nebulization, immediately before intubation, and at 10, 20, 30, 60, 90 and 120 minutes after intubation. Additional measurements were recorded immediately before extubation and during the postoperative period. The primary outcome was the comparison of haemodynamic responses during laryngoscopy and endotracheal intubation among the three groups. Secondary outcomes included haemodynamic changes during extubation, severity of cough, and the incidence of postoperative sore throat and hoarseness of voice within 24 hours. Cough response during extubation was graded as absent (no cough), mild (single cough), moderate (cough lasting less than 5 seconds) or severe (continuous coughing lasting more than 5 seconds). Postoperative sore throat was assessed at 0–6, 6–12 and 12–24 hours after extubation using a four-point scale, with grade 0 indicating no sore throat, grade 1 mild sore throat, grade 2 moderate sore throat and grade 3 severe sore throat associated with hoarseness or pain. Hoarseness of voice was assessed at extubation and within 24 hours post-extubation using a four-point grading scale ranging from 0 to 3. All observations were systematically documented for subsequent analysis. The sample size was estimated considering a study power of 90% and an alpha error of 0.08. The expected proportion was assumed to be 0.5, with a margin of error of 0.3. Considering an anticipated dropout rate of 10%, a total sample size of 105 patients, with 35 participants in each group, was considered. Data were entered into Microsoft Excel 2019 and analysed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Comparisons among the three groups were performed using one-way ANOVA or the Kruskal–Wallis test, as appropriate. Repeated haemodynamic measurements were analysed using repeated-measures ANOVA, and categorical variables were compared using the Chi-square test. A p-value of less than 0.05 was considered statistically significant.

A total of 105 patients were enrolled in the study and allocated equally into three groups: Group R (ropivacaine), Group D (dexmedetomidine) and Group L (lignocaine), with 35 patients in each group. The demographic characteristics and baseline clinical parameters were comparable among the three groups. The three groups were comparable in terms of age, gender, BMI, ASA physical status and duration of surgery, with no statistically significant differences observed (p > 0.05) (Table 1). Table 1: Comparison of demographic and clinical characteristics among the three groups Variable Ropivacaine (Mean ± SD) Dexmedetomidine (Mean ± SD) Lignocaine (Mean ± SD) p-value Age (years) 42.5 ± 10.2 40.8 ± 9.5 41.2 ± 10.8 0.72 Male (%) 60% 58% 62% 0.85 Female (%) 40% 42% 38% 0.85 BMI (kg/m²) 25.3 ± 3.1 24.9 ± 2.8 25.1 ± 3.0 0.68 ASA I (%) 55% 57% 53% 0.79 ASA II (%) 45% 43% 47% 0.79 Duration of Surgery (min) 150 ± 30 155 ± 28 152 ± 29 0.81 *Values are expressed as mean ± standard deviation or percentage, as appropriate. ASA: American Society of Anesthesiologists; BMI: Body mass index. p < 0.05 was considered statistically significant. The baseline heart rate was comparable among the three groups before nebulization (p = 0.72). Following nebulization, a greater reduction in heart rate was observed in Group D compared with Groups R and L (72 vs 79 and 80 beats/min, respectively; p less than 0.01). Immediately before intubation, the mean heart rate was 87 beats/min in Group R, 74 beats/min in Group D and 85 beats/min in Group L. Following intubation, heart rate increased in all three groups, with the highest value observed in Group R (102 beats/min), followed by Group L (97 beats/min) and Group D (88 beats/min). This difference was statistically significant (p less than 0.01). The lower heart rate in Group D persisted during subsequent observations, including 10 and 30 minutes after intubation and before and after extubation (fig 1). Following nebulization, systolic blood pressure decreased in all groups, with a greater reduction in Group D. Immediately before intubation, the corresponding values were 96, 85 and 94 mmHg, respectively. Following intubation, systolic blood pressure increased in all three groups, reaching 110 mmHg in Group R, 94 mmHg in Group D and 105 mmHg in Group L (p less than 0.01). The same trend was observed at 10 and 30 minutes after intubation and during extubation, with Group D consistently demonstrating lower systolic blood pressure values compared with Groups R and L (fig 2). The incidence of postoperative sore throat was lower in Group D compared with Groups R and L at