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IOSR Journal Of Pharmacy
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
www.iosrphr.org Volume 4, Issue 2(February 2014), Pp 28-38

Comparison of Dexmedetomidine with Fentanyl in Attenuation of
Pressor Response during Laryngoscopy and Intubation
1,

Dr Sagar Gandhi , 2,Dr VigyaGoyal , 3,Dr Krishnaprabha Radhakrishnan ,
4,
Dr Mahesh Balakrishnan
1

,Practisinganaesthetist
3 year resident ,BJMC Ahmedabad
3, rd
3 year resident ,BJMC Ahmedabad
4, rd
2 year resident ,BJMC Ahmedabad

2, nd

ABSTRACT
INTRODUCTION
The pressure response, which is part of a huge spectrum of stress response, results from the increase in
sympathetic and sympathoadrenalactivity.Acomparision between dexmeditomedine and fentanyl in suppressing
the pressorresponse is studied.
OBJECTIVE
This study was done to compare the effectiveness of Dexmedetomidine with Fentenyl in attenuating the pressor
responses associated with laryngoscopy and endotracheal intubation in groups belonging to normotensive ASA
grade 1, 2 risk surgical patients.
MATERIAL
The study was carried out on 100 patients belonging to ASA grade I and II, aged 15 to 65 years, including either
gender, scheduled for elective surgical procedures under general anesthesia.
RESULT
DEXMEDETOMIDINE when used as I.V. premedicant in dose of 0.6 μg/kg provides beneficial effect in
attenuation of pressor response to laryngoscopy and endotracheal intubation as compare to FENTANYL in dose
of 2 μg/kg .

I.

INTRODUCTION

Intubation has been practiced following its description by Rowbatham and Magill in 1921. The
circulatory responses to laryngeal and tracheal stimulation following laryngoscopy and intubation were
documented by Reid and Brace in 1940 and king et al in 1951. The pressure response, which is part of a huge
spectrum of stress response, results from the increase in sympathetic and sympathoadrenal activity, as evidence
by increased plasma catecholamines concentration in patients undergoing surgery under general anaesthesia.
Increase in mean arterial pressure of an average of 25mm Hg was observed in normotensive patients following
laryngoscopy and intubation under anesthesia with thiopentone, nitric oxide, oxygen and suxamethonium.
The rise in the heart rate and blood pressure is usually transient, variable and unpredictable. Usually these
changes are well tolerated by healthy individuals. However these changes may be fatal in patient with
hypertension, coronary artery disease or intracranial hypertension. Left ventricular failure, myocardial ischemia,
cerebral hemorrhage may occur in high risk patients. Convulsions may be precipitated in pre-eclamptic patients
To blunt this pressor response, various methods have been tried including,
 Deeper plane of anaesthesia with intravenous or inhalation agent

Use of Propofol
 Curtailing the duration of laryngoscopy to less than 15 seconds
 Sympathetic blockage
 Lidocaine spray or gargles 3 minutes prior to intubation
 Use of intravenous Lidocaine to blunt the pressor response
 Use of ACE inhibitors e.g. Captopril, Enalapril 45 minutes prior to intubation
 Use of Magnesium sulphate
 Various antihypertensive and vasodilators e.g. IV Hydralazine, Ca +2 channel blocker like Nifedipine, beta
blockers like Esmolol
 Use of Nicardipine
 Use of Opiods prior to induction e.g. Fentanyl, SuFentanyl or AlFentanyl

28
Comparison Of Dexmedetomidine With Fentanyl…




Use of Nitroglycerine ointment, intravenous, sublingual spray, intranasal spray
Use of Gabapentin
Alpha -2 agonists like Clonidine

II.

MATERIAL AND METHOD

Patient selection :
 After approval from ethical committee, civil hospital, Ahmedabad, the study was carried out on 100 patients
belonging to ASA grade I and II, aged 15 to 65 years, including either gender, scheduled for elective
surgical procedures under general anesthesia.
EXCLUSION CRITERIA:
The patients with baseline heart rate < 60 bpm, baseline blood pressure < 100/50 mm of Hg, reactive
airway disease, history of cardiac disease and hypertensive patient, on treatment with adrenergic augmenting or
depleting drugs, PR interval > 0.24 seconds on ECG, 2nd and/or 3rd degree heart block, requiring 2 or more
attempts for laryngoscopy and intubation were excluded from the study. Patients were randomly divided into
two groups of 50 each. Group D received 0.6 mcq / kg Dexmedetomidine and Group F received 2 mcq / kg
Fentanyl diluted in 10 ml normal saline 10 minutes before laryngoscopy and intubation.
Preoperative evaluation :
 Patients were subjected to routine investigations like blood sugar, Hb level, renal and liver function test.
 Airway of patients that were likely to be anticipated for difficult intubation was evaluated.
Preoperative preparation :
 The procedure was explained to the patient and written informed consent was taken.
 All patients were preloaded with crystalloid fluid, 8-10 ml/kg.
 All patients were pre-medicated with inj. Glycopyrrolate 0.04mg/kg iv and inj.Ondansetron 0.15 mg/kg i.v.
 Heart rate, systolic and diastolic blood pressure was recorded before pre-medication and 10 minutes after
pre-medication in patients.
Selection of groups:
(1) Group D – Dexmeditomidine (0.6 mcg/kg diluted in 5ml saline IV over 1 min)
(2) Group F – Fentanyl (2 mcg/kg diluted in 5ml saline IV over 1 min)


III.

