Endotracheal intubation, though essential for airway management during general anesthesia, is associated with significant hemodynamic perturbations due to intense sympathetic stimulation. Laryngoscopy and tracheal tube placement activate glossopharyngeal and vagal afferents, provoking catecholamine release that manifests as tachycardia and hypertension. While transient in healthy patients, this pressor response can precipitate myocardial ischemia, arrhythmias or cerebrovascular complications in high-risk individuals, making its attenuation a critical anesthetic goal. [1–4] Various non-pharmacological and pharmacological measures have been explored to blunt this sympathetic surge. Non-pharmacological strategies such as minimizing laryngoscopy duration and using supraglottic airway devices have limited applicability. Pharmacological agents including opioids, beta-blockers, calcium channel blockers, vasodilators and lidocaine have demonstrated varying degrees of efficacy, but none has emerged as an ideal option due to inconsistent results, side-effects or dosing limitations. [5–9]

Alpha-2 adrenergic agonists have gained prominence in recent years for their ability to attenuate sympathetic responses, reduce anesthetic and opioid requirements and provide perioperative hemodynamic stability [10–12]. Clonidine, a partial alpha-2 agonist with an alpha-2:alpha-1 selectivity ratio of 220:1, has long been used as an antihypertensive and anesthetic adjuvant. It prolongs sedation, decreases anesthetic consumption and blunts pressor responses, though its relatively longer half-life may limit flexibility [13–15]. Dexmedetomidine, a newer and more selective agent (alpha-2:alpha-1 ratio 1620:1), offers greater potency, shorter half-life and favorable sedative, anxiolytic and analgesic properties without significant respiratory depression, making it an attractive alternative. [16,17] Several randomized controlled trials and meta-analyses suggest that dexmedetomidine may provide superior attenuation of intubation-related pressor responses compared to clonidine, owing to its higher receptor selectivity and potent sympatholytic action. However, clonidine remains relevant, particularly in resource-limited settings, due to its lower cost and wider availability [17–19]. This choice becomes especially pertinent in the Indian scenario, where the prevalence of cardiovascular comorbidities is high and perioperative resources are constrained. Given the need for context-specific evidence, this randomized, double-blind, controlled study was undertaken to compare the efficacy of intravenous clonidine and dexmedetomidine in attenuating the pressor response to laryngoscopy and endotracheal intubation.

OBJECTIVE

To compare the efficacy of intravenous clonidine and intravenous dexmedetomidine in lowering pressor response during endotracheal intubation.

Study Design and Setting: This prospective, randomized, double-blind, controlled study was conducted in the Department of Anaesthesiology at a tertiary care centre after obtaining institutional ethical clearance. Written informed consent was obtained from all patients.

Study Population: The study population comprised patients aged 18–60 years, of either gender, belonging to the American Society of Anaesthesiologists (ASA) physical status I or II, scheduled for elective surgeries under general anaesthesia. Patients with known drug allergies or anticipated difficult intubation were excluded.

Sampling Technique: Simple random sampling was employed to allocate patients into two groups.

Sample Size Calculation: The sample size was calculated based on expected differences in systolic blood pressure (SBP) between intravenous clonidine and dexmedetomidine during laryngoscopy and intubation, using data from a previous randomized controlled trial by Hussain et al. (2018) [20]. In that study, the mean SBP after clonidine was 107.8 mmHg (SD 7.5) and after dexmedetomidine was 109.7 mmHg (SD 14.5).

The following assumptions were applied:

• Confidence level (α): 95% (Zα/2 = 1.96)
• Power (1–β): 80% (Zβ = 0.84)
• Pooled standard deviation (σ): 11.54 (calculated from group SDs)
• Expected mean difference (Δ): 5.39 mmHg

Thus, the minimum required sample size was 36 patients per group. To account for potential dropouts and enhance study power, 40 patients were included in each group, giving a total sample size of 80 patients.

Randomization and Blinding: Patients were randomized into two groups (n=40 each) using a computer-generated randomization table. The anaesthesiologist administering the drug and the observer recording the parameters were blinded to group allocation.

• Group C (Clonidine group): Received 1 μg/kg intravenous clonidine diluted in 100 ml normal saline, infused over 10 minutes.
• Group D (Dexmedetomidine group): Received 1 μg/kg intravenous dexmedetomidine diluted in 100 ml normal saline, infused over 10 minutes.

