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Journal de Gynecologie, Obstetrique Et... May 2001Use of beta-sympatomimetics for threatening preterm delivery: a critical review. Preterm birth is the principal cause of perinatal and neonatal mortality and morbidity.... (Review)
Review
Use of beta-sympatomimetics for threatening preterm delivery: a critical review. Preterm birth is the principal cause of perinatal and neonatal mortality and morbidity. Over the past 40 years, numerous treatments have been tested and used to try to inhibit preterm labor. This literature review is limited to the published studies of beta-adrenergic agonists (beta-sympathomimetics). Among 36 articles that have examined the treatment of acute phase preterm labor by intravenous beta-sympathomimetic administration, 26 are clinical studies with severe biases that make them unacceptable for analysis: non-randomized clinical trials, retrospective studies or retrospective control groups, inadequate recording of pregnancy outcome, exclusion of patients after randomization, confounding factors due to the use of multiple therapeutic agents, inadequate study power.Of the 10 acceptable placebo-controlled trials, seven, including the largest (the Canadian Preterm Labor Investigators' Group, with 708 women), found that beta-sympathomimetics were not better than placebo in prolonging pregnancy or reducing neonatal morbidity. Only three studies found that they were superior to placebo. These agents cause numerous maternal side effects that may be life-threatening, because beta-adrenergic receptors are present in many organs. The cardiovascular system is the most severely affected, but side effects also concern the pancreas, kidneys, intestines, and liver. beta-Sympathomimetics cross the placenta rapidly. Fetuses probably respond in the same way their mothers do to stimulation of their beta-adrenergic receptors. Nonetheless, data from the controlled clinical trials show no difference in neonatal mortality or severe morbidity between children born to mothers treated with beta-sympathomimetics and those born to mothers in control groups. The efficacy of preventive treatment by oral or subcutaneous administration of beta-sympathomimetics has also been assessed: a meta-analysis and 2 large randomized placebo-controlled trials have showed that oral maintenance treatment offers no advantages over placebo during the latency phase or for the recurrence rate of preterm labor and the rate of preterm delivery. A single - and smaller - placebo-controlled study found that oral maintenance treatment with ritodrine was beneficial. Treatment trials of subcutaneous administration of beta-sympathomimetics have been performed with a portable subcutaneous pump. Ten studies of this method have been reported, but only two were randomized trials. They found no significant difference in either the mean time until delivery or neonatal morbidity.
Topics: Adrenergic beta-Agonists; Clinical Trials as Topic; Female; Humans; Obstetric Labor, Premature; Placebos; Pregnancy; Pregnancy Outcome; Retrospective Studies; Tocolysis
PubMed: 11397997
DOI: No ID Found -
American Journal of Obstetrics and... Jul 1990Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this prospective, randomized trial to evaluate the efficacy and maternal, fetal, and neonatal outcome associated with tocolysis with nifedipine or ritodrine. Delivery was delayed for 48 hours, 7 days, and until the thirty-sixth week of gestation in 84%, 70%, and 41%, respectively, of patients in the nifedipine group, compared with 72%, 63%, and 52% of patients in the ritodrine group (difference not significant). Maternal side effects were more common and more serious in the group of patients who received ritodrine compared with those who received nifedipine (18 of 38 versus 5 of 38, p less than 0.01); however, fetal and neonatal outcome appeared to be similar when the groups were compared. On the basis of this study, it appears that tocolysis with either nifedipine or ritodrine is equally efficacious; however, maternal side effects are less common with nifedipine treatment. We conclude that nifedipine may have a role in the treatment of preterm labor but suggest further careful evaluation of this agent before it is considered for routine clinical use.
Topics: Female; Humans; Nifedipine; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Prospective Studies; Randomized Controlled Trials as Topic; Ritodrine; Tocolytic Agents
PubMed: 2197860
DOI: 10.1016/s0002-9378(11)90679-6 -
Case Reports in Women's Health Jan 2020Ritodrine hydrochloride is still widely used as a tocolytic agent in Japan, but it can cause maternal pulmonary edema, which may paradoxically induce preterm birth. Here...
INTRODUCTION
Ritodrine hydrochloride is still widely used as a tocolytic agent in Japan, but it can cause maternal pulmonary edema, which may paradoxically induce preterm birth. Here we present a case of severe pulmonary edema due to <48 h of ritodrine administration.
CASE
A 46-year-old woman was diagnosed with threatened preterm labor (TPL) and placenta previa at 26 weeks of gestation. She had mild uterine contractions and genital bleeding. Ritodrine hydrochloride, magnesium sulfate, and betamethasone were administered. She developed dyspnea 46 h after starting ritodrine administration. Chest X-ray showed pulmonary edema. Even after cessation of ritodrine, dyspnea did not lessen and there were regular uterine contractions with abdominal pain. Emergency caesarean section was performed. A female neonate was delivered and admitted to the neonatal intensive care unit. After surgery, maternal dyspnea decreased without any complications.