METHOD OF STUDY :

With patient in supine position , Injection DEXMEDETOMIDINE 0.6 mcq/kg diluted in 10 ml saline and
Injection FENTANYL 2 mcq/kg diluted in 10 ml saline in groups D and F respectively , were administered
intranvenously 10 minutes before laryngoscopy and intubation.
 Heart rate, systolic and diastolic blood pressure, SPO2 was recorded at 1 minute interval of drug
administration.
 Patients were induced with inj. Pentothal (4-7 mg/kg) i.v. and inj. Suxamethonium (2mg/kg) i.v. followed
by Laryngoscopy and intubation.
 Variables to be monitored were heart rate, systolic blood pressure, diastolic blood pressure, SPO 2 and ECG.
 All parameters were recorded at following stages:
Before pre-medication (BPM)
After pre-medication (APM)
30 seconds after endotracheal intubation (AEI)
And then every one minute up to 10 minute (AEI)
 All intubation were accomplished within 15 seconds by an expert anaesthesiologist.
 Only one attempt of intubation was accepted in the study.
 Patient who had coughed or bucked during procedure were excluded from study.
 After intubation, patients were maintained with Isoflurane(0.4 % v/v) or Sevoflurane(0.8% v/v), O2 (50%)
,N2o (50%) and non-depolarizing muscle relaxant.
 At the end of surgery, patients were reversed with inj. Glycopyrrolate and inj. Neostigmine.
Patients were watched for any complication like tachycardia, hypotension, arrhythmias, bronchospasm during
intraoperative and post operative period
This study was conducted to evaluate the efficacy of intravenous Dexmedetomidine and Fentanyl in attenuation
of stress response to laryngoscopy and intubation. A hundred adult patients of either gender, belonging to ASA
grade I or II were selected for the study. Statistical data wasanalyzed by using Z test wherever required.

29
Comparison Of Dexmedetomidine With Fentanyl…

(1 )Patient demographics :
a) Age:
The mean age of the patients in group D and F were 37.76 ± 10.41 years and 38.96 ± 9.94 respectively.
b) Weight :
The mean weight of patients in groups D and F were 63.7 ± 6.57 and 64.58 ± 5.16 respectively
Table 1. Demographic data
Age
(in years)
Group D
(DEXMEDETOMIDIN
E

Group F
(FENTANYL)

Number of Patients

Weight
(in kgs)

Males

Females

37.76 ± 10.41*

20

30

63.7 ± 6.57*

38.96 ± 9.94*

21

29

64.58 ± 5.16*

Age and weight of the all patients in both groups are comparable to each other and there is no
statistical difference between them ( * - p value > 0.05).
Figure 1. Mean age of the patients in all groups (n=100)

Figure 2. Mean weight of the patients in all groups (n=100)

30
Comparison Of Dexmedetomidine With Fentanyl…

(2 ) HEART RATE :
The heart rate was measured at baseline, after IV premedication for every one minute interval till 10
minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after intubation (Table 2 ).
It was observed that the heart rate increased in both groups immediately after endotracheal intubation. The heart
rate started to return to normal values at the end of 10 minutes post intubation.
Table 2. Changes in heart rate
Heart rate
(beats per
Minute)
Mea
Group D
n
±SD
Mea
Group F n
±SD

At
baseline

1 min
after ETI

2 min
after ETI

3 min
after ETI

5 min
after ETI

7 min
after ETI

82.78#

10 min
after
premed
68.88*

76.2*

78.6*

78.22*

73.38*

70.76*

10 min
after
ETI
68.58*

9.18#
82.04#

9.68*
80.3*

11.88*
94.28*

11.91*
99.48*

13.42*
98.54*

10.74*
94.22*

10.34*
92.28*

9.83*
90.34*

10.11#

10.35*

9.50*

11.88*

11.25*

10.54*

11.18*

12.15*

# - Base line heart rate of all patients of both groups are comparable to each other and there is no
statistical difference between them (p value > 0.05).
*-The increase was highly significant in group F as compared to group D during laryngoscopy and after
intubation ( p value <0.001 ).

31
Comparison Of Dexmedetomidine With Fentanyl…
Figure 3. Heart rate in all groups at various time intervals

(3) Systolic blood pressure:
The systolic blood pressure was measured at baseline, after IV premedication for every one
minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes
after intubation (Table 3). It was observed that the systolic blood pressure increased in both groups immediately
after endotracheal intubation. The systolic blood pressure started to return to normal values at the end of 10
minutes post intubation.
Table 3. Changes in systolic blood pressure
At
baseline

10 min
after
premed

1 min
after
ETI

2 min
after
ETI

3 min
after
ETI

5 min
after ETI

7 min
after ETI

10 min
after ETI

Mean

130.88#

112.96*

122.96*

125.24*

122.32*

116.04*

111.6*

107.1*

±SD

8.52#

10.86*

14.47*

15.19*

15.40*

14.21*

12.94*

10.78*

Mean

129.38#

121.58*

131.44*

146.56*

143.14*

135.46*

126.56*

117.72*

±SD

9.97#

9.98*

7.28*

7.99*

7.62*

7.02*

7.56*

4.73*

Systolic blood
pressure
(mmHg)
Group
D

Group
F

# - Base line systolic blood pressore of all patients of both groups are comparable to each other and
there is no statistical difference between them (p value > 0.05).
*- The increase was highly significant in group F as compared to group D during laryngoscopy and
after intubation (p<0.001).

32
Comparison Of Dexmedetomidine With Fentanyl…
Figure 4. Systolic blood pressure in all groups at

various time intervals

(4) Diastolic blood pressure:
The diastolic blood pressure was measured at baseline, after IV premedication for every one minute
interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after
intubation (Table 4). It was observed that the diastolic blood pressure was increased significantly from the
baseline during laryngoscopy and after intubation in both groups and returned to normal at the end of 10
minutes post intubation in all the groups.

Table 4. Changes in Diastolic blood pressure
1 min
after
ETI
75.1*

2 min
after
ETI
77.12*

3 min
after ETI

5 min
after ETI

78.32#

10 min
after
premed
69.02*

75.7*

±SD

5.65#

8.09*

10.76*

10.74*

Mean

77.08#

73.48*

78.38*

±SD

2.57#

3.13*

2.81*

Systolic blood
pressure
(mmHg)
Group D Mean

Group F

At
baseline

10 min
after ETI

71.72*

7 min
after
ETI
68.42*

10.13*

9.50*

9.03*

7.65*

82.68*

81.72*

80.26*

78.88*

77.14*

2.90*

2.49*

2.36*

1.61*

1.95*

65.92*

# - Base line diastolic blood pressore of all patients of both groups are comparable to each other and
there is no statistical difference between them (p value > 0.05).
* - The increase was highly significant in group F as compared to group D during laryngoscopy and
after intubation (p<0.001).