Study Protocol: All patients fasted for at least six hours before surgery. Intravenous access was secured with an 18G cannula and crystalloid infusion was started. Standard monitors (ECG, NIBP, SpO₂) were applied and baseline values of heart rate (HR), SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and SpO₂ were recorded.

Study drugs were administered over 10 minutes and hemodynamic parameters were recorded at:

• Baseline (before drug administration)
• 5 minutes after drug infusion
• At the end of infusion (10 minutes)
• At 1,3,5 and 10 minutes following laryngoscopy and intubation

General anaesthesia was induced and maintained with N₂O + O₂, isoflurane, vecuronium and appropriate analgesics.

Outcome Measures: The primary outcome was attenuation of the pressor response, assessed by changes in HR, SBP, DBP and MAP at defined intervals. Secondary outcomes included safety profile and adverse events associated with each drug.

Statistical Analysis: Data were entered in Microsoft Excel and analyzed using SPSS version 24.0 (IBM, USA). Quantitative variables were expressed as mean ± standard deviation (SD) and compared using the unpaired t-test. Qualitative data were expressed as proportions and analyzed using the Chi-square test or Fisher’s exact test. A p-value <0.05 was considered statistically significant.

A total of 80 patients were enrolled and randomized equally into two groups of 40 each. Baseline demographic and clinical characteristics are shown in Table 1. The majority of patients in the clonidine group (45%) were between 31–40 years, while the dexmedetomidine group showed a more even distribution, with this subgroup difference reaching statistical significance (p=0.04). Gender distribution was similar in both groups, with a female predominance (65% in Group C vs. 70% in Group D, p>0.05). Mean age and mean body weight were comparable and did not differ significantly between the groups. Baseline hemodynamic parameters are summarized in Table 2. At baseline, both groups were comparable in systolic blood pressure and SpO₂. However, diastolic blood pressure, heart rate and mean arterial pressure were significantly higher in Group D compared to Group C (p<0.05). At the start of infusion, heart rate was significantly higher in Group C, but other parameters remained comparable.

Hemodynamic changes during infusion are depicted in Table 3. At 1 minute, heart rate was significantly lower in the dexmedetomidine group compared to clonidine (p=0.004). At 5 minutes, the difference in heart rate remained highly significant (p<0.0001). By 10 minutes, dexmedetomidine demonstrated significantly greater reductions in systolic BP, diastolic BP, MAP and HR compared to clonidine (p<0.05 for all). SpO₂ values remained stable and comparable across both groups at all intervals. The hemodynamic parameters after induction and immediately after intubation are shown in Table 4. Following induction, both groups showed a fall in hemodynamic variables, but the reduction was significantly greater with dexmedetomidine (p<0.001 for SBP, DBP, HR and MAP). After laryngoscopy and intubation, Group C exhibited a marked pressor and tachycardic response, whereas Group D showed significant blunting. SBP, DBP, MAP and HR immediately after intubation were significantly lower in Group D compared to Group C (p<0.001).

Post-intubation trends up to 15 minutes are presented in Table 5. At 1 and 3 minutes after intubation, SBP, HR and MAP were significantly lower in Group D compared to Group C (p<0.001). At 5 minutes, HR remained highly significant (p<0.0001), while SBP and MAP differences narrowed and were not statistically significant. At 10 minutes, HR continued to be significantly lower in Group D (p=0.04), though SBP and MAP differences were not significant. By 15 minutes, Group D maintained significantly lower SBP, DBP, HR and MAP compared to Group C (p<0.05). Oxygen saturation remained stable and comparable in both groups throughout the study period.

Table 1: Baseline Demographic and Clinical Characteristics

C = Clonidine group; D = Dexmedetomidine group. Values expressed as mean ± SD or number (%). p < 0.05 significant.

