Investigation of the effects of intravenous magnesium sulphate on cardiac rhythm in acute myocardial infarction. Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy. Protective effect of intravenous magnesium in acute myocardial infarction following thrombolytic therapy. Effects of intravenous magnesium sulphate in suspected acute myocardial infarction on acute arrhythmias and long-term outcome. Adjunctive magnesium infusion therapy in acute myocardial infarction. Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial. A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty. Correction of ionized plasma magnesium during cardiopulmonary bypass reduces the risk of postoperative cardiac arrhythmia. [Intravenous magnesium in acute myocardial infarct].
To examine the effect of doubling serum magnesium concentration on the incidence of arrhythmias in patients with suspected acute myocardial infarction.
                Randomised double blind clinical trial.
                Coronary care unit of a teaching hospital.
                Clinical data were collected on 2316 randomised patients with suspected acute myocardial infarction. Holter monitoring was performed in a subgroup of 70 patients and analysed in 48 patients in whom acute myocardial infarction was confirmed.
                By random allocation, patients received either an intravenous loading dose of 8 mmol magnesium sulphate over five minutes plus 65 mmol over the next 24 hours, or equal volumes of saline.
                (a) Clinically documented arrhythmias; (b) use of antiarrhythmic treatments, cardioversion, and insertion of a pacemaker; (c) incidence of all abnormal rhythms during Holter monitoring.
                In the main trial the incidence of rhythm disturbance while in the coronary care unit (expressed as the odds ratio (OR) for magnesium: placebo and its 95% confidence interval) was not significantly different between treatment groups for ventricular fibrillation (OR 0.74; 0.46 to 1.20), ventricular tachycardia (OR 0.87; 0.63 to 1.20), supraventricular tachycardia (OR 0.69; 0.38 to 1.26), atrial fibrillation (OR 0.92; 0.69 to 1.23), or heart block of any degree (OR 1.17; 0.83 to 1.65). Sinus bradycardia was significantly more common in the magnesium group (OR 1.38; 1.03 to 1.85; p = 0.02). These findings were corroborated by the use of treatments for rhythm disturbance and the data from Holter monitoring.
                The regimen of intravenous magnesium sulphate used here had no significant effect on arrhythmia in acute myocardial infarction. The reduction in mortality that has been shown with this form of treatment is not attributable to suppression of life threatening rhythm disturbances. Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI. The role of intravenous magnesium therapy in patients with acute myocardial infarction (AMI) who received thrombolytic therapy is controversial. The results from previous clinical trials were not in consonance. We therefore conducted a prospective, randomized, double-blind, placebo controlled study in 350 patients with confirmed AMI during the period January 1994 to December 1996. The role of intravenous magnesium sulphate therapy (2 g over 5 min followed by 16 g over 24 h) was evaluated in patients with AMI who received thrombolytic therapy. Study group consisted of 169 patients who were administered magnesium sulphate. Control group comprised of 181 patients who were given isotonic saline. Among those in the magnesium group, 70% received magnesium within 6 h after the onset of symptoms. All patients received magnesium immediately after the completion of thrombolytic therapy. Patients were followed up for 30 days after AMI. The number of deaths in the study group was 6 (3.5%) compared with control arm in which 18 patients (9.9%) died (P value <0.01 95% Confidence intervals [CI] 1.2 to 11.6). Ventricular arrhythmias were also less in the magnesium arm; 27 patients (13%) compared with 83 patients (48.6%) in the control arm (P value 0.00001 95% Cl 26.7 to 44.5). In the magnesium group 15 patients (8.8%) had re-infarction compared with 23 patients (12.7%) in the placebo arm (P value not significant). Post myocardial infarction angina was observed in 47 patients (27.8%) in the magnesium arm compared with 60 patients (33.1%) in the placebo arm (P value not significant). The main side effect of intravenous magnesium was transient flushing observed in 152 (90%) patients. Intravenous magnesium sulphate in patients with AMI is a safe and useful adjunct to thrombolytic therapy in reducing the short-term mortality and ventricular arrhythmias after AMI. A total of 252 patients with suspected acute myocardial infarction were included in a double blind study and randomised to 50 mmol magnesium sulfate infusion under 20 h or corresponding placebo. Acute myocardial infarction was verified in 117 patients and 59% of these had concomitant treatment with thrombolysis. One-hundred ninety-four patients had Holter registrations during the first day in the coronary care unit. Intention-to-treat analysis showed an increase in long RR-intervals (> 3 s) in the magnesium treated group (P = 0.006) and a tendency toward a reduction in episodes of ventricular premature complexes in triplets (P = 0.09). During hospital stay and a mean of 22 months follow-up, 23 fatal events occurred in the magnesium allocated group and 31 fatal events among the placebo allocated group (P = 0.1). Mortality rate from cardiac disease was reduced by 54% (95% C.I. 30-99%, P < 0.05). Subgroup analysis on acute myocardial infarction patients showed a 48% mortality risk reduction in the magnesium treated acute myocardial infarction group compared to the placebo treated acute myocardial infarction group (95% C.I. 23-104%, P = 0.06). There was no significant interaction between the effects of magnesium and thrombolytic treatment on total mortality or cardiac events. This study supports the results of other small double blind placebo controlled studies regarding effects of magnesium therapy on mortality in acute myocardial infarction, but are in discordance to the conclusion from the ISIS-4 study. The reasons for these discrepancies cannot be elucidated by our data. 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. Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction.
