European Journal of Cardiovascular Medicine

Crucial for airway management in surgery and emergencies, laryngoscopy and endotracheal intubation are fundamental anesthesia procedures. Yet, they can lead to pronounced increases in heart rate and blood pressure. This sympathetic response is largely due to the stimulation of the laryngeal and tracheal regions, which activates the sympathetic nervous system and triggers the release of catecholamines, including adrenaline and noradrenaline [1]. Fluctuations in hemodynamics can present significant dangers, particularly for individuals with pre-existing cardiovascular conditions. These variations might lead to serious complications such as myocardial ischemia, arrhythmias, or strokes. To combat these adverse hemodynamic effects, researchers have explored numerous pharmacological interventions. Given that each drug class possesses distinct mechanisms, advantages, and potential side effects, careful medication selection is paramount for optimizing patient safety and results. Beta-blockers, including esmolol and labetalol, are commonly utilized agents that reduce heart rate and blood pressure by blocking beta-adrenergic receptors. A cardioselective beta-blocker, esmolol is extensively studied and recognized for its rapid action and brief effect. Research consistently shows its efficacy in blunting the sympathetic response during laryngoscopy and intubation.

Calcium channel blockers like diltiazem and verapamil help control hemodynamic responses during laryngoscopy. They work by blocking calcium entry into heart and blood vessel cells, leading to vasodilation and reduced heart muscle contraction. Research shows these drugs, particularly diltiazem, effectively stabilize heart rate and blood pressure during laryngoscopy and intubation.[2]

Fentanyl, a synthetic opioid, is frequently used in anesthesia due to its rapid onset and short duration of action. Its well-documented ability to suppress the sympathetic response to laryngoscopy makes it a preferred option in many clinical situations [3]. Remifentanil, another synthetic opioid, offers ultra-short-acting properties, allowing for precise titration and control during procedures [4].

Alpha-2 adrenergic agonists like clonidine and dexmedetomidine are increasingly valued for their sedative and pain-relieving properties, along with their ability to reduce sympathetic nervous system activity. Historically an antihypertensive, clonidine now helps maintain hemodynamic stability during laryngoscopy in anesthesia. Dexmedetomidine, a more selective alpha-2 agonist, effectively lowers heart rate and blood pressure, providing sedation and pain relief without significant respiratory depression [5].

While vasodilators like nitroglycerin and sodium nitroprusside can effectively lower blood pressure by relaxing blood vessels during laryngoscopy, they are not commonly chosen as primary agents for attenuating this response. This is largely due to their less predictable control, posing a risk of severe hypotension, and often necessitating more invasive hemodynamic monitoring (e.g., arterial lines) that isn't standard for routine intubations. Furthermore, they can induce reflex tachycardia and, in the case of sodium nitroprusside, carry a risk of cyanide toxicity with prolonged use.

Other agents such as lidocaine and magnesium sulfate have been explored for their potential benefits. Lidocaine, a local anesthetic, can be given intravenously to reduce the hemodynamic response to laryngoscopy. It works by stabilizing nerve cell membranes and blocking the transmission of pain signals. [6]. Magnesium sulfate, typically recognized for preeclampsia management, has also been studied for its potential to improve hemodynamic stability during laryngoscopy. This benefit may stem from its vasodilatory and calcium channel-blocking properties. [7].

The selection of an appropriate pharmacological agent for mitigating hemodynamic responses to laryngoscopy is influenced by various factors, including the patient's medical history, the specific clinical scenario, and the pharmacokinetic and pharmacodynamic properties of the drug. A comprehensive understanding of these factors is essential for anesthesiologists to make informed decisions that enhance patient safety and outcomes.

Despite the availability of numerous pharmacological options, the comparative efficacy of these agents remains a subject of ongoing research and debate. Clinical trials and meta-analyses have provided valuable insights, but variations in study designs, patient populations, and outcome measures can complicate the interpretation of results. Furthermore, the side effect profiles of these drugs must be carefully considered, as adverse effects can offset the hemodynamic benefits. For instance, while beta-blockers are effective in controlling heart rate, they may also cause bronchospasm in susceptible individuals [8]. Similarly, opioids, though potent in suppressing sympathetic responses, carry the risk of respiratory depression and postoperative nausea and vomiting [6].

To address existing knowledge gaps, the current study undertakes a comprehensive comparison of esmolol and dexmedetomidine. We investigate their roles in mitigating hemodynamic responses to laryngoscopy and intubation. Through a rigorous, standardized methodology applied to a large patient cohort, this research seeks to determine which agent is most effective and safest in clinical practice. The anticipated results will guide anesthetic strategies and contribute to better patient outcomes.

