Hypertension Research

28
Management ofInhypertension
Pregnancy by intravenous nicardipine

ORIGINAL ARTICLE Reprint request to:

Tamao Yamamoto, M.D., Ph.D.,

Management of severe Department of Obstetrics and

Gynecology, Mammy Rose Clinic,
Morishita 1, Takasu-Cho,
hypertension by nicardipine Toyahashi 441-8006, Japan.
E-mail: tamao-y@outlook.com

intravenous infusion in pregnancy Key words:

gestational hypertension,
induced hypertension after intravenous nicardipine infusion,
preeclampsia, severe

cesarean section hypertension, sliding scale

Received: February 14, 2015

Revised: April 2, 2015
Ayano Matsuura1, Tamao Yamamoto2, Tomoe Arakawa3, Accepted: April 20, 2015
Yoshikatsu Suzuki1 DOI:10.14390/jsshp.3.28

1
Department of Obstetrics and Gynecology, Nagoya City West Medical Center, Nagoya, Japan,
2
Department of Obstetrics and Gynecology, Mammy Rose Clinic, Toyohashi, Japan,
3
Department of Pharmacy, Nagoya City West Medical Center, Nagoya, Japan

Aim: The aim was to retrospectively investigate whether intravenous administration of nicardipine might be useful
for managing blood pressure (BP) after cesarean section in women with severe pregnancy induced hypertension
(PIH).
Methods: Fifty-one postpartum women after cesarean section with severe hypertension (systolic BP [SBP] ≥ 160
mmHg) (28 preeclampsia [PE] and 23 gestational hypertension [GH]) were enrolled. According to the modified
nicardipine sliding scale procedure, a continuous intravenous infusion of nicardipine at 1 to 6 mg /h was given to
goal (SBP 120–140 mmHg) by evaluation every 30 min.
Results: Initial SBPs were 172 ± 10 mmHg in PE and 175 ± 11 mmHg in GH. The stable dose of nicardipine was
1.9 ± 0.8 mg /h in PE and 1.4 ± 0.6 mg /h in GH. The stable dose was greater in PE than in GH. Stable SBPs were
133 ± 11 mmHg in PE and 136 ± 11 mmHg in GH. SBP decrease rates were 23 ± 6% in PE and 23 ± 6% in GH.
Conclusion: In this retrospective study, intravenous administration of nicardipine using a sliding scale appeared
useful for decreasing BP in both PE and GH.

Introduction decreased by 15% to 20%.3)

The treatment should be switched to intravenous
Pregnancy induced hypertension (PIH) is classified injection therapy, such as nicardipine or hydralazine,
according to the severity of hypertension, with mild when BP control by oral drugs is inappropriate, during
type (blood pressure [BP] ranges from 140/90 to labor, and in postpartum women after cesarean section.
159 / 109 mmHg) and severe type (BP ≥ 160 / 110 The guidelines recommend intravenous nicardipine
mmHg), according to the Japan Society for the Study infusion using a sliding scale in both pregnancy and
of Hypertension in Pregnancy (JSSHP) criteria.1,2) In postpartum based on the DBP. In pregnant women,
the 2009 PIH management guidelines of the JSSHP, the administration should be started when DBP is ≥ 110
administration of oral antihypertensive drugs for PIH mmHg, with a BP goal of DBP from 90 to 109 mmHg.
should be started when the BP is ≥ 160/110 mmHg to In the postpartum period, administration should be started
prevent maternal organ damage (cerebrovascular, cardiac, when DBP is ≥ 90 mmHg, and the BP goal is DBP < 90
or renal damage) by prompt antihypertensive treatment.3) mmHg.3)
As the BP goal, systolic BP (SBP) ranges from 140 to The Japan Society of Hypertension (JSH) Guidelines
159 mmHg, diastolic BP (DBP) ranges from 90 to 109 2014 for the Management of Hypertension state that the
mmHg, and mean arterial pressure (MAP) should be basic treatment for PIH is the interruption of pregnancy,

28 Hypertens Res Pregnancy 2015; 3: 28–31 Hypertension Research in Pregnancy © 2015 Japan Society for the Study of Hypertension in Pregnancy
 A. Matsuura et al.

