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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-


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

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- 2.2. Continuous epidermal analgesia administration
order is systemic small artery spasm [8]. The stress response
induced by the pain during labor process can aggregate patients Patients in the analgesia group requested analgesia after enter-
condition, or even cause some severe complications such as ing the first labor stage voluntarily, when fetal heart rate were nor-
eclampsia [9]. For pregnancies with such symptoms, obstetric doc- mal, patients were informed and consent agreements were signed
tors are prone to choose cesarean section in order to reduce the with the anesthesiologist, continuous epidural anesthesia was
risk for the delivery. Recently, some studies have indicated that administrated at lumbar 23 or 34 gap by puncture and cephalic
labor analgesia can ameliorate the stress response and control epidural catheter 3 cm, 5 ml of 2 mg/ml ropivacaine was given first
blood pressure caused by the pain [10]. Effective labor analgesia and patients were monitored for 5 min, followed with 1015 ml
can increase the blood supply of the uterus and placenta as well mixture of 1 mg/ml ropivacaine and 0.5 mg/ml sufentanil, 30 min
as reduce the occurrence of fetal distress in uterus. However, the later, epidural analgesia pump was connected to the epidural
advantage or disadvantage of epidural labor analgesia for maternal catheter, the analgesia mixture in the pump was 1 mg/ml ropiva-
hypertensive disorder patients based on a large cohort investiga- caine and 0.5 lg/ml sufentanil, the baseline infusion dose was
tion is still unclear. Here, we retrospectively analyzed 232 patients 5 ml/h, the PCA was 5 ml every time and fixed for 15 min. Patients
who diagnosed as maternal hypertensive disorder (including 28 were encouraged to rest or move appropriately to facilitate fetal
cases of severe preeclampsia) in Beijing Obstetrics and Gynecology loss and labor process, when the analgesic effect diminished,
Hospital since 2015 and evaluated the therapeutic outcome of patients could adjust epidural administration by controlling
epidural labor analgesia. 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-
2. Material and methods tional weeks; the period for the first and second labor stage; the
incidence of eclampsia, natural labor, cesarean section, forceps
2.1. Patients delivery, postpartum hemorrhage; recorded the usage of oxytocin
and antihypertensive during the delivery progress; recorded the
We collected 232 patients who diagnosed as maternal hyper- neonate weight, Apgar score and performed the umbilical cord
tensive disorder (including 28 cases of severe preeclampsia) in blood gas analysis. Postpartum hemorrhage was defined as vaginal
our hospital since 2015. The patients are ranging from 20 to bleeding over 500 ml after delivery in 24 h.
35 years old who are pregnant for the first time, single embryo,
and the gestational weeks are between 36 and 41 weeks. 126
3. Statistics
patients were given continuous epidural labor analgesia, including
28 cases of severe preeclampsia; the other 106 patients were
Data was shown as mean SEM and analyzed using unpaired t-
untreated as controls.
test. For categorical data like adverse events, Chi-square test was
The diagnostic criteria for maternal hypertensive disorder com-
applied. In this study, P < 0.05 was accepted to be statistically
plicating pregnancy are described as follows:
significant.
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, 4. Results
urine protein is negative, the symptoms are disappeared and
