Direct laryngoscopy and tracheal intubation remain among the most potent routine stimuli encountered during induction of general anesthesia. Mechanical stimulation of the oropharyngeal and laryngeal structures activates sympathetic pathways, increasing blood pressure and heart rate. Although transient in healthy patients, these changes may be clinically relevant in individuals with cardiovascular or cerebrovascular vulnerability.¹,² Pharmacologic attenuation has therefore been studied using opioids, beta-blockers, alpha-2 agonists, local anesthetics and vasodilators. Topical lignocaine reduces airway afferent signaling and may attenuate reflex sympathetic discharge, whereas nitroglycerin produces nitric-oxide-mediated vasodilation and directly lowers vascular tone.³–⁵ Evidence comparing NTG with lignocaine is heterogeneous because studies differ in dose, route, timing, monitoring method and comparator groups. A prospective randomized study by Varshney et al. found NTG spray more effective than lignocaine for reducing blood-pressure and rate-pressure-product responses.⁶ Kumari et al. demonstrated dose-dependent attenuation of intubation-induced blood-pressure responses with NTG lingual spray.⁷ Other studies have similarly reported favorable blood-pressure effects of NTG, while some suggest that lignocaine may be useful for airway-reflex control.⁸–¹⁰ The submitted thesis directly compared 10% lignocaine spray with NTG spray in 80 elective surgical patients and used invasive arterial pressure monitoring with repeated observations through two hours. The present manuscript reports those data in a publication-oriented format, emphasizing the distinction between statistically significant blood-pressure differences and the absence of a consistent heart-rate effect. Aim and objectives The aim was to compare NTG spray with lignocaine spray in blunting the hemodynamic response to direct laryngoscopy and endotracheal intubation in elective surgical patients.

Study design and participants. The thesis describes a randomized controlled, single-blind study conducted over 18 months at Raipur Institute of Medical Sciences. Eighty ASA I–II patients aged 18–50 years scheduled for elective surgery under general anesthesia with endotracheal intubation were included. Mallampati I–II patients were eligible. Patients with difficult airway, BMI >30 kg/m², cardiovascular disease, pregnancy, antipsychotic medication, ASA III–IV status or allergy to study drugs were excluded. Randomization and interventions- Computer-based randomization using CLINSTAT assigned 40 patients to lignocaine and 40 to NTG. The lignocaine group received 10% lignocaine spray (10 mg per puff) and the NTG group received nitroglycerin spray at 400 μg per puff. The thesis protocol describes administration to the oropharyngeal mucosa before induction. Standardized premedication, propofol/vecuronium induction and volatile-anesthetic maintenance were used. Monitoring- After a positive Allen test, radial arterial cannulation was performed for beat-to-beat blood-pressure measurement. SBP, DBP, MAP, heart rate and SpO₂ were recorded at baseline and predefined intervals including immediately after intubation and 1, 3, 5, 10, 30 minutes, 1 hour and 2 hours. Adverse events included hypotension, bradycardia, arrhythmias and postoperative complaints. Statistics- SPSS 20.0 was used. Continuous variables were expressed as mean±SD and compared using unpaired t-test for normally distributed data or Mann–Whitney U test otherwise. Categorical variables were analyzed with chi-square or Fisher exact tests. p<0.05 was considered significant. Ethical approval and written informed consent were obtained.

