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Original
Article The effects of dexmedetomidine on
attenuation of stress response to
endotracheal intubation in patients
undergoing elective off‑pump
coronary artery bypass grafting
Sajith Sulaiman, Ranjith Baskar Karthekeyan, Mahesh Vakamudi1, Ayya Syama Sundar,
Harish Ravullapalli, Ravikumar Gandham
Departments of Cardiac Anaesthesiology, 1Anaesthesiology and Critical Care, Sri Ramachandra Medical College and
Research Institute, Porur, Chennai, India

ABSTRACT
Received: 09‑06‑11
Accepted: 24‑09‑11
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 off‑pump coronary artery bypass surgery were randomly allocated to receive
dexmedetomidine (0.5 mcg/kg) or normal saline 15 min before intubation. Patients were compared for
hemodynamic changes (heart rate, arterial blood pressure and pulmonary artery pressure) at baseline, 5 min
after drug infusion, before intubation and 1, 3 and 5 min 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 10‑min 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, off‑pump coronary artery bypass grafting, stress response

INTRODUCTION such individuals there is a necessity to blunt

Direct laryngoscopy and endotracheal
intubation following induction of anesthesia
is associated with hemodynamic changes
due to reflex sympathetic discharge caused
by epipharyngeal and laryngopharyngeal
Access this article online stimulation. This increased sympatho–
Website: www.annals.in adrenal activity may result in hypertension,
PMID: tachycardia and arrhythmias. [1,2] This
22234020
increase in blood pressure and heart
DOI:
10.4103/0971-9784.91480 rate are usually transient, variable and
Quick Response Code: 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
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
1–2 min and returns to control levels within
5 min. 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. E‑mail: ranjithb73@gmail.com

Annals of Cardiac Anaesthesia    Vol. 15:1    Jan-Mar-2012 39

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Sulaiman, et al.: 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.
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 10‑min infusion on hemodynamic
responses to laryngoscopy and endotracheal intubation.
The incidence of hypotension and bradycardia was
also assessed.
MATERIALS AND METHODS
This was a prospective, double‑blind, parallel‑group,
randomized, placebo‑controlled clinical trial of
dexmedetomidine for attenuation of stress response to
endotracheal intubation in 60 adult patients scheduled
to undergo elective off‑pump 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, angiotensin-
converting 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 10 mg and pantoprazole
40 mg the night before and on the morning of the
surgery.
Patients were randomly allocated according to
computer‑generated 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
saline were prepared in a double‑blind 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, intra‑arterial blood
pressure, pulmonary arterial pressures nasopharyngeal
temperature, urine output and capnography were
also monitored. After 5 min of stable cardiovascular
variables, baseline hemodynamic variables were
recorded.
Before induction of anesthesia, a single dose of
dexmedetomidine 0.5 µg/kg was administered
intravenously using a syringe pump over 10 min.
The same amount of saline was administered to the
patients in the control group. After 5 min of study
drug infusion, the hemodynamic variables were
recorded again. Infusion of nitroglycerin – 0.2 µg/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 0.1 mg/kg
was administered intravenoulsy to facilitate tracheal
intubation. The trachea was intubated after 3 min 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 th min after intubation. Times
for hemodynamic measurement were defined as
follows: TB=baseline, prior to the start of infusion of
dexmedetomidin or placebo; TA=after 5 min of study
drug infusion; T0=3 min after induction and prior to
intubation; T1=1 min after intubation; T3=3 min after
intubation; T5=5 min after intubation.
Statistical analysis
The sample size was determined by power analysis
performed by a pilot study. A sample size of
18 patients 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 mean±standard
deviation. Independent t‑test was used to compare
the study group and the control group. Paired t‑test
was used to compare the variable before and after
the intervention. Chi‑square test was used to analyze
the categorical data and for testing the association
between the variables. Nonparametric tests (Wilcoxon
signed rank tests [two‑tailed]) were used whenever
Annals of Cardiac Anaesthesia    Vol. 15:1    Jan-Mar-2012
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Sulaiman, et al.: Dexmedetomidine and stress response to tracheal intubation

