CLINICAL REVIEW

Oxytocin: Pharmacology and

Clinical Application
Jerry Kruse, MD
Quincy, Illinois

Oxytocin is a potent uterine stimulant that is used for the induction and
augmentation of labor, antenatal fetal assessment, and control of postpartum
hemorrhage. If used improperly, oxytocin can lead to such complications as
uterine hypercontractility with fetal distress, uterine rupture, maternal
hypotension, water intoxication, and iatrogenic prematurity. These compli­
cations can almost always be avoided if oxytocin is given in proper dosages
and with careful fetal and maternal monitoring. Recent interest in active
management of labor policies has resulted in a reexamination of the use of
oxytocin in the augmentation of the labors of nulliparous women.

FORMS
S ince the production of synthetic oxytocin in the
1950s, there has been increasingly widespread use
Oxytocin was first used for the management of labor in
of oxytocin for a variety of obstetric situations.
Oxytocin is a potent stimulant of uterine contractions the form of a pituitary extract (Pituitrin), which con­
that can cause severe adverse side effects for mother sisted of oxytocin, vasopressin, and various im­
and fetus. In recent years the safety of oxytocin has purities. Oxytocin was synthesized first in 19531 and
been greatly enhanced by the use of continuous mater­ then became available commercially in pure form
nal and fetal monitoring and by the use of controlled (Pitocin, Syntocinon).
intravenous infusion of the drug. A thorough knowl­
edge of the pharmacology and proper clinical use of
oxytocin is needed by all physicians who deliver
babies. PHARMACOLOGIC ACTIONS
Oxytocin has three distinct effects on the myome­
THE PHARMACOLOGY OF OXYTOCIN trium: It increases the excitability of the myometrium,
increases the strength of contraction, and increases the
PRODUCTION velocity and frequency of the contraction waves.2 In
Oxytocin is one of two neurohormones released by the addition to increasing the intrauterine pressure of the
posterior lobe of the pituitary. It has potent primary uterus, oxytocin facilitates the correction of ineffec­
effects on the myometrium during pregnancy, and also tive and irregular uterine contractions.
has secondary effects on the breasts, kidneys, and pe­ The uterine response to oxytocin depends on the
ripheral vessels. Both oxytocin and vasopressin circulating levels of progesterone and estrogen and
(ADH), the other posterior pituitary neurohormone, upon the gestational age. As estrogen levels rise and
are octapeptides. Their structures are similar and they progesterone levels fall (which occurs late in preg­
have somewhat overlapping effects. nancy and to a lesser degree at midcycle of the
menstrual cycle), the uterine response to oxytocin in­
creases.2 Indeed, at times other than midcycle of the
period, the uterus in a nonpregnant state is almost re­
Submitted, revised, July 22, 1986.
fractory to large doses of intravenous oxytocin.
During pregnancy there is a progressive, though ir­
From the Southern Illinois University Department o f Family Practice, regular, increase in sensitivity of the myometrium to
Quincy Family Practice Residency Program, Quincy, Illinois. Requests for oxytocin. The increase in sensitivity begins at 20
reprints should be addressed to Dr. Jerry Kruse, Quincy Family Practice
Residency Program, 1246 Broadway, Quincy, IL 62301.
weeks, and there is a sharp rise after 30 weeks. The
© 1986 Appleton-Century-Crofts

THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 5: 473-479, 1986 473
OXYTOCIN

