European Journal of Cardiovascular Medicine

Direct laryngoscopy and endotracheal intubation are known to provoke significant sympathetic stimulation, resulting in transient but marked hemodynamic responses such as tachycardia, hypertension, and increased myocardial oxygen demand [1]. These responses are primarily mediated by catecholamine release due to stimulation of the oropharyngeal and laryngotracheal structures [2]. While healthy individuals usually tolerate these changes well, they can be detrimental in patients with limited cardiovascular reserve, leading to complications such as myocardial ischemia, dysrhythmias, cerebrovascular accidents, and increased intracranial pressure [3,4].

The pressor response to laryngoscopy and intubation typically begins within seconds, peaks within the first minute, and may persist for 5–10 minutes [5]. Attenuation of this response is therefore a critical component of anesthetic management, especially in adult surgical patients. Various pharmacological strategies have been explored to blunt this response, including opioids, vasodilators, calcium channel blockers, beta-adrenergic blockers, and local anesthetics, each with varying efficacy and side-effect profiles [6,7].

Lignocaine, a widely used local anesthetic, has been employed intravenously to suppress airway reflexes and blunt cardiovascular responses during laryngoscopy [8]. However, its efficacy in consistently controlling tachycardia and hypertension remains variable. Esmolol, an ultra-short-acting cardioselective β1-adrenergic blocker, has gained popularity due to its rapid onset, short duration of action, and favorable safety profile, making it suitable for transient sympathetic surges during intubation [9]. Labetalol, a combined α- and β-adrenergic blocker, offers the advantage of reducing both heart rate and blood pressure by decreasing systemic vascular resistance as well as myocardial contractility [10].

Despite multiple studies evaluating these agents individually, direct comparative data on the incidence of adverse hemodynamic events among lignocaine, esmolol, and labetalol during laryngoscopy and endotracheal intubation remain limited, particularly in the Indian population. Moreover, the choice of an ideal agent continues to be debated due to differences in onset time, duration of action, and side-effect profile [11,12].

The present prospective comparative study was therefore designed to evaluate and compare the incidence of adverse hemodynamic events associated with intravenous esmolol, labetalol, and lignocaine administered prior to laryngoscopy in adult patients undergoing elective surgery under general anesthesia. This study aims to identify the most effective and hemodynamically stable agent for attenuation of the pressor response to laryngoscopy and intubation, thereby contributing to safer anesthetic practice

Study Design and Setting

This prospective, randomized, double-blinded comparative study was conducted in the Department of Anaesthesiology at Dharanidhar Medical College and Hospital over a defined study period after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to enrollment.

Study Population

Seventy-five adult patients of either sex, aged 20–60 years, belonging to American Society of Anesthesiologists (ASA) physical status I and II, scheduled for elective surgical procedures under general anesthesia requiring endotracheal intubation were included in the study.

Inclusion Criteria

1. ASA physical status I and II

2. Age between 20 and 60 years

3. Body mass index (BMI) <30 kg/m²

4. Patients willing to provide written informed consent

Exclusion Criteria

1. ASA physical status III or above

2. Pregnant and lactating women

3. History of bronchial asthma, cardiovascular disease, or morbid obesity

4. Patients receiving antihypertensive therapy

5. Known allergy to study drugs

6. Anticipated difficult airway or intubation duration >20 seconds

Randomization and Group Allocation

Patients were randomly allocated into three equal groups (n = 25 each) using a computer-generated randomization table:

Group LG (Lignocaine group): Intravenous lignocaine hydrochloride 1 mg/kg

Group ES (Esmolol group): Intravenous esmolol hydrochloride 0.5 mg/kg

Group LB (Labetalol group): Intravenous labetalol hydrochloride 0.25 mg/kg

All study drugs were diluted to 10 mL with normal saline and administered intravenously over 30 seconds, 2 minutes prior to laryngoscopy. Both the patient and the observer recording hemodynamic variables were blinded to group allocation.

Pre-anaesthetic Preparation

All patients underwent detailed pre-anaesthetic evaluation including airway assessment, cardiovascular and respiratory system examination, and routine laboratory investigations. Patients were kept nil per oral for 8 hours prior to surgery. On the night before surgery, oral alprazolam 0.25 mg and ranitidine 150 mg were administered.

