Magnesium Sulfate In Preeclampsia Research Articles

Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors.

Background and ObjectiveThe pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO4 PK.MethodsA prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates.ResultsThe study population consisted of 109 patients. The PK profile of MgSO4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO4 CL and V, respectively. The model was parameterized as CL and V.ConclusionThe PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate.

Posterior reversible encephalopathy syndrome in preeclampsia and eclampsia: The role of hypomagnesemia

PurposePosterior reversible encephalopathy syndrome (PRES), defined by its clinical and imaging manifestations, is a critical maternal complication. The specific pathophysiological mechanism of PRES has not been fully elucidated and remains controversial. Recently, several case studies reported that hypomagnesemia is present in the acute phase of PRES regardless of its etiology. Moreover, magnesium sulfate is a conventional treatment for preeclampsia (PE) and eclampsia; therefore, we hypothesized that hypomagnesemia might play an important role in the cascades involved in PRES in PE or eclampsia. MethodWe consecutively collected PE and eclampsia patients who were examined via magnetic resonance imaging (MRI) and tested for magnesium levels between January 2013 and January 2017. All patients were grouped into PRES and non-PRES groups based on MRI results. Demographic data, magnesium levels and imaging features were collected retrospectively. ResultsA total of 72 patients met the inclusion criteria; these participants were sorted into PRES (n = 38) and non-PRES (n = 34) groups. Twenty-four patients (63%) in the PRES group and 2 patients (6%) in the non-PRES group presented hypomagnesemia. Moreover, magnesium levels were significantly lower in the PRES group during both the acute phase (p < 0.001) and the post-phase (p = 0.04) than in the non-PRES group. However, there was no correlation between magnesium levels and edema severity during the acute phase. ConclusionsThese results demonstrate that hypomagnesemia frequently occurs in the acute phase of obstetric PRES and suggest a potential relationship between them. Such a connection would support the application of magnesium sulfate in PE and eclampsia patients to prevent PRES. However, additional randomized trials are needed.

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

Metabolomic Profiles of Placenta in Preeclampsia.

Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide. We have previously reported that magnesium sulfate therapy is effective for early-onset (EO) preeclampsia. To investigate the molecular mechanisms underlying this favorable effect, metabolomics analysis of magnesium sulfate-treated preeclamptic placentas was performed using capillary electrophoresis time of flight mass spectrometry. There were significant metabolic differences between EO-preeclamptic placentas (n=7) and other placentas (late-onset preeclampsia [n=3], normal pregnancies [n=10]). In EO-preeclamptic placentas, the glutathione metabolism pathway was markedly upregulated, whereas single-sample gene-set enrichment analysis using a publicly available microarray dataset (GSE75010) showed that the glutathione metabolism pathway was significantly downregulated in EO-preeclamptic placentas compared with nonpreeclamptic controls. Metabolomic profiles showed that magnesium sulfate significantly promoted glutathione production in an immortalized trophoblast cell line under oxidative stress conditions but not under normal conditions. Magnesium sulfate suppressed hydrogen peroxide-induced production of reactive oxygen species. Exploratory analysis revealed that urinary 8-isoprostane was decreased in all 5 women treated with magnesium sulfate for preeclampsia with severe features. These findings suggest that magnesium sulfate is effective for treating EO-preeclampsia partly because of its antioxidant effects on trophoblasts.

Sulfato de magnesio y el cerebro en la preeclampsia

El sulfato de magnesio ha sido el medicamento de elección en la profilaxis y tratamiento de la eclampsia. Sin embargo, la compresión de las manifestaciones neurológicas producidas por la preeclampsia englobadas dentro de la leucoencefalopatía posterior reversible ha puesto en evidencia que los mecanismos propuestos basados en estudios en animales son ciertos, revalorando más a este antiguo fármaco. Desde el estudio MAGPIE hasta nuestros días son muchas las interrogantes aun no resueltas con respecto al sulfato de magnesio en la preeclampsia, pero es indudable su valor como tratamiento de primera línea para las manifestaciones cerebrales en dicha complicación.

