Ritodrine Tocolysis Research Articles

Effect of ritodrine tocolysis on fetal cardiac output distribution to the placenta

Background: Adequate placental perfusion is important for fetal development and well-being, but the effect of tocolysis on placental perfusion is unclear. The aim of this study was to evaluate changes in fetal cardiac output distribution to the placenta following ritodrine tocolysis. Methods: This retrospective study involved 244 ultrasound findings in 142 singleton cases of appropriate for gestational age fetuses. The fetal cardiac output distribution to the placenta was defined and calculated as the percentage of umbilical vein flow volume (UVFV) based on the combined cardiac output (CCO). Ultrasound findings of 28 patients in the ritodrine group and 114 patients in the control group were compared using the unpaired t-test and Mann-Whitney U-test. Results: The CCO and UVFV increased as gestation progressed. On the other hand, distribution to the placenta was constant at approximately 15% from 28 to 35 weeks of gestation. Compared with the control group, the ritodrine group showed a significant increase in fetal heart rate, and the CCO also increased. The increase in UVFV in the ritodrine group was attributed to a significant increase in both the umbilical vessel diameter and blood flow velocity. As a result, distribution to the placenta in the ritodrine group was constant at about 20% and had a 5% increase at each week of gestation compared to the control group. Conclusions: To conclude, ritodrine tocolysis increased the fetal cardiac output distribution to the placenta. Additional research is required to determine whether tocolysis improves the placental perfusion in fetal growth restriction due to reduced placental perfusion.

Evaluation of Creatine Kinase, Lactate Dehydrogenase, and Amylase Concentrations in Umbilical Blood of Preterm Infants after Long-Term Tocolysis

Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of this study was to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood. This study included 215 preterm infants born to women treated with and without ritodrine hydrochloride. CK, LDH, and amylase levels in the umbilical blood at delivery were determined. Infants were divided according to the ritodrine tocolysis, as follows: Group A (n = 91), not exposed to ritodrine; Group B (n = 44), IV ritodrine for <1 week; Group C (n = 80), IV ritodrine for ≥1 week. The CK concentration in cord blood of Group C (198.8 ± 14.2 IU/L) was significantly higher in comparison with Group A (155.0 ± 7.3 IU/L, P < 0.05). There was no significant difference in LDH and amylase levels in the three groups. The CK significantly correlated with gestational age (r = 0.42, P < 0.01) and birth weight (r = 0.38, P < 0.01). LDH and amylase levels did not change with gestational age nor birth weight. In conclusion, long-term ritodrine tocolysis leads to increased umbilical blood CK level.

Risk factors for cerebral palsy in preterm infants

Objective To identify crucial factors that precipitate cerebral palsy by controlling confounding factors in logistic regression analyses. Design and patients We retrospectively investigated a cohort of all 922 infants with gestational ages of less than 34 weeks (22–33 weeks), who were admitted to our neonatal intensive care unit between 1990 and 1998. Thirty (3.7%) were diagnosed to have cerebral palsy. We analyzed the prenatal and postnatal clinical variables of the cerebral palsy cases and compared them with 150 randomly selected controls. Results Risk factors for cerebral palsy identified in univariate analysis were: twin pregnancy, long-term ritodrine tocolysis, respiratory distress syndrome, air leak, surfactant administration, intermittent mandatory ventilation, high frequency oscillation, lowest PaCO 2 levels, prolonged hypocarbia during the first 72 h of life, and postnatal steroid therapy. In a conditional multiple logistic model, long-term ritodrine tocolysis, prolonged hypocarbia and postnatal steroid therapy remained associated with an increased risk of cerebral palsy after adjustment for other antenatal and postnatal variables (OR [Odds Ratio]=8.62, 95% CI [Confidence Interval], 2.18–33.97; OR=7.81, 95% CI, 1.42–42.92; OR=21.37, 95% CI, 2.01–227.29, respectively). Conclusions Our results suggest that long-term ritodrine tocolysis underlines the development of cerebral palsy. Further assessments of the effect of ritodrine on fetal circulation and nervous system are required. Moreover, possible alternatives to systemic postnatal steroids are needed, and carbon dioxide levels should be more strictly controlled.

