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129]

Original Article

Attenuation of haemodynamic responses to

laryngoscopy and endotracheal intubation with
intravenous dexmedetomidine: A comparison
between two doses

Address for correspondence: Bon Sebastian, Anand T Talikoti, Dinesh Krishnamurthy

Dr. Anand T Talikoti, Department of Anaesthesia, SDUMC, Kolar, Karnataka, India
53, Manjunatha Krupa,
First Main, Second Cross,
C. Byregowda Nagar, ABSTRACT
Kolar - 563 102,
Karnataka, India.
Background and Aims: Laryngoscopic manipulation and endotracheal intubation are noxious
E-mail: drttanand@yahoo.com
stimuli capable of producing tachycardia, arrhythmias and hypertension. The aim of this study
was to arrive at an optimal dose of dexmedetomidine by comparing two doses with placebo to
attenuate stress response during laryngoscopy and endotracheal intubation. Methods: It was
a randomised, prospective, double-blind placebo-controlled study. After Institutional Ethical
Committee clearance, ninety patients of American Society of Anesthesiologists Physical Status
1 were enrolled in the study and divided into three equal groups. Group A received normal
saline, Group B received injection dexmedetomidine 0.5 µg/kg and Group C received injection
dexmedetomidine 0.75 µg/kg as infusion over 10 min. The general anaesthesia technique was
standardised for all three groups. The primary outcome measures were haemodynamic response at
1, 3 and 5 min after intubation. The secondary outcome measures were to note down any adverse
Access this article online effects associated with drugs. The statistical package used was SPSS version 15. Results: Groups
Website: www.ijaweb.org were well matched for their demographic data. There was a statistically significant difference
(P < 0.05) between dexmedetomidine and normal saline in heart rate, systolic, diastolic and mean
DOI: 10.4103/0019-5049.198404
arterial pressures at all time points after tracheal intubation with dexmedetomidine 0.75 µg/kg
Quick response code
being most effective. Sedation scores were more with dexmedetomidine. None of the patients had
any adverse effects such as hypotension, bradycardia, respiratory depression and fall in oxygen
saturation. Conclusion: Dexmedetomidine in a dose of 0.75 µg/kg intravenous is the optimal
dose to attenuate stress response to laryngoscopy and endotracheal intubation.

Key words: Anaesthesia, dexmedetomidine, general, intubation, laryngoscopy

INTRODUCTION of stress response to laryngoscopy and endotracheal

intubation.[2-4] Although they found promising results,
The augmented cardiovascular reflexes in the the higher dose of 1 µg/kg was associated with increased
form of tachycardia and hypertension brought incidence of cardiovascular compromise in the form of
about by the noxious stimulus of laryngoscopy hypotension and bradycardia.[3,4] It has also been found
and intubation can prove to be detrimental for to be associated with increased sedation.[5] There are
patients with cardiovascular and cerebrovascular
This is an open access article distributed under the terms of the Creative
diseases.[1] Several drugs and techniques have been Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
tried by anaesthesiologists to attenuate the stress others to remix, tweak, and build upon the work non‑commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
response to laryngoscopy and endotracheal intubation.
For reprints contact: reprints@medknow.com
α-2 agonists such as clonidine and dexmedetomidine
have been used by some researchers for attenuation How to cite this article: Sebastian B, Talikoti AT, Krishnamurthy
of the stress response to laryngoscopy. Few authors D. Attenuation of haemodynamic responses to laryngoscopy and
have used dexmedetomidine in a dose of 0.5 and endotracheal intubation with intravenous dexmedetomidine: A
comparison between two doses. Indian J Anaesth 2017;61:48-54.
1 µg/kg and found them to be effective in attenuation

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Sebastian, et al.: Attenuate intubation response with dexmedetomidine

no studies until date with dexmedetomidine in a dose Group A received 20 ml normal saline IV as infusion
of 0.75 µg/kg. Hence, this study was undertaken with over 10 min. Group B received IV dexmedetomidine
different doses of dexmedetomidine and comparing 0.5 µg/kg diluted to 20 ml with normal saline as infusion
it with normal saline to arrive at an optimal dose of over 10 min. Group C received IV dexmedetomidine
dexmedetomidine for attenuation of stress response to 0.75 µg/kg diluted to 20 ml with normal saline as
laryngoscopy and endotracheal intubation. infusion over 10 min.

