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Background: Recent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated., Methods: In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes., Results: Thirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10-1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07-0.96, p = 0.04)]., Conclusions: Administration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy., (© 2021. Springer Nature Switzerland AG.)

Objective: To evaluate whether obese women need greater doses of magnesium sulfate to obtain therapeutic serum concentrations for eclamptic seizure prevention., Methods: Women with preeclampsia and a body mass index (BMI) of 35 or higher were randomly allocated to either the Zuspan regimen of magnesium sulfate (4-g intravenous [IV] loading dose, then a 1-g/h infusion) or to alternate dosing (6-g IV loading dose, then a 2-g/h infusion). Women had serum magnesium concentrations obtained at baseline, as well as after administration of magnesium sulfate at 1 hour, 4 hours, and delivery. The primary outcome was the proportion of women who had subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration. A sample size of 18 women per group was planned to compare the proportion of women with subtherapeutic serum magnesium concentrations in each group., Results: From July 12, 2016, to March 14, 2019, 89 women with preeclampsia were screened and 37 were enrolled: 18 to the Zuspan regimen and 19 to the alternate regimen. A significantly greater proportion of women administered the Zuspan regimen had subtherapeutic serum magnesium concentrations at 4 hours (100% [95% CI 59-100] vs 63% [95% CI 41-81]; P=.01) compared with women administered the alternate higher dose regimen. At 4 hours, mean concentrations were significantly higher in the alternate regimen group (3.53 mg/dL±0.3 [Zuspan regimen] vs 4.41±0.5 [alternate regimen]; P<.01)., Conclusion: The alternate dosing regimen of a 6-g IV loading dose followed by a 2-g/h IV maintenance dose more reliably achieves therapeutic serum magnesium concentrations (as defined by a concentration of at least 4.8 mg/dL) in obese women with preeclampsia., Clinical Trial Registration: ClinicalTrials.gov, NCT02835339.

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO 4 ) to healthy horses. MgSO 4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO 4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg 2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg 2+ increased nearly fivefold, ionized calcium (Ca 2+ ) decreased by nearly 10%, and the Ca 2+ to Mg 2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca 2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO 4 ., (© 2020 John Wiley & Sons Ltd.)

Background: Magnesium sulfate (MgSO 4 ) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8-3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO 4 in patients with severe preeclampsia., Methods: Patients with severe preeclampsia who received MgSO 4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO 4 , and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration., Results: A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time from start of MgSO4 infusion to blood draw for serum sampling) as independent risk factors for sub-therapeutic serum magnesium concentration (P < 0.05). ROC curve analysis indicated that the continuous variable Ccr had a significant predictive value for the serum magnesium concentration, which resulted in a cutoff point of 133 mL/min; while measurement time had limited predictive value, with cutoff point of 2.375 h., Conclusions: Ccr, whether the loading dose was given, and measurement time were independent risk factors for sub-therapeutic serum magnesium concentration. A loading dose of MgSO 4 everytime before the maintenance dose, as well as the duration of MgSO4 maintenance dose of more than 2.375 h are recommended for all the patients with severe PE. Routine evaluation of serum magnesium levels is a recommended practice for women with severe PE and whose Ccr is ≥133 mL/min.

Background and Objective: The pharmacokinetic basis of magnesium sulphate (MgSO 4 ) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO 4 in PE, and to determine key covariates having an effect in MgSO 4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO 4 PK., Methods: A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO 4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO 4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates., Results: The study population consisted of 109 patients. The PK profile of MgSO 4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO 4 CL and V, respectively. The model was parameterized as CL and V., Conclusion: The PK of MgSO 4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO 4 . Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO 4 elimination rate.

Objective: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia., Patients and Methods: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor β1(TGF-β1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues., Results: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-β1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-β1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05)., Conclusions: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Purpose: Evaluation of mechanisms used to cope with an i.v. fluid shortage to determine if prescribing habits were changed and if substitution of an i.v. dose of magnesium with an oral dose impacted patient outcomes., Methods: A single-center, retrospective analysis of electronic medical record (EMR) alerts and medical records covering 6-month periods before and during an i.v. fluid shortage was conducted. Records of adult medical and surgical inpatients admitted during these periods who had an order for i.v. or oral magnesium were screened for inclusion. The primary outcome of part 1 of the study was the percent acceptance of drug shortage-related EMR alert recommendations associated with i.v. magnesium. The primary outcome of part 2 of the study was the change in serum magnesium concentration (SMC) after an i.v. or oral dose of magnesium was administered., Results: Of the 7,476 EMR alerts generated during provider ordering of i.v. magnesium products, 4.8% resulted in the provider accepting the recommendation to switch to an oral alternative, 89% resulted in continuation of an i.v. magnesium order, and 6.2% resulted in order cancellation. Among patients who received magnesium doses, SMC values increased by a mean (SD) of 0.135 (0.08) mg/dL per gram of i.v. magnesium sulfate administered (n = 251), compared to an increase of 0.058 (0.08) mg/dL per 400-mg tablet of magnesium oxide administered (n = 42)., Conclusion: Acceptance of the EMR alert recommendations was low. Both i.v. magnesium sulfate and oral magnesium oxide are viable options for increasing SMC., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: In this study, changes in lactate clearance following magnesium supplementation were evaluated in critically ill patients with severe sepsis., Methods: Fifty-eight patients with severe sepsis were randomly assigned to receive either magnesium (n = 30) or placebo (n = 28). Patients in the magnesium group received intravenous magnesium sulfate to maintain serum magnesium level around 3 mg/dL for 3 days. The placebo group received the same volume of normal saline. Change in lactate clearance was considered primary outcome of the study., Results: Mean increase in the lactate clearance in the magnesium group was significantly higher than the placebo group on day 2 (27.53% vs. 23.79% respectively, p < 0.001) and day 3 (49.83% vs. 37.02% respectively, p < 0.001). Time to lactate clearance was also significantly shorter in the magnesium group than the placebo group (47.28 ± 20.59 vs. 61.20 ± 24.31 h respectively, p = 0.03). Sepsis-related mortality was not significantly different but median length of ICU stay was significantly shorter in the magnesium group than the placebo group (8 vs. 15 days respectively, p < 0.01)., Conclusions: Magnesium supplementation increased lactate clearance in critically ill patients with severe sepsis. Optimizing serum magnesium level near the upper limit of the normal range may improve severe sepsis outcomes.