sensitivity is maximal during spontaneous labor at 1. Montevideo units =The summation of the intensity of
term.3 each contraction (mmHg)
Oxytocin has pharmacologic action on organs other occurring in a 10-minute period
than the uterus. It causes milk ejection from the gravid or
or puerperal breast.1Suckling, breast stimulation, and
uterine manipulation cause oxytocin release and sub­ 2. Montevideo units in ten sity of one contraction
(mmHg)
sequent contraction of myoepithelial cells in the
breast.3 Oxytocin also has mild properties of
antidiuretic hormone, and water intoxication can 10 min
X ____________________________________________________
occur if large amounts of oxytocin are given with large interval (min) from peak of contractions
amounts of dilute electrolyte solution.4 Usually, a total
of 40 to 50 units of oxytocin is required for antidiuretic The average number of Montevideo units generated
effects to occur. at various times during normal pregnancies is shown in
Table l.8
OXYTOCIN AND THE NATURAL OCCURRENCE
OF LABOR PREDICTABILITY OF RESPONSE
There is evidence that the concentration of circulating During spontaneous labor, about 90 percent of women
oxytocin rises gradually throughout pregnancy and will have increased intensity of contraction and about
peaks during the second stage of labor.5 This progres­ 75 percent will have increased frequency of contrac­
sive rise in concentration is probably due to low-level tions when oxytocin is infused.2 After maximal effi­
spurts of oxytocin from the posterior pituitary, which ciency of contractions is reached, an increase in the
increase in frequency until delivery. There is also evi­ infusion rate will result in a decrease in the intensity of
dence that there is significant excretion of fetal oxyto­ contraction. This decrease in intensity occurs because
cin during labor.6 the base-line uterine tonus increases and also because
There is probably a complex interaction between the frequency of contraction increases to such a degree
endogenous oxytocin and prostaglandins that initiates that the relaxation phase of the contraction is inter­
labor. Recent evidence suggests that prostaglandin rupted by the next contraction.9
production is a prerequisite for the maintenance of ef­ The uterus always responds to oxytocin infusion
ficient uterine contractions, and that oxytocin stimu­ with an increase in tonus, even with small doses. The
lates production of prostaglandins in the uterus during important increases in tonus are seen, however, when
pregnancy under conditions predisposing to the occur­ oxytocin is given with an already maximal uterine con­
rence of labor.7-8 So it seems plausible that oxytocin tractility or when starting an infusion at a high rate.9
from maternal and fetal sources triggers uterine con­
tractions that become efficient when oxytocin induces
an increase in uterine prostaglandin production. CLINICAL APPLICATION OF OXYTOCIN
The normal uterine contraction begins in the fundus ADMINISTRATION
at the cornual areas, the thickest parts of the uterine
wall. The contraction wave is propagated in all direc­ Oxytocin should be administered as a dilute intrave­
tions and covers the entire uterus in 20 to 30 seconds. nous solution. Usually 10 or 20 units of oxytocin is
The origin, propagation, strength, and duration of an mixed with 1 L of balanced salt solution. The starting
effective contraction all predominate in the fundus and dose should be small, 0.5 to 1.0 mU/min. (In a solution
progressively diminish as they reach the cervix. Intra­ of 20 units of oxytocin per liter, an infusion rate of 3
venous infusions of oxytocin can often correct con­ mL/h equals 1 mU/min).
traction patterns that do not follow this orderly se­ The maximal effect of oxytocin occurs in 20 to 60
quence.2 minutes, depending on the concentration of oxyto­
cin.10 Lower concentrations will require more time
than higher concentrations to reach maximal effect. If
QUANTIFICATION OF UTERINE ACTIVITY
the rate of infusion is increased too rapidly,
hyperstimulation may occur. The rate of infusion
Quantification of uterine activity is important in un­ should be doubled every 20 to 30 minutes until the
derstanding the proper use of oxytocin. Uterine activ­ desired effect is obtained.
ity is conveniently measured in Montevideo units. At term, 2 to 8 mU/min is usually sufficient to obtain
Montevideo units measure the uterine work done in 10 labor-like contractility. Seldom is more than 20
minutes. The uterine work is defined as the summation mU/min required. When oxytocin is used to stimulate
of the intensity of uterine contractions, which is the the preterm uterus, much higher concentrations may
amplitude of the contraction minus the baseline tonus be required to obtain comparable uterine activity. At
of the uterus. Montevideo units can be calculated in 32 weeks’ gestation an average of 20 to 40 mU/min is
the following two ways: required.2

474 THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 5, 1986

OXYTOCIN

section scar), or when the uterus is manipulated.