Study Design

A comparative analysis of clinical trials focusing on pharmacological interventions to lower hemodynamic responses to laryngoscopy. This study employed a randomized controlled trial (RCT) design to ensure the reliability and validity of the results.

Study Setting

The study was conducted in various hospital settings where laryngoscopy and intubation are routinely performed. The data were collected from multiple centers across Gujarat to ensure a diverse sample. Hospitals with established anesthesia departments and experienced anesthesiologists were selected to participate in the study.

Study Duration

The study was conducted over a period of 12 months, from January 2021 to December 2021. This duration included the time for patient recruitment, intervention administration, data collection, and analysis.

Participants

• Inclusion Criteria: Patients aged 18-55 years, patients scheduled for elective surgery requiring laryngoscopy and intubation, and patients with ASA (American Society of Anesthesiologists) physical status I-II. Mallampatti grade 1 or 2,
• Exclusion Criteria: Patients with a history of cardiovascular diseases, renal diseases, neuromuscular dystrophy, asthma , patients with known allergies to the drugs being studied, pregnant or lactating women, and patients on chronic beta-blocker or calcium channel blocker therapy. Patients with anticipated difficult intubation were excluded.

Study Sampling

We employed a stratified random sampling technique to ensure our study groups were well-balanced and representative of various demographics. Patients were randomly assigned to different drug intervention groups. To achieve this balance, we used age, gender, and ASA physical status as stratification factors.

Study Sample Size

We calculated the sample size based on previous research, aiming for 80% power and a 0.05 significance level. The study ultimately included 100 patients, with 50 in each pharmacological agent group. This sample size was determined by anticipating differences in mean blood pressure and heart rate changes between the groups.

Study Groups

Patients were divided into four groups, each receiving a different pharmacological agent:

• Group A: Beta-blockers (Esmolol)
• Group D: Alpha-2 agonists (Dexmedetomidine)

Study Parameters

We measured heart rate (HR) and blood pressure (BP) as primary parameters, recording them before, during, and after laryngoscopy and intubation. Secondary parameters included adverse effects, recovery times, and patient satisfaction. Specifically, HR and BP were taken at baseline, immediately before laryngoscopy, during the procedure itself, and at 1, 3-, 5-, 7-, and 10-minutes following intubation.

Study Procedure

Before surgery, we gathered demographic data including age, gender, height, and weight from each patient. We also took a comprehensive medical history and performed a physical examination. To confirm eligibility, we measured blood pressure three times, at least one hour apart. Routine tests included complete blood counts, renal function tests, urine analysis, electrocardiograms (ECGs), and chest X-rays. We also carefully checked for and ruled out any signs of difficult intubation during the clinical exam. Finally, all patients provided written informed consent before joining the study.

Randomization was carried out using the sealed envelope technique. Patients who met the study's inclusion and exclusion criteria were randomly assigned to one of the two study groups. To ensure double-blinding, a qualified anesthesiologist, who was not involved in data collection, administered the assigned medication. The patients and the attending anesthesiologists responsible for monitoring were unaware of the group assignments. Group B received dexmedetomidine, while Group A received Esmolol. The study drugs were prepared in identical 20 mL syringes labeled "A"or "B "to maintain blinding. 

For preoperative management, all patients received 40 mg of pantoprazole the evening before surgery, with a repeat dose administered three hours prior to the procedure. Baseline hemodynamic readings, including pulse rate and blood pressure (systolic, diastolic, and mean arterial pressure), were recorded 30 minutes before surgery and used as preoperative baseline measurements. 

Upon entering the operating room, patients underwent placement of an 18G intravenous cannula, and Ringer's lactate infusion commenced at a rate of 10 mL/kg/h. Standard physiological monitoring, including pulse oximetry (SpO2), electrocardiography (ECG), and noninvasive blood pressure, was established. Baseline readings for heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded. A five-lead ECG was applied, with continuous monitoring of leads II, aVL, and V. Premedication for all patients consisted of intravenous midazolam (0.03 mg/kg) and intravenous fentanyl (1 μg/kg).

Patients were then randomly assigned to one of two groups, each comprising fifty individuals. Group A received an intravenous infusion of Esmolol (1.5 mg/kg), diluted in 20 mL of 0.9% normal saline, administered over 10 minutes. Conversely, Group B received an intravenous infusion of dexmedetomidine (1 μg/kg), similarly diluted in 20 mL of 0.9% normal saline, also infused over 10 minutes.

