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ORIGINAL ARTICLE
Year : 2018  |  Volume : 12  |  Issue : 4  |  Page : 792-796  

Evaluation and comparison of clonidine and dexmedetomidine for attenuation of hemodynamic response to laryngoscopy and intubation: A randomized controlled study


1 Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
2 Department of Anaesthesiology, INHS Kalyani, Vishakhapatnam, Andhra Pradesh, India

Date of Web Publication18-Dec-2018

Correspondence Address:
Dr. Sana Yasmin Hussain
D-95, Al Helal Apartment, Shaheen Bagh, Okhla, New Delhi - 110 025
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_123_18

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   Abstract 

Background: Laryngoscopy and tracheal intubation are noxious stimuli which evoke a transient but marked sympathetic response. Alpha-2 adrenoceptor agonists attenuate the sympathoadrenal responses by inhibiting noradrenaline release. Aim: This study aims to evaluate and compare the effect of intravenous dexmedetomidine and clonidine on cardiovascular response resulting from laryngoscopy and endotracheal intubation. Settings and Design: This was a prospective randomized controlled study carried out in the operating room. Materials and Methods: Ninety American Society of Anesthesiologists Physical Status I and II patients were randomly allocated into three groups, that is, Group C (clonidine 2 μg/kg), Group D (dexmedetomidine 1 μg/kg), and Group S (normal saline) infused over 10 min. Blood pressures – systolic (SBP) and diastolic (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded after drug administration and intubation at subsequent intervals. Statistical Analysis Used: Quantitative data were analyzed using ANOVA test (with post hoc Bonferroni correction for intragroup comparison). Qualitative data were analyzed using Chi-square test. P < 0.05 was considered statistically significant. Results: HR, SBP, DBP, and MAP were lower in Group C and D compared to Group S at all times measured. HR was significantly lower in Group D compared to Group C after drug infusion. At 1 min after intubation, SBP and MAP were lower in Group D compared to Group C. At 3, 5, and 10 min after intubation, SBP, DBP, and MAP were lower in Group D compared to Group C. Conclusion: There was significant reduction in hemodynamic response by dexmedetomidine and clonidine as compared to controls. Furthermore, attenuation of the pressor response to intubation was better following premedication with dexmedetomidine than with clonidine.

Keywords: Clonidine, dexmedetomidine, intubation, laryngoscopy


How to cite this article:
Hussain SY, Karmarkar A, Jain D. Evaluation and comparison of clonidine and dexmedetomidine for attenuation of hemodynamic response to laryngoscopy and intubation: A randomized controlled study. Anesth Essays Res 2018;12:792-6

How to cite this URL:
Hussain SY, Karmarkar A, Jain D. Evaluation and comparison of clonidine and dexmedetomidine for attenuation of hemodynamic response to laryngoscopy and intubation: A randomized controlled study. Anesth Essays Res [serial online] 2018 [cited 2019 Jan 23];12:792-6. Available from: http://www.aeronline.org/text.asp?2018/12/4/792/247634


   Introduction Top


Laryngoscopy and tracheal intubation are noxious stimuli which evoke a transient but marked sympathetic response manifesting as increase in heart rate (HR) and blood pressure (BP). These changes are maximum immediately after intubation and last for 5–10 min. In patients with cardiovascular disease, these hemodynamic changes can lead to life-threatening complications such as acute heart failure, myocardial ischemia, and cerebrovascular accidents.[1]

Conventional treatment methods include topical lignocaine sprays, deeper planes of anesthesia by inhalational/intravenous (IV) agents or opioids, calcium channel blockers, and vasodilators such as sodium nitroprusside and nitroglycerine.[2] Although there are various methods, research is still in progress for techniques of attenuation of pressor response to laryngoscopy and intubation.[3]

Alpha-2 (α2)-adrenoceptor agonists may provide an alternative technique to the currently used adjunctive anesthetic agents because of their hemodynamic stabilizing and anesthetic-sparing effects.[4]

Premedication with clonidine, an α2-adrenergic agonist, has been recently shown to blunt the stress response to the surgical stimuli and reduce the narcotic and anesthetic requirements.[5] In addition, clonidine increases the cardiac baroreceptor reflex sensitivity to an increase in the systolic BP (SBP), and hence stabilizes the BP.[6],[7] However, its mild selectivity to α2 adrenoceptors and long half-life has limited its use. Dexmedetomidine is a newer imidazole derivative which is a highly selective α2-adrenergic receptor agonist.[8] α2-agonists produce hyperpolarization of noradrenergic neurons and suppression of neuronal firing in the locus ceruleus leading to decreased systemic noradrenaline release. This results in attenuation of sympathoadrenal responses and hemodynamic stability during laryngoscopy and tracheal intubation.[9]

Studies have been done to evaluate the effects of clonidine and dexmedetomidine on the hemodynamic response during laryngoscopy and tracheal intubation. α2-adrenergic agonist have been shown to be beneficial in preventing cardiac complications,[10] however, a recent meta-analysis did not show mortality benefit in cardiac patients.[11] The present study was designed to evaluate and compare the effects of IV dexmedetomidine and clonidine in attenuating the pressor response to laryngoscopy and endotracheal intubation. The objectives of the study were to measure and compare HR, SBP, diastolic BP (DBP), and mean arterial pressure (MAP) before and after laryngoscopy and intubation of patients who were given either clonidine or dexmedetomidine or normal saline (NS) as placebo.


