Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338

Contents lists available at ScienceDirect

Pregnancy Hypertension: An International Journal of

Womens Cardiovascular Health
journal homepage: www.elsevier.com/locate/preghy

A comprehensive analysis of continuous epidural analgesias effect on

labor and neonates in maternal hypertensive disorder patients
Bin Han, Mingjun Xu
Department of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

a r t i c l e i n f o a b s t r a c t

Article history: Background: Maternal hypertensive disorder is one of the most common and severe medical complica-
Received 15 July 2016 tions during pregnancy. Epidural analgesia administration is widely used during labor process.
Received in revised form 21 December 2016 Aim: To evaluate the potential advantage or disadvantage of continuous epidural analgesias on labor and
Accepted 22 December 2016
neonates for maternal hypertensive disorder patients comprehensively.
Available online 24 December 2016
Methods: We have retrospectively analyzed 232 patients who diagnosed as maternal hypertensive disor-
der in our hospital since 2015. Among which, 126 patients including 28 cases of severe preeclampsia
Keywords:
were administrated with continuous epidural analgesia (Analgesia group), the other 106 patients were
Continuous epidural analgesia
Labor analgesia
untreated (Control group). We have compared the maternal age, body weight, gestational weeks, period
Maternal hypertensive disorder for the first and second labor stage; the incidence of eclampsia, natural labor, cesarean section, forceps
Neonate delivery and postpartum hemorrhage between these two groups respectively; furthermore, we recorded
patients who received oxytocin and antihypertensive treatment during the delivery progress as well as
evaluated the neonate body weight, Apgar score and performed umbilical cord blood gas analysis.
Results: Continuous epidural analgesia does not affect the first and second labor stage period
Results: (p = 0.36), However, there is a significantly higher demand for oxytocin treatment (36.5% Vs
19.8%, p < 0.01) and a significantly lower requirement for antihypertensive treatment (22.2% Vs 81.1%,
p < 0.001) in analgesia group compared to control group.
Results: We also notice that the natural delivery ratio in analgesia group is higher than control group
and most importantly, continuous epidural analgesia can increase 1 min Apgar score and has no other
effect on neonates body weight, umbilical cord blood gas parameters, 5 min and 10 min Apgar score.
Conclusions: Our result based on a large cohort comprehensive analysis indicates that continuous epidu-
ral analgesia can benefit both maternal hypertensive disorder patients and neonates without any side
effect.
2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All
rights reserved.

1. Introduction nated intravascular coagulation (DIC) [4]; cardiovascular complica-

Maternal hypertensive disorder is a special disease during preg-
nancy, which occurred about 10% of pregnancies globally [1], and it
is one of the most serious complications during pregnancy [2]. The
patients usually exhibit high blood pressure and proteinuria, which
normally disappear after delivery [3]. Clinically, the routine ther-
apy includes antispasmodic, antihypertensive and some other sup-
portive treatment, or in some scenario, terminating the pregnancy
at the right time [3]. In western countries, the major complications
result from maternal hypertensive disorder are hemolysis, elevated
liver enzymes, low platelet count (HELLP syndrome) and Dissemi-
Corresponding author.
E-mail address: snake_650222@126.com (M. Xu).
tions and cerebrovascular accidents are rarely reported; whereas in
china, it is documented that maternal hypertensive disorder usu-
ally induces severe complications such as cerebrovascular acci-
dent, heart failure, acute renal failure, HELLP syndrome and
pulmonary edema [5].
Many studies have confirmed that continuous epidural anesthe-
sia administration is a safe and efficient way for labor analgesia
and can benefit both pregnant women and neonate [6,7]. This
approach allows the analgesic to release plane and steady, reduces
the motor block and the occurrence of hypotension. Furthermore,
patients can adjust dosage and frequency for the administration
themselves according to their own demand, therefore the adminis-
tration is more personalized, and the outcome is much better with
fewer side effects.

