|Year : 2014 | Volume
| Issue : 2 | Page : 94-98
A comparative study of clonidine and gabapentin for attenuating hemodynamic responses to laryngoscopy and tracheal intubation
Nagol Shekharappa Shreedhara, Nongthombam Ratan Singh, Haorongbam Shanti Singh, Langpoklakpam Chaoba Singh, Takhelmayum Hemjit Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||18-Sep-2014|
Dr. Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Laryngoscopy and intubation causes reflex sympatho-adrenal response in the form of tachycardia and hypertension. The present study compared oral gabapentin with oral clonidine for attenuating hemodynamic responses to laryngoscopy and tracheal intubation. Materials and Methods: Ninety patients of American society of Anesthesiologists (ASA) I and II in the age-group of 18-60 years, of either sex, posted for elective surgeries under general anesthesia were randomly divided into three groups (n = 30). On the morning of surgery, the study medications were given orally with sips of water 2 hour pre-operatively as: Group I received 200 μg clonidine, Group II received 900 mg gabapentin, and Group III received placebo. The heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were observed and recorded as 0 minute (baseline) and at 1, 3, 5, and 10 minutes after endotracheal intubation. Results: Oral clonidine (200 mcg) attenuated the increase in systolic blood pressure, diastolic blood pressure, and mean arterial pressure better than oral gabapentin (900mg). The increase in heart rate was significantly attenuated by clonidine as compared to gabapentin and placebo (P < 0.001). Gabapentin also attenuated tachycardiac response but it was not completely eliminated. As compared with placebo, gabapentin attenuated rise in diastolic blood pressure and mean arterial pressure at 3 and 5 minutes after intubation (P < 0.38, 0.007 at 3 and 5 minutes. Conclusion: Both clonidine and gabapentin attenuate hemodynamic response to laryngoscopy and tracheal intubation. Clonidine is a better drug compared to gabapentin and tachycardiac response was significantly attenuated.
Keywords: Attenuation, Clonidine, Gabapentin, Hemodynamic response, Intubation
|How to cite this article:|
Shreedhara NS, Singh NR, Singh HS, Singh LC, Singh TH. A comparative study of clonidine and gabapentin for attenuating hemodynamic responses to laryngoscopy and tracheal intubation. J Med Soc 2014;28:94-8
|How to cite this URL:|
Shreedhara NS, Singh NR, Singh HS, Singh LC, Singh TH. A comparative study of clonidine and gabapentin for attenuating hemodynamic responses to laryngoscopy and tracheal intubation. J Med Soc [serial online] 2014 [cited 2020 May 29];28:94-8. Available from: http://www.jmedsoc.org/text.asp?2014/28/2/94/141090
| Introduction|| |
Since the inception of general anaesthesia it has been well-recognized that laryngoscopy followed by tracheal intubation is a noxious stimulus, which can provoke untoward response in the cardiovascular (ischemic ST changes, tachycardia, hypertension, etc.), respiratory, and other physiological systems which are transient. These variations are undesirable with few patients like raised intraocular pressure, intracranial pressure. Significant tachycardia, hypertension, and dysrhythmias can occur with tracheal intubation.  With induction of general anaesthesia protective airway reflexes were diminished or absent and airway is secured with endotracheal tube. Several techniques have been proposed to prevent or attenuate these hemodynamic responses such as deepening the plane of anesthesia  , pre-treatment with nitroglycerin  , beta-blockers  , and opioids.  Many studies have shown clonidine, a selective α2 adrenoceptor agonist with sedative and analgesic effects, to be an effective drug for attenuation of hemodynamic responses to laryngoscopy and intubation.  Gabapentin, an anti-epileptic is also being used. Recently, few studies , have shown it to be useful for attenuation of intubation responses. This study was undertaken to evaluate the efficacy of gabapentin in attenuating hemodynamic responses to laryngoscopy and intubation and how it fares in comparison with clonidine.
| Materials and Methods|| |
A prospective, randomized and double-blinded study was conducted in a tertiary health care teaching hospital at Imphal during the period of 2 years (from September 2011 to September 2013) on patients undergoing general anesthesia fulfilling the inclusion criteria viz. patients with American society of Anesthesiologists (ASA) physical status I or II, aged between18-60 years of both sexes. A sample size of 28 patients per group was calculated based on a minimum clinically significant difference between the groups and taking α = 0.05 and β = 0.8 based on previous study done by Marashi SM et al.  In order to improve the quality of results of the study, 30 patients were taken for each group. The patients were randomly allocated into three groups by computer generated randomization chart to receive the following drugs during the study:
Group I Received 200 μg clonidine.
Group II Received 900 mg gabapentin.
Group III Received placebo.
