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Acute Pulmonary Edema in Pregnancy

Article in Obstetrics and Gynecology April 2003
DOI: 10.1016/S0029-7844(02)02733-3 Source: PubMed

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Anthony C Sciscione

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Christiana Care Health System

University of North Carolina at Chapel Hill

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Acute Pulmonary Edema in Pregnancy

Anthony C. Sciscione, DO, Thomas Ivester, MD, Marissa Largoza, MD, James Manley, MD,
Philip Shlossman, MD, and Garrett H. C. Colmorgen, MD
OBJECTIVE: To describe the incidence, predisposing conditions, and inciting factors culminating in pulmonary
edema in the pregnant patient.
METHODS: A review of 62,917 consecutive pregnancies delivered at our institution from January 1, 1989 to June 1,
1999 was undertaken for the diagnosis of pulmonary
edema. Each chart was reviewed for maternal demographics, admission diagnoses, medication use, gestational age at
diagnosis, fluid balance, coexisting maternal illness, tocolytic use, evidence of preeclampsia, and diagnostic criteria.
After careful review of the records, the most likely cause of
pulmonary edema was assigned.
RESULTS: Fifty-one women (0.08%) were diagnosed with
acute pulmonary edema during pregnancy or in the postpartum period. The mean patient age at the time of diagnosis was 27.6 6.4 years. The mean gestational age at the
time of diagnosis was 31.5 6.8 weeks. The diagnosis of
pulmonary edema was made during the antepartum period in 24 patients (47%), the intrapartum period in seven
(14%), and the postpartum period in 20 (39%). The most
common attributable causes were tocolytic use (13 patients
[25.5%]), cardiac disease (13 patients [25.5%]), fluid overload (11 patients [21.5%]), and preeclampsia (nine patients
[18%]). Those with fluid overload identified as the likely
etiology had a significantly greater mean positive fluid
balance (6022 3340 mL). All patients whose pulmonary
edema was secondary to tocolytic use received multiple
simultaneous tocolytic agents; the most common combination was intravenous magnesium sulfate and subcutaneous
terbutaline. Six of the 13 women with cardiac disease were
found to have previously undiagnosed structural heart
disease.
CONCLUSION: The most common causes of pulmonary
edema are the use of tocolytic agents, underlying cardiac
disease, fluid overload, and preeclampsia. (Obstet Gynecol 2003;101:5115. 2003 by The American College
of Obstetricians and Gynecologists.)

Pulmonary edema is defined as the accumulation of fluid

in the pulmonary interstitial spaces and alveoli, which
prevents the adequate diffusion of both oxygen and
From the Department of Obstetrics and Gynecology, Christiana Care Health
Services, Newark, Delaware.

carbon dioxide. Although an uncommon event in pregnancy, it is associated with an increased risk of maternal
and fetal morbidity and mortality.1 Several risk factors
have been identified: preeclampsia or eclampsia,13 use
of tocolytic therapy,4 10 severe infection,3,8,9 cardiac disease,11 iatrogenic fluid overload,5,11 and multiple gestation. Furthermore, the physiologic changes associated
with pregnancy may predispose the pregnant patient to
pulmonary edema.1215 Despite the multiple causes of
pulmonary edema, there is no clear consensus on the
role that each of these risk factors plays in the pregnant
population.
A MEDLINE search for the key words pulmonary
edema or heart failure and pregnancy from 1966 to
2001 revealed case reports of acute pulmonary edema in
pregnancy and diagnosis-specific reviews. There are no
reports of the etiologies and outcomes in a large cohort.
We sought to describe the attributable causes and overall
and cause-specific rates of pulmonary edema in a large
cohort.