Introduction: There is little information on the effect of maternal characteristics and on-admission laboratory parameters to the therapeutic serum magnesium sulfate (MgSO 4 ) levels in women with preeclampsia (PE). We sought to identify factors that may predict timely attainment of therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis. Materials and methods: On-admission factors of 360 women with PE who received intravenous MgSO 4 (4-g loading and 2-g/h maintenance) for seizure prophylaxis were retrospectively reviewed. Parameters of those who attained therapeutic serum concentrations (4.8-8.4 mg/dL) within 2 h (Group A) and those who did not (Group B) were compared. Results: There was no seizure or magnesium toxicity in this cohort. Median (min-max) level of serum magnesium was 4.3 (2.5-8.4) mg/dL. Women in Group A ( n  = 105) had lower gestational age, body mass index (BMI), and platelets count, higher blood urea nitrogen (BUN), serum creatinine, uric acid, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin, and partial thromboplastin times than those in Group B ( n  = 255) ( p  < .05). Women with mild PE were less likely to attain therapeutic serum magnesium levels compared with those with severe phenotypes (adjusted OR 23.57, 95% CI 8.20-67.76 versus adjusted OR 14.72, 95% CI 3.56-60.89, respectively; p  < .05), which may be explained by their significantly lower serum BUN and uric acid ( p  < .05). Conclusions: On-admission factors, especially BMI and renal clearance indices, of women with PE may affect timely attainment of therapeutic serum magnesium levels. Validation of its clinical impact requires further study focusing on women with severe PE.

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure-response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve-eclampsia rate relationship. Our exposure-response model-estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration < 3.5 mmol/L (empiric safety threshold) and eclampsia rate ≤ 0.7% (observed response threshold), including 4 g intravenously plus 10 g intramuscularly followed by either 8 g intramuscularly every 6 hours × 3 doses or 10 g intramuscularly every 8 hours × 2 doses and 10 g intramuscularly every 8 hours × 3 doses. Several alternative magnesium sulfate regimens with comparable model-predicted efficacy and safety were identified that merit evaluation in confirmatory clinical trials., (© 2019 Meck Sharp & Dohme Corp. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Background: Magnesium sulfate is the ideal drug for the prevention and treatment of eclampsia. Nevertheless, the best regimen for protection against eclampsia with minimal side effects remains to be established. This study aimed to compare serum magnesium levels during intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose to prevent eclampsia in pregnant and postpartum women with severe preeclampsia., Methods: A randomized, triple-blind clinical trial was conducted, comparing serum magnesium levels during the intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose for the prevention of eclampsia in 62 pregnant and postpartum women with severe preeclampsia, 31 in each group. An intravenous loading dose of 6 grams of magnesium sulfate was administered over 30 minutes in both groups. The patients were then randomized to receive a maintenance dose of either 1 or 2 grams/hour for 24 hours. Primary outcomes consisted of serum magnesium levels at the following time points: baseline, 30 minutes, every 2 hours until the end of the first 6 hours, and every 6 hours thereafter until the termination of magnesium sulfate infusion. Side effects, maternal complications, and neonatal outcomes were the secondary outcomes., Results: Serum magnesium levels were higher in the 2-gram/hour group, with a statistically significant difference from 2 hours after the beginning of the magnesium sulfate infusion (P <.05). Oliguria was the most common complication recorded in both groups, with no significant difference between the 2 regimens (RR 0.88; 95% CI: 0.49-1.56; P = .65). No cases of eclampsia occurred. Side effects were more common in the 2-gram/hour group (RR 1.89; 95% CI: 1.04-3.41; P = .02); however, all were mild. There were no differences between the 2 groups regarding neonatal outcomes, except for admission to neonatal intensive care, which was more frequent in the 1-gram/hour group (25% vs 6.3%; P = .04)., Conclusion: Magnesium sulfate therapy at the maintenance dose of 1 gram/hour was just as effective as the 2-gram maintenance dose, with fewer side effects.

With our study, we searched the medical literature to find magnesium (Mg) correlation with Emergency situations or its use in Emergency Medicine. Our aim is to fill the gap that we find in our daily routine between Mg studies on its role in Emergency and the real conception that doctors have of it in medical practice. We searched the literature for terms as magnesium or magnesium sulphate, magnesium in emergency, eclampsia, arrhythmias, acute asthma exacerbation, magnesium, and pediatric population. After a thorough research, we divided our discoveries into chapters to sort out a large amount often discordant articles.

Background: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain., Methods: Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum., Results: Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity., Conclusions: Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Background: Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate., Methods and Findings: Trials in which women considered at risk of preterm birth (<37 weeks' gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited., Conclusions: Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

Postpartum anxiety and depression are prevalent disorders. The authors of this study aimed to determine the effects of zinc and magnesium supplements on depressive symptoms and anxiety in postpartum women referred to three governmental, educational hospitals in Tabriz, Iran during 2014-2015. In this triple-blind, randomized, controlled clinical trial, the participants were randomly assigned to the zinc sulfate, magnesium sulfate, and placebo groups (n = 33 per group). The intervention groups received a 27-mg zinc sulfate tablet or 320-mg magnesium sulfate tablet per day for 8 weeks, whereas the control group received a placebo tablet each day during the same period. The Edinburgh Postnatal Depression Scale and the Spielberger State-Trait Anxiety Inventory were completed before and 8 weeks after the intervention. Blood samples were drawn from each participant to determine serum levels of zinc and magnesium before intervention at 48 hours after delivery. Also, a 24-hour dietary questionnaire was used during the first and last 3 days of the intervention. Adjusting for baseline scores as well as zinc and magnesium serum levels, no significant difference was observed between groups 8 weeks after delivery in mean scores of depressive symptoms (p = .553), state anxiety (p = .995), and trait anxiety (p = .234). This study concluded magnesium and zinc did not reduce postpartum anxiety and depressive symptoms.

Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants., (© 2017 American Association of Neuropathologists, Inc. All rights reserved.)

Aim: Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects., Main Methods: Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV., Key Findings: L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro., Significance: BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.

