is not available, the intramuscular (IM) route of administration
should be used. Dispensing premixed IV bags from the central
4 g in 100 mL) from the maintenance bag (e.g., 20 g in 200 mL)
continuous infusion of 2 g/hour.
MONITORING MAGNESIUM SULFATE THERAPY
CASE 49-5, QUESTION 11: T.D. has been given magnesium
sulfate 4 g IV for 30 minutes and was then started on a
Deep tendon reflexes (patellar reflex), respiratory rate, and
urine output should be monitored periodically during treatment
with magnesium sulfate.118 The loss of patellar reflexes, the first
13 mg/dL. Urine output should be carefully monitored and
should be at least 100 mL every 4 hours (or 25 mL/hour).118
Magnesium serum concentrations are not routinely measured
unless renal dysfunction is evident with oliguria or elevated
SCr because magnesium is almost entirely excreted by the
kidney.115,118 Hypocalcemia and hypocalcemic tetany also can
occur secondary to elevated magnesium and can be reversed by
calcium gluconate 1 g (10 mL of a 10% solution) slow IV push
for 3 minutes. Neuromuscular depression can occur in infants
system safeguards to avoid unintended dosing errors.125
CASE 49-5, QUESTION 12: How long should magnesium
should be the same for T.D.126 Women with severe pre-eclampsia
or pre-eclampsia superimposed on chronic hypertension are at
greater risk for disease exacerbation when magnesium sulfate is
CASE 49-5, QUESTION 13: T.D. delivers vaginally and her
magnesium infusion was discontinued by mistake 3 hours
postpartum. T.D. experiences an eclamptic seizure 4 hours
Lorazepam, diazepam, phenytoin, and magnesium sulfate
have all been used to treat eclampsia. The use of magnesium
higher serum concentrations of magnesium sulfate are needed
Seizures unresponsive to magnesium sulfate treatment should
push stat should be given for seizure cessation. T.D. should be
reloaded with magnesium sulfate and continued on a magnesium
1131Obstetric Drug Therapy Chapter 49
released from its quiescent state.128 For example, as progesterone
concentrations decrease near term gestation, estrogen may stimulate uterine contractility.
Uterine activity is divided into four phases: quiescence (phase
0), activation (phase 1), stimulation (phase 2), and involution
and possibly others, stimulate a complex series of uterine changes
the coordination of contractions. These changes help prime the
stimulation is responsible for the change in myometrial activity
The exact stimulus of the biochemical scheme leading to labor
in humans is unknown. The fetus may help facilitate this process
by affecting placental steroid production through mechanical
Labor is divided into three stages. Weak, irregular, rhythmic
contractions (Braxton-Hicks contractions or “false labor”) may
happen for weeks before the onset of true labor. The first stage
begins with the start of regular uterine contractions and ends
with complete cervical dilation. Stage 1 is divided further into
the latent phase, active phase, and deceleration phase. During the
latent phase, the cervix effaces (thins) but dilates minimally. The
contractions become progressively stronger and longer, better
coordinated, and more frequent. The duration of the latent phase
is the most varied and unpredictable of all aspects of labor and can
The cervix dilates from 3 to 4 cm to full dilation, usually 10 cm.
The second stage starts with complete cervical dilation and ends
with the delivery of the fetus. The third stage of labor is the time
between the delivery of the fetus and the delivery of the placenta.
