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Ronald F Lamont - One of the best experts on this subject based on the ideXlab platform.

  • Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour
    Current pharmaceutical design, 2019
    Co-Authors: Ronald F Lamont, Jan Stener Jørgensen
    Abstract:

    Background Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using Tocolytics to inhibit spontaneous preterm labour. Objective We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents. Results The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses. Conclusion The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

  • The safety of Tocolytics used for the inhibition of preterm labour
    Expert opinion on drug safety, 2016
    Co-Authors: Callum D Lamont, Jan Stener Jørgensen, Ronald F Lamont
    Abstract:

    ABSTRACTIntroduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%.Areas covered: Following a systematic review of the literature, we have provided an overview of the use of Tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use.Expert opinion: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base...

  • Preterm labor: current tocolytic options for the treatment of preterm labor
    Expert opinion on pharmacotherapy, 2014
    Co-Authors: Jan Stener Jørgensen, Louise Katrine Kjær Weile, Ronald F Lamont
    Abstract:

    While tocolytic therapy may not be indicated in all cases of spontaneous preterm labor (SPTL), the evidence that they are superior to placebo is robust. The perfect tocolytic that is 100% efficacious and 100% safe does not exist and efforts should continue to develop and introduce safer and more effective agents. A reduction in the rate of neonatal mortality and morbidity using tocolysis has not been shown but no tocolytic study has been powered by numbers sufficient to demonstrate such an effect. Tocolytics can delay delivery long enough to administer a course of antepartum glucocorticoids and arrange in utero transfer to a center with neonatal intensive care facilities, both of which reduce neonatal mortality and morbidity. Few Tocolytics (β₂-agonists and atosiban) are licensed for use as Tocolytics and only one was developed specifically to treat preterm labor (atosiban). Accordingly, most Tocolytics have multi-organ adverse effects. Currently, based on the evidence of safety and efficacy, atosiban should be the first-choice tocolytic for the treatment of SPTL to prevent or delay preterm birth.

  • Atosiban as a tocolytic for the treatment of spontaneous preterm labor
    Expert Review of Obstetrics & Gynecology, 2008
    Co-Authors: Ronald F Lamont, Ky Ronald Kam
    Abstract:

    Preterm birth is the major cause of perinatal mortality and morbidity in the developed world, imposing a huge burden on healthcare costs. Tocolytic drugs inhibit contractions and delay delivery in the hope of improving survival and preventing handicap. Historically, most Tocolytics were not initially developed to treat preterm labor, and so are not uterospecific and have multiorgan side effects. Atosiban (Tractocile®) is a vasopressin-oxytocin receptor antagonist, which is much more uterospecific than previous Tocolytics, and, consequently has placebo-level side effects. Atosiban has a strong evidence base and is a significant addition to the treatment options for preterm labor and should be used for first-line therapy.

  • The development and introduction of anti‐oxytocic Tocolytics
    BJOG: An International Journal of Obstetrics and Gynaecology, 2003
    Co-Authors: Ronald F Lamont
    Abstract:

    The perfect tocolytic agent, which is completely safe for both the mother and fetus and, which will inhibit uterine contractions and stop preterm labour in every case does not exist and the search continues. Recently, research into a new group of tocolytic agents (the oxytocic antagonists) has led to the introduction of a new licensed drug, atosiban. Since the early 1950s, modifications of the oxytocin molecule have resulted in many analogues and antagonists, though initially none emerged as potentially useful drugs. Further modifications resulted in full uterotonic antagonism in animal models before an analogue was found that inhibited vasopressin-stimulated uterine contractions in non-pregnant healthy women. In vitro and animal models suggested the molecule was fully antagonistic, although it was found to be only partially agonistic in women. Further developments led to two modified oxytocin molecules with higher receptor affinity for human myometrium, both of which lacked agonism in humans. The analogue, atosiban, was found to be more potent and so was chosen for clinical evaluation in dysmenorrhoea and preterm labour. The first clinical reports were open label, observational pilot studies. Randomised, double-blind, phase II placebo-controlled studies followed showing that atosiban was significantly more effective than placebo with very few side effects. Dose-response studies and phase III studies in which study or placebo groups could use alternative tocolytic agents also suggested that atosiban was an effective tocolytic agent with very few adverse events. The recent worldwide comparative study of atosiban versus different beta-agonists represents the largest and most strictly controlled study of Tocolytics ever published. Atosiban was found to be at least as effective as the beta-agonists as a tocolytic agent, but significantly less likely to result in maternal cardiovascular side effects or the need to discontinue therapy as a result of unacceptable side effects.

Yaakov Beilin - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of Nitroglycerin and Terbutaline for External Cephalic Version in Women Who Received Neuraxial Anesthesia: A Retrospective Analysis.
    Anesthesia & Analgesia, 2020
    Co-Authors: Daniel Katz, Kyle J Riley, Elizabeth Kim, Yaakov Beilin
    Abstract:

    External cephalic version is a technique that decreases the need for cesarean delivery in patients with breech presentation. Several techniques exist to increase the success of external cephalic version; however, there are no studies comparing different Tocolytics in patients who also received neuraxial anesthesia. We, therefore, performed a review of 198 patients who presented for external cephalic version and compared their success rates based on the tocolytic medication utilized. The external cephalic version success rate for patients who received terbutaline was significantly higher than for those who received nitroglycerin (N [%]: 57 [65.6] terbutaline group versus 40 [36.0] nitroglycerin group; P < .001).