http://dx.doi.org/10.1016/j.preghy.2016.12.003
2210-7789/ 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
34 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338
The basic pathological character for maternal hypertensive dis-
order is systemic small artery spasm [8]. The stress response
induced by the pain during labor process can aggregate patients
condition, or even cause some severe complications such as
eclampsia [9]. For pregnancies with such symptoms, obstetric doc-
tors are prone to choose cesarean section in order to reduce the
risk for the delivery. Recently, some studies have indicated that
labor analgesia can ameliorate the stress response and control
blood pressure caused by the pain [10]. Effective labor analgesia
can increase the blood supply of the uterus and placenta as well
as reduce the occurrence of fetal distress in uterus. However, the
advantage or disadvantage of epidural labor analgesia for maternal
hypertensive disorder patients based on a large cohort investiga-
tion is still unclear. Here, we retrospectively analyzed 232 patients
who diagnosed as maternal hypertensive disorder (including 28
cases of severe preeclampsia) in Beijing Obstetrics and Gynecology
Hospital since 2015 and evaluated the therapeutic outcome of
epidural labor analgesia.
2. Material and methods
2.1. Patients
We collected 232 patients who diagnosed as maternal hyper-
tensive disorder (including 28 cases of severe preeclampsia) in
our hospital since 2015. The patients are ranging from 20 to
35 years old who are pregnant for the first time, single embryo,
and the gestational weeks are between 36 and 41 weeks. 126
patients were given continuous epidural labor analgesia, including
28 cases of severe preeclampsia; the other 106 patients were
untreated as controls.
The diagnostic criteria for maternal hypertensive disorder com-
plicating pregnancy are described as follows:
Gestational hypertension is defined as that hypertension is only
detected for the first time during pregnancy, systolic blood pres-
sure P140 mmHg and(or) diastolic blood pressure P90 mmHg,
urine protein is negative, the symptoms are disappeared and
patients are back to normal within 12 weeks after delivery.
Severe preeclampsia is defined as: (1) blood pressure is persis-
tently rising: systolic blood pressure P160 mmHg and (or) dias-
tolic blood pressure P110 mmHg; (2) persistent headache, visual
disturbances or other central nervous system abnormalities; (3)
persistent upper abdominal pain and liver subcapsular hematoma
or symptoms of liver rupture; (4) liver enzyme abnormalities:
increased serum alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) levels; (5) impaired renal function: urine
protein >2.0 g/24 h; oliguria (24 h urine output <400 ml, or hourly
urine output <17 ml), or serum creatinine >106 lmol/L; (6) hypoal-
buminemia with ascites, pleural or pericardial effusion; (7) blood
abnormalities: sustained decreased platelet count (<100  109/L);
microvascular hemolysis (anemia, jaundice, or increased blood lac-
tate dehydrogenase (LDH) levels); (8) heart failure; (9) pulmonary
edema; (10) fetal growth restriction or oligohydramnios, fetal
death, early placenta abruption and so on.
Mild preeclampsia is defined as: systolic blood pressure
P140 mmHg and (or) diastolic blood pressure P90 mmHg after
20 weeks of gestation, and accompanied with any of the following
symptoms: proteinuria P0.3 g/24 h, or urine protein/creatinine
P0.3, or random urine protein positive (when proteinuria determi-
nation is not applicable); when proteinuria is negative but associ-
ated with any of the following organ or system dysfunction: such
as heart, lung, liver, kidney, or blood system, digestive system, ner-
vous system, or placenta fetus abnormality.
2.2. Continuous epidermal analgesia administration
Patients in the analgesia group requested analgesia after enter-
ing the first labor stage voluntarily, when fetal heart rate were nor-
mal, patients were informed and consent agreements were signed
with the anesthesiologist, continuous epidural anesthesia was
administrated at lumbar 23 or 34 gap by puncture and cephalic
epidural catheter 3 cm, 5 ml of 2 mg/ml ropivacaine was given first
and patients were monitored for 5 min, followed with 1015 ml
mixture of 1 mg/ml ropivacaine and 0.5 mg/ml sufentanil, 30 min
later, epidural analgesia pump was connected to the epidural
catheter, the analgesia mixture in the pump was 1 mg/ml ropiva-
caine and 0.5 lg/ml sufentanil, the baseline infusion dose was
5 ml/h, the PCA was 5 ml every time and fixed for 15 min. Patients
were encouraged to rest or move appropriately to facilitate fetal
loss and labor process, when the analgesic effect diminished,
patients could adjust epidural administration by controlling
micro-pump. When the cervix was almost fully open, the analgesia
administration was terminated.
For the control group: patients refused any continuous epidural
labor analgesia during delivery progress.
We documented maternal patients age, body weight and gesta-
tional weeks; the period for the first and second labor stage; the
incidence of eclampsia, natural labor, cesarean section, forceps
delivery, postpartum hemorrhage; recorded the usage of oxytocin
and antihypertensive during the delivery progress; recorded the
neonate weight, Apgar score and performed the umbilical cord
blood gas analysis. Postpartum hemorrhage was defined as vaginal
bleeding over 500 ml after delivery in 24 h.
3. Statistics
Data was shown as mean SEM and analyzed using unpaired t-
test. For categorical data like adverse events, Chi-square test was
applied. In this study, P < 0.05 was accepted to be statistically
significant.
4. Results
We had compared patients age, body weight, gestational weeks
between analgesia and control group, but didnt detect any differ-
ence (Fig. 1), which indicated that our study was unbiased.
4.1. No difference was detected for the period of first and second labor
stage between analgesia and control group
We had compared the periods for the first and second labor
stage between control and analgesia group respectively, and we
noticed that both first and second labor stage were slightly pro-
longed in analgesia group, but there was no significant difference
detected (Fig. 2).
4.2. Continuous epidural analgesia treated maternal hypertensive
disorder patients required more oxytocin but much less
antihypertensive treatment
21 patients (19.8%) in control group were treated with oxytocin,
while 46 patients (36.5%) in analgesia group required oxytocin
treatment, in contrast, 86 patients (81.1%) in control group com-
pared to 28 patients (22.2%) in analgesia group required antihyper-
tensive treatment (Fig. 3), this result suggested that patients
treated with continuous epidermal analgesia usually need treat-
ments to induce labor but much less measures to control blood
pressure.
 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338 35

