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JAMA Network Open May 2024Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death.
OBJECTIVE
To determine whether MgSO4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO4.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks' Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing.
EXPOSURES
Women received 4 g of MgSO4 or isotonic sodium chloride solution given intravenously over 30 minutes.
MAIN OUTCOMES AND MEASURES
Prior to data collection, it was hypothesized that infants who were exposed to MgSO4 would show enhanced functional connectivity compared with infants who were not exposed.
RESULTS
A total of 45 infants were included in the analysis: 24 receiving MgSO4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g, 0.47 [95% CI, -0.13 to 1.07]), transitivity (Hedge g, 0.51 [95% CI, -0.10 to 1.11]), local efficiency (Hedge g, 0.40 [95% CI, -0.20 to 0.99]), and global efficiency (Hedge g, 0.31 [95% CI, -0.29 to 0.90]), representing enhanced functional segregation and integration.
CONCLUSIONS AND RELEVANCE
In this cohort study, infants exposed to MgSO4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.
Topics: Humans; Magnesium Sulfate; Female; Pregnancy; Infant, Newborn; Magnetic Resonance Imaging; Male; Adult; Gestational Age; Cohort Studies; Premature Birth; Infant; Brain; Prenatal Care; Cerebral Palsy
PubMed: 38805222
DOI: 10.1001/jamanetworkopen.2024.13508 -
International Journal of Molecular... Mar 2023Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of...
Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of cromoglycate and magnesium in the orofacial model of pain and the histological profile of the effect of magnesium in orofacial pain. In male Wistar rats, formalin (1.5%, 100 µL) was injected subcutaneously into the right upper lip of rats after cromoglycate and/or magnesium. Pain was measured as the total time spent on pain-related behavior. Toluidine blue staining was used to visualize mast cells under the light microscope. In the formalin test, in phase 1, magnesium antagonized the antinociceptive effect of cromoglycate, while in phase 2, it potentiated or inhibited its effect. Magnesium significantly reduced mast cell degranulation in the acute phase by about 23% and in the second phase by about 40%. Pearson's coefficient did not show a significant correlation between mast cell degranulation and pain under treatment with magnesium. The cromoglycate-magnesium sulfate combination may prevent the development of inflammatory orofacial pain. The effect of a combination of cromoglycate-magnesium sulfate depends on the nature of the pain and the individual effects of the drugs. Magnesium reduced orofacial inflammation in the periphery, and this effect did not significantly contribute to its analgesic effect.
Topics: Rats; Animals; Male; Magnesium Sulfate; Magnesium; Cromolyn Sodium; Rats, Wistar; Cell Degranulation; Neuroinflammatory Diseases; Mast Cells; Facial Pain; Inflammation; Analgesics
PubMed: 37047214
DOI: 10.3390/ijms24076241 -
BMJ Clinical Evidence Jan 2016About 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... (Review)
Review
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.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adult; Anti-Asthmatic Agents; Asthma; Humans; Magnesium Sulfate
PubMed: 26761432
DOI: No ID Found -
Drug Design, Development and Therapy 2016Evaluation of the efficacy of nebulized magnesium sulfate (MgSO4) alone and in combination with salbutamol in acute asthma.
OBJECTIVE
Evaluation of the efficacy of nebulized magnesium sulfate (MgSO4) alone and in combination with salbutamol in acute asthma.
METHODS
A double-blind randomized controlled study was conducted in Chest and Emergency Departments. Thirty patients of acute attack of bronchial asthma were randomized into three groups: MgSO4 nebulization (group A), salbutamol nebulization (group B), and their combination (group C). All patients were monitored before and after nebulization (each 20 minutes) for peak expiratory flow rate (PEFR), respiratory rate (RR), heart rate (HR), blood pressure, pulsus paradoxus, oxygen saturation, clinical examination, and Fischl index.
RESULTS
A highly significant improvement in PEFR, PEFR percentage, and Fischl index and significant decrease in RR and HR was observed in all groups. A similar improvement in PEFR was observed in group A and group B (P=0.389). The difference in peak expiratory flow (PEF) improvement was insignificant between group B and group C (P=0.101), while there was a significant difference between group A and group C (P=0.014) in favor of group C.
CONCLUSION
Nebulized MgSO4 alone or combined with salbutamol has a clinically significant bronchodilator effect in acute asthma and leads to clinical improvement, increase in PEFR, reduction in HR, and reduction in RR. The response to nebulized MgSO4 alone (PEFR improvement 54±35.6 L/min, P=0.001) is comparable (P=0.389) to that of nebulized salbutamol (PEFR improvement 67.0±41.9 L/min, P=0.001) and is significantly less than (P=0.014) that of nebulized combination (PEFR improvement 92.0±26.9 L/min, P=0.000).
Topics: Acute Disease; Administration, Inhalation; Airway Obstruction; Albuterol; Asthma; Double-Blind Method; Humans; Magnesium Sulfate; Peak Expiratory Flow Rate
PubMed: 27354766
DOI: 10.2147/DDDT.S103147 -
BMC Pregnancy and Childbirth Feb 2013Pre-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... (Review)
Review
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.
Topics: Anticonvulsants; Eclampsia; Female; Humans; Magnesium Sulfate; Maternal Mortality; Pre-Eclampsia; Pregnancy; Prospective Studies; Seizures
PubMed: 23383864
DOI: 10.1186/1471-2393-13-34 -
Jornal de Pediatria 2017To describe the role of intravenous magnesium sulfate (MgSO) as therapy for acute severe asthma in the pediatric emergency department (ED). (Review)
Review
OBJECTIVES
To describe the role of intravenous magnesium sulfate (MgSO) 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 MgSO for severe asthma. The pharmacokinetics of MgSO is often not taken into account with a consequent impact in its pharmacodynamics properties. The cumulative evidence points to the effectiveness of intravenous MgSO 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 MgSO bolus in avoiding admissions and expediting discharges from the ED. HDMI appears to be cost-effective if applied early to a selected population. Intravenous MgSO has a similar safety profile than other asthma therapies.