33
Comparison Of Dexmedetomidine With Fentanyl…
Figure 5.Diastolic Blood Pressure in all groups at

various time intervals

(5) Mean Arterial Blood Pressure:
The mean arterial blood pressure was measured at baseline, after IV premedication for every one
minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes
after intubation (Table 5). It was observed that the mean arterial blood pressure was increased significantly
from the baseline during laryngoscopy and after intubation in both groups and returned to normal at the end of
10 minutes post intubation in all the groups.
Table 5. Changes in Mean Arterial Pressure
Mean arterial
pressure
(mmHg)
Group
Mean
D
±SD
Group F Mean
±SD

At
baseline
95.66#
5.95#
94.34#
3.69#

10 min
after
premed
83.52*
8.64*
89.35*
4.13*

1 min
after
ETI
90.89*
11.44*
95.89*
3.20*

2 min
after
ETI
93*
11.76*
103.76*
3.30*

3 min
after ETI

5 min
after ETI

7 min
after ETI

10 min
after ETI

91.08*
12*
101.99*
3.36*

86.35*
10.77*
98.48*
2.98*

82.67*
9.95*
94.61*
2.85*

79.51*
8*
90.53*
2.22*

# - Base line Mean Arterial Blood Pressure of all patients of both groups are comparable to each other
and there is no statistical difference between them (p value > 0.05).

* - The increase was highly significant in group F as compared to group D during laryngoscopy and
after intubation (p<0.001).
(6) Effect OfDexmedetomodine On Hemodynamic Parameter:
After pre medication with Dexmedetomidine , initially there is a increase in blood pressure after that there is
decrease in blood pressure. Heart rate decrease after application of Dexmedetomidine.

34
Comparison Of Dexmedetomidine With Fentanyl…
Figure 6 : Effects Of Dexmedetomidine On Hemodynamic Parameter

Dex - Dexmedetomidine
DISCUSSION
Stress response under anesthesia has been universally recognized phenomenon which may be in the
form of endocrine or autonomic disturbance. The pressor response to laryngoscopy and endotracheal intubation
in form of tachycardia, hypertension and arrhythmias may be potentially dangerous. This hemodynamic change
is due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. This
increase in blood pressure and heart rate are usually transient, variable and unpredictable. Transient
hypertension and tachycardia are probably of no consequence in healthy individuals, but either or both may be
hazardous to those with hypertension, myocardial insufficiency and cerebrovascular disease.33The periintubation period is one of the most stressing moments of general anesthesia 2. These changes are the maximum
at 1 minute after intubation and last for 5-10 minutes.Stretching of pharyngeal and laryngeal tissue during
laryngoscopy as the major causes of haemodynamic response.Stimulation of supraglottic region during
laryngoscopy was a major cause of hemodynamic catecholamine response and that contributed to very little
additional stimulation.
A wide variety of pharmacological agents were used to attenuate the haemodynamic response: Surface anaesthesia of larynx and pharynx with Lidocaine spray proved unsuccessful because of the need to
perform laryngoscopy with resultant stretching and pressure on tissue of larynx and pharynx.
 Lidocaine 1.5mg/kg does not markedly attenuate the stress response.
 Deep plane of anaesthesia with volatile agents control changes in heart rate and arterial pressure but it is not
useful for rapid sequence intubation may lead to hypotension and prolonged recovery.
 Sodium nitoprusside : 1-2µg/kg
This vasodilator may also lead to intra operative hypotension and
may require invasive arterial pressure monitoring.
 Other drugs like…
 Labetolol : but has long half life
 Diltiazem
 Verapamil
 Nicardipine
 Opoids like Fentanyl, Buprenorphine
The search for ideal technique or agents for attenuation of haemodynamic changes still continues.Complications
of pressor responses that follow laryngoscopy include myocardial ischaemia, cardiac failure, intracranial
haemorrhage and increase in ICP.

35
Comparison Of Dexmedetomidine With Fentanyl…
Studies of hypertensive patients have shown than pressure responses to laryngoscopy is exaggerated in
these patients that is associated with a marked increase in nor-adrenaline concentration in the blood.37,41Recent
studies with alpha-2 adrenoceptor agonists have demonstrated beneficial effects in anesthetized patients.
Clonidine attenuates hemodynamic responses during laryngoscopy and endotracheal intubation. It also reduces
dose requirements of inhaled anesthetics and potentiates effects of opioids during surgical stimulation. In
addition, alpha-2 adrenoceptor agonists may have clinically significant anxiolytic activity. Dexmedetomidine is
a highly specific, potent, and selective alpha-2 adrenoceptor agonist.Dexmedetomidine caused a dose-dependent
decrease in arterial blood pressure and heart rate (HR), and reduction in sympathetic nervous activity was
manifested as a dose-dependent decline in plasma levels of norepinephrine. Single intravenous doses of
Dexmedetornidine administered 15 min before the induction of anesthesia decreased Thiopental requirements,
attenuated the hemodynamic responses to laryngoscopy and endotracheal intubation, and diminished Isoflurane
requirements.8,10,11The present study was conducted to compare the efficacy of premedication with
Dexmedetomidine and Fentanyl on hemodynamic parameters after laryngoscopy and endotracheal intubation.
The study was carried out in 100 patients of ASA grade I and II who were divided into 2 groups of 50 each. The
first group (group D) was given InjDexmedetomidine 0.6 µg/kg and second group ( group F) was given Inj
Fentanyl 2 µg/kg, 10 minutes before laryngoscopy and intubation. Hemodynamic parameters like, heart rate,
systolic blood pressure, diastolic blood pressure were measured at different time intervals in each patient. The
results and observations were recorded and compared