Control
Analgesia

35 p=0.26 100 p=0.11 40 p=0.45

30
80
30
25

kilogram
60

week
20
years

20
15
40

10
10
20
5

0 0 0

Patients ages Body weight Gestational weeks

Fig. 1. Statistical analysis of patients age, body weight and gestational week between control and analgesia group. Data are shown as means SEM. P values are indicated for
each bar graph (unpaired, two-sided t-test).

p=0.805 p=0.385 Control

600 70 Analgesia
500 60

50
400
minutes

minutes

40
300
30
200
20

100 10

0 0

The first lab stage The second lab stage

Fig. 2. Quantification for the period of first and second labor stage in both continuous epidural analgesia treated patients and control patients. Quantification data are shown
as means SEM. P values are indicated for each bar graph (unpaired, two-sided t-test).

4.3. The natural delivery ratio is higher in continuous epidural
analgesia treated maternal hypertensive disorder patients
We had analyzed all patients for their delivery methods and
categorized them into 3 subgroups, natural delivery, forceps and
cesarean section. We noticed that the ratio for natural delivery
was higher in analgesia group compared to control group (Fig. 4).
Furthermore, no difference was detected for postpartum hemor-
rhage (4.71% in control group compared to 4.76% in analgesia
group) and eclampsia (no occurrence in both groups) between
analgesia and control group.
5 min, 10 min Apgar score and umbilical cord blood gas analysis
result, of note, 1 min Apgar score in analgesia group was signifi-
cantly higher than control group, none of the other characters were
significantly different between analgesia group and control group,
thus, we conclude that continuous epidural analgesia administra-
tion can improve neonates condition immediately after delivery
but has no further effect in maternal hypertensive disorder
patients (Fig. 5).
5. Discussion

The major pathological features for maternal hypertensive dis-

4.4. Continuous epidural analgesia administration increases 1min
Apgar score but does not have any other effect in neonates
We had carefully evaluated and compared the neonates body
weight in both control and analgesia group, our result suggested
that continuous epidural analgesia administration did not affect
the neonates body weight. Furthermore, we analyzed 1 min,
order are systemic small blood vessel spasm and decreasing organ
perfusion [7]. During delivery progress, patients are usually anx-
ious and painful, which induces catecholamine release and
increases blood pressure, and may cause severe cardiovascular
accidents or eclampsia in some cases. Therefore, the maternal
hypertensive disorder patients have a higher risk when they take
vaginal delivery. Currently, in our department, the obstetricians
36 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338

Control
Analgesia
P=0.005 P<0.001
40% 100%

80%
30%

60%
20%
40%

10%
20%

0% 0%

Oxytocin treatment Antihypertensive treatment

Fig. 3. Statistical comparison of patients who received oxytocin and antihypertensive treatment between control and analgesia group. The results are shown as percentage. P
values are indicated for each bar graph. P < 0.05 was accepted to be statistically significant (Chi-square test).

