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A comparative study of intravenous
low doses of dexmedetomidine,
fentanyl, and magnesium sulfate for
attenuation of hemodynamic response
to endotracheal intubation
Website:
www.ijp‑online.com
DOI:
10.4103/ijp.ijp_923_20 Sharmishtha Shukla, Reena R. Kadni1, Joel J. Chakravarthy1,
K. Varghese Zachariah1
Abstract:
BACKGROUND: Endotracheal intubation is an integral part of general anesthesia. The hemodynamic
stress responses associated with it, though transient, are unpredictable and variable. In comparison
with healthy individuals, those with comorbid health issues can have life‑threatening complications with
this sympathetic response. Hence, in this study, we compared the efficacy of intravenous low doses
of dexmedetomidine, fentanyl, and magnesium sulfate (MgSO4) in reduction of the hemodynamic
response to endotracheal intubation.
MATERIALS AND METHODS: This prospective randomized study compared three groups of
dexmedetomidine (0.6 µg/kg) (Group D), fentanyl (2 µg/kg) (Group F), and MgSO4 30 mg/kg (Group M).
A total of 105 American Society of Anesthesiologist’s 1 and 2 patients were selected with 35 in each
group. The hemodynamic variables recorded at baseline, during induction and intubation up to ten
minutes were pulse rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure.
The assessment of quantitative and qualitative data was done with the one‑way ANOVAs, Student’s
t‑test, and Chi‑square test. Analysis of variance was done by post hoc tests.
RESULTS: There were statistically significant differences that were observed with dexmedetomidine
and fentanyl groups in respect to heart rate and blood pressure responses to laryngoscopy and
intubation when compared to MgSO4. A significant attenuation of response from baseline values
was also noted with dexmedetomidine and fentanyl groups.
CONCLUSION: Efficacy of low doses of both dexmedetomidine and fentanyl was equipotent in
attenuating response in comparison with MgSO4, and we conclude that dexmedetomidine can serve
Department of as an alternative to fentanyl.
Anaesthesia, University
Hospitals of Derby Keywords:
and Burton NHS Trust, Dexmedetomidine, fentanyl, intubation response, low dose, magnesium sulfate
Derby, United Kingdom,
1
Department of
Anaesthesia, Bangalore
Baptist Hospital, Introduction nociceptors leading to hemodynamic stress
Bengaluru, Karnataka, response which can be deleterious to patients
E
India with limited cardiac reserve and with other
ndotracheal intubation is an important
Address for procedure practiced in the field of comorbid conditions such as valvular
correspondence: anesthesia. It is associated with airway heart disease, abnormal cardiac rhythms,
Dr. Reena R. Kadni, manipualation which stimulates the heart blocks, difficult airway, uncontrolled
Senior Consultant, pharyngeolaryngeal and tracheolaryngeal hypertension, raised intracranial pressure,
Department of
Anaesthesia, Bangalore pulmonary hypertension, asthamatics, or
This is an open access journal, and articles are
Baptist Hospital, distributed under the terms of the Creative Commons
Bangalore-560024, India. Attribution‑NonCommercial‑ShareAlike 4.0 License, which How to cite this article: Shukla S, Kadni RR,
E-mail: docreena1@gmail. allows others to remix, tweak, and build upon the work Chakravarthy JJ, Zachariah KV. A comparative
com non‑commercially, as long as appropriate credit is given and study of intravenous low doses of dexmedetomidine,
Submitted: 19‑Sep‑2020 the new creations are licensed under the identical terms. fentanyl, and magnesium sulfate for attenuation of
Revised: 20‑Oct‑2022 hemodynamic response to endotracheal intubation.
Accepted: 09‑Nov‑2022 Indian J Pharmacol 2022;54:314-20.
Published: 13-Dec-2022 For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
314 © 2022 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow

