Int J Curr Pharm Res, Vol 17, Issue 1, 53-56Original Article

COMPARISON OF TWO DIFFERENT DOSES OF TABLET CLONIDINE (100MCG AND 150MCG) GIVEN 90 MIN PRIOR TO SURGERY TO ATTENUATE HAEMODYNAMIC CHANGES DURING ENDOTRACHEAL INTUBATION

SHEETAL GAMBHIR*, SWATI CHOUDHARY, S. P. SHARMA

Department of Anaesthesiology, Jaipur National University Institute of Medical Sciences and Research Centre, Jaipur, India
*Corresponding author: Sheetal Gambhir; *Email: gambhiramanpreet6@gmail.com

Received: 23 Oct 2024, Revised and Accepted: 08 Dec 2024

ABSTRACT

Objective: Endotracheal intubation can elicit significant haemodynamic responses, posing risks for patients with cardiovascular conditions. Clonidine, an alpha-2 adrenergic agonist, is used to mitigate these responses, but the optimal dosing is uncertain. This study compares the efficacy and safety of two doses of oral clonidine, 100 μg and 150 μg, administered 90 min before surgery.

Methods: Sixty patients aged 18–55 y, classified as ASA physical status I or II and scheduled for elective lower abdominal surgeries, were randomly assigned to two groups. Group A received 100 μg of oral clonidine, and Group B received 150 μg. Haemodynamic parameters-heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)-were recorded at baseline, during induction, immediately after intubation, and at intervals up to 15 min post-intubation. Side effects and the need for rescue analgesia were also assessed.

Results: Group A demonstrated significantly lower SBP and HR at induction and during the immediate post-intubation period compared to Group B (p < 0.05). No significant differences were observed in DBP and MAP at most time points. The incidence of hypotension was higher in Group B but not statistically significant. Group B required significantly less rescue analgesia postoperatively (p < 0.001).

Conclusion: A 100 μg dose of oral clonidine is more effective in attenuating haemodynamic responses during endotracheal intubation compared to a 150 μg dose. While the higher dose offers improved postoperative analgesia, it does not enhance haemodynamic stability and may increase the risk of hypotension.

Keywords: Clonidine, Haemodynamic response, Endotracheal intubation, Premedication, Alpha-2 agonist, Analgesia

© 2025 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
DOI: https://dx.doi.org/10.22159/ijcpr.2025v17i1.6022 Journal homepage: https://innovareacademics.in/journals/index.php/ijcpr

INTRODUCTION

Endotracheal intubation is a critical component of general anesthesia, enabling secure airway management and ventilation during surgical procedures. However, the process of laryngoscopy and intubation is known to provoke significant sympathetic stimulation, leading to acute haemodynamic responses such as hypertension and tachycardia [1]. While these transient cardiovascular changes are often tolerated by healthy individuals, they can pose substantial risks to patients with preexisting cardiovascular conditions, potentially precipitating myocardial ischemia, arrhythmias, or cerebrovascular events [2].

Attenuation of these haemodynamic responses is therefore a vital consideration in anesthetic practice. Various pharmacological agents have been employed to mitigate these effects, including opioids, beta-blockers, calcium channel blockers, and vasodilators [3]. Clonidine, a selective alpha-2 adrenergic agonist, has emerged as a particularly effective agent due to its ability to decrease central sympathetic outflow, resulting in reduced heart rate and blood pressure [4]. Additionally, clonidine possesses sedative and analgesic properties, which can enhance patient comfort and reduce anesthetic requirements [5].

Oral clonidine premedication has been demonstrated to effectively blunt the haemodynamic responses associated with laryngoscopy and intubation [6]. However, the optimal dosing regimen remains a subject of clinical interest. Higher doses may offer greater haemodynamic stability but are associated with an increased risk of adverse effects such as excessive sedation, hypotension, and bradycardia [7]. Conversely, lower doses may be insufficient to adequately attenuate sympathetic responses. Despite its widespread use, there is limited comparative data on the efficacy and safety of different oral clonidine doses administered prior to surgery [8].

This study aims to compare the effects of two different doses of oral clonidine-100 μg and 150 μg-administered 90 min before surgery on haemodynamic changes during endotracheal intubation. By evaluating these dosing strategies, we seek to determine the dose that optimally balances efficacy in haemodynamic attenuation with safety and minimal side effects. The findings from this research could have significant implications for perioperative management, potentially guiding dosage recommendations and improving patient outcomes, particularly in individuals at elevated cardiovascular risk.

