Eur J Anaesthesiol 2018; 35:372–378

ORIGINAL ARTICLE

Dexmedetomidine as a part of general anaesthesia

for caesarean delivery in patients with pre-eclampsia
A randomised double-blinded trial
Ashraf M. Eskandr, Ahmed A. Metwally, Abd-Elrahman A. Ahmed, Elham M. Elfeky,
Islam M. Eldesoky, Manar A. Obada and Osama A. Abd-Elmegid
Downloaded from http://journals.lww.com/ejanaesthesiology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 09/22/2021

BACKGROUND During general anaesthesia, endotracheal
intubation of patients with pre-eclampsia causes stimulation of
the sympathetic nervous system and catecholamine release,
which may lead to maternal and neonatal complications.
OBJECTIVE To attenuate both the stress response and the
haemodynamic response to tracheal intubation in patients
with pre-eclampsia.
DESIGN A randomised, double-blind, controlled study.
SETTING Single University Hospital.
PATIENTS Sixty patients aged 18 to 45 years with pre-
eclampsia receiving general anaesthesia for caesarean section.
INTERVENTIONS The patients were randomly allocated to
three groups. Groups D1and D2 received an infusion of
dexmedetomidine 1 mg kg1 over the 10 min before induc-
tion of general anaesthesia, then 0.4 and 0.6 mg kg1 h1
dexmedetomidine, respectively. Group C received equivalent
volumes of 0.9% saline.
MAIN OUTCOME MEASURES The primary outcome was
the effect of dexmedetomidine on mean arterial blood pres-
sure measured before induction of general anaesthesia at
1 and 5 min after intubation, and then every 5 min until 10 min
after extubation. The secondary outcomes were blood glu-
cose and serum cortisol (measured before induction of
general anaesthesia, and at 1 and 5 min after intubation),
postoperative visual analogue pain scores, time to first request
for analgesia, the total consumption of analgesia, Ramsay
sedation score, maternal and placental vein blood serum levels
of dexmedetomidine and neonatal Apgar score at 1 and 5 min.
RESULTS At all assessment times, the mean arterial pressures
were significantly lower in the dexmedetomidine groups than in
the control group. Compared with group C, the heart rate was
significantly lower in both groups D1 and D2. In group D2, the
heart rate was lower than in group D1. Serum glucose and
cortisol were significantly higher in the controls than in either
group D1 or D2. Group D2 patients were significantly more
sedated on arrival in the recovery room followed by D1. Time to
first analgesia was significantly longer in groups D2 and D1 than
in group C, and the visual analogue pain scores were signifi-
cantly lower in groups D1 and D2 than in group C at 1, 2, 3 and
5 h. Total morphine consumption was significantly lower in
groups D1 and D2 than in the control group. There was no
difference in Apgar scores across the three groups despite
significantly higher dexmedetomidine concentrations in group
D2 (both maternal and placental vein) than in group D1.
CONCLUSION Administration of dexmedetomidine in doses
0.4 and 0.6 mg kg1 h1 was associated with haemodynamic
and hormonal stability, without causing significant adverse
neonatal outcome.
TRIAL REGISTRATION Pan African Clinical Trial Registry
(PACTR201706002303170), (www.pactr.org).
Published online 10 February 2018

Introduction
Pre-eclampsia has an adverse effect on maternal and Although neuraxial anaesthesia is generally the tech-
perinatal health, especially in the developing countries.1 nique of choice in patients with pre-eclampsia, it is not

From the Department of Anesthesia, ICU and Pain Therapy, Faculty of Medicine (AME, AAM, A-EAA, EME, IME), Department of Biochemistry, National Liver Institute,
Menoufiya University, Shibin El-koom (MAO) and Department of Bioequivalence, Egyptian Centre for Research and Development, Cairo, Egypt (OAA-E)
Correspondence to Ashraf M. Eskandr, MD, Department of Anesthesia, ICU and Pain Therapy, Faculty of Medicine, Menoufiya University, 3 Yassin Abd-Elghafar Street,
Shibin El-koom, Egypt
E-mail: ameskandr@yahoo.com

0265-0215 Copyright ß 2018 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000000776

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.


