How much magnesium sulfate is needed to "keep total serum magnesium above 2.0 mg/dL"?

For patients at increased risk of life-threating ventricular arrythmias, hospitalists often administer intravenous magnesium sulfate to maintain total serum magnesium concentration (TsMg) above 2 mg/dL. How long each dose keeps TsMg above this threshold is not well known, however. We collected TsMg values from 12,618 veterans who were given 24,363 doses of intravenous magnesium sulfate during 14,901 hospitalizations for acute heart failure. Across dose amounts, the average TsMg dropped below 2.0 mg/dL within 24 h of administration. When we limited our analysis to 2 g doses (the most common dose) and adjusted for baseline TsMg, estimated glomerular filtration rate, oral magnesium supplementation, and loop diuretic dosing, we found that less than half of the adjusted TsMg values remained above 2.0 mg/dL just 12 h after dose administration. Hospitalists should expect, on average, to administer 2 g intravenous magnesium sulfate at least twice daily to maintain total serum magnesium above 2 mg/dL.

Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial.

PURPOSE: Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery. METHODS: In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat. RESULTS: Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80). CONCLUSION: Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

Intravenous Magnesium Sulfate Reduces Tremor Severity: A Case Series.

Introduction: Tremors involve involuntary muscle contractions that can occur at rest or during movement. Parkinson's disease (PD), the most common form of resting tremor, is conventionally treated with dopamine agonists, a therapy with a limited window of efficacy as the disease progresses due to levodopa tachyphylaxis. Complementary and Integrative Health (CIH) interventions represent low-cost options for a disease which is expected to double in prevalence in the next decade. Based on its use in many conditions, magnesium sulfate may have therapeutic potential for patients with tremors. This case series presents findings on the use of intravenous magnesium sulfate for the management of four patients with tremors. Methods: All four patients were seen at the National University of Natural Medicine clinic and screened for contraindications and safety considerations prior to each treatment using the acronym, ATHUMB: allergies, treatment response, health history, urinalysis, medications, and breakfast/meal timing. Magnesium sulfate is given in an initial dose of 2000 mg increasing in increments of 500 mg over the next one-to-two office visits up to a 3500 mg maximum. Results: Reductions in tremor severity were noticed for each patient during and following treatment. All patients reported a 24-48-hour window of relief and improvement in activities of daily living after each IV; 3 of 4 patients reported that window extended to 5-7 days. Conclusion: IV magnesium sulfate was effective in decreasing tremor severity. Future research should explore the impact of IV magnesium sulfate on tremors using objective and self-reported measures to quantify the size and duration of its effect.

Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial.

Background Magnesium supplements may have beneficial effects on arterial stiffness. Yet, to our knowledge, no head-to-head comparison between various magnesium formulations in terms of effects on arterial stiffness has been performed. We assessed the effects of magnesium citrate supplementation on arterial stiffness and blood pressure and explored whether other formulations of magnesium have similar effects. Methods and Results In this randomized trial, subjects who were overweight and slightly obese received either magnesium citrate, magnesium oxide, magnesium sulfate, or placebo for 24 weeks. The total daily dose of magnesium was 450 mg/d. The primary outcome was carotid-to-femoral pulse wave velocity, which is the gold standard method for measuring arterial stiffness. Secondary outcomes included blood pressure and plasma and urine magnesium. Overall, 164 participants (mean±SD age, 63.2±6.8 years; 104 [63.4%] women) were included. In the intention-to-treat analysis, neither magnesium citrate nor the other formulations had an effect on carotid-to-femoral pulse wave velocity or blood pressure at 24 weeks compared with placebo. Magnesium citrate increased plasma (+0.04 mmol/L; 95% CI, +0.02 to +0.06 mmol/L) and urine magnesium (+3.12 mmol/24 h; 95% CI, +2.23 to +4.01 mmol/24 h) compared with placebo. Effects on plasma magnesium were similar among the magnesium supplementation groups, but magnesium citrate led to a more pronounced increase in 24-hour urinary magnesium excretion than magnesium oxide or magnesium sulfate. One serious adverse event was reported, which was considered unrelated to the study treatment. Conclusions Oral magnesium citrate supplementation for 24 weeks did not significantly change arterial stiffness or blood pressure. Magnesium oxide and magnesium sulfate had similar nonsignificant effects. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03632590.