PATIENT DEMOGRAPHICS
As shown in Table 1, there was no statistical significant difference between the mean age (in years) and mean
weight (in kgs) among two groups. The gender distribution was almost equal both groups.
Heart rate
In both groups the heart rate started decreasing up to 10 minutes after premedication with study drug in
respective group. These observations are comparable to those by B. Scheininet al 10, A. EsraSagiroglu et al26,
Anila D. Malde et al20, Sam Chung et al9, Sukhminderjit Singh Bajwa et al32, Shobhana Gupta et al31,
SajithSulaiman et al33. In our study, we observed a decrease of 16.8% heart rate in Group D and 2.12% heart
rate in group F from base line value.In both groups, heart rate was increased immediately after laryngoscopy and
intubation. However increased in heart rate was more in Group F as compare to Group D.This increase was
highly significant (p<0.001). These observations are comparable to those by Martina Ahoet al 8, Sukhminderjit
Singh Bajwa et al32, N. Turgut et a22. However Sukhminderjit Singh Bajwaet al 32 used Dexmedetomidine in
dose of 1 µg/kg and N. Turgut et al22 used Fentanyl in dose of 1 µg/kg.
Systolic Blood Pressure
After premedication with study drug in respective group systolic blood pressure started decreasing
from its baseline value. These observations are comparable to those by Martina Ahoet al 8, Sukhminderjit Singh
Bajwa et al32, PekkaTalke et al 14, Varshali M Keniya et al29, FerdiMenda et al25, Maria Cristina Smania et al23,
John P. Ebert et al6, Sam Chung et al9. In our study, we observed a decrease of 13.70% systolic blood pressure
in group D and 6.03% systolic blood pressure in group F from base line value. In our study, it is evident that the
systolic blood pressure was significantly increased in both the groups after laryngoscopy and intubation
(p<0.05). The peak increase in systolic blood pressure was seen just after intubation and cuff inflation (after1&2
minute). The increase in systolic blood pressure is less in group D as compared to group F and this difference is
statistical highly significant ( p<0.001). In contrast to present study result, Martina Aho et al 8 did not find any
difference in blood pressure response between Fentanyl and Dexmedetomidine groups. The systolic blood
pressure came back to near normal within 10 minutes post intubation.
Diastolic Blood Pressure
After premedication with study drug in respective group, diastolic blood pressure started decreasing
from its beseline value. These observations are comparable to those by Martina Aho et al 8, Sukhminderjit Singh
Bajwa et al32, PekkaTalke et al 14, Varshali M Keniya et al29, FerdiMenda et al25, Maria Cristina Smania et al
23
,John P Ebert et a 6, Sam Chung et al9. In our study, we observed a decrease of 11.88% diastolic blood pressure
in Group D and 4.68% diastolic blood pressure in group F from base line value. In our study, the diastolic blood
pressure was significantly increased in both the groups after laryngoscopy and intubation (p<0.05). The peak
increase in diastolic blood pressure was seen just after intubation and cuff inflation (after 1&2 minute). The
increase in diastolic blood pressure is less in group D as compared to group F and this difference is statistical
highly significant ( p<0.001). In contrast to present study result, Martina Aho et al 8 did not find any difference
in blood pressure response between Fentanyl and Dexmedetomidine groups. The diastolic blood pressure came
back to near normal within 10 minutes post intubation.

36
Comparison Of Dexmedetomidine With Fentanyl…
Mean Arterial Blood Pressure
The mean arterial blood pressure was significantly increased in both the groups after laryngoscopy and
intubation (p<0.05). The peak increase in mean arterial blood preesure was seen just after intubation and cuff
inflation (after 1&2 minute). The increase in mean arterial blood pressure is less in group D as compared to
group F and this difference is statistical highly significant ( p<0.001). These observations are comparable to
those by Sukhminderjit Singh Bajwaet al32 and N.Turgut et al.22 However Sukhminderjit Singh Bajwa et al 32
used Dexmedetomidine in dose of 1 µg/kg and N.Turgut et al 22 used Fentanyl in dose of 1 µg/kg.
Side effects and complications
In our study side effects and complications like bradycardia, hypotension, respiratory depression etc
encountered were very few and could be easily treated.
CONCLUSION AND SUMMARY
The present study was carried out “To compare the efficacy of intravenous DEXMEDETOMIDINE and
FENTANYL in attenuation of stress response to laryngoscopy and intubation” in 100 adult patients,
scheduled for various surgical procedures under general anaesthesia during February 2012 to August 2012 at
civil hospital Ahmedabad. After approval from ethical committee of hospital, the patients were randomly
divided into 2 groups:
 Group D: Received DEXMEDETOMIDINE 0.6 μg/kg intravenously.
 Group F: Received FENTANYL 2 μg/kg intravenously.
The following observations were made:
[1] It was observed that the heart rate increased after laryngoscopy and intubation in both groups and it started
to return to near normal values at the end of 10 minutes post intubation. The increase in heart rate was
highly significant in group F as compared to group D during laryngoscopy and after intubation.
Dexmedetomidine produces more significant attenuation of increase in heart rate during laryngoscopy and
intubation as compared to Fentanyl.
[2] There is significant increase in systolic blood pressure during laryngoscopy and endotracheal intubation in
Fentanyl group as compared Dexmedetomidine group (p<0.001). Dexmedetomidine produces more
significant attenuation of increase in systolic blood pressure during laryngoscopy and intubation as
compared to Fentanyl.
[3] There is significant increase in diastolic blood pressure during laryngoscopy and endotracheal intubation in
Fentanyl group as compared to the Dexmedetomidinegroup(p<0.001). Dexmedetomidine produces more
significant attenuation of increase in diastolic blood pressure during laryngoscopy and intubation as
compared to Fentanyl.
[4] It was seen that with Dexmedetomidine, there is transient increase in blood pressure followed by decrease
in blood pressure and heart rate.
Thus it was concluded that DEXMEDETOMIDINE when used as I.V. premedicant in dose of 0.6 μg/kg
provides beneficial effect in attenuation of pressor response to laryngoscopy and endotracheal intubation as
compare to FENTANYL in dose of 2 μg/kg .

