BJOG: an International Journal of Obstetrics and Gynaecology

April 2004, Vol. 111, pp. 380 381

DOI: 1 0 . 1 1 1 1 / j . 1 4 7 1 - 0 5 2 8 . 2 0 0 4 . 0 0 0 9 2 . x

CASE REPORT

Maternal hypoxia associated with nifedipine

for threatened preterm labour
Ryan Hodgesa, Andrea Barkehall-Thomasb,*, Christine Tippettb
Case report
A 31 year old woman, gravida 3 para 1, presented at 32
weeks of gestation with threatened preterm labour. She had
an asymptomatic ventricular septal defect diagnosed and
subjected to incomplete surgical repair in childhood. Despite this, she had good pre-pregnancy exercise tolerance
and did not suffer dyspneic episodes. Her obstetric history
included a first trimester termination of pregnancy and a
subsequent normal vaginal delivery of a healthy female
infant. She recalled some shortness of breath that prolonged
her hospital stay by seven days after that delivery.
In this pregnancy, an echocardiogram undertaken in early
pregnancy showed normal left ventricular size and function
and she was asymptomatic until she presented at 32 weeks.
She reported sudden onset of episodic lower back and
suprapubic pain consistent with uterine contractions but
without associated vaginal bleeding, rupture of membranes
or dysuria. She was haemodynamically stable, with no
clinical evidence of infection or placental abruption. Repeated vaginal examination showed no cervical change
(1 cm dilated, 1 cm long). She received betamethasone, three
20 mg doses of nifedipine orally, 20 minutes apart, for
preterm labour tocolysis, and 1 g amoxicillin intravenously
for bacterial endocarditis prophylaxis.
Within 10 minutes of the second dose of nifedipine, she
experienced shortness of breath with no associated chest
pain, cough, haemoptysis, fever or calf pain. Her symptoms
worsened overnight and by 20 hours post nifedipine, the
respiratory distress necessitated transfer to the intensive
care unit. On examination the patient had a pulse rate of
120 per minute, blood pressure 130/65 and was afebrile.
The respiratory rate was 32 per minute and mild cyanosis,
bilateral peripheral oedema and raised jugular venous

Department of Obstetrics and Gynaecology, Monash

University, Clayton, Victoria, Australia
b
Maternal Fetal Medicine Unit, Monash Medical Centre,
Southern Health, Clayton, Victoria, Australia
* Correspondence: Dr A. Barkehall-Thomas, Maternal Fetal Medicine
Unit, Monash Medical Centre, Clayton, Victoria 3168, Australia.
D RCOG 2004 BJOG: an International Journal of Obstetrics and Gynaecology

pressure (10 cm) were evident. There was a loud systolic

murmur at the left sternal edge, consistent with her known
ventricular septal defect, right ventricular heave, and decreased breath sounds at the bases of both lungs. Her calves
were soft and non-tender. Abdominal examination revealed
a soft uterus, symphysis fundal height consistent with
gestation, and a cephalic presentation with a fixed position
four-fifths above the brim.
Her arterial oxygen saturation was 93% on room air
(95% on 6 L O2/minute) and arterial blood gas analysis
revealed a PO2 of 76 mmHg, a metabolic acidosis [pH 7.34,
HCO3 11 mmol/L (21 30)], a compensatory respiratory
alkalosis ( PCO2 21 mmHg) and an increased anion gap
of 23 mmol/L. She had 3+ ketones in the urine, normal
serum lactate 1.0 mmol/L (0.5 2.0) and urea 2.0 mmol/L
(2.5 7.8). Despite an elevated D-dimer assay 0.44 units
(<0.20) and electrocardiograph changes consistent with a
pulmonary embolism (a deep S wave in lead I, a Q wave
and an inverted T wave in lead III), venous thromboembolism was excluded by a normal ventilation perfusion
(V Q) lung scan and Doppler ultrasound of the leg veins.
A therapeutic heparin infusion was commenced but ceased
after the negative V Q scan.
Normal chest X-ray, sputum culture and atypical serology
excluded pneumonia and a mid-stream specimen of urine
revealed no growth on culture. The white cell count was 13.3
 109/L, normal for pregnancy and post-corticosteroids.1
There was no evidence of placental abruption with a normal
obstetric ultrasound revealing growth consistent with gestation and Kleihauer Betke test revealed no evidence of a
feto-maternal haemorrhage. Transthoracic echocardiogram
showed hyperdynamic systolic function with normal left
and right ventricle size, no evidence of cardiomyopathy,
mildly dilated right atrium consistent with pregnancy and a
small perimembranous ventricular septal defect with a
restricted left to right shunt. Troponin I was not elevated
(<0.04 Ag/L) to indicate myocardial ischaemia. The fetus
was active with a normal cardiotocogram.
With conservative management the unexplained dyspnea
and hypoxia gradually settled and she was discharged seven
days later with uneventful weekly antenatal clinic review.
She went into spontaneous labour at 36 weeks plus five days
gestation and delivered a healthy female infant weighing
www.blackwellpublishing.com/bjog

