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PLoS Medicine Dec 2019There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes.
METHODS AND FINDINGS
CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only.
CONCLUSIONS
Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.
Topics: Case-Control Studies; Eclampsia; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Parturition; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Prospective Studies
PubMed: 31809499
DOI: 10.1371/journal.pmed.1002988 -
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 -
Tropical Medicine & International... Oct 2021Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality...
Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.
Topics: Anticonvulsants; Humans; Magnesium Sulfate; Tetanus
PubMed: 34403179
DOI: 10.1111/tmi.13667 -
Cureus Dec 2020Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue... (Review)
Review
Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke. Minocycline (MC) and Magnesium (Mg) are promising therapies for ischemic stroke, especially in the pre-hospital setting. These drugs are readily available, inexpensive, and generally safe. We decided to investigate these drugs' neuroprotective effects in treating ischemic stroke in the acute and chronic setting. We conducted a systematic review of the published literature on MC and Mg's functional outcome in ischemic stroke. This paper's methodology included only clinical trials published in the last 15 years, using PubMed as a database. The systematic review demonstrated that MC infusion in the pre-hospital and hospital setting improved functional outcomes and disability scores. Furthermore, MC also decreased matrix metalloproteinase 9 (MMP-9) levels. MC might have a more significant effect on men than women because different molecular pathways of cerebral ischemia seem to be involved between both genders. The systematic review showed that patients with ischemic stroke did not benefit from magnesium sulfate infusion in the pre-hospital and hospital setting. Nevertheless, patients with lacunar strokes and patients who supplemented their meals with potassium-magnesium salt in the diet had better functional outcomes. Future studies would need a more significant sample of participants and a better selection to increase the study's power and avoid selection bias, respectively. Further publications could benefit from subcategorizing strokes and investigating the gender role in stroke treatment. These directives could give a more robust conclusion regarding the neuroprotective effects of these drugs.
PubMed: 33520535
DOI: 10.7759/cureus.12339 -
Developmental Medicine and Child... Nov 2022We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat... (Meta-Analysis)
Meta-Analysis Review
AIM
We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.
METHOD
All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.
RESULTS
Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO combination, high dose ACTH (with/without vitamin B ), high dose prednisolone, and low dose ACTH were 'best'.
INTERPRETATION
Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.
WHAT THIS PAPER ADDS
Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Child; Humans; Infant; Magnesium Sulfate; Methylprednisolone; Network Meta-Analysis; Spasms, Infantile; Treatment Outcome; Vitamins
PubMed: 35765990
DOI: 10.1111/dmcn.15330 -
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 Pediatrics 2022Magnesium sulfate is a second-tier therapy for asthma exacerbations in children; guidelines recommend a single-dose to improve pulmonary function and decrease the odds...
OBJECTIVES
Magnesium sulfate is a second-tier therapy for asthma exacerbations in children; guidelines recommend a single-dose to improve pulmonary function and decrease the odds of admission to the in-patient setting. However, many clinicians utilize prolonged magnesium sulfate infusions for children with refractory asthma. The purpose of this review is to describe the efficacy and safety of magnesium sulfate infusions administered over ≥ 1 h in children with status asthmaticus.
METHODS
Medline was searched using the keywords "magnesium sulfate" and "children." Articles evaluating the use of magnesium sulfate infusions for ≥1 h published between 1946 and August 2021 were included. Published abstracts were not included because of lack of essential details. All articles were screened by two reviewers.
RESULTS
Eight reports including 447 children were included. The magnesium regimens evaluated included magnesium delivered over 1 h ( = 148; 33.1%), over 4-5 h ( = 105; 23.5%), and over >24 h ( = 194; 43.4%). Majority of patients received a bolus dose of 25-75 mg/kg/dose prior to initiation of a prolonged infusion ( = 299; 66.9%). For the patients receiving magnesium infusions over 4-5 h, the dosing regimen varied between 40 and 50 mg/kg/h. For those receiving magnesium infusions >24 h, the dosing varied between 18.4 and 25 mg/kg/h for a duration between 53.4 and 177.5 h. Only three reports including 186 patients (41.6%) included an evaluation of clinical outcomes including evaluation of lung function parameters, reduction in PICU transfers, and/or decrease in emergency department length of stay. Five reports including 261 patients (58.4%) evaluated magnesium serum concentrations. In most reports, the goal concentrations were between 4 and 6 mg/dL. Only 3 (1.1%) out of the 261 patients had supratherapeutic magnesium concentrations. The only reports finding adverse events attributed to magnesium were noted in those receiving infusions for >24 h. Clinically significant adverse events included hypotension ( = 74; 16.6%), nausea/vomiting ( = 35; 7.8%), mild muscle weakness ( = 22; 4.9%), flushing ( = 10; 2.2%), and sedation ( = 2; 0.4%).
CONCLUSION
Significant variability was noted in magnesium dosing regimens, with most children receiving magnesium infusions over >4 h. Most reports did not assess clinical outcomes. Until future research is conducted, the use of prolonged magnesium sulfate infusions should be reserved for refractory asthma therapy.
PubMed: 35391743
DOI: 10.3389/fped.2022.853574 -
European Journal of Anaesthesiology Oct 2023Pain after craniotomy can be intense and its management is often suboptimal.
BACKGROUND
Pain after craniotomy can be intense and its management is often suboptimal.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy.
DESIGN
A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken.
DATA SOURCES
Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases.
ELIGIBILITY CRITERIA
Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance.
RESULTS
Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block.
CONCLUSIONS
The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Humans; Pain Management; Dexmedetomidine; Acetaminophen; Analgesics; Pain, Postoperative; Craniotomy; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37417808
DOI: 10.1097/EJA.0000000000001877 -
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 -
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