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BMC Pregnancy and Childbirth Jun 2024To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in...
OBJECTIVE
To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE.
METHODS
Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates.
RESULTS
A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4.
CONCLUSIONS
The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO was completed through Monte Carlo simulation.
Topics: Humans; Female; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Adult; Prospective Studies; China; Young Adult; Dose-Response Relationship, Drug; East Asian People
PubMed: 38872116
DOI: 10.1186/s12884-024-06620-x -
Frontiers in Synaptic Neuroscience 2021Synaptic signaling is integral for proper brain function. During fetal development, exposure to inflammation or mild hypoxic-ischemic insult may lead to synaptic changes... (Review)
Review
Synaptic signaling is integral for proper brain function. During fetal development, exposure to inflammation or mild hypoxic-ischemic insult may lead to synaptic changes and neurological damage that impairs future brain function. Preterm neonates are most susceptible to these deleterious outcomes. Evaluating clinically used and novel fetal neuroprotective measures is essential for expanding treatment options to mitigate the short and long-term consequences of fetal brain injury. Magnesium sulfate is a clinical fetal neuroprotective agent utilized in cases of imminent preterm birth. By blocking N-methyl-D-aspartate receptors, magnesium sulfate reduces glutamatergic signaling, which alters calcium influx, leading to a decrease in excitotoxicity. Emerging evidence suggests that melatonin and N-acetyl-L-cysteine (NAC) may also serve as novel putative fetal neuroprotective candidates. Melatonin has important anti-inflammatory and antioxidant properties and is a known mediator of synaptic plasticity and neuronal generation. While NAC acts as an antioxidant and a precursor to glutathione, it also modulates the glutamate system. Glutamate excitotoxicity and dysregulation can induce perinatal preterm brain injury through damage to maturing oligodendrocytes and neurons. The improved drug efficacy and delivery of the dendrimer-bound NAC conjugate provides an opportunity for enhanced pharmacological intervention. Here, we review recent literature on the synaptic pathways underlying these therapeutic strategies, discuss the current gaps in knowledge, and propose future directions for the field of fetal neuroprotective agents.
PubMed: 34248595
DOI: 10.3389/fnsyn.2021.680899 -
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 -
Nefrologia Apr 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.
PubMed: 33892977
DOI: 10.1016/j.nefro.2020.11.020 -
Cureus Mar 2024In the field of general anesthesia, magnesium sulfate (MgSO4) has become a valuable adjunct because it provides a range of benefits that enhance and optimize... (Review)
Review
In the field of general anesthesia, magnesium sulfate (MgSO4) has become a valuable adjunct because it provides a range of benefits that enhance and optimize conventional aesthetic procedures. This review highlights the various intra-anesthetic benefits of MgSO4 while examining its complex function in the treatment using anesthesia. Magnesium inhibits the release of acetylcholine at the motor endplate and blocks calcium channels at presynaptic nerve terminals. This reduces the amplitude of endplate potential and the excitability of muscle fibers, which increases the potency of a neuromuscular blockade by nondepolarizing neuromuscular blockers. This activity may lessen the need for primary muscle relaxants. Moreover, its capacity to potentially reduce the total amount of main aesthetic agents needed emphasizes its function in maximizing anesthesia dosage, ensuring sufficient depth while perhaps potentially reducing adverse effects linked with increased dosages. MgSO4's adaptable qualities present a viable path for improving anesthetic outcomes, possibly improving patient safety and improving surgical results.
PubMed: 38633961
DOI: 10.7759/cureus.56348 -
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 -
Journal of Korean Medical Science Nov 2023Though antenatal magnesium sulfate (MgSO) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO have been raised.
BACKGROUND
Though antenatal magnesium sulfate (MgSO) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO have been raised.
METHODS
We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24-31 weeks.
RESULTS
Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18-24 months and 3 years of age did not decrease in the MgSO group (infants who were exposed to MgSO for any purpose) or neuroprotection group (infants who were exposed to MgSO for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO). The z-scores of weight, height, and head circumference did not increase in the MgSO group or neuroprotection group compared with the control group.
CONCLUSION
Antenatal MgSO including MgSO for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.
Topics: Infant; Humans; Pregnancy; Female; Infant, Newborn; Magnesium Sulfate; Premature Birth; Neuroprotective Agents; Prenatal Care; Infant, Very Low Birth Weight
PubMed: 37967876
DOI: 10.3346/jkms.2023.38.e350 -
Turkish Journal of Medical Sciences 2023This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and...
BACKGROUND/AIM
This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and magnesium sulfate (MgSO) used separately and together on feto-maternal outcomes.
MATERIALS AND METHODS
We created PE in rats using a reduced uterine perfusion pressure (RUPP) animal model and recorded blood pressure (BP), embryonic survival (ES), and embryonic weight (EW) and evaluated cochlear morphology by electron microscopy.
