A CLINICAL STUDY TO EVALUATE THE ROLE OF INTRAOPERATIVE MAGNESIUM SULPHATE FOR PROPHYLAXIS AGAINST ARRHYTHMIAS IN PATIENTS UNDERGOING ELECTIVE OPEN HEART SURGERY

Background: Hypomagnesemia seems to be a frequent finding in patients subjected to cardiac surgery under cardiopulmonary bypass (CPB) due to multifactorial etiology. Hypomagnesemia may be one of the many contributory factors that predispose towards the development of postoperative arrhythmias. Prophylactic magnesium administration in the perioperative period may be beneficial in the control of supraventricular tachyarrhythmias and ventricular ectopics after cardiac surgery. Hence we evaluated the role of intraoperative magnesium sulfate for prophylaxis against arrhythmias in patients undergoing elective open heart surgery under cardiopulmonary bypass.

Magnesium is an important mineral in the maintenance of normal cellular and bodily functions.1,2 It is an important regulator of multiple cardiovascular processes including myocardial conduction, myocardial contractility, transmembrane calcium flux, potassium transport, vascular smooth muscle tone, coronary vascular reactivity and nitric oxide synthesis.

2,3
Hypomagnesemia seems to be a frequent finding in patients undergoing cardiac surgery under cardiopulmonary bypass due to multifactorial etiologies like pharmacological treatment with β blockers, digitalis or diuretics, exogenous or endogenous catecholamine stimulation and diet deficiencies.The intraoperative decrease in serum magnesium is explained by dilution of extracellular volume by non magnesium containing fluids.5 It is also possible that high flow perfusion may greatly increase urinary loss of magnesium especially when mannitol is added to the priming fluid.4 Magnesium is a mineral that is involved in transmembrane and intracellular modulation of specific ion channels and ion transport processes.Overt Mg deficiency (<1.8 mg/dl) has been associated with ventricular arrhythmias, and correcting plasma levels of magnesium is certainly warranted. 7 Arrhythmias are common after open heart surgery and may be related to hypomagnesemia due to CPB. 8 The other factors that may contribute to dysrhythmias include digitalis, hypokalemia, volume overload, hypovolemia, pH changes and post cardiotomy irritability.6 Magnesium suppresses arrhythmias by multiple mechanisms which include a direct myocardial membrane stabilising effect, a direct or indirect effect on cellular potassium and sodium concentration, antagonism of calcium entry into cell, prevention of coronary artery vasospasm, antagonism of catecholamine action and improvement of the myocardial oxygen supply and demand ratio.

9,10
Prophylactic magnesium administration in the perioperative period may be beneficial in the control of supraventricular tachyarrhythmias and ventricular ectopics after cardiac surgery.The aim of the present study was to evaluate the role of intraoperative magnesium sulfate for prophylaxis against arrhythmias in patients undergoing elective open heart surgery under cardiopulmonary bypass.