always appropriate, or may be refused by the mother. In
this situation, general anaesthesia remains the only
option. However, in response to endotracheal intubation,
there is stimulation of the sympathetic nervous system
with catecholamine release and subsequent increases in
blood pressure (BP), heart rate (HR) and left ventricular
afterload. These changes may result in both maternal and
neonatal complications. Therefore, the attenuation of the
haemodynamic responses to tracheal intubation in these
patients is a requirement for both the health of the
mother and the foetus.2,3
Many different sedative and opioid drugs have been used
to blunt the stress response associated with endotracheal
intubation but, as such drugs cross the uteroplacental
barrier, their use has always been controversial because of
possible effects on the foetus.4–6 The continued search
for a drug that inhibits the stress response to surgical
stimuli in these clinical settings has led to increasing use
of a2 adrenergic agonists.2 Dexmedetomidine is a highly
selective a2 adrenergic receptor agonist which, when
used as an adjunct to general anaesthesia, has several
useful actions, including sedation, anxiolysis, sympatho-
lysis, analgesia, decreased intra-operative anaesthetic
requirements, cardiovascular stability and smooth recov-
ery.7 Dexmedetomidine is highly lipophilic and, because
of this property, it tends to be retained in placental
tissues, thus reducing the amount crossing the uteropla-
cental barrier to the foetal circulation. However, despite
the above advantages, the off-label use of dexmedeto-
midine for labour analgesia or as an adjunct to general
anaesthesia for caesarean section must be justified.8
The current study used two different doses of dexme-
detomidine (0.4 and 0.6 mg kg1)9 as a part of general
anaesthesia for patients with pre-eclampsia undergoing
caesarean delivery, and we assessed the effects on the
intubation-related stress response, intra-operative hae-
modynamics, postoperative analgesia, foetal outcome
and the correlation between the maternal and the foetal
plasma levels of dexmedetomidine.
Methods
Ethical approval was obtained from the Local Ethics and
Research Committee of the Anaesthesia Department, Fac-
ulty of Medicine, Menoufiya University Hospitals, Menou-
fiya, Egypt (Chairperson Prof A. Abdelraouf) on 3 July 2016.
The study was also registered at the Pan African Clinical
Trial Registry (PACTR201706002303170), (www.pactr.org).
The current prospective double-blind, randomised con-
trolled trial involved 60 patients with pre-eclampsia
undergoing caesarean section from August 2016 to May
2017. Inclusion criteria were 18 to 40 years old, a gesta-
tional age at least 34 weeks, hypertension (but
SBP < 160 mmHg and a DBP < 110 mmHg) proteinuria
(urinary protein dipstick þ or þþ) and without other
signs of systemic effects. Exclusion criteria were patient
Eur J Anaesthesiol 2018; 35:372–378
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Dexmedetomidine as a part of general anaesthesia 373
refusal, allergy to dexmedetomidine, BMI more than
40 kg m2, systemic diseases (e.g. cardiac, pulmonary,
hepatic, renal, neurological, neuromuscular, diabetes
mellitus, anaemia, coagulation disorders, bleeding disor-
ders, seizures), HELLP syndrome, patients receiving
anticoagulant or antipsychotic drugs, ante partum hae-
morrhage, foetal distress and multiple pregnancy.
Before surgery, all the patients had their hypertension
treated with methyldopa and, pre-operatively, underwent
a thorough clinical examination with laboratory investi-
gations. The visual analogue pain score (VAS) was
explained to the patients (score 0 to 10 cm with 0 ¼ no
pain and 10 ¼ worst pain imaginable).
When the patient arrived in the pre-operative holding
area, a wide bore cannula was inserted, and an infusion of
Ringer’s lactate solution was commenced. The following
monitors were applied: noninvasive BP, pulse oximetry
and ECG. Patients were divided randomly into three
groups of 20 with codes contained in sealed, opaque
envelopes: two dexmedetomidine groups (D1, D2) and
a control group (C). Before the planned surgery, the
pharmacy department supplied three ready-made infu-
sions to the anaesthesia department, and the appropriate
volume was administered using a controlled infusion
device. Neither the anaesthesia provider nor the assessors
knew the contents of the infusion.
The sealed, opaque envelopes were opened by the
pharmacist to allocate the patients to a group. Patients
in groups D1 and D2 received a dexmedetomidine
1 mg kg1 loading dose over 10 min, then either an infu-
sion of dexmedetomidine at a rate of 0.4 mg kg1 h1 (D1)
or at a rate of 0.6 mg kg1 h1 (D2). The infusions con-
tinued throughout surgery until skin closure. Patients in
group C (control group) received similar volumes of 0.9%
saline. The doses of dexmedetomidine chosen were
based on similar doses used as part of a general anaes-
thesia technique in healthy parturients during caesarian
section.9
Induction of general anaesthesia was started at the end of
the loading dose infusion of dexmedetomidine. Rapid
sequence induction was performed with propofol
(2.5 mg kg1) followed by rocuronium (0.6 mg kg1): a
dexmedetomidine infusion of 1 mg kg1 for 10 min
reduces the required intubating dose of rocuronium to
0.6 mg kg1.10 Anaesthesia was maintained with sevoflur-
ane in oxygen, at a minimal alveolar concentration of one
minimum alveolar concentration (inspired) with
0.1 mg kg1 increments of rocuronium as required. After
delivery of the baby, 1 mg kg1 of fentanyl was adminis-