Increased Risk of Meconium-Related Ileus in Extremely Premature Infants Exposed to Antenatal Magnesium Sulfate.

INTRODUCTION: We experienced an increased incidence of meconium-related ileus (MRI) in extremely premature infants (EPIs) while adopting the antenatal magnesium sulfate (MgSO4) protocol for fetal neuroprotection in our neonatal intensive care unit. This study aimed to test whether antenatal MgSO4 use was associated with increased risk of MRI in EPIs. METHODS: The incidences of complicated MRI requiring aggressive enema or surgical intervention and other intestinal complications were compared among period 1 (January 2012-December 2013, n = 79), before adoption of the antenatal MgSO4 protocol for fetal neuroprotection; period 2 (January 2014-March 2016, n = 72), when the protocol was adopted; and period 3 (April 2016-September 2018, n = 75), when the protocol was temporarily withdrawn due to concern regarding intestinal complications in EPIs. RESULTS: Despite similar baseline clinical characteristics among infants across the study periods, the MRI and MRI with surgical treatment incidences were higher in period 2 than those in periods 1 and 3 (13% vs. 8% and 6%, p = 0.391, and 11% vs. 0% and 1%, p = 0.001, respectively). In multivariable analysis, exposure to antenatal MgSO4 independently increased the risk of MRI (adjusted odds ratio, 3.8; 95% confidence interval, 1.4, 10.6). CONCLUSION: Antenatal MgSO4 may increase the risk of MRI, frequently requiring surgical intervention, in EPIs with a gestational age of 25 weeks or less.

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

The Effect of Early Treatment with Intravenous Magnesium Sulfate on the Incidence of Cardiac Comorbidities in Hospitalized Stroke Patients.

BACKGROUND: Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. METHODS: This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. RESULTS: Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. CONCLUSION: Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.

Magnesium Sulfate Administration in Moderate Coronary Artery Disease Patients Improves Atherosclerotic Risk Factors: A Double-Blind Clinical Trial Study.

Magnesium (Mg) deficiency is known to promote vascular and cardiac dysfunctions such as atherosclerosis. This study investigated the effect of oral MgSO4 therapy to improve lipid profile and serum oxidized LDL level and its receptor (LOX1) in moderate coronary atherosclerotic patients. In this randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease were selected according to angiography findings. Participants were divided into 2 groups including Mg-treated (n = 32) and placebo (n = 32) The patients received either placebo or MgSO4 supplement capsule, containing 300 mg MgSO4 for 6 months on a daily basis. Lipid profile, HbA1c, 2h postprandial (2hpp) blood glucose, fasting blood sugar, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), oxidized low-density lipoprotein, and lectin-like ox-LDL receptor 1 (LOX1) concentrations were measured at baseline and every 3 months. HbA1c, serum LOX1, and oxidized low-density lipoprotein concentrations were significantly lower in the Mg-treated group than the placebo group 3 months after MgSO4 administration. 2hpp, serum low-density lipoprotein cholesterol, SGPT, SGOT levels, and HbA1c levels significantly improved in the Mg-treated group compared with the placebo-received group. Overall, the results of this study showed that magnesium treatment improved some of the major risk factors of atherosclerosis. According to the results of liver function tests (SGOT and SGPT), magnesium therapy seems to be safe in patients with moderate atherosclerotic plaque. Therefore, it is suggested that magnesium to be used along with other atherosclerosis control drugs.

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford.

The Effect of Manual Acupressure (Point BL32) on Pain Associated with Intramuscular Injections of Magnesium Sulfate.

The aim of this study was determining the effect of acupressure on the severity of pain associated with intramuscular injections of magnesium sulfate administered by the Z-track technique in patients with eclampsia and preeclampsia. Forty-eight patients participated in this single-group clinical trial, which was conducted in three stages. For each patient, three intramuscular injections were administered by the Z-track technique. The first injection was administered by the conventional method. The second injection at a sham control point and the third injection using acupressure (BL32) were administered. Pain severity was measured on a visual analogue scale. The mean pain intensity was 7.22 in the first, 4.75 in the second and 1.94 in the third injections (p < 0.001). The results of the study showed that acupressure at the BL32 point before intramuscular injection of magnesium sulfate significantly reduced the injection-related pain.