patients are back to normal within 12 weeks after delivery. We had compared patients age, body weight, gestational weeks
Severe preeclampsia is defined as: (1) blood pressure is persis- between analgesia and control group, but didnt detect any differ-
tently rising: systolic blood pressure P160 mmHg and (or) dias- ence (Fig. 1), which indicated that our study was unbiased.
tolic blood pressure P110 mmHg; (2) persistent headache, visual
disturbances or other central nervous system abnormalities; (3)
4.1. No difference was detected for the period of first and second labor
persistent upper abdominal pain and liver subcapsular hematoma
stage between analgesia and control group
or symptoms of liver rupture; (4) liver enzyme abnormalities:
increased serum alanine aminotransferase (ALT) and aspartate
We had compared the periods for the first and second labor
aminotransferase (AST) levels; (5) impaired renal function: urine
stage between control and analgesia group respectively, and we
protein >2.0 g/24 h; oliguria (24 h urine output <400 ml, or hourly
noticed that both first and second labor stage were slightly pro-
urine output <17 ml), or serum creatinine >106 lmol/L; (6) hypoal-
longed in analgesia group, but there was no significant difference
buminemia with ascites, pleural or pericardial effusion; (7) blood
detected (Fig. 2).
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 4.2. Continuous epidural analgesia treated maternal hypertensive
edema; (10) fetal growth restriction or oligohydramnios, fetal disorder patients required more oxytocin but much less
death, early placenta abruption and so on. antihypertensive treatment
Mild preeclampsia is defined as: systolic blood pressure
P140 mmHg and (or) diastolic blood pressure P90 mmHg after 21 patients (19.8%) in control group were treated with oxytocin,
20 weeks of gestation, and accompanied with any of the following while 46 patients (36.5%) in analgesia group required oxytocin
symptoms: proteinuria P0.3 g/24 h, or urine protein/creatinine treatment, in contrast, 86 patients (81.1%) in control group com-
P0.3, or random urine protein positive (when proteinuria determi- pared to 28 patients (22.2%) in analgesia group required antihyper-
nation is not applicable); when proteinuria is negative but associ- tensive treatment (Fig. 3), this result suggested that patients
ated with any of the following organ or system dysfunction: such treated with continuous epidermal analgesia usually need treat-
as heart, lung, liver, kidney, or blood system, digestive system, ner- ments to induce labor but much less measures to control blood
vous system, or placenta fetus abnormality. 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 5 min, 10 min Apgar score and umbilical cord blood gas analysis
analgesia treated maternal hypertensive disorder patients result, of note, 1 min Apgar score in analgesia group was signifi-
cantly higher than control group, none of the other characters were
We had analyzed all patients for their delivery methods and significantly different between analgesia group and control group,
categorized them into 3 subgroups, natural delivery, forceps and thus, we conclude that continuous epidural analgesia administra-
cesarean section. We noticed that the ratio for natural delivery tion can improve neonates condition immediately after delivery
was higher in analgesia group compared to control group (Fig. 4). but has no further effect in maternal hypertensive disorder
Furthermore, no difference was detected for postpartum hemor- patients (Fig. 5).
rhage (4.71% in control group compared to 4.76% in analgesia
group) and eclampsia (no occurrence in both groups) between
5. Discussion
analgesia and control group.

