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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 194-199

Effects of intravenous clonidine or dexmedetomidine on haemodynamic responses to laryngoscopy and endotracheal intubation and sedation: A randomised double-blind clinical efficacy study


Department of Anaesthesiology and Critical Care Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Submission25-May-2020
Date of Decision16-Sep-2020
Date of Acceptance30-Sep-2020
Date of Web Publication5-Jan-2021

Correspondence Address:
Shameem Sunkesula
Assistant Professor, Department of Anaesthesiology and Critical Care Medicine, Sri Venkateswara Institute of Medical Sciences, Alipiri Road, Tirupati 517 507, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_43_20

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  Abstract 


Background: Laryngoscopy and tracheal intubation (LTI) is associated with undesirable haemodynamic (HD) responses. Both clonidine and dexmedetomidine have been tried to attenuate this HD response. The present study was to assess whether single pre-induction dose of intravenous clonidine (2 μg/Kg) or dexmedetomidine (1 μg/Kg) is more efficient to attenuate the HD response to LTI.
Methods: Sixty patients belonging to American Society of Anesthesiologists Grade I and II were randomly divided into two groups: group C (clonidine 2 μg/Kg) and Group D (dexmedetomidine 1 μg/Kg). Study drug was given as an infusion over 10 Min before induction of anaesthesia followed by standardised anaesthetic technique. Heart rate (HR) and blood pressure (BP) were studied at baseline, before study drug infusion (BSD), after study drug infusion, before LTI and at 1, 2, 3, 5 and 10 m in after intubation. Sedation score was analysed BSD, after study drug infusion and at the end of surgery
Results: This study revealed suppression of HR and BP at all time points in both the groups without any significant difference in suppression of HR between the groups. The magnitude of fall in BP in the clonidine group is more compared to the dexmedetomidine group before LTI and at 3, 5, and 10 min after tracheal intubation. The patients in the dexmedetomidine group were more sedated than in the clonidine group at the end of the study drug infusion.
Conclusions: Both clonidine and dexmedetomidine were effective in attenuating HD response to LTI. Dexmedetomidine appears to be superior to clonidine in maintaining stable HD.

Keywords: Clonidine, dexmedetomidine, laryngoscopy and tracheal intubation, sedation


How to cite this article:
Samantaray A, Rao MH, Divya R N, Sunkesula S. Effects of intravenous clonidine or dexmedetomidine on haemodynamic responses to laryngoscopy and endotracheal intubation and sedation: A randomised double-blind clinical efficacy study. J Clin Sci Res 2020;9:194-9

How to cite this URL:
Samantaray A, Rao MH, Divya R N, Sunkesula S. Effects of intravenous clonidine or dexmedetomidine on haemodynamic responses to laryngoscopy and endotracheal intubation and sedation: A randomised double-blind clinical efficacy study. J Clin Sci Res [serial online] 2020 [cited 2021 Jan 27];9:194-9. Available from: https://www.jcsr.co.in/text.asp?2020/9/4/194/306192