Eighty participants were included, 40 per group. Age distribution was comparable (p=0.752), as were sex distribution (p=0.823), mean age (33.20±9.667 vs 34.30±10.011 years; p=0.454) and weight (68.72±11.60 vs 73.80±12.44 kg; p=0.573). All participants had a positive Allen test. Baseline invasive DBP was 80.10±6.155 mmHg in the lignocaine group and 78.00±5.449 mmHg in the NTG group (p=0.330). After intervention, DBP differed significantly at 0, 1, 3, 5, 10 and 30 minutes, 1 hour and 2 hours. Baseline SBP was 119.53±4.915 versus 116.68±5.451 mmHg (p=0.445). SBP was significantly lower with NTG at 0 minutes (117.30 vs 120.78; p=0.018), 3 minutes (117.63 vs 118.95; p=0.041), 10 minutes (116.45 vs 118.75; p=0.032) and 2 hours (116.25 vs 119.90; p=0.021). MAP showed the most consistent between-group difference. Baseline MAP was 106.382±3.989 versus 103.778±4.637 mmHg (p=0.273), while NTG values were lower at every post-intervention interval: 0 min 103.792 vs 106.795 (p=0.042), 1 min 104.627 vs 105.605 (p=0.006), 3 min 104.643 vs 105.713 (p=0.005), 5 min 104.320 vs 104.593 (p=0.006), 10 min 104.023 vs 105.455 (p=0.003), 30 min 103.527 vs 104.420 (p=0.043), 1 h 103.702 vs 107.050 (p=0.009), and 2 h 103.365 vs 106.393 (p=0.017). SpO₂ remained comparable at all time points. Heart rate was also statistically similar throughout. Sore throat was reported in 13/40 lignocaine and 19/40 NTG patients (p=0.065). Headache occurred in 2/40 lignocaine and 6/40 NTG patients (p=0.036). Hematoma occurred in 2/40 versus 3/40 patients (p=0.075). Table 1. Baseline characteristics Variable Lignocaine (n=40) NTG (n=40) p Mean age, years 33.20±9.667 34.30±10.011 0.454 Mean weight, kg 68.72±11.600 73.80±12.437 0.573 Female 20 (50%) 19 (47.5%) 0.823 Male 20 (50%) 21 (52.5%) Positive Allen test 40 (100%) 40 (100%) 1.000 Table 2. Invasive blood pressure comparison Time SBP L SBP N MAP L MAP N Baseline 119.53±4.92 116.68±5.45 106.38±3.99 103.78±4.64 0 min 120.78±5.82 117.30±5.46 106.80±4.56 103.79±4.21 1 min 118.55±6.04 118.08±5.89 105.61±4.84 104.63±4.71 3 min 118.95±5.44 117.63±6.02 105.71±4.41 104.64±4.37 5 min 117.23±5.81 116.98±5.80 104.59±4.60 104.32±4.32 10 min 118.75±6.43 116.45±6.26 105.46±4.80 104.02±5.11 30 min 117.30±6.39 117.30±5.38 104.42±4.66 103.53±3.74 1 h 120.83±5.43 117.43±5.42 107.05±4.30 103.70±4.02 2 h 119.90±5.43 116.25±6.53 106.39±3.58 103.37±4.50 Table 3. Safety outcomes Outcome Lignocaine NTG p Sore throat 13/40 (32.5%) 19/40 (47.5%) 0.065 Headache 2/40 (5.0%) 6/40 (15.0%) 0.036 Hematoma 2/40 (5.0%) 3/40 (7.5%) 0.075

The main finding was a consistent blood-pressure advantage for NTG over lignocaine, particularly for MAP. This result is pharmacologically coherent: NTG increases nitric-oxide signaling and relaxes vascular smooth muscle, reducing vascular tone and arterial pressure, whereas topical lignocaine primarily limits sensory afferent transmission from the airway. The two drugs therefore target different components of the pressor response. The present findings are consistent with the randomized study by Varshney et al., in which NTG spray produced greater attenuation of systolic blood pressure and rate-pressure product than lignocaine.⁶ Kumari et al. also demonstrated that NTG lingual spray attenuated post-intubation blood-pressure increases in a dose-dependent manner.⁷ Gopal and colleagues reported lower SBP and DBP with oral NTG compared with oropharyngeal lignocaine, while Hajian et al. showed that intravenous NTG can prevent increases in SBP, DBP and MAP without a significant heart-rate effect.⁸,¹¹ An important feature of the present study is that the heart-rate response did not differ significantly between groups. This contrasts with some prior reports in which NTG reduced the heart-rate response more than lignocaine, but agrees with other work showing similar chronotropic responses.⁶–⁹ The discrepancy likely reflects differences in anesthetic depth, opioid coadministration, timing of measurement, dose and duration of laryngoscopy. Thus, the present data support a blood-pressure effect rather than a universal reduction in heart rate. The MAP finding is particularly relevant because MAP integrates systolic and diastolic effects and remained significantly lower with NTG at every post-intervention time point. However, the absolute differences were generally modest. Statistical significance should therefore not be equated automatically with clinical superiority in every patient. In high-risk patients, even modest attenuation of a peri-intubation pressure surge may be valuable, but the present study excluded patients with cardiovascular disease and difficult