METHODS All patients were monitored with electrocardiography,

pulse oximetry and non-invasive blood pressure. An IV
After obtaining Institutional Ethical Committee line was secured, and the patients were administered IV
clearance, the study was conducted at our Medical fluid Ringer’s lactate. IV glycopyrrolate 0.2 mg and IV
College Hospital. Ninety patients belonging to ondansetron 50 µg/kg IV were given half an hour before
American Society of Anesthesiologists (ASA) Physical induction. Baseline heart rate (HR), systolic blood
Status 1 in the age group of 18 –50 years of either sex, pressure (SBP), diastolic blood pressure (DBP), mean
posted for elective surgeries under general anaesthesia, arterial blood pressure (MAP) and oxygen saturation
were enrolled for the study. Patients who were (SpO2) were measured after premedication. After
physically dependent on narcotics, those with a history 10 min, study drug infusion was given over 10 min.
of bronchial asthma, drug or alcohol abuse, known Any hypotension (SBP fall >20% from the baseline)
drug allergy to either clonidine or dexmedetomidine, was treated with increments of IV mephentermine
cerebrovascular, neurologic, respiratory or ischemic 3 mg, and incidence of bradycardia (HR <50 beats)
heart disease (history of angina, previous myocardial was treated with IV atropine 0.6 mg. After completion
infarction) and renal and hepatic dysfunction were of drug infusion, sedation was assessed at 2, 5 and
excluded from the study. Patients with hypertension, 10 min using Ramsay sedation score.[6] After noting the
diabetes mellitus, phaeochromocytoma, patients sedation scores and monitoring the haemodynamics
on β-blockers, antidepressants, anxiolytics, for 10 min, the anaesthetic procedure was initiated.
anticonvulsant or antipsychotics and any predicted All the patients were pre-oxygenated for 3 min.
difficult airway were also excluded from the study. General anaesthesia technique was standardised for
Patients in whom laryngoscopy time exceeded 15 s all the three groups. Then, patients were induced
were excluded from analysis. with IV propofol 2 mg/kg bodyweight with IV
lignocaine (preservative free) in concentration of 0.1%
All patients were provided with patient information (1 mg of lignocaine to 1 ml of propofol), IV fentanyl
sheet and written informed consent was obtained. 1 µg/kg and IV succinylcholine 2 mg/kg body weight.
All patients were evaluated a day before surgery. The Following laryngoscopy and endotracheal intubation,
patients were kept fasting overnight after 10:00 pm the parameters recorded were HR, SBP, DBP and
and received tablet ranitidine 150 mg orally and tablet MAP at 1, 3 and 5 min after intubation. Anaesthesia
alprazolam 0.5 mg orally as premedication at night was maintained with O2 and N2O in a ratio of 50%
before surgery. Patients were randomly divided into each and isoflurane 0.4%. Muscle relaxation was
three groups of thirty each. Randomisation was done maintained with IV vecuronium 0.1 mg/kg with top
using computer-generated random number table. The ups of 0.04 mg/kg. After surgery, reversal was achieved
double-blinding procedure was followed, in which the with IV neostigmine 0.05 mg/kg and IV glycopyrrolate
person administering the drug and the patients both 0.01 mg/kg. After adequate recovery, patients were
were unaware as to which group the patient belonged shifted to post-anaesthesia care unit and monitored for
to. One consultant anaesthesiologist prepared the 12 h and later shifted to ward.
intravenous (IV) infusions and coded them. The
infusions were handed over to the resident anaesthetist The primary objective of the study was to arrive at an
to be administered to the patients. The resident optimal dose of IV dexmedetomidine by comparing
anaesthetist was unaware of the contents of the different doses of the drug with normal saline in terms
syringe. The resident anaesthetist who administered of attenuation of haemodynamic stress response to
the infusions recorded the parameters. The patients laryngoscopy and endotracheal intubation.
were unaware as to which group they belonged to.
The results of the study were analysed at the end of The statistician was involved before the start of the
the study and then the decoding procedure was done. study. As per directions from statistician, a pilot study