   Materials and Methods Top


This prospective, double-blinded, randomized controlled study was carried out after obtaining institutional ethical committee clearance and written informed consent from all patients in a tertiary care hospital. The American Society of Anesthesiologists (ASA) physical status Classes I or II aged 20–40 years undergoing elective surgical procedures were included. Patients with anticipated difficult airway, history of hypertension, diabetes mellitus, heart disease, and intubation time with >20 s were excluded from the study. Using a computer-generated random number table, 90 patients were randomized to three groups of 30 patients each. Allocation concealment was performed using sequentially numbered, coded sealed envelopes.

On the day before surgery, preanesthetic evaluation was done with the detailed history of the cardiovascular system, respiratory system, central nervous system, drug therapy, and drug allergy. A thorough clinical examination of the patient was performed including general physical examination and systemic examination. Airway assessment was done by Mallampati grading to anticipate the possibility of difficult intubation. All patients were explained about the anesthetic technique and written informed consent was obtained.

Basal SBP, DBP, MAP, and HR were recorded.

Patients were premedicated with glycopyrrolate 0.2 mg IV, ondansetron 4 mg IV, and fentanyl 1 μg/kg IV.

The anesthesiologist in the operating room opened the sealed envelope and prepared the drug solution in 100 mL NS.

Group C: Received IV clonidine 2 μg/kg in 100 mL NS over 10 min.

Group D: Received IV dexmedetomidine 1 μg/kg in 100 ml NS over 10 min.

Group S: Received 100 mL of NS over 10 min, constituting the control group.

After 10 min, SBP, DBP, MAP, and HRs were recorded. All patients were preoxygenated and induced with 4–6 mg/kg thiopentone sodium IV (2.5%) till loss of eyelash reflex. After successful trial of ventilation, vecuronium 0.1 mg/kg IV was given. After 3 min of ventilation, laryngoscopy and intubation were done. SBP, DBP, MAP, and HR was recorded at 1 min, 3 min, 5 min, and 10 min after laryngoscopy and intubation, respectively. Surgery was commenced 10 min after laryngoscopy and intubation. No stimulus was applied during the study period.

During surgery any fall in the MAP more than 20% from the baseline was treated with phenylephrine 20 μg IV aliquots, and bradycardia (HR <40/min) was treated with atropine 0.3 mg IV These patients were excluded from the final analysis and extra patients were recruited to make it 30 in each group. All the hemodynamic data were recorded by an independent observer who was blinded to the study solution.

Statistical analysis

SPSS Statistics for Windows, version 17.0 (SPSS Inc., Chicago, Ill., USA) was used for statistical analysis. Quantitative data were presented as mean and standard deviation and analyzed using ANOVA test (with post hoc Bonferroni correction for intragroup comparison). Qualitative data were presented as frequency and percentage and analyzed using Chi-square test. P < 0.05 was considered statistically significant.


   Results Top


One hundred and forty-five patients were recruited from December 2012 to January 2014. Demographic and baseline hemodynamic data is presented in [Table 1] and was comparable among the groups.
Table 1: Demographic and baseline hemodynamic data

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HR, SBP, DBP, and MAP all were significantly lower in medication groups (P < 0.01) compared to control group after 10 min of drug administration, while no difference was observed between Group C and D except for HR. HR was significantly lower in Dexmedetomidine group compared to Clonidine group [Table 2].
Table 2: Distribution based on general examination findings 10 min after drug administration

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HR, SBP, DBP, and MAP all were significantly lower in medication groups compared to control group after 1 min of intubation, while no difference was observed between Group C and D except for SBP and MAP. SBP and MAP were significantly lower in Dexmedetomidine group compared to Clonidine group. At 3, 5, and 10 min after intubation, SBP, DBP, and MAP were lower in Dexmedetomidine group compared to Clonidine group [Table 3]. The variations in HR and MAP among the groups are shown in [Figure 1] and [Figure 2].
Table 3: Distribution based on general examination findings after intubation

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Figure 1: Variation in heart rate/Min

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Figure 2: Variation in mean arterial pressure (mmHg)

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Two patients had bradycardia after giving dexmedetomidine. They were treated with atropine 0.3 mg intravenously. These patients were excluded from the final analysis.