Conservative surgical management of placenta percreta: two cases with an emphasis on tubal patency

A 32-year-old woman, gravida 2 para 1, was hospitalized in the 31st week of gestation with a diagnosis of preterm labor. Ritodrine tocolysis failed to control uterine contractions, and an emergency cesarean section was performed for a decelerative fetal heart rate tracing. After the infant was delivered, ligation of the bilateral uterine arteries and their anastomoses with the ovarian arteries was performed. A 4×6-cm ellipsoid area of the anterior uterine corpus with placenta percreta was excised. Unilateral tubal occlusion was noted on hysterosalpingography 3 months after surgery, but the patient refused further interventions. The second case we present is that of a 28-year-old woman, gravida 3 para 2, who had her third cesarean delivery at the 38th week of gestation because of bleeding from placenta previa. We performed a repeat laparotomy for decreasing hemoglobin levels and drained 1,600 ml of blood from the abdomen. The bilateral uterine arteries and their anastomoses with ovarian arteries were ligated. Retained placental fragments were removed, and the bleeding areas were sutured. Despite resuturing of the vertical incision, uterine bleeding and hypotonia were observed, and transuterine sutures were inserted. Unilateral left tubal occlusion was observed on hysterosalpingography 3 months after surgery, and hysteroscopic balloon tuboplasty and laparoscopic tubal adhesiolysis were performed.

Tocolysis in term breech external cephalic version

Objectives To study the effect of ritodrine tocolysis on the success of external cephalic version (ECV) and to assess the role of ECV in breech presentation at our centre. Material and methods A prospective randomized double-blind-controlled trial comparing ritodrine and placebo in ECV of singleton term breech pregnancy at a tertiary hospital. Results Among the 60 patients who were recruited, there was a success rate of 36.7%. Ritodrine tocolysis significantly improved the success rate of ECV (50% vs. 23%; P=0.032). There was a marked effect of ritodrine tocolysis on the ECV success in nulliparae (36.4% vs. 13.0%) and multiparae (87.5% vs. 57.1%). External cephalic version has shown to reduce the rate of cesarean section for breech presentation by 33.5% in our unit. Conclusion External cephalic version significantly reduced the rate of cesarean section in breech presentation, and ritodrine tocolysis improved the success of ECV and should be offered to both nulliparous and parous women in the case of term breech presentation.

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis

Objectives: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. Methods: For an open randomized study, patients with preterm labor ( N=185) were allocated to groups to receive ritodrine intravenously ( N=90) or nifedipine orally ( N=95). Results: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65±12 vs. 70±8, P=0.001) and 48 h (65±12 vs. 71±8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105±17 vs. 86±13, P<0.0001) and 48 h (100±21 vs. 85±12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68±2.53 vs. 4.93±1.23, P=0.0016), while mean potassium levels were lower (3.52±0.84 vs. 3.81±0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. Conclusions: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

Changes in fetal hemodynamics with ritodrine tocolysis.

To evaluate the effect of ritodrine on the fetal cardiovascular system. Cardiac and extracardiac Doppler waveforms were recorded in 12 fetuses prior to and during ritodrine therapy used for preterm labor. Maternal and fetal heart rates, the Doppler pulsatility indices of the umbilical artery, middle cerebral artery, descending thoracic aorta and renal artery, and time velocity integrals of the atrioventricular valves and the ductus arteriosus, were measured. Ritodrine infusion caused an increase in maternal and fetal heart rates, the left cardiac output as measured by the product of time velocity integral and heart rate, and the pulsatility index of the middle cerebral artery, and a decrease in the pulsatility index of the umbilical artery. Ritodrine infusion may alter placental and cerebral blood flow and may have a selective effect on the left side of the heart.

Effects of tocolytic treatment with ritodrine on cardiovascular autonomic regulation.

To study the acute effects of tocolytic treatment with intravenous ritodrine on cardiovascular autonomic regulation. Validated methods to assess cardiovascular autonomic nervous function-heart rate and blood pressure variability and vagal cardiac baroreflex sensitivity-were measured before and during ritodrine infusion. Turku University Central Hospital, Turku, Finland. Twelve pregnant women admitted to hospital for threatened preterm labour. Electrocardiogram and continuous noninvasive finger blood pressure signals were recorded in each woman, resting in a supine position. Autoregressive spectrum analysis was used to quantify short term heart rate and blood pressure variability. Vagal cardiac baroreflex sensitivity was measured as the bradycardia response to an intravenous bolus injection of phenylephrine. Vagal cardiac baroreflex sensitivity and spectrum analysis indices of short term heart rate and blood pressure variability. Ritodrine significantly decreased vagal cardiac baroreflex sensitivity as well as total (0.00-0.40 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power bands of the heart rate variability spectrum. Ritodrine significantly increased mean heart rate and the low frequency power band of the systolic blood pressure variability spectrum. In pregnant women with threatened preterm labour intravenous administration of ritodrine decreases vagal cardiac baroreflex sensitivity and vagal modulation of heart rate, and increases sympathetically mediated blood pressure variability. Decreased baroreflex sensitivity and heart rate variability are known to be associated with a poor prognosis in some patient groups, so the effects of ritodrine tocolysis may be unfavourable in women with impaired circulatory homeostasis.

