Pulsatile administration enhances the effect and reduces the dose of oxytocin required for induction of labor

Pulsatile administration of oxytocin was compared with continuous infusion of oxytocin for induction of labor in pregnant rats. The dosages consisted of intravenous injections of 0, 2.5, and 5 mU oxytocin every 10 minutes and intravenous infusion of 1 mU/minute of oxytocin in 0.9% sodium chloride. These doses are within the range of endogenously secreted pulses. All treatments began on day 22 at 2 p.m. and continued for 8 hours. Pulsatile administration resulted in a marked reduction in the dose of oxytocin required to induce labor. Using 5 mU pulses, birth was induced with 18.4%, and using 2.5 mU pulses, with 24% of the dose needed using continuous infusion. Parturition was advanced by 12 hours on the average by oxytocin treatment, but no significant differences were observed between the various oxytocin dosage regimens in this regard or in regard to gestation length, induction-delivery interval, duration of delivery, or the proportion of living or dead pups. Significantly more uterine activity was induced with each mU of oxytocin using pulsatile administration than using continuous infusion. There was no evidence for down-regulation of oxytocin receptors during a continuous infusion of oxytocin. We postulate that the greater efficacy of oxytocin pulses to induce uterine activity and delivery in comparison to continuous infusions is due to a more effective stimulation of prostaglandin F2 alpha release from the decidua. The amount of oxytocin needed for induction of labor with 2.5 mU pulses was similar to the decrease in neurohypophyseal oxytocin content during the first stage of spontaneous labor, and uterine activity elicited was also similar to that observed during spontaneous labor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsatile oxytocin for induction of labor: a randomized prospective controlled study

In a prospective randomized study, 20 patients with term pregnancies underwent induction of labor with either continuous or pulsed (every 8 minutes) intravenous oxytocin infusion. There were no significant differences with respect to induction-labor interval, induction-delivery interval, cesarean section rates, need for pain relief and Apgar scores. Sixty percent of patients receiving continuous oxytocin infusion developed uterine hyperstimulation but only 10% receiving pulsed oxytocin did so. However, the difference was not significant. The mean +/- SEM total amount of oxytocin given by continuous infusion was 4237 +/- 1066 mU which was 70% more than by pulsatile infusion (2454 +/- 808 mU). The highest rate of oxytocin infused was significantly lower by pulsatile administration (5.2 +/- 0.8 mU/min) than by continuous infusion (9.2 +/- 1.8 mU/min, p = less than 0.05). Our study demonstrates that pulsed administration of oxytocin every 8 minutes is as effective and safe as continuous intravenous infusion of oxytocin for induction of labor, requires less oxytocin with therefore, a wider margin of safety and is consistent with the pulsatile release of oxytocin during normal labor.     

Active-phase labor arrest: oxytocin augmentation for at least 4 hours

OBJECTIVE: To assess a labor-management protocol that mandated at least 4 hours of oxytocin augmentation before cesarean delivery for active-phase labor arrest. METHODS: We prospectively evaluated term gravidas in spontaneous labor with active-phase labor arrest (cervix at least 4 cm dilated and 1 cm or less of cervical progress in 2 hours). Exclusion criteria included nonvertex presentation, previous cesarean, multiple gestation, and a nonreassuring fetal heart rate tracing or chorioamnionitis at the time of labor arrest. After the diagnosis of active-phase arrest, oxytocin was initiated with an intent to achieve a sustained uterine contraction pattern of greater than 200 Montevideo units. Cesarean delivery was not performed for labor arrest until at least 4 hours of a sustained uterine contraction pattern of greater than 200 Montevideo units, or a minimum of 6 hours of oxytocin augmentation if this contraction pattern could not be achieved. RESULTS: Five hundred forty-two women were managed by the protocol, and 92% delivered vaginally. The subsequent vaginal delivery rate for parous women who had not progressed (1 cm of cervical dilation or less) despite 2 hours of oxytocin augmentation was 91%, and it was 74% for nulliparas. With no labor progress after 4 hours of oxytocin augmentation, the subsequent vaginal delivery rates were 88% for parous women and 56% for nulliparas. There were no severe maternal complications. One neonate had persistent fetal circulation and one had a positive blood culture, but both did well. CONCLUSION: Extending the minimum period of oxytocin augmentation for active-phase labor arrest from 2 to at least 4 hours was effective and safe.     

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.     

High and low dose oxytocin in augmentation of labor.

OBJECTIVE: To compare the efficacy and safety of high dose oxytocin in the augmentation of labor. METHOD: Two hundred pregnant women requiring augmentation of labor were randomly assigned to receive oxytocin by either a low dose protocol (1.5 microm/min initially, increased by 1.5 microm/min every 30 min) or a high dose protocol (4.5 microm/min initially, increased by 4.5 microm/min every 30 min). RESULTS: High dose of oxytocin was associated with a significant shortening of labor 4 (1.10-10) vs. 6 (1-10) h, p<0.0001 without a significant difference in cesarean delivery rate, neonatal and maternal outcome. CONCLUSION: The use of high dose oxytocin is associated with significantly shorter labor without any adverse fetal and maternal effects.     

Does oxytocin augmentation increase perinatal risk in primigravid labor?