airway, so extrapolation to high-risk populations should be cautious. Oxygenation remained stable in both groups, suggesting that neither spray adversely affected peri-intubation oxygenation within the study conditions. Because the study used standardized anesthetic management and experienced intubators, the stable SpO₂ is reassuring but does not establish superiority for respiratory outcomes. Adverse-event findings provide an important counterbalance to the efficacy results. Headache was significantly more frequent with NTG, occurring in 15% versus 5% of patients. This is pharmacologically plausible because headache is a recognized consequence of nitrate-mediated cerebral and extracranial vasodilation. All reported headaches were described in the thesis as mild enough to be managed conservatively. Sore throat and hematoma did not differ significantly. The lack of a clear reduction in sore throat with lignocaine suggests that postoperative throat discomfort depends on multiple procedural factors beyond topical airway anesthesia. The study has several methodological strengths, including balanced randomization, invasive arterial pressure measurement, repeated time-point assessment, and simultaneous evaluation of efficacy and adverse effects. The principal limitations are the modest single-center sample, restriction to low-risk elective patients, short observation period, absence of a no-treatment control group, and potential variability in laryngoscopy technique and anesthetic depth. In addition, multiple time-point comparisons increase the possibility of type-I error if no correction is applied. The results should therefore be interpreted as hypothesis-supporting rather than definitive for all surgical populations. Overall, the evidence supports NTG spray as a useful option when blood-pressure attenuation is the primary goal during elective intubation, while lignocaine retains value when topical airway anesthesia is desired and avoidance of nitrate-related headache or hypotension is important. Future multicenter studies should standardize dose and timing, include high-risk cardiovascular populations, and use clinically meaningful composite outcomes such as rate-pressure product, myocardial injury and arrhythmia. Strengths and limitations Strengths included randomized allocation, equal group size, invasive arterial pressure monitoring and repeated measurements through two hours. Limitations included the single-center setting, modest sample size, exclusion of high-risk cardiovascular patients and difficult airways, absence of a placebo/control group, short follow-up, and potential variability in laryngoscopy duration and anesthetic depth. Multiple time-point comparisons were reported without evidence of multiplicity adjustment.

Among 80 low-risk elective surgical patients, NTG spray produced more consistent attenuation of invasive blood-pressure responses than 10% lignocaine spray, particularly for MAP, while heart rate and SpO₂ remained comparable. NTG was associated with a higher incidence of headache. The findings support individualized use of NTG when blood-pressure control is the primary objective, with careful attention to contraindications and hemodynamic monitoring. Additional background: mechanisms of the intubation pressor response The cardiovascular response to laryngoscopy is produced by stimulation of mechanosensitive and nociceptive receptors in the oropharynx, hypopharynx and laryngeal structures, with activation of sympathetic pathways and catecholamine release. The response is influenced by laryngoscopy duration, depth of anesthesia, airway anatomy, age, baseline cardiovascular status and the experience of the operator.¹,² A drug that attenuates the response should ideally reduce clinically important blood-pressure and heart-rate surges without producing excessive hypotension, bradycardia or other adverse effects. Lignocaine and nitroglycerin approach this problem differently. Topical lignocaine decreases sensory transmission from the airway and can blunt reflex responses to instrumentation. Its effectiveness depends on concentration, total dose, timing and distribution over the relevant mucosal surfaces. Previous trials have shown that topical lignocaine can reduce but does not completely abolish the pressor response.³ NTG, in contrast, is a nitric-oxide donor that relaxes vascular smooth muscle and reduces systemic vascular tone. Its predictable vasodilator effect makes it attractive when blood-pressure control is the primary objective, but headache and hypotension are recognized limitations.