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38

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E0422028038

  • 1. IOSR Journal Of Pharmacy (e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 www.iosrphr.org Volume 4, Issue 2(February 2014), Pp 28-38 Comparison of Dexmedetomidine with Fentanyl in Attenuation of Pressor Response during Laryngoscopy and Intubation 1, Dr Sagar Gandhi , 2,Dr VigyaGoyal , 3,Dr Krishnaprabha Radhakrishnan , 4, Dr Mahesh Balakrishnan 1 ,Practisinganaesthetist 3 year resident ,BJMC Ahmedabad 3, rd 3 year resident ,BJMC Ahmedabad 4, rd 2 year resident ,BJMC Ahmedabad 2, nd ABSTRACT INTRODUCTION The pressure response, which is part of a huge spectrum of stress response, results from the increase in sympathetic and sympathoadrenalactivity.Acomparision between dexmeditomedine and fentanyl in suppressing the pressorresponse is studied. OBJECTIVE This study was done to compare the effectiveness of Dexmedetomidine with Fentenyl in attenuating the pressor responses associated with laryngoscopy and endotracheal intubation in groups belonging to normotensive ASA grade 1, 2 risk surgical patients. MATERIAL The study was carried out on 100 patients belonging to ASA grade I and II, aged 15 to 65 years, including either gender, scheduled for elective surgical procedures under general anesthesia. RESULT DEXMEDETOMIDINE when used as I.V. premedicant in dose of 0.6 μg/kg provides beneficial effect in attenuation of pressor response to laryngoscopy and endotracheal intubation as compare to FENTANYL in dose of 2 μg/kg . I. INTRODUCTION Intubation has been practiced following its description by Rowbatham and Magill in 1921. The circulatory responses to laryngeal and tracheal stimulation following laryngoscopy and intubation were documented by Reid and Brace in 1940 and king et al in 1951. The pressure response, which is part of a huge spectrum of stress response, results from the increase in sympathetic and sympathoadrenal activity, as evidence by increased plasma catecholamines concentration in patients undergoing surgery under general anaesthesia. Increase in mean arterial pressure of an average of 25mm Hg was observed in normotensive patients following laryngoscopy and intubation under anesthesia with thiopentone, nitric oxide, oxygen and suxamethonium. The rise in the heart rate and blood pressure is usually transient, variable and unpredictable. Usually these changes are well tolerated by healthy individuals. However these changes may be fatal in patient with hypertension, coronary artery disease or intracranial hypertension. Left ventricular failure, myocardial ischemia, cerebral hemorrhage may occur in high risk patients. Convulsions may be precipitated in pre-eclamptic patients To blunt this pressor response, various methods have been tried including,  Deeper plane of anaesthesia with intravenous or inhalation agent  Use of Propofol  Curtailing the duration of laryngoscopy to less than 15 seconds  Sympathetic blockage  Lidocaine spray or gargles 3 minutes prior to intubation  Use of intravenous Lidocaine to blunt the pressor response  Use of ACE inhibitors e.g. Captopril, Enalapril 45 minutes prior to intubation  Use of Magnesium sulphate  Various antihypertensive and vasodilators e.g. IV Hydralazine, Ca +2 channel blocker like Nifedipine, beta blockers like Esmolol  Use of Nicardipine  Use of Opiods prior to induction e.g. Fentanyl, SuFentanyl or AlFentanyl 28
  • 2. Comparison Of Dexmedetomidine With Fentanyl…    Use of Nitroglycerine ointment, intravenous, sublingual spray, intranasal spray Use of Gabapentin Alpha -2 agonists like Clonidine II. MATERIAL AND METHOD Patient selection :  After approval from ethical committee, civil hospital, Ahmedabad, the study was carried out on 100 patients belonging to ASA grade I and II, aged 15 to 65 years, including either gender, scheduled for elective surgical procedures under general anesthesia. EXCLUSION CRITERIA: The patients with baseline heart rate < 60 bpm, baseline blood pressure < 100/50 mm of Hg, reactive airway disease, history of cardiac disease and hypertensive patient, on treatment with adrenergic augmenting or depleting drugs, PR interval > 0.24 seconds on ECG, 2nd and/or 3rd degree heart block, requiring 2 or more attempts for laryngoscopy and intubation were excluded from the study. Patients were randomly divided into two groups of 50 each. Group D received 0.6 mcq / kg Dexmedetomidine and Group F received 2 mcq / kg Fentanyl diluted in 10 ml normal saline 10 minutes before laryngoscopy and intubation. Preoperative evaluation :  Patients were subjected to routine investigations like blood sugar, Hb level, renal and liver function test.  Airway of patients that were likely to be anticipated for difficult intubation was evaluated. Preoperative preparation :  The procedure was explained to the patient and written informed consent was taken.  All patients were preloaded with crystalloid fluid, 8-10 ml/kg.  All patients were pre-medicated with inj. Glycopyrrolate 0.04mg/kg iv and inj.Ondansetron 0.15 mg/kg i.v.  Heart rate, systolic and diastolic blood pressure was recorded before pre-medication and 10 minutes after pre-medication in patients. Selection of groups: (1) Group D – Dexmeditomidine (0.6 mcg/kg diluted in 5ml saline IV over 1 min) (2) Group F – Fentanyl (2 mcg/kg diluted in 5ml saline IV over 1 min)  III. METHOD OF STUDY : With patient in supine position , Injection DEXMEDETOMIDINE 0.6 mcq/kg diluted in 10 ml saline and Injection FENTANYL 2 mcq/kg diluted in 10 ml saline in groups D and F respectively , were administered intranvenously 10 minutes before laryngoscopy and intubation.  Heart rate, systolic and diastolic blood pressure, SPO2 was recorded at 1 minute interval of drug administration.  Patients were induced with inj. Pentothal (4-7 mg/kg) i.v. and inj. Suxamethonium (2mg/kg) i.v. followed by Laryngoscopy and intubation.  Variables to be monitored were heart rate, systolic blood pressure, diastolic blood pressure, SPO 2 and ECG.  All parameters were recorded at following stages: Before pre-medication (BPM) After pre-medication (APM) 30 seconds after endotracheal intubation (AEI) And then every one minute up to 10 minute (AEI)  All intubation were accomplished within 15 seconds by an expert anaesthesiologist.  Only one attempt of intubation was accepted in the study.  Patient who had coughed or bucked during procedure were excluded from study.  After intubation, patients were maintained with Isoflurane(0.4 % v/v) or Sevoflurane(0.8% v/v), O2 (50%) ,N2o (50%) and non-depolarizing muscle relaxant.  At the end of surgery, patients were reversed with inj. Glycopyrrolate and inj. Neostigmine. Patients were watched for any complication like tachycardia, hypotension, arrhythmias, bronchospasm during intraoperative and post operative period This study was conducted to evaluate the efficacy of intravenous Dexmedetomidine and Fentanyl in attenuation of stress response to laryngoscopy and intubation. A hundred adult patients of either gender, belonging to ASA grade I or II were selected for the study. Statistical data wasanalyzed by using Z test wherever required. 29