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Shukla, et al.: Low dose dexmedetomidine: A valid choice for pressor response
chronic obstructive lung diseases. Extreme hemodynamic Materials and Methods

variations with marked sympathetic activity such as
tachycardia and hypertension are observed with airway This study is a prospective, double‑blinded and
handling procedures.[1,2] Due to imbalanace in oxygen randomized clinical trial and was carried out after
demand and supply to the heart, this stress response can be getting approval from the Institutional Ethics committee
detrimental to an extent leading to myocardial infarction, reference number ANA/67/2014 dated December
pulmonary edema, arrythmias, cerebrovascular accidents 23, 2014, and was conducted from January 2015 to
such as hemorrhage, and other complications in susceptible December 2015. It adheres to the applicable CONSORT
patients. Dexmedetomidine, fentanyl, and magnesium guidelines [Figure 1].
sulfate (MgSO4) are studied and known to decrease the
Patients aged between 18 and 55 years, belonging
hmodynamic response during intubation in various
to American Society of Anesthesiologist’s (ASA)
doses. The following study compared the effects of low
grade 1and 2 for elective surgeries under GA with
doses of intravenous (IV) dexmedetomidine, fentanyl, and
controlled mechanical ventilation were selected. These
MgSO4 on hemodynamic variables during endotracheal
patients were included after obtaining informed written
intubation under general anesthesia (GA). All three are
consent. Patients with uncontrolled hypertension,
potent analgesics, decrease catecholamine levels and are ischemic heart disease, arrhythmias, on beta‑blockers,
commonly used drugs in anesthesia practice.[3] Lower heart blocks, atrioventricular dysfunction, anticipated
dosages of each drug were chosen to help in providing difficult intubation/multiple attempts more than
opiod‑free balanced anesthesia, assist enhanced recovery 2 or time duration of laryngoscopy more than 20 s of
from anesthesia, and reduced the incidence of side effects intubation were excluded from the study.
associated with these drugs such as bradycardia, sedation,
and delayed recovery from anesthesia. The sample size was 105, patients were randomly
allocated to three different groups (D, F and M) with
We hypothesized that low dose of dexmedetomidine 35 in each using block allocation and concealment
(0.6 µg/kg) can be more effective than low doses of method as described. The number in each block was
fentanyl (2 µg/kg) and MgSO4 (30 mg/kg) in reducing calculated using the formula 2n (where n is the number
the hemodynamic stress response during laryngoscopy of drugs). We got a block size of 6. With the sample
and intubation. size of 105, we got a total of 18 blocks. All possible
Enrollment Exclusion criteria

• Pts for elective fulfilling inclusion criteria • Pt refusal for consent
◦ ASA I, II , (18-55 yrs) elective Surgery under GA • Pt with uncontrolled HTN,IHD,
arrythmias, on beta blockers,
heart blocks, AV Dysfunction
• MPC III & IV with anticipitated
difficult intubation
Informed consent • Allergic to any of the drugs
• HR < 60/min SBP<90
• Unexpected difficult intubation
Randomization(n = 90)
Allocation
(n = 90 into three n = 30 group)
Allocation to Dexmedetomidine Allocation to Fentanyl Allocation to Magnesium

group A (n = 30) group B (n = 30) Sulphate group C (n = 30)
Analysis
Hemodynamic Response Hemodynamic Response Hemodynamic Response

@1,3,5,10 mins for @1,3,5,10 mins for @1,3,5,10 mins for Magnesium
Dexmedetomidine group A(n = 30) Fentanyl group B(n = 30) Sulphate group C(n = 30)
Figure 1: Consort flow diagram
Indian Journal of Pharmacology - Volume 54, Issue 5, September-October 2022 315