MATERIALS AND METHODS

After approval by the Christiana Hospital institutional
review board and human experimentation committee,
we reviewed our obstetric database for the diagnosis of
pulmonary edema at our institution between January 1,
1989 and June 1, 1999. This obstetric database is repeatedly validated and found to be 98% accurate. From the
computerized database, we identified patients using
Classification of Diseases, 9th Revision codes for the
following diagnoses: pulmonary edema (646.13), heart
failure (669.43 and 428.9), severe preeclampsia (642.53),
pulmonary embolus (673.83), pneumonia (673.83 and
481), and pulmonary complications or assisted ventilation (946.56 and 946.57). When reviewing the charts for
the diagnosis of pulmonary edema, all of the following
criteria were necessary for entry into the study: significant shortness of breath, tachypnea, rales or rhonchi
upon auscultation, evidence of hypoxia by pulse oximetry or arterial blood gas, and chest x-ray findings consistent with pulmonary edema.

VOL. 101, NO. 3, MARCH 2003

2003 by The American College of Obstetricians and Gynecologists. Published by Elsevier.

0029-7844/03/$30.00
PII S0029-7844(02)02733-3

511

Table 1. Maternal Demographics

Antepartum Intrapartum Postpartum
(n 24)
(n 7)
(n 20) P
Mean age (y)
27.5 6.3
Mean EGA (wk) 26.5 6.0
Multiparas
6
Race (% white)
87.5

30.3 6.9
29.5 4.3
1
85.7

25.6 5.5
35.2 6.0
2
80

.36
.48
.27
.64

EGA estimated gestational age.

Medical records were reviewed by the authors for

maternal demographics, gestational age by a reliable last
menstruation and/or early sonogram, gravidity, parity,
number of fetuses, admission diagnosis, preexisting maternal disease, obstetric complications, drug and medication use, tobacco use, maternal symptoms, physical findings, laboratory studies, imaging studies, fluid balance,
tocolytic use and type, evidence of preeclampsia,16 infection, and therapeutic measures. The timing of pulmonary edema in pregnancy and outcomes were recorded.
The probable cause of the pulmonary edema was determined by the authors based on history, physical examinations, and laboratory and radiologic findings. In a few
cases, more than one attributable cause was possible, and
in those cases, the most likely diagnosis was chosen.
Pregnancy outcomes included gestational age at delivery, birth weight, mode of delivery, and Apgar scores.
Applied therapies such as supplemental oxygen, need for
ventilatory support, fluid restriction, diuretic usage, cessation of tocolytics, antihypertensive use, termination of
pregnancy, and antiarrhythmic usage were recorded.
The data were analyzed using a subgroup analysis by
analysis of variance, MantelHaenszel, or Fisher exact
test where appropriate. A P value of .05 was considered
statistically significant.
RESULTS
During the study time period, 62,917 women delivered
at our institution. Fifty-one patients (0.08%) were diagnosed with pulmonary edema during pregnancy or in
the immediate postpartum period (24 hours or less). The
cases were evenly distributed across the 10-year period.
Pulmonary edema was most commonly diagnosed during the antepartum (47%) and postpartum (39%) periods
(Table 1).
The mean maternal age of those diagnosed with pulmonary edema was 27.6 6.4 years, with a range of
18 42 and a mean gestational age at diagnosis of 31.5
6.8 weeks. Nineteen patients were delivered by cesarean.
There was no difference between the subgroups with
regard to maternal age or gestational age at diagnosis
(Table 1).

512

Sciscione et al

Acute Pulmonary Edema

Table 2. Etiologies and Timing of Onset of Pulmonary

Edema
Risk factor
Tocolysis
Preeclampsia
Fluid overload
Cardiac
Infection
Other
Total