Intravenous magnesium sulphate infusion as first-line therapy in the control of spasms and muscular rigidity in childhood tetanus.

Background: Reports suggest that, in tetanus, magnesium sulphate (MgSO4) alone may control muscle spasms, thereby avoiding sedation and mechanical ventilation. Aim: To study the efficacy and safety of intravenous MgSO4 in controlling spasms and rigidity in children with tetanus. Methods: All children with tetanus consecutively admitted over a 2-year period in a tertiary-care teaching hospital were recruited. In addition to human tetanus immunoglobulin and parenteral metronidazole, patients received MgSO4 100 mg/kg intravenously followed by infusion at 40 mg/kg/hr. The infusion rate was increased by 5 mg/kg/hr every 6 h until cessation of spasms or abolition of the patellar tendon reflex. Efficacy was determined by control of spasms. Time to commencement of feeds, frequency of autonomic instability, the need for ventilatory support, duration of hospitalisation and mortality were also recorded. Results: Twenty-seven children with tetanus aged between 18 months and 10 years were recruited. A contaminated wound was the most common portal of entry of tetanus spores. The incidences of severity were: grade I, 3; grade II, 7; grades IIIa and b, 17. Rigidity and spasms were controlled by magnesium therapy alone in 14 patients. Additional sedation was required for 13 patients (grade II, 1; grade III, 12). Feeding could be commenced early in five patients. Mechanical ventilation was required in eight patients. The mean (SD) duration of hospitalisation was 26.5 (12.0) days. Five patients died (18.5%). Asymptomatic hypocalcaemia was a universal finding and was treated with calcium supplements. Conclusion: MgSO4 alone is effective in mild-to-moderate tetanus but not when it is severe.

Evaluating the effect of magnesium supplementation and cardiac arrhythmias after acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Atrial and ventricular cardiac arrhythmias are one of the most common early complications after cardiac surgery and these serve as a major cause of mortality and morbidity after cardiac revascularization. We want to evaluate the effect of magnesium sulfate administration on the incidence of cardiac arrhythmias after cardiac revascularization by doing this systematic review and meta-analysis. METHODS: The search performed in several databases (SID, Magiran, IranDoc, IranMedex, MedLib, PubMed, EmBase, Web of Science, Scopus, the Cochrane Library and Google Scholar) for published Randomized controlled trials before December 2017 that have reported the association between Magnesium consumption and the incidence of cardiac arrhythmias. This relationship measured using odds ratios (ORs) with a confidence interval of 95% (CIs). Funnel plots and Egger test used to examine publication bias. STATA (version 11.1) used for all analyses. RESULTS: Twenty-two studies selected as eligible for this research and included in the final analysis. The total rate of ventricular arrhythmia was lower in the group receiving magnesium sulfate than placebo (11.88% versus 24.24%). The same trend obtained for the total incidence of supraventricular arrhythmia (10.36% in the magnesium versus 23.91% in the placebo group). In general the present meta-analysis showed that magnesium could decrease ventricular and supraventricular arrhythmias compared with placebo (OR = 0.32, 95% CI 0.16-0.49; p < 0.001 and OR = 0.42, 95% CI 0.22-0.65; p < 0.001, respectively). Subgroup analysis showed that the effect of magnesium on the incidence of cardiac arrhythmias was not affected by clinical settings and dosage of magnesium. Meta-regression analysis also showed that there was no significant association between the reduction of ventricular arrhythmias and sample size. CONCLUSION: The results of this meta-analysis study suggest that magnesium sulfate can be used safely and effectively and is a cost-effective way in the prevention of many of ventricular and supraventricular arrhythmias.

Inhaled magnesium sulfate in the treatment of acute asthma.