tered and 20 U of oxytocin was added to 200 ml 0.9%
saline and infused through a separate line. If hypotension
(defined as a decrease in the maternal mean arterial BP by
20%) developed, 5-mg incremental doses of ephedrine
were given. If bradycardia occurred (defined as a decrease
in the HR to <50 bpm), 0.5-mg doses of atropine were
 374 Eskandr et al.
given. If hypertension occurred [defined as an increase in
mean arterial pressure (MAP) by 20%], a nitroglycerine
infusion was commenced and the patient was excluded
from the study. After the completion of surgery, the
patient’s trachea was extubated after administering
50 mg kg1 prostigmine and 20 mg kg1 atropine to
reverse the muscle relaxant. Postoperatively, incremental
doses of 2-mg morphine (intravenous) were given when
the VAS was at least 4.
Intra-operative maternal measurements
(1) The primary outcomes were mean arterial BP and
HR measured before giving the loading dose of
dexmedetomidine, after the loading dose of dexme-
detomidine (just before induction of general anaes-
thesia), 1 and 5 min after intubation, and then every
5 min until 10 min after extubation.
(2) Blood samples for glucose and serum cortisol were
obtained before and after the dexmedetomidine
loading dose, and at 1 and 5 min after intubation.
(3) A blood sample was obtained for maternal dexme-
detomidine concentration at the time of the uterine
incision.
Postoperative maternal measurements
(1) Time to first request for analgesia (measured from
time of extubation).
(2) Postoperative VAS after end of surgery, every hour
for 6 h, then every 6 h up to 48 h.
(3) The total consumption of morphine in the first 48 h.
(4) Ramsay sedation score (RSS) on arrival in the
recovery room, and then every 15 min until the score
reached 2.
Foetal measurements
(1) Foetal HR before the dexmedetomidine/0.9% saline
infusions commenced.
(2) Neonatal Apgar score at 1 and 5 min.
(3) Dexmedetomidine concentration from the umbilical
vein.
Sample size calculation
When designing the study, we assumed the differences in
MAP between the dose groups and the SDs would be
25%. Setting alpha to 0.05 and beta to 20%, we calculated
that an appropriate group size would require 16 patients.
We planned to include 20 patients per group (n¼60) to
allow for potential dropouts or protocol violations
Statistical analysis
Statistical analysis was done using Statistical Package for
Social Science program (SPSS, version 13; SPSS Inc,
Chicago, Illinois, USA). Data are presented as numerical
or categorical, as appropriate, and were tested for nor-
mality using Kolmogorov–Smirnov test and are
Eur J Anaesthesiol 2018; 35:372–378
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
expressed as mean  SD unless stated otherwise. Analy-
sis of variance and Kruskal–Wallis tests were used as
appropriate to measure association between quantitative
variables, with Student’s Newman–Keuls post hoc test.
The mother’s and infant’s dexmedetomidine levels were
further compared by Student’s t tests or Mann–Whitney
U tests, as appropriate. The x-squared test was used
to measure association between qualitative variables.
P (probability) of 0.05 or less was considered to be of
statistical significance.
Results
From the 65 women randomised, five assigned to the
control group required nitroglycerine for hypertension
and were excluded from further analysis. The remaining
60 women completed the study (Fig. 1). The maternal,
foetal and surgical characteristics were comparable in all
groups (Table 1).
The HR was significantly lower in both groups D1 and
D2 than in the control group before induction of general
anaesthesia, 1 min after induction and 1 min after extuba-
tion. In general, HR in D2 was significantly lower than
both D1 and C groups (Fig. 2). MAP was significantly
lower in both D1 and D2 groups than group C at all times.
MAP was significantly lower in D2 than D1 group at 1 and
5 min after induction, whereas the rest of measures
showed no significant difference (Fig. 3). No patients
required ephedrine but nine required atropine (three in
group D1, five in group D2, one in group C): these
differences were not statistically significant.
Compared with the control group, the glucose concentra-
tion was significantly lower in D1 and D2 at 1 and 5 min
after induction, but there were no significant differences
between groups D1 and D2 at any time (Table 2). There
were no significant differences in cortisol levels across the
three groups before induction and 1 min after induction,
but at 5 min after induction, the level was significantly
higher in the control group than in either groups D1 or
D2. There were no significant differences in cortisol
levels between groups D1 and D2 (Table 2).
On arrival in the recovery room, the sedation scores were
significantly higher in the dexmedetomidine groups than
in the control, and group D2 patients were more sedated
than those in group D1 (Table 3). At 15 and 30 min, there
was no statistically significant difference in the RSS
between D1 and D2, although both of these groups were
still significantly more sedated than group C. By 45 min,
RSS was comparable in all three groups (Table 3).
The time to first request for analgesia after surgery was
significantly longer in the dexmedetomidine groups than
in group C, and this time was also significantly longer
in group D2 than group D1 (Table 1). The VAS
was significantly lower in the two dexmedetomidine
groups than in the control group at 1, 2, 3 and 5 h, whereas
the VAS was comparable in both D1 and D2 groups
 Dexmedetomidine as a part of general anaesthesia 375