allocation sequence was assigned numbers from 1 to planned to be treated with IV ephedrine 3 to 6 mg and
20. The computer‑generated random numbers were bradycardia with HR <60 beats/min with IV atropine
taken. The first digit of each number was taken to give 0.6 mg. No form of the stimulus was applied during
the corresponding allocation sequence to each block. If this period. Analgesics such as morphine, paracetamol,
the first number was 0, then the second number would and fentanyl were given to all three groups after 10 min.
be taken for the same. The surgery commenced after 10 min of intubation as
per the GA protocol. Patients were extubated at the end
This allocation sequence was revealed by an of the surgery.
anesthesiologist not paticipating in the study. The
primary investigator was kept unaware of the allocation The comparison of quantitative data and descriptive
sequences. Random numbers were concealed using statistical methods (mean, standard deviation) was done
the opaque envelopes and were opened just before the with one‑way ANOVA and Student’s t‑test. Qualitative
administration of block. The drugs were loaded and data were assessed by the Chi‑square test. The comparisons
given according to the sequence. were considered statistically significant with (P < 0.05)
and extremely significant with (P < 0.001) in a confidence
The study instrument was the patient pro forma which interval of 95%. Statistical analysis was done with
included patient’s name, age, gender, weight, ASA 1 SPSS (Statistical Package for the Social Sciences) SPSS Inc.
or 2, patient’s particulars, indication for surgery, and IBM, Chicago, United States, for Windows version 16.0. Post
hemodynamic parameters were recorded at baseline (T0) hoc tests used in analysis of variance were Tukey’s Honestly
and 5 (T1) and 10 (T2) min after test drug and 1 (T4), significant difference (HSD) and Scheffe’s test.
3 (T5), 5 (T6), and 10 (T7) min after intubation.
The sample size was calculated based on the mean HR
Fasting guidelines were adhered to and premedication after 5 min between two groups (dexmedetomidine and
with oral ranitidine 150 mg and diazepam 10 mg was MgSO4). The difference in HR was maximum in these
done. On arrival at the operation theater, patient’s two groups; hence, these two groups were used to get a
baseline hemodynamic parameters were recorded (basal higher sample size. At a power of 90% and a confidence
reading T0) and IV cannula was secured. interval of 99%, the sample size was calculated as 35 per
group. The total sample size was 105. On compensating
According to the randomization, the patients received for loss to follow‑up, an additional 15% of the sample
IV dexmedetomidine 0.6 µg/kg or IV fentanyl 2 µg/kg size was added.
or IV MgSO4 30 mg/kg in 10 ml normal saline through
a syringe pump over a period of 10 min at the rate of Results
60 ml/h before induction. After 5 min of stabilization (T1)
and at 10 min of giving the test drug (T2) systolic blood The three groups had no significant differences with
pressure, diastolic blood pressure, and mean blood subject to the demographic profile of the patients (P > 0.05)
pressure (SBP, DBP, and MAP), heart rate (HR), and and were comparable concerning age, gender, weight,
oxygen saturation (SPO2) were recorded. Patients were and ASA physical status.
monitored with ASA standard monitors (Philips).
The comparison of the three groups in respect to HR
After preoxygenation, IV Propofol 2 mg/kg was used showed statistically significant increases after giving
as an induction agent and neuromuscular block was test drugs, (T1, T2), after induction agent (T3) and after
achieved with IV Atracurium 0.5 mg/kg. Oxygenation intubation (T5 and T6) [Table 1]. The baseline values
and depth of anesthesia were maintained by mask were comparable without any significant differences.
ventilation with 50% O2, 50% air and isoflurane to The increase in HR in the MgSO 4 group was more
maintain a minimum alveolar concentration of one significant than the other two groups after giving test
through anesthesia work station (Datex Ohmeda). drug, at induction and 3–5 min after intubation but
BP, HR, and SPO2 were recorded at 2 min (T3) settled by 10 min.
after induction. Intubation done with endotracheal
tube (Smiths Portex) was done by a consultant more than There were more statistically significant differences on post
3 years’ experience and confirmation of its position were hoc tests intergroup comparison of HR between fentanyl
done by auscultation and capnography at 3 min after and MgSO4 groups on effects on HR after intubation
induction. The patient was put on the volume control with P < 0.05, whereas between dexmedetomidine and
mode on a ventilator to maintain EtCO2 of 30–35 mmHg. MgSO4, significant differences were not observed after
At 1 min (T4), 3 min (T5), 5 min (T6), and 10 min (T7) intubation [Table 2]. Dexmedetomidine and fentanyl
after laryngoscopy and intubation, hemodynamic were comparable before and after intubation in their
parameters were recorded. Any fall in SBP to < 20% was responses.
316 Indian Journal of Pharmacology - Volume 54, Issue 5, September-October 2022
On comparing the three drugs for their effects on SBP, in controlling the SBP response after intubation than
significant differences (with P < 0.05) were found MgSO4.
after giving induction agent (T3) and at all times after
intubation (T4, 5, 6, 7) [Table 3]. There was a drop in SBP On comparing the three drugs with relation to DBP and
in all groups after induction of anesthesia and significant MAP, there was a statistically significant decrease seen
rise was observed in M group at 1 min after intubation. with P = 0.018 at 5 min after intubation (T6). Intergroup
Post hoc intergroup comparison of SBP showed
comparison showed a significant difference between
statistically significant differences between fentanyl and
fentanyl and MgSO4 at T6 for DBP. With MAP, there was
MgSO4 from time of induction agent given till 10 min
after intubation [Table 4]. Between dexmedetomidine a significant difference between fentanyl and MgSO4 and
and MgSO4 groups, there were significant differences dexmedetomidine and MgSO4 at T6. Dexmedetomidine
at 3 min after intubation till 10 min. Fentanyl and and fentanyl groups did not show any significant
dexmedetomidine were comparable and were better differences concerning DBP and MAP.
Table 1: Comparison of heart rate (bpm) in three groups of patients

