A C TA Obstetricia et Gynecologica

AOGS S H O R T RE S E A R CH RE P OR T

B-type natriuretic peptide measurement for early diagnosis

of acute pulmonary edema during pregnancy
JEREMY SEROR1,2, GUILLAUME LEFEVRE3, NATHALIE BERKANE4, FREDERIC RICHARD1,2,
MARIE BORNES1,2, SERGE UZAN1,2 & NADIA BERKANE1,2
1

University Pierre et Marie Curie (UPMC), Paris, 2Department of Gynecology and Obstetrics and Reproductive Medicine,
Tenon Hospital, Assistance Publique Paris Hospitals, Paris, 3Department of Biochemistry, Tenon Hospital,
Assistance Publique Paris Hospitals, Paris, and 4Department of Cardiology, Broussailles Hospital, Cannes, France

Key words
Acute pulmonary edema, calcium-channel
blockers, tocolysis, pregnancy, B-type
natriuretic peptide
Correspondence
Jer
emy Seror, Tenon Hospital Gynecology
and Obstetrics, 4 rue de la Chine, Paris
75020, France.
E-mail: seror.je@laposte.net
Conflict of interest
The authors have stated explicitly that there
are no conflicts of interest in connection with
this article.

Abstract
Calcium-channel blockers administered to pregnant women as tocolytic agents
can cause acute pulmonary edema. The first signs of this severe complication
can be atypical and so delay introduction of appropriate therapy. We describe
three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could
contribute to timely diagnosis and improve follow-up.
Abbreviations:

BNP, B-type natriuretic peptide.

Please cite this article as: Seror J, Lefevre G,

Berkane N , Richard F, Bornes M, Uzan S,
et al. B-type natriuretic peptide measurement
for early diagnosis of acute pulmonary edema
during pregnancy. Acta Obstet Gynecol
Scand 2014; 93: 13171319.
Received: 5 February 2014
Accepted: 5 August 2014
DOI: 10.1111/aogs.12472

Introduction
Acute pulmonary edema induced by calcium-channel
blockers is a situation not sufficiently recognized by clinicians, despite several publications on the condition.
The first clinical signs of acute pulmonary edema are
nonspecific and could delay effective treatment. Calciumchannel blockers are used worldwide (1) and are recommended with atosiban in France as first-line tocolytic
agents. Considering the difference in cost and efficiency of
these two tocolytics, nicardipine remains the main tocolytic
agent used in French maternity units. Calcium-channel
blockers replaced b-adrenergic agonists in an attempt to
reduce severe side effects such as acute pulmonary edema.

The role of B-type natriuretic peptide (BNP) measurement

in the early detection of acute pulmonary edema in pregnant women has not been reported previously.

Material and methods

Case 1
A 36-year-old woman, gravida 3, para 3, with a history of
conization, was admitted for preterm labor at 30 weeks
of gestation. Oral nicardipine (50 mg twice/day) had been
initiated at 22 weeks for early cervical changes. Intravenous nicardipine was added, with a maximal flow-rate of
3 mg/h, and maximal dose of 72 mg/day for 72 h (total

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BNP for diagnosis of acute pulmonary edema

nicardipine dose 5600 mg). She also received intramuscular betamethasone injections for fetal lung maturation
(12 mg/day for 2 days). She developed acute dyspnea
72 h after admission. Tachycardia was recorded in spite
of normal systemic arterial pressure. There was a normal
electrocardiogram, as well as cardiac auscultation, chest
radiograph and arterial blood gases. D-dimer with
enzyme-linked immunosorbent assay technique and troponin levels were within normal ranges. However, the
BNP value (Architect Abbott, www.abbott.com) was
increased at 425 pmol/mL. Nicardipine was immediately
discontinued. Furosemide and nasal oxygen resulted in
clinical improvement, confirming the diagnosis of acute
pulmonary edema induced by calcium-channel blockers.
Acute dyspnea disappeared and the BNP concentration
decreased following discontinuation of treatment. She
delivered at 32 weeks of gestation.