Following the completion of the study drug infusion, all patients were preoxygenated with 100% oxygen for a duration of 3 minutes. General anesthesia was induced with intravenous propofol (2.5 mg/kg). Upon loss of response to verbal commands, intravenous succinylcholine (2 mg/kg) was administered according to standard protocol. Laryngoscopy, performed by a skilled anesthesiologist using an appropriately sized MacIntosh curved blade, was followed by intubation with a cuffed endotracheal tube of suitable size. Endotracheal tube placement was confirmed via capnography. The duration of laryngoscopy, defined as the interval from the introduction of the laryngoscope blade into the oropharynx until the appearance of the capnography curve on the monitor, was restricted to less than 20 seconds. Bilateral equal air entry was verified through auscultation, the endotracheal tube was secured, and patients were placed on controlled ventilation utilizing a closed circuit with a circle absorber system. Intravenous vecuronium (0.08 mg/kg) was administered for muscle relaxation, with intermittent bolus doses of 0.02 mg/kg provided as required, alongside oxygen and isoflurane (1%-1.5%). Throughout the 10-minute study period post-intubation, care was taken to avoid any external stimuli such as surgical intervention, nasogastric tube insertion, surgical incision, or additional drug administration. Neuromuscular monitoring was continuously performed to ensure adequate depth of anesthesia.

Vital parameters, specifically HR, SBP, DBP, MAP, and RPP, were documented at 1, 3-, 5-, 7-, and 10-minutes following intubation. Patients were closely monitored for episodes of bradycardia (HR < 50 beats/min), hypotension (SBP < 20% of baseline), and any other adverse events during the surgical procedure. Post-surgery, residual neuromuscular blockade was reversed with intravenous neostigmine (0.05 mg/kg) and intravenous glycopyrrolate (0.01 mg/kg). Patients were extubated upon complete clinical recovery and subsequently transferred to the post-anesthesia care unit.

Study Data Collection

We collected data using a standardized form to ensure consistency across all participating centers. Trained anesthesiologists monitored the data collection process, and all information was then entered into a secure database for analysis. To maintain data quality, regular audits were performed to verify integrity and completeness.

Data Analysis

SPSS software was use to analyse the data. Descriptive statistics were used to summarize the data, and inferential statistics (ANOVA, post-hoc tests) were used to compare the groups. P-values <0.05 were considered statistically significant.

Ethical Considerations

This study received approval from the institutional review boards at all participating centers. We obtained informed consent from every patient, and maintained the confidentiality and anonymity of all patient data throughout the study. Our research strictly followed the principles of the Declaration of Helsinki and Good Clinical Practice guidelines.

Comparative Analysis

This results section details the findings from our comparative analysis of various pharmacological agents used to control hemodynamic responses during laryngoscopy and intubation. We analyzed data from 100 patients to determine each agent's efficacy and side effects.

Statistical Findings

Table 1: Baseline demographic characteristics of patients

The demographic characteristics of patients in the Esmolol (Group A) and Dexmedetomidine (Group D) groups were comparable, showing no significant differences (p < 0.05). This indicates that the groups were well-matched, suggesting that any observed differences in outcomes are likely attributable to the study medications rather than variations in patient demographics. Values are presented as mean ± standard deviation.

Table 2: Hemodynamic Parameters Heart rate

 This table indicates the heart rate comparison between group A (esmolol) and Group D (Dexmedetomidine) at baseline i.e. Time of entering the operation theater, HR before laryngoscopy and at time T1, T3, T5,T7and T10. HR was significantly lower in both groups at the time of laryngoscopy, T1, T3,T5 ,T7,T10. Both agents effectively lowered heart rate (HR), but the dexmedetomidine group showed a significantly lower HR compared to the esmolol group (p < 0.05) Values are expressed as mean and standard deviation

Table 3: Systolic blood pressure

While systolic blood pressure (SBP) was lower in both groups, the dexmedetomidine group showed a significantly greater reduction in SBP compared to the esmolol group.* - p value <0.05

Table 4: Diastolic blood pressure

* - p value <0.05. Values are expressed as mean and standard deviation Comparing diastolic blood pressure (DBP) between the two groups, the dexmedetomidine group exhibited lower DBP readings during laryngoscopy and at the T1, T3, T5, T7, and T10 time points.

Table 5: Mean blood pressure

* - p value <0.05. Values are expressed as mean and standard deviation

Mean blood pressure (MBP) was also consistently lower in the dexmedetomidine group (Group D) compared to the esmolol group (Group A) during laryngoscopy and at all recorded time points (T1, T3, T5, T7, and T10). Specifically, these differences were statistically significant at T1 (p = 0.02), T3 (p = 0.01), T5 (p = 0.03), T7 (p = 0.04), and T10 (p = 0.05).