Time (min) Dexmedetomidine (Group D) Fentanyl (Group F) MgSO4 (Group M) P
T0 (baseline) 84.66±15.420 83.46±15.583 85.37±12.381 0.857
T1 (5 min after test drug) 77.8±16.435 80.8±13.807 88.06±12.923 0.012
T3 (2 min after induction agent and muscle relaxant) 92.37±18.114 83.46±16.325 93.23±16.804 0.034
T4 (1 min after intubation) 99.11±18.467 95.91±12.937 103.97±16.452 0.114
MgSO4=Magnesium sulfate
Table 2: Intergroup comparison of P values of heart rate among three groups dexmedetomidine, fentanyl, and
magnesium sulfate in based on post hoc test results
Time (min) Group D verses Group F versus Group D versus
Group F (P) Group M (P) Group M (P)
T1 (5 min after test drug) 0.662 0.095 0.010
T2 (10 min after test drug) 0.866 0.013 0.049
T3 (2 min after induction agent and muscle relaxant) 0.079 0.049 0.976
T5 (3 min after intubation) 0.404 0.010 0.220
Table 3: Comparison of systolic blood pressure (mmHg) in three groups of patients

Time (min) Dexmedetomidine (Group D) Fentanyl (Group F) MgSO4 (Group M) P
T0 (when patient is shifted to OT) 123.37±15.469 130.06±18.859 127.57±13.245 0.216
T3 (2 min after induction agent and muscle relaxant) 103.89±19.406 99.4±15.884 111.74±16.389 0.013
T5 (3 min after intubation) 113.63±13.500 112±19.043 128.83±23.465 0.011
T7 (10 min after intubation) 102.23±12.293 102±14.576 113.49±20.147 0.004
OT=Operation theater, MgSO4=Magnesium sulfate
Table 4: Intergroup comparison of systolic blood pressure (mmHg) among three groups dexmedetomidine,
fentanyl, and magnesium sulfate based on post hoc test results
Time (min) Group D versus Group F (P) Group F versus Group M (P) Group D versus Group M (P)
T3 (2 min after induction 0.526 0.010 0.144
agent and muscle relaxant)