Magnesium sulfate is now widely recommended for neuroprotection for preterm birth; however, this has been controversial because there is little evidence that magnesium sulfate is neuroprotective. Preterm fetal sheep (104 days gestation; term is 147 days) were randomly assigned to receive sham occlusion (n = 7), i.v. magnesium sulfate (n = 10) or saline (n = 8) starting 24 h before asphyxia until 24 h after asphyxia. Sheep were killed 72 h after asphyxia. Magnesium sulfate infusion reduced electroencephalograph power and fetal movements before asphyxia. Magnesium sulfate infusion did not affect electroencephalograph power during recovery, but was associated with marked reduction of the post-asphyxial seizure burden (mean ± SD: 34 ± 18 min vs. 107 ± 74 min, P < 0.05). Magnesium sulfate infusion did not affect subcortical neuronal loss. In the intragyral and periventricular white matter, magnesium sulfate was associated with reduced numbers of all (Olig-2+ve) oligodendrocytes in the intragyral (125 ± 23 vs. 163 ± 38 cells/field) and periventricular white matter (162 ± 39 vs. 209 ± 44 cells/field) compared to saline-treated controls ( P < 0.05), but no effect on microglial induction or astrogliosis. In conclusion, a clinically comparable dose of magnesium sulfate showed significant anticonvulsant effects after asphyxia in preterm fetal sheep, but did not reduce asphyxia-induced brain injury and exacerbated loss of oligodendrocytes.

Aims: This study aims to compare different doses of magnesium administered via cardioplegic solutions to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery., Methods: A total of 120 patients who were scheduled for elective CABG surgery using cardiopulmonary bypass were enrolled in this double-blind, randomized clinical trial. After fulfilling the inclusion criteria, they were randomly allocated into three groups (A, B, and C). Patients in groups A, B, and C received 60, 80, and 100 mg/kg of magnesium sulfate via cardioplegic solutions during aortic cross-clamp, respectively. Postoperative AF was assessed by continuous ECG monitoring during 3 days after surgery. Also serum magnesium, potassium, and calcium levels were assessed during the study period., Results: The findings revealed significant differences in four point measurements of serum magnesium level after surgery (P<.001). In particular, it was observed that 10 (26.3%) patients in group A, 4 (10%) patients in group B, and 2 (5.4%) patients in group C had AF after surgery. This indicates patients receiving magnesium at doses of 80 and 100 mg/kg had lower rates of AF occurrence than those receiving 60 mg/kg dose of magnesium (P=.02). Additionally, no significant difference was found in serum calcium and potassium concentration between the three groups throughout the study period., Conclusion: Magnesium administration via the cardioplegic solution during aortic cross-clamping at doses of 80 and 100 mg/kg can reduce the risk of AF occurrence after CABG compared to the dose of 60 mg/kg. Considering the lower rate of AF incidence and shorter length of ICU stay in patients receiving 100 mg/kg of magnesium, it seems reasonable to administer 100 mg/kg magnesium during aortic cross-clamp to prevent postoperative AF., (© 2016 John Wiley & Sons Ltd.)