Anaesthetic Technique

Upon arrival in the operating room, an 18-gauge intravenous cannula was secured and Ringer’s lactate infusion was started. Standard non-invasive monitoring including electrocardiography, pulse oximetry, and non-invasive blood pressure was applied. Baseline heart rate and blood pressure parameters were recorded.

Premedication included intravenous glycopyrrolate, midazolam (0.05 mg/kg), and nalbuphine (0.2 mg/kg), administered 10 minutes before the study drug to minimize drug interaction effects. Patients were pre-oxygenated with 100% oxygen for 3 minutes. Induction was carried out using thiopentone sodium (5 mg/kg) followed by vecuronium bromide (0.1 mg/kg). Laryngoscopy was performed using a Macintosh laryngoscope, and endotracheal intubation was achieved within 20 seconds.

Anesthesia was maintained with nitrous oxide (60%), oxygen (40%), isoflurane (1 MAC), and intermittent doses of vecuronium bromide.

Hemodynamic Monitoring

Hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and rate pressure product (RPP) were recorded at baseline, immediately before intubation, and at 1, 3, 5, 7, and 10 minutes after intubation.

Assessment of Adverse Hemodynamic Events

Adverse events were defined as:

• Hypotension: SBP <90 mmHg or >30% decrease from baseline

• Hypertension: SBP >150 mmHg or >30% increase from baseline

• Tachycardia: HR >25% increase from baseline

• Bradycardia: HR <60 beats/min

• Any dysrhythmia

Patients were monitored postoperatively for two hours in the post-anesthesia care unit for adverse effects such as nausea, vomiting, hypotension, bradycardia, and sedation.

Statistical Analysis

Data were analyzed using SPSS version 22.0. Continuous variables were expressed as mean ± standard deviation and categorical variables as numbers and percentages. Intergroup comparisons were performed using ANOVA followed by post-hoc Tukey test. Intragroup comparisons were done using paired t-test. A p-value <0.05 was considered statistically significant and <0.001 highly significant.

A total of 75 patients were included in the study and randomly allocated into three equal groups (n = 25 each): Lignocaine (LG), Esmolol (ES), and Labetalol (LB). All patients completed the study, and data from all subjects were analyzed.

Demographic Characteristics

The three groups were comparable with respect to age, gender distribution, and body weight. No statistically significant difference was observed among the groups (p > 0.05).

Table 1: Demographic profile of patients

Heart Rate (HR)

Baseline heart rate and heart rate after administration of study drugs were comparable among the three groups (p > 0.05). At laryngoscopy and intubation, a significant increase in heart rate was observed in all groups. However, the increase was significantly lower in the Labetalol group, followed by the Esmolol group, compared to the Lignocaine group (p < 0.001).

Table 2: Comparison of heart rate (beats/min) at different time intervals

Figure 1: Line graph showing changes in heart rate following laryngoscopy and intubation in the three groups.

Systolic Blood Pressure (SBP)

All groups showed a rise in SBP at intubation. The increase was maximum in the Lignocaine group and minimum in the Labetalol group. SBP values were significantly lower in the Labetalol group compared to Esmolol and Lignocaine at most time intervals (p < 0.001).

Table 3: Comparison of systolic blood pressure (mmHg)

Diastolic Blood Pressure (DBP)

DBP increased significantly at intubation in all groups. The rise was significantly attenuated in both Esmolol and Labetalol groups compared to Lignocaine at intubation and at 1 minute post-intubation (p < 0.05). Thereafter, differences were statistically insignificant.

Table 4: Comparison of diastolic blood pressure (mmHg)

Mean Arterial Pressure (MAP)

MAP increased significantly following intubation in all groups. Labetalol demonstrated superior attenuation of MAP response compared to Esmolol and Lignocaine at intubation and early post-intubation periods.

Table 5: Comparison of mean arterial pressure (mmHg)

Rate Pressure Product (RPP)

RPP increased significantly at laryngoscopy and intubation in all groups. The increase was markedly higher in the Lignocaine group. Labetalol showed the greatest reduction in RPP throughout the observation period.

Table 6: Comparison of rate pressure product (mmHg/min)

Adverse Hemodynamic Events

The incidence of tachycardia and hypertension was highest in the Lignocaine group. Labetalol was associated with the least incidence of adverse hemodynamic events. No serious adverse effects such as severe hypotension, bradycardia, or dysrhythmias were observed.