Obstetric risk factors for periventricular leukomalacia among preterm infants.

To evaluate the obstetric antecedents of cystic periventricular leukomalacia and transient echodense periventricular lesions among preterm infants. A cohort study of preterm singleton infants born between 25 and 33 weeks gestation. Pavia, Italy. Three hundred and forty-nine infants admitted to a Division of Neonatal Intensive Care who were screened for periventricular leukomalacia. The obstetric factors in infants with either cystic periventricular leukomalacia or transient echodense periventricular lesions were compared to those in infants with negative cranial ultrasonographic findings. Stepwise multiple logistic regression analysis was used to evaluate the association between risk factors and outcomes adjusting for confounders. The prevalence of cystic periventricular leukomalacia and transient echodense lesions was 5.7% (20/349) and 14% (49/349), respectively. The main risk factors for cystic leukomalacia were first trimester haemorrhage (OR 4.49; 95% CI 1.63-12.39), maternal urinary tract infection on admission (OR 5.71; 95% CI 1.91-17.07), and neonatal acidosis (pH < 7.2) at birth (OR 5.97; 95% CI 1.93-18.52). Meconium-stained amniotic fluid (OR 3.95; 95% CI 1.42-10.98) and long term (> 72 hours) ritodrine tocolysis (OR 2.54; 95% CI 1.28-5.05) were associated with an increased risk of echodense lesions. The likelihood of overall leukomalacia (cystic plus echodense periventricular lesions) was increased among cases with meconium-stained amniotic fluid (OR 4.06; 95% CI 1.65-10.0), long-term ritodrine tocolysis (OR 2.56; 95% CI 1.38-4.72), maternal infection (OR 1.73; 95% CI 1.0-3.0), and acidosis at birth (OR 1.98; 95% CI 1.0-3.98). This study confirms that maternal infection, acidosis at birth, and meconium-stained amniotic fluid increase the risk of periventricular leukomalacia in preterm infants. Long-term ritodrine use seems to increase the risk for transient echodense lesions.

Does the use of a tocolytic agent affect the success rate of external cephalic version?

OBJECTIVE: Our purpose was to study the effect of ritodrine tocolysis on the success rate of external cephalic version at ≥36 weeks' gestation. STUDY DESIGN: This was a prospective, double-blinded, randomized study. All patients were at ≥36 weeks' gestation, confirmed by early ultrasonography. External cephalic version assessment included nonstress testing before and after external cephalic version and ultrasonographic evaluation of type of breech, estimated fetal weight, position of placenta and fetal spine, and amniotic fluid index. Patients were excluded if the breech was not mobile or if they had any contraindications to tocolysis or external cephalic version. After randomization 283 patients received either ritodrine (111 μg/min) or identical placebo by intravenous infusion for ≥20 minutes. Up to three attempts at external cephalic version under ultrasonographic surveillance were performed. With an α error of 0.05 and a β of 0.2, 264 patients were required to complete this study. RESULTS: There were no differences between study groups in maternal age, body mass index, gestational age, amniotic fluid index, position of fetal spine, and placental location. Statistical analysis controlled for parity because parity had a major influence on success rates. There was a higher success rate in the group receiving ritodrine tocolysis (52% vs 42%, p = 0.028). Ritodrine improved success rates in nulliparous patients (43% vs 25%, p = 0.026) but not in parous subjects (66% vs 58%, p = 0.385). CONCLUSION: Ritodrine tocolysis improves the success rate of external cephalic version performed at ≥36 weeks in nulliparous patients. (Am J Obstet Gynecol 1996;175:859-61.)

The impact of external cephalic version on the rate of vaginal and cesarean breech deliveries: a 3-year cumulative experience

The authors have reviewed the impact of their practice of external cephalic version (ECV) at term, with respect to success rate, factors associated with successful version and the effect of this protocol on the overall breech and cesarean breech rate. Two hundred and forty-nine parturients identified as having a breech presenting fetus after the 36th gestational week over a 3-year period, after excluding contraindicated cases, were offered a trial of ECV, with the use of ritodrine tocolysis. ECV was effected by one operator, using the minimally effective force necessary. Successful ECV was achieved in 196 attempts (78.7%). No deleterious effects in fetuses or mothers were noted. Of successfully turned fetuses, 78% eventually had a vaginal vertex delivery. Parity, birthweight and amount of amniotic fluid were found to have a significant effect on the success rate of ECV, whereas gestational age at version or placental location were not found to have a significant effect on success rate. Introduction of the ECV protocol effected a significant decrease in breech presentation at term, from 3.9 to 2.4% ( P < 0.01), which can be translated into a decrease of 5.5% in the overall cesarean section rate. The authors conclude that ECV is a safe and effective procedure, in properly selected cases. Institution of a screening protocol to identify breech presentation after 36 weeks, and utilizing ECV where possible, may lead to a significant reduction in the breech delivery rate, and may prevent serious infant morbidity.