RESULTS
The PE group had elevated BP, a decreased number and weight of live pups, and significant degeneration in the cochlea compared to the sham group. In the PEV group, we observed significant beneficial effects of Vit D supplementation at 14.5 and 19.5 dpc in terms of BP (p < 0.05), EW (p < 0.001), and cochlear degeneration compared to the PE group. In the PEM group, BP (p < 0.05) and cochlear degeneration nearly reached the level found in the sham group. However, although the EW was statistically different in the PE group, it did not reach sham group levels. We also observed that BP returned to sham level (p < 0.01) and noticed significant increases in the EW (p < 0.0001) and ES (p = 0.017) in the PEMV group compared to the PE group. According to the scanning electron microscope results, combined administration of VitD and MgSO is more effective than separate administration in improving cochlear degeneration induced by PE.
CONCLUSION
The administration of Vit D and MgSO during pregnancy has beneficial effects on PE pathology and may play a significant role in preventing PE-related complications, including cochlear degeneration.
Topics: Animals; Magnesium Sulfate; Pre-Eclampsia; Female; Pregnancy; Cochlea; Vitamin D; Rats; Disease Models, Animal; Rats, Sprague-Dawley
PubMed: 38813514
DOI: 10.55730/1300-0144.5730 -
Frontiers in Pediatrics 2022There is a paucity of data on the use of intravenous magnesium sulfate infusion in children with refractory status asthmaticus. The purpose of this study was to evaluate...
OBJECTIVES
There is a paucity of data on the use of intravenous magnesium sulfate infusion in children with refractory status asthmaticus. The purpose of this study was to evaluate the efficacy and safety of prolonged magnesium sulfate infusion as an advanced therapy.
METHODS
This is a single center retrospective study of children admitted to our pediatric intensive care unit (PICU) with status asthmaticus requiring continuous albuterol. Treatment group included patients receiving magnesium for ≥4 h and control group included those on other therapies only. Patients were matched 1:4 based on age, sex, obesity, pediatric index of mortality III and pediatric risk of mortality III scores. Primary outcomes included PICU length of stay (LOS) and mechanical ventilation (MV) requirement. Secondary outcomes included mortality, extracorporeal membrane oxygenation (ECMO) requirement, analyses of factors associated with PICU LOS and MV requirement and safety of magnesium infusion. Logistic and linear regressions were employed to determine factors associated with MV requirement and PICU LOS, respectively.
RESULTS
Treatment and control groups included 27 and 108 patients, respectively. Median initial infusion rate was 15 mg/kg/hour, with median duration of 28 h. There was no difference in the MV requirement between the treatment and control groups [7 (25.9%) vs. 20 patients (18.5%), = 0.39]. Median PICU LOS and ECMO use were significantly higher in treatment vs. control group [(3.63 vs. 1.09 days, < 0.01) and (11.1 vs. 0%, < 0.01), respectively]. No mortality difference was noted. On regression analysis, patients receiving ketamine and higher prednisone equivalent dosing had higher odds of MV requirement [OR 19.29 (95% CI 5.40-68.88), < 0.01 and 1.099 (95% CI 1.03-1.17), < 0.01, respectively]. Each mg/kg increase in prednisone equivalent dosing corresponded to an increase in PICU LOS by 0.13 days (95% CI 0.096-0.160, < 0.01). Magnesium infusions were not associated with lower MV requirement or lower PICU LOS after controlling for covariates. Fourteen (51.9%) patients in the treatment group had an adverse event, hypotension being the most common.
CONCLUSION
Magnesium sulfate infusions were not associated with MV requirement, PICU LOS or mortality.
PubMed: 35757130
DOI: 10.3389/fped.2022.860921 -
Brazilian Journal of Anesthesiology... 2021Opioids have usually been used as intraoperative analgesic components, regardless of the many adverse effects they are associated with, such as nausea, vomiting,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION AND OBJECTIVE
Opioids have usually been used as intraoperative analgesic components, regardless of the many adverse effects they are associated with, such as nausea, vomiting, respiratory depression, and hyperalgesia. Several approaches have been investigated to reduce doses used, and magnesium sulfate has been shown to be a valuable analgesic adjunct. The main objective of the present trial was to evaluate the effectiveness of magnesium sulfate as the chief intraoperative analgesic, and the secondary objectives were to assess propofol consumption, postoperative analgesia, and intraoperative hemodynamic stability.
METHODS
In this prospective, double-blind trial, 50 patients scheduled to undergo post-bariatric abdominoplasty under general intravenous anesthesia were divided into two groups, to receive remifentanil or magnesium sulfate as intraoperative analgesic. Fentanyl 1 µg kg was the rescue analgesic.
RESULTS
Among the patients in the group receiving Magnesium Sulfate (MSG), 64% did not need supplemental analgesia and none of the patients in the Remifentanil Group (RG) required fentanyl. MSG patients showed propofol consumption 36.6% higher (guided by the Bispectral Index - BIS). MSG patients consumed significantly less ephedrine (mean ± SD) than RG patients, respectively 1.52 ± 4.38 mg and 10 ± 10.39 mg, p < 0.001. Mean values of blood concentrations of magnesium were comparable to values previously described in the literature.
CONCLUSION
Magnesium sulfate is a safe and effective option for intraoperative analgesia, when avoiding or decreasing opioid use is required.
Topics: Analgesics; Analgesics, Opioid; Anesthesia, Intravenous; Double-Blind Method; Fentanyl; Humans; Magnesium Sulfate; Pain, Postoperative; Prospective Studies
PubMed: 34537125
DOI: 10.1016/j.bjane.2021.02.008