Background: Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications., Objective: The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics., Study Design: This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition., Results: Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15., Conclusions: The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: We aimed to assess whether the efficacy of pre-hydration with 15 mEq magnesium prevents cisplatin-induced nephrotoxicity in cisplatin regimens (dosage: 50 mg/m(2)or more) for gynecological cancer., Patients and Methods: This historical, prospective cohort study compared nephrotoxicity in patients who received pre-hydration with or without magnesium sulfate (Mg-hydration group, n=37; non-Mg-hydration group, n=37). We used serum creatinine (Scr), creatinine clearance (Ccr) and Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) criteria., Results: A change of Scr and Ccr in the Mg-hydration group was higher than in the non-Mg-hydration group. Based on the RIFLE criteria, the number of moderate renal dysfunction patients classified as "Risk" in the Mg-hydration group was significantly lower than in the non-Mg-hydration group (Mg-hydration group=21.6%; non-Mg-hydration group=51.4%; p<0.01). Serum magnesium levels in the Mg-hydration group significantly declined during chemotherapy (p<0.01)., Conclusion: We found that a 15 mEq magnesium as pre-hydration provided nephroprotective effects in patients receiving this cisplatin regimen. Future research should involve finding appropriate magnesium doses., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Magnesium sulphate is a standard therapy for eclampsia in pregnancy and is widely recommended for perinatal neuroprotection during threatened preterm labour. MgSO4 is a vasodilator and negative inotrope. Therefore the aim of this study was to investigate the effect of MgSO4 on the cardiovascular and cerebrovascular responses of the preterm fetus to asphyxia. Fetal sheep were instrumented at 98 ± 1 days of gestation (term = 147 days). At 104 days, unanaesthetised fetuses were randomly assigned to receive an intravenous infusion of MgSO4 (n = 6) or saline (n = 9). At 105 days all fetuses underwent umbilical cord occlusion for 25 min. Before occlusion, MgSO4 treatment reduced heart rate and increased femoral blood flow (FBF) and vascular conductance compared to controls. During occlusion, carotid and femoral arterial conductance and blood flows were higher in MgSO4-treated fetuses than controls. After occlusion, fetal heart rate was lower and carotid and femoral arterial conductance and blood flows were higher in MgSO4-treated fetuses than controls. Femoral arterial waveform height and width were increased during MgSO4 infusion, consistent with increased stroke volume. MgSO4 did not alter the fetal neurophysiological or nuchal electromyographic responses to asphyxia. These data demonstrate that a clinically comparable dose of MgSO4 increased FBF and stroke volume without impairing mean arterial pressure (MAP) or carotid blood flow (CaBF) during and immediately after profound asphyxia. Thus, MgSO4 may increase perfusion of peripheral vascular beds during adverse perinatal events., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Tocolytic use of magnesium sulphate is associated with excess neonatal mortality and has been proposed to follow a dose-response relationship. This study aimed to define the correlation between maternal and neonatal magnesium blood concentrations. Magnesium blood concentrations were retrospectively obtained for mother-neonate pairs who were cared for at an Intermountain Healthcare facility from January 2009 to October 2011. Complete data were available for 231 mother-neonate pairs. Mean (±SD) maternal and neonatal magnesium concentrations were 5.43±1.69 and 2.98±0.94 mg/dL, respectively. Maternal and neonatal magnesium concentrations were highly correlated (p<0.001). In univariate analyses, residual unexplained variability was high (r2=0.19). However, further multivariate analyses revealed that caesarian section, severe pre-eclampsia and Apgar score at 5 min. were significantly associated with neonatal magnesium concentrations (p<0.05 for all). Maternal magnesium concentrations correlate with neonatal exposure. This finding suggests that maternal monitoring deserves further evaluation as a marker of foetal toxicity., (© 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Study Objective: To study the minimal effective dose of magnesium sulfate to control blood pressure (BP) during intubation in hypertensive patients., Design: Prospective, randomized, double-blind study., Setting: Operating room of an academic medical center., Patients: 80 adult, ASA physical status 1 and 2, controlled hypertensive patients undergoing elective surgery under general anesthesia and requiring endotracheal intubation., Interventions: Patients were randomized to 4 groups. Patients in study groups received a magnesium sulfate infusion at a dose of 30 (Group I), 40 (Group II), or 50 mg/kg (Group III) before induction of anesthesia, while patients in control group (Group IV) received a 1.5 mg/kg lidocaine bolus 90 seconds before intubation. Anesthesia was induced and maintained with a propofol infusion. Laryngoscopy and intubation were performed 4 minutes after administration of vecuronium., Measurements: Heart rate (HR) and BP were recorded before, during, and after endotracheal intubation for 10 minutes. Measures to manage hemodynamic instability were recorded. Serum magnesium levels were also recorded., Main Results: The changes in HR were comparable among groups. Mean arterial pressure (MAP) was maintained within normal limits in Group I patients while Groups II and III patients showed a significant decrease in MAP (P = 0.01) compared with baseline. A total of 6 patients (30%) in Group II and 10 patients (50%) in Group III required interventions (P = 0.001). No patient in Group I and only one patient (5%) in Group IV required intervention., Conclusions: Magnesium 30 mg/kg is the optimum dose to control BP during intubation in hypertensive patients. A further increase in the dose of magnesium may cause significant hypotension., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Hypomagnesemia has been linked with increased morbidity and mortality in critically ill patients. Since the condition is common after cardiopulmonary bypass surgery, the objective of this study was to determine whether magnesium supplementation in the immediate postoperative period may improve outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. This prospective, randomized, double-blind, placebo-controlled study was conducted in a third-level, cardiac surgery intensive care unit (ICU) at a university hospital. Two hundred and sixteen patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive either an intravenous bolus of 1.5 g of magnesium sulphate followed by an infusion of 12 g of the same salt in 24 h (105 patients), or placebo (111 patients) administered according to the same schedule as the treatment group. No significant differences were found either in the primary end point (hours of intubation) or in the secondary end points (length of inotropic support, new atrial fibrillation, ventricular tachycardia or ventricular fibrillation, length of intensive care unit stay, or ICU or hospital mortality). Hypomagnesemia was present in 12% of patients on admission to the intensive care unit. The magnesium group had a greater need for pacemaker stimulation. In conclusion, under the conditions of the present study, magnesium supplementation after cardiac surgery with cardiopulmonary bypass does not favourably affect clinical outcomes.

Purpose: The results of an investigation of serum magnesium concentrations (SMCs) after i.v. versus oral delivery of magnesium in cardiovascular critical care are presented., Methods: A retrospective case review was conducted to compare the net gain of magnesium after i.v. (n = 188) or oral (n = 164) magnesium therapy for the prevention of ventricular fibrillation and arrhythmias in patients hospitalized for serious cardiovascular disorders, as determined by assessing SMCs. The primary study outcome was the change from baseline SMC values 6-24 hours after the completion of magnesium courses; secondary outcomes included the impact of renal impairment, concomitant medication use, and other clinical variables on SMC changes., Results: Although consistent elevations in SMC were produced by oral magnesium delivery, i.v. administration resulted in greater and more rapid elevations relative to baseline SMC. The degree of change in SMC was significantly influenced by the timing of SMC measurement after a magnesium course, by renal function, and by concomitant use of i.v. loop diuretics., Conclusion: A comparison of 24-hour courses of magnesium replacement therapy showed that magnesium sulfate 2 g i.v. was associated with larger changes in SMC than magnesium oxide 800, 1200, or 1600 mg orally when the baseline SMC was 1.4-1.8 mg/dL. At baseline SMCs of 1.4-1.8 mg/dL, oral magnesium oxide provided a consistent median increase in SMC of 0.1 mg/dL. The change in the number of bowel movements did not differ significantly between courses of i.v. magnesium sulfate and oral magnesium oxide.

Objective: To assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates., Study Design: This was a secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks' gestation and randomly allocated them to receive either intravenous magnesium sulfate or placebo. The cohort included 1507 infants with data available on total cord blood Mg concentration and delivery room resuscitation. Multivariate logistic regression was used to estimate the association between cord blood Mg concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation, and chest compressions., Results: There was no relationship between cord blood Mg and delivery room resuscitation (OR, 0.92 for each 1.0-mEq/L increase in Mg; 95% CI, 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR, 2.51; 95% CI, 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR, 0.63; 95% CI, 0.60-0.66)., Conclusion: Cord blood Mg concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Unlabelled: Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, two-way analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF., Conclusion: Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Background: Magnesium sulphate is shown to be the drug of choice in the management of severe pre-eclampsia-eclampsia for over two decades. However, the drug was introduced in practice in teaching hospitals in Addis Ababa recently. Hence, it is important to audit its use at this stage., Objectives: To audit the experience of magnesium sulfate use for management of severe pre-eclampsia and eclampsia on its introduction in teaching hospitals in Addis Ababa., Methodology: A retrospective medical record review was conducted to audit use of magnesium sulfate, MgSO4, in two teaching hospitals in Addis Ababa between February and August 2006., Results: One hundred three women received magnesium sulfate during the study period (February to August, 2006). It was possible to retrieve the charts of 95 women (92.2% chart retrieval rate). Seventy-four percent (54/73) of the eligible cases from Tikur Anbesa Hospital and 63.6% (49/77) from Gandhi Memorial Hospital received the drug. Patient selection for administration of magnesium sulfate was appropriate in 93.7% (89/95) of women with hypertension in pregnancy. Correct loading dose of MgSO4 was given for 90.4% (85/95) of the patients. No woman with severe pre-eclampsia convulsed after initiation of magnesium sulfate, while four of the eclamptic mothers had recurrence of seizures. The overall clinical monitoring of patients who were on treatment was inadequate with respect to the protocol of the hospitals. Only one (1.1%) woman was reported to have developed signs of a major side effect of magnesium sulfate and two mothers died. Both of these deaths were not attributed to magnesium sulfate toxicity., Conclusion and Recommendations: This study showed that a good proportion (more than two-thirds) of the eligible cases has received magnesium sulfate. It is recommended that the respective hospitals should give due attention to the suboptimal patient monitoring.