⁵,⁹ Detailed interpretation of blood-pressure findings The most consistent finding in the present study was the lower MAP in the NTG group at every recorded post-intervention interval. MAP is clinically useful because it summarizes the systolic and diastolic components of arterial pressure and is closely related to organ perfusion. The baseline values were statistically comparable, reducing concern that the post-intervention differences simply reflected baseline imbalance. The systolic response was also more favorable with NTG at selected time points. The largest immediate difference was observed at 0 minutes, followed by additional significant differences at 3 minutes, 10 minutes and 2 hours. The absence of significance at some intervening time points is important: the data support a consistent overall direction but not a uniformly significant SBP difference at every measurement. This distinction should be retained in a publication to avoid overstating efficacy. The DBP findings showed significant differences at many time points, although the absolute differences were small. The pattern is compatible with the vasodilatory action of NTG. Comparable results have been reported in randomized studies of NTG spray, including the Varshney trial, in which NTG was more effective than lignocaine for blood-pressure and rate-pressure-product attenuation.⁶ Kumari et al. also found dose-dependent attenuation of the pressor response using NTG lingual spray.⁵ These external findings strengthen the biological plausibility of the present results. Heart rate, oxygenation and safety Heart rate did not differ significantly between groups at any measured time point. This is clinically informative because it indicates that the main advantage of NTG in this study was blood-pressure attenuation rather than chronotropic suppression. Published evidence is mixed: some studies report lower post-intubation heart rates with NTG, while others report similar heart-rate responses.⁶–⁹ Differences in anesthetic depth, premedication, opioid use and the timing of observations may explain this heterogeneity. SpO₂ remained comparable from baseline through two hours, with no clinically relevant desaturation signal. The stability of oxygen saturation is reassuring but should be interpreted in the context of a carefully monitored elective population and standardized airway management. The study was not designed or powered to detect uncommon respiratory complications. Headache was significantly more frequent in the NTG group, 15% versus 5%. This is consistent with nitrate pharmacology and represents the principal tolerability trade-off identified by the study. The absolute number of events was small and the thesis states that symptoms were mild and managed conservatively. Sore throat did not differ significantly, despite the theoretical local anesthetic benefit of lignocaine. This suggests that postoperative throat discomfort is multifactorial and affected by tube size, cuff pressure, duration and technique of airway manipulation. Hematoma rates were low and statistically similar, likely reflecting procedural factors associated with arterial cannulation rather than study-drug effects. Clinical interpretation and comparison with recent evidence The present findings are also consistent with contemporary comparative literature. A 2025 randomized clinical trial comparing intraoral NTG with intraoral lignocaine reported that NTG produced favorable control of blood-pressure responses, although the exact dosing and population differed from the present study.¹⁵ A 2021 randomized trial of intravenous NTG likewise found prevention of increases in systolic, diastolic and mean arterial pressure after intubation without a significant heart-rate effect.⁹ These studies support the concept that NTG can preferentially influence vascular components of the pressor response. At the same time, topical lignocaine remains a rational intervention because it directly reduces airway sensory input and has a long history of use. Recent work comparing different lignocaine delivery routes suggests that efficacy depends strongly on mucosal distribution and administration technique.