                One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat.
                There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 +/- 0.61 vs 1.85 +/- 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% +/- 11% vs 50% +/- 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 +/- 2359 vs 2404 +/- 1673,P =.052).
                Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty. We conducted this randomized controlled trial to determine whether the intraoperative measurement and correction of ionized plasma magnesium can reduce the risk of cardiac arrhythmia after cardiopulmonary bypass. Eighty-five patients presenting for coronary artery bypass grafting were randomly assigned either to the magnesium-corrected group, which received magnesium sulfate on the basis of measured levels of ionized plasma magnesium (n = 43), or to the control group, in which magnesium levels were identified but not corrected (n = 42). Ionized magnesium was determined with an ion-selective electrode with minimal delay, and further samples were taken for laboratory analysis of total plasma magnesium. All patients had Holter electrocardiogram monitoring for 72 h after surgery. Total hypomagnesemia (45 patients; 53% of all patients) was more common than ionized hypomagnesemia (11 patients; 13%) before cardiopulmonary bypass. Both total and ionized magnesium levels declined further during the course of cardiopulmonary bypass in the control group. The incidence of ventricular tachycardia in the first 24 h was less frequent in the magnesium-corrected group (3 patients; 7%) than the control group (12 patients, 30%; P < 0.01). Patients in the magnesium-corrected group were more likely to display continuous sinus rhythm (Lown Grade 0) in the first 24 h (14 patients; 34%) than patients in the control group (2 patients, 5%; P < 0.001). Our results suggest that the intraoperative correction of ionized magnesium is associated with a reduction in postoperative ventricular arrhythmia in cardiac surgical patients.
                In this study the correction of ionized plasma magnesium during cardiopulmonary bypass was guided by measurements from an ion-selective electrode. This intervention resulted in a reduction in the incidence of postoperative ventricular tachycardia and an increased frequency of continuous sinus rhythm. Ion-selective electrodes constitute a convenient near-patient test, providing a basis for the targeted replacement of ionized plasma magnesium. The effects of magnesium (Mg) on the incidence of arrhythmias and on mortality were evaluated in 61 patients with documented acute myocardial infarction (AMI), in a randomized, double blind placebo controlled study. During the first 24 hours 31 patients received infusion of 1000 ml isotonic saline with 17 g MgSO4 and 30 ones received only equal volumes of saline as placebo. The baseline characteristics of the population including serum Mg and potassium were similar in the two groups. Severe arrhythmias were not as frequent in the Mg group (22%) as in the placebo one (36%), but the difference was not statistically significant (p = 0.05). There is no significant difference between the groups neither in mortality (3.2%; 0%) nor in conduction disturbances (3.2%; 3%). The adverse effects of Mg therapy were transient and therapy interruption was not required.
                Although the trial is not an extensive one, and the results are nonsignificant, we consider intravenous Mg therapy to be simple and cheap with its place in the treatment of AMI in properly selected patients. According to available data it should be administered as soon as possible after the onset of AMI symptoms, before thrombolytic therapy, in 24-hrs. dose not exceeding 50-65 mmol probably through several days, but the optimal duration of therapy should be further investigated.
Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treated with thrombolysis.