Maternal Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome and Neonatal Magnesium Toxicity: A Case Report

Introduction: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a progressive disorder associated with neurologic, cardiac, neuromuscular, hepatic, metabolic and gastrointestinal dysfunction, including potential anesthetic and obstetrical complications. Increased susceptibility to drugs in patient with MELAS syndrome can be due to drug-induced mitochondrial toxicity and/or decreased elimination. We present here a case of severe neonatal magnesium sulfate toxicity in the context of MELAS syndrome. Case presentation: A 43-year-old, gravida 5, para-5 (4 prior vaginal deliveries and the current cesarean section) woman with asymptomatic MELAS syndrome (carrier of the genetic variant NC_012920.1: m3243A>G in 20% of the mitochondrial DNA) was given intravenous magnesium sulfate for preeclampsia shortly before an emergency cesarean section at 33 weeks. The newborn presented a severe toxic effect characterized by cardio-respiratory arrest. Genetic evaluation revealed that he carried the same maternal mutation, but at a higher rate (80%). There was no other risk factor for cardio-respiratory arrest other than the potential interaction between the maternal/ neonatal mitochondrial disease and the medication, thus potentially leading to the risk of overdose. Conclusion: The cause of the severe toxicity is uncertain, but it may have resulted from magnesium accumulation in the mother and/or the newborn due the presence of the MELAS syndrome in the neonate. A close assessment of potential severe drug toxicity in mothers and neonates with MELAS syndrome is warranted.

Magnesium sulphate is it necessary to prevent eclampsia?

Background: Preeclampsia was reported to account for 15 % of all antenatal hospitalization for pregnancy complications. It causes maternal as well as fetal death by developing eclampsia Since the turn of the century, obstetrician have to decrease the incidence of eclampsia i.e hypertension complicated with seizures in pregnant women by treating them magnesium sulfate in preeclampsia. In our study we tried to find out Magnesium sulphate really helpful in prevention of eclampsia or not. Methods: This prospective study was carried out by the department of Pharmacology with the help from department of obstetrics and gynecology, in rural hospital and medical college i.e Mahatma Gandhi Institute of Medical sciences Sewagram, Wardha, Maharashtra, India during January 2007 to January 2008. A total of 100 subjects registered in inpatient department were included in this study. Patients were divided in to two group one group receiving nifedipine (calcium channel blockers) and other group receive combination of nifedipine and magnesium sulfate. We compared the delivery outcome of both the group. Results: Patients receiving nifedipine had good pregnancy outcome with less side effects than the patients receiving combination of nifedipine and magnesium sulphate. Conclusions: Magnesium sulphate is not necessary drug for prophylaxis of eclampsia.

Blood loss at cesarean delivery in women on magnesium sulfate for preeclampsia

Objective: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD).Methods: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were “magnesium sulfate”, “preeclampsia” and “randomized”. Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia.Results: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88–1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28–0.57).Conclusions: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage.

Similar Outcomes among Women Treated with 12-Hour Compared with 24-Hour Postpartum Magnesium Sulfate for Preeclampsia

Similar Outcomes among Women Treated with 12-Hour Compared with 24-Hour Postpartum Magnesium Sulfate for Preeclampsia

Possible therapeutic effect of magnesium sulfate in pre-eclampsia by the down-regulation of placental tumor necrosis factor-alpha secretion

To examine the effect of magnesium sulfate (MgSO(4)) on tumor necrosis factor-alpha (TNF-alpha) secretion by preeclamptic placentas. Cotyledons of six, term, normotensive and ten, pre-eclamptic placentas were dually perfused for six hours (6h), with MgSO(4) (6-7 mg %) in the maternal reservoir [normotensive (n = 3); pre-eclamptic (n = 5)], and with control medium (without MgSO(4)) [normotensive (n = 3); pre-eclamptic (n = 5)]. Perfusate samples from the maternal and the fetal circulations were collected every 30 min throughout the 6h of perfusion, and examined for TNF- alpha levels using ELISA. Statistical significance was determined using a 2-way analysis of variance. Pre-eclamptic placentas perfused with control medium (without MgSO(4)) secreted higher levels of TNF-alpha into the fetal and the maternal circulations (1.60 +/- 0.59 pg/mL/g of cotyledon and 14.28 +/- 2.69 pg/mL/g of cotyledon, respectively), as compared to the fetal and maternal circulations of normotensive placentas (0.25 +/- 0.09 pg/mL/g of cotyledon and 6.73 +/- 1.11 pg/mL/g of cotyledon, respectively) (p < 0.01). Addition of MgSO(4) to normotensive placentas did not affect TNF-alpha levels in the fetal or maternal circulations. However, exposure of pre-eclamptic placentas to MgSO(4) significantly decreased TNF-alpha levels in both the fetal (0.89 +/- 0.09 pg/mL/g of cotyledon versus 1.6 +/- 0.59 pg/mL/g of cotyledon; p < 0.05) and the maternal circulations (4.74 +/- 2.78 pg/mL/g of cotyledon versus 14.28 +/- 2.69 pg/mL/g of cotyledon; p < 0.01). Down-regulation of placental TNF-alpha secretion by MgSO(4) in pre-eclampsia might indicate a possible therapeutic effect for this agent in reducing maternal, endothelial dysfunction and in improving neonatal outcome in pre-eclampsia, by reducing TNF-alpha levels in maternal and fetal circulations.