Fig. 1

Enrolment
Assessed for eligibility (n = 75)

Excluded (n =10)
 Not meeting inclusion criteria (n = 6)
 Declined to participate (n = 2)
 Other reasons (n = 2)

Randomised (n = 65)

Allocation
Allocated to dexmedetomidine two groups (n = 40) Allocated to control group (n = 25)
 Received allocated interventions (n = 40)  Received allocated intervention (n = 25)
 Did not receive allocated intervention (n = 0)  Did not receive allocated intervention (n = 0)

Follow-up
Lost to follow-up (n = 0) Lost to follow-up (n = 0)

Discontinued intervention (n = 0) Discontinued intervention (n = 5), given

nitroglycerine

Analysis
Analysed (n = 40) Analysed (n = 20)
 Excluded from analysis (n = 0)  Excluded from analysis (n = 0)

Flow chart illustrating the recruitment and loss of patients in control and dexmedetomidine groups.

(Table 4). Six hours after the end of surgery, the VAS was
comparable in the three groups. Compared with the
control group, total morphine consumption was signifi-
cantly lower in both the dexmedetomidine groups, and
patients in group D2 required significantly less morphine
those in group D1 (Table 1).
The 1 and 5 min Apgar scores were comparable among
the three groups (Table 1). There was a significant
difference in the maternal dexmedetomidine
concentrations between the D1 and D2 groups. There
was also a significant difference in the placental vein
dexmedetomidine concentrations between the D1
and D2 groups. However, the placental vein : maternal
dexmedetomidine ratio was similar between the two
groups (Table 5). The foetal HR was comparable among
the studied groups before the start of the dexmedeto-
midine or 0.9% saline infusions, and the neonatal
HR was comparable when assessed as part of the
Apgar score.