External cephalic version after previous cesarean section—a clinical dilemma

OBJECTIVES: To describe our limited experience with external cephalic version from breech to vertex presentation at term, with the use of ritodrine tocolysis, in women who had undergone a previous cesarean delivery. METHODS: Eleven parturients after previous cesarean delivery underwent external version after 36 gestational weeks, utilizing tocolysis with ritodrine, after excluding cases of lowlying placenta, severe oligohydramnion or ruptured membranes. Patients were then followed until delivery and scar examination was carried out after vaginal delivery, or at re-cesarean section, according to mode of delivery. RESULTS: All 11 attempted versions were successful. Six patients subsequently delivered vaginally and five by re-cesarean section. None of the uterine scars showed any signs of dehiscence. Three of the five infants delivered by re-cesarean section weighed over 4000 g, whereas all of the vaginally-delivered infants weighed under 3500 g. CONCLUSIONS: External cephalic version to vertex presentation after previous cesarean section was successful in all 11 carefully selected patients. No untoward effects were noted, and no signs of scar dehiscence were found. The safety and efficacy of this procedure after previous cesarean delivery should be examined further.

Fetal cardiac effects of oral ritodrine tocolysis.

The beta-sympathomimetic oral tocolytic ritodrine can cause maternal tachycardia and hypotension, and may cross the placenta. A new echocardiographic technique has been developed to explore fetal and placental ritodrine effects. Values in 76 healthy historic controls were compared to 18 studies in 16 patients performed while receiving stable oral ritodrine therapy, measured both at baseline and 30 minutes after a dose. Data collected included maternal pulse and blood pressure (BP), fetal cerebral and umbilical Doppler waveforms, and fetal heart rate. A new index of fetal myocardial contractility, combined ventricular shortening fraction, was derived from two-dimensionally directed M-mode. Maternal pulse and BP, fetal heart rate and heart size, and all Doppler indices were normal, without demonstrable dose-response effects. In the control subjects, combined ventricular shortening fraction fell with increasing gestational age (combined ventricular shortening fraction = -0.27 estimated gestational age + 49; r = 0.27; P < or = 0.02; standard error of the estimate, 11%). However, combined ventricular shortening fraction in ritodrine patients was abnormally decreased in 72% of cases. The mean index in normal subjects was 43 +/- 5%, but in ritodrine patients it was only 31%. We conclude that a history of premature labor or oral ritodrine, or both, is associated with reduced shortening fraction. Since there was no change in placental resistance, cerebral hypoxia, fetal heart rate, or heart size (preload), then low shortening fraction may be due to increased fetal systemic vascular resistance (BP) or decreased myocardial contractility.

Currently recommended oral regimens for ritodrine tocolysis result in extremely low plasma levels

Our aim was to compare plasma drug levels in patients receiving ritodrine intravenously with those in patients receiving ritodrine orally at recommended dosages. Plasma samples from 20 pregnant patients treated with intravenous ritodrine (50 to 300 micrograms/min), 9 patients treated with oral ritodrine only (60 to 120 mg per 24 hours), and 9 patients treated first with intravenous and subsequently with oral ritodrine were analyzed for ritodrine concentration with the use of high-performance liquid chromatography. Average plasma ritodrine levels of patients receiving different intravenous dosages ranged from 27.8 +/- 3.5 to 113.3 +/- 38.8 ng/ml. Levels during oral therapy ranged between 9.8 +/- 3.2 and 13.8 +/- 4.4 ng/ml. In both modes of drug delivery, concentrations were significantly correlated with doses. In patients treated first with intravenous ritodrine and subsequently with the oral form, plasma concentrations during oral therapy averaged 27.7% +/- 18.8% of those obtained during intravenous infusion. Subtherapeutic plasma concentrations might be responsible for the failure to demonstrate clinical benefits of oral ritodrine in prevention of recurrent preterm labor. A twofold to threefold increase in the maximum recommended oral dosage of ritodrine should be considered, especially for patients who had previously required relatively high intravenous infusion rates (> 100 micrograms/min).

