Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial. A randomized, double-blind, placebo-controlled pilot trial of intravenous magnesium sulfate in acute stroke. Dose optimization of intravenous magnesium sulfate after acute stroke. Magnesium sulfate therapy after aneurysmal subarachnoid hemorrhage. Adjunctive magnesium infusion therapy in acute myocardial infarction. Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality.
Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients.
                In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number .
                Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect.
                Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury. Magnesium reverses cerebral vasospasm and reduces infarct volume after experimental subarachnoid hemorrhage (SAH) in rats. We aimed to assess whether magnesium reduces the frequency of delayed cerebral ischemia (DCI) in patients with aneurysmal SAH.
                Patients were randomized within 4 days after SAH. Magnesium sulfate therapy consisted of a continuous intravenous dose of 64 mmol/L per day, to be started within 4 days after SAH and continued until 14 days after occlusion of the aneurysm. The primary outcome DCI (defined as the occurrence of a new hypodense lesion on computed tomography compatible with clinical features of DCI) was analyzed according to the "on-treatment" principle. For the secondary outcome measures "poor outcome" (Rankin >3) and "excellent outcome" (Rankin 0), we used the "intention-to-treat" principle.
                A total of 283 patients were randomized. Magnesium treatment reduced the risk of DCI by 34% (hazard ratio, 0.66; 95% CI, 0.38 to 1.14). After 3 months, the risk reduction for poor outcome was 23% (risk ratio, 0.77; 95% CI, 0.54 to 1.09). At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9).
                This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. A next step should be a phase III trial to confirm the beneficial effect of magnesium therapy, with poor outcome as primary outcome. Magnesium ions act as endogenous vasodilators of the cerebral circulation and act pharmacologically as noncompetitive antagonists of the N-methyl-D-aspartate receptor by virtue of their role as endogenous voltage-sensitive blockers of the ion channel. The preclinical efficacy of magnesium has been demonstrated in standard models of stroke.
                Sixty patients were randomized to magnesium sulfate (8 mmol IV over 15 minutes and 65 mmol over 24 hours) or placebo within 12 hours of clinically diagnosed middle cerebral artery stroke. Pulse, blood pressure, and serum magnesium levels were monitored. Primary outcome was death or significant functional impairment (Barthel Index score < 60) at 3 months.
                Magnesium was well tolerated, with no significant adverse effects and no change in blood pressure or pulse rate. Laboratory and electrocardiographic variables did not differ significantly between placebo- and magnesium-treated groups. Serum magnesium rose from 0.76 mmol/L to 1.42 mmol/L over 24 hours and remained significantly higher than in the placebo group at 48 hours. Thirty percent of magnesium-treated and 40% of placebo-treated patients were dead or disabled (Barthel Index score < 60) at 3 months (P = .42). There was a decrease in the number of early deaths in the magnesium-treated group (P = .066, log-rank test).
                Magnesium sulfate is well tolerated after acute stroke and has no deleterious hemodynamic effects at this dose. Further trials are required to determine efficacy. Parenterally administered MgSO4 is neuroprotective in standard animal models of focal cerebral ischemia and in many other paradigms of brain injury. Previous small clinical trials in stroke patients have explored the safety and tolerability of different infusion regimens. This study was undertaken to optimize the regimen for a multicenter trial.
                Within 24 hours of the onset of clinically diagnosed stroke, patients were randomized to receive placebo or one of three intravenous MgSO4 infusions: a loading infusion of 8, 12, or 16 mmol, followed by 65 mmol over 24 hours. Cardiovascular parameters, serum magnesium concentrations, and blood glucose concentrations were determined. Outcome at 30 and 90 days was recorded.
                Twenty-five patients were recruited and treated at a mean time of 20 hours after stroke. No tolerability problems were identified. No effects of magnesium on heart rate, blood pressure, or blood glucose were evident. Serum magnesium concentrations rose to target levels most rapidly in the highest loading infusion group and were maintained in all groups for at least 24 hours.
                MgSO4 infusions that rapidly elevate the serum magnesium concentration to potentially therapeutic levels are well tolerated and have no major hemodynamic effects in patients with acute stroke. The 16-mmol loading infusion achieved target serum concentrations most rapidly and has been chosen for further trials. Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH.
                A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II-IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 +/- 0.68 in the MgSO4 treatment group and 2.3 +/- 0.73 in the control group (mean +/- standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 +/- 27 cm/second in MgSO4-treated patients and 102 +/- 34 cm/second in the control group (mean +/- SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 +/- 1.6 and 3.6 +/- 1.5 (mean +/- SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur.
                Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further. Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown to be beneficial in many studies. However, these effects are not consistent from one trial to another, and their clinical significance is often questionable. A total of 78 consecutive patients were included in a prospective placebo controlled, randomized study of the effects of intravenous magnesium sulfate infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and the rest belonged to a non-thrombolysed group. These patients were randomized to receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24 h) or placebo. The end points were serious arrhythmias, left ventricular ejection fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P = 0.40). However, the LVEF of the placebo-treated thrombolysed group was higher than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of nonsustained ventricular tachycardia (NSVT) was higher with placebo than with magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28 days was also similar in both the groups. Thus, the administration of magnesium infusion as an adjunct to thrombolytic therapy remains to be of questionable benefit. To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery.
                Randomized, double-blind, placebo-controlled trial.
                A tertiary acute-care 500-bed university teaching hospital.
                Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied.
                Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass.
                Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia.
                Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period. The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).
                In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.
                Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).
                Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion. Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study.
There is currently no evidence to support the use of magnesium salts in patients with acute traumatic brain injury.