TABLE 1. AVERAGE UTERINE ACTIVITY AT VARIOUS
TIMES OF PREGNANCY
Cibils2reports only one case of uterine rupture in 6,000
consecutive oxytocin inductions over a ten-year
Uterine Activity period at the Chicago Lying-In Hospital. No cases of
(Montevideo Units) uterine rupture occurred during the oxytocin induc­
tions of 1,022 high-risk patients in South Africa in
Prelabor 50 1976.11 In a review of 181 consecutive cases of uterine
(Braxton-Hicks contractions rupture, Trivedi et al12 reported no cases of uterine
of late pregnancy) rupture among nulliparous patients.
Early first stage 125
Mid-first stage 180
Second stage 250 Hypotension. Oxytocin in bolus intravenous doses
causes significant hypotension.13 As little as 2 units
given by rapid intravenous bolus can cause a 30 per­
cent drop in mean arterial pressure.214 Accordingly,
There is a continuous increase in spontaneous oxytocin used for control or prevention of postpartum
uterine activity throughout labor that will be superim­ hemorrhage should be given by controlled intravenous
posed on the effects of infused oxytocin. Needless to infusion or intramuscular injection. Bolus intravenous
say, careful monitoring of the fetal heart rate and ma­ doses should never be given.
ternal contractions is mandatory when oxytocin is
being administered. The dose of oxytocin may need to
be decreased or discontinued altogether as labor pro­ Wafer Intoxication. Chemically, oxytocin is closely re­
gresses. lated to vasopressin and has weak intrinsic antidiuretic
properties. Water intoxication can occur when large
doses of oxytocin are given with electrolyte-free intra­
PRECAUTIONS AND RISKS WITH THE USE OF venous solutions.4 Water intoxication is completely
OXYTOCIN preventable if intravenous fluids of the proper amount
When used carefully, intravenous oxytocin is a very and composition are given.
safe pharmacologic agent. Complications caused by
oxytocin are almost always due to improper dose or Neonatal Hyperbilirubinemia. There is disagreement
inadequate supervision. about the effects of oxytocin upon the development of
neonatal jaundice. The most recent evidence suggests
Uterine Hyperstimulation and Fetal Distress. Uterine that infants at a higher risk of developing jaundice
hypercontractility is by far the most common compli­ associated with oxytocin administration are those
cation of the use of oxytocin. Uterine hypercontractil­ whose mothers received a total of 20 units of oxytocin
ity is usually defined as either uterine activity exceed­ or more during their labors.15 This dose is extremely
ing 250 Montevideo units, coupling of uterine contrac­ large. For example, if oxytocin were infused at 12
tions, or more than five contractions in a ten-minute mU/min, it would take about 20 hours to reach a total
period. Hypercontractility causes a decrease in the dose of 20 units.
intravillous blood flow, and fetal distress is often the
result. Hypercontractility is usually quickly reversible Iatrogenic Prematurity. When oxytocin is used for the
by discontinuation of the oxytocin. To maximize fetal elective induction of labor, there is a chance that iatro-
oxygenation, oxygen should be administered and the genically premature infants may be delivered. In a
patient should be placed in the left lateral position. study of 1,000 newborn infants referred to a regional
Morbidity from hypercontractility can be minimized neonatal intensive care unit, Flaksman et al16 found
by careful fetal monitoring. that 32 were premature infants who had been born to
Hypercontractility may progress to tetanic contrac­ mothers in whom labor had been electively induced.
tions. Tetanic contractions may be quite prolonged, up All 32 infants had serious respiratory complications.
to 10 to 20 minutes, after oxytocin is discontinued.2 Twenty-five of these infants were bom by “ early” re­
With proper monitoring, hypercontractility should be peat cesarean section, and the other seven were prod­
noted before tetanic contractions occur. There is no ucts of oxytocin induction. All were presumed to be
scientific basis for the notion of "pitting through mature prior to delivery, but their gestational ages by
hyperstimulation” by continuing to increase oxytocin Dubowitz scores were 33 to 37 weeks. Blacow et al17
infusion rates. studied 200 consecutive elective inductions and found
that, when assessed by Dubowitz scores, 27 of the
Uterine Rupture. Uterine rupture is an extremely rare babies were more than 2 weeks younger than assumed.
occurrence, particularly in the primigravid uterus. The true incidence of iatrogenic prematurity is un­
When oxytocin is being used, uterine rupture appears known, but this complication should be preventable by
to occur only when oxytocin is grossly misused, when accurate dating of pregnancies and the appropriate use
the uterus is defective (eg, from a previous cesarean of ultrasound examinations and amniocentesis.
475
THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 5, 1986
OXYTOCIN