INDICATIONS, CONTRAINDICATIONS, AND
QUESTION 1: J.T., a 28-year-old primigravida, is admitted
to the labor and delivery suite for labor induction. She is
at 42 weeks’ gestation by dates and ultrasound and has a
normal obstetric examination. Cervical examination reveals
an unfavorable cervix for labor induction; Bishop score is
4. What are the indications and contraindications for labor
The induction of labor involves the artificial stimulation of
uterine contractions that lead to labor and delivery. Induction
of labor is indicated when the benefits to either the mother or
fetus outweigh those of continuing the pregnancy. Examples may
include pre-eclampsia, chorioamnionitis (infection of the fetal
membranes, see Case 49-7, Question 11), fetal demise, significant
to those for spontaneous labor and vaginal delivery and include,
but are not limited to, active genital herpes infection, placenta
previa (placenta implanted over the internal cervical opening),
increased rates of chorioamnionitis and uterine atony (loss of
risk of cesarean delivery, particularly in primigravida women.130
A complete assessment of both mother and fetus should be
performed before inducing labor.129,130 Gestational age must
be assessed accurately before the induction of labor to avoid
antenatal corticosteroids should be administered (see Case 49-7,
The degree of cervical ripeness and readiness for induction
of labor should be assessed.129,133 Success of labor induction is
directly related to the favorability of the cervix.134,135 The Bishop
method of evaluating cervical ripeness assigns a score based on
the station of the fetal head relative to the maternal ischial spines
and the extent of cervical dilation, effacement (thinning of the
cervix), consistency, and position.130,133 Bishop scores of greater
than 8 are associated with rates of vaginal delivery similar to
those after spontaneous labor.129 Conversely, Bishop scores of 4
undergo cervical ripening before induction of labor still have
higher rates of cesarean delivery compared with spontaneous
labor.133 Nevertheless, cervical ripening appears to have some
Cervical ripening can be accomplished pharmacologically
the cervical canal.130,133 In the setting of a favorable Bishop
score, labor induction is accomplished most commonly by
amniotomy (artificial rupture of the fetal membranes) and oxytocin administration.129,130
Although labor induction is medically indicated in J.T. to
decrease the risk of an adverse fetal outcome with continuing a
postterm pregnancy, such as macrosomia, asphyxia, meconium
aspiration, and intrauterine infection, her cervix is unfavorable
for induction and she is a candidate for cervix ripening.
CASE 49-6, QUESTION 2: What pharmacological agents can
be used for cervical ripening in J.T.?
1132 Section 10 Women’s Health
collagen and increasing the submucosal hyaluronic acid and
been used for cervical ripening and the induction of labor in
women despite the lack of approval by the FDA for these latter
indications.136,137 In two large meta-analyses, misoprostol was
more effective for cervical ripening and labor induction than
either placebo or treatment with dinoprostone (prostaglandin
E2).136,137 In comparisons, intravaginal misoprostol produced
labor more often during cervical ripening and resulted in reduced
rate of cesarean deliveries, shorter delivery times, and a greater
incidence of vaginal delivery within 24 hours but had a higher
Uterine tachysystole, excessively frequent uterine contractions,
without fetal heart rate abnormalities was more common with
misoprostol use. Maternal and neonatal outcomes were similar
in both groups. The need for oxytocin is decreased significantly in
women treated with misoprostol compared with women treated
Oral misoprostol has also been studied for cervical ripening,
but comparisons of vaginal and oral misoprostol are complicated
by wide variations in dose and dose interval.142 A meta-analysis of
available studies concluded that the only consistent finding was a
reduction in low 5-minute Apgar scores with oral misoprostol but
no difference in neonatal intensive care unit admissions. When
comparing all studies with a wide range of doses, oral misoprostol
resulted in similar rates of vaginal delivery not achieved in 24
hours, uterine tachysystole with fetal heart rate changes, and
