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PloS One 2012Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following acute treatment of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following acute treatment of preterm contractions. The effectiveness and safety of this maintenance tocolysis have not been clearly established. We aimed to systematically evaluate the effectiveness and safety of subcutaneous (SQ) terbutaline infusion by pump for maintenance tocolysis.
METHODOLOGY/PRINCIPAL FINDINGS
MEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews and Dissemination databases, post-marketing surveillance data and grey literature were searched up to April 2011 for relevant experimental and observational studies. Two randomized trials, one nonrandomized trial, and 11 observational studies met inclusion criteria. Non-comparative studies were considered only for pump-related harms. We excluded case-reports but sought FDA summaries of post-marketing surveillance data. Non-English records without an English abstract were excluded. Evidence of low strength from observational studies with risk of bias favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks, mean days of pregnancy prolongation, and neonatal death. Observational studies of medium to high risk of bias also demonstrated benefit for other surrogate outcomes, such as birthweight and neonatal intensive care unit (NICU) admission. Several cases of maternal deaths and maternal cardiovascular events have been reported in patients receiving terbutaline tocolysis.
CONCLUSIONS/SIGNIFICANCE
Although evidence suggests that pump therapy may be beneficial as maintenance tocolysis, our confidence in its validity and reproducibility is low, suggesting that its use should be limited to the research setting. Concerns regarding safety of therapy persist.
Topics: Adult; Birth Weight; Delivery, Obstetric; Female; Gestational Age; Humans; Infant, Newborn; Infusion Pumps; Pregnancy; Premature Birth; Publication Bias; Terbutaline; Treatment Outcome; Young Adult
PubMed: 22363704
DOI: 10.1371/journal.pone.0031679 -
Acta Obstetricia Et Gynecologica... Apr 2023Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice,...
INTRODUCTION
Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β -mimetic terbutaline and magnesium sulfate (MgSO ) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia-inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents.
MATERIAL AND METHODS
In the isolated organ bath studies, rhythmic contractions of 22-day- pregnant Sprague-Dawley rats were stimulated with KCl, and cumulative dose-response curves were constructed in the presence of MgSO or terbutaline. The uterus-relaxing effects of terbutaline were also investigated in the presence of MgSO in both normal buffer and Ca -poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate.
RESULTS
Both MgSO and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca -poor environment, MgSO was not able to increase the effect of terbutaline, indicating the role of MgSO as a Ca channel blocker. In the cardiovascular studies, MgSO significantly decreased the tachycardia-inducing effect of terbutaline in late pregnant rats.
CONCLUSIONS
The combined application of MgSO and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO could substantially reduce the tachycardia-inducing side effect of terbutaline.
Topics: Pregnancy; Female; Rats; Animals; Terbutaline; Magnesium Sulfate; Rats, Sprague-Dawley; Tocolytic Agents; Uterus
PubMed: 36808376
DOI: 10.1111/aogs.14532 -
The Cochrane Database of Systematic... Jul 2018Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents. Tachysystole may reduce fetal oxygenation by interrupting maternal blood flow to the placenta during contractions. Reducing uterine contractions may improve placental blood flow, improving fetal oxygenation. This review aimed to evaluate the use of tocolytics to reduce or stop uterine contractions for improvement of the condition of the fetus in utero. This new review supersedes an earlier Cochrane Review on the same topic.
OBJECTIVES
To assess the effects of the use of acute tocolysis during labour for uterine tachysystole or suspected fetal distress, or both, on fetal, maternal and neonatal outcomes.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (2 February 2018), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating acute tocolysis for uterine tachysystole, intrapartum fetal distress, or both.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane.