  Introduction Top


Laryngoscopy and tracheal intubation (LTI) often provokes an undesirable increase in arterial blood pressure (BP) and/or heart rate (HR).[1] The magnitude of haemodynamic (HD) changes observed may be dependent on various factors such as depth of anaesthesia, use of drugs before airway manipulation, the anaesthetic agent used and the duration of LTI. To date, the exact mechanism of HD responses to LTI has not been clarified. The proposed mechanism for the perturbed HD response during LTI is short-lasting sympatho-neuroendocrine stimulation.[2],[3],[4] The increase in HR and BP is usually transitory, variable and unpredictable. Transitory hypertension and tachycardia are probably of no consequences in healthy individuals. However, either or both may be hazardous to those with cardiovascular or cerebrovascular disease.[5],[6],[7] Induction agents do not adequately or predictably suppress the HD responses induced by LTI. Hence, before initiating laryngoscopy, additional pharmacological measures such as use of volatile anaesthetics,[8] topical and intravenous(IV) lidocaine,[9],[10] opioids,[11],[12],[13] vasodilators,[14],[15] calcium channel blockers[16],[17],[18] and β-blockers[19],[20],[21] have been tried by various investigators. Alpha 2-agonists are assuming greater importance as anaesthetic adjuvants and analgesics. Their primary effect is sympatholytic. Conventionally, they have been used as antihypertensive drugs, but applications based on their sedative, anxiolytic and analgesic properties are being developed. Clonidine, prototypical drug of this class, is a selective partial agonist for alpha-2 adrenoceptor, with a ratio of approximately 200:1 (alpha-2:alpha-1). It is conventionally used as an antihypertensive agent. It also has analgesic and sedative properties. Dexmedetomidine is an alpha-2 adrenoceptor agonist with sympatholytic, sedative, anxiolytic, anaesthetic-sparing and HD-stabilising properties without significant respiratory depression.

The present study was to assess whether single pre-induction dose of IV clonidine or dexmedetomidine is more efficient to attenuate HD response to LTI.


  Material and Methods Top


This was a prospective, randomised, double-blind clinical efficacy study conducted in various surgical operation theatres of university teaching hospital in South India, after obtaining approval from the Institutional Ethics Committee. Written informed consent of all the patients was taken, and randomisation was done by generating a computerised random number table and sealed opaque envelope technique. Randomisation sequence was generated before recruiting study participants. The double-blind nature of the study was ensured by having an independent anaesthesiologist, not participating in the study, preparing clonidine (2 μg/Kg) or dexmedetomidine (1 μg/Kg) in ready to inject form for a total volume of 10 ml using 0.9% normal saline.

Sample size of minimum 24 per group was derived using Cohen's formula based on the assumption of alpha error of 5% (α = 0.05) at a study power of 80% (β = 0.2) to detect at least 25% difference in the intubation response (HR and BP) between the groups. We have included 30 patients per group to compensate for post-randomisation drop-outs.

Sixty patients of American Society belonging to Anesthesiologists Physical Status Grade I and II, aged between 18 and 65 years of either sex, undergoing elective surgical procedures, were included in the study. Patients with history of any cerebrovascular, neurological, cardiovascular, pulmonary, metabolic or neuromuscular disease and those on medications that would influence autonomic or cardiovascular response to intubation and predicted difficult intubation (Mallampati class III and IV)[11] were excluded from the study. All patients received premedication of tablet alprazolam 0.25 mg per orally at night before surgery. After arrival in the operating room, an iv catheter was placed and monitoring of electrocardiogram, noninvasive BP, pulse oximetry, and end-tidal carbon dioxide (EtCO2) monitoring followed by infusion of the study drugs over 10 Min using a syringe pump. At the end of infusion of study drugs, patients' level of sedation was assessed by sedation score over 15 Sec followed by pre-oxygenation with 100% oxygen. Anaesthesia was induced intravenously by midazolam (0.04 mg/Kg), fentanyl (2 μg/Kg) and thiopentone sodium (till loss of eye lash reflex +25 mg). This was followed by iv vecuronium (0.12 mg/Kg) to facilitate intubation. Three minutes later, laryngoscopy was performed and intubation of the trachea was done using appropriate-sized tracheal tube (size 7.0–8.5). After confirmation of tracheal tube position, the patient's lungs were ventilated with 50% oxygen in air. Ventilation was controlled to normocapnia using EtCO2 monitor. The following parameters were studied for comparison: HR, systolic BP (SBP), diastolic BP (DBP) and mean arterial blood pressure (MAP) at baseline (BL), just before study drug infusion (BSD), after administration of study drugs (ASD), before laryngoscopy and tracheal intubation (BLTI) and at 1 (T1), 2 (T2), 3 (T3), 5 (T5) and 10 (T10) Min after intubation. Sedation score before infusion, at the end of study drug infusion and at the end of surgery after reversing neuromuscular blockade was assessed using Modified Observer's Assessment of Alertness/Sedation Scale (Annexure 1).