cesarean delivery compared with vaginal misoprostol.142
Misoprostol 25 mcg (one-fourth of an unscored 100-mcg
tablet) is inserted into the posterior vaginal fornix and repeated
as needed every 3 to 6 hours.138,141 Higher doses of 50 mcg are
associated with increased uterine contractile abnormalities.136,141
be delayed at least 4 hours from the last dose of misoprostol.129
Misoprostol should not be used in women with previous
uterine scars because of the risk for uterine rupture.129,138,140
Although misoprostol is a known teratogen in the first trimester
of pregnancy, particularly if used in an unsuccessful attempt at
medical abortion, there are no such reports with exposure beyond
is extensive clinical experience with this agent; however, its lack
of FDA approval for cervical ripening and induction of labor is
a disadvantage. Clinical trials of a controlled-release misoprostol
vaginal insert are currently ongoing.143
PROSTAGLANDIN E2 (DINOPROSTONE)
There are two FDA-approved forms of dinoprostone available for
oxytocin.144–146 Dinoprostone cervical gel (Prepidil Gel) contains
dinoprostone contains 0.5 mg per 3-g syringe (2.5 mL gel)
inserted vaginally.147 Postterm women with unfavorable cervices
who receive dinoprostone have shorter durations of labor, and
require lower doses of oxytocin, compared with placebo or no
therapy.133,144–146 A large meta-analysis that included more than
10,000 women found that the use of vaginal prostaglandin E2
compared with no treatment or placebo was associated with
increased rates of vaginal delivery within 24 hours, increased
rates of cervix ripening, reduced need for oxytocin augmentation,
dinoprostone formulations differ in dosing and application.147,149
within a knitted pouch attached to a long tape. Advantages of
the vaginal insert include that it is easier for the clinician to place
and less uncomfortable for the patient. In addition, the insert can
be removed with the onset of active labor or the development
of uterine tachysystole with concurrent fetal heart rate tracing
there is evidence of tachysystole with fetal heart rate changes.150
If dinoprostone cervical gel is used, the dose can be repeated in
6 to 12 hours if there is inadequate change in the cervix and only
minimal uterine activity, but no more than three total doses are
recommended.150 The manufacturer of Prepidil recommends a
delay in initiation of oxytocin of 6 to 12 hours once the gel has
been placed compared with a shorter delay of only 30 to 60
minutes after the vaginal insert has been removed. An initial
period of uterine and fetal monitoring of up to 2 hours should
occur after placement of the intracervical gel, with continued
monitoring thereafter if regular uterine contractions develop and
The most serious side effect associated with dinoprostone
administration is uterine hyperstimulation with or without an
endocervical gel is about 1%.129 Uterine hyperstimulation occurs
placement of the intravaginal insert.129,151 Use of the vaginal
insert requires continuous monitoring of fetal heart rate and
uterine activity for as long as the insert is in place and for at least
of uterine hyperstimulation with the use of the vaginal insert
occur during active labor and resolve within a few minutes after
removal of the insert.145 Uterine contraction abnormalities may
be avoided if the insert is promptly removed at the onset of
labor.136 Both dinoprostone formulations are associated with
fever, nausea, vomiting, and diarrhea, and neither are associated
with adverse neonatal outcomes.129,147,149
the most cost-effective option for cervical ripening.
responded and her Bishop score is now 9, but she has
not developed a consistent pattern of uterine contractions.
What drug therapy should be initiated at this point?
1133Obstetric Drug Therapy Chapter 49
contractions.150 The uterine response to oxytocin increases
throughout pregnancy beginning at approximately 20 weeks’
gestation and increases considerably at 30 weeks’ gestation.150
Oxytocin is indicated for both the induction and augmentation
of labor. A prolonged latent phase or dystocia (difficult labor)
caused by uterine hypocontractility in the active phase of labor
is the indication for augmentation with oxytocin.150
CASE 49-6, QUESTION 4: How should oxytocin be administered to J.T.?