BACKGROUND: Asthma exacerbations can be frequent and range in severity from mild to life-threatening. The use of magnesium sulfate (MgSO4) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO4 has been demonstrated, the role of inhaled MgSO4 is less clear. OBJECTIVES: To determine the efficacy and safety of inhaled MgSO4 administered in acute asthma. SPECIFIC AIMS: to quantify the effects of inhaled MgSO4 I) in addition to combination treatment with inhaled ß2-agonist and ipratropium bromide; ii) in addition to inhaled ß2-agonist; and iii) in comparison to inhaled ß2-agonist. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Group register of trials and online trials registries in September 2017. We supplemented these with searches of the reference lists of published studies and by contact with trialists. SELECTION CRITERIA: RCTs including adults or children with acute asthma were eligible for inclusion in the review. We included studies if patients were treated with nebulised MgSO4 alone or in combination with ß2-agonist or ipratropium bromide or both, and were compared with the same co-intervention alone or inactive control. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial selection, data extraction and risk of bias. We made efforts to collect missing data from authors. We present results, with their 95% confidence intervals (CIs), as mean differences (MDs) or standardised mean differences (SMDs) for pulmonary function, clinical severity scores and vital signs; and risk ratios (RRs) for hospital admission. We used risk differences (RDs) to analyse adverse events because events were rare. MAIN RESULTS: Twenty-five trials (43 references) of varying methodological quality were eligible; they included 2907 randomised patients (2777 patients completed). Nine of the 25 included studies involved adults; four included adult and paediatric patients; eight studies enrolled paediatric patients; and in the remaining four studies the age of participants was not stated. The design, definitions, intervention and outcomes were different in all 25 studies; this heterogeneity made direct comparisons difficult. The quality of the evidence presented ranged from high to very low, with most outcomes graded as low or very low. This was largely due to concerns about the methodological quality of the included studies and imprecision in the pooled effect estimates. Inhaled magnesium sulfate in addition to inhaled ß2-agonist and ipratropiumWe included seven studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, results were inconsistent overall and the largest study reporting this outcome found no between-group difference at 60 minutes (MD -0.3 % predicted peak expiratory flow rate (PEFR), 95% CI -2.71% to 2.11%). Admissions to hospital at initial presentation may be reduced by the addition of inhaled magnesium sulfate (RR 0.95, 95% CI 0.91 to 1.00; participants = 1308; studies = 4; I² = 52%) but no difference was detected for re-admissions or escalation of care to ITU/HDU. Serious adverse events during admission were rare. There was no difference between groups for all adverse events during admission (RD 0.01, 95% CI -0.03 to 0.05; participants = 1197; studies = 2). Inhaled magnesium sulfate in addition to inhaled ß2-agonistWe included 13 studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, none of the pooled results showed a conclusive benefit as measured by FEV1 or PEFR. Pooled results for hospital admission showed a point estimate that favoured the combination of MgSO4 and ß2-agonist, but the confidence interval includes the possibility of admissions increasing in the intervention group (RR 0.78, 95% CI 0.52 to 1.15; participants = 375; studies = 6; I² = 0%). There were no serious adverse events reported by any of the included studies and no between-group difference for all adverse events (RD -0.01, 95% CI -0.05 to 0.03; participants = 694; studies = 5). Inhaled magnesium sulfate versus inhaled ß2-agonistWe included four studies in this comparison. The evidence for the efficacy of ß2-agonists in acute asthma is well-established and therefore this could be considered a historical comparison. Two studies reported a benefit of ß2-agonist over MgSO4 alone for PEFR and two studies reported no difference; we did not pool these results. Admissions to hospital were only reported by one small study and events were rare, leading to an uncertain result. No serious adverse events were reported in any of the studies in this comparison; one small study reported mild to moderate adverse events but the result is imprecise. AUTHORS' CONCLUSIONS: Treatment with nebulised MgSO4 may result in modest additional benefits for lung function and hospital admission when added to inhaled ß2-agonists and ipratropium bromide, but our confidence in the evidence is low and there remains substantial uncertainty. The recent large, well-designed trials have generally not demonstrated clinically important benefits. Nebulised MgSO4 does not appear to be associated with an increase in serious adverse events. Individual studies suggest that those with more severe attacks and attacks of shorter duration may experience a greater benefit but further research into subgroups is warranted.Despite including 24 trials in this review update we were unable to pool data for all outcomes of interest and this has limited the strength of the conclusions reached. A core outcomes set for studies in acute asthma is needed. This is particularly important in paediatric studies where measuring lung function at the time of an exacerbation may not be possible. Placebo-controlled trials in patients not responding to standard maximal treatment, including inhaled ß2-agonists and ipratropium bromide and systemic steroids, may help establish if nebulised MgSO4 has a role in acute asthma. However, the accumulating evidence suggests that a substantial benefit may be unlikely.

Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: a double-blind randomized controlled trial.

STUDY OBJECTIVE: The aim of this study is to compare the analgesic effect of intravenous infusion of magnesium sulfate to ketorolac during laparoscopic surgeries. DESIGN: Double-blind randomized controlled trial. SETTING: University-affiliated teaching hospital. PATIENTS: Sixty women submitted to laparoscopic gynecologic oncology surgeries. INTERVENTIONS: Intravenous ketorolac 30 mg in bolus followed by saline infusion (group K), intravenous magnesium sulfate 20 mg/kg in bolus followed by magnesium 2 mg kg(-1) h(-1) (group M) or intravenous saline solution 20 mL in bolus followed by saline infusion during the entire procedure (group S). MEASUREMENTS: Postoperative pain, nausea, vomiting, sedation, opioid consumption, time to first dose of analgesic. MAIN RESULTS: Magnesium sulfate reduced opioid consumption compared with placebo in the postoperative, but not in the intraoperative, period. Nausea, not vomiting, was reduced in ketorolac but not in the magnesium group. Pain intensity was higher in placebo than in the other 2 groups during all periods of observation. In the first 60 minutes, pain intensity was lower in the magnesium than in the ketorolac or the placebo group. CONCLUSION: Intraoperative magnesium sulfate improves postoperative pain control, acting as an opioid-sparing adjuvant, and is similar to ketorolac 30 mg administered in the beginning of surgery.

Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study.

PURPOSE: To compare the effects of magnesium sulfate and ketamine on postoperative pain and total morphine consumption in a placebo-controlled design. METHODS: One hundred and twenty women scheduled for total abdominal hysterectomy were included in this prospective, randomized, double-blind study. Postoperatively, when the Numeric Pain Rating Scale (NPRS) was four or more, IV-PCA morphine was applied to all patients. The patients were randomized into three groups: Group K ketamine, Group M magnesium, and Group C saline received as infusion. Total morphine consumption for 48h, pain scores, adverse effects, and patients' satisfaction were evaluated. RESULTS: Total morphine consumption was significantly lower in Group K (32.6±9.2 mg) than in Group M (58.9±6.5 mg) and in Group C (65.7±8.2 mg). The satisfaction level of patients in Group K was higher than the other two groups (p<0.05). Pruritus and nausea were observed more frequently in Group C. CONCLUSION: The addition of ketamine to IV-PCA morphine reduces the total consumption of morphine without psychotic effects; however, magnesium did not influence morphine consumption.

Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study

PURPOSE: To compare the effects of magnesium sulfate and ketamine on postoperative pain and total morphine consumption in a placebo-controlled design. METHODS: One hundred and twenty women scheduled for total abdominal hysterectomy were included in this prospective, randomized, double-blind study. Postoperatively, when the Numeric Pain Rating Scale (NPRS) was four or more, IV-PCA morphine was applied to all patients. The patients were randomized into three groups: Group K ketamine, Group M magnesium, and Group C saline received as infusion. Total morphine consumption for 48h, pain scores, adverse effects, and patients' satisfaction were evaluated. RESULTS: Total morphine consumption was significantly lower in Group K (32.6±9.2 mg) than in Group M (58.9±6.5 mg) and in Group C (65.7±8.2 mg). The satisfaction level of patients in Group K was higher than the other two groups (p<0.05). Pruritus and nausea were observed more frequently in Group C. CONCLUSİON: The addition of ketamine to IV-PCA morphine reduces the total consumption of morphine without psychotic effects; however, magnesium did not influence morphine consumption.

High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study.

OBJECTIVE: To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma. DESIGN: Prospective, randomized, open-label study. SETTING: Twenty-nine-bed pediatric emergency department located in a children's hospital in Asuncion, Paraguay. PATIENTS: All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma. INTERVENTIONS: Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications. MEASUREMENTS AND MAIN RESULTS: Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events. CONCLUSIONS: The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4 hr), for non-infectious mediated asthma, expedites discharges from the emergency department with significant reduction in healthcare cost.

Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour.