  • 3. Comparison Of Dexmedetomidine With Fentanyl… (1 )Patient demographics : a) Age: The mean age of the patients in group D and F were 37.76 ± 10.41 years and 38.96 ± 9.94 respectively. b) Weight : The mean weight of patients in groups D and F were 63.7 ± 6.57 and 64.58 ± 5.16 respectively Table 1. Demographic data Age (in years) Group D (DEXMEDETOMIDIN E Group F (FENTANYL) Number of Patients Weight (in kgs) Males Females 37.76 ± 10.41* 20 30 63.7 ± 6.57* 38.96 ± 9.94* 21 29 64.58 ± 5.16* Age and weight of the all patients in both groups are comparable to each other and there is no statistical difference between them ( * - p value > 0.05). Figure 1. Mean age of the patients in all groups (n=100) Figure 2. Mean weight of the patients in all groups (n=100) 30
  • 4. Comparison Of Dexmedetomidine With Fentanyl… (2 ) HEART RATE : The heart rate was measured at baseline, after IV premedication for every one minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after intubation (Table 2 ). It was observed that the heart rate increased in both groups immediately after endotracheal intubation. The heart rate started to return to normal values at the end of 10 minutes post intubation. Table 2. Changes in heart rate Heart rate (beats per Minute) Mea Group D n ±SD Mea Group F n ±SD At baseline 1 min after ETI 2 min after ETI 3 min after ETI 5 min after ETI 7 min after ETI 82.78# 10 min after premed 68.88* 76.2* 78.6* 78.22* 73.38* 70.76* 10 min after ETI 68.58* 9.18# 82.04# 9.68* 80.3* 11.88* 94.28* 11.91* 99.48* 13.42* 98.54* 10.74* 94.22* 10.34* 92.28* 9.83* 90.34* 10.11# 10.35* 9.50* 11.88* 11.25* 10.54* 11.18* 12.15* # - Base line heart rate of all patients of both groups are comparable to each other and there is no statistical difference between them (p value > 0.05). *-The increase was highly significant in group F as compared to group D during laryngoscopy and after intubation ( p value <0.001 ). 31
  • 5. Comparison Of Dexmedetomidine With Fentanyl… Figure 3. Heart rate in all groups at various time intervals (3) Systolic blood pressure: The systolic blood pressure was measured at baseline, after IV premedication for every one minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after intubation (Table 3). It was observed that the systolic blood pressure increased in both groups immediately after endotracheal intubation. The systolic blood pressure started to return to normal values at the end of 10 minutes post intubation. Table 3. Changes in systolic blood pressure At baseline 10 min after premed 1 min after ETI 2 min after ETI 3 min after ETI 5 min after ETI 7 min after ETI 10 min after ETI Mean 130.88# 112.96* 122.96* 125.24* 122.32* 116.04* 111.6* 107.1* ±SD 8.52# 10.86* 14.47* 15.19* 15.40* 14.21* 12.94* 10.78* Mean 129.38# 121.58* 131.44* 146.56* 143.14* 135.46* 126.56* 117.72* ±SD 9.97# 9.98* 7.28* 7.99* 7.62* 7.02* 7.56* 4.73* Systolic blood pressure (mmHg) Group D Group F # - Base line systolic blood pressore of all patients of both groups are comparable to each other and there is no statistical difference between them (p value > 0.05). *- The increase was highly significant in group F as compared to group D during laryngoscopy and after intubation (p<0.001). 32
  • 6. Comparison Of Dexmedetomidine With Fentanyl… Figure 4. Systolic blood pressure in all groups at various time intervals (4) Diastolic blood pressure: The diastolic blood pressure was measured at baseline, after IV premedication for every one minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after intubation (Table 4). It was observed that the diastolic blood pressure was increased significantly from the baseline during laryngoscopy and after intubation in both groups and returned to normal at the end of 10 minutes post intubation in all the groups. Table 4. Changes in Diastolic blood pressure 1 min after ETI 75.1* 2 min after ETI 77.12* 3 min after ETI 5 min after ETI 78.32# 10 min after premed 69.02* 75.7* ±SD 5.65# 8.09* 10.76* 10.74* Mean 77.08# 73.48* 78.38* ±SD 2.57# 3.13* 2.81* Systolic blood pressure (mmHg) Group D Mean Group F At baseline 10 min after ETI 71.72* 7 min after ETI 68.42* 10.13* 9.50* 9.03* 7.65* 82.68* 81.72* 80.26* 78.88* 77.14* 2.90* 2.49* 2.36* 1.61* 1.95* 65.92* # - Base line diastolic blood pressore of all patients of both groups are comparable to each other and there is no statistical difference between them (p value > 0.05). * - The increase was highly significant in group F as compared to group D during laryngoscopy and after intubation (p<0.001). 33
  • 7. Comparison Of Dexmedetomidine With Fentanyl… Figure 5.Diastolic Blood Pressure in all groups at various time intervals (5) Mean Arterial Blood Pressure: The mean arterial blood pressure was measured at baseline, after IV premedication for every one minute interval till 10 minutes, during laryngoscopy and intubation and for every one minute till 10 minutes after intubation (Table 5). It was observed that the mean arterial blood pressure was increased significantly from the baseline during laryngoscopy and after intubation in both groups and returned to normal at the end of 10 minutes post intubation in all the groups. Table 5. Changes in Mean Arterial Pressure Mean arterial pressure (mmHg) Group Mean D ±SD Group F Mean ±SD At baseline 95.66# 5.95# 94.34# 3.69# 10 min after premed 83.52* 8.64* 89.35* 4.13* 1 min after ETI 90.89* 11.44* 95.89* 3.20* 2 min after ETI 93* 11.76* 103.76* 3.30* 3 min after ETI 5 min after ETI 7 min after ETI 10 min after ETI 91.08* 12* 101.99* 3.36* 86.35* 10.77* 98.48* 2.98* 82.67* 9.95* 94.61* 2.85* 79.51* 8* 90.53* 2.22* # - Base line Mean Arterial Blood Pressure of all patients of both groups are comparable to each other and there is no statistical difference between them (p value > 0.05). * - The increase was highly significant in group F as compared to group D during laryngoscopy and after intubation (p<0.001). (6) Effect OfDexmedetomodine On Hemodynamic Parameter: After pre medication with Dexmedetomidine , initially there is a increase in blood pressure after that there is decrease in blood pressure. Heart rate decrease after application of Dexmedetomidine. 34