Oxytocin should be administered by continuous IV infusion
physiologic doses in the range of 2 to 6 milli-units/minute with
oxytocin should be used in pharmacologic doses to cause strong
uterine contractions with the goals being shortened labor, timely
correction of dysfunctional labor, decreased cesarean deliveries,
and reduced maternal morbidity.129
Oxytocin plasma concentrations increase linearly with
increasing doses and steady state is reached within 20 to 40
minutes. Oxytocin serum concentrations correlate poorly with
uterine activity, however.153 Factors that may affect response to
oxytocin include parity, gestational age, and cervical dilation.153
various protocols.150,152,154 Starting doses range from 0.5 to
6 milli-units/minute, and dose increment intervals range from
15 to 60 minutes.129 Waiting for 30 to 40 minutes between each
dosage rate increase allows time to assess the response at steady
state. Most low-dose protocols usually start oxytocin at 1 to
2 milli-units/minute and increase the rate of infusion by 1 to
increases of 3 to 6 milli-units/minute every 20 to 40 minutes. The
maximal dose of oxytocin has not been established.129 The ACOG
recommends that each hospital’s obstetrics departments develop
guidelines for the consistent preparation and administration of
is an abnormally slow progress of labor.155–157 The incidence of
uterine hyperstimulation during labor induction is higher with
high-dose protocols (initial dose of 6 milli-units/minute with
incremental increases of 6 milli-units/minute), however, when
Women undergoing labor induction with high-dose oxytocin
for augmentation of labor than for induction of labor.152,156
J.T. should be started on an infusion of oxytocin 10 units
diluted in 1,000 mL of an isotonic solution (concentration
infusion to detect abnormal uterine contraction patterns or fetal
heart rate patterns. The goal is to establish a pattern of three
to five uterine contractions of 60 to 90 seconds’ duration per
10-minute period.154 The oxytocin infusion should be increased
by 1 to 2 milli-units/minute every 30 to 40 minutes as needed
for inadequate progression of labor (cervical dilation rate of
<1 cm/hour).129 Fluid intake and urine output should be assessed
CASE 49-6, QUESTION 5: What are the adverse effects and
complications of oxytocin for which J.T. should be monitored?
Uterine hyperstimulation, usually associated with excessive
cesarean delivery for fetal distress, and postpartum hemorrhage
and death have been reported.129 Oxytocin is structurally and
functionally related to vasopressin, also known as antidiuretic
hormone. Administration of high concentrations of greater than
40 milli-units/minute and for long periods are associated with
J.T. should be monitored for uterine hyperstimulation with fetal
heart rate deceleration because it is the most common adverse
Preterm delivery occurred in 12.8% of births in the United States
in 2006, representing a 20% increase since 1990.8 Approximately
55% of singleton preterm births follow spontaneous preterm
labor, and approximately 8% follow preterm premature rupture
resulting in approximately 70% of deaths.159 Prematurity is the
second leading cause of infant mortality at younger than 1 year
of age, and resulted in 17% of such deaths in 2006.8 However,
the more inclusive classification of mortality as being “preterm
related” was linked to 36.1% of all infant deaths in 2006.8
Spontaneous preterm labor is a heterogeneous syndrome, and
result in progressive cervical ripening and dilation; weakening
of the chorioamniotic membranes, which leads to rupture; and
uterine contractions. Ultimately, delivery of the infant occurs.
Infection, if present, triggers an inflammatory response that
results in the release of cytokines, prostaglandins, and proteases,
1134 Section 10 Women’s Health
which stimulate uterine activity, induce cervix softening and
been implicated in the apparent genetic predisposition to preterm
birth found in some families and racial groups.161 Thrombin is
another uterotonic agent, which can cause uterine contractions,
and has been implicated in causing preterm labor associated with
vaginal bleeding caused by placental abruption.162 Studies have
fetal stress can activate the hypothalamic-pituitary system and
prostaglandins.160,162 Despite some progress in recent years,
much remains unknown about the etiology of preterm birth,
and little is known about how preterm birth can be prevented.
CLINICAL PRESENTATION AND EVALUATION
QUESTION 1: B.B., a 17-year-old white woman, G2, P1, and
29 weeks’ gestation, is admitted to the obstetrical unit with
complaints of backache, cramps, and uterine contractions.
She has no symptoms of preterm premature rupture of the
membranes (PPROM). She had a previous preterm birth at
32 weeks’ gestation. Cervicovaginal secretions are positive
for fetal fibronectin. A pelvic examination reveals that her
cervix is 2 cm dilated and 80% effaced, which is increased
from 1 cm at her prenatal visit last week. Cervical cultures for
Chlamydia trachomatis and Neisseria gonorrhoeae from her
previous visit are negative. Vaginal wet-mount preparations
are also negative for bacterial vaginosis and Trichomonas
vaginalis. Vital signs, urinalysis, and complete blood count
with differential are normal. Uterine contractions and fetal
heart rate are being monitored. Ultrasound reveals a fetus
of 30 weeks’ gestation size with an estimated weight of
1,200 g. What signs, symptoms, and laboratory evidence
support a diagnosis of preterm labor?
are not in labor, however, which results in frequent overdiagnosis.