Table 1 Maternal, foetal and surgical characteristics

Group D1, nU20 D2, nU20 C, nU20 P value

Maternal age (years) 26.7  4.9 25.4  3.7 24.7  2.5 0.244
Gestational age (weeks) 38  1 38.45  1.19 38.2  1.15 0.453
Weight (kg) 81.3  12.2 77.7  10.14 78.6  8.2 0.523
Height (cm) 159.6  7.5 160.6  9.0 158.8  6.9 0.760
BMI (kg m2) 31.6  8.2 30.3  9.34 31.4  7.6 0.638
Duration of surgery (min) 37.5  3.24 37.8  2.47 38.6  2.8 0.482
Time to first analgesia (min) 90.0  27.4a,b 125.2  45.1c 8.8  3.1 <0.0001M
Total morphine consumption 8.2  2.8a,b 6.3  1.7c 15.1  1.8 <0.0001M
Apgar (1 min) 8 (7 to 10) 8 (7 to 10) 8 (7 to 10) 0.924
Apgar (5 min) 9 (8 to 10) 9 (8 to 10) 9 (8 to 10) 0.943

Group D1 received 0.4 mg kg1 h1 dexmedetomidine. Group D2 received 0.6 kg1 h1 dexmedetomidine. Group C is the control group. n, number of patients. a Indicates
a significant difference between group D1 and group C. b Indicates a significant difference between group D2 and group C. c Indicates a significant difference between
group D1 and group D2. M P < 0.05 indicates a significant difference between the three groups.

Eur J Anaesthesiol 2018; 35:372–378

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 376 Eskandr et al.

Fig. 2 Fig. 3

120 140

Mean arterial pressure (MAP) (mmHg)

*†‡# 130 *†‡#
110 *†‡# *†‡# *†‡
*†‡ *†‡#
120
*†‡
*†‡
Heart rate (bpm)

100 D1
110 *†‡ *†‡ *†‡ *†‡
D2
90 *‡# D1 100 C
*‡# *‡# *‡# D2
*‡# 90
C
80
80
70 70

60 60

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10 n a ind tion

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Heart rate changes in the three groups: D1, D2, C. Group D1 received
0.4 mg kg1 h1 dexmedetomidine. Group D2 received 0.6 mg kg1 h1
dexmedetomidine. Group C is the control group. N, number of patients.
 P < 0.05 indicates a significant difference between the three groups.
y
Indicates a significant difference between group D1 and group C.
z
Indicates a significant difference between group D2 and group C.
#
Indicates a significant difference between group D1 and group D2.
Mean arterial pressure changes in the three groups: D1, D2, C. Group
D1 received 0.4 mg kg1 h1 dexmedetomidine. Group D2 received
0.6 mg kg1 h1 dexmedetomidine. Group C is the control group.
N, number of patients. , P < 0.05 indicates a significant difference
between the three groups. y Indicates a significant difference
between group D1 and group C. z Indicates a significant difference
between group D2 and group C. # Indicates a significant
difference between group D1 and group D2.

Discussion
stress response to the stimulation of both intubation and
The current randomised double-blind controlled trial asses-
surgery. This result is consistent with the observed effects
sing the effects of dexmedetomidine on maternal and foetal
of dexmedetomidine during general anaesthesia in other
outcome in patients with pre-eclampsia undergoing caesar-
studies of pregnant and nonpregnant patients.10–15 In
ean section with general anaesthesia showed that dexme-
addition, Abu-Halaweh et al.16 used a dexmedetomidine
detomidine blunted the stress response associated with
infusion for labour analgesia in pre-eclamptic patients
endotracheal intubation (i.e. reduced MAP, HR and serum
without any significant maternal and neonatal side effects.
cortisol compared with the control group) and also improved
The observed decreases in maternal HR and BP may be
postoperative analgesia (i.e. decreased morphine require-
related to dexmedetomidine-activating central postsynap-
ment) without any effect on the newborn Apgar scores.
tic a-2 adrenoceptors, leading to decreased sympathetic
Compared with the control group, the decrease in MAP activity with consequent decreases in BP and HR.17 Baro-
and HR in the dexmedetomidine groups was never more receptor reflexes are well preserved in the presence of
than 20% of baseline, indicating that dexmedetomidine dexmedetomidine, and bradycardia, should it occur, is
maintains haemodynamic stability while reducing the easily treated.18

Table 2 The serum glucose and cortisol changes in the groups

D1 group, nU20 D2 group, nU20 C group, nU20 P value

Serum glucose
Baseline 81.15  7 81.9  7 82.1  8.6 0.917
Before induction 99.7  14.7 97.2  10.46 94.9  9.2 0.446
1 min after induction 93.6  14.3a 92.9  6.5b 142.1  17.9 <0.0001M
5 min after induction 86.5  7.9a 85.8  6.7b 152.7  15.7 <0.0001M
Serum cortisol
Baseline 21.92  4.35 21  3.35 20.7  4 0.634
Before induction 25.12  4.8 25.74  5.45 24.25  3.6 0.607
1 min after induction 23.05  4.7 23.6  4.51 26.1  5.47 0.123
5 min after induction 22.3  3.9a 21.9  2.9b 32.89  5.1 <0.0001M