Background: In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP)., Methods: We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h., Results: The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered., Conclusions: I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

Background: Magnesium sulfate (MgSO(4)) has been used as a tocolytic agent in cases of refractory preterm labor. Prolonged maternal administration of MgSO(4) may induce bone demineralization in the neonate. However, the effects of MgSO(4) on serum biochemistry related to bone metabolism in neonates remain unclear., Aim: To assess the effects of prolonged maternal administration of MgSO(4) on fetuses and neonates., Study Design: This retrospective case-control study examined 167 neonates. Cases comprised 58 neonates whose mothers had received intravenous MgSO(4) administration for >5 days. Neonatal serum levels of magnesium (Mg), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were reviewed. We also investigated whether subject neonates showed appearance of osteopenia at the metaphyseal lines on radiography at birth., Results: Mean serum Mg and P levels were significantly higher, and Ca levels were significantly lower, in cases than in controls at birth. Mean serum ALP level was 1188.5IU/l in cases, significantly higher than that in controls at birth. Bone abnormalities were noted on radiography in 2 subjects. By 3 weeks old, serum ALP levels did not differ significantly between cases and controls. Logistic regression analysis revealed maternal administration of MgSO(4) and multiple pregnancies were significantly related to serum ALP level in neonates at birth., Conclusion: Prolonged maternal administration of MgSO(4) significantly affects neonatal serum biochemistry related to bone metabolism. Potential long-term adverse effects on neonates and how Mg affects fetal bone metabolism in utero need to be investigated in future studies., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of this study was to determine whether magnesium serum concentrations in patients with severe preeclampsia or eclampsia treated with two different magnesium sulfate schemes were different., Methods: Fourteen patients were randomly assigned in the alternative scheme group and 15 in the Zuspan's group. The difference between the groups was that the intravenously administered maintenance dose was done with 1 g/h by continuous intravenous infusion in the Zuspan's group and 2g in bolus every two hours in the alternative scheme. Blood samples were collected previously to treatment and every 15 minutes during four hours after the beginning of treatment. The primary outcome measure was area under the curve and the t-test was used for statistical analysis with level of statistical significance of 5%. The evaluation of the punctual means at all moments in the alternative group was done with the repeated measures analysis of variance., Results: There was no significant difference in the baseline characteristics between groups. In both schemes, magnesium serum concentration reaches a peak within 15 minutes and a new peak was observed after maintenance dose in the alternative scheme. The area under the curve was significantly lower in the alternative scheme than in the Zuspan's scheme (702.1 +/- 73.5 mg/dL vs 796.1 +/- 94.6 mg/dL)., Conclusion: The serum magnesium concentration of this randomized clinical trial doesn't support the use of the alternative scheme of magnesium sulfate to prevent or treat eclampsia.

Background: In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements., Methods: Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery., Results: Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups., Conclusions: I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

Severe tetanus is characterised by muscle spasms and autonomic dysfunction. We recently reported the results of a randomised placebo controlled trial of magnesium sulphate infusions for the treatment of severe tetanus which showed magnesium was associated with improved muscle spasm and cardiovascular control. We hypothesised that magnesium controlled autonomic dysfunction by reducing catecholamine release and thus urinary excretion. Urinary adrenaline and noradrenaline concentrations were measured during the first 24 h of therapy in 180 adults with severe tetanus randomised to treatment with magnesium (n = 92) or placebo (n = 88). Magnesium therapy was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion. High urinary adrenaline concentrations were associated with documented autonomic dysfunction. Patients given magnesium had significantly less autonomic dysfunction, required less cardiovascular stabilising drugs, and had lower urinary concentrations of adrenaline. These findings suggest adrenaline is important in the pathophysiology of severe tetanus and magnesium controls autonomic dysfunction by reducing adrenaline release.

We have compared intravenous magnesium sulphate vs. inhaled nitric oxide in the therapy of moderate persistent pulmonary hypertension of the neonate. A retrospective collection of clinical data from 58 neonates was carried out in six neonatal intensive care units of Southern Italy sharing the same operational protocols. In our setting, both drugs were effective in treating moderate persistent pulmonary hypertension of the neonate but nitric oxide (NO) treatment resulted in much faster amelioration of oxygenation index, taken as a marker of the underlying condition. No significant difference was recorded in immediate or long-term complications. We conclude that, wherever NO facilities are not readily available, magnesium sulphate is a safe and cheaper alternative for first-line treatment of moderate persistent pulmonary hypertension of the neonate.