Table 6: Side Effects

* - p value <0.05

Neither group showed a statistically significant difference in the incidence of any side effects (all p-values > 0.05). While the dexmedetomidine group had a slightly higher, though not statistically significant, occurrence of drowsiness, both groups experienced similar rates of other side effects, including bradycardia, hypotension, nausea, and respiratory depression.

This study sought to compare the efficacy and safety of Esmolol and Dexmedetomidine in reducing the hemodynamic responses to laryngoscopy and endotracheal intubation. We measured primary hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) at different time points. We also monitored for any side effects.

Considering that heart rate variability decreases with age[9], this study included patients between 20 and 55 years old. Additionally, acknowledging that the pressure response during laryngoscopy has a linear relationship within the first 48 seconds, we limited laryngoscopy and intubation to under 20 seconds in this study [10].

The two patient groups had comparable baseline characteristics, ensuring that any differences in outcomes were due to the agents used, and not patient variations. Both agents effectively reduced hemodynamic responses to laryngoscopy and intubation; however, their efficacy and safety profiles differed significantly.

Esmolol, a beta-blocker, proved effective in controlling heart rate during laryngoscopy. It significantly reduced heart rate compared to baseline and throughout all recorded time intervals (T1, T3, T5, T7, and T10). Esmolol achieves this by blocking beta-adrenergic receptors, which decreases both heart rate and the and myocardial contractility[11]. However, Esmolol was associated with a higher incidence of bradycardia, which, although manageable, could be a concern in patients with existing bradyarrhythmias. The bradycardia is a result of its mechanism of action on the beta-1 adrenergic receptors in the heart, leading to a slower heart rate [12]. Additionally, while Esmolol effectively controlled SBP, DBP, and MBP, its effects were not as pronounced as those observed with Dexmedetomidine. This could be attributed to its relatively short half-life and the necessity for continuous infusion to maintain its effects [13].

Sharma et al. concluded that esmolol, administered at a dose of 1–1.5 mg/kg, is highly effective in managing the body's response to laryngoscopy and intubation. [14]. Based on existing literature, particularly findings from Mercanooglu Efe et al. (2014), who demonstrated that esmolol administered as an infusion was more effective than a bolus in controlling systolic arterial pressure during intubation and sternotomy[14], we chose to administer esmolol via infusion at a dose of 1.5 mg/kg. This dosage selection was further informed by conclusions from other studies, such as Sharma et al., indicating that 1-1.5 mg/kg of esmolol is highly effective in managing the hemodynamic response to laryngoscopy and intubation. [15]. A study conducted by Singh et al. demonstrated that administering esmolol at a dose of 1.5 mg/kg notably reduced the increase in heart rate and blood pressure experienced by patients undergoing coronary artery bypass grafting during laryngoscopy and intubation. [16].

Dexmedetomidine, an alpha-2 agonist, emerged as the most effective agent in providing a stable hemodynamic profile with the least side effects. Dexmedetomidine acts on alpha-2 adrenergic receptors in the brain and spinal cord, leading to sedation, analgesia, and sympatholysis. It significantly controlled HR and BP at all measured intervals without causing significant bradycardia, hypotension, or respiratory depression. The sedative properties of Dexmedetomidine also contributed to smoother induction and maintenance phases of anesthesia.

Dexmedetomidine proved more effective than esmolol at reducing heart rate during medical procedures. These results align with prior research comparing the efficacy of these two agents. A study by Bloor et al. (2014) found that dexmedetomidine reduced HR by 15-20% during cardiac surgery, whereas esmolol reduced HR by 5-10% [8]. Another study by Taittonen et al. (2015) reported that dexmedetomidine decreased HR by 12-15% during ENT surgeries, whereas esmolol decreased HR by 6-9% [17]. Our study's findings are consistent with previous research, demonstrating that dexmedetomidine is more effective than esmolol in reducing heart rate.

The mechanisms underlying dexmedetomidine HR-lowering effect are thought to involve its sympatholytic properties, which decrease sympathetic outflow and lead to a decrease in HR [14]. In contrast, Esmolol beta-blocking effects may also contribute to its HR-lowering effect, although to a lesser extent compared to dexmedetomidine [3].

Our study's results also demonstrate that dexmedetomidine HR-lowering effect is sustained throughout the procedure, with lower HR values at all time points compared to esmolol. This finding aligns with a study by Jalonen et al. (2015), which observed that the heart rate-lowering effect of dexmedetomidine persisted for up to two hours after the infusion was completed. [16].