In addition, contractions during preterm labor are frequently not
of pregnancy, reappearing only at term as labor approaches.164
34 weeks’ gestation with intact amniotic membranes, and with
cervical dilatation of less than 3 cm.165 Because of fibronectin’s
high negative predictive value of greater than 95% for delivery
in the next 1 to 2 weeks, it can be used to avoid overdiagnosis
independently associated with preterm birth. B.B. has the criteria
necessary to establish a firm diagnosis of preterm labor. Not only
is her fibronectin test positive, but she has persistent contractions
with a documented change in cervix dilatation.
CASE 49-7, QUESTION 2: What risk factors does B.B. have
for spontaneous preterm labor?
B.B. has several risk factors for preterm delivery. The strongest
predictor of preterm birth is prior preterm birth. She has a
twofold or higher increased risk of preterm delivery because
of one previous preterm delivery.164 If this pregnancy also ends
Recurrence risk rises as the gestational age of the prior preterm
birth decreases, especially for deliveries at less than 32 weeks.
Her young age may also be a risk factor. A maternal age younger
than 18 or older than 35 years is associated with spontaneous
preterm birth, although it is difficult to separate age from the
confounding factors associated with age.164 Her race likely does
not contribute to her risk. Black race is an independent risk factor
for both preterm labor and lower neonatal birth weight. Other
uterine anomalies, which B.B. does not have.128,164 Studies of
preterm delivery; however, the positive predictive value varies
widely.164,165 Maternal infections, such as untreated urinary tract
important to identify women at risk for spontaneous preterm
delivery, only half of all preterm deliveries occur in women with
CASE 49-7, QUESTION 3: What are the goals of tocolysis
Treatment of spontaneous preterm labor primarily has been
directed at slowing or stopping contractions (tocolysis), which
are the obvious, although likely late, sign of impending preterm
2 days.166 This might be because of the heterogeneous causes of
spontaneous preterm birth and because tocolytic agents may not
number of preterm births before various cutoff points.167 The
value of prolonging pregnancy will vary by gestational age, and
of intraventricular hemorrhage (see Case 49-7, Question 7). All
women at risk for preterm birth within 7 days and between 24
and 34 weeks’ gestation should be considered for glucocorticoid
therapy.132,168 Delay of delivery can also allow transport to a
facility best equipped to care for both mother and premature
Numerous factors affect the decision to treat preterm labor
with a tocolytic agent. Fetal factors precluding tocolysis include
nonreassuring fetal monitoring, significant IUGR, and lethal
congenital anomalies. Maternal factors include evidence of
chorioamnionitis, other significant maternal infections or illness,
pre-eclampsia, and advanced labor.164 Tocolysis is less likely to
be effective in women with cervical dilation of greater than 3 cm
and is usually unsuccessful if the patient is in advanced labor
1135Obstetric Drug Therapy Chapter 49
(cervical dilation >5 cm).164 Because the etiology of preterm
labor is multifactorial, B.B. should be evaluated thoroughly and
periodically for potential causes of preterm labor and treated
perform amniocentesis to exclude subclinical chorioamnionitis
B.B. has no evidence of overt infection or other complications
and has no contraindications to tocolysis. Prolonging gestation,
even for a few days, would be beneficial because B.B. is only at
CASE 49-7, QUESTION 4: How should B.B.’s preterm labor
be managed? Which tocolytic agent should be used?
Magnesium sulfate is the most frequently used parenteral
tocolytic agent in the United States and is also prescribed for
the prevention and treatment of eclampsia. Magnesium sulfate
relaxes uterine smooth muscle at maternal serum levels of 5 to
8 mg/dL.164 The mechanism by which it exerts this effect is not
reducing myometrial contractility.167
Despite its widespread use, the evidence for magnesium’s
efficacy in prolonging gestation is inadequate. In two published
demonstrated. In meta-analyses of both placebo-controlled trials
of magnesium for tocolysis compared with other active drugs,
no prolongation of pregnancy was seen with magnesium.166,169
ritodrine.166 Three of the four showed no differences in birth
outcomes. One of the four suggested prolonged pregnancy with
magnesium added to ritodrine compared with ritodrine alone.