There was a statistically significant increase in HR with all Fentanyl is regularly used opioid analgesic and as an
three drugs when compared to their baseline values and induction agent in cardiac patients for its hemodynamic
to the mean values over 10 min after intubation and more stability. Carotid sinus baroreceptor reflex control
significantly with MgSO4. Extremely significant reduction of HR is depressed by fentanyl. Bradycardia is more
of SBP and MAP was seen with dexmedetomidine and prominent with fentanyl, as it slows atrioventricular
fentanyl groups when compared to their baseline values. conduction. A fall in systemic vascular resistance resuts
DBP was extremely reduced with fentanyl than with in hypotension after larger doses of fentanyl.[8,9]
dexmedetomidine.[Table 5].
The study aimed to observe whether dexmdetomidine or
Discussion MgSO4 could replace fentanyl in its pharmacodynamic
action.
The aim of endotracheal intubation is to secure a
Saraf et al.[10] observed IV dexmedetomidine 0.6 µg/kg
definitive airway. Unfortunately, it leads to a undesirable
attenuated the pressor response during intubation with
cascade of pathophysiological responses. This may cause
a minimal incidence of bradycardia and hypotension.
adverse outcomes in the selected patient population who
Panda et al.[11] compared the different doses of IV MgSO4
possess comorbid health issues. Various medications are
and concluded that 30 mg/kg as the optimum dose for
in use to reduce this hemodynamic response, but not all
attenuating the rise in blood pressure during laryngoscopy.
are beneficial in aspects of analgesia and amnesia which
Fentanyl 2 µg/kg IV, which is a routine dose, was used in
can further assist the anaesthesia service to the patient.
attenuating pressor response during tracheal intubation.
Furthermore, the upcoming role of opiod‑free anesthesia
led us to this trial to compare nonopioid drugs like Based on the above studies, we compared these low doses
dexmedetomidine and MgSO4 with fentanyl. of IV dexmedetomidine 0.6 µg/kg, IV MgSO4 30 mg/kg
and IV fentanyl 2 µg/kg. Low doses were used for trial
The receptor selectivity of dexmedetomidine is to balance the benefits versus the untoward effects of
dose‑dependent, more of α‑2 selectivity is observed with these drugs but keeping the advantages of analgesia and
slow infusions, and both α‑1 and α‑2 activities resulted amnesia during surgery.
from high doses or rapid infusions.[4] The baroreceptor
reflex response is known to be well preserved in patients No statistically significant difference was found between
who received dexmedetomidine.[5] Higher doses are dexmedetomidine and fentanyl in all the hemodynamic
associated with bradycardia, hypotension, and sedation. variables but there were significant differences in
hemodynamic profile when the two drugs were
The vasodilatory and antidysrhythmic effects of MgSO4 compared individually with MgSO4.
have been presumed to protect against hypertensive
responses to direct laryngoscopy and tracheal intubation. Heart rate dynamics
It performs as a cardioprotective drug by reducing the All the three drugs showed statistically increase in HR
increase in intracellular calcium ion flux that accompanies from baseline values when compared to mean value
myocardial ischemia followed by reperfusion.[6,7] MgSO4 over 10 min after intubation. On intergroup comparison,
toxicity is associated with prolonged neuromuscular M group had a significant increase in HR after giving test
block and sedation. drugs, at induction and 3 min, 5 min after intubation.
Table 5: Comparison of baseline values (T0) with mean value over 10 min after intubation in each group for all
parameters
Parameters Group Baseline value (T0) Mean value over 10 min after intubation P
HR Dexmedetomidine 84.66±15.420 94.315±17.494 0.001
Fentanyl 83.46±15.583 89.435±14.422 0.027
MgSO4 85.97±12.381 99.47±18.8095 0.000
SBP Dexmedetomidine 123.37±15.469 111.825±13.963 0.000
Fentanyl 130.06±18.859 111.015±18.619 0.000
MgSO4 127.57±13.245 124.90±23.897 0.208
DBP Dexmedetomidine 75.8±12.697 70.53±12.253 0.025
Fentanyl 78.54±9.596 69.57±13.99 0.00
MgSO4 78.54±12.229 76.37±16.43 0.289
MAP Dexmedetomidine 88.83±11.388 80.81±11.09 0.00
Fentanyl 91.4±12.605 80.05±14.47 0.00
MgSO4 85.23±9.828 87.9±18.85 0.171
MgSO4=Magnesium sulfate, HR=Heart rate, SBP=Systolic blood pressure, DBP=Diastolic blood pressure, MAP=Mean arterial pressure

