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Original
Article

The effects of dexmedetomidine on

attenuation of stress response to
endotracheal intubation in patients
undergoing elective offpump
coronary artery bypass grafting
Sajith Sulaiman, Ranjith Baskar Karthekeyan, Mahesh Vakamudi1, Ayya Syama Sundar,
HarishRavullapalli, Ravikumar Gandham
Departments of Cardiac Anaesthesiology, 1Anaesthesiology and Critical Care, Sri Ramachandra Medical College and
Research Institute, Porur, Chennai, India

ABSTRACT

Received: 090611
Accepted: 240911

This study was designed to study the efficacy of intravenous dexmedetomidine for attenuation of cardiovascular
responses to laryngoscopy and endotracheal intubation in patients with coronary artery disease. Sixty adult
patients scheduled for elective offpump coronary artery bypass surgery were randomly allocated to receive
dexmedetomidine (0.5mcg/kg) or normal saline 15min before intubation. Patients were compared for
hemodynamic changes (heart rate, arterial blood pressure and pulmonary artery pressure) at baseline, 5min
after drug infusion, before intubation and 1, 3 and 5min after intubation. The dexmedetomidine group had a
better control of hemodynamics during laryngoscopy and endotracheal intubation. Dexmedetomidine at a dose
of 0.5 mcg/kg as 10min infusion was administered prior to induction of general anesthesia attenuates the
sympathetic response to laryngoscopy and intubation in patients undergoing myocardial revascularization.
The authors suggest its administration even in patients receiving beta blockers.
Key words: Dexmedetomidine, laryngoscopy, offpump coronary artery bypass grafting, stress response

INTRODUCTION

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Website: www.annals.in
PMID:
22234020
DOI:
10.4103/0971-9784.91480
Quick Response Code:

Direct laryngoscopy and endotracheal

intubation following induction of anesthesia
is associated with hemodynamic changes
due to reflex sympathetic discharge caused
by epipharyngeal and laryngopharyngeal
stimulation. This increased sympatho
adrenal activity may result in hypertension,
tachycardia and arrhythmias. [1,2] 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,[3] myocardial insufficiency[4]
and cerebrovascular diseases.[5] At least in

such individuals there is a necessity to blunt

this response.
The magnitude of the response is greater with
increasing force and duration of laryngoscopy.[6]
The elevation in arterial pressure typically starts
within five seconds of laryngoscopy, peaks in
12min and returns to control levels within
5min. Reid and Brace in 1940 were the first
to report the circulatory responses to laryngeal
and tracheal stimulation in an anesthetized
man.[7] A variety of drugs have been used to
control this hemodynamic response, such as
vasodilators, beta blockers, calcium channel
blockers, alfa2 agonists and opioids. However,
no modality was devoid of drawbacks and
limitations. Dexmedetomidine is a highly
selective alfa 2 adrenergic agonist that has

Address for correspondence: Dr. Ranjith Baskar Karthekeyan, Department of Cardiac Anaesthesiology, Sri Ramachandra Medical College and Research
Institute, No 1, Ramachandra Nagar, Porur, Chennai 600116, India. Email: ranjithb73@gmail.com

Annals of Cardiac AnaesthesiaVol. 15:1Jan-Mar-2012

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Sulaiman, etal.: Dexmedetomidine and stress response to tracheal intubation

sedative and analgesic effects. Dexmedetomidine has

been shown to decrease induction doses of intravenous
anesthetics and to decrease intraoperative opioid and
volatile anesthetic requirements for maintenance of
anesthesia. In addition, it has been shown to decrease
perioperative catecholamine concentrations and
promote perioperative hemodynamic and adrenergic
stability. The present study was designed to investigate
the effect of dexmedetomidine on hemodynamic
responses to orotracheal intubation.

saline were prepared in a doubleblind fashion

by a team member who was not involved in data
recording. Peripheral, central venous and arterial
cannulations were performed under local anesthesia.
Electrocardiogram, pulse oximetry, intraarterial blood
pressure, pulmonary arterial pressures nasopharyngeal
temperature, urine output and capnography were
also monitored. After 5min of stable cardiovascular
variables, baseline hemodynamic variables were
recorded.

Objectives
The objective of this study was to evaluate the effect
of a single preoperative dose of dexmedetomidine at a
dose of 0.5 mcg/kg as 10min infusion on hemodynamic
responses to laryngoscopy and endotracheal intubation.
The incidence of hypotension and bradycardia was
also assessed.

