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Developmental Medicine and Child... Mar 2024To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). (Review)
Review
AIM
To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE).
METHOD
This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability).
RESULTS
Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision.
INTERPRETATION
Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.
PubMed: 38468452
DOI: 10.1111/dmcn.15899 -
PLOS Global Public Health 2024The quality of medicines for the prevention and management of hypertensive disorders of pregnancy globally is a critical challenge in the reduction of maternal mortality...
The quality of medicines for the prevention and management of hypertensive disorders of pregnancy globally is a critical challenge in the reduction of maternal mortality rate. We aimed to conduct a systematic review of available studies on the quality of the eight medicines recommended globally for the prevention and management of hypertensive disorders of pregnancy. We searched five electronic databases- Ovid MEDLINE, EMBASE, CINAHL, ProQuest and Cochrane Library, and also grey literature, without year or language limitations. Any study assessing the quality parameters (Active Pharmaceutical Ingredients, pH, sterility, solubility, impurities) of medicines by using any valid laboratory methods was eligible. Two reviewers independently screened the studies, extracted data and applied Medicine Quality Assessment Reporting Guidelines tool for quality assessment. Results were narratively reported and stratified by the drug types. Of 5669 citations screened, 33 studies from 27 countries were included. Five studies reported on the quality of magnesium sulphate-two (Nigeria and USA) found substandard medicine due to failing API specification and contaminants, respectively. Another study from Nigeria and a multi-country study (10 lower-middle- and low-income countries) found poor-quality due to failing the pH criteria. Seven of eight studies evaluating aspirin found quality issues, including degraded medicines in five studies (Brazil, USA, Yugoslavia and Pakistan). Five studies of calcium supplements found quality issues, particularly heavy metal contamination. Of 15 antihypertensives quality studies, 12 found substandard medicines and one study identified counterfeit medicines. This systematic review identified pervasive issues of poor-quality medicines across all recommended medicines used to prevent or treat hypertensive disorders of pregnancy, raising concerns regarding their safety and effectiveness.
PubMed: 38412179
DOI: 10.1371/journal.pgph.0002962 -
Paediatric Respiratory Reviews Feb 2024Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well... (Review)
Review
BACKGROUND
Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well established. However, secondary treatments, including intravenous magnesium sulfate (IV-MgSO4), remain variable due to scarcity of data on its efficacy and safety.
OBJECTIVE
To assess the effectiveness and safety of IV-MgSO4 as a second line of treatment in managing children with asthma exacerbations.
METHODS
We searched five databases from inception until April 2023 on randomized clinical trials of IV-MgSO4 in children with acute asthma exacerbations. The primary outcomes were hospitalization rate and length, and change in the severity score. Secondary outcomes included percentage increase in peak expiratory flow rate (PEFR), hospital re-admission rate, need and length for pediatric intensive care unit (PICU) treatment, and adverse effects. Meta-analysis was performed for three outcomes with estimated odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs).
RESULTS
Eleven studies met the final criteria. In comparison to control, administration of IV-MgSO4 was associated with a reduced hospitalization risk (OR 0.15; 95%CI: 0.03, 0.73) in four studies, and improvement of lung function (MD 26.77% PEFR; 95%CI: 18.41, 54.79) in two studies. There were no significant differences in the length of stay between groups. Due to heterogeneity, a narrative synthesis of other outcomes was performed.
CONCLUSION
The use of IV-MgSO4 demonstrated a reduction in the hospitalization rate and PEFR improvement in children with asthma exacerbations. Adverse effects were rare. Further well-designed studies are needed to better determine the efficacy and safety profile of IV-MgSO4.
PubMed: 38395640
DOI: 10.1016/j.prrv.2024.01.003 -
Frontiers in Neurology 2023The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium...
INTRODUCTION
The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials.
METHODS
PubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality.
RESULTS
Of the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, = 0.04, 95% confidence interval (CI) (0.37-0.99)], DCI [OR = 0.57, = 0.01, 95% CI (0.37-0.88)], secondary cerebral infarction [OR = 0.49, = 0.01, 95% CI (0.27-0.87)] and neurological dysfunction [OR = 0.55, = 0.04, 95% CI (0.32-0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, = 0.47, 95% CI (0.73-1.15)] and rebleeding [OR = 0.68, = 0.55, 95% CI (0.19-2.40)] between the two groups.