Attenuation of the hemodynamic response to laryngoscopy and endotracheal intubation remains a key objective in anesthetic practice, particularly to prevent adverse cardiovascular events. The present prospective comparative study evaluated the incidence of adverse hemodynamic events following administration of intravenous lignocaine, esmolol, and labetalol in adult patients undergoing laryngoscopy and intubation.

In the present study, baseline demographic variables and pre-induction hemodynamic parameters were comparable among the three groups, ensuring uniformity and minimizing confounding factors. This finding is consistent with previous pharmacological and clinical anesthesia literature emphasizing the importance of comparable baseline characteristics in studies assessing cardiovascular responses to airway manipulation [15].

The results demonstrated that all three agents attenuated the pressor response to some extent; however, labetalol was most effective, followed by esmolol, while lignocaine was least effective in controlling heart rate and blood pressure responses. Labetalol produced a significantly lower rise in heart rate, systolic blood pressure, mean arterial pressure, and rate pressure product at laryngoscopy and during the early post-intubation period. These findings can be attributed to the combined α- and β-adrenergic blocking properties of labetalol, which reduce both systemic vascular resistance and myocardial contractility [15,16].

Esmolol, a cardioselective β1-blocker with rapid onset and short duration of action, demonstrated effective attenuation of tachycardia and moderate control of blood pressure. This is in agreement with studies reporting esmolol’s efficacy in suppressing sympathetic surges associated with airway instrumentation, particularly heart rate responses, while maintaining hemodynamic stability [16,17]. However, the lack of α-blocking activity may explain its relatively lesser effect on systolic blood pressure compared to labetalol.

Intravenous lignocaine showed limited efficacy in attenuating the cardiovascular response to laryngoscopy and intubation. Although lignocaine is known to blunt airway reflexes and suppress cough, its role in consistently controlling sympathetic cardiovascular responses has been shown to be variable, as also observed in previous clinical pharmacology studies [18]. The significantly higher heart rate, blood pressure, and rate pressure product observed in the lignocaine group in the present study further support these observations.

Rate pressure product, an indirect indicator of myocardial oxygen consumption, was significantly lower in the labetalol group throughout the observation period. This suggests superior myocardial protection with labetalol during the stress of laryngoscopy and intubation, a finding supported by pharmacological principles and previous comparative studies [19].

Importantly, none of the study drugs were associated with serious adverse effects such as severe hypotension, bradycardia, or dysrhythmias. The incidence of adverse hemodynamic events was lowest in the labetalol group, highlighting its favorable safety profile when used in appropriate doses [20].

The present prospective comparative study demonstrates that laryngoscopy and endotracheal intubation are associated with significant hemodynamic responses in adult patients undergoing general anesthesia. Among the three agents evaluated, intravenous labetalol was the most effective in attenuating adverse hemodynamic events, providing superior control of heart rate, systolic blood pressure, mean arterial pressure, and rate pressure product during laryngoscopy and the early post-intubation period. Esmolol showed moderate efficacy, particularly in controlling tachycardia, while intravenous lignocaine was least effective in blunting the cardiovascular response.

All three drugs were well tolerated, with no serious adverse effects observed, indicating their safety when administered in appropriate doses. The combined α- and β-adrenergic blocking action of labetalol offers an added advantage in achieving better hemodynamic stability during airway manipulation.

Based on the findings of this study, intravenous labetalol can be considered a preferred agent for attenuation of the pressor response to laryngoscopy and endotracheal intubation in adult patients with normal cardiovascular function. Further studies involving high-risk patients and larger sample sizes are recommended to validate these findings and expand their clinical applicability.