MAIN RESULTS
We included eight studies (734 women), conducted in hospital settings, predominantly in high-income countries (USA, Austria, Uruguay). Two trials were conducted in upper and lower middle-income countries (South Africa, Sri Lanka). The hospital facilities all had the capacity to perform caesarean section. Overall, the studies had a low risk of bias, except for methods to maintain blinding. All of the trials used a selective beta (ß)-adrenergic agonist in one arm, however the drug used varied, as did the comparator. Limited information was available on maternal outcomes.Selective ß-adrenergic agonist versus no tocolytic agent, whilst awaiting emergency deliveryThere were two stillbirths, both in the no tocolytic control group (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.01 to 4.55; 2 studies, 57 women; low-quality evidence). One had gross hydrocephalus and the second occurred with vaginal delivery after waiting 55 minutes for caesarean section. The decision for caesarean section delivery was an inclusion criterion in both studies so we could not assess this as an outcome under this comparison. Abnormal fetal heart trace is probably lower with tocolytic treatment (RR 0.28, 95% CI 0.08 to 0.95; 2 studies, 43 women; moderate-quality evidence). The effects on the number of babies with Apgar score below seven were uncertain (low-quality evidence).Intravenous (IV) atosiban versus IV hexoprenaline (1 study, 26 women) One infant in the hexoprenaline group required > 24 hours in the neonatal intensive care unit (NICU) following a forceps delivery (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence). There were no fetal or neonatal mortalities and no Apgar scores below seven. There was one caesarean delivery in the IV hexoprenaline group (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence), and one case of abnormal fetal heart score in the atosiban group (RR 3.00, 95% CI 0.13 to 67.51; very low-quality evidence).IV fenoterol bromhydrate versus emergency delivery (1 study, 390 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. IV fenoterol probably increases the risk of caesarean delivery (RR 1.12, 95% CI 1.04 to 1.22; moderate-quality evidence). Fenoterol may have little or no effect on the risk of Apgar scores below seven (RR 1.28, 95% CI 0.35 to 4.68; low-quality evidence).IV hexoprenaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 37 women) No data were reported for perinatal death or severe morbidity. There were two fetal deaths in the no tocolytic control group (RR 0.23, 95% CI 0.01 to 4.55; low-quality evidence). The rate of caesarean delivery was not reported. There were two babies with Apgar scores below seven in the control group and none in the hexoprenaline group (RR 0.24, 95% CI 0.01 to 4.57; 35 women; low-quality evidence).Subcutaneous terbutaline versus IV magnesium sulphate (1 study, 46 women)No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. The decision for caesarean section was an inclusion criterion, so we could not assess this. The effects on abnormal fetal heart trace are uncertain (very low-quality evidence).Subcutaneous terbutaline with continuation of oxytocic infusion versus cessation of oxytocic infusion without tocolytic agent (1 study, 28 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery in the subcutaneous terbutaline (8/15) and control groups (4/13) (RR 1.73, 95% CI 0.68 to 4.45; low-quality evidence). There were no cases of Apgar scores below seven or abnormal fetal heart trace.Subcutaneous terbutaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 20 women) No data were reported for perinatal death or severe morbidity. There were no fetal or neonatal mortalities. The decision for caesarean section was an inclusion criterion, so we could not assess this. There were two babies with Apgar scores below seven in the control group and none in the terbutaline group (RR 0.17, 95% CI 0.01 to 3.08; low-quality evidence).IV terbutaline versus IV nitroglycerin (1 study, 110 women)No data were reported for perinatal death or severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery between the IV terbutaline (30/57) and control groups (29/53) (RR 0.96, 95% CI 0.68 to 1.36; low-quality evidence). There were no cases of Apgar scores below seven.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine the effects of tocolytics for uterine tachysystole or suspected fetal distress during labour. The clinical significance for some of the improvements in measures of fetal well-being with tocolytics is unclear. The sample sizes were too small to detect effects on neonatal morbidity, mortality or serious adverse effects. The majority of studies are from high-income countries in facilities with access to caesarean section, which may limit the generalisability of the results to lower-resource settings, or settings where caesarean section is not available.Further well-designed and adequately powered RCTs are required to evaluate clinically relevant indicators of maternal and neonatal morbidity and mortality.
Topics: Adrenergic beta-2 Receptor Agonists; Cesarean Section; Female; Fenoterol; Fetal Distress; Hexoprenaline; Humans; Nitroglycerin; Perinatal Death; Pregnancy; Randomized Controlled Trials as Topic; Terbutaline; Tocolysis; Tocolytic Agents; Uterine Contraction; Vasotocin
PubMed: 29971813
DOI: 10.1002/14651858.CD009770.pub2 -
American Journal of Translational... 2021To investigate the efficacy of glucocorticoid and terbutaline in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
BACKGROUND
To investigate the efficacy of glucocorticoid and terbutaline in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
METHODS
248 patients with AECOPD were assigned into two groups, 124 patients in the control group were only given terbutaline treatment, while 124 patients in the experimental group were treated with glucocorticoid and terbutaline. The effect on lung function and blood gas indexes were compared between the two groups.
RESULTS
The total effective rate of the treatment with glucocorticoid and terbutaline was higher than that of control group (P < 0.05). After treatment, the pulmonary function indexes such as FEV, FVC and PaO levels in the two groups were significantly higher than those before treatment, PaCO levels were significantly lower than that before the treatment (P < 0.05).
CONCLUSIONS
The combined use of glucocorticoid and terbutaline could effectively improve the lung function and blood gas indexes. It's of great significance to promote the rehabilitation of patients with AECOPD, and it provides insights for future clinical practice.