the mean value was less than two times the standard No statistical significance was noted in systolic
deviation. A P value of less than 0.05 was considered pulmonary artery pressure between groups at baseline,
statistically significant. The package SPSS 17.0 before intubation and 3rd and 5th min after intubation.
(SPSS Inc., Chicago, IL, USA) was used for statistical There was a statistical significance noted in systolic
analysis. pulmonary artery pressure after drug administration
and 1 min after intubation. At any time period of
RESULTS measurement, the mean pulmonary artery pressure
was similar in both groups. Except at 5 min post
The groups were well-matched for their demographic intubation, diastolic pulmonary artery pressures
data, regional wall motion abnormality and number were similar between the two groups. Overall, the
of coronary vessels involved. No patient was excluded dexmedetomidine group was better controlled than
from the study. Ejection fraction was significantly the control group [Table 4]. There were no incidences
higher in the dexmedetomidine group [Table 1]. of hypotension (systolic blood pressure ≤25% of
The presence of risk factors and preoperative baseline), arrhythmias or other Electrocardiography
cardiovascular medications were comparable between (ST depression ≥1 mm below the baseline) observed
the groups [Table 2]. Except heart rate, all other during the study period in any group.
baseline hemodynamic variables were similar in both
groups [Table 3]. Heart rate values were statistically DISCUSSION
significantly lower in the dexmedetomidine group at all
time intervals when compared with the control group. Laryngoscopy and endotracheal intubation are
There was a statistical significance in the systolic considered as the most critical events during general
arterial pressure, mean arterial pressure and diastolic anesthesia. They provoke a transient, but marked,
arterial pressure between groups after drug at the 1st,
sympathetic and sympathoadrenal response. In
3rd and 5th min post intubation. The dexmedetomidine
patients undergoing coronary artery bypass (CABG)
group had a better control of heart rate and blood
surgery, tachycardia and hypertension increase
pressure than the control group [Table 3].
the risk of perioperative myocardial ischemia and
infarction. Alfa2‑adrenergic drugs, such as clonidine or
Table 1: Patient characteristics dexmedetomidine, attenuate these potentially harmful
Variable Dexmedetomidine Placebo P value cardiovascular reactions during induction of anesthesia.
Mean age in years 56.73 57.37 0.790
In our study, we compared dexmedetomidine, a
Male sex (n) 20 23 0.39
newer alfa 2 ‑agonist, with additional properties
Mean body mass 22.88 22.53 0.647
index
such as sedation, anxiolysis and sympatholysis for
Mean ejection 60.73 56.13 0.035* attenuating the hemodynamic response to laryngoscopy
fraction % and tracheal intubation.
No. of diseased 2.40 2.50 0.498
coronary vessels
Dexmedetomidine offers a unique pharmacological
Regional wall motion 16 15 0.796
abnormality (n)
profile with sedation, sympatholysis, analgesia,
*Statistically significant (P<0.05); n  ‑  Number of patients
cardiovascular stability and with great advantage to avoid
respiratory depression. In particular, dexmedetomidine
Table 2: Risk factors and medication can provide a dose‑dependent cooperative sedation
Variable Group A Group B P value that allows ready interaction with the patient. All
Angina (NYHA II) 22 22 1.000
these above-said aspects of its pharmacological profile
Angina (NYHA III) 8 8 1.000
render it suitable as an anesthetic adjuvant and also as
Hypertension 17 18 0.793
Diabetes mellitus 16 14 0.606
intensive care unit sedation.
Old myocardial infarction 13 10 0.426
Beta blockers 24 23 0.754 Dexmedetomidine increases the hemodynamic stability
CCB 8 5 0.347 by altering the stress‑induced sympathoadrenal
ACEI 14 15 0.796 responses to intubation during surgery and during
Diuretics 5 3 0.448 emergence from anesthesia.[8] Jaakola et al.,[9] in their
CCB ‑  Calcium channel blockers; ACEI ‑ Angiotensin-converting
enzyme inhibitors; NYHA ‑  New  York Heart Association. All values are
study concluded that dexmedetomidine attenuates
expressed in numbers the increase in heart rate and blood pressure

Annals of Cardiac Anaesthesia    Vol. 15:1    Jan-Mar-2012 41

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Sulaiman, et al.: Dexmedetomidine and stress response to tracheal intubation