Understanding the dose-response relationship of clonidine in this context is crucial for anesthesiologists aiming to optimize perioperative care. This study not only addresses a gap in the existing literature but also strives to enhance clinical protocols for managing the haemodynamic challenges associated with endotracheal intubation.

MATERIALS AND METHODS

Study design and setting

This observational comparative study was conducted in the Department of Anesthesiology at Jaipur National University Institute of Medical Sciences and Research Centre, Jaipur, Rajasthan, from September 2022 to May 2024.

Sample size and groups

A total of 60 patients scheduled for elective lower abdominal surgeries under general anesthesia were enrolled. They were randomly divided into two groups (n=30 each):

Inclusion criteria

Exclusion criteria

Preoperative assessment

All patients underwent a thorough pre-anesthetic evaluation, including:

Anesthetic protocol

Data collection

Hemodynamic parameters were recorded at specific intervals:

Parameters measured included:

Intraoperative management

Equipment used

Postoperative care

Patients were monitored in the recovery room for hemodynamic stability and any adverse events before being transferred to the ward.

Statistical analysis

Data were entered into Microsoft Excel and analyzed using SPSS version 25. Quantitative variables were expressed as mean±standard deviation (SD) or median±interquartile range (IQR). Qualitative variables were presented as frequencies and percentages. Statistical comparisons between groups were made using appropriate tests (e. g., Student's t-test, Chi-square test). A p-value < 0.05 was considered statistically significant.

Ethical considerations

The study was approved by the Institutional Ethical Committee of Jaipur National University Institute of Medical Sciences and Research Centre. Written informed consent was obtained from all participants. Patient confidentiality was maintained, and data were used exclusively for research purposes.

RESULTS

A total of 60 patients were enrolled in the study, evenly divided into two groups of 30 each. Group A received 100 μg of oral clonidine, while Group B received 150 μg. The demographic and baseline characteristics are summarized in table 1. The mean age was significantly lower in Group B (33.73±11.09 y) compared to Group A (39.67±10.49 y, p = 0.03). However, there were no significant differences between the groups regarding gender distribution, body mass index (BMI), or American Society of Anesthesiologists (ASA) physical status classification.

Hemodynamic parameters

Systolic blood pressure (SBP) readings at various time intervals are presented in table 2. Baseline SBP and SBP after premedication showed no significant differences between the groups. However, at the time of induction, Group B exhibited a significantly higher SBP compared to Group A (107.57±6.04 mm Hg vs. 102.40±11.66 mm Hg, p = 0.03). This trend continued immediately after intubation and at 1, 3, and 5 min post-intubation, with Group B consistently showing higher SBP readings (p < 0.001). No significant differences were observed at 10 and 15 min post-intubation.

Heart rate (HR) measurements are detailed in table 3. There were no significant differences in baseline HR between the groups. Similar to SBP, Group B had significantly higher HR at induction (81.77±10.88 beats/min) compared to Group A (76.17±9.30 beats/min, p = 0.045). This significant difference persisted immediately after intubation and at 1, 3, and 5 min post-intubation (p < 0.01). By 10 and 15 min post-intubation, HR differences were no longer significant.

Side effects

The incidence of side effects is summarized in table 4. Hypotension occurred in 4 patients (13.3%) in Group A and 8 patients (26.7%) in Group B, but this difference was not statistically significant (p = 0.19). Pruritus was observed in 1 patient (3.3%) in Group B and none in Group A (p > 0.05). Shivering was reported in 2 patients (6.7%) in Group A and 1 patient (3.3%) in Group B, with no significant difference between the groups.

Analgesic requirements

As shown in table 5, a significantly lower number of patients in Group B required rescue analgesia at 6 h postoperatively compared to Group A (3 patients [10%] vs. 25 patients [83.3%], p < 0.001). This suggests a potential analgesic benefit with the higher dose of clonidine.