PubMed: 34306459
DOI: No ID Found -
Lancet (London, England) Sep 2010Children who are referred to specialist care with asthma that does not respond to treatment (problematic severe asthma) are a heterogeneous group, with substantial... (Review)
Review
Children who are referred to specialist care with asthma that does not respond to treatment (problematic severe asthma) are a heterogeneous group, with substantial morbidity. The evidence base for management is sparse, and is mostly based on data from studies in children with mild and moderate asthma and on extrapolation of data from studies in adults with severe asthma. In many children with severe asthma, the diagnosis is wrong or adherence to treatment is poor. The first step is a detailed diagnostic assessment to exclude an alternative diagnosis ("not asthma at all"), followed by a multidisciplinary approach to exclude comorbidities ("asthma plus") and to assess whether the child has difficult asthma (improves when the basic management needs, such as adherence and inhaler technique, are corrected) or true, therapy-resistant asthma (still symptomatic even when the basic management needs are resolved). In particular, environmental causes of secondary steroid resistance should be identified. An individualised treatment plan should be devised depending on the clinical and pathophysiological characterisation. Licensed therapeutic approaches include high-dose inhaled steroids, the Symbicort maintenance and reliever (SMART) regimen (with budesonide and formoterol fumarate), and anti-IgE therapy. Unlicensed treatments include methotrexate, azathioprine, ciclosporin, and subcutaneous terbutaline infusions. Paediatric data are needed on cytokine-specific monoclonal antibody therapies and bronchial thermoplasty. However, despite the interest in innovative approaches, getting the basics right in children with apparently severe asthma will remain the foundation of management for the foreseeable future.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Allergens; Anti-Asthmatic Agents; Asthma; Azathioprine; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Clinical Trials as Topic; Comorbidity; Cyclosporine; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Eosinophils; Ethanolamines; Formoterol Fumarate; House Calls; Humans; Immunoglobulin E; Interdisciplinary Communication; Methotrexate; Off-Label Use; Risk Factors; Severity of Illness Index; Spirometry; Terbutaline; Tobacco Smoke Pollution; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 20816548
DOI: 10.1016/S0140-6736(10)61054-9 -
Kidney International Jun 1997The effects of ritodrine and terbutaline on potassium homeostasis, renal function, and cardiac rhythm were assessed in women treated with these drugs for preterm labor.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effects of ritodrine and terbutaline on potassium homeostasis, renal function, and cardiac rhythm were assessed in women treated with these drugs for preterm labor. Timed blood and urine samples were obtained for two hours before and during six hours of intravenous ritodrine (N = 5) and terbutaline (N = 5) administered in pharmacologically equivalent doses. No differences were found in any parameters affecting potassium homeostasis or renal function between these drugs. A decrease in mean plasma potassium of 0.9 mEq/liter occurred after 30 minutes of drug infusion (4.2 +/- 0.1 to 3.3 +/- 0.1 mEq/liter, P < 0.005) before any significant changes in plasma glucose (75.0 +/- 4.7 to 93.7 +/- 6.1 mg/dl, P = NS) or plasma insulin (12.4 +/- 6.0 to 28.4 +/- 5.1 mU/ml, P = NS). The mean plasma potassium after four hours of drug infusion was 2.5 +/- 0.1 mEq/liter. Plasma insulin rose to a level known to induce cellular potassium uptake (39.2 +/- 7.7 mU/ml) after 60 minutes of drug therapy and remained at this level for four hours. Hyperlactatemia occurred at four hours (4.7 +/- 0.8 mmol/liter) and the plasma lactate/pyruvate ratio increased in a 10:1 ratio. Both drugs significantly reduced glomerular filtration rate, sodium, potassium, and chloride excretion and urinary flow rate. Changes in acid-base homeostasis, plasma aldosterone, or renal potassium excretion did not contribute to ritodrine-or terbutaline-induced hypokalemia. In 83 women with preterm labor randomly assigned to ritodrine (N = 42) or terbutaline (N = 41), the maximum decrease in plasma potassium occurred after six hours of drug infusion. During Holter monitoring, 3 of 14 women treated with ritodrine or terbutaline developed symptomatic cardiac arrhythmias at the lowest plasma potassium while no women treated with saline and morphine (N = 12) developed cardiac arrhythmias (P = 0.14). We conclude that ritodrine and terbutaline induce profound hypokalemia by stimulating cellular potassium uptake and both drugs cause significant renal sodium and fluid retention and cardiac arrhythmias. Careful monitoring of electrolytes, fluid balance, and cardiac rhythm should occur during tocolytic therapy with ritodrine or terbutaline.
Topics: Adolescent; Adult; Aldosterone; Blood Glucose; Female; Heart Rate; Humans; Hypokalemia; Injections, Intravenous; Insulin; Kidney; Obstetric Labor, Premature; Potassium; Pregnancy; Pregnancy Complications; Renin; Ritodrine; Terbutaline
PubMed: 9186877
DOI: 10.1038/ki.1997.255 -
Molecules (Basel, Switzerland) Dec 2023Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol...
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC > 100,000 nM, IC = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer's disease.
Topics: Humans; Rivastigmine; Butyrylcholinesterase; Alzheimer Disease; Cholinesterase Inhibitors; Pain; Terbutaline
PubMed: 38202655
DOI: 10.3390/molecules29010072 -
Toxicology May 2018Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in...
Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Cell Differentiation; Dexamethasone; Drug Synergism; Embryonic Stem Cells; Female; Glucocorticoids; Neuroglia; Neurons; Neurotoxicity Syndromes; Obstetric Labor, Premature; PC12 Cells; Pregnancy; Rats; Terbutaline
PubMed: 29524569
DOI: 10.1016/j.tox.2018.03.001 -
PloS One 2020In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of...
In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM- 10 μM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.
Topics: Animals; Aqueous Humor; Bodily Secretions; Bronchodilator Agents; Calcium; Cattle; Cells, Cultured; Colforsin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Terbutaline
PubMed: 33347508
DOI: 10.1371/journal.pone.0244253