Table 2: Baseline Hemodynamic Parameters

Table 3: Hemodynamic Changes During Infusion (1, 5, 10 min)

Table 4: Hemodynamic Parameters After Induction and Intubation

Table 5: Hemodynamic Parameters After Intubation (1–15 Minutes)

In the present comparative study of intravenous clonidine and dexmedetomidine for attenuation of the pressor response during endotracheal intubation, the distribution of age across the two groups was generally comparable, with most patients in the clonidine group belonging to the 31–40 years range, while the dexmedetomidine group had a relatively higher proportion in the 41–50 years range. Although a significant difference was noted in the 31–40 years category (p = 0.04), no differences were observed in the other groups (p > 0.05). These findings align with Rai U, et al., (2021) [17], Suryawanshi CM, et al., (2018) [21] and Rawate RB, et al., (2021) [22], who reported no significant age differences between clonidine and dexmedetomidine groups. Similar comparability was also noted by Vijay P, et al., (2025) [19] and Ali N, et al., (2024) [23], suggesting that age distribution does not influence group allocation or outcomes in such studies. In this study, both groups showed a female predominance (65% in clonidine vs 70% in dexmedetomidine), with no statistically significant difference. Comparable gender distribution was reported by Rai U, et al., (2021) [17], Suryawanshi CM, et al., (2018) [21], Rawate RB, et al., (2021) [22], Vijay P, et al., (2025) [19] and Ali N, et al., (2024) [23], all of whom found no significant gender variation between the two groups.

In the present study, the mean age in the clonidine group (Group C) was 38.42 ± 10.22 years, while in the dexmedetomidine group (Group D) it was 40.72 ± 11.34 years (t = 0.95, p = 0.34). Likewise, the mean weight was 58.24 ± 8.24 kg in Group C and 57.20 ± 7.36 kg in Group D (t = –0.59, p = 0.55). These findings showed no statistically significant differences. Similar observations were reported in earlier studies conducted by Rai U, et al., (2021) [17], Suryawanshi CM, et al., (2018) [21], Rawate RB, et al., (2021) [22] and Ali N, et al., (2024) [23]. However, contrasting results were noted in the study by Vijay P, et al., (2025) [19], where the mean weight in Group C was 68.7 ± 10.39 kg compared to 63.4 ± 10.2 kg in Group D (p = 0.05), suggesting clonidine patients had slightly higher mean weight.

At baseline, patients who received clonidine demonstrated comparatively lower systolic and diastolic blood pressures, heart rate and mean arterial pressure than those who received dexmedetomidine. These differences were statistically significant (p < 0.05) for all parameters except oxygen saturation, which remained comparable (p > 0.05). This suggested that clonidine maintained a more favorable hemodynamic profile even before laryngoscopy and intubation. This finding was consistent with Bharti D, et al., (2016) [24], who reported that clonidine (3 μg/kg) was more effective than dexmedetomidine (0.2 μg/kg) in blunting the hemodynamic responses to laryngoscopy. Conversely, studies by Rai U, et al., (2021) [17], Suryawanshi CM, et al., (2018) [21], Ali N, et al., (2024) [23] and Singh J, et al., (2024) [25] showed that both dexmedetomidine and clonidine were effective, with no clear superiority. In contrast, Rawate RB, et al., (2021) [22], Vijay P, et al., (2025) [19] and Mondal S, et al., (2014) [26] concluded that dexmedetomidine was superior in reducing hemodynamic response.

At the start of infusion, systolic blood pressure, diastolic blood pressure, mean arterial pressure and oxygen saturation were comparable between groups (p > 0.05). However, heart rate was significantly higher in the clonidine group (94.86 ± 7.94 vs 90.32 ± 8.58 beats/min, p = 0.01), indicating a slight tachycardic tendency in clonidine patients. Suryawanshi CM, et al., (2018) [21] reported reductions in SBP with both drugs, while Vijay P, et al., (2025) [19] proposed dexmedetomidine infusion might provide superior attenuation of responses during intubation. Ali N, et al., (2024) [23] also noted a significant fall in HR with dexmedetomidine following infusion (p = 0.034) and after induction (p = 0.020). Agarwal S, et al., (2016) [27] found hemodynamic variations were more pronounced in clonidine patients compared to dexmedetomidine, supporting its stronger bradycardic effect.

At 1 minute, SBP, DBP, MAP and SpO₂ were comparable between groups (p > 0.05), but HR was significantly lower in dexmedetomidine (86.92 ± 8.84 vs 92.28 ± 7.65 beats/min, p = 0.004). At 5 minutes, HR reduction was more pronounced in dexmedetomidine (80.14 ± 8.92 vs 88.32 ± 7.28 beats/min, p < 0.0001), while BP and MAP remained comparable. By 10 minutes, SBP, DBP, MAP and HR were all significantly lower in dexmedetomidine (p ≤ 0.02 for BP/MAP, p < 0.0001 for HR). These results align with Rawate RB, et al., (2021) [22], who found comparable parameters at 1 and 5 minutes, but significantly lower values with dexmedetomidine by 10 minutes. Similar results were observed by Vijay P, et al., (2025) [19], Ali N, et al., (2024) [23], Singh J, et al., (2024) [25], Mondal S, et al., (2014) [26] and Agarwal S, et al., (2016) [27], confirming dexmedetomidine’s superiority for early attenuation.