TABLE 2. CONDITIONS IN WHICH THE INDUCTION OF TABLE 3. THE BISHOP METHOD OF PELVIC SCORING*
LABOR MAY BE INDICATED
Score
Prolonged pregnancy
Preeclampsia 0 1 2 3
Chronic hypertension
Diabetes mellitus Station -3 -2 -1 orO + 1 or +2
Rh isoimmunization Cervix
Previous stillbirth Dilation (cm) 0 1-2 3-4 5-6
Advanced maternal age Effacement 0-30 40-50 60-70 80-100
Intrauterine death (%)
Intrauterine growth retardation Consistency Firm Medium Soft
Major fetal anomalies Position Posterior Middle Anterior
Hydramnios
*Reprinted with permission from the American College o f Obste­
tricians and G ynecologists 19

Abnormal Neurobehavioral Status of Infants. It has

been suggested that infants born after oxytocin stimu­
lation may have a higher risk of developing neurologic overdistention from multiple gestation or hydramnios,
or behavioral abnormalities. The most recent studies (5) absence of major bleeding from placenta previa or
suggest, however, that the neurologic and behavioral abruptio placentae, (6) absence of uterine surgical scar,
status at and before age 2 months of infants born after (7) absence of an unfavorable fetal position or presen­
oxytocin stimulation is no different from that of those tation, (8) absence of grand multiparity, (9) absence of
born spontaneously or after prostaglandin stimula­ a history of uterine trauma or infection, (10) estimated
tion.18 fetal weight less than 4,300 g, and (11) Bishop score
indicative of successful induction.
Uterine Atony. In women of high parity, the use of A more liberal use of oxytocin for induction is es­
oxytocin is thought to be associated with an increased poused by Cibils,2 who writes “ the only contraindica­
incidence of uterine atony and postpartum hemor­ tion to the proper use of intravenous oxytocin are the
rhage. contraindications to spontaneous labor.” He finds no
satisfactory reason to deny the potential benefit of a
THE INDUCTION OF LABOR WITH OXYTOCIN carefully controlled uterine stimulation with oxytocin
to patients with twins, breech presentations, distended
Indications and Contraindications. Induction of labor uteri, or grand multiparity.
may be indicated if continuation of pregnancy or spon­
taneous labor poses a threat to fetal or maternal well­ Factors Affecting Success of Induction. By far the most
being or if the fetus is dead. Conditions in which these important factor affecting the success of the induction
criteria are often met are listed in Table 2. Obviously, of labor is the state of the cervix, or cervical ripeness.
the mere presence of these conditions is not an indica­ Various methods of assessing cervical ripeness have
tion for the induction of labor. Careful consideration been developed, the most widely used being the
must be given to the optimal timing of the induction of Bishop method of pelvic scoring, which takes into ac­
labor, and before induction is begun, the following count the cervical condition and station of the infant.19
questions need to be addressed: This method was developed in 1964 and has been used
1. Do the risks of continuation of pregnancy out­ to determine the optimal time for the induction of
weigh the risks of the use of oxytocin? labor. The Bishop scoring method is shown in Table 3.
2. Is delivery best accomplished by induction of Scores are assigned for station of the fetal head and for
labor or cesarean section? four characteristics of the cervix, which are then
3. Is the fetus mature? If not, do the risks of con­ added to obtain the Bishop score. A score of 9 or more
tinuation of pregnancy outweigh the risks of pre­ was uniformly associated with a successful induction.
maturity? Recently Lange et al20have proposed a modification
As are the indications for the induction of labor, the of the Bishop method. This modification, which has
contraindications for the use of oxytocin are quite con­ better accuracy and reproductibility than the tradi­
troversial. In most textbooks of obstetrics, long lists of tional Bishop method, eliminates the cervical consis­
criteria for the use of oxytocin can be found. Petrie1 tency and position and weighs more heavily the cervi­
suggests that the following criteria be met before using cal dilation. The modification by Lange et al is shown
oxytocin: (1) data supporting fetal maturity or benefit in Table 4.
of premature delivery outweighing prematurity, (2) ab­ Lange et al found that, in a series of over 1,000
sence of fetal distress, (3) absence of absolute patients, 100 percent of patients with a score of 8 or
cephalopelvic disproportion, (4) absence of uterine greater and 75 percent of patients with a score of 5 to 7