The major pathological features for maternal hypertensive dis-


4.4. Continuous epidural analgesia administration increases 1min order are systemic small blood vessel spasm and decreasing organ
Apgar score but does not have any other effect in neonates perfusion [7]. During delivery progress, patients are usually anx-
ious and painful, which induces catecholamine release and
We had carefully evaluated and compared the neonates body increases blood pressure, and may cause severe cardiovascular
weight in both control and analgesia group, our result suggested accidents or eclampsia in some cases. Therefore, the maternal
that continuous epidural analgesia administration did not affect hypertensive disorder patients have a higher risk when they take
the neonates body weight. Furthermore, we analyzed 1 min, 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 which induced by stress response [11]. Recently, many studies
is safer for patients and neonates according to our experience, have reported that labor analgesia can reduce stress response in
however, cesarean section does not significantly improve neonates maternal hypertension disorders patients during vaginal childbirth
condition [8], and can cause some complication such as neonatal induced by pain stimulation, especially in the first stage of labor, it
respiratory distress syndrome, neonatal transient tachypnea and can significant decrease catecholamines, endorphins, ACTH and
allergic asthma [11]. Furthermore, cesarean section can induce cortisol release as well as improve uteroplacental blood flow,
much more postpartum hemorrhage and amniotic embolism than which might be relevant to NO and PGI elevation [14]; small doses
natural delivery, and incidences for uterine scar pregnancy, pla- of low concentration drugs can also avoid low blood pressure and
centa previa or placental abruption are also higher for cesarean protect placental switching function, thus improve blood flow
section patients when they are pregnant for next time [12]. between among fetal villus. Pregnancies with less maternal stress
Continuous epidural analgesia administration can block dam- response during delivery process can maintain better physiological
age stimulation input and sympathetic output, therefore effec- homeostasis and normal lung ventilation, thus to reduce oxygen
tively reduce catecholamines, b- endorphin, adrenocorticotropic consumption to avoid acidosis and facilitate fetal oxygen supply
hormone (ACTH) and cortisol release, it can also reduce cardiac [15,16].
output and blood pressure which increased by pain, furthermore, Many studies have proved that continuous epidural anesthesia
it can decrease stress response and maternal oxygen consumption, during labor process is safe and beneficial for both mothers and
epinephrine level in plasma and can the incidence of fetal acidosis neonates [10,11]. Some studies have focused on the placenta fetal
[13]. For maternal hypertensive disorders in pregnancy, efficient endocrine function, which they show that labor analgesia can
analgesia can block the sympathetic, dilate blood vessels and help reduce maternal cortisol level in peripheral blood, thereby reduce
to control blood pressure, moreover, it can increase kidney and the stress response, while the cortisol concentration has not been
uterine blood flow and perfusion, and it can control blood pressure 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- caine can block sensory and motor nerve separately without affect-
terone level, plasma prostaglandin E2 (PGE2) and IL-1b secretion ing placental blood supply. Sufentanil is a strong analgesic with
are not affected by labor analgesia [11]. Other studies have sug- long term effect, which can enhance the effect and reduce the
gested that analgesia can increase nitric oxide in the blood, which dosage of local anesthetic when used together. Thus, combination
is beneficial to stabilize maternal hemodynamics [18]. of ropivacaine and sufentanil can efficiently block sensory neuron
Lighton et al. have proved that epidural analgesia has no effect with limited effect on motor neuron, which can reduce the impact
on the ratio of cesarean section, instrumental delivery and the per- on pregnant women compared to other anesthetics, however,
iod of first labor stage but can prolong the second labor stage, and some studies have reported that long labor analgesia can increase
increase oxytocin requirement [7]. Another study has shown that the during of labor period and usage of oxytocin and reduce the
epidural labor analgesia can decrease uterine contractility but natural delivery ratio [11,20]. This is consistent to our study, which
not the uterine contraction hormone, and have no adverse effects we also find that the usage of oxytocin is significantly more often
on the whole delivery process [19]. Sharma et al. have suggested in analgesia group, indicating that uterine smooth muscle contrac-
that labor analgesia can increase oxytocin requirement, prolong tion is suppressed while pain relived, which might be relevant to
the first and second labor stage, increase instrumental delivery decline of prostaglandin in uterus upon analgesia treatment [9].
ratio but efficiently reduce the ratio of cesarean section [8]. Once withdrawal the analgesia, the effect will gradually disappear
Regarding the timing of analgesia implementation, it is gener- and have less and less impact on the second stage of labor. Accord-
ally considered to apply neuraxial analgesia during active stage ing to conventional clinical requirement, it is important to actively
when cervix opening to 3 cm, it is also concerned the first lab stage take some measures during second stage of labor to prevent
will be prolonged and cesarean section risk will be increased if eclampsia for maternal hypertension patients when give vaginal
introduce analgesia too early. Thus, the clinical guidelines of Amer- childbirth, thus without prolonged second stage of labor and fetal
ican College of Obstetrics and Gynecology (ACOG) in 2000 suggest distress, doctors usually will use forceps to facilitate delivery, this
analgesia should be introduced until cervix opening to 45 cm. is the reason why forceps delivery ratio is relatively higher in both
Some reports indicate that application of analgesia in latency stage groups in our study.
may result in prolonged active period, more oxytocin requirement Importantly, in our study, the use of antihypertensive drugs in
or even cesarean section [20], however, our results suggest that control group is significantly much more than analgesia group,
labor analgesia during early stage of labor can relieve pain, control suggesting the blood pressure in patients without continuous
blood pressure, increase uterine blood perfusion and improve fetal epidural analgesia increase significantly during delivery process,
oxygen supply in maternal hypertensive disorder patients, even and obstetricians need to give additional antihypertensive drugs
with preeclampsia. to control it, which further confirmed that continuous epidural
Ropivacaine is a long-acting amide like local anesthetic which analgesia is beneficial for maternal hypertensive patients.
has very low heart and central nervous system toxicity. Ropiva-
38 B. Han, M. Xu / Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health 7 (2017) 3338

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ported by Promotion program of appropriate scientific and
technological projects, Beijing Municipal Health and Family Plan-
ning Commission (TG-2014-12).