Natural delivery
P<0.05 Forceps
Cesarean section

Control Analgesia
Fig. 4. Statistical analysis of ratios for natural delivery, forceps assistant delivery and cesarean section in both control and analgesia group. Note that natural delivery ratio in
analgesia group is significantly higher than control group. P value is indicated and P < 0.05 is accepted to be statistically significant (Chi-square test).

usually choose cesarean section to terminate such pregnancy as it
is safer for patients and neonates according to our experience,
however, cesarean section does not significantly improve neonates
condition [8], and can cause some complication such as neonatal
respiratory distress syndrome, neonatal transient tachypnea and
allergic asthma [11]. Furthermore, cesarean section can induce
much more postpartum hemorrhage and amniotic embolism than
natural delivery, and incidences for uterine scar pregnancy, pla-
centa previa or placental abruption are also higher for cesarean
section patients when they are pregnant for next time [12].
Continuous epidural analgesia administration can block dam-
age stimulation input and sympathetic output, therefore effec-
tively reduce catecholamines, b- endorphin, adrenocorticotropic
hormone (ACTH) and cortisol release, it can also reduce cardiac
output and blood pressure which increased by pain, furthermore,
it can decrease stress response and maternal oxygen consumption,
epinephrine level in plasma and can the incidence of fetal acidosis
[13]. For maternal hypertensive disorders in pregnancy, efficient
analgesia can block the sympathetic, dilate blood vessels and help
to control blood pressure, moreover, it can increase kidney and
uterine blood flow and perfusion, and it can control blood pressure
which induced by stress response [11]. Recently, many studies
have reported that labor analgesia can reduce stress response in
maternal hypertension disorders patients during vaginal childbirth
induced by pain stimulation, especially in the first stage of labor, it
can significant decrease catecholamines, endorphins, ACTH and
cortisol release as well as improve uteroplacental blood flow,
which might be relevant to NO and PGI elevation [14]; small doses
of low concentration drugs can also avoid low blood pressure and
protect placental switching function, thus improve blood flow
between among fetal villus. Pregnancies with less maternal stress
response during delivery process can maintain better physiological
homeostasis and normal lung ventilation, thus to reduce oxygen
consumption to avoid acidosis and facilitate fetal oxygen supply
[15,16].
Many studies have proved that continuous epidural anesthesia
during labor process is safe and beneficial for both mothers and
neonates [10,11]. Some studies have focused on the placenta fetal
endocrine function, which they show that labor analgesia can
reduce maternal cortisol level in peripheral blood, thereby reduce
the stress response, while the cortisol concentration has not been
affected in umbilical cord blood and amniotic fluid before and after
 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338 37

Control
Analgesia

3500 P=0.326 8 P=0.534 50 P=0.322 40 P=0.692

3000 7
40
2500 6 30
5

mmHg

mmHg
30
gram

2000
4 20
1500
3 20
1000
2 10
10
500 1
0 0 0 0

Neonate body weight Blood pH Blood pCO2 Blood O2

P=0.043 10 P=0.447 P=0.78

10
0 10
9 9
9
-1 8 8
8
7 7
-2 7
6 6
6
-3 5 5 5
4 4 4
-4 3 3 3
2 2 2
-5
1 1 1
-6 P=0.533 0 0 0

BE 1min Apgar 5min Apgar 10min Apgar

Fig. 5. Quantification results of neonate body weight, blood pH, blood pCO2, blood pO2, BE, 1 min Apgar, 5 min Apgar, 10 min Apgar in both control and analgesia group. Note
continuous epidural analgesia administration increases 1 min Apgar score but does not have any other effect in neonates. P values are indicated for each bar graph. P < 0.05
was accepted to be statistically significant (unpaired, two-sided t-test).

