Significance of serum magnesium levels in reference to acute myocardial infarction and role of intravenous magnesium therapy in prevention of cardiac arrhythmias following myocardial infarction

Address for the Correspondence: Dr. Dhanesh M. Mhaskar, Department of Medicine, Krishna Institute of Medical Sciences University, Dhebewadi Road, Karad 415 110, Satara, Maharashtra, India. E-mail: drdhaneshmh@yahoo.com Significance of serum magnesium levels in reference to acute myocardial infarction and role of intravenous magnesium therapy in prevention of cardiac arrhythmias following myocardial infarction

myocardial metabolism, protect against catecholamine-induced myocardial necrosis, and stabilize cell membranes.It is also cheap and easy to handle.Thus, it would appear to be an excellent contender for a place in the routine treatment of myocardial infarction, but it has not achieved this status yet.Therefore, the use of magnesium in myocardial infarction is a worthy topic of serious consideration.We, therefore, decided that we would evaluate the effect of I.V. magnesium supplement therapy in patients admitted for acute myocardial infarction and if this would be helpful in reducing the morbidity and mortality in patients.

MATERIALS AND METHODS
The study was carried out as a prospective randomized controlled trial of magnesium therapy in acute myocardial infarction, admitted in the medical intensive care unit of Krishna Hospital and Medical Research Centre.This study was approved by the ethical committee and an informed consent was taken from all the patients included in our study.100 patients with acute myocardial infarction (AMI) were, at random, divided into two groups of 50 patients each, one for trial and other for placebo therapy.Control group consisted of 20 healthy volunteers of the same age group.All of the 100 patients included in the study had reported within 12 hours of the onset of chest pain.
Group-I: 50 patients included in the placebo group received 1,000 ml of normal saline in the fi rst 24 hours and 1,000 ml in the second 24 hours period.
Group-II: The 50 patients in this group received magnesium infusion.During the 1 st 24 hours, all 50 patients received a bolus of 2 g over 15 minutes followed by an infusion of 18 g over 24 hours.
Group-III: The control group included 20 healthy subjects in the age group of 40-65 years.Serum magnesium levels of these controls were determined on one occasion only.
Reagents consisted of Calmagite 100 mol/L, ethyleneglycotetraacetic acid (EGTA) 1.09 mmol/L.The Calmagite reacts with the Mg present in the sample in the alkaline medium resulting in the formation of a coloured complex that can be measured by spectrophotometry.The concentration of Mg in the sample is directly proportional to the color of the complex.EGTA is included in the reagent to remove calcium interference.Normal value of Mg is 0.66-1.07mmol/L or 1.6-2.6 mg/dl.Apart from MgSO 4 , patients were treated with routine treatment of AMI and its complication as and when the need arose.Patients received analgesics, routine sedatives, vasodilators, thrombolytics, and were on anti-platelet and anticoagulant therapy during their hospital stay.
During the fi rst 7 days, all the patients of Group I and Group II were constantly monitored electrocardiographically.All arrhythmias and/or conduction abnormalities were recorded.Mortality and the causes of death were noted.Patients were followed for 4 weeks.
The data was tabulated and statistically evaluated by the student's 't' test and Chi-square test.

RESULTS
The mean age in the Group I and II were 59.52 years ± 15.03 and 59.14 years ± 13.41, respectively.There was no signifi cant difference in sex distribution of patients in Group I and Group II [Figure 1].
Serum magnesium level on admission was higher in the healthy controls than in the patients of acute myocardial infarction [Table 1].
Our study reveals a statistically signifi cant decrease in the incidence of arrhythmias in Group II [4/50 (8%)].The pattern of arrhythmias seen was as follows: Group-I: Supraventricular arrhythmias seen in four patients and ventricular arrhythmias seen in 13 patients Group-II: Supraventricular arrhythmias seen in one patient and ventricular arrhythmias seen in three patients.
Seven out of 50 (14%) patients of Group I had conduction disturbance, whereas two out of 50 (4%) patients of Group II had conduction disturbances.However, 25 out of 50 (50%) patients of Group I developed heart failure, whereas only 15 out of 50 (30%) patients of Group II developed this complication.The difference was statistically signifi cant (P < 0.005) [Figure 2].Hospital mortality in the 4-week-period after myocardial infarction was 10 out of 50 (20%) in Group I and three out of 50 (6%) in Group II which was statistically signifi cant (P < 0.05) [Figure 3].The causes of death comprised of cardiogenic shock, arrhythmias, pulmonary edema, pulmonary embolism, reinfarction, and myocardial rupture etc., [Table 2].
Table 2 also shows the clinical data of the 10 patients who expired in Group I of which the cause of death in six patients was cardiogenic shock, two patients died of pulmonary edema, one patient died of ventricular tachycardia, and one patient died of ventricular fi brillation.In Group II, in all three patients, the cause of death was cardiogenic shock.
As expected we found an increase in the serial magnesium concentration in the sample taken from patients of group II on day 2 and 5, which gradually decreased after cessation of magnesium sulfate infusion.Above levels of serum magnesium between the two groups were statistically signifi cant (P < 0.0001).There was no statistical difference in serum magnesium levels between survivors and non survivors in both the groups [Table 3].