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Sebastian, et al.: Attenuate intubation response with dexmedetomidine

was conducted. The sample size was estimated using groups. Maximum intubation response was seen at
the mean HR at 5 min in three groups after pilot study. 1 min post-intubation in all the three groups. The
At 95% confidence limit and 90% power, a sample size haemodynamic variables never reached the baseline
of 26 was obtained in each group by taking largest mean by 5 min in case of Group A. In Group B, they
difference at 7.91 and expected background standard approached near the baseline by 3 min. In Group C,
deviation (SD) of 9.1. With 10% non-response sample the variables fell below the baseline by 3 min. The
size of 26 + 2.6, 30 participants were included in the group A had statistically higher values of HR, SBP, DBP
study in each group. and MAP at all time intervals post-intubation when
compared to Group B and Group C. Hence, it can be
Descriptive and inferential statistical analyses were inferred that the haemodynamic response was better
carried out in the present study. software, statistical obtunded in Group B and Group C, when compared
package for social sciences (SPSS) version 15 SPSS with Group A. Although there was no statistically
Inc, Chicago, USA. was used to analyse the data. significant difference between Group B and Group C in
Results on continuous measurements are presented as any of the parameters at any point of time, in Group C
mean ± SD and results on categorical measurements patients, the intubation response was completely
are presented in number (%). Significance was obtunded when compared to Group B. In Group C, the
assessed at 5 % level of significance. parameters fell below the baseline value at 3 min after
intubation. This indicates that dexmedetomidine in a
Analysis of variance was used to find the significance dose of 0.75 µg/kg was superior to dexmedetomidine
of study parameters between three or more groups in a dose of 0.5 µg/kg in completely attenuating the
of patients. Post hoc Tukey test was used to find intubation response [Tables 2-5]. Neither bradycardia
the pairwise significance (statistically significant nor hypotension was observed in any of the patients.
P < 0.05). The sedation scores were more in Group B and
Group C when compared to Group A [Table 6]. In none
RESULTS of the patients of any group did the SpO2 fall below
95%. None of the patients in any of the group needed
The groups were well matched for their demographic oxygen supplementation.
data [Table 1]. The surgeries routinely performed in
our institute such as tympanoplasty, mastoidectomy, DISCUSSION
functional endoscopic sinus surgeries, breast surgeries
such as fibroadenoma excision, laparoscopic surgeries The introduction of general anaesthesia made it
such as appendicectomy and cholecystectomy possible to induce a state of controlled unconsciousness
and various orthopaedic surgeries such as upper so that the patient is insensitive to pain and unaware
limb fractures and microlumbar discectomies were of the events occurring during the surgical procedure.
included in our study. The basal readings of HR, The anaesthetised patients are unable to maintain an
SBP, DBP and MAP were similar in all the three adequate airway on their own, and there arises the
need to employ artificial airway maintenance devices
Table 1: Demographic details of patients such as endotracheal tube. Traditionally, laryngoscopy
Groups Mean age (years)±SD Male (%) Female (%) and endotracheal intubation has been the mainstay in
Group A 32.50±9.12 15 (50) 15 50) safeguarding the airway in such patients. Although
Group B 36.96±10.33 17 (56.7) 13 (43.3)
intubation has its own advantages such as a safe
Group C 31.20±9.30 14 (46.7) 16 (53.3)
P=0.100 for age distribution of patients (Chi‑square test), P=0.733 for gender
and secured airway and prevention of aspiration
distribution of patients (Chi‑square test). SD – Standard deviation and delivery of anaesthetic gases, it is not without

Table 2: Comparison of heart rate between three groups

HR (beats/ Group A Group B Group C P Pairwise significance
min) Group A versus Group A versus Group B versus
Group B Group C Group C
Baseline 80.40±5.67 81.50±5.30 81.47±5.28 0.672 0.712 0.727 1.399
1 min 112.23±5.8 85.57±5.41 84.37±5.51 <0.001** <0.001** <0.001** 1.439
3 min 104.03±4.63 83.73±4.95 80.83±5.40 <0.001** <0.001** <0.001** 1.293
5 min 92.87±5.08 79.47±4.65 75.03±5.8 <0.001** <0.001** <0.001** 1.343
**Highly significant (test of significance used is ANOVA and post hoc Tukey test). HR – Heart rate