Objective: To evaluate the effect of pre- and intraoperatively administered magnesium sulphate (MgSO(4)) on the induction dose of thiopental and of halothane for maintenance of anaesthesia in dogs undergoing ovariohysterectomy (OHE)., Study Design: Prospective, double-blind, randomized, placebo-controlled study., Animals: Forty-six healthy, ASA physical status 1 dogs, scheduled for elective OHE., Methods: The dogs were randomly assigned to receive a bolus of 50 mg kg(-1) MgSO(4) intravenously (IV), just before induction of anaesthesia, followed by a constant rate infusion (CRI) of 12 mg kg(-1) hour(-1) MgSO(4) intraoperatively (group Mg, n = 27) or a placebo bolus and CRI of 0.9% sodium chloride (NaCl) (group C, n = 19), approximately 30 minutes after premedication with acepromazine (0.05 mg kg(-1), intramuscularly, IM) and carprofen (4 mg kg(-1), subcutaneously, SC). Anaesthesia was induced with thiopental administered to effect and maintained with halothane in oxygen. End-tidal halothane (ET(hal)) was adjusted to achieve adequate depth of anaesthesia. Blood samples were obtained pre- and postoperatively for measurement of total serum magnesium concentration., Results: The mean dose of thiopental was statistically lower (p < 0.0005) and the mean standardized ET(hal) concentration and end-tidal carbon dioxide partial pressure (Pe'CO(2)) areas under the curve were statistically smaller (p < 0.0005 and 0.014 respectively) in group Mg. Postoperatively the mean total serum magnesium concentration was statistically higher than the preoperative value (p < 0.0005) in group Mg, but not in group C. Nausea, associated with the MgSO(4) bolus injection, was observed in six dogs in group Mg, two of which vomited prior to induction of anaesthesia., Conclusions and Clinical Relevance: Magnesium sulphate administration reduced the induction dose of thiopental and ET(hal) concentration for maintenance of anaesthesia in dogs undergoing OHE. Observed side effects were nausea and vomiting.

Objective: The purpose of this study was to investigate the effect of magnesium sulfate on pain management for post-thoracotomy patients., Design: A prospective, randomized, controlled clinical study., Setting: University hospital., Participants: Twenty-four patients undergoing thoracotomy., Interventions: After thoracotomy operations, patients were assigned to 2 groups. The control group received intravenous morphine (0.5 mg/h infusion, 0.3 mg patient-controlled anesthesia dose, 15-minute lockout time) via patient-controlled analgesia, and the magnesium group received magnesium sulfate (30-mg/kg bolus, 10 mg/kg/h infusion for 48 hours) plus the same patient-controlled analgesia protocol., Measurements and Main Results: Visual analog scale for pain score, sedation score, mean arterial pressure, heart rate, and valid and invalid analgesic demand were recorded. Serum magnesium levels were determined at postanesthesia care unit admission, at 24 hours, and at 48 hours. Side effects were also recorded. There were no significant differences between groups with respect to demographics, sedation score, and pain score. Cumulative mean morphine consumption was found to be higher in the control group compared with the magnesium group at 4, 8, and 48 hours (5.6 +/- 1 mg v 3.2 +/- 0.6 mg [p < 0.0001], 10.2 +/- 1.8 mg v 7.2 +/- 1.6 mg [p = 0.0003), and 40.2 +/- 4.5 mg v 34.8 +/- 6.3 mg [p = 0.02], respectively)., Conclusion: Postoperative use of magnesium sulfate reduced opioid consumption for pain after thoracotomy operations.

Prevention of paraplegia remains an imperative issue in thoracoabdominal aortic surgery. The aim of this study was to assess the efficacy of a prophylactic magnesium infusion in a rat spinal cord ischemia model and to demonstrate spinal blood flow increase caused by the infusion. The study was conducted in two parts. Firstly, the neuroprotective effect of magnesium was assessed using a rat model with two different ischemic times: 10 min and 14 min. Spinal cord ischemia was induced by occlusion of the descending aorta. Rats in the treatment group were given a 100 mg/kg magnesium sulfate infusion before ischemia. Secondly, relative changes in spinal cord blood flow before and during ischemia were recorded using the laser Doppler flowmetry technique. Changes in blood flow were compared between the magnesium and control groups. Rats pretreated with magnesium showed good overall recovery after both 10 min (incidence of paraplegia 62.5% control vs. 37.5% Mg, n = 8 each) and 14 min (85.7% control vs. 57.1% Mg, n = 7 each) of ischemia, although the differences compared with controls were statistically insignificant. However, the magnesium group showed significantly better neurological performance during the early postischemic period. Comparison of changes in spinal circulation revealed less reduction in blood flow during ischemia in the magnesium-treated group. In conclusion, magnesium may have potential prophylactic benefits during ischemia by exerting a neuroprotective effect through vasodilation of the spinal cord vasculature. To our knowledge, this vasodilatory effect on the spinal cord has not previously been investigated. Optimization of the treatment regimen, however, is required.

Aim: As ionized magnesium is the active form of magnesium and exerts a therapeutic effect, the present study was performed to determine the levels and correlations between ionized and total magnesium under baseline and therapeutic conditions in patients with severe preeclampsia and eclampsia receiving magnesium sulfate., Methods: Fifty singleton patients with severe preeclampsia received a loading dose of 4 g of magnesium sulfate, followed by 2 g per hour as maintenance dose until 24 h after delivery, or 24 h after the last seizure in case of postpartum convulsions. Serial blood samples were taken before magnesium sulfate infusion, 30 min and 240 min after the initiation of the infusion and 4 h after the discontinuation of the drug. Data were analyzed by repeated measure ANOVA and paired t-test., Results: Baseline levels of total and ionized magnesium were 2.4+/-0.6 mEq/L and 1.3+/-0.5 mEq/L (mean+/-SD), respectively. Putative level of 4 mEq/L of total magnesium was not obtained in up to 42% of patients during the treatment. There was not any significant correlation between the two forms of magnesium under baseline and therapeutic conditions., Conclusion: Despite the effectiveness of the standard regimen of magnesium sulfate in the treatment and prevention of eclamptic seizures, it can not provide the proposed therapeutic level of magnesium in all patients. With respect to the lack of correlation between ionized and total magnesium, further studies are necessary to investigate the superiority of measurement of ionized, rather than total magnesium, for titration of therapeutic magnesium sulfate infusion.

Objective: To evaluate the effects of ketamine, magnesium sulfate, and their combination on the minimum alveolar concentration (MAC) of isoflurane (ISO-MAC) in goats., Animals: 8 adult goats., Procedures: Anesthesia was induced with isoflurane delivered via face mask. Goats were intubated and ventilated to maintain normocapnia. After an appropriate equilibration period, baseline MAC (MAC(B)) was determined and the following 4 treatments were administered IV: saline (0.9% NaCl) solution (loading dose [LD], 30 mL/20 min; constant rate infusion [CRI], 60 mL/h), magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h), ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min), and magnesium sulfate (LD, 50 mg/kg; CRI, 10 mg/kg/h) combined with ketamine (LD, 1 mg/kg; CRI, 25 microg/kg/min); then MAC was redetermined., Results: Ketamine significantly decreased ISOMAC by 28.7 +/- 3.7%, and ketamine combined with magnesium sulfate significantly decreased ISOMAC by 21.1 +/- 4.1%. Saline solution or magnesium sulfate alone did not significantly change ISOMAC., Conclusions and Clinical Relevance: Ketamine and ketamine combined with magnesium sulfate, at doses used in the study, decreased the end-tidal isoflurane concentration needed to maintain anesthesia, verifying the clinical impression that ketamine decreases the end-tidal isoflurane concentration needed to maintain surgical anesthesia. Magnesium, at doses used in the study, did not decrease ISOMAC or augment ketamine's effects on ISOMAC.

