The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24%(95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25%(7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

Since 1955, a standardized treatment regimen has been used to manage 245 cases of eclampsia at Parkland Memorial Hospital. Magnesium sulfate alone effectively controlled controlled convulsions in the great majority of cases. The only maternal death among the 245 cases reemphasizes the risk of respiratory arrest that is inherent in the administration of magnesium sulfate when given in large doses intravenously. Hydralazine to lower the diastolic blood pressure somewhat, when it was 110 mm Hg or higher, prevented intracranial hemorrhage. Avoidance of diuretics and hyperosmotic agents and limitation of fluid intake were not associated with severe renal failure. Pulmonary edema was rare. Vaginal delivery was achieved in the majority of cases. Oxytocin often proved effective for initiating and maintaining labor even remote from term. The results obtained with this regimen justify its continued clinical application.

Conventional nebulized beta-agonist therapy has met with disappointing results in an increasing number of moderate to severe asthmatics who may be characterized as "poor responders." Thirty-eight patients suffering from acute exacerbations of moderate to severe asthma were treated in an emergency department with an intravenous infusion of saline placebo or 1.2 g of magnesium sulfate after conventional beta-agonist therapy failed to produce significant improvement in peak expiratory flow rate. Nineteen patients were randomized into each of two groups in a placebo-controlled, double-blind clinical trial. The treatment group demonstrated an increase in peak expiratory flow rate from 225 to 297 L/min as compared with 208 to 216 L/min seen in the placebo group. In addition, the number admitted vs discharged was significantly better for the treatment group (7 vs 12) than the placebo group (15 vs 4). Intravenous magnesium sulfate may represent a beneficial adjunct therapy in patients with moderate to severe asthma who show little improvement with beta-agonists.

BACKGROUND AND PURPOSE 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. METHODS 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. RESULTS 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). CONCLUSIONS Magnesium sulfate is well tolerated after acute stroke and has no deleterious hemodynamic effects at this dose. Further trials are required to determine efficacy.

The increasing use of coronary infusates for the protection of the human heart drug ischemic cardiac arrest has placed great emphasis on the need for a rational and safe formulation of any infusion solution. Using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest, we have found magnesium to be a highly effective component of protective infusates which can be additive to hypothermia and other protective agents. However, the concentration of magnesium bears a complex relationship to the degree of protection, a fact which stresses the need for the establishment of the correct concentration for optimal protection.

The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction. Treatment, according to a double-blind randomised protocol, was started with a loading injection, before any thrombolytic therapy, and continued with a maintenance infusion for a further 24 h. Cause-specific mortality of randomised patients has now been examined over 1.0-5.5 (mean 2.7) years of follow-up. Mortality rate from ischaemic heart disease was reduced by 21%(95% CI 5-35%, p = 0.01) and all-cause mortality rate reduced by 16%(2-29%, p = 0.03) in magnesium-treated patients. Magnesium protects the contractile function of the myocardium from reperfusion injury ("stunning") in experimental models; this observation accords with the 25%(7-39%, p = 0.009) reduction in early left ventricular failure in the magnesium group of LIMIT-2. For such protection to occur, magnesium must be raised by the time of reperfusion since the injury is immediate. In the clinical context the timing of magnesium treatment in relation to thrombolytic therapy or spontaneous reperfusion is likely to be critical. The early benefits of this simple and safe intervention are reflected in improved long-term survival.

BACKGROUND Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days. METHODS 2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done. FINDINGS The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group. INTERPRETATION Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively. In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15). In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17). Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum. By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

STUDY OBJECTIVE This study was conducted to determine whether intravenous magnesium sulfate (MgSO4), when used as part of a standardized treatment protocol, can improve pulmonary function and decrease admission rate in patients presenting to the emergency department with exacerbations of asthma. DESIGN In this randomized double-blind placebo-controlled study, patients with acute asthma were treated with inhaled beta-agonists at regular intervals and intravenous (IV) steroids. At 30 min after entry, patients received either 2 g IV MgSO4 or IV placebo. Patients were monitored for up to 4 h with regular measurements of pulmonary function. Patients who were discharged from the emergency department were contacted at 1 day and 7 days for follow-up. SETTING Emergency departments of a university-affiliated, voluntary hospital and municipal hospital. PARTICIPANTS Asthmatics aged 18 to 65 years during acute exacerbation with FEV1 less than 75% predicted both before and after a single albuterol treatment. INTERVENTIONS Patients were given 2 g of MgSO4 or placebo as an adjunct to standardized emergency department procedure for acute asthma. MEASUREMENTS AND RESULTS One hundred thirty-five patients were studied. Hospital admission rates were 35.3% for placebo-treated group and 25.4% for the magnesium-treated group (p = 0.21). FEV1 measured at 120 min was 56% predicted for the placebo-treated group and 55% predicted for the magnesium-treated group.(p = 0.92) For subgroup analysis, patients were divided into "severe"(baseline FEV1 < 25% predicted on presentation) or "moderate"(baseline FEV1, 25 to 75% predicted on presentation). For the severe group, admission rates were 78.6%(11/14) for the placebo-treated group and 33.3%(7/21) for the magnesium-treated group (p = 0.009). For the moderate patients, admission rates were 22.4%(11/49) for the placebo-treated group and 22.2%(10/25) for the magnesium-treated group (p = 0.98). There was no significant improvement in FEV1 in the moderate group for magnesium-treated patients. However, in the severe group, there was a significant improvement in FEV1 at 120 min and 240 min (p = 0.014 and 0.026, respectively). CONCLUSION Intravenous MgSO4 decreased admission rate and improved FEV1 in patients with acute severe asthma but did not cause significant improvement in patients with moderate asthma.