Measurement of pulmonary capillary pressure during ritodrine tocolysis in twin pregnancies: a new noninvasive technique.

Five twin pregnant women were studied during treatment of preterm labor with ritodrine. Maternal pulmonary capillary pressure (PCP) and cardiac function were measured by noninvasive simultaneous recordings of the indirect carotid pulse, electrocardiography, phonocardiography, and M-mode echocardiography. Pulmonary capillary pressure significantly increased from the control value of 9 +/- 3.0 to 18 +/- 2.2 mmHg during the infusion period of therapy. Cardiac index and preejection period to left ventricular ejection time ratio were also increased during treatment with ritodrine. Our findings suggest that noninvasive measurement of PCP and cardiac function may be useful in monitoring twin pregnancies that develop cardiovascular side effects during tocolytic therapy.

171 Adverse Fetal Cardiac Effects of Oral Ritodrine Tocolysis

171 Adverse Fetal Cardiac Effects of Oral Ritodrine Tocolysis

External cephalic version of term singleton breech presentations with tocolysis: a retrospective study in a community hospital.

External version with the use of tocolysis in low-risk patients has been shown to be relatively safe and effective. A retrospective analysis was undertaken to see if version was practical for a smaller community-based hospital. Thirty-two antepartum external cephalic versions with ritodrine tocolysis during a 4-year period were reviewed. Successful version occurred in 59.4% of attempts. Of patients with a successful version, 68.4% delivered vaginally. One successful version occurred spontaneously with ritodrine tocolysis alone. A stillbirth due to abruptio placentae occurred 20 hours after a failed version attempt.

Awaiting cervical change for the diagnosis of preterm labor does not compromise the efficacy of ritodrine tocolysis

We retrospectively studied 209 patients treated with ritodrine hydrochloride to determine whether change in cervical effacement or dilatation during a period of observation before therapy would result in decreased efficacy of ritodrine, as measured by delivery delays of 48 hours, 1 week, or until ≥37 weeks' gestation; neonatal intensive care unit admission; and neonatal respiratory distress syndrome. Patients who were ≥3 cm dilated on admission were at high risk of therapy failure by all outcome measures compared with patients <3 cm dilated. For patients <3 cm dilated on admission, there was no difference in outcome when patients treated for contractions only were compared with those treated after change in effacement or dilatation had been documented. We conclude that awaiting change in cervical effacement or dilatation to be more certain of the diagnosis of preterm labor will not compromise the efficacy of ritodrine tocolysis.

Electrocardiographic Abnormalities During Ritodrine Administration

Electrocardiographic abnormalities have been reported during ritodrine tocolysis. No previous studies, however, have included controls. The purpose of this study is to evaluate the electrocardiographic tracings of patients receiving ritodrine tocolysis and compare them with those of matched controls. Holter monitors were placed on eight patients receiving ritodrine tocolysis and eight control patients for 24 hours to make continuous electrocardiographic records. Twelve-lead electrocardiograms, serum glucose, and electrolyte concentrations were monitored serially in all patients. Four of the eight patients receiving ritodrine tocolysis demonstrated ST segment depression, while none of the control patients manifested any electrocardiographic abnormalities. The observed ST segment depression appears to be related to the degree of maternal tachycardia and the level of hypokalemia and hyperglycemia that occurs during early ritodrine tocolysis.

Cardiovascular and metabolic effects associated with nifedipine and ritodrine tocolysis

Recent investigations have indicated that nifedipine, a calcium channel entry blocker, may be useful in the treatment of preterm labor. This prospective, randomized study compares cardiovascular and metabolic effects measured in association with sublingual and oral administration of nifedipine with those noted with the intravenous and oral administration of the R-adrenergic agent ritodrine. Serial measurements of cardiovascular parameters, hematocrit, electrolytes, glucose, blood urea nitrogen, creatinine, calcium, and serum glutamic-oxaloacetic and glutamic-pyruvic transaminase were compared between groups. Sublingual and oral nifedipine caused minimal cardiovascular alterations. At doses sufficient to achieve tocolysis, ritodrine caused more pronounced cardiovascular changes than nifedipine. Both agents had a hemodilutional effect, but nifedipine was not associated with alterations in serum electrolytes or a dramatic hyperglycemia. On the basis of this study, it appears that the use of nifedipine for preterm labor management is associated with hemodilutional changes but not the adverse cardiovascular or metabolic effects often associated with ritodrine tocolysis.