• If SBP remains ≥ 160 mmHg, Nicardipine stock solution (1 mg /ml) is given

intravenously with a syringe pump, starting with an initial dose of 1 mg /h.
• The SBP goal is ranged from 120 to 140 mmHg.
• BP is measured closely and evaluated after 30 min.

SBP (mmHg) Dose of nicardipine (mg /h) Evaluation of BP

SBP ≥ 140 The dose is increased by 1mg /h to a Every 30 min
maximum dose of 6 mg /h.
Call Dr. if the dose is more than 6 mg /h.
120 ≤ SBP < 140 The dose is maintained. Every 60 min
SBP < 120 The dose is reduced by 1 mg /h or stopped. Every 60 min

Figure 1. The sliding scale of continuous nicardipine intravenous infusion.

BP, blood pressure; SBP, systolic blood pressure.

and antihypertensive therapy should be given for this study was approved by the Clinical Investigation
maternal protection. It recommends that methyldopa, Ethics Committee of Nagoya City West Medical Center.
hydralazine, labetalol, and long-acting nifedipine (only Informed consent was obtained from each patient. PIH
after 20 weeks of gestation) should be used as the was retrospectively diagnosed 3 months after delivery
first-choice antihypertensive oral drugs. Intravenous according to the JSSHP criteria.3)
administration should be selected when a hypertensive
emergency (BP ≥ 180/120 mmHg) occurs.4) Statistical analysis
According to the JSSHP definitions, preeclampsia is Data are expressed as mean ± SD. Statistical analysis
present with hypertension and proteinuria, and gestational was performed using Excel Toukei 2012 (SSRI Co.,
hypertension is hypertension without proteinuria.1) The Ltd., Tokyo, Japan). The data were evaluated using the
pathogenic mechanisms of preeclampsia and gestational unpaired t-test, the Mann-Whitney U test, and the chi-
hypertension may differ. square test comparing the preeclampsia and gestational
In this retrospective study, whether intravenous hypertension groups. The level of significance was set
administration of nicardipine using a sliding scale might at P < 0.05.
be useful for the management of preeclampsia and
gestational hypertension was investigated, focusing on Results
changes in SBP.
Decrease in SBP with drug administration
Methods Initial SBPs were 174 ± 10 mmHg in all patients,
172 ± 10 mmHg in preeclampsia, and 175 ± 11 mmHg
Fifty-one postpartum women after cesarean section with in gestational hypertension (Table 1). All patients
SBP ≥ 160 mmHg, 28 with preeclampsia and 23 with reached a stable SBP within 6 h (107 ± 63 min in all
gestational hypertension, were enrolled. They included patients, 108 ± 66 min in preeclampsia, 106 ± 60 min in
14 patients (4 with preeclampsia and 10 with gestational gestational hypertension). Stable SBPs were 134 ± 11
hypertension) with a hypertensive emergency ( ≥ 180 mmHg in all patients, 133 ± 11 mmHg in preeclampsia,
mmHg). and 136 ± 11 mmHg in gestational hypertension (Table
If SBP remained ≥ 160 mmHg, a continuous 1). The SBP decrease rates were 22 ± 7% in all patients,
intravenous infusion of nicardipine at 1 to 6 mg/h using a 23 ± 6% in preeclampsia, and 23 ± 6% in gestational
sliding scale was given. The SBP goal was < 140 mmHg. hypertension (Table 1). Stable SBP > 140 mmHg was
The sliding scale procedure is shown in Figure 1. seen in 10 patients overall (6 with preeclampsia and 4
The decrease in SBP was observed during drug with gestational hypertension).
administration. When SBP reached the appropriate SBP The severity of SBP was divided into two levels, with
( < 140 mmHg) for more than 30 min, this was considered level I SBP from 160 to 180 mmHg and level II SBP at
a stable BP. Initial SBP, stable SBP, stable dose of more than 180 mmHg (hypertensive emergency). Level
nicardipine, and the SBP decrease rate (stable SBP/initial I was present in 24 of 28 preeclampsia cases and in 13
SBP) were evaluated. of 23 gestational hypertension cases. The severity of
This study was retrospectively conducted in the SBP differed between the preeclampsia and gestational
Department of Obstetrics and Gynecology at Nagoya City hypertension cases (P = 0.015, chi-square test).
West Medical Center from 2011 to 2014. The protocol of Stable SBPs were similar between the preeclampsia