476 THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 5, 1986

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TABLE 4. THE MODIFIED BISHOP SCORING SYSTEM* TABLE 5. FREQUENCY OF CESAREAN DELIVERIES
ACCORDING TO DIAGNOSTIC CATEGORIES*
Cm Score
Percentage of Births
Station -3 0
United States Dublin
-2 1
1978 1980
-1 orO 2
+ 1 or 2 3
Dystocia 4.7 0.7
Dilation 0 0 (Cephalopelvic
1-2 2 disproportion)
3-4 4 4.7 1.1
Repeat section
>4 6 1.8 0.6
Breech
Length of cervix 3 0 Fetal distress 0.8 0.5
2 1 Other 3.2 1.9
1 2 Total 15.2 4.8
0 3
*Reprinted with permission from the American College o f Obste­
*Reprinted with permission from the American College of Obste­ tricians and Gynecologists 26
tricians and Gynecologists20

undergo successful inductions. Induction of labor in­ first stage of labor, progress is measured in terms of
variably fails in patients with scores of 4 or less. cervical dilation, which is plotted on a graph. The
slowest acceptable rate is 1 cm/h, which allows ten
hours for complete dilation. In nulliparous women,
ELECTIVE INDUCTION OF LABOR
lack of acceptable progress is treated promptly with
The elective induction of labor at a predetermined time oxytocin if there is a single fetus in vertex presentation
in pregnancy, the so-called planned delivery, has and no fetal distress. Lack of progress in multiparous
gained widespread acceptance in many parts of the women is seldom treated with oxytocin. A prospective
world. It is estimated that 35 to 50 percent of all hospi­ study of this policy was reported for the labors of 1,000
tal deliveries in Britain are induced, and many of these nulliparous women in 1973.25 Only 45 of their infants
inductions occur in the absence of clearcut medical were not delivered within 12 hours, and only nine
indication.21 Advocates of the planned delivery argue cesarean sections were performed for cephalopelvic
that this type of delivery can be of great practical and disproportion or prolonged labor. About 40 percent
social benefit to both obstetrician and mother.22 of the women received oxytocin.
Despite the widespread use of this method, the only For the past 15 years this active management policy
controlled trials comparing the outcomes of electively has been used at the National Maternity Hospital. The
induced labors and spontaneous labors have involved cesarean section rate has remained at 4.8 percent,
too few cases to draw definite conclusions.23 Since compared with a rise from 4 percent to over 15 percent
there are definite, though infrequent, complications in the United States. The perinatal mortality rate has
associated with the use of oxytocin, elective induction fallen from 42.1 per 1,000 to 16.8 per 1,000 infants, a
of labor purely for the sake of convenience or social decrease similar to that seen in the United States. The
benefit seems unwise in most instances. rates of cesarean section for various indications for
O’Driscoll’s group and for the United States are listed
AUGMENTATION OF LABOR WITH OXYTOCIN
in Table 5.26-28
The difference in cesarean section rates between the
When there is a failure of progression of labor due to Dublin group and similar centers in the United States
inadequate uterine activity, oxytocin may be used to seems to be accounted for mainly by a different ap­
augment labor by the same technique as used for in­ proach to the management of labor in nulliparous
duction. The timing of the use of oxytocin in such women and by a rejection of the precept once a cesar­
circumstances is controversial. Recently much atten­ ean section, always a cesarean section. The diagnosis
tion has been given to the “ active management of of cephalopelvic disproportion was made in less than 1
labor” method espoused by O’Driscoll et al.24-27 The percent of these women.
obstetricians at the National Maternity Hospital in Though the views of O’Driscoll’s group represent
Dublin, Ireland, have made a systematic attempt to one extreme, the results of their work are impressive.
curtail the duration of labor and to promote early de­ Considering the potential complications of prolonged
livery. Their goal is to assure every woman that the labors in nulliparous women (eg, maternal fatigue,
duration of labor will not exceed 12 hours. The active complications of prolonged rupture of membranes,
management policy includes the following: During the complications of prolonged anesthesia), the active