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Sebastian, et al.: Attenuate intubation response with dexmedetomidine

Table 3: Comparison of systolic blood pressure between three groups

SBP Group A Group B Group C P Pairwise significance
(mmHg) Group A versus Group A versus Group B versus
Group B Group C Group C
Base line 128.07±7.90 128.73±9.82 130.07±8.04 0.660 0.952 0.643 0.821
1 min 160.13±6.08 134.60±9.74 133.27±7.75 <0.001** <0.001** <0.001** 2.065
3 min 148.33±5.87 129.87±9.75 124.67±8.41 <0.001** <0.001** <0.001** 2.110
5 min 139.60±4.94 126.07±9.78 117.80±7.49 <0.001** <0.001** <0.001** 1.978
**Highly significant (test of significance used is ANOVA and post hoc Tukey test). ANOVA – Analysis of variance; SBP – Systolic blood pressure

Table 4: Comparison of diastolic blood pressure between three groups

DBP Group A Group B Group C P Pairwise significance
(mmHg) Group A versus Group A versus Group B versus
Group B Group C Group C
Baseline 76.40±6.94 77.27±4.91 74.87±5.16 0.266 0.829 0.557 0.243
1 min 91.27±6.02 81.67±4.52 77.33±5.26 <0.001** <0.001** <0.001** 1.369
3 min 88.13±5.63 76.67±4.62 72.47±5.16 <0.001** <0.001** <0.001** 1.331
5 min 84.67±5.21 74.33±4.52 69.53±4.66 <0.001** <0.001** <0.001** 1.241
**Highly significant (test of significance used is ANOVA and post hoc Tukey test). ANOVA – Analysis of variance; DBP – Diastolic blood pressure

Table 5: Comparison of mean arterial pressure between three groups

MAP Group A Group B Group C P Pairwise significance
(mmHg) Group A versus Group A versus Group B versus
Group B Group C Group C
Baseline 93.83±6.36 94.70±5.75 93.27±5.53 0.639 0.836 0.926 0.615
1 min 114.57±5.14 98.87±5.86 96.33±5.40 <0.001** <0.001** <0.001** 1.414
3 min 108.47±4.97 94.83±5.13 90.27±5.49 <0.001** <0.001** <0.001** 1.343
5 min 103.37±4.51 91.80±5.48 85.47±5.08 <0.001** <0.001** <0.001** 1.301
**Highly significant (test of significance used is ANOVA and post hoc Tukey test). ANOVA – Analysis of variance; MAP – Mean arterial pressure

Table 6: Sedation Scores between the three groups

Sedation Group A Group B Group C
Score 2 min 5 min 10 min 2 min 5 min 10 min 2 min 5 min 10 min
1 6 (20%) 4 (13.33%) 3 (10%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
2 21 (70%) 23 (76.67%) 24 (80%) 16 (53.33%) 13 (43.33%) 11 (36.67%) 13 (43.33%) 8 (26.67%) 2 (6.67%)
3 3 (10%) 3 (10%) 3 (10%) 14 (46.67%) 15 (50%) 19 (63.33%) 17 (56.67%) 18 (60%) 22 (73.33%)
4 0 (0%) 0 (0%) 0 (0%) 0 (0%) 2 (6.67%) 0 (0%) 0 (0%) 4 (13.33%) 6 (20%)
5 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
6 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
P value 2 MINUTES 5 MINUTES 10 MINUTES
Group A vs B P<0.001* Group A vs B P<0.001* Group A vs B P<0.001*
Group A vs C P<0.001 Group A vs C P<0.001* Group A vs C P<0.001*
Group B vs C P<0.001* Group B vs C P>0.05 Group B vs C P<0.001*
** ‑ highly significant P>0.05‑ not significant

