Dataset Information

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

ABSTRACT:

Background

The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.

Objectives

To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia.

Search strategy

MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies.

Selection criteria

All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia.

Data collection and analysis

Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens.

Main results

Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations.

Conclusion

The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens.

Tweetable abstract

Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.

SUBMITTER: Okusanya BO

PROVIDER: S-EPMC4737322 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

Okusanya B O BO Oladapo O T OT Long Q Q Lumbiganon P P Carroli G G Qureshi Z Z Duley L L Souza J P JP Gülmezoglu A M AM

BJOG : an international journal of obstetrics and gynaecology 20151124 3

<h4>Background</h4>The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.<h4>Objectives</h4>To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia.<h4>Search strategy</h4>MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies.<h4>Selection criteria</h4>All study types investigating pharmacokinetic ...[more]

PMID: 26599617

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Project description:BackgroundHypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO4 remains underused, particularly in low- and middle-income countries (LMICs).ObjectiveThis qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO4 to prevent or treat pre-eclampsia/eclampsia.Search strategyWe searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021.Selection criteriaPrimary qualitative and mixed-methods studies on factors affecting use of MgSO4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion.Data collection and analysisWe applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO4 .Main resultsWe included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation.ConclusionsThese findings can inform policy and guideline development and improve implementation of MgSO4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used.Tweetable abstractGlobal qualitative review identifies factors affecting underutilisation of MgSO4 for pre-eclampsia and eclampsia.

Project description:BACKGROUND: The Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia. 10,141 women were recruited, 8804 before delivery. Overall, 9024 children were included in the analysis of outcome at discharge from hospital. Magnesium sulphate more than halved the risk of eclampsia, and probably reduced the risk of maternal death. There did not appear to be any substantive harmful effects on the baby, in the short term. It is now important to assess whether these benefits persist, and to provide adequate reassurance about longer term safety.The main objective of the Magpie Trial Follow Up Study is to assess whether in utero exposure to magnesium sulphate has a clinically important effect on the child's chance of surviving without major neurosensory disability. Other objectives are to assess long term outcome for the mother, and to develop and assess appropriate strategies for following up large numbers of children in perinatal trials. STUDY DESIGN: Follow up is only feasible in selected centres. We therefore anticipate contacting 2800-3350 families, for 2435-2915 of whom the woman was randomised before delivery. A further 280-335 children would have been eligible for follow up if they had survived. The total sample size for the children is therefore 3080-3685, 2680-3210 of whom will have been born to women randomised before delivery.Families eligible for the follow up will be contacted, and surviving children screened using the Ages and Stages Questionnaires. Children who screen positive, and a sample of those who screen negative, will whenever possible have a paediatric and neurodevelopmental assessment. When women are contacted to ask how their child is, they will also be asked about their own health. The primary outcome is a composite measure of death or neurosensory disability for the child at 18 months. DISCUSSION: The Follow Up Study began in 2002, and now involves collaborators in 19 countries. Data collection will close at the end of 2003.

Project description:ObjectiveA model that can predict reliably the risk of pre-eclampsia (PE)-related pregnancy complications does not exist. The aim of this study was to develop and validate internally a clinical prediction model to predict the risk of a composite outcome of PE-related maternal and fetal complications within 7, 14 and 30 days of testing in women with suspected or confirmed PE.MethodsThe data for this study were derived from a prospective, multicenter, observational cohort study on women with a singleton pregnancy and suspected or confirmed PE at 20 to < 37 weeks' gestation. For the development of the prediction model, the possible contribution of clinical and standard laboratory variables, as well as the biomarkers soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and their ratio, in the prediction of a composite outcome of PE-related complications, consisting of maternal and fetal adverse events within 7, 14 and 30 days, was explored using multivariable competing-risks regression analysis. The discriminative ability of the model was assessed using the concordance (c-) statistic. A bootstrap validation procedure with 500 replications was used to correct the estimate of the prediction model performance for optimism and to compute a shrinkage factor for the regression coefficients to correct for overfitting.ResultsAmong 384 women with suspected or confirmed PE, 96 (25%) had an adverse PE-related outcome at any time after hospital admission. Important predictors of adverse PE-related outcome included sFlt-1/PlGF ratio, gestational age at the time of biomarker measurement and protein-to-creatinine ratio as continuous variables. The c-statistics (corrected for optimism) for developing a PE-related complication within 7, 14 and 30 days were 0.89, 0.88 and 0.87, respectively. There was limited overfitting, as indicated by a shrinkage factor of 0.91.ConclusionsWe propose a simple clinical prediction model with good discriminative performance to predict PE-related complications. Determination of its usefulness in clinical practice awaits further investigation and external validation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Project description:ObjectivesTo develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.DesignProspective multicentre cohort.SettingFive centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland.Participants3572 "healthy" nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%).Main outcome measurePre-eclampsia defined as ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks' gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37(+0) weeks' gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia.ResultsOf the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks' gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively.ConclusionsThe ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

Dataset Information

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

Background

Objectives

Search strategy

Selection criteria

Data collection and analysis

Main results

Conclusion

Tweetable abstract

Publications

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

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