Effect of the Loading Dose of Magnesium Sulfate (MgSO4) on the Parameters of Doppler Flow Velocity in the Uterine, Umbilical and Middle Cerebral Arteries in Severe Preeclampsia

Objective. To evaluate Doppler velocimetry parameters (resistance index [RI], pulsatility index [PI] and systolic/diastolic [S/D] ratio) of maternal-fetal circulation before and after magnesium sulfate administration in pregnant women with severe preeclampsia. Methods. A prospective observational cohort analysis of 40 women with severe preeclampsia was performed. Doppler ultrasonography scans were performed before and 20 minutes after intravenous administration of magnesium sulfate. Maternal parameters such as heart rate, and systolic, diastolic and mean arterial pressure were recorded. Doppler flow velocity parameters (RI, PI and S/D ratio) were evaluated in the uterine, umbilical and middle cerebral arteries. The different mean values obtained before and after magnesium sulphate were analyzed using the paired t-test. Results. There was a statistically significant increase in mean maternal heart rate and a statistically significant decrease in systolic, diastolic and mean maternal blood pressure before and after administration of magnesium sulphate (p < 0.001). Resistance index decreased in the umbilical (p = 0.003; 95% CI: 0.008 - 0.03) and middle cerebral artery (p = 0.001; 95% CI: 0.01 - 0.05) and in both uterine arteries. Likewise, there was a significant reduction in the PI and S/D ratio in all the arteries assessed. Conclusions. Maternal administration of intravenous magnesium sulfate in preeclampsia leads to an increase in maternal heart rate and a decrease in systolic, diastolic and mean arterial blood pressure. A reduction in the resistance index, pulsatility index and S/D ratio was recorded in the uterine, umbilical and cerebral arteries.

Reducing stillbirths: interventions during labour.

BackgroundApproximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.MethodsWe undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.ResultsWe found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.ConclusionAlthough the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.

491: Effect of intravenous magnesium sulfate on markers of oxidative stress in women with preelclampsia

Lipid markers of oxidative stress have found to be increased in patients with preeclampsia. Little is known concerning the effects of intravenous magnesium sulfate on markers of oxidative stress in patients with preeclampsia. We investigated the potential ameliorative effects of intravenous magnesium sulfate in preeclampsia by measuring its effects on 8-isoprostane and TBARS, both markers of oxidative stress.

490: Effect of intravenous magnesium sulfate on free intracellular calcium and magnesium measured in peripheral blood monocytes of women with preeclampsia