¹⁶ Thus, the current findings should not be interpreted as demonstrating that lignocaine has no role; rather, within this protocol and selected population, NTG produced more consistent blood-pressure attenuation. The clinical decision should therefore be individualized. NTG may be attractive when a peri-intubation blood-pressure surge is the dominant concern, provided contraindications to nitrates are excluded and the patient is not hypovolemic. Lignocaine may remain useful when topical airway anesthesia and reflex suppression are desired, particularly when avoidance of nitrate-related headache or hypotension is important. Methodological considerations and future research The use of invasive arterial pressure monitoring is a major methodological strength because it provides high-frequency and sensitive measurement of SBP, DBP and MAP. The universal positive Allen test also indicates that the study applied a standardized vascular-access safety assessment. However, invasive monitoring can itself introduce local complications and is not representative of routine monitoring in all elective cases. The study used repeated between-group comparisons at numerous time points. Although each p value was reported as part of the thesis analysis, the manuscript does not introduce a multiplicity correction that was not performed in the original work. Consequently, the repeated significance findings should be considered in the context of potential type-I error. A future trial should predefine a primary hemodynamic endpoint, such as maximum change in MAP or rate-pressure product, and use a repeated-measures model with appropriate adjustment for multiple comparisons. Future research should include larger multicenter randomized trials, patients with controlled cardiovascular disease, standardized laryngoscopy duration, objective documentation of anesthetic depth, and clinically meaningful outcomes such as myocardial injury, arrhythmia, rate-pressure product and recovery quality. Direct comparisons among NTG, lignocaine, dexmedetomidine, beta-blockers and opioid-based strategies may help identify the optimal intervention for specific patient-risk profiles. Expanded clinical discussion The present study provides a clinically useful distinction between attenuation of blood-pressure response and attenuation of heart-rate response. NTG consistently influenced MAP and affected selected SBP and DBP measurements, whereas heart rate remained similar. This suggests that the hemodynamic benefit of NTG in this protocol was predominantly vascular. Such a distinction matters because the desired pharmacologic target may vary by patient: a patient with severe hypertension may benefit particularly from blood-pressure control, whereas another patient may have a more clinically relevant tachycardic response. The magnitude of the observed differences should also be interpreted alongside the clinical context. The absolute MAP differences were generally modest, even when p values were significant. A statistically significant difference is not automatically equivalent to a clinically important difference. The benefit may be more meaningful in patients for whom even brief pressure surges are hazardous, but those patients were excluded from the present study. The appropriate conclusion is therefore that NTG demonstrated superior attenuation of measured blood-pressure parameters in this selected population, not that it prevents cardiovascular complications. The absence of a control group is particularly relevant. Both NTG and lignocaine may attenuate the pressor response relative to untreated laryngoscopy, but the present two-arm design cannot quantify the absolute benefit of either agent. Previous controlled studies provide evidence that both interventions can reduce the response compared with controls.⁵,⁶ A future three-arm trial including placebo would allow estimation of the absolute treatment effect while retaining the direct NTG-versus-lignocaine comparison. The study also used a standardized anesthetic protocol, which is a strength because anesthetic depth strongly influences sympathetic responses. Nevertheless, depth was not objectively measured. Use of bispectral index or another depth-of-anesthesia metric in future research would help determine whether residual differences in anesthetic depth contributed to the observed hemodynamic patterns. Similarly, recording laryngoscopy duration and number of attempts would allow adjustment for airway-manipulation intensity. The adverse-event profile illustrates why efficacy should not be considered in isolation. NTG produced better pressure control but more headache. Lignocaine did not show a statistically significant advantage for sore-throat prevention in this dataset, although topical airway anesthesia remains clinically useful for other indications. The practical choice therefore depends on the endpoint that matters most in a particular patient. A balanced protocol may ultimately combine adequate anesthetic depth, skilled airway technique and a pharmacologic adjunct selected according to cardiovascular risk rather than relying on a single universal drug.