DISCUSSION
Rasmussen et al., [5] came to similar conclusions where the complications in patients who received magnesium therapy was   linked with a fall in the number of arrhythmias which needed treatment during the fi rst week in hospital.Magnesium therapy inhibits the post-infarctional hypomagnesemia.
Iseri et al., [6] in their study treated multifocal atrial tachycardias successfully with parenteral magnesium and potassium.Magnesium administered together with potassium, stabilizes the ionic balance of the cells and thus prevents spontaneous ectopics.
Lezek Ceremuzynski et al., [7] proved that life threatening arrhythmias in AMI are prevented by I.V. magnesium sulfate.This was in agreement with the fi ndings of Rasmussen et al., and Smith et al., [8] Schechter et al., [9] and this encourages implementation of magnesium treatment into clinical practice.
Ising et al., [10] performed the following study.Seven 24 hours electrocardiograph (ECG) recordings and blood samples were taken within 3 weeks in 42 patients.Ca ++ , K + , and Mg ++ concentrations in serum, and K + and Mg ++ in the erythrocytes, were determined by atomic absorption spectroscopy.One half of the patients were infused with 81 mmol/day as MgSO 4 for 3 days.In patients who exhibited intense electrolytic alterations 10-20 days after AMI, there was a signifi cantly higher rate in the frequency of couplets and/or tachycardia in the 2-20 days period after AMI.In patients infused with MgSO 4 , the fl uctuation in serum electrolytes and the rate of arrhythmias were signifi cantly reduced.
Kent L. Woods et al. proved in "Leicester Intravenous magnesium intervention trials", the effi cacy of I.V. magnesium in reducing the mortality in patients of acute myocardial infarction.They conducted a double blind placebo controlled study in 2,316 patients who received either I.V. magnesium sulfate or physiological saline.The primary outcome measure was the 28 days mortality which was ascertained in 99.3% of patients.The groups were well balanced for prognostic factors.By intention to treat, mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group, a relative reduction of 2-4%.Koon K. Teo [11] conducted a study of the seven randomized trials conducted by The Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) included 2,316 patients, who were randomized to receive I.V. magnesium sulfate or matching placebo.Patients received placebo or magnesium for 5 min before initiation of thrombolytic therapy, followed by an infusion for the next 24 h.It concluded that there was 24% reduction in 28-day mortality, a 25% reduced incidence of left ventricular failure, and an improvement in long-term survival in terms of reduction of long-term mortality from ischemic heart disease (average follow-up period of 2.7 years). [12,13]gnesium treatment may reduce the incidence of ventricular fi brillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia, and fl ushing. [14]gnesium probably functions as an inorganic calcium channel blocker and there are several plausible mechanisms for a benefi cial effect in acute myocardial infarction (Woods 1991) ).Thus, magnesium-infusion started early after the onset of myocardial ischemia might limit infarct size, prevent serious arrhythmias, and reduce mortality.
Time is critical in management of AMI.If thrombolytic treatment is not given, spontaneous reperfusion occurs in at least a third of patients during the fi rst 12-24 hours after AMI (Woods 1995).The benefi ts from supplemental magnesium administration may be lost when there is a delay of more than 15-45 minutes after the onset of reperfusion (Antman 1995b).Careful laboratory studies, conducted since the Fourth International Study of Infarct Survival (ISIS-4) fi ndings, have continued to explore the role of magnesium in reducing myocardial damage around the time of reperfusion, and have demonstrated its critical nature, with any benefi t lost if treatment is delayed (Christensen 1995; Herzog 1995; Ravn 1999).

CONCLUSIONS
Serum magnesium levels on admission were significantly low in patients of acute myocardial infarction as compared with healthy controls.Hypomagnesemia is often associated with acute myocardial infarction.Our study proves that exogenously administered magnesium to patients of acute myocardial infarction in the immediate post infarctional period (<12 hours) has a cardio protective action, thus reducing the incidence of arrhythmias and the mortality during the fi rst 4 weeks after myocardial infarction.
Magnesium therapy reduces the incidence of arrhythmias and mortality even in the absence of demonstrable magnesium defi ciency.The present study is a good enough reason to include I.V. magnesium sulfate as an add-on prophylactic treatment in the acute coronary syndrome's management protocol.
International Journal of Medicine and Public Health | Jul-Sep 2013 | Vol 3 | Issue 3

Figure 1 :
Figure 1: Chart showing no difference in the age and sex distribution of the patients in Group I and Group II

Figure 2 :Figure 3 :
Figure 2: Incidence of arrhythmias, heart failure, and in-hospital mortality is signifi cantly lower in Group II as compared to Group I

Table 1 : The higher serum magnesium level on admission (mean±S.D.) (in mg/dl) in the healthy controls as compared to that in the patients of acute myocardial infarction (P<0.0001) Group No. of patients Serum magnesium levels on admission Healthy
controls n=20 2.2±0.20 Patients of AMI n=100 1.4±0.27AMI=Acute myocardial infarction, S.D=Standard deviation

Table 3 : Mean serum magnesium levels in all patients of acute myocardial infarction was signifi cantly higher in Group II patients on day 2 and
5 (***P<0.0001)(****P<0.0003)