After induction, clonidine patients had higher SBP (111.02 ± 8.12 vs 106.28 ± 9.41 mmHg, p = 0.01), DBP (70.48 ± 7.38 vs 62.12 ± 5.71 mmHg, p < 0.0001) and HR (79.42 ± 7.25 vs 65.78 ± 8.63 beats/min, p < 0.0001). MAP was also higher (83.94 ± 6.57 vs 76.84 ± 5.48 mmHg, p < 0.0001), while SpO₂ was comparable (p = 0.52). These findings were consistent with Rawate RB, et al., (2021) [22], Ali N, et al., (2024) [23] and Agarwal S, et al., (2016) [27], all reporting effective attenuation with dexmedetomidine. Moharram AA, et al., (2019) [28] also showed dexmedetomidine maintained target MAP during lumbar fixation, further supporting its role.

Following intubation, dexmedetomidine patients demonstrated significantly lower SBP, DBP, HR and MAP (p < 0.01), while SpO₂ remained comparable. This suggests dexmedetomidine more effectively blunted the pressor response. This aligns with Sarkar A, et al., (2014) [18], who recommended dexmedetomidine for attenuation. Findings were also consistent with Rawate RB, et al., (2021) [22], Vijay P, et al., (2025) [19], Ali N, et al., (2024) [23], Singh J, et al., (2024) [25] and Scheinin B, et al., (1992) [29], all of whom reported superior suppression with dexmedetomidine.

Dexmedetomidine consistently maintained lower HR and, by 15 minutes, also lower BP and MAP, while SpO₂ remained stable. This reflects its superior hemodynamic control. Singh J, et al., (2024) [25] reported HR, DBP and MAP differed significantly between groups at 10 minutes post-induction and intubation. Mondal S, et al., (2014) [26] also confirmed dexmedetomidine efficiently attenuated BP compared to clonidine at all post-intubation intervals. Additional support came from Vijay P, et al., (2025) [19] and Kholi AV, et al., (2017) [30], both showing significant HR reductions with dexmedetomidine.

In this study, intravenous dexmedetomidine at a dose of 1 µg/kg, diluted in 100 ml of normal saline and infused over 10 minutes, demonstrated superior efficacy compared to an equivalent dose of clonidine (1 µg/kg in 100 ml normal saline over 10 minutes) in attenuating the hemodynamic responses associated with endotracheal intubation and induction of anesthesia. Patients receiving dexmedetomidine exhibited significantly lower systolic and diastolic blood pressures, mean arterial pressures and heart rates at multiple time points during and after intubation, while oxygen saturation remained stable and comparable between the groups. The pressor and tachycardic responses to laryngoscopy and intubation were markedly blunted with dexmedetomidine, indicating better cardiovascular stability. Furthermore, dexmedetomidine produced an early and sustained reduction in heart rate without causing significant hypotension or hypoxia. These findings suggest that dexmedetomidine, administered at 1 µg/kg over 10 minutes, is more effective and reliable than clonidine for maintaining hemodynamic stability during the peri-intubation period, making it a preferable agent for anesthetic management in patients at risk of exaggerated sympathetic responses.

Limitations

This study has certain limitations that should be acknowledged. First, it was a single-center study with a relatively small sample size (n = 80), which may limit the generalizability of the findings. Second, patients with Mallampatti grade III and IV airways were excluded, thereby restricting the applicability of the results to patients with potentially difficult airways. Third, individuals with comorbid conditions such as hypertension and diabetes were not included; hence, the comparative benefits of clonidine and dexmedetomidine in patients with systemic diseases could not be evaluated. Additionally, only intravenous administration and fixed doses of clonidine and dexmedetomidine were studied, which does not allow extrapolation to other routes, regimens or dose titrations. Hemodynamic monitoring was limited to the short-term peri-intubation period and long-term outcomes were not assessed. Finally, the depth of anesthesia and adequacy of neuromuscular relaxation, factors that could influence hemodynamic responses, were not monitored in this study.

IEC Approval: Yes

Conflict of Interest: Nil

Funding: Nil

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