complications. Laryngoscopy and endotracheal laryngoscopy, peaks in 1–2 min and returns to normal
intubation are noxious stimuli capable of producing a levels by 5 min.[8] These changes are usually short
huge spectrum of stress responses such as tachycardia, lived and well tolerated by normal patients. In patients
hypertension, laryngospasm, bronchospasm, raised with cardiovascular disease, it can incite harmful
intracranial pressure and intraocular pressure.[1] effects such as myocardial ischaemia, ventricular
dysrrhythmias, ventricular failure and pulmonary
The haemodynamic changes brought about by oedema. It can also lead to cerebrovascular accidents
laryngoscopy and intubation was first described by in cerebrovascular disease patients.[9]
Reid and Brace.[7] The haemodynamic response is
initiated within seconds of direct laryngoscopy and Various drug regimens and techniques such as
further increases with the passage of the endotracheal lignocaine, opioids, nitroglycerine, calcium channel
tube. The response is initiated within 5 s of blockers such as diltiazem and β-blockers such as

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Sebastian, et al.: Attenuate intubation response with dexmedetomidine

esmolol have been tried for obtunding the stress premedicant, to decrease the secretions and offer ideal
response.[8,10-13] α-2 receptor agonists mediate their intubating conditions on one side and not to interfere
action through α-2A receptors located in locus in haemodynamic parameters much with its moderate
caeruleus, the predominant noradrenergic nuclei effect on the HR on the other side. The baseline values
of upper brainstem. The presynaptic activation of were recorded after glycopyrrolate administration to
α-2A receptors in the locus caeruleus inhibits the account for any small changes in readings. Further,
noradrenaline release and brings about sedation and it has been administered to all groups to eliminate
hypnosis. Post-synaptic activation of α-2 receptors any bias in readings. With this, any change in
in central nervous system brings about decreased haemodynamic parameters recorded can be attributed
sympathetic activity leading to bradycardia and to administration of study drug.
hypotension.[14]
Smitha et al. compared the effect of 0.5 and 1 µg/kg
Dexmedetomidine is eight times more potent α-2 of dexmedetomidine with normal saline in attenuating
receptor agonist than clonidine. The action of stress response. They found out that dexmedetomidine
dexmedetomidine is short lived with an elimination 1 µg/kg was more effective than dexmedetomidine
half-time of 2 h. Dexmedetomidine has a reversal 0.5 µg/kg in controlling haemodynamic responses
drug for its sedative effect called as atipamezole. to tracheal intubation. The intergroup comparison
Atipamezole acts by increasing the central turnover of revealed a statistically significant reduction in HR
noradrenaline. These factors make dexmedetomidine by dexmedetomidine than normal saline.[19] These
superior to clonidine.[15,16] findings correlated with findings in our study.

Dexmedetomidine has been studied by few authors Menda et al. conducted a study on ischaemic heart
in a dose of 0.5 and 1 µg/kg.[2-4] No study has been disease patients undergoing fast-track coronary artery
done to see the efficacy of dexmedetomidine in a bypass graft comparing dexmedetomidine 1 µg/kg
dose of 0.75 µg/kg for attenuation of laryngoscopy and and placebo. They inferred that in the placebo group,
intubation response. Hence, in this study, we chose the systolic arterial pressure increased significantly
to include injection dexmedetomidine in a dose of 0.5 after the intubation when compared to pre-intubation
and 0.75 µg/kg and compare it with normal saline for period, whereas it did not change significantly in the
attenuation of laryngoscopy and intubation response. dexmedetomidine group.[4]
The control group was used to ascertain whether
dexmedetomidine has a favourable action or not. The Two different doses of dexmedetomidine 1 and 0.5 µg/kg
two doses of dexmedetomidine were used which were were compared with lignocaine 1.5 mg/kg to maintain
felt as appropriate. haemodynamic stability associated with intubation by
Gulabani et al. Dexmedetomidine 1 µg/kg was found
To lessen stress response to laryngoscopy and to be more effective than dexmedetomidine 0.5 µg/kg
endotracheal intubation, it is prudent to keep the and lignocaine.[20] Hence, it is of clinical use in cardiac
laryngoscopy time as less as possible and limit the patients in whom the stress response to laryngoscopy
duration of noxious stimulus. Hence, the laryngoscopy and intubation is highly unacceptable. The variations
time has been limited to 15 s in this study. in DBP were in accordance with the recordings of our
Laryngoscopy time was monitored with a stopwatch, clinical trial. The variation in MAPs was parallel to
and cases in whom the time exceeded 15 s have been the magnitude of change in SBP and DBP. In our study,
excluded from the study. Further one more factor that though there was no statistical difference between
influences the stress response to laryngoscopy and dexmedetomidine 0.5 µg/kg and 0.75 µg/kg, the latter
endotracheal intubation is the intubating conditions. It more effectively attenuated the intubation response.
has been shown by studies that use of anticholinergic In fact, the values of the parameters fell below the
drugs before intubation has provided good intubating baseline by 3 and 5 min following intubation with
conditions.[17] Anticholinergics by virtue of their dexmedetomidine 0.75 µg/kg.
antisialagogue action offer good intubating conditions
by decreasing the secretions. Amongst anticholinergic The sedation scores obtained were higher for
glycopyrrolate has got good antisialagogue action dexmedetomidine group than normal saline in our
with less chance of causing increase in HR.[18] study. A study by Manne et al. noting the effects of
Hence, injection glycopyrrolate was chosen as good low-dose dexmedetomidine infusion on haemodynamic

