Labor induction and augmentation with oxytocin: pharmacokinetic considerations

Traditional protocols for oxytocin infusion regimens recommend increases of infusion rate at 15–20 min intervals. However recent clinical studies agree that prolonged intervals of 30-40 or even 60 minutes are superior to shorter dosage intervals in terms of safety and efficacy. These results are in good agreement with recent pharmacologic data on oxytocin in pregnant women, showing a half-life of about 15 minutes, and of current pharmacokinetic principles, which indicate that at least 3 half-lives of constant infusion will elapse before the corresponding clinical effect may be established. Increasing the oxytocin infusion earlier, could cause excessive uterine contractions and fetal distress. Correspondence to: M. Gonser     

A randomized control study of oxytocin augmentation of labour. 2. Uterine activity

Uterine activity was measured in 60 women whose first labour was progressing slowly in the active phase. The mean level of active contraction area (uterine activity integral, UAI) before oxytocin augmentation was 898 (SD 458) kPas/15 min. UAI increased significantly with time, even in women not given oxytocin. UAI increased logarithmically with increasing oxytocin infusion rate. Levels of uterine activity before and after oxytocin infusion are correlated positively such that the higher the initial level of UAI the higher the UAI in response to oxytocin. However, the regression line approaches the line of identity such that even with high doses of oxytocin UAI would not be likely to exceed 2500 kPas/15 min. There is a positive correlation between uterine activity and cervical dilatation rate in unstimulated labour; however, this is less evident following oxytocin infusion. Increases in uterine activity below 1200 kPas/15 min result from both higher frequency and active pressure, whereas above 1200 kPas/15 min any increase is due mainly to a rise in frequency.     

Clinicians' guide to the use of oxytocin for labor induction and augmentation

Oxytocin is commonly used in obstetrics for labor induction and augmentation. Careful assessment of the individual clinical situation based on indications and contraindications is essential to enhancing safe and effective use. Counseling the woman and her partner regarding potential risks and benefits before use is necessary to promote informed consent. At least 39 weeks of gestation is required for elective labor induction. Recent research has shown that deferring elective induction until cervical readiness has been achieved without the use of pharmacologic agents can be beneficial in reducing the risk of cesarean birth associated with elective induction. A conservative physiologic oxytocin protocol for labor induction and augmentation is recommended to minimize the risk of side effects. Although treatment of excessive uterine activity related to oxytocin has not been studied prospectively, several interventions such as maternal repositioning, an intravenous fluid bolus, and discontinuation of the oxytocin infusion are beneficial in returning uterine activity to normal, based on retrospective review of oxytocin-induced tachysystole. Perinatal quality measures from the National Quality Forum and the Joint Commission can be useful in monitoring care related to induction of labor. These include elective births before 39 weeks of pregnancy and cesarean births for low-risk, first-birth mothers.     

Uterine contraction assessment

Few approaches to preterm birth prevention have been as thoroughly studied yet as enigmatic as uterine contraction assessment. Despite multiple randomized clinical trials (level 1 evidence), the effectiveness of home uterine contraction assessment as an adjunct to the clinical management of women at risk for preterm birth remains controversial. This article reviews these trials with particular attention to study design and patient inclusion criteria. The data are absolutely clear that home uterine contraction monitoring with or without frequent perinatal nursing contact can reduce the risk of preterm birth and improve perinatal outcomes and that both are independently superior to standard preterm birth prevention education and care.     

Uterine action after induction of labour with oral prostaglandin E2 tablets compared with intravenous oxytocin.

Uterine action throughout the whole of labour induced by low amniotomy and either oral prostaglandin E2 tablets or intravenous ocytocin was studied in 10 randomly matched pairs of patients. Oral prostaglandin E2 tablets induced fewer contractions per hour, and these contractions were longer and more variable in length than those induced by intravenous oxytocin. There was no difference in basal uterine tone or in the amplitude of contractions. A comparison was made between the outcome of labour induced by low amniotomy and either oral prostaglandin E2 tablets 0-5 mg. hourly in 65 patients, or intravenous ocytocin in 41 patients. This dose of prostaglandin E2 tablets was an inadequate adjunct to low amniotomy in nulliparous patients. Despite this, the induction-delivery interval for the whole prostaglandin group was not significantly greater than that for the oxytocin group. There were no significant differences in fetal heart rate pattern, or in the incidence of gastro-intestinal side-effects between the two groups.     

Randomized, double-masked comparison of oxytocin dosage in induction and augmentation of labor.