BACKGROUND: Magnesium sulphate has been used to inhibit preterm labour to prevent preterm birth. There is no consensus as to the safety profile of different treatment regimens with respect to dose, duration, route and timing of administration. OBJECTIVES: To assess the efficacy and safety of alternative magnesium sulphate regimens when used as single agent tocolytic therapy during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing different magnesium sulphate treatment regimens when used as single agent tocolytic therapy during pregnancy in women in preterm labour. Quasi-randomised trials were eligible for inclusion but none were identified. Cross-over and cluster trials were not eligible for inclusion. Health outcomes were considered at the level of the mother, the infant/child and the health service. INTERVENTION: intravenous or oral magnesium sulphate given alone for tocolysis.Comparison: alternative dosing regimens of magnesium sulphate given alone for tocolysis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: Three trials including 360 women and their infants were identified as eligible for inclusion in this review. Two trials were rated as low risk of bias for random sequence generation and concealment of allocation. A third trial was assessed as unclear risk of bias for these domains but did not report data for any of the outcomes examined in this review. No trials were rated to be of high quality overall.Intravenous magnesium sulphate was administered according to low-dose regimens (4 g loading dose followed by 2 g/hour continuous infusion and/or increased by 1 g/hour hourly until successful tocolysis or failure of treatment), or high-dose regimens (4 g loading dose followed by 5 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment, or 6 g loading dose followed by 2 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment).There were no differences seen between high-dose magnesium sulphate regimens compared with low-dose magnesium sulphate regimens for the primary outcome of fetal, neonatal and infant death (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.12 to 1.56; one trial, 100 infants). Using the GRADE approach, the evidence for fetal, neonatal and infant death was considered to be VERY LOW quality. No data were reported for any of the other primary maternal and infant health outcomes (birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome).There were no clear differences seen between high-dose magnesium sulphate regimens compared with low-dose magnesium sulphate regimens for the secondary infant health outcomes of fetal death; neonatal death; and rate of hypocalcaemia, osteopenia or fracture; and secondary maternal health outcomes of rate of caesarean birth; pulmonary oedema; and maternal self-reported adverse effects. Pulmonary oedema was reported in two women given high-dose magnesium sulphate, but not in any of the women given low-dose magnesium sulphate.In a single trial of high and low doses of magnesium sulphate for tocolysis including 100 infants, the risk of respiratory distress syndrome was lower with use of a high-dose regimen compared with a low-dose regimen (RR 0.31, 95% CI 0.11 to 0.88; one trial, 100 infants). Using the GRADE approach, the evidence for respiratory distress syndrome was judged to be LOW quality. No difference was seen in the rate of admission to the neonatal intensive care unit. However, for those babies admitted, a high-dose regimen was associated with a reduction in the length of stay in the neonatal intensive care unit compared with a low-dose regimen (mean difference -3.10 days, 95% confidence interval -5.48 to -0.72).We found no data for the majority of our secondary outcomes. AUTHORS' CONCLUSIONS: There are limited data available (three studies, with data from only two studies) comparing different dosing regimens of magnesium sulphate given as single agent tocolytic therapy for the prevention of preterm birth. There is no evidence examining duration of therapy, timing of therapy and the role for repeat dosing.Downgrading decisions for our primary outcome of fetal, neonatal and infant death were based on wide confidence intervals (crossing the line of no effect), lack of blinding and a limited number of studies. No data were available for any of our other important outcomes: birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome. The data are limited by volume and the outcomes reported. Only eight of our 45 pre-specified primary and secondary maternal and infant health outcomes were reported on in the included studies. No long-term outcomes were reported. Downgrading decisions for the evidence on the risk of respiratory distress were based on wide confidence intervals (crossing the line of no effect) and lack of blinding.There is some evidence from a single study suggesting a reduction in the length of stay in the neonatal intensive care unit and a reduced risk of respiratory distress syndrome where a high-dose regimen of magnesium sulphate has been used compared with a low-dose regimen. However, given that evidence has been drawn from a single study (with a small sample size), these data should be interpreted with caution.Magnesium sulphate has been shown to be of benefit in a wide range of obstetric settings, although it has not been recommended for tocolysis. In clinical settings where health benefits are established, further trials are needed to address the lack of evidence regarding the optimal dose (loading dose and maintenance dose), duration of therapy, timing of therapy and role for repeat dosing in terms of efficacy and safety for mothers and their children. Ongoing examination of different regimens with respect to important health outcomes is required.