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Combination treatments with therapeutic hypothermia for hypoxic-ischemic neuroprotection.
Zhou, KQ, Davidson, JO, Bennet, L, Gunn, AJ
Developmental medicine and child neurology. 2020;(10):1131-1137
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Abstract
Therapeutic hypothermia is now proven to reduce death or disability in term and near-term born infants with moderate to severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite treatment with hypothermia. Recent preclinical and clinical studies suggest that current protocols for therapeutic hypothermia are near-optimal. The obvious strategy, in addition to improving early initiation of therapeutic hypothermia after birth, is to combine hypothermia with other neuroprotective agents. We review evidence that the mechanisms of action of many promising agents overlap with the anti-excitotoxic, anti-apoptotic, and anti-inflammatory mechanisms of hypothermia, leading to a lack of benefit from combination treatment. Moreover, even apparently beneficial combinations have failed to translate in clinical trials. These considerations highlight the need for preclinical studies to test clinically realistic protocols of timing and duration of treatment, before committing to large randomized controlled trials.
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Preterm premature rupture of membranes.
Meller, CH, Carducci, ME, Ceriani Cernadas, JM, Otaño, L
Archivos argentinos de pediatria. 2018;(4):e575-e581
Abstract
Preterm premature rupture of membranes occurs in around 3% of pregnancies, and several aspects related to its management are still controversial. The objective of this update is to provide a detailed review of strategies aimed at reducing morbidity and mortality associated with this maternal condition. We will discuss the available evidence regarding the maternal use of antibiotics, the use of corticosteroids according to gestational age, the use of magnesium sulphate for fetal neuroprotection, the use of tocolytic agents, and the best moment for and route of delivery. This review also covers the effects of prolonged preterm premature rupture of membranes, infant morbidity and mortality in the short and long term, the harmful effects of antibiotics after delivery, including the effects on neurodevelopment and the presence of longterm chronic diseases.
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Magnesium sulfate infusion for acute asthma in the emergency department.
Irazuzta, JE, Chiriboga, N
Jornal de pediatria. 2017;:19-25
Abstract
OBJECTIVES To describe the role of intravenous magnesium sulfate (MgSO4) as therapy for acute severe asthma in the pediatric emergency department (ED). SOURCE Publications were searched in the PubMed and Cochrane databases using the following keywords: magnesium AND asthma AND children AND clinical trial. A total of 53 publications were retrieved using this criteria. References of relevant articles were also screened. The authors included the summary of relevant publications where intravenous magnesium sulfate was studied in children (age <18 years) with acute asthma. The NAEPP and Global Initiative for Asthma expert panel guidelines were also reviewed. SUMMARY OF THE DATA There is a large variability in the ED practices on the intravenous administration of MgSO4 for severe asthma. The pharmacokinetics of MgSO4 is often not taken into account with a consequent impact in its pharmacodynamics properties. The cumulative evidence points to the effectiveness of intravenous MgSO4 in preventing hospitalization, if utilized in a timely manner and at an appropriate dosage (50-75mg/kg). For every five children treated in the ED, one hospital admission could be prevented. Another administration modality is a high-dose continuous magnesium sulfate infusion (HDMI) as 50mg/kg/h/4h (200mg/kg/4h). The early utilization of HDMI for non-infectious mediated asthma may be superior to a MgSO4 bolus in avoiding admissions and expediting discharges from the ED. HDMI appears to be cost-effective if applied early to a selected population. Intravenous MgSO4 has a similar safety profile than other asthma therapies. CONCLUSIONS Treatment with intravenous MgSO4 reduces the odds of hospital admissions. The use of intravenous MgSO4 in the emergency room was not associated with significant side effects or harm. The authors emphasize the role of MgSO4 as an adjunctive therapy, while corticosteroids and beta agonist remain the primary acute therapeutic agents.
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Pathophysiology and Current Clinical Management of Preeclampsia.
Amaral, LM, Wallace, K, Owens, M, LaMarca, B
Current hypertension reports. 2017;(8):61
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Abstract
Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.
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Asthma in adults (acute): magnesium sulfate treatment.
Green, RH
BMJ clinical evidence. 2016
Abstract
INTRODUCTION About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild to moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This overview does not endorse or follow any particular protocol, but presents the evidence about a specific intervention, magnesium sulfate. METHODS AND OUTCOMES We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of magnesium sulfate for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS At this update, searching of electronic databases retrieved 50 studies. After deduplication and removal of conference abstracts, 24 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 10 studies and the further review of 14 full publications. Of the 14 full articles evaluated, one systematic review was updated and one systematic review was added at this update. We performed a GRADE evaluation for five PICO combinations. CONCLUSIONS In this systematic overview, we categorised the efficacy for two comparisons based on information about the effectiveness and safety of magnesium sulfate (iv) versus placebo and magnesium sulfate (nebulised) plus short-acting beta2 agonists (inhaled) versus short-acting beta2 agonists (inhaled) alone.
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Intravenous magnesium sulfate for treating children with acute asthma in the emergency department.