OBJECTIVE: To test the hypothesis that high-dose oxytocin, when used in a masked fashion, would result in shorter labors and less need for cesarean delivery. METHODS: We conducted randomized, double-masked trials of high-dose compared with low-dose oxytocin for augmentation and induction of labor. Patients were randomly assigned to receive oxytocin by either a low-dose protocol (1.5 mU/minute initially, increased by 1.5 mU/minute every 30 minutes) or a high-dose protocol (4.5 mU/minute initially, increased by 4.5 mU/minute every 30 minutes). Oxytocin solutions were prepared by a central pharmacy and infusion volumes (mL/hour) were identical, thus ensuring double masking. RESULTS: A total of 1307 patients were randomized (induction, 816; augmentation, 491). In the group receiving oxytocin for induction, high-dose oxytocin was associated with a significant shortening of labor (oxytocin to complete dilatation: 9.7+/-0.3 compared with 7.8+/-0.2 hours, P<.001; oxytocin to delivery: 10.5+/-0.3 compared with 8.5+/-0.3 hours, P<.001). The cesarean delivery rate with low-dose oxytocin was 15.0%, compared with 11.3% with high-dose oxytocin (P = .17). For nulliparous women undergoing induction, cesarean delivery rates were as follows: Total 17.3% (low dose) compared with 11.7% (high dose), P = .15; cephalopelvic disproportion 11.9% (low dose) compared with 5.9% (high dose), P = .06. When used for augmentation, high-dose oxytocin again was associated with a significant shortening of labor without a significant difference in cesarean birth rates. No differences in neonatal outcomes were noted between the groups for either augmentation or induction. CONCLUSION: When used in a double-masked fashion, high-dose oxytocin is associated with significantly shorter labors without any demonstrable adverse fetal or neonatal effects.     

The effects on the fetus of an abnormal contraction pattern in the induction of labor with oxytocin

In a group of 29 pregnant women labor was induced with the help of an oxytocin infusion. The intrauterine pressure and fetal heart rate were monitored continuously; at the same time the pH, pCO₂, buffer base, and base excess of the fetus were repeatedly measured. The same measurements were carried out in a control group consisting of 47 pregnant women, who gave birth spontaneously at term without pathology occurring. Thirteen times (nine times in the oxytocin group and four times in the control group) there was initially a period of irregular uterine activity, accompanied by an increased basal tone (≥ 20 mm. Hg). It seems that during this period there may be a deterioration in the acid-base balance of the child. The possible etiology and consequences of these phenomena are discussed with respect to induction by an oxytocin infusion in a pregnancy in which the fetomaternal exchange is already disturbed.     

Trial of scar with induction/oxytocin in delivery following prior section

During the ten year study period, April 1972 to March 1982, there were 1,498 patients, with one or more prior caesarean section delivered at the Regional Hospital, University College, Galway. Trial of scar (TOS) was undertaken in 844 (56.34%) patients and the remaining 654 (43.66%) had a repeat elective caesarean section. There were 546 (64.69%) TOS patients who had some form of induction/augmentation and in 269 (49.26%) oxytocin was used, singularly and in combination with other induction methods and successful vaginal delivery was attained in 222 (82.52%) patients. There was no increased incidence of true rupture (TR) or bloodless dehiscence (BD) associated with the use of induction/augmentation or oxytocin in this series. There was a 50% perinatal mortality associated with TR, but there was no maternal death in TOS patients, with or without a successful trial. An incidence of TR of 1:169 patients is no justification for the "once a section, always a section" idiology, widely practiced in North America today.     

Pulsatile administration of oxytocin for augmentation of labor

In a randomized study, 94 patients with term pregnancies underwent augmentation of labor with either continuous or pulsed (every 8 minutes) intravenous oxytocin infusion. There were no significant differences with respect to the maternal characteristics, cervical dilatation and effacement, induction-to-labor interval, induction-to-delivery interval, cesarean section rate, analgesia for labor, or low Apgar scores. No hyperstimulation was noted in either group. In each group, 20% of the patients had dysfunctional labor patterns, with coupling and tripling of the uterine contractions. The mean +/- SEM oxytocin administered in the pulsed-infusion group was significantly lower than that in the continuous-infusion group (2.1 +/- 0.4 versus 4.1 +/- 0.4 mU/minute; P less than .001). The mean +/- SEM total amount of oxytocin administered was 1300 +/- 332 mU for the pulsed group and 1803 +/- 302 mU for the continuous group, indicating that lower amounts of oxytocin were required for pulsed administration. Our study demonstrates that pulsatile administration of oxytocin is similar in efficacy to our standard continuous oxytocin infusion and requires a lower total amount and rate of oxytocin administered, which may afford a greater margin of safety.     

Uterine and fetal Doppler flow changes after misoprostol and oxytocin therapy for induction of labor in post-term pregnancies.

OBJECTIVES: To compare the effect of misoprostol vs. oxytocin on blood flow in uteroplacental circulation during labor induction. METHODS: Ninety-one women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or intravenous oxytocin by means of a randomization table generated by computer. Doppler velocimetry of umbilical, uterine and arcuate arteries was performed immediately before and 2-3 h after administration of misoprostol or oxytocin. Pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratios were measured for these arteries. The SAS system was used to perform statistical analysis. RESULTS: There were no significant changes of PI, RI and S/D ratios in umbilical arteries during misoprostol and oxytocin inductions. Vaginal application of misoprostol significantly increased PI, RI and S/D ratios in arcuate arteries and S/D ratio in uterine arteries. CONCLUSIONS: Our results indicate that intravaginal misoprostol administration increases uteroplacental resistance but probably does not substantially affect placental perfusion.