DISCUSSION
Excessive use of ritodrine or its use in combination with other tocolytic agents can cause maternal pulmonary edema, even with <48 h of use. Adverse maternal side-effects and rebound uterine contractions due to cessation of ritodrine may paradoxically trigger preterm birth. Strict patient selection for tocolytic therapy is essential and ritodrine requires caution because of its potential side-effects.
PubMed: 31956518
DOI: 10.1016/j.crwh.2020.e00173 -
JA Clinical Reports 2017A 36-year-old parturient with a suspicion of placenta accreta under tocolytic therapy with ritodrine infusion underwent emergency cesarean section under general...
A 36-year-old parturient with a suspicion of placenta accreta under tocolytic therapy with ritodrine infusion underwent emergency cesarean section under general anesthesia with propofol, ketamine, and remifentanil because massive bleeding was anticipated. The ritodrine infusion was discontinued 1 h before cesarean section. The baby was delivered 6 min after induction of anesthesia. However, after the manual removal of the placenta from the uterus, the bleeding was massive and uncontrollable. We rapidly transfused crystalloid, colloid, and red blood cells through potassium removal filter. Hyperkalemia (5.8 mmol/L) was detected just before blood transfusion. One hour later, hemostasis was still difficult, and hyperkalemia was promoted (6.1 mmol/L). Thus, glucose insulin therapy started with intravenous furosemide to treat hyperkalemia. Gynecologists decided to induce the Bakri balloon tamponade for the treatment of postpartum hemorrhage. At the end of surgery, plasma potassium level also reduced to 5.5 mmol/L. In the ICU, the bleeding still continued, and then radiologists performed bilateral internal iliac artery embolization for full hemostasis. Postoperative plasma potassium level was stable and 3.3 mmol/L in the next morning. Although one of the common adverse reactions of ritodrine is hypokalemia, we should also beware of a rebound hyperkalemia after its cessation.
PubMed: 29492442
DOI: 10.1186/s40981-016-0071-4 -
The New England Journal of Medicine Jul 1992Beta-adrenergic agonists are commonly used to arrest premature labor. Although treatment of preterm labor with these agents can delay delivery by 24 to 48 hours, the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Beta-adrenergic agonists are commonly used to arrest premature labor. Although treatment of preterm labor with these agents can delay delivery by 24 to 48 hours, the potential risks and benefits to the mother and infant before and after delivery have not been adequately assessed.
METHODS
We randomly assigned 708 women with preterm labor at six hospitals to receive an intravenous infusion of either the beta-adrenergic agonist ritodrine (n = 352) or placebo (n = 356). Assignment was made with stratification according to four categories of gestational age (20 to 23 weeks, 24 to 27 weeks, 28 to 31 weeks, and 32 to 35 weeks). The primary objective was to assess the effect of ritodrine on perinatal mortality. Secondary objectives were the evaluation of the causes of perinatal death, the extent to which delivery was delayed with ritodrine, and the effects on birth weight, maternal morbidity, neonatal morbidity, and infant morbidity at 18 months of postnatal age, corrected for preterm delivery.
RESULTS
Among the 771 infants born to the women in the study (including 63 pairs of twins), there were 23 deaths (6.1 percent) in the ritodrine group and 25 deaths (6.4 percent) in the placebo group (event-rate difference, -0.3 percent; 95 percent confidence interval, -3.7 percent to 3.1 percent). There was no difference between the groups in the extent of delay of delivery, the incidence of delivery before 37 weeks' gestation, the proportion of babies weighing less than 2500 g, or measures of neonatal morbidity. Maternal morbidity (such as chest pain and cardiac arrhythmias) occurred more frequently but not exclusively in the ritodrine group. One infant born to a woman in the ritodrine group and five infants born to women in the placebo group had cerebral palsy (P = 0.09). There was a slight but not significant trend toward an improved score on the Bayley Psychomotor Development Index at 18 months of age among the infants of the ritodrine-treated women.
CONCLUSIONS
We found that the use of ritodrine in the treatment of preterm labor had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight.
Topics: Birth Weight; Female; Fetal Death; Follow-Up Studies; Gestational Age; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Ritodrine
PubMed: 1620169
DOI: 10.1056/NEJM199207303270503 -
BMC Pediatrics Aug 2021Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this...
BACKGROUND
Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature.
CASE PRESENTATION
A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 μg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified.
CONCLUSIONS
This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.