all three assessment intervals. During the first 6 hours, sore throat was reported in 15% of patients in Group D, compared with 30% in Group R and 40% in Group L (p less than 0.05). A similar trend was observed during the 6–12-hour and 12–24-hour periods. Hoarseness of voice was also less frequent in Group D. At extubation, it was observed in 18% of patients in Group D, compared with 35% in Group R and 42% in Group L. Within 24 hours, the incidence decreased to 12%, 25% and 35%, respectively. Regarding cough response during extubation, mild cough was reported in 25% of patients in Group D, 40% in Group R and 50% in Group L. Moderate cough occurred in 15%, 25% and 35%, respectively. Severe cough was not observed in Group D, whereas it occurred in 5% of Group R and 10% of Group L (Table 2) Table 2: Comparison of postoperative airway-related complications Symptom Time Point Ropivacaine (R) Dexmedetomidine (D) Lignocaine (L) p-value Sore Throat 0-6 hours 30% 15% 40% <0.05* 6-12 hours 40% 20% 50% <0.05* 12-24 hours 20% 10% 30% <0.05* Hoarseness At Extubation 35% 18% 42% <0.05* Within 24 hours 25% 12% 35% <0.05* Cough Mild 40% 25% 50% <0.05* Moderate 25% 15% 35% <0.05* Severe 5% 0% 10% <0.05* Values are expressed as percentages. R: Ropivacaine; D: Dexmedetomidine; L: Lignocaine. *p < 0.05 was considered statistically significant. Pairwise comparison demonstrated a statistically significant difference between Groups R and D (mean difference 22.125; p = 0.001569). However, the difference between Groups R and L (mean difference 13.125; p = 0.062858) and between Groups D and L (mean difference −9; p = 0.24717) was not statistically significant (Table 3). Table 3: Pairwise comparison among the three study groups Comparison Mean Difference p-value Significant (p < 0.05) Ropivacaine vs Dexmedetomidine 22.125 0.001569 significant Ropivacaine vs Lignocaine 13.125 0.062858 Not significant Dexmedetomidine vs Lignocaine -9 0.24717 Not significant R: Ropivacaine; D: Dexmedetomidine; L: Lignocaine. Mean difference represents the difference between the respective groups. *p < 0.05 was considered statistically significant.

Laryngoscopy and endotracheal intubation are associated with a well-recognized sympathetic stress response, resulting in transient increases in heart rate and blood pressure. Although generally well tolerated in healthy individuals, these haemodynamic alterations may have important clinical implications in patients with cardiovascular and cerebrovascular comorbidities. Attenuation of this response is therefore an important consideration in anaesthetic practice. The present study compared three nebulized agents, namely 0.75% ropivacaine, dexmedetomidine (1 µg/kg) and 4% lignocaine, with respect to their effects on haemodynamic responses during intubation and extubation and postoperative airway-related complications. A total of 105 patients were included, with 35 patients in each group. The three groups were comparable with respect to demographic characteristics, BMI, ASA physical status and duration of surgery. This comparability is important because differences in baseline patient characteristics may influence cardiovascular responses to airway manipulation. The absence of statistically significant differences in these variables supports the validity of subsequent intergroup comparisons. Heart rate responses were comparable at baseline but decreased more markedly after nebulization with dexmedetomidine. Following intubation, heart rate increased in all groups, with the lowest values observed in Group D (88 beats/min), compared with Group R (102 beats/min) and Group L (97 beats/min). This trend persisted during the subsequent observation period and after extubation, suggesting better attenuation of sympathetic stimulation with dexmedetomidine. Its central α₂-adrenergic action, which suppresses sympathetic outflow and norepinephrine release, may explain this effect. Kumar et al. (2020) reported attenuation of blood pressure responses with nebulized dexmedetomidine, although heart rate differences were not significant (p = 0.990) [8]. Similarly, Saxena et al. (2024) observed significant intergroup differences in heart rate after intubation and extubation, supporting the role of nebulized dexmedetomidine in blunting haemodynamic responses to airway manipulation [11]. These findings are consistent with those of Kumar et al. (2020), who evaluated nebulized dexmedetomidine at a dose of 1 µg/kg in 100 patients undergoing general anaesthesia. In their study, the dexmedetomidine group demonstrated