Table 3: Heart rate and arterial pressure

Variable Group TB TA T0 T1 T3 T5
HR Dex 68.77 ± 8.2 62.37 ± 8.6 62.03 ± 9.4 69.10 ± 10.7 66.93 ± 9.5 66.37 ± 9.8
Con 74.27 ± 10.1 73.23 ± 10 71.93 ± 9.2 84.67 ± 11.3 81.47 ± 10.6 76.93 ± 8.2
P value 0.025* 0.000* 0.000* 0.000* 0.000* 0.000*
SBP Dex 144.7 ± 16.2 121.10 ± 13 107.40 ± 10.03 120.63 ± 12.6 116.53 ± 13.2 112.07 ± 15.6
Con 144.87 ± 14 131.87 ± 21 109.27 ± 16.9 148.33 ± 19.8 140.13 ± 16.9 128.73 ± 13.2
P value 0.98 0.025* 0.606 0.000* 0.000* 0.000*
MAP Dex 99.03 ± 11 83.67 ± 10 77.10 ± 8.5 87.43 ± 9.9 84.07 ± 10.2 80.43 ± 12.00
Con 101.10 ± 10 93.20 ± 129 78.73 ± 10.3 107.23 ± 14.3 100.63 ± 10.6 93.60 ± 8.4
P value 0.477 0.003* 0.509 0.000* 0.000* 0.000*
DBP Dex 74.13 ± 9.6 61.70 ± 13 61.37 ± 7.9 69.50 ± 8.9 66.70 ± 9.0 63.00 ± 12.1
Con 76.13 ± 8.7 71.50 ± 7.9 62.83 ± 7.5 62.83 ± 7.5 78.07 ± 8.5 74.17 ± 7.4
P value 0.403 0.001* 0.464 0.000* 0.000* 0.000*
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; TA ‑ After drug; T0 ‑  Before intubation; T1 ‑  First minute after intubation; T3 ‑  Third minute
after intubation; T5 ‑  Fifth minute after intubation; values are expressed as mean±standard deviation (SD)

Table 4: Pulmonary artery pressure

Variable Group TB TA T0 T1 T3 T5
SPAP Dex 25.80 ± 4.6 21.23 ± 3.4 20.73 ± 3.3 23.37 ± 4.02 23.07 ± 3.7 22.20 ± 5.04
Con 25.57 ± 6.1 24.10 ± 4.3 21.67 ± 4.1 26.73 ± 6.08 24.63 ± 4.5 23.67 ± 4.66
P value 0.869 0.006* 0.336 0.014* 0.152 0.247
MPAP Dex 15.50 ± 3.1 13.00 ± 3.2 13.03 ± 2.9 14.80 ± 2.9 14.30 ± 3.3 13.77 ± 3.07
Con 15.30 ± 3.9 14.10 ± 3.2 13.00 ± 2.9 16.33 ± 4.07 15.37 ± 3.5 14.83 ± 3.2
P value 0.828 0.198 0.965 0.099 0.236 0.197
DPAP Dex 9.60 ± 3.2 8.27 ± 3.1 8.77 ± 2.5 9.83 ± 2.5 9.03 ± 3.0 8.53 ± 2.5
Con 9.80 ± 3.4 8.67 ± 3.2 8.60 ± 3.0 10.60 ± 3.9 9.83 ± 3.4 10.10 ± 2.9
P value 0.817 0.627 0.818 0.373 0.349 0.034*
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; TA ‑ After drug; T0 ‑  Before intubation; T1 ‑  First minute after intubation;
T3 ‑  Third minute after intubation; T5 ‑  Fifth minute after intubation. Values are expressed as mean±standard deviation

during intubation. The dose used for this study was
0.6 mcg/kg, which is almost similar to the dose used
by us.
Scheinin et al., studied the effect of dexmedetomidine
[8]
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.
Lawrence et al.,[10] found that a single dose of 2 mcg/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 0.5 mcg/kg as an
infusion over 10 min. Hemodynamic response was
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 high‑risk
patients. Nevertheless, the mean intubation induced
pressor response was modest in our control group,
which suggests that a relatively low intensity of
stress is associated with the present anesthetic
technique.
The hypotension and bradycardia caused by
dexmedetomidine, theoretically, could limit its usage
in previously beta‑blocked 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.

42 Annals of Cardiac Anaesthesia    Vol. 15:1    Jan-Mar-2012

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Sulaiman, et al.: Dexmedetomidine and stress response to tracheal intubation
A biphasic cardiovascular response has been described
after the administration of dexmedetomidine.[13] A bolus
of 1 mcg/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 10 min. In our study, this effect was not noticed
due to the slow infusion of the drug over 10 min.
Studies suggest that perioperative use of
dexmedetomidine may result in a decreased risk of
adverse cardiac events, including myocardial ischemia.
[14]
Alfa‑adrenoreceptors 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 0.5 mcg/kg as 10‑min 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 Anaesthesia    Vol. 15:1    Jan-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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