CONCLUSION
The superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.
PubMed: 38020616
DOI: 10.3389/fneur.2023.1249369 -
The Cochrane Database of Systematic... Oct 2023Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years,... (Review)
Review
BACKGROUND
Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010.
OBJECTIVES
To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment.
DATA COLLECTION AND ANALYSIS
For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias. Treatment of women with eclampsia (four comparisons) One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence). One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence). One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence). One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. Prevention of eclampsia for women with pre-eclampsia (five comparisons) Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women). One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence). Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women). Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women). One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials.
AUTHORS' CONCLUSIONS
Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.
Topics: Humans; Pregnancy; Infant, Newborn; Female; Pre-Eclampsia; Magnesium Sulfate; Eclampsia; Perinatal Death; Stillbirth; Maternal Death; Seizures
PubMed: 37815037
DOI: 10.1002/14651858.CD007388.pub3 -
Archives of Gynecology and Obstetrics Mar 2024Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence.
METHODS
We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers.
RESULTS
Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death.
CONCLUSION
Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Chorioamnionitis; Magnesium Sulfate; Stillbirth; Fetal Diseases; Perinatal Death
PubMed: 37768342
DOI: 10.1007/s00404-023-07221-3 -
Archives of Academic Emergency Medicine 2023There has been growing interest in the potential role of adjunctive magnesium sulfate in improving pain management. This systematic review and meta-analysis aimed to...
INTRODUCTION
There has been growing interest in the potential role of adjunctive magnesium sulfate in improving pain management. This systematic review and meta-analysis aimed to assess the effect of intra-operative adjunctive magnesium sulfate on pain management and opioid consumption in total knee arthroplasty (TKA).
METHODS
A comprehensive search was conducted in Medline, Embase, Scopus, Web of Science, and Cochrane Library databases, covering studies up to April 2023. The extracted data included pain management outcomes, opioid consumption, and adverse effects from the selected studies. Standardized mean differences (SMDs) were calculated for continuous outcomes, while risk ratios (RRs) were calculated for dichotomous outcomes. Meta-analysis was conducted employing random-effects models in STATA 17.
RESULTS
In this meta-analysis of 8 randomized controlled trials involving 536 patients, adjunctive magnesium sulfate in TKA was found to significantly reduce opioid consumption during the first 24 hours after operation (SMD: -1.88, 95% confidence interval (CI): [-3.66 to -0.10]; p = 0.038). It also resulted in lower pain scores at rest 24 hours after surgery (SMD: -1.53, 95% CI: [-2.70 to -0.37]; p = 0.010). There were no significant differences in time to first rescue analgesic and adverse effects between the groups. The included studies were assessed to have low to high levels of risk of bias.
CONCLUSION
This study presents evidence at low to moderate levels supporting the use of intra-operative adjunctive magnesium sulfate in TKA for improved pain management and reduced opioid consumption. However, further research is needed to address the heterogeneity and to explore optimal dosing regimens and routes of administration to maximize the benefits of magnesium sulfate in TKA.
PubMed: 37671273
DOI: 10.22037/aaem.v11i1.2058 -
Magnesium sulfate treatment for acute severe asthma in adults-a systematic review and meta-analysis.Frontiers in Allergy 2023Add-on magnesium sulfate (MgSO4) for refractory asthma exacerbation has been much debated. The aim of this review and meta-analysis is, therefore, to provide an update... (Review)
Review
INTRODUCTION
Add-on magnesium sulfate (MgSO4) for refractory asthma exacerbation has been much debated. The aim of this review and meta-analysis is, therefore, to provide an update on the current evidence for the efficacy of MgSO4 in exacerbations of asthma in adults refractory to standard of care treatment.
METHODS
A systematic review was performed in accordance with the PRISMA guidelines. The search was performed in the PubMed database (updated April 2023). For the meta-analysis, a random-effects model was applied using the metaphor package for RStudio (RStudio, Inc.).