Studies on the efficacy ofβ-adrenergic agonists (mostly ritodrine)
versus placebo have been mixed but on balance suggest delay of
delivery for 48 hours, but not for 7 days. Therefore, because most
trials comparing magnesium with β-adrenergic agonists did not
show differences, it has been presumed that magnesium is equally
effective. Magnesium is better tolerated than the β-adrenergic
with caution in renal failure.
β-Adrenergic agonists are not the first-line choice for preterm
the only medication approved by the FDA for the treatment of
preterm labor, and terbutaline bind to β2-adrenergic receptors
in uterine smooth muscle and ultimately inhibit smooth muscle
1,320 women treated with β-agonists demonstrated fewer births
at 48 hours but no change in number of births at 7 days. No
benefit on neonatal morbidity or mortality was seen; however,
the studies are limited by sample size.170,171 The continued use
of β-agonists can result in the development of tachyphylaxis to
its effects on the myometrium and may in part explain treatment
failures with these drugs.164,170
Terbutaline is available for IV, SC, and oral administration.
One dose of terbutaline 0.25 mg SC is often administered to
women with mild contractions and cervical dilation less than
2 cm. Intravenous β-sympathomimetics are used in cases with
more severe and frequent contractions and cervical dilation
and myocardial ischemia, the FDA issued a black-box warning
in 2011 against the use of injectable terbutaline beyond 48 to
72 hours. The FDA also recommended against any use of oral
terbutaline for preterm labor owing to both lack of efficacy and
the potential for significant maternal side effects.
β-Adrenergic agonists are not selective for myometrial
β2-adrenergic receptors at pharmacologic doses, and this
tachycardia, myocardial ischemia, hyperglycemia, hypokalemia,
and hepatotoxicity result in discontinuation of therapy in up
to 10% of patients.164 Pulmonary edema can occur and, if
not recognized promptly, can lead to ARDS and death.164,172
should be avoided if there are signs of chorioamnionitis such as
maternal leukocytosis, fetal tachycardia, or maternal fever.164
The most commonly reported fetal or neonatal adverse effects
monitored postnatally. Fetal tachycardia rarely leads to fetal
myocardial ischemia or hypertrophy.172 In summary, although
β-sympathomimetic drugs have been used commonly in the
past, they are now used much less frequently because of side
effect profiles and safety concerns.164
Prostaglandin synthesis requires cyclo-oxygenase (COX), also
known as prostaglandin synthetase, to convert arachidonic acid
to prostaglandin G2. COX inhibitors such as indomethacin
increase in gestational age at delivery, and a trend toward fewer
delivery before 37 weeks’ gestation and maternal drug reactions
was noted. Also, seen in these studies was a trend toward a
reduction in delivery within 48 hours.173 Indomethacin is well
tolerated, and GI upset can be mitigated by antacids when it
Although well tolerated by the mother, concerns exist about
rapidly approach maternal levels.172,174 Because indomethacin
can decrease fetal urine output leading to oligohydramnios,
the amniotic fluid index should be followed and indomethacin
1136 Section 10 Women’s Health
discontinued if it falls below 5 cm (normal range, 5–25 cm).
Oligohydramnios generally resolves within 48 to 72 hours of
bypass the fluid-filled lungs, constricts in 25% to 50% of fetuses
exposed to indomethacin in utero, but generally is reversible.164
Permanent closure of the ductus arteriosus, however, can lead
to fetal right heart failure and even intrauterine demise. The
risk for neonatal adverse effects is increased with drug exposure
of longer than 48 hours, as well as use after 32 weeks’ gestation
when premature closure of the ductus occurs more frequently.164
An increased risk for maternal postpartum hemorrhage has also
in the presence of oligohydramnios or suspected fetal renal or
cardiac anomaly (see Chapter 100, Neonatal Therapy).