All patients were examined a day before surgery, kept nil orally after 10:00 pm and received tab. alprazolam 0.5 mg orally and tab. ranitidine 300 mg as pre-medication on the night before surgery. On the morning of surgery, the study medications were given orally with sips of water 2 hour pre-operatively by a staff nurse who was not involved in the study. Patients were pre-medicated with inj. glycopyrrolate 4 μgm/kg i.m, inj ranitidine 1 mg/kg i.v, and inj ondensetron 0.08 mg/kg i.v 30 minutes before the induction of anesthesia.
After preoxygenating patients with 100% oxygen for 3 minutes anesthesia was induced with intravenous propofol 2 mg/kg till loss of patient response to verbal commands and loss of eyelash reflex; laryngoscopy and intubation was facilitated with intravenous suxamethonium 2 mg/kg. Anesthesia was maintained with N 2 O + O 2 + Isofurane and muscle relaxation was achieved with intravenous atracurium 0.5 mg/kg (loading dose) and 0.01 mg/kg (maintenance dose).
The baseline heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and rate pressure product (RPP) were observed and recorded as 0 minute value. Thereafter, the heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and rate pressure product were recorded at 1, 3, 5, and 10 minutes after endotracheal intubation. Any side effects like drowsiness, dizziness, and bradycardia were recorded, and any episode of bradycardia (HR <60) was treated by injection atropine 0.6 mg i.v stat. At the conclusion of surgery, isoflurane was stopped 5 minutes before skin closure and nitrous oxide was cut when patient had movements. Muscle relaxants were reversed with inj. glycopyrrolate 10 mcg/kg and inj. neostigmine 40 mcg/kg. Patients were extubated after the return of protective airway reflexes and observed in post anesthesia care unit. The findings of the study were recorded and the analysis of variance (ANOVA), Student T-test (independent) was used for statistical analysis using Statistical Package for the Social Sciences (SPSS) 20.
| Results|| |
There was no statistically significant difference in the age, sex, weight, and ASA grade among the three groups as shown in [Table 1].
As shown in [Figure 1], at 1, 3, 5, and 10 minutes, heart rate response to laryngoscopy and intubation was clinically lesser in clonidine group as compared to gabapentin and placebo group but statistically significant (P < 0.001 at 1, 3, 5, and 10 minutes). In the gabapentin group, there was a statistically significant reduction in heart rate at 1, 3, and 5 minutes (P < 0.03, P < 0.01, P < 0.08, respectively) as compared to placebo but higher mean heart rate as compared to clonidine group. In clonidine group, heart rate was less than baseline for the initial 10 minutes of observation. The mean arterial pressure at 3 and 5 minute interval after intubation were low in the clonidine group when compared to gabapentin group [Figure 1]. When compared to placebo group reduction in the mean arterial blood pressure at 3, 5, and 10 minutes were statistically significant (P < 0.001 at 3, 5, and 10 minutes) in the clonidine group. There was also reduction in the mean arterial blood pressure at 3 and 5 minute in the gabapentin as compared to placebo group (P < 0.038, 0.007 at 3 and 5 minutes).
|Figure 1: Showing the mean heart rate and mean arterial pressure (MAP) in the three groups at different time intervals (mean ± SD)|
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The mean systolic blood pressure was lesser in the clonidine group at 5 minutes as compared to placebo group and it was statistically significant (P < 0.001). Systolic blood pressure was low in clonidine group but not statistically significant in comparison with gabapentin and placebo group [Figure 2]. The mean diastolic blood pressures were low in clonidine group at 1, 3, and 5 minutes after intubation as compared to gabapentin group but not statistically significant. It was statistically significant at 1, 3, 5, and 10 minutes after intubation in clonidine group when compared to placebo group (P < 0.001). There was decrease in diastolic blood pressure in gabapentin group when compared to placebo group and it was not statistically significant. Overall, when compared to placebo group there was not much increase in the diastolic blood pressure in the gabapentin group and significant decrease in the clonidine group.
|Figure 2: Showing the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the three groups at different time intervals (mean ± SD)|
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Mean and standard deviation of RPP of clonidine group are statistically significant at 1, 3, 5, and 10 minutes interval after intubation as compared to gabapentin group and placebo (P < 0.001 at respective time intervals). In comparison with placebo group, gabapentin showed better results at 3 and 5 minutes (P < 0.003, P < 0.005, respectively). Gabapentin also showed reduction in the RPP at 1 minute (P = 0.02) and at 10 minutes (P = 0.041) [Figure 3]. Clonidine reduced the oxygen consumption better than gabapentin significantly.
|Figure 3: Showing the mean rate pressure product (RPP) in the three groups|
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As shown in [Table 2], the overall various side effects in gabapentin group was 13.33% out of which drowsiness was in 6.7% and dizziness in 6.6%, whereas rest of them did not report any side effects. In clonidine group, the overall incidence of side effects was 56.7% out of which 50.0% of the patients complained of drowsiness, whereas 6.7% (2 patients) had an episode of bradycardia.
| Discussion|| |
The mechanism by which gabapentin attenuates the pressor response to laryngoscopy and intubation is unknown. The inhibition of Ca2 + flux in muscle cells with a consequent inhibition of smooth muscle contraction might explain the effectiveness of gabapentin in attenuation of the pressor response to laryngoscopy. Thus, it may act in a manner similar to Ca2 + channel blockers as reported by Kiran S et al.  .