Group D1 received 0.4 mg kg1 h1 dexmedetomidine. Group D2 received 0.6 kg1 h1 dexmedetomidine. Group C is the control group. n, number of patients. a Indicates
a significant difference between group D1 and group C. b Indicates a significant difference between group D2 and group C. M P < 0.05 indicates a significant difference
between the three groups.

Eur J Anaesthesiol 2018; 35:372–378

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 Dexmedetomidine as a part of general anaesthesia 377

Table 3 The Ramsay sedation scores after arrival in the postanaesthesia recovery room

D2 group, nU20 D1 group, nU20 C group, nU20 P value

On arrival 2 (1 to 3)a,b 3 (2 to 4)c 1 (1 to 2) <0.0001M
15 min after arrival 2 (2 to 3)a 2 (2 to 3)c 1.5  0.51 <0.0001M
30 min after arrival 2 (2 to 2)a 2 (2 to 2)c 2 (1 to 2) 0.012M
45 min after arrival 2 (2 to 2) 2 (2 to 2) 2 (2 to 2) 0.374
60 min after arrival 2 (2 to 2) 2 (2 to 2) 2 (2 to 2) 1.00

Group D1 received 0.4 mg kg1 h1 dexmedetomidine. Group D2 received 0.6 kg1 h1 dexmedetomidine. Group C is the control group. n, number of patients. a Indicates
a significant difference between group D1 and group C. b Indicates a significant difference between group D1 and group D2. c Indicates a significant difference between
group D2 and group C. M P < 0.05 indicates a significant difference between the three groups.