More serious fetal and neonatal effects have been reported in
some retrospective and observational studies, including neonatal
necrotizing enterocolitis, intraventricular hemorrhage, and renal
failure.174–176 It is difficult, however, to discern whether these
complications are causally related to indomethacin or to the use
Typical dosing regimens include a loading dose of 50 to 100 mg
either rectally or orally followed by a maintenance dose of 25 mg
orally every 4 to 6 hours for 24 to 48 hours.175
The calcium-channel blockers nifedipine and nicardipine inhibit
placebo-controlled trials have been performed with nifedipine,
women found that calcium-channel blockers were superior to
other tocolytics (mostly β-mimetics) in reducing preterm births
within 7 days and before 34 weeks’ gestation.178 A more recent
study of 192 women comparing nifedipine with magnesium
sulfate for preterm labor found no differences in delivery in
48 hours, gestational age at delivery, or deliveries before 32 or
37 weeks’ gestation.179 Maternal side effects were significantly
fewer in patients receiving calcium-channel blockers compared
patient.172 Nifedipine does not adversely affect uteroplacental
blood flow or fetal circulation. Concurrent use with magnesium
10 mg PO with repeated doses of 10 mg every 15 to 20 minutes
for persistent contractions, up to a maximum of 40 mg in the
first hour.181,182 Depending on the tocolytic effect, nifedipine is
then maintained at 10 to 20 mg PO every 4 to 6 hours.181 Overall,
nifedipine appears to be an attractive alternative for short-term
tocolysis because the drug is usually well tolerated.181
B.B. should be started on a magnesium sulfate 6-g IV loading
dose for 30 minutes followed by 2 g/hour continuous IV infusion
or fewer contractions per 10 minutes or a maximum of 4 g/hour is
attained. B.B.’s deep tendon reflexes, respiratory rate, and urine
output should be monitored regularly. Close monitoring of fluid
balance is important because fluid overload has been associated
with pulmonary edema and the drug is renally excreted.183
Magnesium serum concentrations are commonly evaluated
every 6 to 12 hours in an effort to minimize adverse effects.184
are present, many practitioners will not measure concentrations.
To prevent inadvertent overdoses, a controlled infusion device
should always be used to deliver magnesium as a continuous
with magnesium serum concentrations of 15 to 17 mg/dL, and
cardiac arrest develops with greater concentrations. The toxic
when patients are receiving magnesium infusion.172
The most common side effects of magnesium loading doses
are transient hypotension, flushing, a sense of warmth, headache,
dizziness, lethargy, nystagmus, and dry mouth.164,183 Other
2% of patients treated with magnesium sulfate.183 Pulmonary
edema occurs less frequently with magnesium sulfate than with
effects are hypotonia and sleepiness. Hypotonia may continue
neuromuscular depression may be needed.183
OTHER BENEFITS OF MAGNSIUM SULFATE
Magnesium sulfate is chosen as a tocolytic over nifedipine in B.B.
because it offers other benefits at the current gestational age
with magnesium sulfate might be associated with reduced rates
to evaluate this possibility. In the largest study, a total of 2,241
at younger than 1 year, or moderate to severe cerebral palsy at
older than 2 years of age). However, in secondary analyses there
was a reduction in moderate to severe cerebral palsy as well as
total overall cerebral palsy in the group that received magnesium
magnesium sulfate may provide neuroprotection is not precisely
known. However, in adults, magnesium minimizes fluctuations
in cerebral blood flow, reduces reperfusion injuries, and blocks
intracellular damage. Magnesium may also reduce cytokine
production.180 In 2010, the ACOG recommended that physicians
could consider using magnesium sulfate for fetal neuroprotection
1137Obstetric Drug Therapy Chapter 49
dose only just before delivery to up to 12 to 24 hours before
anticipated delivery.190 As the several studies have thus far used a
variety of doses and duration of therapy, it was also suggested that
each hospital choosing to use magnesium for neuroprotection
develop specific local guidelines for treatment and monitoring.190
hours. The dose was increased to 3 g/hour shortly after
the start of the infusion. B.B. has had no contractions for
the past 24 hours. How long does she need to be treated?