The attenuating effect of clonidine on hemodynamic responses to airway manipulation has previously been documented by many studies. Talebi H et al.  have documented that orally administered clonidine in pre-anesthetic period attenuates the stress response to laryngoscopy and intubation. The findings of the present study are well correlated with studies done by workers like Yokota S et al.,  and Singh S et al. 
Raval DL et al.[ 10] observed reductions in SBP and DBP following premedication with oral clonidine 0.2 mg by 7.63%. In post intubation period, SBP and DBP remained below baseline value producing significant attenuation of rise in SBP due to laryngoscopy and intubation. These findings may be favourably compared with the findings of the present study. Singh S et al. also showed that premedication oral clonidine 150 μg resulted in better hemodynamic stability and less anesthetic requirement.
Memis D et al.  and Fassalouki A et al. have specified doses of 800-1200 mg for attenuation of hemodynamic responses for laryngoscopy and intubation. According to a study by Mishra et al.,  900 mg of gabapentin administered orally 2 hours before induction of anaesthesia abolished the hemodynamic response after skull pin insertion. With this background, in this study, 900 mg of gabapentin was given 2 hours before intubation.
Gabapentin efficacy on attenuating hemodynamic responses following laryngoscopy was revealed by Fassoulaki et al.  In their study, they administered gabapentin 1600 mg in four divided doses, at 6 hours intervals (starting the day before surgery). SBP and DBP were significantly lower in the gabapentin group than in the control group (P < 0.05) immediately and also in 1, 3, 5, and 10 minutes after laryngoscopy but HR did not differ between the two groups at any of the times. In the present study, gabapentin, which was used in a dose of 900 mg 120 minutes prior to surgery, was found to attenuate the rise in DBP and MAP at 3, 5 and 10 minutes after intubation. This correlates with the studies done by Fassoulaki et al. and Memis et al. But the increase in heart rate in group gabapentin was not much more than the baseline values. When compared with the placebo group, gabapentin showed to attenuate the heart rate response to laryngoscopy and intubation indicating that it maintains the heart rate closer to baseline than clonidine group in which the heart rate decreased to less than baseline values.
In the present study, better control of systolic, diastolic, and mean arterial pressures was observed in clonidine group than gabapentin group (P < 0.001). It is in contrast to the findings of Marashi SM et al. and Kaya FN et al.  We found that clonidine attenuated heart rate response better than gabapentin at all time intervals. The differences in heart rate between their study and ours could have been due to the type of inhalational agent used and its concentration variation.
Previous studies have shown that arterial pressure and heart rate responses are greater when the duration of laryngoscopy exceeds 30 seconds.  In present study, the mean duration of laryngoscopy and intubation did not exceed 15seconds.
At 1, 3, 5, and 10 minutes, there were significant differences between the groups regarding heart rate changes in this study. Clonidine had better results in reducing the heart rate than gabapentin (P < 0.001 at all time intervals). The fall to baseline value in the gabapentin group was at the 5 th minute and in clonidine group, it was lower than baseline at all time intervals. This indicates that clonidine group showed significant reduction in heart rate compared to gabapentin group.
In a study by Montazeri K et al.,  SAP, DAP, MAP, and RPP at 1, 3, 5, 10, and 15 minutes after intubation were significantly lower in gabapentin group compared with placebo group (P < 0.05). There was no significant difference between clonidine group and placebo group in this regard. In the present study, mean and standard deviations of rate pressure product (RPP) of clonidine group were lower and statistically significant at 1, 3, 5, and 10 minutes interval after intubation as compared to gabapentin group and placebo (P < 0.001 at respective time intervals). In comparison with placebo group, gabapentin showed better results at 3 and 5 minutes (P < 0.003, P < 0.005 respectively). Gabapentin also showed reduction in the RPP at 1 minute (P = 0.02) and at 10 minutes (P = 0.041).
The most common adverse effects of gabapentin are somnolence (20%), ataxia (13%), fatigue (11%), and dizziness (8%). The other complications are nystagmus, headache, diplopia, tremor, and nausea, each one fewer than 10%.  There was no difference between the clonidine and gabapentin groups in these side effects in a study by Montazeri K et al. In present study, the overall incidence of side effects was higher in the clonidine group.
There are few limitations of this study:
- The study was conducted in a single center. A multi-centered larger study may be more informative.
- There was no measurement of stress mediators, i.e., endogenous plasma catecholamines or cortisol values perioperatively.
- The present study did not include elderly people in study group.
| Conclusion|| |
Both clonidine and gabapentin attenuate hemodynamic response to laryngoscopy and tracheal intubation. Clonidine is a better drug compared to gabapentin and tachycardiac response was significantly attenuated.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]