Table 1: Demographic and baseline characteristics of patients

Parameter Group A<br>(Clonidine 100 μg)<br>n=30 Group B<br>(Clonidine 150 μg)<br>n=30 p-value
Age (y, mean±SD) 39.67±10.49 33.73±11.09 0.03*
Age Groups, n (%)
-<30 y 6 (20%) 12 (40%) 0.21
-31–45 y 14 (46.7%) 12 (40%)
-46–55 y 10 (33.3%) 6 (20%)
Gender, n (%)
-Male 18 (60%) 20 (66.7%) 0.59
-Female 12 (40%) 10 (33.3%)
Body Mass Index (BMI), n (%) 0.17
-Normal (18.5–22.9 kg/m²) 11 (36.7%) 5 (16.7%)
-Overweight (23–24.9 kg/m²) 14 (46.7%) 16 (53.3%)
-Obese (>25 kg/m²) 5 (16.7%) 9 (30%)
ASA Physical Status, n (%) 0.28
-I 21 (70%) 17 (56.7%)
-II 9 (30%) 13 (43.3%)

Table 2: Systolic blood pressure (SBP) at different time intervals

Time interval Group A<br>(mean±SD) Group B<br>(mean±SD) p-value
Baseline (Pre-op) 120.23±5.89 121.00±5.08 0.72
After premedication 119.40±13.00 116.80±11.79 0.40
At induction 102.40±11.66 107.57±6.04 0.03*
Immediately after intubation 101.70±7.34 112.23±5.03 <0.001*
1 Minute post-Intubation 96.70±6.83 104.87±4.21 <0.001*
3 Min post-intubation 92.57±6.53 98.77±3.29 <0.001*
5 Min post-intubation 89.70±6.53 95.97±3.24 <0.001*
10 Min post-intubation 111.97±13.91 115.20±11.78 0.33
15 Min post-intubation 112.60±13.17 116.67±11.05 0.20

Table 3: Heart rate (HR) at different time intervals

Time interval Group A<br>(mean±SD) Group B<br>(mean±SD) p-value
Baseline (Pre-op) 79.23±3.89 80.03±4.08 0.74
After premedication 85.97±9.66 83.90±10.86 0.44
At induction 76.17±9.30 81.77±10.88 0.045*
Immediately after intubation 72.23±9.37 85.57±11.22 0.006*
1 Minute post-intubation 66.97±8.42 81.67±9.45 0.001*
3 Min post-intubation 62.83±7.52 80.30±8.53 0.01*
5 Min post-intubation 57.77±7.29 78.73±7.69 0.01*
10 Min post-intubation 71.83±10.49 73.37±15.49 0.65
15 Min post-intubation 71.23±9.47 74.10±13.51 0.34

Table 4: Side effects observed in both groups

Side effect Group A<br>(n=30) Group B<br>(n=30) p-value
Hypotension 4 (13.3%) 8 (26.7%) 0.19
Pruritus 0 (0%) 1 (3.3%) >0.05
Shivering 2 (6.7%) 1 (3.3%) >0.05

Table 5: Need for rescue analgesia at 6 H postoperatively

Need for rescue analgesia Group A<br>(n=30) Group B<br>(n=30) p-value
Yes 25 (83.3%) 3 (10%) <0.001*
No 5 (16.7%) 27 (90%)

DISCUSSION

The present study aimed to compare the efficacy of two doses of oral clonidine-100 μg and 150 μg-administered 90 min before surgery in attenuating haemodynamic responses during endotracheal intubation. Our findings indicate that the lower dose of clonidine (100 μg) was more effective in stabilizing systolic blood pressure (SBP) and heart rate (HR) during induction and intubation compared to the higher dose (150 μg) [9].

Contrary to the expectation that a higher dose would provide better haemodynamic stability, Group B (150 μg clonidine) exhibited higher SBP and HR readings immediately after intubation and in the subsequent minutes. This suggests that increasing the dose beyond 100 μg may not confer additional benefits and could potentially lead to diminished efficacy. Similar observations were reported by Parikh et al. (2015), who found that escalating doses of clonidine did not proportionally enhance haemodynamic control during laryngoscopy and intubation [9, 10].

One possible explanation for the diminished efficacy at higher doses is the saturation of central alpha-2 adrenergic receptors, beyond which additional clonidine may not produce further sympatholytic effects. Moreover, higher doses could stimulate peripheral alpha-1 receptors, leading to vasoconstriction and counteracting the desired haemodynamic effects [11, 12].

The higher incidence of hypotension in Group B, although not statistically significant, raises concerns about the safety profile of the 150 μg dose. Hypotension can compromise organ perfusion, particularly in patients with limited cardiovascular reserve. Khan et al. (2016) also reported an increased risk of hypotension with higher doses of clonidine, emphasizing the need for careful dose selection [13].

Interestingly, Group B required significantly less rescue analgesia postoperatively, indicating enhanced analgesic benefits with the higher dose. Clonidine's analgesic properties are well-documented and are attributed to its action on alpha-2 adrenergic receptors in the spinal cord, which inhibit nociceptive neurotransmission [12]. This aligns with the findings of Bajwa et al. (2012), who demonstrated improved postoperative analgesia with higher doses of clonidine [13].

