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. ince the production of synthetic oxytocin in the FORMS S 1950s, there has been increasingly widespread use of oxytocin for a variety of obstetric situations. Oxytocin was first used for the management of labor in 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 fractory to large doses of intravenous oxytocin. Submitted, revised, July 22, 1986. During pregnancy there is a progressive, though ir­ From the Southern Illinois University Department of 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 o r or puerperal breast.1 Suckling, breast stimulation, and uterine manipulation cause oxytocin release and sub­ 2. Montevideo units intensity of one contraction sequent contraction of myoepithelial cells in the (mmHg) breast.3 Oxytocin also has mild properties of 10 min antidiuretic hormone, and water intoxication can 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 Cibils2 reports only one case of uterine rupture in 6,000 TIMES OF PREGNANCY 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