Antepartum Intrapartum Postpartum Total

9
5
2
5
2
1
24

3
1
0
2
0
1
7

1
3
9
6
0
1
20

13
9
11
13
2
3
51

The attributable causes and onset of pulmonary

edema are described in Table 2. Pulmonary edema was
most commonly secondary to tocolytic use and underlying cardiac disease. All women for whom tocolytic use
was the probable cause of pulmonary edema were
treated with multiple simultaneous tocolytics. The most
common combination was intravenous magnesium sulfate and subcutaneous terbutaline (eight of 13 patients),
with three of 13 receiving indomethacin with magnesium
sulfate and two receiving magnesium sulfate, indomethacin, and terbutaline. Magnesium sulfate was administered as a 4 6-g bolus dose, followed by 25 g per hour.
Indomethacin was administered as 50 mg per rectum
every 6 hours and terbutaline as 250 g every 20 minutes for a maximum of six doses, until diminution of
contractions or a heart rate of at least 120 beats per
minute.
Thirteen women (25.5%) diagnosed with pulmonary
edema had underlying cardiac disease (Table 3). Although most women with underlying cardiac disease
had valvular disease, structural cardiac disease was
newly diagnosed in six women (11.7%) after the diagnosis of pulmonary edema. One woman without underlying heart disease had idiopathic supraventricular tachycardia, which was ultimately controlled with digoxin and
verapamil.
Iatrogenic fluid overload was a common attributable
cause, with 11 patients (21.5%) having this diagnosis.

Table 3. Cardiac Diagnosis Implicated in Onset of Pulmonary Edema

Newly diagnosed
Severe mitral regurgitation (2)
Severe mitral insufficiency
Moderate mitral stenosis
Decreased left ventricular
function
Global hypokinesis

Previously diagnosed
Aortic regurgitation (2)
Aortic stenosis (2)
Idiopathic hypertrophic
subaortic stenosis
Dilated
cardiomyopathy (2)

OBSTETRICS & GYNECOLOGY

Women who had this as their etiology had no other risk

factor identified. This was the most common reason for
pulmonary edema in the postpartum time period (Table
2). All patients received isotonic fluid. Two patients
received blood products for postpartum hemorrhage.
Those women with fluid overload identified as their
likely etiology had a significantly greater mean positive
fluid balance during the 48 hours preceding the diagnosis
(6022 3340 mL versus 1017 2757 mL, P .003).
Nine patients (18%) developed pulmonary edema secondary to preeclampsia. Five of those patients had preexisting essential hypertension. The majority (56%) of
pulmonary edema due to preeclampsia occurred in the
antepartum period. There were no cases of eclampsia in
this group.
Two patients (3.9%) had infection as the probable
cause of their pulmonary edema. One patient had sepsis
secondary to pyelonephritis. The other patient had left
lower lobe pneumonia.
Pulmonary edema was attributed to incidents of each
of the following: immunoglobulin A nephropathy and
renal failure, acute fatty liver of pregnancy, and a paradoxical reaction to general anesthesia. One maternal
mortality occurred in a patient with type I diabetes
mellitus, who developed pulmonary edema secondary to
infection. The patient recovered from pulmonary edema
and was doing well when she developed diabetic ketoacidosis and adult respiratory distress syndrome.
Although pulmonary edema did not directly cause
any neonatal morbidity, the underlying causes or preterm labor were associated with premature birth and the
resultant neonatal morbidities. There were no neonatal
deaths.
DISCUSSION
This is the first report examining a large cohort of
pregnant women with the diagnosis of pulmonary
edema for individual etiology and outcomes. In this
cohort study, we report a review of all women diagnosed
with acute pulmonary edema over a 10-year period in a
busy tertiary care hospital. We found that the rate of
acute pulmonary edema in pregnancy was 0.08%. Despite the low rate of occurrence, there was significant
morbidity and one mortality associated with this diagnosis.
We found the most common time for the occurrence
of pulmonary edema in our study was the antepartum
period, closely followed by the postpartum period. Although this corroborates the findings by Mabie et al,17 it
differs from two previous reports that found pulmonary
edema in the postpartum period to be most common.12,18 This difference is most likely due to the differ-