Background: It is still controversial that intrapartum exposure to magnesium may or may not reduce brain damage in premature infants in human and animal models., Aims: We investigated the effect of hypoxemia alone under magnesium exposure on fetal cardiovascular changes in chronically catheterized goat fetuses., Study Design: We performed a 3-day experimental protocol with control (10% glucose) on day 1, recovery on day 2, and magnesium on day 3. Magnesium sulfate was directly infused to fetuses in a bolus dose of 270 mg/kg followed by 80 mg/kg/h. Hypoxemia was induced by maternal inhalation of nitrogen gas on day 1 and on day 3. Cerebral blood flow was measured by colored microsphere techniques. Repeated measure ANOVA and Bonferroni's/Dunn's test were used for comparison., Subjects: Six Japanese Saanen goats at 0.85 gestation., Outcome Measures: Fetal heart rate, blood pressure, and cerebral blood flow., Results: Ionized magnesium concentrations were significantly increased. Fetal PO2 decreased significantly from 30 mmHg to 14 mmHg without acidemia. Magnesium exposure significantly attenuated hypoxemia-induced bradycardia but did not affect blood pressure. Hypoxemia significantly increased fetal brain blood flow from the pre-hypoxic levels on day 1. Magnesium exposure further increased hypoxemia-induced brain blood flow on day 3, but statistical significance was limited to the cerebral cortex., Conclusion: In near-term, initially healthy goat fetuses, brain blood flow during acute hypoxemia was significantly increased with magnesium sulfate exposure.

Objective: To investigate the effect of magnesium sulfate on the fetal rats of fetal growth retardation (FGR) and its relation with expression of caspase-3 on the placenta of maternal rat., Methods: Model of FGR was constructed according to the method of passive smoking. The pregnant rats were divided into control group (n = 10), therapy group (n = 18) and FGR group (n = 10). The therapy group rats were given different doses of magnesium sulfate by subcutaneous injection: low dose group (300 mg/kg, n = 10), high dose group (600 mg/kg, n = 8). Serum concentration of magnesium sulfate was monitored. The expression of caspase-3 was measured by immunohistochemistry method and RT-PCR., Results: Both of the concentration of magnesium sulfate in high and low dose groups (0.72 +/- 0.13), (0.61 +/- 0.03) mmol/L were higher than the FGR group (0.55 +/- 0.03) mmol/L (P < 0.01); the weight of placenta and fetal rat in high dose group [(0.80 +/- 0.16) and (3.58 +/- 0.10) g] were more than those of FGR group [(0.63 +/- 0.05) and (2.95 +/- 0.46) g] (P < 0.05, P < 0.01); the expression of mRNA and protein of caspase-3 in high dose group [(0.361 +/- 0.030), (183.0 +/- 3.3)] was lower than the FGR group [(0.626 +/- 0.036), (199.5 +/- 4.7)] (P < 0.05); the expression of mRNA in low dose group (0.525 +/- 0.029) was higher than the high dose group (P < 0.05); serum concentration of magnesium sulfate of maternal rat was correlated with the weight of fetal rat (r = 0.899, P = 0.038) and the expression of mRNA and protein of caspase-3 in placenta (r = -0.747, P = 0.033; r = -0.915, P = 0.001)., Conclusion: It is suggested that magnesium sulfate increases the weight of fetal rat probably by depressing the expression of caspase-3 of placenta, which improves the placental function.

Background: Increasing circulating magnesium concentrations to 2-fold over normal baseline may afford a neuroprotective effect in patients with acute cerebral ischemia., Objectives: As patients receiving magnesium sulfate (MgSO(4)) in human clinical trials may also be candidates for subsequent thrombolytic therapy with tissue plasminogen activator (t-PA), preclinical assessment of possible inhibition or potentiation of fibrinolytic activity by MgSO(4) has important clinical relevance., Methods: We utilized an in vitro system, in which D-dimer release served as a reflection of t-PA-induced clot lysis, to measure the effect of magnesium at the target concentration being tested in human stroke clinical trials, and at 2- and 3-fold higher levels. Clots from normal volunteers were exposed to t-PA at concentrations that correspond to therapeutic or endogenous plasma t-PA levels., Results: MgSO(4) had no effect on t-PA-induced clot lysis at up to 3-fold target magnesium concentration (6x normal serum concentration)., Conclusions: MgSO(4) concentrations well above the targeted level in therapeutic stroke trials does not affect t-PA-induced fibrinolytic activity, and therefore is a suitable agent for trials of combined neuroprotective and thrombolytic therapy in patients with acute ischemic stroke.

Objective: We sought to evaluate magnesium as a neuroprotectant in patients undergoing cardiac surgery with cardiopulmonary bypass., Methods: From February 2002 to September 2003, 350 patients undergoing elective coronary artery bypass grafting, valve surgery, or both were enrolled in a randomized, blinded, placebo-controlled trial to receive either magnesium sulfate to increase plasma levels 1(1/2) to 2 times normal during cardiopulmonary bypass (n = 174) or no intervention (n = 176). Neurologic function, neuropsychologic function, and depression were assessed preoperatively, at 24 and 96 hours after extubation (neurologic) and at 3 months (neuropsychologic, depression). Neurologic scores were analyzed using ordinal longitudinal methods, and neuropsychologic and depression inventory data were summarized by principal component analysis, followed by linear regression analysis using component scores as response variables., Results: Seven (2%) patients had a postoperative stroke, 2 (1%) in the magnesium and 5 (3%) in the placebo group (P = .4). Neurologic score was worse postoperatively in both groups (P < .0001); however, magnesium group patients performed better than placebo group patients (P = .0001), who had prolonged declines in short-term memory and reemergence of primitive reflexes. Three-month neuropsychologic performance and depression inventory score were generally better than preoperatively, with few differences between groups (P > .6); however, older age (P = .0006), previous stroke (P = .003), and lower education level (P = .0007) were associated with worse performance., Conclusions: Magnesium administration is safe and improves short-term postoperative neurologic function after cardiac surgery, particularly in preserving short-term memory and cortical control over brainstem functions. However, by 3 months, other factors and not administration of magnesium influence neuropsychologic and depression inventory performance.