a significant reduction in systolic blood pressure, with values of 126.64 ± 26.37 mmHg at 1 minute, 109.50 ± 16.83 mmHg at 5 minutes and 106.94 ± 17.01 mmHg at 10 minutes following intubation. Corresponding mean arterial pressure values were 99.68 ± 19.22, 84.08 ± 13.66 and 81.74 ± 14.79 mmHg, respectively. The authors concluded that nebulized dexmedetomidine effectively attenuated the haemodynamic stress response to laryngoscopy and intubation. Although their study did not demonstrate a significant intergroup difference in heart rate (p = 0.990), the reduction in blood pressure supports the sympatholytic properties of nebulized dexmedetomidine. [8] The systolic blood pressure response in the present study followed a similar pattern. Baseline systolic blood pressure was 92, 91 and 93 mmHg in the ropivacaine, dexmedetomidine and lignocaine groups, respectively (p = 0.80). Following nebulization, the values decreased to 88, 84 and 89 mmHg. Immediately after intubation, systolic blood pressure increased to 110 mmHg in the ropivacaine group, 94 mmHg in the dexmedetomidine group and 105 mmHg in the lignocaine group. At 10 minutes after intubation, the respective values were 102, 88 and 98 mmHg, while at 30 minutes they were 96, 85 and 92 mmHg. Following extubation, systolic blood pressure increased to 106, 90 and 101 mmHg, respectively. The consistently lower values observed in the dexmedetomidine group indicate better attenuation of the systolic pressor response. The findings are also supported by Saxena et al. (2024), who conducted a randomized, double-blind, placebo-controlled study involving 180 patients allocated equally into three groups receiving nebulized 0.75% ropivacaine, dexmedetomidine (1 µg/kg) or normal saline. They reported a statistically significant difference in haemodynamic responses among the groups, particularly during the immediate post-intubation and post-extubation periods. Their heart rate comparisons demonstrated significant differences immediately after intubation and immediately after extubation (p < 0.0001), as well as five minutes after extubation (p < 0.005). Their observations support the beneficial effects of nebulized dexmedetomidine and ropivacaine in attenuating cardiovascular responses associated with airway manipulation. [11] The efficacy of topical local anaesthetic agents in reducing airway-related haemodynamic responses has also been demonstrated in previous investigations. Thangavelu et al. (2018) compared nebulized 0.25% ropivacaine, 2% lignocaine and normal saline in 75 patients undergoing general anaesthesia. They observed that ropivacaine significantly attenuated haemodynamic responses during intubation and extubation compared with saline. At extubation, the mean heart rate was 96.40 ± 9.97 beats/min in the ropivacaine group compared with 103.72 ± 10.36 beats/min in the lignocaine group, although this difference was not statistically significant (p = 0.103). Similarly, mean arterial pressure was 95.88 ± 8.87 mmHg and 101.60 ± 11.73 mmHg, respectively (p = 0.153). These findings suggest that ropivacaine may provide better numerical haemodynamic stability than lignocaine during extubation, although a statistically significant difference between the two local anaesthetic agents was not established. In the present study, ropivacaine and lignocaine also demonstrated less attenuation of haemodynamic responses than dexmedetomidine, with relatively small numerical differences between the two local anaesthetic groups. The difference in ropivacaine concentration should also be considered, as Thangavelu et al. used 0.25%, whereas the present study employed 0.75% ropivacaine. [3] The effect of topical ropivacaine during emergence from general anaesthesia was further evaluated by Fang et al. (2018) in a randomized, double-blind study involving 54 patients undergoing thyroid surgery. They administered 0.75% ropivacaine topically to the tracheal mucosa, epiglottis, base of the tongue and glottic region. The incidence of cough during extubation was significantly lower in the ropivacaine group than in the control group (34.62% versus 76.92%; p = 0.002). They also reported a lower postoperative sore throat score at 12 hours in the ropivacaine group compared with the control group (2.00 versus 3.50; p = 0.040). These findings support the role of topical ropivacaine in reducing airway irritation and reflex responses during emergence. Although their method of administration involved direct topical application rather than nebulization, the findings provide supportive