These findings highlight the complex pharmacodynamics of clonidine, where a balance must be struck between haemodynamic stability and analgesic efficacy. While a higher dose may enhance analgesia, it does not necessarily improve haemodynamic control and may increase the risk of adverse effects.

LIMITATIONS

This study has limitations that should be considered. The sample size was relatively small and conducted at a single center, which may affect the generalizability of the results. Additionally, we did not assess sedation levels or measure plasma catecholamine levels, which could provide deeper insights into the pharmacological effects of clonidine at different doses.

FUTURE DIRECTIONS

Further research with larger, multicenter trials is necessary to confirm these findings and establish optimal dosing guidelines. Studies exploring intermediate doses between 100 μg and 150 μg could help identify a dose that offers both haemodynamic stability and analgesic benefits with minimal adverse effects. Monitoring additional parameters, such as sedation scores and catecholamine levels could enhance our understanding of clonidine's dose-response relationship.

CONCLUSION

In conclusion, administering 100 μg of oral clonidine 90 min prior to surgery is more effective in attenuating haemodynamic responses during endotracheal intubation compared to a 150 μg dose. While the higher dose provides better postoperative analgesia, it does not enhance haemodynamic stability and may increase the risk of hypotension. Therefore, a lower dose of clonidine may be preferable for patients where haemodynamic control during intubation is the primary concern.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

All authors have contributed equally

CONFLICT OF INTERESTS

Declared none

REFERENCES

  1. Reid LC, Brace DE. Irritation of the respiratory tract and its reflex effect upon heart. Surgery. 1940;7(4):487-502.

  2. Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology. 1977;47(6):524-5. doi: 10.1097/00000542-197712000-00013, PMID 337858.

  3. Bruder N, Ortega D, Granthil C. Consequences and prevention methods of hemodynamic changes during laryngoscopy and intratracheal intubation. Ann Fr Anesth Reanim. 1992;11(1):57-71. doi: 10.1016/s0750-7658(05)80321-1, PMID 1359816.

  4. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. hemodynamic changes. Anesthesiology. 1992;77(6):1134-42. doi: 10.1097/00000542-199212000-00014, PMID 1361311.

  5. Filos KS, Goudas LC, Patroni O, Polyzou V. Hemodynamic and analgesic profile after intrathecal clonidine in humans a dose-response study. Anesthesiology. 1994;81(3):591-601. doi: 10.1097/00000542-199409000-00011, PMID 8092504.

  6. Raval DL, Mehta MK. Oral clonidine premedication for attenuation of haemodynamic response to laryngoscopy and intubation. Indian J Anaesth. 2002;46(2):124-9.

  7. Quintin L, Bonnet F, Macquin I. Comparison of clonidine and fentanyl combinations for elective abdominal aortic surgery. Anesthesiology. 1990;72(5):805-10.

  8. Ghignone M, Quintin L, Duke PC, Kehler CH, Calvillo O. Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation. Anesthesiology. 1986;64(1):36-42. doi: 10.1097/00000542-198601000-00007, PMID 3942335.

  9. Parikh DA, Kolli SN, Karnik HS, Lele SS, Tendolkar BA. A prospective randomized double-blind study comparing clonidine and dexmedetomidine for attenuation of haemodynamic stress response during laparoscopic cholecystectomy. Indian J Anaesth. 2015;59(5):448-53.

  10. El Sharrawy AM, Abdellatif AA. Comparison of the effects of different doses of clonidine on perioperative haemodynamic stability and analgesic requirements in patients undergoing abdominal hysterectomy. Egypt J Anaesth. 2014;30(4):343-8.

  11. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists their pharmacology and therapeutic role. Anaesthesia. 1999;54(2):146-65. doi: 10.1046/j.1365-2044.1999.00659.x, PMID 10215710.

  12. Bernard JM, Hommeril JL, Passuti N, Pinaud M. Postoperative analgesia by intravenous clonidine. Anesthesiology. 1991;75(4):577-82. doi: 10.1097/00000542-199110000-00006, PMID 1928767.

  13. Bajwa SJ, Kaur J, Singh A, Parmar S, Singh G, Kulshrestha A. Attenuation of pressor response and dose sparing of opioids and anaesthetics with pre-operative dexmedetomidine. Indian J Anaesth. 2012;56(2):123-8. doi: 10.4103/0019-5049.96303, PMID 22701201.