High-dosage, tocolytic magnesium sulfate (MgSO4) administered to pregnant women during preterm labor can be toxic, and sometimes lethal, for their newborns (Cochrane Database of Systematic Reviews (relative mortality risk 2.82, 95% confidence interval 1.2-6.6)). Based on the results of the Magnesium and Neurologic Endpoints Trial and the work of many others, a unifying triangular concept is proposed to account for the increased prevalence of brain lesions, with their likely resultant mortality, in neonates and infants exposed to high-dose MgSO4 in the context of preterm labor. We review the evidence that: (1) elevated circulating levels of serum ionized magnesium occurring in mothers, and therefore in their babies, at the time of delivery are associated with subsequent neonatal intraventricular hemorrhage (IVH); (2) neonatal IVH is strongly associated with lenticulostriate vasculopathy (LSV), an unusual mineralizing lesion involving the thalami and basal ganglia of the neonate; and, (3) exposure to 50 g or more of tocolytic MgSO4 during preterm labor is associated with the development of LSV.

1. Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the complications of diabetes. The purpose of the present study was to determine the relationship between oral Mg supplementation and changes in plasma glucose, calcium, haemoglobin, Ca/Mg ratio, blood pressure and the histology of the pancreas and vascular system in streptozotocin-induced diabetic rats. 2. Ten days after the induction of diabetes in male Wistar rats, half the diabetic animals were divided into six groups, receiving 0, 1, 3, 10, 30 or 50 g/L MgSO4 added into the drinking water for 8 weeks. Plasma glucose and Mg were measured at days 1, 2, 3, 5, 7, 14 and 21 to find the optimum dose of Mg and the time-course of its effect. In addition, histological observations were undertaken. Eight weeks later, all animals were decapitated, the pancreas and thoracic aorta were removed carefully and immersed immediately in 10% formaldehyde for histological study. 3. To evaluate the effects of Mg on plasma glucose, calcium, haemoglobin, Mg and blood pressure, another group of animals was divided into four experimental groups, as follows: (i) non-diabetic controls received tap water for 8 weeks; (ii) acute diabetics received tap water for 10 days; (iii) chronic diabetic controls received tap water for 8 weeks; and (iv) Mg-treated chronic diabetic rats received 10 g/L MgSO4 added into the drinking water 10 days after the induction of diabetes for 8 weeks. 4. Magnesium dose dependently affects plasma glucose levels. The peak effect was reached during the first 24 h following oral administration. Administration of 10 g/L MgSO4 results in the return of normal structure in the diabetic pancreas and aorta. Moreover, this concentration of MgSO4 causes glucose, haemoglobin, calcium, the Ca/Mg ratio and blood pressure to reach normal levels. Although the Mg level increases slightly following the administration of 10 g/L MgSO4 to diabetic rats, it never reaches control levels. 5. On the basis of the results of the present study, it may be concluded that chronic Mg administration may have beneficial effects on diabetes.

Background: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous haemodynamic responses and prevents further hypothermia. Magnesium is an attractive anti-shivering agent because it is used for treatment of postoperative shivering and provides protection against ischaemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness., Methods: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: (1) control and (2) magnesium (80 mg kg(-1) followed by infusion at 2 g h(-1)). Lactated Ringer's solution (4 degrees C) was infused via a central venous catheter over a period of approximately 2 h to decrease tympanic membrane temperature by approximately 1.5 degrees C h(-1). A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs core temperature regression. Sedation was evaluated using a verbal rating score (VRS) from 0 to 10 and bispectral index (BIS) of the EEG. Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analysed using repeated measures anova; P<0.05 was statistically significant., Results: Magnesium reduced the shivering threshold (36.3 [SD 0.4] degrees C vs 36.6 [0.3] degrees C, P = 0.040). It did not affect the gain of shivering (control, 437 [289] ml min(-1) degrees C(-1); magnesium, 573 [370] ml min(-1) degrees C(-1); P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength., Conclusions: Magnesium significantly reduced the shivering threshold. However, in view of the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia.

Over the last decade there has been an increase in the use of MgSO4 for the prevention of seizures in women with severe pre-eclampsia or eclampsia. At the Rotunda Hospital it is regularly used for this purpose. The aim of this study was to audit the use of MgSO4 at the hospital, to determine whether the drug was being used according to the hospital's protocol and to observe its effectiveness in the prevention of eclampsia in our population. A retrospective chart review over the two years from 1/1/2000 to 31/12/2001 was undertaken. Outcome measures assessed were; Patient selection, Administration of the drug - whether recommended protocols were adhered, Effectiveness of therapy for seizure prophylaxis, Maternal and neonatal outcomes. There were 12,910 deliveries at the Rotunda hospital over this period of time. Fifty of these women were treated with MgSO4 (0.4%). Patient selection was appropriate in all cases. The correct loading dose of MgSO4 was administered in all cases, however MgSO4 levels were recorded in only 30 (60%) of women. There were no seizures in the treated group. Two women presented with seizures (one was antenatal the other post-natal period), both were treated with MgSO4. There were no maternal or neonatal mortality. Seventy two percent (36) of these women were delivered by lower segment caesarean section. The mean gestation at delivery was 36 weeks (range 28-41 weeks). Thirty eight percent (13) of babies required admission to the neonatal intensive care unit. The mean birth weight at delivery was 2.54 kg (range 1.11-3.68 kg). MgSO4 use in the Rotunda hospital appears to be safe and effective for the prevention of seizures in women with severe pre-eclampsia or eclampsia. Serum MgSO4 levels were only recorded in 60% of patients and the hospital's protocol was not adhered to regarding monitoring of patients on treatment. This needs to be addressed.