  • 8. Comparison Of Dexmedetomidine With Fentanyl… Figure 6 : Effects Of Dexmedetomidine On Hemodynamic Parameter Dex - Dexmedetomidine DISCUSSION Stress response under anesthesia has been universally recognized phenomenon which may be in the form of endocrine or autonomic disturbance. The pressor response to laryngoscopy and endotracheal intubation in form of tachycardia, hypertension and arrhythmias may be potentially dangerous. This hemodynamic change is due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. This increase in blood pressure and heart rate are usually transient, variable and unpredictable. Transient hypertension and tachycardia are probably of no consequence in healthy individuals, but either or both may be hazardous to those with hypertension, myocardial insufficiency and cerebrovascular disease.33The periintubation period is one of the most stressing moments of general anesthesia 2. These changes are the maximum at 1 minute after intubation and last for 5-10 minutes.Stretching of pharyngeal and laryngeal tissue during laryngoscopy as the major causes of haemodynamic response.Stimulation of supraglottic region during laryngoscopy was a major cause of hemodynamic catecholamine response and that contributed to very little additional stimulation. A wide variety of pharmacological agents were used to attenuate the haemodynamic response: Surface anaesthesia of larynx and pharynx with Lidocaine spray proved unsuccessful because of the need to perform laryngoscopy with resultant stretching and pressure on tissue of larynx and pharynx.  Lidocaine 1.5mg/kg does not markedly attenuate the stress response.  Deep plane of anaesthesia with volatile agents control changes in heart rate and arterial pressure but it is not useful for rapid sequence intubation may lead to hypotension and prolonged recovery.  Sodium nitoprusside : 1-2µg/kg This vasodilator may also lead to intra operative hypotension and may require invasive arterial pressure monitoring.  Other drugs like…  Labetolol : but has long half life  Diltiazem  Verapamil  Nicardipine  Opoids like Fentanyl, Buprenorphine The search for ideal technique or agents for attenuation of haemodynamic changes still continues.Complications of pressor responses that follow laryngoscopy include myocardial ischaemia, cardiac failure, intracranial haemorrhage and increase in ICP. 35
  • 9. Comparison Of Dexmedetomidine With Fentanyl… Studies of hypertensive patients have shown than pressure responses to laryngoscopy is exaggerated in these patients that is associated with a marked increase in nor-adrenaline concentration in the blood.37,41Recent studies with alpha-2 adrenoceptor agonists have demonstrated beneficial effects in anesthetized patients. Clonidine attenuates hemodynamic responses during laryngoscopy and endotracheal intubation. It also reduces dose requirements of inhaled anesthetics and potentiates effects of opioids during surgical stimulation. In addition, alpha-2 adrenoceptor agonists may have clinically significant anxiolytic activity. Dexmedetomidine is a highly specific, potent, and selective alpha-2 adrenoceptor agonist.Dexmedetomidine caused a dose-dependent decrease in arterial blood pressure and heart rate (HR), and reduction in sympathetic nervous activity was manifested as a dose-dependent decline in plasma levels of norepinephrine. Single intravenous doses of Dexmedetornidine administered 15 min before the induction of anesthesia decreased Thiopental requirements, attenuated the hemodynamic responses to laryngoscopy and endotracheal intubation, and diminished Isoflurane requirements.8,10,11The present study was conducted to compare the efficacy of premedication with Dexmedetomidine and Fentanyl on hemodynamic parameters after laryngoscopy and endotracheal intubation. The study was carried out in 100 patients of ASA grade I and II who were divided into 2 groups of 50 each. The first group (group D) was given InjDexmedetomidine 0.6 µg/kg and second group ( group F) was given Inj Fentanyl 2 µg/kg, 10 minutes before laryngoscopy and intubation. Hemodynamic parameters like, heart rate, systolic blood pressure, diastolic blood pressure were measured at different time intervals in each patient. The results and observations were recorded and compared PATIENT DEMOGRAPHICS As shown in Table 1, there was no statistical significant difference between the mean age (in years) and mean weight (in kgs) among two groups. The gender distribution was almost equal both groups. Heart rate In both groups the heart rate started decreasing up to 10 minutes after premedication with study drug in respective group. These observations are comparable to those by B. Scheininet al 10, A. EsraSagiroglu et al26, Anila D. Malde et al20, Sam Chung et al9, Sukhminderjit Singh Bajwa et al32, Shobhana Gupta et al31, SajithSulaiman et al33. In our study, we observed a decrease of 16.8% heart rate in Group D and 2.12% heart rate in group F from base line value.In both groups, heart rate was increased immediately after laryngoscopy and intubation. However increased in heart rate was more in Group F as compare to Group D.This increase was highly significant (p<0.001). These observations are comparable to those by Martina Ahoet al 8, Sukhminderjit Singh Bajwa et al32, N. Turgut et a22. However Sukhminderjit Singh Bajwaet al 32 used Dexmedetomidine in dose of 1 µg/kg and N. Turgut et al22 used Fentanyl in dose of 1 µg/kg. Systolic Blood Pressure After premedication with study drug in respective group systolic blood pressure started decreasing from its baseline value. These observations are comparable to those by Martina Ahoet al 8, Sukhminderjit Singh Bajwa et al32, PekkaTalke et al 14, Varshali M Keniya et al29, FerdiMenda et al25, Maria Cristina Smania et al23, John P. Ebert et al6, Sam Chung et al9. In our study, we observed a decrease of 13.70% systolic blood pressure in group D and 6.03% systolic blood pressure in group F from base line value. In our study, it is evident