Statistical analysis

Independent Student's 't-test' was used to compare the continuous variable between the two groups. Chi-square test and Fisher's exact test were used to analyse the categorical data and to test the association between the variables. Wilcoxon signed-rank test (2-tailed) was used for non-normal distributed data. Intragroup comparisons of HD variables were made with BL as control value using repeated-measures analysis of variance (ANOVA) followed by post hoc comparison using Bonferri correction. The results were considered significant when P value <0.05.


  Results Top


The study plan is shown in [Figure 1]. There was no significant difference between the two groups with regard to demographic data. Both groups had comparable HR at all time points BSD and after study drug infusion. In Group C, the change in HR was not statistically significant compared to BL at any time point. In Group D, we found a significant reduction in HR compared to baseline at three time points, i.e., ASD, BLTI and T10 [Table 1].
Figure 1: Study plan

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Table 1: Comparison of heart rate (beats/minute) between the study groups*

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Both groups had comparable SBP at BL, BSD, ASD and T2. The fall in SBP in Group C was statistically significant compared to Group D at five time points, i.e., BLTI, T1, T3, T5 and T10. In Group C, the change in SBP was statistically significant compared to baseline at five time points, i.e., ASD, BLTI, T3, T5 and T10. In Group D, the change in SBP was statistically significant compared to baseline at five time points, i.e., ASD, BLTI, T3, T5 and T10 [Table 2].
Table 2: Comparison of blood pressure and mean arterial pressure

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Both groups had comparable DBP at all time points, except at two time points, i.e., BLTI and T5 where changes in DBP in Group C are lower compared to Group D which are statistically significant. In Group C, the change in DBP was statistically significant at five time points, i.e., ASD, BLTI, T3, T5 and T10. In Group D, the change in DBP was statistically significant at four time points, i.e., BLTI, T3, T5 and T10 after tracheal intubation [Table 2].

Both groups had comparable MAP at BL and BSD. After study drug infusion, the change in MAP was significantly lower in Group C compared to Group D at four time points, i.e., BLTI, T3, T5 and T10. In Group C, the change in MAP was statistically significant compared to baseline at five time points, i.e., ASD, BLTI, T3, T5 and T10. In Group D, the change in MAP was statistically significant compared to baseline at five time points, i.e., ASD, BLTI, T3, T5 and T10 [Table 2].

All the patients were awake and alert (SS-5) at the beginning of the study (i.e., BL and BSD), and therefore, no statistical comparison could be made. After study drug infusion, the patients in both the groups were sedated and had a lower sedation score compared to BL. The patients in Group D tend to be more sedated compared to Group C after study drug infusion. At the end of surgery, all the patients were responding to their name spoken verbally, and there was no statistically significant difference in mean sedation score between the groups [Table 3]. Patients from Group C were infused with more fluid (mL) compared to Group D (405.0±72.3 Vs 340.0±102.8; P= 0.006).
Table 3: Comparison of sedation score

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More patients from the clonidine group had hypotension during the study period and consequently received a higher mean dose of ephedrine to counteract hypotension. One patient from clonidine group also had tachycardia after study drug administration [Table 4]. In contrast to none from clonidine group, two patients had bradycardia and one patient had ventricular ectopics from dexmedetomidine group. Both the patients from the dexmedetomidine group received atropine to revert bradycardia, but ventricular ectopics resolved spontaneously within 15 Sec, and the patient had not received any treatment for the same.
Table 4: Comparison of adverse cardiovascular events

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  Discussion Top


LTI often provokes an undesirable increases in arterial BP and/or HR.[1] The proposed mechanism for the perturbed HD response during LTI are short-lasting sympatho-neuroendocrine stimulation.[2],[3],[4] The present study was to assess whether single pre-induction dose of iv clonidine or dexmedetomidine is more efficient to attenuate HD response to LTI.