THE JOURNAL OF FAMILY PRACTICE, VOL. 23, NO. 5, 1986 477

OXYTOCIN

management of labor method, even in a modified form, Contraction Stress Test. The contraction stress test
may be of great benefit to mother, infant, and physi­ (CST, or oxytocin challenge test) is used in the
cian. antepartum period to assess fetal well-being when
there is a possibility of fetal compromise. The indica­
ALTERNATIVE METHODS FOR INDUCTION AND
tions for and administration of the CST will not be
AUGMENTATION OF LABOR
discussed here. Only rare complications have been re­
ported. One concern about the use of CSTs prior to 38
Induction and augmentation of labor have been at­ weeks' gestation has been the possibility of the initia­
tempted using other methods and techniques, both tion of premature labor. Recent studies have shown
alone and in combination with oxytocin. Some of these that there is no difference in the incidence of spon­
methods are summarized briefly below. taneous labor in a five-day period for women who re­
ceive a CST prior to that period or for women who
Prostaglandins. Prostaglandins have become widely receive no test.34
used in many countries for the induction of labor but
have not yet gained approval from the Food and Drug Placental Separation. Oxytocin is often given after the
Administration for this indication. They are usually delivery of the anterior shoulder to hasten placental
given either intravenously or as intravaginal sup­ separation. This technique seldom offers any real ad­
positories. Prostaglandins also may be very effective vantages. It also does not appear to increase the
when used to ripen the cervix. chance of placental entrapment.

Amniotomy. Rupture of the membranes results in the

rapid release of prostaglandin metabolites into the CONCLUSIONS
bloodstream.29 In nulliparous women at term, rupture
of membranes will be followed by labor within 12 Oxytocin is a potent stimulant of uterine contractions
hours in about 80 percent of women.30 The onset of that has widespread use among all physicians who de­
labor following amniotomy in multiparous women is liver babies. In addition to increasing the intensity and
not nearly so predictable. frequency of contractions, oxytocin facilitates the cor­
rection of ineffective or irregular uterine contractions
Vigorous Vaginal Examination. In animals any vigorous during labor. If properly used, oxytocin is a very safe
vaginal examination results in the release of prosta­ pharmacologic agent. Complications resulting from the
glandins from fetal membranes.31 There is no evi­ improper use of oxytocin can be severe, but can usu­
dence, however, that vigorous vaginal examinations ally be avoided by proper administration of the drug
help to initiate labor in humans. and careful fetal and maternal monitoring. Recent evi­
dence suggests that a more aggressive use of oxytocin
Stimulation of the Breasts. Stimulation of the breasts in the augmentation of labor, particularly in nullipar­
results in the release of endogenous oxytocin. If the ous patients, may be of great benefit. Oxytocin should
uterus is sensitive to oxytocin (eg, late pregnancy), probably not be used to induce labor in the absence of
uterine contractions theoretically should result. This medical indications.
method of inducing labor has not been well studied.
References
M aternal Position. Several studies have shown that the
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2. Cibils LA: Electronic Fetal-Maternal Monitoring:
duration of labor.32’33Ambulation, however, requires a Antepartum/lntrapartum. Boston, PSG, 1981
nonmedicated, nonexhausted patient with no evidence 3. Caldeyro-Barcia R, Serono JA: The response of the human
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cervix. The use of ambulation for the augmentation of Barcia R, Heller H (eds): Oxytocin. New York, Pergamon,
1961
labor may become more feasible with the development 4. Whalley PJ, Pritchard JA: Oxytocin and water intoxication.
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5. Dawood MY, Rhagavan KS, Pociask C, et al: Oxytocin in
human pregnancy and parturition. Obstet Gynecol 1978;
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