To assess the influence of high-dose oxytocin augmentation of spontaneous labor, a consecutive series of 30,874 primigravid term deliveries were analyzed for adverse perinatal outcome. In spite of a longer mean duration of labor, the frequencies of asphyxial perinatal death, neonatal seizures, and abnormal neonatal neurologic behavior were not significantly increased in 14,119 (45%) oxytocin-treated patients. There was no case of uterine rupture in any primigravid labor during the study. These results from 13 years of clinical practice provide reassurance about maternal and fetal safety if oxytocin is used as part of a protocol of active management to correct dystocia when spontaneous primigravid labor with vertex presentation fails to progress.     

Pulsatile versus continuous oxytocin infusion for the oxytocin challenge test

In a prospective study, 140 patients had an oxytocin challenge test with either a continuous or a pulsed infusion (one minute of infusion in every five minutes). Both infusion regimens had similar success rates in terms of uterine contractions (97.1 vs 98.6%). The potency ratio (pulsed versus continuous infusion) was significant at 2.7 (1.27 to 5.2), which means that more uterine activity was induced with each mU of oxytocin with pulsatile than with continuous administration. The total amount of oxytocin required to obtain three good contractions in 10 minutes was about 40% less with pulsed administration than with continuous infusion, but the test took 40 minutes longer with the pulsed than with the continuous infusion (P<0.01).     

Oxytocin augmentation of dysfunctional labor. V. An alternative oxytocin regimen

A regimen is described in which the time from the start of a large dose of oxytocin to a myometrial response was used for selection of a maintenance dose. The method is based on our experience that continuous intravenous doses of oxytocin in the therapeutic range for the augmentation of labor require about 40 minutes of intravenous infusion to achieve a steady-state plasma concentration of oxytocin. The method effectively identified the proper maintenance dose on the first attempt in 43 of 59 patients (73%) and on the second in 58 of 59. The doses selected effected cervical dilatation in 55 of 59 cases (93%). Comparison of the timed dose method with an arithmetic progression regimen revealed the former method to select the minimum effective dose more rapidly, but that method had no advantage in shortening the time from the start of oxytocin to complete cervical dilatation. Examination of the plasma concentration of oxytocin by radioimmunoassay demonstrates that the maintenance dose selected by the duration of the interval from the start of infusion to a myometrial response sustains the plasma oxytocin concentration obtained by the initial dose. These data lend additional evidence that any particular dose of oxytocin in the therapeutic range requires approximately 40 minutes to achieve a steady-state plasma concentration.     

Low-dose versus high-dose oxytocin augmentation of labor — A randomized trial

OBJECTIVE: Our purpose was to compare the efficacy and safety of low-dose versus high-dose oxytocin regimens in the augmentation of labor.STUDY DESIGN: Three hundred ten term pregnancies requiring augmentation of labor underwent randomization to receive either a low-dose or high-dose oxytocin augmentation regimen. Maternal demographics, labor-delivery data, and neonatal outcome were compared.RESULTS: The hgih-dose oxytocin group had a significant lower cesarean section rate, regarless of parity (10.4% vs 25.7%. p < 0.001), with no differences in maternal complications and neonatal outcomes. The time needed to correct the labor abnormality as also significantly decreased (1.24 ± 1.4 hours vs 3.12 ± 1.6 hours, p < 0.001) in the high-dose group.CONCLUSIONS: The use of a high-dose oxytocin regimen benefits both nulliparous and multiparous women requiring labor augmentation by significantly lowering both the time necessary to correct the labor normality and the need for cesarean section.     

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.     

Nipple stimulation for labor augmentation

A randomized, prospective study was undertaken to evaluate the efficacy of nipple stimulation with a breast pump as compared to oxytocin for augmentation of labor. The average and maximal uterine activity achieved was significantly higher in the oxytocin-stimulated group, without significant differences in the length of labor stages, cesarean section rate, Apgar scores or umbilical artery pH. Fifty percent of the patients failed to respond to nipple stimulation after 30 minutes and were switched to oxytocin. These patients experienced a more rapid rate of cervical dilation in the active phase and reached higher maximal uterine activity with oxytocin stimulation; however, the cesarean section rate was highest in this group. Nipple stimulation with a breast pump appears to be a safe and effective alternative to oxytocin for the augmentation of labor.     

Prospective randomized trial of oxytocin administration for active management of the third stage of labor

Objective

To determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor.

Methods

A prospective randomized study was done at one center in Ankara, Turkey, between January and October 2010. Women with a singleton pregnancy (> 37 weeks) who had a live vaginal birth were randomly allocated to four groups: iv-A (intravenous oxytocin after delivery of the fetus), iv-B (when anterior shoulder seen), im-A (intramuscular oxytocin after delivery), and im-B (when anterior shoulder seen). Postpartum blood loss within the first hour, hemoglobin, hematocrit, and duration of the third stage were compared.

Results

A total of 600 eligible women were recruited; 150 were assigned to each group. Postpartum blood loss, prepartum and postpartum hemoglobin and hematocrit, and need for additional uterotonics were similar among groups (P > 0.05). The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B (P < 0.05). Among women not exposed to oxytocin before delivery, postpartum blood loss was significantly lower in group iv-B (P = 0.019). Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A.

Conclusion

Although postpartum blood loss was similar in all groups, early intravenous administration seemed to have beneficial effects.ClinicalTrials.gov: NCT01954186.