Several studies[22],[23],[24] have successfully used 2 μg/Kg of clonidine for attenuating HD response to tracheal intubation. Other studies[25],[26],[27] have used dexmedetomidine 1 μg/Kg iv and found it to be effective in attenuating the pressor response during laryngoscopy. Hence, we have compared clonidine (2 μg/Kg) and dexmedetomidine (1 μg/Kg) on HD responses to laryngoscopy and endotracheal intubation and sedation.

In our study, we have used dexmedetomidine (1 μg/Kg) and clonidine (2 μg/Kg) as an infusion over 10 min before induction of general anaesthesia as clinically significant episodes of bradycardia and sinus arrest have been associated with dexmedetomidine during rapid iv administration (e.g., bolus administration). We found a decrease in HR in both the groups after infusion of study drugs, but this decrease in HR was maintained for dexmedetomidine group throughout the study period and reached statistically significant level at three points (ASD, BLTI and T10), whereas in the clonidine group, the initial decrease in HR was offset by a 10% increase HR (76–84 bpm) at T1, but it did not reach statistical significance. Both the groups reduced the blood pressure (SBP, DBP and MAP) at the end of infusion (P-value < 0.05). A 9%–10% increase in SBP, DBP and MAP was found in the clonidine group at 1 Min after LTI without reaching any statistical significance, whereas in the dexmedetomidine group, the SBP, DBP and MAP remained more or less same as BL values at T1. However, unlike other studies, the SBP, DBP and MAP remained below the BL values at T3–T10 and it was statistically significant. The magnitude of fall in BP was more in the clonidine group compared to dexmedetomidine group even at 3 Min after intubation (T3–T10) and significantly more number of patients from the clonidine group had hypotension and received significantly more fluid and more number of doses of ephedrine to counteract the hypotension. Nevertheless, the low BP resulted at the end study (T10) is well within the predefined clinical ranges of BP fluctuation (30% from the baseline variables) in both the groups.

Studies[28],[29],[30] comparing iv clonidine and dexmedetomidine demonstrated that both dexmedetomidine (1 μg/Kg) and clonidine (2–3 μg/Kg) effectively attenuated the HD response to LTI but could not abolish the catecholaminic sympathetic cardiovascular response completely. There was an increase in HR and BP for a variable period ranging from 1 to 3 Min after LTI. A study[29] confirmed that both clonidine and dexmedetomidine are superior to placebo in attenuating the HD response, whereas other two studies opined the superiority of dexmedetomidine over clonidine as a better attenuating agent for tachycardiac response to LTI. In contrast, the level of sedation as analysed with Modified Observer's Assessment of Alertness/Sedation Scale differs from that used in another study[29] with a significantly higher sedation score in the clonidine group (P < 0.05) at the end of study drug infusion. However, none of our patients from any group had low saturation or respiratory depression because of study drug infusion.

In a study[31] compared the effect of iv dexmedetomidine (1 μg/Kg) and clonidine (2 μg/Kg) versus placebo (normal saline) on cardiovascular response resulting from laryngoscopy and endotracheal intubation, they concluded that there was significant reduction in HD response by dexmedetomidine and clonidine as compared to controls and furthermore better following premedication with dexmedetomidine than with clonidine.

From our study, we conclude that both clonidine and dexmedetomidine were able to attenuate the undesirable HD responses to LTI. The magnitude of fall in HR was comparable between the dexmedetomidine and clonidine group, whereas the magnitude of fall in SBP, DBP and MAP was more pronounced in clonidine group. Patients from dexmedetomidine group were more sedated compared to clonidine group, but the level of sedation was clinically insignificant. One μg/Kg of dexmedetomidine 10 min before induction of anaesthesia is superior to 2 μg/Kg IV clonidine for attenuating the HD response to LTI with lesser incidence of hypotension and a comparable attenuation of tachycardia response.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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