evidence for the beneficial effects of prolonged airway sensory blockade. [6] Postoperative airway-related complications were also evaluated in the present study. The incidence of sore throat was consistently lower in the dexmedetomidine group at all postoperative assessment intervals. During the first 6 hours, sore throat was reported in 15% of patients in the dexmedetomidine group, compared with 30% in the ropivacaine group and 40% in the lignocaine group. During 6–12 hours, the corresponding incidences were 20%, 40% and 50%, while during 12–24 hours they were 10%, 20% and 30%, respectively. Similarly, hoarseness at extubation was observed in 18% of patients receiving dexmedetomidine, compared with 35% and 42% in the ropivacaine and lignocaine groups. Within 24 hours, the incidence decreased to 12%, 25% and 35%, respectively. The lower incidence of these complications in the dexmedetomidine group may be associated with its analgesic and sympatholytic properties. Nevertheless, direct anti-inflammatory effects following nebulized administration were not evaluated in the present study. Cough response during extubation is another important indicator of airway irritation and emergence-related reflex stimulation. In the present study, mild cough occurred in 25% of patients in the dexmedetomidine group, compared with 40% in the ropivacaine group and 50% in the lignocaine group. Moderate cough was observed in 15%, 25% and 35%, respectively. Severe cough was not observed in the dexmedetomidine group, whereas it occurred in 5% of patients receiving ropivacaine and 10% receiving lignocaine. These findings indicate a comparatively lower severity of cough following nebulized dexmedetomidine. Thangavelu et al. reported cough during extubation in 40% of patients receiving ropivacaine compared with 88% receiving lignocaine and 92% receiving saline (p < 0.001). Their findings support the effectiveness of ropivacaine in suppressing airway reflexes and demonstrate its advantage over lignocaine in reducing cough during extubation. Similarly, Fang et al. reported a reduction in cough incidence from 76.92% in the control group to 34.62% with topical ropivacaine. The findings of these studies are consistent with the beneficial effects of topical airway anaesthesia observed in the present investigation. [3,6] The comparatively better performance of dexmedetomidine in the present study may be explained by its distinct pharmacological mechanism. Ropivacaine and lignocaine primarily act through blockade of voltage-gated sodium channels, thereby inhibiting sensory impulse transmission from the airway. Ropivacaine, owing to its longer duration of action, may provide more sustained suppression of airway reflexes than lignocaine. Dexmedetomidine, in contrast, produces central sympatholysis through alpha-2 adrenergic receptor stimulation and also possesses sedative and analgesic properties. Consequently, its effects may extend beyond peripheral sensory blockade and contribute to attenuation of sympathetic responses during both intubation and extubation. The findings of Kumar et al. and Saxena et al. provide additional support for the use of nebulized dexmedetomidine in this context. [8,11] The present study has certain limitations. It was conducted at a single tertiary care centre and included a relatively small sample size, which may limit the generalizability of the findings. Only patients belonging to ASA physical status I and II were included; therefore, the results cannot be directly extrapolated to patients with significant cardiovascular or cerebrovascular comorbidities. Further multicentric randomized controlled trials involving larger patient populations are warranted to establish the comparative efficacy, optimal dosage and safety profile of these interventions.

The findings of the present study suggest that nebulized dexmedetomidine provides greater attenuation of haemodynamic responses to laryngoscopy, endotracheal intubation and extubation compared with nebulized ropivacaine and lignocaine. It was also associated with a lower observed incidence of postoperative sore throat, hoarseness and cough. Nebulized ropivacaine demonstrated beneficial effects on airway-related responses, while lignocaine showed comparatively less attenuation in the present study. These observations support the potential role of nebulized dexmedetomidine as an adjunct to general anaesthesia for reducing cardiovascular and airway reflex responses during airway manipulation.

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