Griffiths, B, Kew, KM
The Cochrane database of systematic reviews. 2016;(4):CD011050
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BACKGROUND Acute asthma in children can be life-threatening and must be treated promptly in the emergency setting. Intravenous magnesium sulfate is recommended by various guidelines for cases of acute asthma that have not responded to first-line treatment with bronchodilators and steroids. The treatment has recently been shown to reduce the need for hospital admission for adults compared with placebo, but it is unclear whether it is equally effective for children. OBJECTIVES To assess the safety and efficacy of intravenous magnesium sulfate (IV MgSO4) in children treated for acute asthma in the emergency department (ED). SEARCH METHODS We identified studies by searching the Cochrane Airways Review Group Specialised Register up to 23 February 2016. We also searched ClinicalTrials.gov and reference lists of other reviews, and we contacted study authors to ask for additional information. SELECTION CRITERIA We included randomised controlled trials of children treated in the ED for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS Two review authors screened the results of the search and independently extracted data from studies meeting the inclusion criteria. We resolved disagreements through discussion and contacted study authors in cases of missing data and other uncertainties relating to the studies.We analysed dichotomous data as odds ratios and continuous data as mean differences, both using fixed-effect models. We assessed each study for risk of bias and rated the quality of evidence for each outcome with GRADE and presented the results in a 'Summary of findings' table. There was insufficient evidence to conduct the planned subgroup analyses. MAIN RESULTS Five studies (182 children) met the inclusion criteria, and four contributed data to at least one meta-analysis. The included studies were overall at low risk of bias, but our confidence in the evidence was generally low, mainly due to the small sample sizes. Treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.74; children = 115; studies = 3; I(2) = 63%). This result was based on data from just three studies including 115 children. Meta-analysis for the secondary outcomes was extremely limited by paucity of data. We performed meta-analysis for the outcome 'return to the emergency department within 48 hours', which showed a very imprecise effect estimate that was not statistically significant (OR 0.40, 95% CI 0.02 to 10.30; children = 85; studies = 2; I(2) = 0%). Side effects and adverse events were not consistently reported and meta-analysis was not possible, however few side effects or adverse events were reported. AUTHORS' CONCLUSIONS IV MgSO4 may reduce the need for hospital admission in children presenting to the ED with moderate to severe exacerbations of asthma, but the evidence is extremely limited by the number and size of studies. Few side effects of the treatment were reported, but the data were extremely limited.
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What we learned about the role of antenatal magnesium sulfate for the prevention of cerebral palsy.
Rouse, DJ, Hirtz, D, ,
Seminars in perinatology. 2016;(5):303-6
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Based on the convincing case control study of Nelson and Grether which suggested that the administration of magnesium sulfate to mothers prior to early preterm birth might protect their offspring from cerebral palsy, and a pilot study by John Hauth et al. at the University of Alabama at Birmingham, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, with co-funding from the National Institute of Neurologic Disorders and Stroke embarked on the Beneficial Effects of Antenatal Magnesium (BEAM) Trial in 1997.
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An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management.
Smith, JM, Lowe, RF, Fullerton, J, Currie, SM, Harris, L, Felker-Kantor, E
BMC pregnancy and childbirth. 2013;:34
Abstract
BACKGROUND Pre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate. METHODS An integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use. RESULTS A total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0-8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies. CONCLUSION Concerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice.
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Magnesium sulfate for the treatment of eclampsia: a brief review.
Euser, AG, Cipolla, MJ
Stroke. 2009;(4):1169-75
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BACKGROUND AND PURPOSE Magnesium sulfate is used extensively for prevention of eclamptic seizures. Empirical and clinical evidence supports the effectiveness of magnesium sulfate; however, questions remain as to its safety and mechanism. This review summarizes current evidence supporting the possible mechanisms of action and several controversies for magnesium sulfate treatment. SUMMARY OF REVIEW Several mechanisms are presented, including the effects of magnesium sulfate on peripheral and cerebral vasodilation, blood-brain barrier protection, and as an anticonvulsant. CONCLUSIONS Though the specific mechanisms of action remain unclear, the effect of magnesium sulfate in the prevention of eclampsia is likely multi-factorial. Magnesium sulfate may act as a vasodilator, with actions in the peripheral vasculature or the cerebrovasculature, to decrease peripheral vascular resistance or relieve vasoconstriction. Additionally, magnesium sulfate may also protect the blood-brain barrier and limit cerebral edema formation, or it may act through a central anticonvulsant action.
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Magnesium sulfate for persistent pulmonary hypertension of the newborn.
Ho, JJ, Rasa, G
The Cochrane database of systematic reviews. 2007;(3):CD005588
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BACKGROUND Persistent pulmonary hypertension of the newborn (PPHN) occurs in approximately 1.9 per 1000 newborns and may be more frequent in developing countries. There is strong evidence for the use of inhaled nitric oxide (iNO) and extra corporeal membrane oxygenation (ECMO) in the treatment of PPHN. However, many developing countries do not have access or the technical expertise required for these expensive therapies. Magnesium sulfate is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures associated with PPHN. If magnesium sulfate were found to be effective in the treatment of PPHN, this could be a cost effective and potentially life-saving therapy. OBJECTIVES To evaluate the use of magnesium sulfate compared with placebo or standard ventilator management alone, sildenafil infusion, adenosine infusion, or inhaled nitric oxide on mortality or the use of backup iNO or ECMO in term and near-term newborns (> 34 weeks gestational age) with PPHN. SEARCH STRATEGY The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. No language restrictions was applied. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and MEDLINE (1966 to April 20, 2007) were searched for relevant randomized and quasi-randomized trials. In addition the reference lists of retrieved articles were reviewed and known experts were contacted to obtain unpublished data. SELECTION CRITERIA All randomised or quasi-random studies were eligible where one of the treatment groups received magnesium sulfate for PPHN. DATA COLLECTION AND ANALYSIS Standard methods of the Cochrane Collaboration and the CNRG were used, including independent assessment of trial quality and extraction of data by each author. MAIN RESULTS No eligible trials were found AUTHORS' CONCLUSIONS On the basis of the current lack of evidence, the use of magnesium sulphate cannot be recommended in the treatment of PPHN. Randomised controlled trials are recommended.