Induction of Labor With Oxytocin: When Should Oxytocin be Held?

Oxytocin is the most common agent used to induce and augment labor. Oxytocin injection is
approved by the Food and Drug Administration for the initiation or improvement of uterine
contractions to achieve vaginal delivery. It is used to induce labor and stimulate or
reinforce labor.

The relationship of oxytocin and its receptor is crucial in obtaining adequate uterine
activity and thus inducing active labor. Due to this very balanced relationship, a question
exists about the optimal regimen of oxytocin administration for induction of labor and on
how long to continue oxytocin once active labor begins. Some literature suggests that once
in the active phase of labor oxytocin may be discontinued without altering the progression
of labor. The objective of this study is to determine whether there is an increased rate of
cesarean delivery in women undergoing induction of labor when oxytocin is discontinued in
the active phase of labor.

Blair-Bell was the first who, in 1909, demonstrated the uterotonic action of posterior
pituitary extracts at a cesarean delivery. Since then oxytocin, synthesized by du Vigneaud
et al, has been most commonly used for the induction of labor. Oxytocin (OT) is a
polypeptide hormone, synthesized in the hypothalamus and in reproductive tissues during
pregnancy.

Oxytocin stimulates uterine contraction by mechanisms involving the activation of
receptor-operated calcium channels. Calcium-dependent phosphorylation of myosin triggers the
interaction of myosin and actin subunits throughout the uterus leading to contractions.

During labor and parturition the relationship between oxytocin and its receptor is critical
in achieving adequate uterine contractions and thus active labor. If few receptors are
present, as seen in an early gestation, a large amount of OT is required for contractions.
The opposite is true in term pregnancy. OT binding to its receptor is very important because
excess doses of OT are not productive and may have undesirable effects.

The use of OT can cause hyperstimulation (excessive contractions leading to abnormal fetal
heart rate patterns) even when used in adequate doses. Nonetheless, induction of labor with
OT can be beneficial in reducing the incidence of prolonged labor and subsequent cesarean
delivery without increasing perinatal morbidity or mortality.

Currently OT protocols vary throughout hospitals. Both low and high dose regimens as
outlined by the American College of Obstetrician and Gynecologists are appropriate for labor
induction. At our facility intravenous OT is started at 1-2 milliunits per minute and
increased by 2 milliunits every 15 minutes until obtaining normal progression of labor
usually at 150-300 Montevideo units on the contraction monitor. Low dose regimens with
less frequent increases in dose are associated with decreased hyperstimulation. However use
of high-dose oxytocin has not been found to increase the incidence of birth asphyxia or
perinatal morbidity.

As mentioned in the study proposal, the proposed experimental arm is currently not performed
as patient of the oxytocin guidelines at our institution. One study from Israel found no
difference in pregnancy outcomes with the proposed use of oxytocin. Although we are aware of
one provider that stops the oxytocin drip once the patient is in active labor, this is not a
commonly performed procedure at our institution. We are not aware of other institutions
employing the above.

We propose to perform a prospective randomized control trial to compare the rate of cesarean
delivery in women where OT is discontinued once active labor begins (5 cm dilation) when
compared with women where OT is continued at a maintenance level per the usual protocol.

One study group will follow an oxytocin protocol which is incremental until 5 cm dilation
and then maintained at the same level throughout labor. The second arm will follow an
oxytocin protocol also incremental, but then discontinued once the cervix is 5cm. The
primary outcome will be the rate of cesarean delivery between the groups. Groups will be
stratified by parity (nulliparous vs. multiparous). Secondary outcomes to be evaluated will
include duration of the labor, fetal heart rate abnormalities, and frequency of uterine
hyperstimulation, maternal and neonatal outcomes.

Based on our sample size calculation, we will need at least 160 patients in each arm of the
study to find an increase in the cesarean delivery rate from 25% to 40% in women who undergo
induction of labor where oxytocin is discontinued once the active phase of labor begins.
This sample size calculation uses a power of 80% and an alpha level (statistical
significance) of 0.05. The baseline rate of cesarean in the US is 25-30%. We chose 40% as
a significantly increased rate of CS since this rate would represent a 60% increase in CS
from the baseline risk in the population.

We are looking for a difference in cesarean rates between the experimental arm and the
maintenance arm. Evaluating the data as an equivalence study (no difference between the
interventions) would significantly increase the sample size needed for the study. With our
current sample size calculation, if a cesarean rate difference is not found between the
groups (meaning discontinuation of oxytocin is not inferior to the maintenance use of
oxytocin in active labor), we can state that our data do not support a significant increase
(60% increase) in the risk of cesarean delivery rate when reducing the amount of oxytocin
used for induction of labor.

It is not possible to blind the providers, nurses or patients to the arm of the study since
oxytocin infusions need to be titrated and dosing level is important in managing labor. This
will be an intention to treat analysis.

The decision to perform a cesarean delivery will be according to standard obstetric
indications and will be ultimately decided by the treating physician, regardless of
treatment assignment. Obstetric criteria are in place to perform cesarean deliveries. The
treating physician at any time may restart the oxytocin in patients originally assigned to
the oxytocin discontinuation arm.