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Sebastian, et al.: Attenuate intubation response with dexmedetomidine

stress response, sedation and post-operative analgesia Financial support and sponsorship
requirement in patients undergoing laparoscopic Nil.
cholecystectomy also observed increasing sedation
levels with dexmedetomidine.[21] Dexmedetomidine in Conflicts of interest
a dose of 1 µg/kg has been shown to cause increased There are no conflicts of interest.
sedation levels and need for oxygen supplementation
by few authors.[22,23] Dexmedetomidine when REFERENCES
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Announcement

CALENDAR OF EVENTS OF ISA 2017

The cut off dates to receive applications / nominations for various Awards / competitions 2017 is as below. Hard copy with all supportive documents to
be sent by Regd. Post with soft copy (Masking names etc.) of the same by E Mail to secretaryisanhq@gmail.com. The masked soft copy will be circulated
among judges. Only ISA members are eligible to apply for any Awards / competitions. The details of Awards can be had from Hon. Secretary & also
posted in www.isaweb.in
Cut Off Date Name of Award / Competition Application to be sent to
30 June 2017 Bhopal Award for Academic Excellence Hon. Secretary, ISA
30 June 2017 Late Prof. Dr. A .P. Singhal Life Time Hon. Secretary, ISA
Achievement Award
30 June 2017 Rukmini Pandit Award Hon. Secretary, ISA
30 June 2017 Dr. Y. G. Bhoj Raj Award Award Hon. Secretary, ISA
30 Sept. 2017 Kop’s Award Chairperson, Scientific Committee ISACON 2017
copy to Hon. Secretary, ISA
30 Sept. 2017 ISACON Jaipur Award Chairperson, Scientific Committee ISACON 2017
copy to Hon. Secretary, ISA
30 Sept. 2017 Prof. Dr. Venkata Rao Oration 2017 Hon. Secretary, ISA
30 Sept. 2017 Ish Narani Best poster Award Chairperson, Scientific Committee ISACON 2017
30 Sept. 2017 ISA Goldcon Quiz Chairperson, Scientific Committee ISACON 2017
10 Nov. 2017 Late Dr. T. N. Jha Memorial Award Hon. Secretary, ISA, copy to Chairperson
& Dr. K. P. Chansoriya Travel Grant Scientific Committee of ISACON 2017
20 Oct. 2017 Awards (01 Oct 2016 to 30 Sept 2017) Hon. Secretary, ISA
(Report your monthly activity online every month after logging in using Secretary’s log in ID)
1. Best City Branch
2. Best Metro Branch
3. Best State Chapter
4. Public Awareness – Individual
5. Public Awareness – City / Metro
6. Public Awareness - State
7. Ether Day (WAD) 2017 City & State
8. Membership drive
9. Proficiency Awards
Send hard copy (where ever applicable) to
Dr. Venkatagiri K.M.
Hon Secretary, ISA National
“Ashwathi”’ Opp. Ayyappa temple,
Nullippady, Kasaragod 671 121.
secretaryisanhq@gmail.com / 9388030395.

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