CONCLUSIONS
Treatment with intravenous MgSO reduces the odds of hospital admissions. The use of intravenous MgSO in the emergency room was not associated with significant side effects or harm. The authors emphasize the role of MgSO as an adjunctive therapy, while corticosteroids and beta agonist remain the primary acute therapeutic agents.
Topics: Acute Disease; Asthma; Child; Emergency Service, Hospital; Hospitalization; Humans; Infusions, Intravenous; Magnesium Sulfate; Severity of Illness Index
PubMed: 28754601
DOI: 10.1016/j.jped.2017.06.002 -
Journal of Perinatal Medicine Apr 2019Background Magnesium sulfate is an accepted intervention for fetal neuroprotection. There are some perceived differences in the international recommendations on the use...
Background Magnesium sulfate is an accepted intervention for fetal neuroprotection. There are some perceived differences in the international recommendations on the use magnesium sulfate for fetal neuroprotection in preterm labor. Content This systematic review analyses the available clinical guidelines for the use of magnesium sulfate for fetal neuroprotection and compares the recommendations, and assesses the quality of guidelines. This provides the consensus, differences and explores the areas for future collaborative research. We searched databases of PUBMED, EMBASE, COCHRANE, Web of Science, LILACS; and included the national and the international clinical practice guidelines. We included seven guidelines out of 227 search results. We evaluated the methodological quality of guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE II) tool and systematically extracted guideline characters, recommendation and supporting evidence base. Summary Five guidelines were of high quality and two were of moderate quality. One guideline achieved more than an 80% score in all the domains of AGREE II tool. All guidelines recommend use of magnesium sulfate for fetal neuroprotection. However, there are differences in other recommendations such as upper gestational age, dose, duration, repeating treatment and use of additional tocolytics. Outlook Future guidelines should include recommendations on all aspects of magnesium sulfate therapy for fetal neuroprotection. Future research and international collaboration should focus on areas where there are no international consensual recommendations.
Topics: Female; Humans; Magnesium Sulfate; Neuroprotective Agents; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy
PubMed: 30352042
DOI: 10.1515/jpm-2018-0174 -
Anaesthesiology Intensive Therapy 2022The search for an effective sedation schedule in managing delirium tremens that would ensure an adequate sedation level and good safety profile is an urgent problem of... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
INTRODUCTION
The search for an effective sedation schedule in managing delirium tremens that would ensure an adequate sedation level and good safety profile is an urgent problem of modern intensive care medicine. In this respect, the use of dexmedetomidine combined with magnesium preparations seems to be promising.
MATERIAL AND METHODS
A quasi-randomized prospective observational study was conducted on 80 patients with alcoholic delirium, who were divided into 4 groups. Assessment parameters were delirium duration, mean arterial pressure and heart rate, and plasma magnesium, urea, creatinine, transaminase, cortisol, and serotonin levels. The control-group patients underwent standard sedation therapy with benzodiazepines. In group 1, standard sedation was supplemented by magnesium sulphate. In group 2, dexmedetomidine infusion was used. In group 3, dexmedetomidine was supplemented by the correction of hypomagnesemia.
RESULTS
The duration of delirium proved to be significantly shorter in all study groups (3.4 ± 0.6 days in group 1; 1.55 ± 0.61 days in group 2) as compared to the control (5.4 ± 1.48 days), P < 0.001, being the shortest in group 3 (1.1 ± 0.18 days), P < 0.001. Cases of hypotension were detected only in the control group (2 cases [10%]) and group 1 (4 cases [20%]). The patients of groups 2 and 3 showed significant improvement in plasma levels of cortisol (16.7 ± 2.25 nmol L-1; 15.62 ± 1.63 nmol L-1) compared with the control (18.77 ± 2.76 nmol L-1), P = 0.019; P = 0.003. Serotonin level was higher in the experimental group 3 (87.8 ± 7.32 ng mL-1) as compared to the control (62.81 ± 9.81ng mL-1) and group 2 (71.73 ± 9.61 ng mL-1), P < 0.001.
CONCLUSIONS
Dexmedetomidine infusion combined with magnesium sulphate proved to be effective in the treatment of patients with alcohol delirium.
Topics: Humans; Dexmedetomidine; Hypnotics and Sedatives; Magnesium Sulfate; Magnesium; Hydrocortisone; Serotonin; Delirium; Intensive Care Units
PubMed: 36734446
DOI: 10.5114/ait.2022.123137 -
Nefrologia 2021The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups:...
The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin.
Topics: Animals; Colistin; Creatinine; Glutathione; Humans; Magnesium; Magnesium Sulfate; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Renal Insufficiency; Urea
PubMed: 36165156
DOI: 10.1016/j.nefroe.2022.01.005 -
Stroke Apr 2009Magnesium sulfate is used extensively for prevention of eclamptic seizures. Empirical and clinical evidence supports the effectiveness of magnesium sulfate; however,... (Review)
Review
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.
Topics: Anticonvulsants; Blood-Brain Barrier; Eclampsia; Epilepsy; Female; Humans; Magnesium Sulfate; Pregnancy; Vasodilation
PubMed: 19211496
DOI: 10.1161/STROKEAHA.108.527788