RESULTS
A total of 17 randomized controlled trials were included. Three of the nine studies addressing treatment with intravenous (IV) MgSO4 found a significant effect on lung function compared to placebo. Of the eight studies investigating hospital admission rate, only two found a significant effect of MgSO4. Six of the nine studies investigating treatment with nebulized MgSO4 compared to placebo found a favorable effect on forced expiratory volume in 1. second (FEV) and peak expiratory flow rate (PEF). Only two of the five studies investigating the effect on hospital admission rate found an effect of MgSO4. Comparing effect sizes in a meta-analysis revealed a greater effect on PEF in asthma patients treated with nebulized MgSO4 (MD, 23.57; 95% CI, -2.48 to 49.62, < 0.01) compared to placebo. The analysis of patients treated with i.v. MgSO4 compared to placebo showed no statistically significant difference (MD, 5.49; 95% CI, -18.67 to 29.65, = 0.10).
CONCLUSION
Up to two out of three studies revealed an effect of MgSO4 treatment for asthma exacerbation when assessed by FEV/PEF, but fewer studies were positive for the outcome of hospital admissions.
PubMed: 37577333
DOI: 10.3389/falgy.2023.1211949 -
Odontology Jan 2024Trace- and macro-chemical elements are crucial for cellular physiological functioning, and their alterations in biological fluids might be associated with an underlying... (Meta-Analysis)
Meta-Analysis
Trace- and macro-chemical elements are crucial for cellular physiological functioning, and their alterations in biological fluids might be associated with an underlying pathological state. Hence, this study aimed to examine and summarize the published literature concerning the application of salivary ionomics for caries diagnosis. An extensive search of studies was conducted using PubMed, EMBASE, Web of Science, and Scopus, without any language and year restriction for answering the following PECO question: "In subjects (i.e., children, adolescents, or adults) with good systematic health, are there any variations in the salivary concentrations of trace- or macro-elements between caries-free (CF) individuals and caries-active (CA) subjects?" A modified version of the QUADOMICS tool was used to assess the quality of the included studies. The Review Manager Version 5.4.1. was used for data analyses. The analysis of salivary chemical elements that significantly differed between CF and CA subjects was also performed. Thirty-four studies were included, involving 2299 CA and 1669 CF subjects, having an age range from 3 to 64 years in over 16 countries. The meta-analysis revealed a statistically significant difference (p < 0.05) in the salivary levels of calcium, phosphorus, chloride, magnesium, potassium, sodium, and zinc between CA and CF subjects, suggesting higher levels of calcium, phosphorus, potassium, and sodium in CF subjects while higher levels of chloride, magnesium, and zinc in CA patients. Half of the included studies (17/34) were considered high quality, while the remaining half were considered medium quality. Only zinc and chloride ions were found to be higher significantly and consistent in CF and CA subjects, respectively. Conflicting outcomes were observed for all other salivary chemical elements including aluminum, bromine, calcium, copper, fluoride, iron, potassium, magnesium, manganese, sodium, ammonia, nitrite, nitrate, phosphorus, lead, selenium, and sulfate ions.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Middle Aged; Young Adult; Calcium; Dental Caries; Ions; Magnesium; Magnesium Chloride; Phosphorus; Potassium; Sodium; Zinc; Saliva
PubMed: 37526792
DOI: 10.1007/s10266-023-00839-4 -
The Journal of Pediatrics Nov 2023To assess magnesium sulfate (MgSO) as a neuroprotective agent in hypoxic-ischemic encephalopathy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess magnesium sulfate (MgSO) as a neuroprotective agent in hypoxic-ischemic encephalopathy.
STUDY DESIGN
For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3.
RESULTS
Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO group. MgSO was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs).
CONCLUSIONS
Evidence around long-term outcomes of MgSO when used with or without TH was scant. MgSO therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings.
TRIAL REGISTRATION
"Open Science Forum" (https://doi.org/10.17605/OSF.IO/FRM4D).
Topics: Infant, Newborn; Infant; Humans; Magnesium Sulfate; Hypoxia-Ischemia, Brain; Seizures; Hypotension
PubMed: 37468038
DOI: 10.1016/j.jpeds.2023.113610