The blood glucose and cortisol levels were significantly depression in labouring women. Dexmedetomidine is
higher in the control group than in either group D1 or D2 chemically related to clonidine, but is approximately
groups, similar to the findings in patients undergoing eight times more specific for a-2 adrenoceptors, with
general anaesthesia for caesarean section.9 a-2 : a-1 selectivity ratio of 1620 : 1, especially for the
2a subtype. These characteristics make dexmedetomi-
Postoperatively, dexmedetomidine enhanced analgesia,
dine more effective than clonidine for sedation and
as evidenced not only by the longer times to first request
analgesia.21 Dexmedetomidine also incorporates an imi-
for analgesia but also by the lower pain scores and
dazoline structure, thus having an agonist effect on
reduced morphine consumption. Similar analgesic
imidazoline receptors, adding a sedation element to
enhancement by dexmedetomidine has been observed
the a-2 agonist action.22,23
in other studies. Abu-Halaweh et al.16 noted a decrease in
the total dose of opioids required during labour when an The 1 and 5 min Apgar scores were comparable among the
epidural technique was contraindicated, and Park et al.19 studied groups with no correlation between the infant
in their study of patients undergoing laparoscopic chole- dexmedetomidine level and the Apgar scores. These
cystectomy, noted a statistically significant reduction in results concur with case reports on the use of dexmede-
postoperative analgesic requirements. tomidine in labouring women or for caesarean section in
which the infants had normal Apgar scores,14 adding
On arrival in recovery, patients in group D2 were signifi-
further evidence to suggest that even though there is
cantly more sedated than those in group D1, and the
uteroplacental transfer, this does not affect the neonatal
latter were significantly more sedated than those in the
Apgar scores. Also, Mendoza24 published two case reports
control group, but by 45 min, there were no differences
in which dexmedetomidine was used as an adjunct for
across the three groups. In an editorial, Sia and Sng20 felt
labour analgesia along with remifentanil: both babies were
that a low-dose dexmedetomidine infusion in properly
delivered with normal Apgar scores at 1 and 5 min. Like-
selected parturients could provide useful sedation and
wise, Palanisamy et al.15 published a case report in which
haemodynamic stability with minimal risk of respiratory
dexmedetomidine was used in a 31-year-old parturient
with spina-bifida occulta and a tethered spinal cord reach-
Table 4 The visual analogue pain score in the groups after
extubation
ing L5-S1: a healthy baby was delivered with normal Apgar
scores. Li et al.25 compared the effect of remifentanil and
D1 group, nU20 D2 group, nU20 C group, nU20 P value dexmedetomidine during general anaesthesia for caesarian
1h 2.1  0.9a 1.6  0.94b 5.1  1.16 <0.0001 delivery and noted that all neonates had Apgar scores more
2h 3.4  0.99a 2.8  0.93b 4.5  1.14 <0.0001M than 7 at 5 min.
3h 3.4  1.13 2.7  1.1b 3.8  1.3 0.019M
4h 2.5  1.46 2.8  1.3 3.3  0.97 0.143
5h 2.1  0.99a 2.3  1.61b 3.5  1.05 0.001M
6h 2.6  1.3 2.7  1.08 3.4  1.1 0.079
12 h 2.7  1.2 2.9  1.53 3.4  1.3 0.254 Table 5 Dexmedetomidine concentration in maternal and foetal
18 h 3.0  1.3 3.1  0.97 3.3  1.26 0.614 blood and the foetal : maternal ratio of dexmedetomidine
24 h 3.6  1.1 3.4  1.12 3.3  1.25 0.959
30 h 2.9  1.2 2.8  1.45 3.1  1.1 0.665 D1 group, D2 group,
nU20 nU20 P value
36 h 2.8  1.2 2.7  1.1 3.0  0.99 0.691
42 h 2.7  1.3 2.7  1.2 2.8  0.97 0.962 Maternal (pg ml1) 0.454  0.17 0.688  0.11 <0.0001M
48 h 2.6  1.45 2.6  1.3 2.7  1.2 0.972 Placental vein (pg ml1) 0.315  0.13 0.517  0.11 <0.0001M
Placental vein : maternal 70.9  14.2 75.7  14.1 0.292
Group D1 received 0.4 mg kg1 h1 dexmedetomidine. Group D2 received dexmedetomidine ratio (%)
0.6 kg1 h1 dexmedetomidine. Group C is the control group. n, number of
patients; VAS, visual analogue pain score. a Indicates a significant difference D1 group received 0.4 mg kg1 h1 dexmedetomidine: D2 group received
between group D1 and group C. b Indicates a significant difference between 0.6 mg kg1 h1 dexmedetomidine: C, control group; n, number of patients;
group D2 and group C. M P < 0.05 indicates a significant difference between the pg, picograms. M P < 0.05 indicates a significant difference between group
three groups. D1 and group D2.

Eur J Anaesthesiol 2018; 35:372–378

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
 378 Eskandr et al.
Like other anaesthetic drugs, dexmedetomidine can pass
through the placental barrier: foetal : maternal ratios were
similar in the two dexmedetomidine groups (70.9% in
D1 vs. 75.7% in D2). However, the placental transfer
of dexmedetomidine is much lower than that of
clonidine (foetal : maternal ratio, 85%)26 or remifentanil
(foetal : maternal ratio, 88%),27 which may be caused by
dexmedetomidine being more lipid soluble and thus is
retained within placental tissues.26 Concomitant with our
results, Yu et al.11 reported that dexmedetomidine foe-
tal : maternal ratio was 76% without adverse effect on the
newborn: mean Apgar scores were 8 and 9 at 1 and 5 min,
respectively, in the dexmedetomidine group.
Our current study included a relatively small number
of patients and larger studies will be needed to verify
the safety of dexmedetomidine in both mothers with pre-
eclampsia and their infants.
Conclusion
The main finding in the current study was that adminis-
tration of dexmedetomidine in doses of 0.4 to
0.6 mg kg1 h1 was associated with significant haemody-
namic and hormonal stability. In addition, dexmedeto-
midine reduced postoperative analgesic requirements
without causing significant adverse neonatal outcome.
According to our results, we would recommend the use
of 0.6 mg kg1 h1 dexmedetomidine, as this produced
the best haemodynamic, hormonal and analgesic effects.
Acknowledgements relating to this article
Assistance with the study: none.
Financial support and sponsorship: this study was supported by the
Menoufiya University Hospitals, Menoufiya, Egypt and funded by
the authors.
Conflicts of interest: none.
Presentation: none.
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