that the systolic blood pressure was significantly increased in both the groups after laryngoscopy and intubation (p<0.05). The peak increase in systolic blood pressure was seen just after intubation and cuff inflation (after1&2 minute). The increase in systolic blood pressure is less in group D as compared to group F and this difference is statistical highly significant ( p<0.001). In contrast to present study result, Martina Aho et al 8 did not find any difference in blood pressure response between Fentanyl and Dexmedetomidine groups. The systolic blood pressure came back to near normal within 10 minutes post intubation. Diastolic Blood Pressure After premedication with study drug in respective group, diastolic blood pressure started decreasing from its beseline value. These observations are comparable to those by Martina Aho et al 8, Sukhminderjit Singh Bajwa et al32, PekkaTalke et al 14, Varshali M Keniya et al29, FerdiMenda et al25, Maria Cristina Smania et al 23 ,John P Ebert et a 6, Sam Chung et al9. In our study, we observed a decrease of 11.88% diastolic blood pressure in Group D and 4.68% diastolic blood pressure in group F from base line value. In our study, the diastolic blood pressure was significantly increased in both the groups after laryngoscopy and intubation (p<0.05). The peak increase in diastolic blood pressure was seen just after intubation and cuff inflation (after 1&2 minute). The increase in diastolic blood pressure is less in group D as compared to group F and this difference is statistical highly significant ( p<0.001). In contrast to present study result, Martina Aho et al 8 did not find any difference in blood pressure response between Fentanyl and Dexmedetomidine groups. The diastolic blood pressure came back to near normal within 10 minutes post intubation. 36
  • 10. Comparison Of Dexmedetomidine With Fentanyl… Mean Arterial Blood Pressure The mean arterial blood pressure was significantly increased in both the groups after laryngoscopy and intubation (p<0.05). The peak increase in mean arterial blood preesure was seen just after intubation and cuff inflation (after 1&2 minute). The increase in mean arterial blood pressure is less in group D as compared to group F and this difference is statistical highly significant ( p<0.001). These observations are comparable to those by Sukhminderjit Singh Bajwaet al32 and N.Turgut et al.22 However Sukhminderjit Singh Bajwa et al 32 used Dexmedetomidine in dose of 1 µg/kg and N.Turgut et al 22 used Fentanyl in dose of 1 µg/kg. Side effects and complications In our study side effects and complications like bradycardia, hypotension, respiratory depression etc encountered were very few and could be easily treated. CONCLUSION AND SUMMARY The present study was carried out “To compare the efficacy of intravenous DEXMEDETOMIDINE and FENTANYL in attenuation of stress response to laryngoscopy and intubation” in 100 adult patients, scheduled for various surgical procedures under general anaesthesia during February 2012 to August 2012 at civil hospital Ahmedabad. After approval from ethical committee of hospital, the patients were randomly divided into 2 groups:  Group D: Received DEXMEDETOMIDINE 0.6 μg/kg intravenously.  Group F: Received FENTANYL 2 μg/kg intravenously. The following observations were made: [1] It was observed that the heart rate increased after laryngoscopy and intubation in both groups and it started to return to near normal values at the end of 10 minutes post intubation. The increase in heart rate was highly significant in group F as compared to group D during laryngoscopy and after intubation. Dexmedetomidine produces more significant attenuation of increase in heart rate during laryngoscopy and intubation as compared to Fentanyl. [2] There is significant increase in systolic blood pressure during laryngoscopy and endotracheal intubation in Fentanyl group as compared Dexmedetomidine group (p<0.001). Dexmedetomidine produces more significant attenuation of increase in systolic blood pressure during laryngoscopy and intubation as compared to Fentanyl. [3] There is significant increase in diastolic blood pressure during laryngoscopy and endotracheal intubation in Fentanyl group as compared to the Dexmedetomidinegroup(p<0.001). Dexmedetomidine produces more significant attenuation of increase in diastolic blood pressure during laryngoscopy and intubation as compared to Fentanyl. [4] It was seen that with Dexmedetomidine, there is transient increase in blood pressure followed by decrease in blood pressure and heart rate. Thus it was concluded that DEXMEDETOMIDINE when used as I.V. premedicant in dose of 0.6 μg/kg provides beneficial effect in attenuation of pressor response to laryngoscopy and endotracheal intubation as compare to FENTANYL in dose of 2 μg/kg . REFERENCES [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Dahlgren N, Messeter K.- Treatment of stress response to laryngoscopy And intubation with Fentanyl. Anaesthesia 1981; 36(11): 1022 – 6. Kautto UM. Attenuation of the circulatory response to laryngoscopy And intubation by Fentanyl. ActaAnaesthesiolScand 1982; 26(3): 217- 21. D E Martin et al – Low dose Fentanyl blunts circulatory response to tracheal intubation 1982;61:680-4 Dundee JW, Hassard TH. The induction dose of ThiopentoneAnaesthesia 1982; 37: 1176-1184. Splinter WM – Haemodynamic response to laryngoscopy and tracheal intubation in geriatric patients: effects of Fentanyl, Lidocaine and Thiopentone. C J Anes 1989 jul; 36(4):370-6 J P Ebert –Circulatory response to laryngoscopy: the comparative effects of Placebo, Fentanyl and Esmolol can j anes 1989/36:3/pp 301-6 Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Dexmedetomidine premedication for minor gynaecologic surgery. AnesthAnalg1990; 73: 230-35 Aho M, Lehtinen A-M, Erkola 0, Kallio A, Korttila K.-The effect of intravenously administered Dexmedetomidine on perioperative hernodynamics and Isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology1991;74:997-1002 Chung KS, Sinatra RS, Halevy JD, Paige D, Silverman DG.- A comparison of Fentanyl, Esmolol and their combination for blunting the hemodynamic response during rapid-sequence induction. Can J Anaesth 1992; 39(8): 774 – 9. B. Scheinin, L.Lindgren, T.Randell – Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for Thiopentone and preoperative Fentanyl ,BJA 1992; 68 :126-131 37
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