CASE REPORT

2700 g. She received 20 mg furosemide intravenously in

addition to 5 IU syntocinon in the third stage of labour as a
precaution for possible pulmonary oedema. Her delivery
and postnatal recovery was uneventful and the aetiology of
her hypoxia remained undiagnosed.

Discussion
Nifedipine, a calcium channel blocker, has recently been
advocated, with atosiban (an oxytocin antagonist) as a
tocolytic of choice by the RCOG.2 It is an attractive alternative to beta-adrenergic agonists and non-selective cyclooxygenase inhibitors because of comparable effectiveness
and fewer maternal or fetal adverse effects.3 The incidence
of significant pulmonary oedema with beta-adrenergic agonists is estimated at 1:350 1:400 treated patients, with more
than 25 maternal deaths in the literature.4
A meta-analysis has reported that, compared with betaadrenergic agonists, there are fewer interruptions of treatment with nifedipine due to maternal adverse effects and
therapy is more effective in prolonging pregnancy, results
in fewer cases of neonatal respiratory distress syndrome
and fewer transfers to NICU.4 Nifedipine is also advantageous due to a relative lack of influence on A V conduction and maternal cardiac output.5
This case report highlights that nifedipine is nevertheless
not without risk, particularly in a woman with an underlying, albeit asymptomatic and stable, cardiac anomaly. The
increased cardiac demands of pregnancy are well appreciated: hormonally mediated increases in blood volume, red
cell mass and heart rate result in a major increase in cardiac
output6 coupled with increased myocardial oxygen demand. Pre-existing cardiac anomalies may compromise
the ability to meet this demand and may be associated with
cardiac decompensation, particularly in later pregnancy, as
the major increase in cardiac output peaks during the
second trimester and remains constant until term.6
We believe that in this case, the native vulnerability of
her ventricular septal defect with the additional cardiovascular stress of pregnancy potentially compromised her cardiac status. The uninvestigated dyspnea following the first
pregnancy may have indicated borderline decompensation
at that time. In this current pregnancy, the further demands
of corticosteroids of increased extracellular volume, increased systemic vascular resistance and increased cardiac
contractility,7 coupled with the negative inotropic effects of
nifedipine, led to more significant cardiac embarrassment.
The cause of her hypoxia is not clear. Pulmonary embolism, pneumonia, cardiomyopathy, obstructive or restrictive
airways disease and ischaemic heart disease were unlikely
on the basis of history, examination and investigations. The

D RCOG 2004 Br J Obstet Gynaecol 111, pp. 380 381

381

close-time relationship between corticosteroids and nifedipine and the development of respiratory distress and the
spontaneous recovery all point towards a drug effect. One
small study suggested that nifedipine raised pulmonary
artery pressures in non-pregnant patients with underlying
lung disease and pulmonary hypertension.8 It is unlikely
that corticosteroid therapy would have contributed, as this
has been associated with a reduction in pulmonary arterial
pressure and pulmonary vascular resistance.9
We alert the reader to the fact that women with cardiovascular disease or any medical condition contraindicating
tocolysis were excluded from the trials evaluating the efficacy and safety of nifedipine use for preterm labour.5,10 12
This case poses an interesting dilemma of assessing the
suitability of a patient for nifedipine with known cardiac
disease even when entirely asymptomatic and stable; we
believe this is a setting for caution. It articulates well the
significant impact of pregnancy itself on the cardiovascular
system, and how sensitive its workings are to the added
insult of a little hole and a few red pills.

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Accepted 12 December 2003