AND MAGNESIUM MEASURED IN PERIPHERAL BLOOD MONOCYTES OF WOMEN WITH PREECLAMPSIA JAY BRINGMAN, CHARLES GIBBS, ROBERT AHOKAS, RISA RAMSEY, SYAMAL BHATTACHARYA, ROBERT EGERMAN, University of Tennessee Health Science Center, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee Health Science Center, Memphis, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee Health Science Center, Memphis, General Surgery, Memphis, Tennessee, University of Tennessee Health Science Center, Department of Obstetrics and Gynecology and Internal Medicine, Memphis, Tennessee OBJECTIVE: Intracellular calcium and magnesium are responsible for many cellular functions, including vascular tone and arterial blood flow as calcium channels are known to be magnesium-dependent. We investigated the potential ameliorative effects of magnesium sulfate in preeclampsia by measuring its effect on intracellular free calcium and magnesium in peripheral blood mononuclear cells (PBMCs) as a surrogate of maternal smooth muscle. STUDY DESIGN: After informed consent was obtained, peripheral blood was obtained before and after magnesium sulfate administration to preeclamptic gravidas. Patients were determined to have preeclampsia by ACOG criteria. After Histopaque isolation of PBMCs, intracellular free calcium and magnesium levels were measured ratiometrically using the fluorescent molecular probes Fura-2 and mag Fura-2, respectively. RESULTS: Six patients were included in the study. Intravenous magnesium sulfate resulted in a significant decrease in free intracellular calcium and a significant increase in free intracellular magnesium levels in PBMCs (p 0.0313, p 0.0126, respectively). CONCLUSION: Magnesium sulfate infusion resulted in a lowering of free intracellular calcium and an elevation in free intracellular magnesium levels in PBMCs. Some of the ameliorative effects of intravenous magnesium sulfate may be produced by alterations in intracellular ionic calcium as either a direct effect on contractile proteins or as a secondary messenger for additional processes.

Pathophysiology and therapeutic possibilities of calcitonin gene-related peptide in hypertension

Calcitonin gene related peptide (CGRP), a 37 amino acid neuropeptide, is the most potent vasodilator known. Participation of CGRP in hypertension and related diseases, such as preeclampsia or vasospasm after subarachnoid haemorrage, is one of the most studied topics. In this review we summarize the published roles of CGRP in pathophysiology of hypertension in humans and in experimental models. We also discuss the effects of direct administration of CGRP in the treatment of hypertension and of anti-hypertensive drugs that enhance the release or response of endogenous calcitonin gene-related peptide: angiotensin converting enzyme inhibitors, selective antagonists for the angiotensin II receptor, beta-blockers, magnesium sulphate for preeclampsia and rutaecarpine, as well as the possibilities using CGRP in gene therapy for prevention of vasospasm after subarachnoid haemorrage.

Trial needed to assess magnesium sulfate in pre-eclampsia

Trial needed to assess magnesium sulfate in pre-eclampsia

Favorable hemodynamic effects of magnesium sulfate in preeclampsia

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of magnesium sulfate in preeclamptic and preterm labor patients. STUDY DESIGN: Fifteen preeclamptic patients at 32.4 ± 3.3 (mean ± SD) weeks' gestation and 11 preterm labor patients (31.3 ± 2.8 weeks) were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance (BoMed, Irvine, Calif.) before and during high-dose magnesium sulfate bolus and infusion. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during magnesium sulfate infusion. All patients received a standard crystalloid infusion. Data analysis continued until the patient received epidural placement or other antihypertensive therapy or was delivered. RESULTS: At baseline the systemic vascular resistance index was 2465 ± 718 F · ohm/m 2 and the cardiac index was 3.6 ± 1.0 L/min/m 2 for the preeclamptic patients. These were significantly different compared with the preterm labor patients, who had a systemic vascular resistance index of 1377 ± 563 F · ohm/m 2 and 4.6 ± 1.2 L/min/m 2. Magnesium sulfate infusion resulted in a rapid, sustained fall in systemic vascular resistance and a rise in cardiac index in the preeclamptic patient. This effect was evident at least 4 hours after initiation of the bolus and infusion. In the preterm labor patients the hemodynamic effects of magnesium sulfate were minimal and were noted only during the magnesium sulfate bolus. CONCLUSION: Magnesium sulfate infusion appears to have a prolonged hemodynamic effect in the preeclamptic patient. Sustained reduction in systemic vascular resistance and an increase in cardiac index is found in patients with preeclampsia but not in preterm labor.

Favorable hemodynamic effects of magnesium sulfate in preeclampsia: [formula omitted], B. Hogg x, R. Newman. Dept. OB/GYN, Medical University of South Carolina, Charleston

Favorable hemodynamic effects of magnesium sulfate in preeclampsia: [formula omitted], B. Hogg x, R. Newman. Dept. OB/GYN, Medical University of South Carolina, Charleston

The Kinetics of Magnesium Sulphate in Pre-eclampsia

The Kinetics of Magnesium Sulphate in Pre-eclampsia