David M. Haas - One of the best experts on this subject based on the ideXlab platform.

  • short term Tocolytics for preterm delivery current perspectives
    International Journal of Women's Health, 2014
    Co-Authors: David M. Haas, Tara Benjamin, Renata Sawyer, Sara K. Quinney
    Abstract:

    Administration of short-term tocolytic agents can prolong pregnancy for women in preterm labor. Prolonging pregnancy has many benefits because it allows for other proven interventions, such as antenatal corticosteroid administration, to be accomplished. This review provides an overview of currently utilized tocolytic agents and the evidence demonstrating their efficacy for prolonging pregnancy by at least 48 hours. General pharmacological principles for the clinician regarding drugs in pregnancy are also briefly discussed. In general, while the choice of the best first-line short-term tocolytic drug is not clear, it is evident that use of these agents has a clear place in current obstetric therapeutics.

  • Short-term Tocolytics for preterm delivery – current perspectives
    International journal of women's health, 2014
    Co-Authors: David M. Haas, Tara Benjamin, Renata Sawyer, Sara K. Quinney
    Abstract:

    Administration of short-term tocolytic agents can prolong pregnancy for women in preterm labor. Prolonging pregnancy has many benefits because it allows for other proven interventions, such as antenatal corticosteroid administration, to be accomplished. This review provides an overview of currently utilized tocolytic agents and the evidence demonstrating their efficacy for prolonging pregnancy by at least 48 hours. General pharmacological principles for the clinician regarding drugs in pregnancy are also briefly discussed. In general, while the choice of the best first-line short-term tocolytic drug is not clear, it is evident that use of these agents has a clear place in current obstetric therapeutics.

  • Tocolytic therapy for preterm delivery: systematic review and network meta-analysis
    BMJ (Clinical research ed.), 2012
    Co-Authors: David M. Haas, Deborah M Caldwell, Page Kirkpatrick, Jennifer Mcintosh, Nicky J Welton
    Abstract:

    Objective To determine the most effective tocolytic agent at delaying delivery. Design Systematic review and network meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. Study selection Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. Data extraction At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). Results Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the Tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). Conclusions Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.

A Ohlsson - One of the best experts on this subject based on the ideXlab platform.

  • Tocolytics for preterm labor: a systematic review.
    Obstetrics and gynecology, 1999
    Co-Authors: K Gyetvai, M E Hannah, E D Hodnett, A Ohlsson
    Abstract:

    To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although Tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.

  • Tocolytics for preterm labor: a systematic review.
    Obstetrics & Gynecology, 1999
    Co-Authors: K Gyetvai, M E Hannah, E D Hodnett, A Ohlsson
    Abstract:

    Abstract Objective: To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. Data Sources: We checked MEDLINE (1966–1998) and the Cochrane Controlled Trials Register for articles, using the search terms “randomized controlled trial” (RCT), “preterm labor,” “tocolysis,” “betamimetics,” “ritodrine,” “terbutaline,” “hexaprenaline,” “isoxuprine,” “prostaglandin synthetase inhibitors,” “indomethacin,” “sulindac,” “calcium channel blockers,” “nifedipine,” “oxytocin receptor blockers,” “atosiban,” “nitroglceride,” and “magnesium sulfate.” Methods of Study Selection: We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. Tabulation, Integration, and Results: Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Conclusion: Although Tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.

Johanne Dubé - One of the best experts on this subject based on the ideXlab platform.

  • Sublingual Nitroglycerine as a Tocolytic in External Cephalic Version: A Comparative Study
    Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2003
    Co-Authors: Emmanuel Bujold, Martin Sergerie, André Masse, Guy Verscheiden, Marie-josée Bédard, Johanne Dubé
    Abstract:

    Abstract Objective: To study the effect of sublingual nitroglycerine as a tocolytic on the success rate of external cephalic version (ECV) in nulliparous and parous women. Methods: A retrospective case-controlled study of all ECV cases from February 1996 to February 2000 in a single centre. The rates of successful ECV were compared between women who had their ECV before February 1998 (control group), those who had their ECV after February 1998 and received 0.8 mg sublingual nitroglycerine spray as a tocolytic agent, and those who had their ECV after February 1998 and received no tocolytic agents. Nulliparous and parous women were studied separately. Data were collected for parity, gestational age, maternal age, placental localization, and side effects. Chi-square and Kruskal-Wallis tests were performed for statistical comparison. Results: Of 150 women who had their ECV after February 1998, 120 (80%) received sublingual nitroglycerine (group I: cases using 0.8 mg sublingual nitroglycerine spray as a tocolytic agent) and were compared to the 30 patients who did not receive sublingual nitroglycerine or other Tocolytics after February 1998 (group 2) and to 137 patients who had their ECV before February 1998 (control group). Of the women who received sublingual nitroglycerine, 5 (4%) had hypotension and 7 (6%) had headaches and/or nausea. The rate of successful ECV was 27% in group I versus 30% in group 2 (p = 0.86) versus 28% in the control group (p = 0.88) for nulliparous patients, and 67% versus 80% (p = 0.30) versus 51 % (p = 0.09) respectively for parous women. However, the success rate was increased overall in parous women after the introduction of nitroglycerine as a tocolytic for ECV in February 1998 (71% vs. 51%, p=0.02). Conclusion: Although the success rate of ECV has increased in recent years, the use of sublingual nitroglycerine as a tocolytic was not associated with this higher success rate. A randomized, controlled trial is needed.