   Discussion Top


Anesthesia and surgery are associated with increased stress which is manifested in the form of tachycardia, hypertension, and increased sympathetic activity. Laryngoscopy and intubation are stressful stimuli which lead to increased catecholamine blood levels, tachycardia, and hypertension. In this study, clonidine 2 μg/kg and dexmedetomidine 1 μg/kg IV was used which resulted in reduction of hypertensive response to laryngoscopy and intubation of similar magnitude. Zalunardo et al.,[12] Altan et al.,[13] and Ray et al.[14] used 2 μg/kg of clonidine for attenuating hemodynamic response to tracheal intubation. Menda et al.,[15] Keniya et al.,[16] and Bajwa et al.[17] concluded that dexmedetomidine 1 μg/kg IV infusion given 10–15 min before laryngoscopy attenuates the pressor response. Based on these studies, 2 μg/kg clonidine and 1 μg/kg dexmedetomidine was chosen in this study. Oral and intramuscular clonidine have been shown to be effective in blunting intubation response but are to be given 90 min prior[18],[19] and hence were not chosen for this study.

No significant difference was observed in participants of all three groups on the basis of baseline HR, SBP, DBP, and MAP. This ensures that any significant observations made during the study were attributed to the effect of study drugs only and not on any premedication differences in the study groups.

Heart rate

After administration of drugs, on an average HR decreased by 15 beats in dexmedetomidine group and 6 beats in clonidine group. Maximum decrease in HR in dexmedetomidine group was 30 beats and in clonidine group, it was 20 beats. At 1 min after intubation, mean HR in dexmedetomidine group was almost same as baseline and in clonidine group, it was 5 beats/min more than baseline. At 3 min after intubation, HR was 3 beats/min lower in dexmedetomidine group and similar to baseline in clonidine group. Thereafter, the HR decline is slightly more in dexmedetomidine group, but the difference was not statistically significant (P > 0.05). However, the HR in control group was significantly high compared to both groups during all the time periods.

Blood pressure

On an average SBP, DBP, and MAP decreased by approximately 10, 9, and 10 mmHg in both the group. There was an increase in BP at intubation in both the groups (but it remained below the preinduction values). Afterward, BP displayed a downward trend and that was significantly more in dexmedetomidine group compared to clonidine group. However, BP in control group was significantly high compared to both groups during all the time periods. No side effects were noted in both the groups.

Jaakola et al. and Aho et al. studied the effects of a single IV dose of dexmedetomidine, on hemodynamic response to laryngoscopy and tracheal intubation, and on anesthetic requirement. Dexmedetomidine was associated with blunting of hemodynamic response to intubation and decreased the anesthetic requirement.[4],[20] Anish Sharma and Shankaranarayana compared dexmedetomidine and clonidine in attenuating intubation response and concluded that dexmedetomidine attenuated the tachycardia response better,[21] similar to our results. Reddy et al. concluded that dexmedetomidine 1 μg/kg provides a consistent, reliable, and effective attenuation of pressure responses when compared to esmolol 2.0 μg/kg.[22] In a similar study by Sarkar et al., both clonidine and dexmedetomidine were effective, but they used higher dose of clonidine of 3 μg/kg while using a lower dexmedetomidine dose of 0.5 μg/kg.[23]

In our study, we used the standard dosage of 1 μg/kg of dexmedetomidine in our study, however, this group had lower MAP values from baseline after intubation. Clonidine, on the other hand, maintained the MAP closer to baseline at doses of 2 μg/kg. Jarineshin et al. compared two different doses of dexmedetomidine and founded no significant difference on hemodynamics.[24] Future studies require to find out the optimal loading dose of dexmedetomidine which will keep the MAP closer to baseline.

Hypotension and bradycardia are considered the major side effects of α2-agonists. In a study, Kakkar et al. demonstrated that both clonidine and dexmedetomidine were effective for preventing hemodynamic response to intubation, but dexmedetomidine was associated with more side effects such as hypotension and bradycardia.[25] In our study, two patients also developed bradycardia which were excluded. The HR was also lower from baseline after drug administration in dexmedetomidine group than clonidine. Therefore, strict monitoring is required while using dexmedetomidine. Other side effects such as dryness of mouth and sedation which is found during the use of α2-agonists was found only in 5 patients (3 in clonidine and 2 in dexmedetomidine group) which did not require any intervention. There were no other serious adverse effects noted in this study.

This study has some limitations. First, catecholamine levels were not measured, which can more accurately reflect the sympathetic attenuation of the drugs. Second, the study was carried out in the ASA physical status Classes 1 and II patients with no cardiac or neurological issues. The population who will most likely benefit was thus not included.

This study adds to the literature that both dexmedetomidine and clonidine are effective in attenuation of the hemodynamic response to intubation. However, this study compares the two drugs determines their efficacy and safety. This has a clinical implication in cardiac and neurological patients where hemodynamic response can be detrimental and strict control is required. Our study has shown dexmedetomidine as an agent of choice in such patients. Further studies with larger sample size and measuring catecholamine levels preferably in cardiac patients are required to accurately compare between dexmedetomidine and clonidine.


   Conclusion Top


There is significant reduction in HR, SBP, DBP, and MAP by dexmedetomidine and clonidine as compared to controls during intubation. Furthermore, attenuation of pressor and tachycardia response to intubation was better following premedication with dexmedetomidine than with clonidine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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