Intended for healthcare professionals

Rapid response to:

Clinical Review

Recent developments in obstetrics

BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7415.604 (Published 11 September 2003) Cite this as: BMJ 2003;327:604

Rapid Response:

tocolytics for preterm labor in cardiac patient

The incidence of preterm delivery is about 10% of all births.more
than 60,000 patients receive intravenous tocolytics. The potential injury
to the healthy mother is limited. This does not hold true for the cardiac
patient for whom the tocolytics represent considerable risk.the prevalence
of cardiac disease amongst pregnant population is 0.5-1.0%. There is a
gradual rise in maternal age(1) due to late marriage and altered socio-econmic enviroment. Increasingly, there are co-existing risk factors like
smoking, obesity, hypertension, diabetes, use of oral contraceptives, and
dyslipidaemias.the incidence of coronary artery disease is rising and even
deaths from acute myocardial infarction has been reported during
pregnancy.(2)

The tocolytics in current use are b-mimetics, magnesium sulfate,
nifedipine, and indomethacin. An important consideration in cardiac
patient is that maternal hypoxia can lead to preterm labor. Here,
optimisation of cardiac status is all that is required. Similarly, fetal
compromise, like iugr, reduced amniotic fluid, bradycardia etc, are in
fact a cry for fetal delivery in an hostile enviroment. Many of the
fetuses, of high risk mothers have cardiac or morphological malformations
which cause preterm delivery.

Intravenous b-mimetics are the current gold standard.all b-mimetics are b2
selective, but have some b1 effects, which cause undesirable side effects.
One principal concern for the healthy mother is the appearance of
pulmonary edema , myocardial ischaemia or unmasking of latent cardiac
disease. In addition, patients on b-mimetic often demonstrate reversible
ecg changes of ischaemia and prolongation of QT interval with
arrythmogenic potential.any healthy patient developing chest pain with b-
mimetic should have it discontinued. Myocardial infarction during
ritodrine infusion has been reported in previously healthy woman.(3)the
most consistent and serious complication is that of pulmonary edema with
an incidence of 1-5%.(4) most cases have been attributed to co-administration of excessive fluids, and concomitant use of steroids,
indomethacin and nifedipine.in vast majority of cases there is no pre-existing cardiac disorder. Another worrisome adverse effect is persistent
maternal bradycardia after ritodrine withdrawal.research revealed use of
ritodrine in treatment of preterm labor had no significant beneficial
effect on perinatal mortality, frequency of prolongation of pregnancy to
term, or birth weight.(5) a variety of cardiac arrhythmias are also
described during terbutaline pump therapy leading to maternal death in one
case. In addition, in several patients initial manifestation of
cardiomyopathy occurred after ritodrine infusion.some authors claim that
this was unmasking of cases of peripartum cardiomyopathy associated with
use of b-mimetic.nevertheless, there was complete recovery on cessation of
therapy.terbutaline pump is gaining popularity, but it is important to be
aware that new onset arrhythmias, pulmonary edema and even death has been
attributed to its usage.(6)however, the adverse cardiac effects have not
been characterised by large randomised trials despite its widespread use.

Other perturbations associated with b-mimetics are hyperglycemia,
ketoacidosis, and lactic acidosis.if this is the state of affairs in
healthy patients, for cardiac patients more justification would be
required for its use.few conditions like pulmonary hypertension, aortic
stenosis, pulmonary stenosis ,and hypertrophic obstructive cardiomyopathy
are contraindicated. They should be also avoided in ischaemia and
arrythmias as both can be aggravated.

Profound hypotension has been reported with use of large bolus of
magnesium sulfate especially when multi agents are used like ritodrine or
nifedipine.magnesium sulfate also have direct cardiac toxicity leading to
PR and QRS prolongation.cardiac arrest is the ultimate consequence.

Pulmonary edema and unexplained hyperkalemia has also been described. Its
use in cardiac patients should be guarded especially when pulmonary
hypertension is present.

Calcium channel blockers, particularly nifedipine appear to be safe.and
result in significant dimunition of uterine contractions. However, this
drug must not be used in large quantities and must never be given
sublingually as it leads to a catastrophic hypotension.the combination
with magnesium sulfate may potentiate magnesium sulfate’s toxicity. The
reported use of calcium channel blockers in cardiac patient is scatchy,
but not so in healthy gravids.(7)

Others advocate antenatal vit k in preterm labor.although if not
beneficial, this appears to be harmless, except when a cardiac patient has
a prosthesis and is on anticoagulant, coumadin.

In conclusion, the management of cardiac patient is similar to non-cardiac
ones, except that vigorous hydration should be avoided and effort made to
understand cause of preterm labor.b-mimetics are contraindicated usually,
magnesium sulfate not given in bolus form.steroids are beneficial for
fetal maturation. Amongst calcium channel blockers, nifedipine or
nicardipine (10) although not extensively studied are useful choices.

The entire treatment with tocolytics in both healthy and cardiac patients
needs to be reviewed.

Ref:

1.rutherford jd: coronary artery disease in the childbearing age. In
elkayam u, gleicher n (eds): cardiac problems in pregnancy. 3rd ed.

2. Roth a, elkayam u: acute myocardial infarction and pregnancy. In
elkayam u, gleicher n (eds): cardiac problems in pregnancy. 3rd ed.

3. Donnelly s, mcging p, sugrue d, myocardial infarction during pregnancy.
Br j obstet gynaecol 1993;100:781-784.

4. Blickstein i, zalel y, katz z, lancet m. Ritodrine induced pulmonary
edema unmasking underlying peripartum cardiomyopathy. Am j obstet gynecol
1988;159:332.

5. Tj benedetti. Treatment of preterm labor with the beta-adrenergic
agonist ritodrin. Engl. J. Med., dec 1992; 327: 1758.

6. Warning on use of terbutaline sulfate for preterm labor
Jama, jan 1998; 279: 9-a.

7. Oral nicardipine inhibits preterm labor
Journal watch women's health, apr 2000; 2000: 10.
8.elimian a et al. Effectiveness of antenatal steroids in obstetrics
subgroups. Obstet gynecol 1999 feb; 93:174-179.[medline abstract][download
citation

9. Neonatal complications after the administration of indomethacin for
preterm laborn. Engl. J. Med., nov 1993; 329: 1602 - 1607.

10. Larmon je et al. Oral nicardipine versus intravenous magnesium sulfate
for the treatment of preterm labor. Am j obstet gynecol 1999 dec; 181:1432
-1437.[medline abstract][download citation]

Competing interests:  
None declared

Competing interests: Serious concern has been voiced regarding use of indomethacin, including neonatal deaths, intra-cranial hemorrhage, enterocolitis (9) and closure of ductal dependant flow.

25 September 2003
manan vasenwala
consultant-cardiologist (non-invasive)
k