Before induction of anesthesia, a single dose of

dexmedetomidine 0.5g/kgwas administered
intravenously using a syringe pump over 10min.
The same amount of saline was administered to the
patients in the control group. After 5min of study
drug infusion, the hemodynamic variables were
recorded again. Infusion of nitroglycerin 0.2g/kg/
min was commenced in all the patients. Induction
of general anesthesia was achieved with intravenous
administration of 50 mcg/kg midazolam, 4 mcg/kg
fentanyl and 0.2 to 0.3 mg/kg of etodmidate. Lack of
response to verbal command was considered as the
end point of induction. Vecuronium bromide 0.1mg/kg
was administered intravenoulsy to facilitate tracheal
intubation. The trachea was intubated after 3min of
mask ventilation. All the intubations were performed
by the same anesthesiologist. Hemodynamic variables
were recorded again, immediately before intubation,
at the 1 st, 3 rd and 5 thmin after intubation. Times
for hemodynamic measurement were defined as
follows: TB=baseline, prior to the start of infusion of
dexmedetomidin or placebo; TA=after 5min of study
drug infusion; T0=3min after induction and prior to
intubation; T1=1min after intubation; T3=3min after
intubation; T5=5min after intubation.

MATERIALS AND METHODS

This was a prospective, doubleblind, parallelgroup,
randomized, placebocontrolled clinical trial of
dexmedetomidine for attenuation of stress response to
endotracheal intubation in 60 adult patients scheduled
to undergo elective offpump coronary artery bypass
grafting. The study protocol was approved by the
institutional ethical committee and written informed
consent was obtained from all the patients. Exclusion
criteria included anticipated difficult intubation,
emergency surgery, left ventricular ejection fraction
<40%, left ventricular aneurysm, associated valvular
lesions, left main coronary artery disease, severe
systemic diseases involving the renal and hepatic
systems, preoperative left bundle branch block and
intubation attempt lasting longer than 15 seconds.
The day before surgery, these patients were
preanesthetically evaluated. Diuretics, angiotensinconverting enzyme inhibitors and calcium channel
blockers were stopped the day before surgery as per
institutional protocol. Beta blockers were continued. All
patients received oral diazepam 10mg and pantoprazole
40mg the night before and on the morning of the
surgery.
Patients were randomly allocated according to
computergenerated randomization to receive either
dexmedetomidine (dexmedetomidine group, n=30) or
0.9% saline (control group, n=30). Syringes containing
aqueous solutions of either dexmedetomidine or
40

Statistical analysis
The sample size was determined by power analysis
performed by a pilot study. A sample size of
18patients per group was required to detect a 20%
change in heart rate, blood pressure and pulmonary
artery pressure between baseline and intubation
time, with a power of 80% at the 5% significance
level. Data are expressed as the meanstandard
deviation. Independent ttest was used to compare
the study group and the control group. Paired ttest
was used to compare the variable before and after
the intervention. Chisquare test was used to analyze
the categorical data and for testing the association
between the variables. Nonparametric tests (Wilcoxon
signed rank tests [twotailed]) were used whenever
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Sulaiman, etal.: Dexmedetomidine and stress response to tracheal intubation

the mean value was less than two times the standard
deviation. A Pvalue of less than 0.05 was considered
statistically significant. The package SPSS 17.0
(SPSS Inc., Chicago, IL, USA) was used for statistical
analysis.
RESULTS
The groups were well-matched for their demographic
data, regional wall motion abnormality and number
of coronary vessels involved. No patient was excluded
from the study. Ejection fraction was significantly
higher in the dexmedetomidine group [Table1].
The presence of risk factors and preoperative
cardiovascular medications were comparable between
the groups [Table2]. Except heart rate, all other
baseline hemodynamic variables were similar in both
groups [Table3]. Heart rate values were statistically
significantly lower in the dexmedetomidine group at all
time intervals when compared with the control group.
There was a statistical significance in the systolic
arterial pressure, mean arterial pressure and diastolic
arterial pressure between groups after drug at the 1st,
3rd and 5thmin post intubation. The dexmedetomidine
group had a better control of heart rate and blood
pressure than the control group [Table3].
Table1: Patient characteristics
Variable
Mean age in years
Male sex (n)

Dexmedetomidine

Placebo

Pvalue

56.73

57.37

0.790

20

23

0.39

Mean body mass

index

22.88

22.53

0.647

Mean ejection
fraction %

60.73

56.13

0.035*

No. of diseased
coronary vessels

2.40

2.50

0.498

16

15

0.796

Regional wall motion

abnormality (n)

*Statistically significant (P<0.05); n Number of patients

Table2: Risk factors and medication

Variable

Group A

Group B

Pvalue

Angina (NYHA II)

22

22

1.000

Angina (NYHA III)

1.000

Hypertension

17

18

0.793

Diabetes mellitus

16

14

0.606

Old myocardial infarction

13

10

0.426

Beta blockers

24

23

0.754

CCB

0.347

ACEI

14

15

0.796

Diuretics

0.448

CCB Calcium channel blockers; ACEIAngiotensin-converting

enzyme inhibitors; NYHA New York Heart Association. All values are
expressed in numbers