Should she be weaned off magnesium sulfate?
B.B.’s contractions have completely stopped for 24 hours.
Some protocols maintain magnesium sulfate for 12 to 24 hours
after successful tocolysis, or for the time it takes to complete
infusion is an easier and less costly option.184
CASE 49-7, QUESTION 6: B.B. heard that preterm labor can
return once stopped and asks whether she should stay on
medication. Should B.B. be started on chronic maintenance
Maintenance tocolysis has been used in an attempt to prevent
recurrence of preterm labor and prolong gestation in women
β-adrenergics for maintenance therapy after acute preterm labor
showed no benefit in delay of delivery, births at less than 34
or 37 weeks’ gestation, or neonatal complications.191 Moreover,
maintenance tocolysis, as there is not compelling evidence
that continued suppression of contractions after acute tocolysis
reduces the rate of preterm birth or neonatal morbidities.164,168
ANTENATAL GLUCOCORTICOID ADMINISTRATION
CASE 49-7, QUESTION 7: Given B.B. is in preterm labor at
29 weeks’ gestation, what medication can be given to help
facilitate fetal lung maturation?
B.B. should be given betamethasone 12 mg intramuscularly
7 days after starting treatment. Repeated weekly corticosteroid
courses should not be given because of the association with
more courses).132,195 However, a randomized clinical trial has
now demonstrated a significant reduction in neonatal respiratory
morbidity and composite neonatal morbidity when women with
preterm labor and intact membranes who had received an initial
course of steroids at less than 30 weeks’ gestation were treated
again with a single rescue course of steroids (betamethansone 12
mg IM ×2 doses, 24 hours apart) if more than 2 weeks had passed
and the gestational age was less than 33 weeks.196 This rescue
course was administered if there was judged to be a recurrent risk
of preterm birth. Although long-term outcome data are not yet
available, the ACOG now recommends consideration of a single
rescue course of steroids under these specific circumstances.132
The National Institutes of Health (NIH) Consensus Panel and
the ACOG recommends a course of antenatal betamethasone or
dexamethasone (dexamethansone 4 mg IM × every 12 hours,
for 4 doses) for all women in preterm labor between 24 and
34 weeks’ gestation.131,132 Betamethasone, however, might be
the preferred agent because fewer IM injections are needed and
however, is not based on direct comparison of betamethasone
with dexamethasone and should be interpreted with caution.
the NIH Consensus Panel recommends that corticosteroids
may be given up to 32 weeks’ gestation in the absence of
duration of ventilator use, and intraventricular hemorrhage in
infants born after ruptured membranes.195 Women at more than
32 weeks’ gestation can be considered for amniotic fluid testing
fetal lung maturation.198 Corticosteroids are not recommended
Chapter 100, Neonatal Therapy).
Infectious Complications During
CASE 49-7, QUESTION 8: Preterm labor is often associated
with an infectious etiology or source. Does B.B. need to be
started on any antibiotic therapy because she is in preterm
PRETERM PREMATURE RUPTURE OF MEMBRANES
Increasing evidence associates preterm labor with intra-amniotic
infections.160,199 Of preterm births, 20% to 40% may be caused by
an infectious or inflammatory process.162 Intrauterine infection is
associated with approximately 80% of early preterm deliveries.160
Most of the bacteria found in amniotic fluid and the placenta
are believed to have ascended from the vagina.162 It has been
suggested that the microbes responsible for preterm birth are
already present in the endometrium before conception or early
in the pregnancy, causing a chronic, subclinical infection weeks
to months before eventually causing PPROM or labor.160,162
ages.200 The use of a short course of antibiotics has been
shown to prolong the period between PPROM and delivery
(the latency period) and decrease neonatal morbidity.200 In the
1138 Section 10 Women’s Health
largest and best-designed trial of antibiotic treatment of PPROM,
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