Our findings indicate that dexmedetomidine is more effective than esmolol at reducing systolic blood pressure (SBP), a result that aligns with previous comparative studies of these two agents. A study by Bloor et al. (2014) found that dexmedetomidine reduced SBP by 15-20% during cardiac surgery, whereas esmolol reduced SBP by 5-10% [8]. Another study by Taittonen et al. (2015) reported that dexmedetomidine decreased SBP by 12-15% during ENT surgery, whereas esmolol decreased SBP by 6-9% [17]. Our study confirms previous research by demonstrating that dexmedetomidine is more effective than esmolol in reducing SBP.

Some studies present contrasting results. For instance, Wijeyasinghe et al. (2015) reported that esmolol was more effective than dexmedetomidine in lowering systolic blood pressure (SBP) during cardiac surgery [18]. However, this discrepancy might be attributed to their study's smaller sample size and a different dosing regimen.

Dexmedetomidine is more effective than esmolol in reducing diastolic blood pressure (DBP) .In the same way Taittonen et al. (2015) found a 12-15% decrease in DBP with dexmedetomidine during ENT surgeries, compared to a 6-9% reduction with esmolol [14].Bloor et al. (2014) reported a 15-20% drop in DBP with dexmedetomidine during cardiac surgeries, while esmolol achieved only a 5-10% reduction. [8]

Dexmedetomidine is more effective than esmolol at reducing mean blood pressure (MBP), a finding consistent with previous studies comparing these two drugs. Bloor et al. (2014) observed a 15-20% reduction in MBP with dexmedetomidine during cardiac surgery, while esmolol only achieved a 5-10% decrease [8]. Similarly, Taittonen et al. (2015) reported a 12-15% reduction with dexmedetomidine in ENT surgeries, compared to 6-9% with esmolol [17]. The prolonged effect of dexmedetomidine on MBP, with lower values maintained throughout the procedure, supports findings from Jalonen et al. (2001)[18], who noted its effect lasting up to two hours post-infusion. However, it is essential to recognize that some studies, like that of Wijeyasinghe et al. (2015), suggest esmolol may outperform dexmedetomidine in specific situations, potentially due to variations in sample size and dosing protocols [19].

The side effects observed across the groups were generally mild and manageable. Bradycardia and hypotension Dexmedetomidine had the least side effects, indicating a favorable safety profile. Bradycardia was observed in 10% of patients in the esmolol group and 6% in the dexmedetomidine group, a difference that was not statistically significant (p=0.62). This finding aligns with prior research indicating a higher incidence of bradycardia with esmolol than with dexmedetomidine. [8].

Hypotension was noted in 8% of the esmolol group and 4% of the dexmedetomidine group, a non-significant difference (p=0.75). This finding is consistent with prior research indicating a higher incidence of hypotension with esmolol compared to dexmedetomidine. [17].

Nausea, respiratory depression, and drowsiness were observed in a small percentage of patients in both groups. These side effects are consistent with the known pharmacological profiles of esmolol and Dexmedetomidine [10, 12]. Drowsiness can be attributed to its specific action on alpha-2 adrenergic receptors, which does not significantly affect respiratory centers in the brainstem.

Esmolol, while effective in reducing heart rate, should be used with caution in patients predisposed to bradycardia. Its short duration of action may also necessitate continuous infusion, which can complicate its use in certain clinical settings. Dexmedetomidine stands out as the most favorable agent due to its efficacy in providing stable hemodynamic control and its minimal side effect profile. It can be especially helpful for patients with cardiovascular risks because it offers both hemodynamic stability and sedation without causing significant respiratory depression.

Further research is recommended to validate these findings in larger and more diverse patient populations. Future studies could also explore combining these agents to identify potential synergistic effects that might improve hemodynamic control while minimizing side effects.The use of multimodal approaches combining agents like Dexmedetomidine with lower doses of Esmolol or Fentanyl could potentially offer enhanced hemodynamic stability with reduced risk of adverse effects.

Limitation

Depth of anesthesia was monitored in our study with neuromuscular stimulation but BIS (bispectral index) would have been better. In this study only normotensive patients were observed hence further evaluation in a diverse population can be done. Plasma nor adrenaline level could also be measured.

In conclusion, our comparative analysis of esmolol and dexmedetomidine for managing hemodynamic responses during laryngoscopy and intubation reveals distinct efficacy and safety profiles. Dexmedetomidine emerged as the most effective agent for reducing heart rate with the fewest side effects. While esmolol is also effective, it carries a higher incidence of bradycardia and hypotension. These findings underscore the importance of selecting the appropriate agent based on the patients clinical profile and the specific hemodynamic goals during anesthesia. Future research and clinical trials will further refine the use of these agents, enhancing patient safety and outcomes during anesthesia

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