Annals of Cardiac AnaesthesiaVol. 15:1Jan-Mar-2012

No statistical significance was noted in systolic

pulmonary artery pressure between groups at baseline,
before intubation and 3rd and 5th min after intubation.
There was a statistical significance noted in systolic
pulmonary artery pressure after drug administration
and 1min after intubation. At any time period of
measurement, the mean pulmonary artery pressure
was similar in both groups. Except at 5 min post
intubation, diastolic pulmonary artery pressures
were similar between the two groups. Overall, the
dexmedetomidine group was better controlled than
the control group [Table4]. There were no incidences
of hypotension (systolic blood pressure 25% of
baseline), arrhythmias or other Electrocardiography
(ST depression 1 mm below the baseline) observed
during the study period in any group.
DISCUSSION
Laryngoscopy and endotracheal intubation are
considered as the most critical events during general
anesthesia. They provoke a transient, but marked,
sympathetic and sympathoadrenal response. In
patients undergoing coronary artery bypass (CABG)
surgery, tachycardia and hypertension increase
the risk of perioperative myocardial ischemia and
infarction. Alfa2adrenergic drugs, such as clonidine or
dexmedetomidine, attenuate these potentially harmful
cardiovascular reactions during induction of anesthesia.
In our study, we compared dexmedetomidine, a
newer alfa 2 agonist, with additional properties
such as sedation, anxiolysis and sympatholysis for
attenuating the hemodynamicresponse to laryngoscopy
andtracheal intubation.
Dexmedetomidine offers a unique pharmacological
profile with sedation, sympatholysis, analgesia,
cardiovascular stability and with great advantage to avoid
respiratory depression. In particular, dexmedetomidine
can provide a dosedependent cooperative sedation
that allows ready interaction with the patient. All
these above-said aspects of its pharmacological profile
render it suitable as an anesthetic adjuvant and also as
intensive care unit sedation.
Dexmedetomidine increases the hemodynamic stability
by altering the stressinduced sympathoadrenal
responses to intubation during surgery and during
emergence from anesthesia.[8] Jaakola et al.,[9] in their
study concluded that dexmedetomidine attenuates
the increase in heart rate and blood pressure
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Sulaiman, etal.: Dexmedetomidine and stress response to tracheal intubation

Table3: Heart rate and arterial pressure

Variable

Group

TB

TA

T0

T1

T3

T5

HR

Dex

68.778.2

62.378.6

62.039.4

69.1010.7

66.939.5

66.379.8

Con

74.2710.1

73.2310

71.939.2

84.6711.3

81.4710.6

76.938.2

0.025*

0.000*

0.000*

0.000*

0.000*

0.000*

Dex

144.716.2

121.1013

107.4010.03

120.6312.6

116.5313.2

112.0715.6

Con

144.8714

131.8721

109.2716.9

148.3319.8

140.1316.9

128.7313.2

0.98

0.025*

0.606

0.000*

0.000*

0.000*

Dex

99.0311

83.6710

77.108.5

87.439.9

84.0710.2

80.4312.00

Con

101.1010

93.20129

78.7310.3

107.2314.3

100.6310.6

93.608.4

0.477

0.003*

0.509

0.000*

0.000*

0.000*

Dex

74.139.6

61.7013

61.377.9

69.508.9

66.709.0

63.0012.1

Con

76.138.7

71.507.9

62.837.5

62.837.5

78.078.5

74.177.4

0.403

0.001*

0.464

0.000*

0.000*

0.000*

Pvalue
SBP

Pvalue
MAP

Pvalue
DBP

Pvalue

Dex Dexmedetomidine group; Con Control group; *Statistically significant (P<0.05). HR Heart rate; SBP Systolic blood pressure; DBP Diastolic
blood pressure; MAP Mean arterial pressure; TB Baseline; TAAfter drug; T0 Before intubation; T1 First minute after intubation; T3 Third minute
after intubation; T5 Fifth minute after intubation; values are expressed as meanstandard deviation (SD)