VOL. 101, NO. 3, MARCH 2003

ent populations studied and/or different practice patterns. These reports attribute the late onset to the
postpartum period mobilization of fluids combined with
a 30% decrease in colloid osmotic pressure. These late
physiologic changes highlight the importance of judicious use of intravenous fluids. In our report, a large
portion of pulmonary edema was secondary to volume
overload from vigorous intravenous hydration commonly associated with tocolytic use. This had become a
common practice in our and other institutions despite
any evidence to support intravenous hydration as a
method to decrease preterm birth.19 Education of the
obstetric staff and guidelines that limit the amount of
hydration have helped us to limit the occurrence of this
preventable cause of pulmonary edema since the completion of this study.
Structural or functional cardiac defects predispose a
patient to developing pulmonary edema.20 However,
cardiac disease is most likely under-diagnosed and under-reported because of under-utilization of diagnostic
modalities such as echocardiography. In one report, 47%
of women who had pulmonary edema had clinically
unsuspected findings on echocardiography.17 The majority of these cases revealed systolic dysfunction or left
ventricular hypertrophy rather than structural disease.
There were no cases of valvular disease. In our report we
also found that unsuspected findings on echocardiography are common, but more importantly, we found a high
incidence of undiagnosed valvular disease.
Preeclampsia was the cause of pulmonary edema in
17.4% of patients in this report.3 These patients are at an
increased risk for the development of pulmonary edema
due to underlying endothelial damage and decreased
colloid osmotic pressure, which cause leakage into the
pulmonary interstitium or alveolar space. Combined
with the left ventricular dysfunction and increase in
peripheral vascular resistance found in preeclamptic patients, pulmonary edema develops. The development of
pulmonary edema appears to be influenced by maternal
age, parity, and preexisting essential hypertension.3 Two
women in this report with chronic hypertension and
superimposed preeclampsia developed pulmonary
edema.
Despite the lack of convincing evidence that tocolytics
improve neonatal outcomes, they are still commonly
used.20 Thirteen patients (25.5%) in this report had their
pulmonary edema attributed to the use of tocolytics. In
our report, -mimetics were the tocolytics used most
frequently. The incidence of pulmonary edema with
-mimetic use alone has been estimated to be 5%.21 In
our report, all women who had pulmonary edema attributed to tocolytics had simultaneous use of multiple tocolytics. The most common combination was subcutane-

Sciscione et al

Acute Pulmonary Edema

513

ous terbutaline and intravenous magnesium sulfate;

although magnesium sulfate has been associated with the
occurrence of pulmonary edema,22 the etiology is less
clear.23
This study has several strengths including the large
population studied and strict outcome and diagnostic
criteria. However, there are limitations:
1) We reviewed our database for the diagnosis codes as
described above. Although this was an exhaustive
review with broad diagnoses, the possibility of underreporting exists.
2) Maternal echocardiograms were performed in 14 of
the patients in this report. Although the cases where
echocardiography was not performed appeared
straightforward, the possibility of women with undetected heart disease exists. In those patients in whom
an underlying etiology could not be detected, it is
reasonable to expect that maternal echocardiography
would have contributed a diagnosis. This would further reinforce the need for maternal echocardiography, especially in patients in whom the diagnosis was
not clear.
3) Some patients had multiple possible etiologies for
their pulmonary edema. Although we chose the most
logical and apparent cause in each case, the possibility
of incorrect assignment or multiple contributing factors must be considered.
4) This report was performed at a large tertiary care
referral center, limiting the application of these findings to a low-risk population.
Several potential risk factors for the development of
pulmonary edema in pregnancy exist. Many such factors
often coexist in a given patient, though often one factor
predominates. Our review of almost 63,000 pregnancies
found the most common etiologies to be the use of
tocolytic agents, cardiac disease, fluid overload, and
preeclampsia. We encourage limiting treatment of preterm labor with a single tocolytic agent, if possible. The
use of simultaneous multiagent therapy should be used
with caution, especially with the lack of convincing evidence of its efficacy. When used, particular attention
should be given to fluid balance, symptomatology, and
physical examination. Although a case could be made for
performing maternal echocardiography in all pregnant
or postpartum women who have pulmonary edema, this
may not be practical in many cases. However, in cases
where no immediate and obvious cause for pulmonary
edema is readily apparent, echocardiography should be
performed early to evaluate the patient for possible
underlying cardiac disease.

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Address reprint requests to: Anthony C. Sciscione, DO, Christiana Care Health Services, MaternalFetal Medicine Division,
4755 OgletownStanton Road, Newark, DE 19718; E-mail:
asciscione@christianacare.org.

Received July 15, 2002. Received in revised form September 23, 2002.
Accepted October 17, 2002.

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Acute Pulmonary Edema

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