Case 2
A 40-year-old-woman, gravida 5, para 3, was admitted
for preterm labor at 28 weeks gestation. Oral nicardipine
(50 mg twice/day) had been initiated prophylactically at
19 weeks of gestation for contractions and major placenta
previa. Intravenous nicardipine was then added, with a
maximal flow-rate of 3 mg/h and maximal dose of
72 mg/day for 96 h (total nicardipine dose 6444 mg). She
was also given intramuscular betamethasone as in Case 1.
She presented with acute dyspnea 96 h after admission, as
well as tachycardia with normal systemic arterial pressure,
while an electrocardiogram, cardiac auscultation, chest
radiograph, arterial blood gases, D-dimer and troponin
levels were within normal ranges. The BNP value was
increased at 539 pmol/mL. Nicardipine was immediately
discontinued and furosemide and nasal oxygen resulted
in a clinical improvement, confirming the diagnosis. The
dyspnea disappeared and the BNP concentration
decreased following this. Delivery was at 34 weeks of
gestation.

Case 3
A 38-year-old-woman, gravida 1, para 1, was admitted to
our emergency department for evaluation of intrauterine
growth retardation at 27 weeks of gestation. Oral nicardipine (50 mg twice/day) had been initiated at 19 weeks
after emergency cervical cerclage. She had no intravenous
nicardipine, and no associated treatment. Two weeks after
admission, she presented with acute dyspnea. The total
dose of nicardipine was 6300 mg. The diagnosis of acute
pulmonary edema was confirmed by a BNP-value of
1224 pmol/mL. Nicardipine was discontinued and the
same treatment as for Cases 1 and 2 resulted in clinical

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J. Seror et al.

improvement, confirming the acute pulmonary edema.

The dyspnea disappeared and the BNP concentration
decreased with delivery at 31 weeks of gestation.
None of the cases were complicated with preeclampsia.
All three women gave written consent for publication.

Discussion
The peptide hormone BNP is mostly synthesized within
cardiac ventricular myocytes in response to volume expansion and/or pressure overload and is routinely used for
the monitoring of patients with cardiopulmonary disorders (2) and for diagnosis of acute pulmonary edema in
nonpregnant patients. Classically, a BNP value <100 ng/L
rules out acute heart failure. In normal pregnancies, median BNP values of <20 ng/L have been reported, around
two-fold higher than those found in nonpregnant women.
They remain stable throughout gestation but are found to
be increased in preeclampsia (3,4).
As nicardipine has no negative inotropic effect, the
pathophysiology of acute pulmonary edema is difficult to
explain. Several factors could play a role in acute pulmonary edema occurrence: an increase in intravascular volume caused by intravenous fluids in combination with a
betamethasone mineralocorticoid effect and/or unknown
individual patient sensitivity. In these three cases, patients
were treated by oral nicardipine during the late second
and early third trimesters of pregnancy. Acute pulmonary
edema appeared after a cumulative dose of approximately
6000 mg. Hence the long-term oral use of calcium-channel blockers could reveal a cohort of patients in whom
this medication does result in left ventricular re-modeling
in the face of hypertensive hypertrophy. Nicardipine
might be reversing, to some degree, the physiologic ventricular hypertrophy that occurs normally in pregnancy,
leaving these women at increased risk for ventricular
insufficiency and acute pulmonary edema when the peak
demand for cardiac output is reached around 30
34 weeks of gestation. In the light of recent publications
comparing maintenance calcium-channel blocker tocolysis
with placebo (5), the benefits and risks of tocolytic treatments, the mode of administration and the duration of
treatment deserve to be evaluated. Atosiban could be a
safer option for the treatment of preterm labor, but it is
not sufficiently available everywhere.
We reported the first three cases of acute pulmonary
edema induced by calcium-channel blockers in whom
BNP measurement proved to be a relevant marker to
confirm early diagnosis and to monitor the patient until
recovery. Although obstetricians are as yet largely
unfamiliar with this recent biomarker, its proven value in
cardiopulmonary disorders should lead to a growing
awareness of the value of this measurement in obstetrics.

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