Table4: Pulmonary artery pressure

Variable

Group

TB

TA

T0

T1

T3

T5

SPAP

Dex

25.804.6

21.233.4

20.733.3

23.374.02

23.073.7

22.205.04

Con

25.576.1

24.104.3

21.674.1

26.736.08

24.634.5

23.674.66

0.869

0.006*

0.336

0.014*

0.152

0.247

Dex

15.503.1

13.003.2

13.032.9

14.802.9

14.303.3

13.773.07

Con

15.303.9

14.103.2

0.828

0.198

0.965

0.099

0.236

0.197

Dex

9.603.2

8.273.1

8.772.5

9.832.5

9.033.0

8.532.5

Con

9.803.4

8.673.2

8.603.0

10.603.9

9.833.4

10.102.9

0.817

0.627

0.818

0.373

0.349

0.034*

Pvalue
MPAP

Pvalue
DPAP

Pvalue

13.002.9

16.334.07

15.373.5

14.833.2

Dex Dexmedetomidine group; Con Control group; *Statistically significant (P<0.05). SPAP Systolic pulmonary artery pressure; DPAP Diastolic
pulmonary pressure; MPAP Mean pulmonary arterial pressure; TB Baseline; TAAfter drug; T0 Before intubation; T1 First minute after intubation;
T3 Third minute after intubation; T5 Fifth minute after intubation. Values are expressed as meanstandard deviation

during intubation. The dose used for this study was

0.6mcg/kg,which is almost similar to the dose used
by us.
Scheinin etal., studied the effect of dexmedetomidine
on tracheal intubation, required dose of induction
agent and preoperative analgesic requirements. They
concluded that the required dose of thiopentone was
significantly lower in the dexmedetomidine group and
the drug attenuated the hemodynamic responses to
intubation. The concentration of noradrenaline in mixed
venous plasma was lesser in the dexmedetomidine
group.
[8]

Lawrence etal.,[10] found that a single dose of 2mcg/kg

of dexmedetomidine before induction of anesthesia
attenuated the hemodynamic response to intubation as
well as that to extubation. Bradycardia was observed
at the 1st and 5th min after administration. This might
have been due to bolus administration. The dose of
dexmedetomidine in our study was 0.5mcg/kg as an
infusion over 10min. Hemodynamic response was
42

better in the dexmedetomidine group and bradycardia

was not observed during our study.
It is a well-known fact that depression of sympathetic
response against laryngoscopy and intubation is
an important advantage, especially in highrisk
patients. Nevertheless, the mean intubation induced
pressor response was modest in our control group,
which suggests that a relatively low intensity of
stressisassociated with the present anesthetic
technique.
The hypotension and bradycardia caused by
dexmedetomidine, theoretically, could limit its usage
in previously betablocked ischemia heart patients.
Few studies used dexmedetomidine as an anesthetic
adjuvant in CABG patients receiving beta blockers,
and reported that the intraoperative incidence of
bradycardia requiring treatment was not more common
in the dexmedetomidine group than in the control
group.[11,12] This finding supports and correlates to our
study.
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Sulaiman, etal.: Dexmedetomidine and stress response to tracheal intubation

A biphasic cardiovascular response has been described

after the administration of dexmedetomidine.[13] A bolus
of 1mcg/kg results in a transient increase in arterial
blood pressure and reflex decrease in heart rate in
young healthy patients. Initial response is due to alfa2
receptor stimulation of vascular smooth muscle. This
response can be markedly decreased by slow infusion
over 10min. In our study, this effect was not noticed
due to the slow infusion of the drug over 10min.
Studies suggest that perioperative use of
dexmedetomidine may result in a decreased risk of
adverse cardiac events, including myocardial ischemia.
[14]
Alfaadrenoreceptors stimulation can beneficially
modulate coronary blood flow during myocardial
ischemia by preventing transmural redistribution of
blood flow away from the ischemic endocardium, by
specific epicardial vasoconstrictive effects, leading to
improvement in endocardial perfusion (the reverse
steal effect) and by decreasing heart rate. This property
along with hemodynamic stability and attenuation of
intubation response makes dexmedetomidine an ideal
anesthetic adjuvant, particularly for patients undergoing
coronary bypass grafting.
There are three important limitations regarding this study.
First, we did not measure the plasma norepinephrine
levels. Secondly, extubation response, postoperative
sedation and hemodynamic variations were not studied.
Finally, the ejection fraction of the dexmedetomidine
group was better than that of the placebo group.
CONCLUSION
It is concluded that pretreatment with dexmedetomidine
at a dose of 0.5mcg/kg as 10min infusion prior to
induction of anesthesia is a safe and effective method
to attenuate the hemodynamic response to laryngoscopy
and intubation. Dexmedetomidine can be considered
before induction of general anesthesia in patients
undergoing myocardial revascularization, even if the
patients are receiving beta blockers.

Annals of Cardiac AnaesthesiaVol. 15:1Jan-Mar-2012

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Cite this article as: Sulaiman S, Karthekeyan RB, Vakamudi M, Sundar AS,
Ravullapalli H, Gandham R. The effects of dexmedetomidine on attenuation
of stress response to endotracheal intubation in patients undergoing elective
off-pump coronary artery bypass grafting. Ann Card Anaesth 2012;15:39-43.
Source of Support: Nil, Conflict of Interest: None declared.

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