Topics: Cesarean Section; Female; Humans; Hyperkalemia; Infant; Infant, Newborn; Male; Obstetric Labor, Premature; Pregnancy; Ritodrine; Tocolytic Agents
PubMed: 34465290
DOI: 10.1186/s12887-021-02840-8 -
Anesthesiology May 1994Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the... (Comparative Study)
Comparative Study
BACKGROUND
Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the parturient receiving a beta-adrenergic agent for tocolysis has not been evaluated extensively. The current study evaluated whether ephedrine or phenylephrine better restores uterine blood flow and fetal oxygenation during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes.
METHODS
Fourteen chronically instrumented gravid ewes between 0.8 and 0.9 timed gestational age were used. On separate days, each animal underwent the experimental protocol with one of three agents: ephedrine, phenylephrine, and normal saline-control. The experimental protocol was as follows: (1) at time zero, intravenous infusion of ritodrine was begun; (2) at 120 min, 2% lidocaine was given epidurally to achieve a sensory level of at least T6; and (3) at 135 min, an intravenous bolus of either ephedrine, phenylephrine, or normal saline-control was given, followed by a continuous intravenous infusion of the same agent for 30 min. In the ephedrine and phenylephrine experiments, the rate of infusion was adjusted to maintain maternal mean arterial pressure close to baseline.
RESULTS
Ritodrine infusion alone significantly increased maternal heart rate and cardiac output in all three groups. Epidural anesthesia during ritodrine infusion significantly decreased maternal mean arterial pressure, heart rate, cardiac output, uterine blood flow, and fetal arterial oxygen tension for each of the three groups. Both ephedrine and phenylephrine restored maternal mean arterial pressure to baseline, as designed. Ephedrine significantly increased uterine blood flow and fetal arterial oxygen tension when compared with normal saline--control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with normal saline--control, but ephedrine did not.
CONCLUSIONS
Although ephedrine and phenylephrine provided similar restoration of maternal mean arterial pressure, ephedrine was superior to phenylephrine in restoring uterine blood flow during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. Also, ephedrine, but not phenylephrine, significantly improved fetal oxygenation, when compared to normal saline--control.
Topics: Acid-Base Equilibrium; Anesthesia, Epidural; Animals; Blood Pressure; Carbon Dioxide; Cardiac Output; Ephedrine; Female; Fetal Blood; Heart Rate; Heart Rate, Fetal; Hemodynamics; Humans; Hypotension; Infusions, Intravenous; Oxygen; Partial Pressure; Phenylephrine; Pregnancy; Regional Blood Flow; Ritodrine; Sheep; Uterus; Vascular Resistance
PubMed: 8017645
DOI: 10.1097/00000542-199405000-00016 -
Computational and Structural... 2023Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current...
Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.
PubMed: 37484490
DOI: 10.1016/j.csbj.2023.07.007 -
Journal of Obstetrics and Gynaecology :... Dec 2023We evaluated the impact of cervical cerclage combined with one or more uterine contraction inhibitors in persistent inhibition of uterine contraction for the treatment...
We evaluated the impact of cervical cerclage combined with one or more uterine contraction inhibitors in persistent inhibition of uterine contraction for the treatment of late abortion and premature delivery. This retrospective case series study analysed the medical data of 58 patients who underwent cervical cerclage for cervical insufficiency and simultaneously received one or more uterine contraction inhibitors (indomethacin, ritodrine, and atosiban) and magnesium sulphate at the Zibo Maternal and Child Health Hospital between January 2019 and December 2020.Patients are normal pregnancy who received cervical cerclage without complications. The rate of successful treatment was 74.14% (43/58). The prolonged gestation duration was 16.42 ± 7.84 weeks, and the average delivery gestational age was 35.91 ± 5.16 weeks. The longest duration of treatment with a uterine contraction inhibitor or inhibitors in combination or with magnesium sulphate alone was 15.34 ± 13.16 days, and nine cases developed adverse reactions. Persistent uterine contraction inhibition after cervical cerclage could prolong pregnancy and improve pregnancy outcomes.Impact statement A crucial reason for treatment failure of cervical cerclage is that uterine contraction was not effectively inhibited. Persistent inhibition of uterine contraction after cervical cerclage prolonged pregnancy duration, increased gestational age at delivery, and improved pregnancy outcomes. This study may provide a clinical basis for prolonging gestational age, preventing late abortion and premature delivery, and improving the survival rate and quality of life of premature infants.
Topics: Pregnancy; Female; Child; Humans; Infant; Tocolytic Agents; Cerclage, Cervical; Magnesium Sulfate; Retrospective Studies; Quality of Life; Premature Birth; Pregnancy Outcome; Uterine Cervical Incompetence; Gestational Age; Pregnancy, Prolonged
PubMed: 36205080
DOI: 10.1080/01443615.2022.2128997 -
Drug Discoveries & Therapeutics 2021
PubMed: 34011822
DOI: 10.5582/ddt.2021.E1