Hypertens Res Pregnancy 2015; 3: 28–31 29

Management of hypertension by intravenous nicardipine

Table 1. Decrease in systolic blood pressure (SBP) with drug treatment

Stable
Initial SBP
Number SBP dose Rate of decrease
(mmHg)
(mmHg) (mg /h) (%)
PE 28 172 ± 10 133 ± 11 1.9 ± 0.8* 23 ± 6
Level I 24 170 ± 7† 132 ± 11 1.9 ± 0.7 22 ± 6
Level II 4 187 ± 10 139 ± 8 2.3 ± 1.0 25 ± 8
GH 23 175 ± 11 136 ± 11 1.4 ± 0.6 23 ± 6
Level I 13 168 ± 7† 136 ± 5 1.2 ± 0.4† 19 ± 4†
Level II 10 186 ± 5 136 ± 16 1.7 ± 0.7 27 ± 9
Total 51 174 ± 10 134 ± 11 1.7 ± 0.7 22 ± 7
Level I ranges from 160 to 180 mmHg, Level II is ≥ 180 mmHg. Data are expressed as mean ± SD. * P < 0.05 vs GH;
†
P < 0.05 vs. Level II.
SBP, systolic blood pressure; PE, preeclampsia; GH, gestational hypertension.

Table 2. Stable doses and reduction rates

Stable dose of nicardipine
1 mg /h (n) 2 mg /h (n) 3 mg /h (n)
PE
Level I (n = 24) 24 ± 7% (8) 21 ± 4% (11) 21 ± 8% (5)
Level II (n = 4) 19% (1) 24% (1) 29 ± 10% (2)
GH
Level I (n = 13) 20 ± 4% (10) 16 ± 1% (3) —
Level II (n = 10) 27 ± 9% (4) 27 ± 11% (5) 24% (1)
Case numbers are in parentheses. Data are expressed as mean ± SD.
PE, preeclampsia; GH, gestational hypertension.

and gestational hypertension cases. The SBP decrease Discussion

rate was greater for level II than for level I in only
gestational hypertension. JSH Guidelines for the Management of Hypertension
2014 state that antihypertensive drug therapy for PIH
Dose of nicardipine with stable SBP should be started at a BP ≥ 160/110 mmHg. However,
The stable dose of nicardipine was 1.7 ± 0.7 mg/h overall, if SBP is greater than 180 mmHg or DBP is greater
1.9 ± 0.8 mg/h in preeclampsia, and 1.4 ± 0.6 mg/h in than 120 mmHg in pregnant or postpartum women,
gestational hypertension. It was greater in preeclampsia antihypertensive treatment should be started under a
than in gestational hypertension (P = 0.0146, unpaired diagnosis of hypertensive emergency using drugs for
t-test and P = 0.0018, Mann-Whitney U test; Table 1). intravenous injection.4)
The dose of nicardipine was greater in level II (1.9 ± 0.7 The 2009 guidelines of PIH management by the
mg/h vs. 2.3 ± 1.0 mg/h in preeclampsia and 1.2 ± 0.4 JSSHP state that the treatment should be switched to
mg/h vs. 1.7 ± 0.7 mg/h in gestational hypertension) than intravenous injection therapy when BP control by oral
in level I in only gestational hypertension (Table 1). drugs is inappropriate, during labor, and postpartum after
In preeclampsia, the dose of nicardipine was greater cesarean section. Intravenous nicardipine infusion using
even though most patients belonged to Level I (24 of 28). a sliding scale in both pregnancy and postpartum based
Seven patients needed a dose of nicardipine of 3 mg/h. on the DBP has been recommended.2)
In gestational hypertension, only one of the 10 level II In our previous study, just before eclampsia, all
patients needed a dose of nicardipine of 3 mg/h (Table 2). patients had a SBP ≥ 160 mmHg, while few had DBP
≥ 110 mmHg. Furthermore, eclamptic women tended to
have a higher SBP than non-eclamptic women, while both