maternal analgesia [17]. It is also proved that estrogen/proges-
terone level, plasma prostaglandin E2 (PGE2) and IL-1b secretion
are not affected by labor analgesia [11]. Other studies have sug-
gested that analgesia can increase nitric oxide in the blood, which
is beneficial to stabilize maternal hemodynamics [18].
Lighton et al. have proved that epidural analgesia has no effect
on the ratio of cesarean section, instrumental delivery and the per-
iod of first labor stage but can prolong the second labor stage, and
increase oxytocin requirement [7]. Another study has shown that
epidural labor analgesia can decrease uterine contractility but
not the uterine contraction hormone, and have no adverse effects
on the whole delivery process [19]. Sharma et al. have suggested
that labor analgesia can increase oxytocin requirement, prolong
the first and second labor stage, increase instrumental delivery
ratio but efficiently reduce the ratio of cesarean section [8].
Regarding the timing of analgesia implementation, it is gener-
ally considered to apply neuraxial analgesia during active stage
when cervix opening to 3 cm, it is also concerned the first lab stage
will be prolonged and cesarean section risk will be increased if
introduce analgesia too early. Thus, the clinical guidelines of Amer-
ican College of Obstetrics and Gynecology (ACOG) in 2000 suggest
analgesia should be introduced until cervix opening to 45 cm.
Some reports indicate that application of analgesia in latency stage
may result in prolonged active period, more oxytocin requirement
or even cesarean section [20], however, our results suggest that
labor analgesia during early stage of labor can relieve pain, control
blood pressure, increase uterine blood perfusion and improve fetal
oxygen supply in maternal hypertensive disorder patients, even
with preeclampsia.
Ropivacaine is a long-acting amide like local anesthetic which
has very low heart and central nervous system toxicity. Ropiva-
caine can block sensory and motor nerve separately without affect-
ing placental blood supply. Sufentanil is a strong analgesic with
long term effect, which can enhance the effect and reduce the
dosage of local anesthetic when used together. Thus, combination
of ropivacaine and sufentanil can efficiently block sensory neuron
with limited effect on motor neuron, which can reduce the impact
on pregnant women compared to other anesthetics, however,
some studies have reported that long labor analgesia can increase
the during of labor period and usage of oxytocin and reduce the
natural delivery ratio [11,20]. This is consistent to our study, which
we also find that the usage of oxytocin is significantly more often
in analgesia group, indicating that uterine smooth muscle contrac-
tion is suppressed while pain relived, which might be relevant to
decline of prostaglandin in uterus upon analgesia treatment [9].
Once withdrawal the analgesia, the effect will gradually disappear
and have less and less impact on the second stage of labor. Accord-
ing to conventional clinical requirement, it is important to actively
take some measures during second stage of labor to prevent
eclampsia for maternal hypertension patients when give vaginal
childbirth, thus without prolonged second stage of labor and fetal
distress, doctors usually will use forceps to facilitate delivery, this
is the reason why forceps delivery ratio is relatively higher in both
groups in our study.
Importantly, in our study, the use of antihypertensive drugs in
control group is significantly much more than analgesia group,
suggesting the blood pressure in patients without continuous
epidural analgesia increase significantly during delivery process,
and obstetricians need to give additional antihypertensive drugs
to control it, which further confirmed that continuous epidural
analgesia is beneficial for maternal hypertensive patients.
38 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338
In the present study, we didnt find any uterus hypertonic in our
patients in both analgesia group and control group, however, Pre-
ston et al. have reported that uterus hypertonic may be a special
complication of intrathecal injection of opioids, and there is no
method to eliminate this effect so far [15], moreover, intrathecal
injection of sufentanil can induce respiratory distress [21], so it is
very important to avoid simple intrathecal administration of
opioids.
We have noticed that the ratio of cesarean section in analgesia
group is significantly less than control group (P < 0.05), one impor-
tant reason is the disease-related symptoms getting worse during
labor process in control group, which makes both doctors and
patients lose their confidence to try vaginal delivery. There are 3
cases of forceps delivery in analgesia group and 7 cases in control
group; the main reason is the significantly elevated blood pressure
and fetal heart rate changes during second stage of labor which
requires the termination of the whole labor process. Furthermore,
we also realize that continuous epidural analgesia administration
can reduce patient stress response to a certain extent, which also
reduce the risk of eclampsia in the second stage of labor. Although
oxytocin usage is higher in analgesia group, (P < 0.05), it does not
affect the analgesic effect and the success ratio of vaginal delivery,
and a proper dosage of oxytocin can avoid prolonged delivery time.
Taken together, we conclude that continuous epidural analgesia
has no significant effect on the period for the first and second labor
stage, but it indeed increases the demand for oxytocin usage and
significantly decreases the requirement for antihypertensive treat-
ment, moreover, our results suggest that labor analgesia can signif-
icantly increase natural delivery ratio compared to non-analgesia
treated patients. Finally, our results indicate that labor analgesia
can benefit 1 min Apgar score for neonates, but has no other effects
on neonates body weight, umbilical cord blood gas parameters, as
well as 5 min and 10 min Apgar score. Our conclusion is slightly
different from some previous studies; we speculate that this is
due to the difference of patients sample size and ethnics.
Finally, our results suggest that continuous epidural analgesia is
a safe and efficient treatment for maternal hypertensive disorder
patients during delivery process.
Conflict of interest
The authors declare that there is no conflict of interest associ-
ated with this manuscript.
Acknowledgements
This study was approved by Ethics Committee of Beijing Obstet-
rics and Gynecology Hospital, Capital Medical University and sup-
ported by Promotion program of appropriate scientific and
technological projects, Beijing Municipal Health and Family Plan-
ning Commission (TG-2014-12).
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