Our study was consistent with Sharma and Parikh[12] intubation followed by a fall in DBP at 5 and 10 min
using a similar dose of fentanyl and found an increase later. The rise of DBP at 1 and 3 min after intubation was
in HR after intubation and a drop after intubation at insignificant statistically.
10 min. MgSO4 group showed an increase in HR after
intubation. Our research results were comparable to Mean blood pressure dynamics
Puri et al.[13] (50% of 0.1 ml/kg MgSO4) and Sharma In all three groups, we observed that there was a fall
et al.[14] (40 mg/kg MgSO4) where an increase in HR after in MAP at 3, 5, and 10 min after intubation which were
intubation was observed. similarly observed in studies by Jain et al.[19] Navid
et al.[17] observed with MgSO4 60 mg/kg a rise in MAP
Reddy et al.[15] using dexmedetomidine 1 µg/kg found a after intubation at 1, 2, and 4 min. Lower dosage of
statistically insignificant rise in HR after intubation. In MgSO4 (30 mg/kg) gave a better result in our research.
contrast, Kharwar et al.[16] observed that dexmedetomidine
1 µg/kg and fentanyl 2 µg/kg resulted in a statistically No side effects of bradycardia and hypotension were
significant decrease in HR from baseline in the observed in all groups.
dexmedetomidine group. Saraf et al.[10] and Jaakola et al.[4]
found significant reduction of HR with dexmedetomidine The use of BIS monitor would have helped to getter better
0.6 µg/kg, which was not observed in our study. results and assessment of response after categorizing the
age groups would have given further insights of these
Systolic blood pressure dynamics drugs. These remain the limitations of this study.
There was fall in SBP in all groups after induction of
anesthesia and a statistically significant fall in SBP Conclusions
was seen with D and F group when their mean values
over 10 min were compared with their baseline values. We conclude that low dose of IV dexmedetomidine
0.6 µg/kg and IV fentanyl 2 µg/kg are equally
In the dexmedetomidine group, we observed a fall in effective in reducing vasopressor response related to
SBP after intubation when compared to baseline. Jaakola laryngoscopy/intubation and their efficacy is more
et al.[4] and Saraf et al.[10] used dexmedetomidine 0.6 µg/kg than MgSO4 (30 mg/kg). Dexmedetomidine can serve
and noticed a fall in SBP after intubation. Sharma and as an alternative to fentanyl in attenuating pressor
Parikh[12] who used a similar dose of fentanyl, noticed a response during laryngoscopy and tracheal intubation.
rise in SBP immediately after intubation and a drop at 5 In contrast, MgSO4 30 mg/kg showed a statistically
and 10 min later. However, the drop in SBP in our study significant increase in HR and blood pressure during
was found to be more than their obervation. laryngoscopy/intubation comparitively, so at this dose
it proved ineffective.
There was a rise in SBP at 1 min after intubation and a fall
was noticed thereafter in the MgSO4 group. In the study Financial support and sponsorship
conducted by Navid et al.,[17] the MgSO4 dose (60 mg/kg) Nil.
was higher than our study and they observed a mean rise in
SBP by 4.7 mmHg, whereas in our study, there was a mean Conflicts of interest
fall by 2.87 mmHg from baseline after intubation. Therefore, There are no conflicts of interest.
attenuation of SBP with low dose MgSO4 (30 mg/kg) gave
a better hemodynamic response in our study. References
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314 © 2022 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow

chronic obstructive lung diseases. Extreme hemodynamic Materials and Methods

Enrollment Exclusion criteria

Allocation to Dexmedetomidine Allocation to Fentanyl Allocation to Magnesium

Hemodynamic Response Hemodynamic Response Hemodynamic Response

Figure 1: Consort flow diagram

Indian Journal of Pharmacology - Volume 54, Issue 5, September-October 2022 315

Table 1: Comparison of heart rate (bpm) in three groups of patients

Table 3: Comparison of systolic blood pressure (mmHg) in three groups of patients

Indian Journal of Pharmacology - Volume 54, Issue 5, September-October 2022 317

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