1. Reid, L. C., and D. E. Brace. “Irritation of the Respiratory Tract and Its Reflex Effect upon Heart Rate.” Anesthesiology, vol. 1, 1940, pp. 399–405.
2. King, B. D., et al. “Reflex Circulatory Responses to Direct Laryngoscopy and Tracheal Intubation Performed during General Anesthesia.” Anesthesiology, vol. 12, 1951, pp. 556–566.
3. Prys-Roberts, C., et al. “Studies of Anaesthesia in Relation to Hypertension: Haemodynamic Consequences of Induction and Endotracheal Intubation.” British Journal of Anaesthesia, vol. 43, 1971, pp. 531–547.
4. Fox, E. J., et al. “Complications Related to the Pressor Response to Endotracheal Intubation.” Anesthesiology, vol. 47, 1977, pp. 524–525.
5. Stoelting, R. K. “Circulatory Changes during Direct Laryngoscopy and Tracheal Intubation—Influence of Duration of Laryngoscopy with or without Lidocaine.” Anesthesiology, vol. 47, 1977, pp. 381–384.
6. Kovac, A. L. “Controlling the Hemodynamic Response to Laryngoscopy and Endotracheal Intubation.” Journal of Clinical Anesthesia, vol. 8, 1996, pp. 63–79.
7. Helfman, S. M., et al. “Which Drug Prevents Tachycardia and Hypertension Associated with Tracheal Intubation: Lidocaine, Fentanyl, or Esmolol?” Anesthesia & Analgesia, vol. 72, 1991, pp. 482–486.
8. Abou-Madi, M. N., et al. “Cardiovascular Reactions to Laryngoscopy and Tracheal Intubation Following Small and Large Intravenous Doses of Lidocaine.” Canadian Anaesthetists’ Society Journal, vol. 24, 1977, pp. 12–19.
9. Miller, D. R., et al. “Bolus Administration of Esmolol for Controlling the Hemodynamic Response to Laryngoscopy and Intubation.” Canadian Journal of Anaesthesia, vol. 38, 1991, pp. 849–858.
10. Kautto, U. M. “Attenuation of the Circulatory Response to Laryngoscopy and Intubation by Labetalol.” British Journal of Anaesthesia, vol. 54, 1982, pp. 213–216.
11. Singh, S. P., et al. “Comparison of Esmolol and Labetalol, in Low Doses, for Attenuation of Sympathomimetic Response to Laryngoscopy and Intubation.” Saudi Journal of Anaesthesia, vol. 4, 2010, pp. 163–168.
12. Gupta, S., and P. Tank. “A Comparative Study of Efficacy of Esmolol and Lignocaine for Attenuation of Cardiovascular Stress Response to Laryngoscopy and Endotracheal Intubation.” Indian Journal of Anaesthesia, vol. 55, 2011, pp. 521–525.
13. Sharma, S., et al. “Comparison of Labetalol and Esmolol for Attenuation of Cardiovascular Response to Laryngoscopy and Tracheal Intubation.” Journal of Anaesthesiology Clinical Pharmacology, vol. 32, 2016, pp. 78–83.
14. Morgan, George E., Jr., et al. Clinical Anesthesiology. 5th ed., McGraw-Hill Education, 2013, pp. 144–147.
15. Stoelting, Robert K., and Stephen C. Hillier. Pharmacology and Physiology in Anesthetic Practice. 4th ed., Lippincott Williams & Wilkins, 2006, pp. 329–335.
16. Miller, D. R., et al. “Bolus Administration of Esmolol for Controlling the Hemodynamic Response to Laryngoscopy and Intubation.” Canadian Journal of Anaesthesia, vol. 38, no. 7, 1991, pp. 849–858.
17. Singh, S. P., et al. “Comparison of Esmolol and Labetalol, in Low Doses, for Attenuation of Sympathomimetic Response to Laryngoscopy and Intubation.” Saudi Journal of Anaesthesia, vol. 4, no. 3, 2010, pp. 163–168.
18. Helfman, S. M., et al. “Which Drug Prevents Tachycardia and Hypertension Associated with Tracheal Intubation: Lidocaine, Fentanyl, or Esmolol?” Anesthesia & Analgesia, vol. 72, no. 4, 1991, pp. 482–486.
19. Kautto, U. M. “Attenuation of the Circulatory Response to Laryngoscopy and Intubation by Labetalol.” British Journal of Anaesthesia, vol. 54, no. 2, 1982, pp. 213–216.
20. Sharma, S., et al. “Comparison of Labetalol and Esmolol for Attenuation of Cardiovascular Response to Laryngoscopy and Tracheal Intubation.” Journal of Anaesthesiology Clinical Pharmacology, vol. 32, no. 1, 2016, pp. 78–83.