1. Hassan HG, El-Sharkawy TY, Renck H, Mansour G, Fouda A. Hemodynamic and catecholamine responses to laryngoscopy with vs without endotracheal intubation. Acta Anaesthesiol Scand. 1991;35:442-447. 2. Bucx MJ, Van Geel RT, Scheck PA, Stijnen T. Cardiovascular effects of forces applied during laryngoscopy: the importance of tracheal intubation. Anaesthesia. 1992;47:1029-1033. 3. Mostafa SM, Murthy BV, Barrett PJ, McHugh P. Comparison of the effects of topical lignocaine spray applied before or after induction of anaesthesia on the pressor response to direct laryngoscopy and intubation. Eur J Anaesthesiol. 1999;16:7-10. doi:10.1046/j.1365-2346.1999.00410.x. 4. Kindler CH, Schumacher PG, Schneider MC, Urwyler A. Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation. J Clin Anesth. 1996;8:491-496. doi:10.1016/0952-8180(94)00013-T. 5. Kumari I, Naithani U, Dadheech VK, et al. Attenuation of pressor response following intubation: efficacy of nitro-glycerine lingual spray. J Anaesthesiol Clin Pharmacol. 2016;32:69-73. doi:10.4103/0970-9185.175668. 6. Varshney RK, Prasad MK, Garg M. Comparison of nitroglycerin versus lignocaine spray to attenuate haemodynamic changes in elective surgical patients undergoing direct laryngoscopy and endotracheal intubation. Sultan Qaboos Univ Med J. 2019;19:e316-e323. doi:10.18295/squmj.2019.19.04.007. 7. Gopal VM, Sangitha. A comparative study of pressor response to laryngoscopy and intubation with oral spray of nitroglycerine and oropharyngeal spray of lignocaine. Asian J Med Res. 2017;6:24-28. doi:10.36347/sjams.2017.v05i04.047. 8. Pegu B, Dutta S, Pathak DG, Deori KC. Attenuation of stress response to laryngoscopy and intubation: sublingual nitroglycerin spray vs intravenous fentanyl and sublingual nitroglycerin spray. Int J Basic Clin Pharmacol. 2017;6:1414. doi:10.18203/2319-2003.ijbcp20172233. 9. Hajian P, Sharifi S, Nikooseresht M, Moradi A. The effects of intravenous nitroglycerin bolus doses in reducing hemodynamic responses to laryngoscopy and endotracheal intubation. Biomed Res Int. 2021;2021:6694150. doi:10.1155/2021/6694150. 10. Hansel J, Rogers AM, Lewis SR, Cook TM, Smith AF. Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation. Cochrane Database Syst Rev. 2022;4. 11. McAtamney D, O'Hare R, Hughes D, Carabine U, Mirakhur R. Evaluation of remifentanil for control of haemodynamic response to tracheal intubation. Anaesthesia. 1998;53:1223-1227. 12. Misra S, Behera BK, Mitra JK, et al. Effect of preoperative dexmedetomidine nebulization on the hemodynamic response to laryngoscopy and intubation. Korean J Anesthesiol. 2021;74:150-157. 13. Arora S, Kulkarni A, Bhargava AK. Attenuation of hemodynamic response to laryngoscopy and orotracheal intubation using intravenous clonidine. J Anaesthesiol Clin Pharmacol. 2015;31:110-114. 14. Channaiah VB, Kurek NS, Moses R, Chandra SB. Attenuation of hemodynamic response to laryngoscopy and endotracheal intubation with preinduction IV fentanyl versus combination of IV fentanyl and sublingual nitroglycerin spray. Med Arch. 2014;68:339-344. doi:10.5455/medarh.2014.68.339-344. 15. Murugavel K, Balasubramanian K, Botta B, Goda JH. Intraoral nitroglycerine spray versus intraoral lignocaine spray to suppress the haemodynamic response to endotracheal intubation. J Clin Diagn Res. 2025;19:UC32-UC36. doi:10.7860/JCDR/2025/81990.22175. 16. Saeed ZM, Jaafar H, Alburkiebh SH. Effect of nebulized lidocaine and intravenous lidocaine on hemodynamic responses to laryngoscopy and endotracheal intubation. Iran J War Public Health. 2024;16:67-74. 17. Mulimani SM, Talikoti DG, Vastrad VV, Sorganvi VM. Efficacy of bolus dose of esmolol and bolus dose of lignocaine for attenuating the pressor response to laryngoscopy and endotracheal intubation. Anesth Essays Res. 2019;13:292-296. doi:10.4103/aer.AER_31_19.