30 Hypertens Res Pregnancy 2015; 3: 28–31

 A. Matsuura et al.

DBP and MAP were similar to those in non-eclamptic hypertension. From our results, it is suggested it might
patients.5) Thus, we focused on SBP. If SBP was ≥ 160 be necessary to terminate the pregnancy earlier in
mmHg, a continuous intravenous infusion of nicardipine preeclampsia than gestational hypertension. However, it
at 1 to 6 mg/h using a sliding scale was given, with an is often difficult to discriminate the two in the clinical
SBP goal of less than 140 mmHg. Another study might course.
be done by using DBP in the future. In this retrospective study, intravenous administration
Using the revised nicardipine sliding scale, in most of nicardipine using a sliding scale appeared useful for
PIH patients with severe hypertension, SBP could be kept the management of both preeclampsia and gestational
under 140 mmHg, and it took 2 h to reach a stable SBP. hypertension.
The concentration of nicardipine hydrochloride
solution is 1 mg/ml. In a hypertensive emergency, Acknowledgments
administration at 0.5 μg/kg/min is started, and it ranges
from 0.5 to 2 μg/kg/min. In women weighing 50 kg, This work was partly supported by a Grant-in-Aid
the starting dose of nicardipine is 1.5 mg/h, and it is for Scientific Research from the Japan Society for the
increased up to 6 mg/h according to this equation. In the Promotion of Science (26462496).
present study, nicardipine was administered at an average
dose of 1.7 mg/h and ranged from 1 to 3 mg/h. Conflict of interest
It is well known that there are differences in
pathogenesis between preeclampsia and gestational None.
hypertension. As for severity, preeclampsia is more
severe than gestational hypertension, and management References
of preeclampsia is more difficult than that of gestational
hypertension. The NICE guidelines thus recommended 1. Watanabe K, Naruse K, Tanaka K, Metoki H, Suzuki Y. Outline
different management strategies for preeclampsia and of definition and classification of pregnancy induced hypertension
gestational hypertension.6) (PIH). Hypertens Res Pregnancy. 2013; 1: 3 – 4.
2. Japan Society for the Study of Hypertension in Pregnancy (JSSHP).
In the present study, in postpartum women given
ed. Guideline 2009 for care and treatment of hypertension in
intravenous administration, the more severe the
pregnancy (PIH). Tokyo: Medical View Co., Ltd., 2009; 179–193.
hypertension was, the higher dose of nicardipine was 3. Naruse K, Suzuki Y, Nakamoto O, et al. A Brief Review of the 2009
needed in gestational hypertension. In preeclampsia, JSSHP Guidelines for the care and treatment of Pregnancy induced
even though most patients had Level I hypertension, Hypertension. Hypertens Res Pregnancy. 2013; 1: 5 – 7.
the dose of nicardipine was greater than in gestational 4. Suzuki H. Hypertension in women. Hypertens Res. 2014; 37:
hypertension. Postpartum, after interrupted pregnancy, 334 – 338.
strict management of preeclampsia should be needed. 5. Matsuura A, Yamamoto T, Watanabe K, Suzuki Y. Characteristics
In a previous study, oral administration of labetalol, changes of systemic blood pressure seen just before onset of
β-receptor, and a selective α 1-receptor blocker eclampsia. Hypertens Res Pregnancy. 2013; 1: 35 – 39.
effectively decreased BP during pregnancy. However, 6. National Collaborating Centre for Women’s and Children’s Health.
ed. NICE Clinical Guideline. Hypertension in pregnancy: the
the effectiveness of labetalol was greater in patients
management of hypertensive disorders during pregnancy. London:
with gestational hypertension (58%) than in those with
National Institute for Health and Clinical Excellence (NICE), 2011.
preeclampsia (27%). This confirmed that labetalol would 7. Matsuura A, Yamamoto T, Arakawa T, Suzuki Y. Oral administration
be more effective in gestational hypertension than in of labetalol might improve not only the blood pressure but also
preeclampsia.7) Thus, the pathogenesis of preeclampsia clinical symptoms in Japanese women with gestational hypertension.
might not be simple. Furthermore, it may be difficult to Hypertens Res Pregnancy. 2014; 2: 82 – 87.
control BP in preeclampsia compared with gestational

Hypertens Res Pregnancy 2015; 3: 28–31 31