Materials & Methods
The study was approved by hospital ethical committee and informed consent from all the participants was obtained.), sleep dose of thiopentone and vecuronium (0.1mg kg -1 ). Patients were intubated with cuffed endotracheal tube of appropriate size and ventilated with a tidal volume sufficient to maintain a PaCO 2 between 35 and 40 mmHg.Anaesthesia was maintained with isoflurane, fentanyl and vecuronium bromide.After this, urinary bladder was catheterised.Temperature and transesophageal echocardiography (TEE) probes were placed in each patient.
Cardiopulmonary bypass was established with a disposable membrane oxygenator pump.Priming fluid for pump contained 1 litre of hydroxyethyl starch, 500ml of ringer's solution, 3 ml kg -1 mannitol, 50 ml sodabicarb and 2g methyl prednisolone.During operation, systemic core temperature was maintained between 28°C to 30°C.Pump flow rate was kept at 2.4 l/min/m 2 body surface area at 37°C.For every 4°C fall in temperature, pump flow rate was reduced by 25%.After the ascending aorta was cross clamped, the cardioplegic solution was injected either into the aortic root or the coronary arteries at a dose of 20ml kg Samples for serum magnesium were taken preoperatively (T 1 ) before induction of anaesthesia, postoperatively (T 2 ) on arrival of patient in the intensive care unit and again after 24 hours (T 3 ).The samples were centrifuged and the serum collected was kept in freezer until analysis was performed.Serum magnesium levels were analysed using "atomic absorption spectrometer" which was standardised each time.The results were expressed in milligram per decilitre (mg dl -1 ).Normal range for serum magnesium with this spectrometer is 1.8 to 2.6 mg dl -1 .
After surgery all patients were shifted to the intensive care unit and intraoperative monitoring was extended there.Postoperative hypertension was managed with intravenous nitroglycerine infusion.Vasopressor support in the form of dopamine and adrenaline infusion was used as per standard protocol.Postoperative mechanical ventilation was continued until the residual effect of anaesthesia waned off and the cardiovascular and respiratory systems were judged to be satisfactory and stable.ECG (lead II, V) was monitored continuously for 24 hours.Whenever arrhythmia was recognised a printed report of the actual ECG was taken.A single patient can have multiple types of arrhythmias.Although all arrhythmic events were noted, occurrence of only first episode of arrhythmia was taken into account to calculate the incidence.The arrhythmias requiring intervention were treated as per standard protocol in both the groups.
Adverse effects that could be related to magnesium were categorised as delayed extubation (>6 hours), sedation and confusion, hypotension (<30% of basal systolic blood pressure), increased postoperative bleeding (>500 ml), and increased energy requirement for defibrillation (10-20 joules direct current used more than once).

Statistical analysis
At the end of study the data was compiled.For analysis of age, weight, sex, bypass time and type of surgery, Fisher's exact test was used.For magnesium levels paired and unpaired ttest was used.Unpaired t-test was used for comparison between groups and paired t-test for comparison within groups.For arrhythmia analysis, differences in proportions were analysed using chi-square test.A p value of less than 0.05 was considered to be statistically significant.

Results
Mean age and weight of patients between study and control group was statistically comparable (Table 1).Distribution of type of surgery in two groups is shown in ( Preoperative hypomagnesemia was seen in 13 patients (32.5%), 7 in study Group and 6 in control Group (Table 4).Preoperative serum magnesium levels in Group I (1.83±0.14mg dl -1 ) and Group II (1.8±0.128mg dl -1 ) were statistically comparable (p>.05) (Table-5).Following CPB, in the immediate postoperative period there was a significant fall in mean magnesium levels in both the groups as compared to preoperative values (p<0.001).This decrease in magnesium levels persisted till 24 hours in both Groups (p<0.001) (Table 5).The incidence of preoperative arrhythmias in two groups was comparable statistically (p>0.05,Table 6).There was a significant increase in the incidence of arrhythmias postoperatively as compared to preoperative values in the study group (20% to 55%, p <0.05) and the control groups (25% to 80%, p<0.001) but the relative risk for the increase in the incidence of arrhythmias was less in the study group as compared to the control group (2.75 vs. 3.2).Distribution of postoperative arrhythmic events is shown in Table - The antiarrhythmic mechanisms of magnesium sulfate are not fully understood.However magnesium sulfate is known to decrease the resting membrane potential and decrease the tendency to abnormal impulse formation.These effects have been suggested to be primarily mediated by an increasing Mg 2+ dependent sodium potassium ATPase activity.Augmentation of sodium potassium ATPase activity elevates the intracellular potassium concentration, thus increasing the membrane threshold potential. 20  Hypomagnesemia has been reported to be a frequent finding in cardiac surgical patients.Scheinman et al found preoperative hypomagnesemia in 44% of cardiac surgery patients.5 Aglio et al reported preoperative hypomagnesemia in 19.2% of patients posted for coronary artery revascularisation.6 Parra et al found 26.6% of the cardiac surgical patients to be hypomagnesemic preoperatively.21 The etiology of preoperative hypomagnesemia in the cardiac patients is multifactorial and it may be because of frequent use of drugs that adversely affect magnesium balance e.g.digoxin and diuretics.19,22 Another factor that contributes to preoperative hypomagnesemia is suboptimal nutritional support due to anxiety, depression or anorexia and nausea produced by many oral drugs they are taking.In our study, preoperative serum magnesium levels were comparable in both the groups.Following CPB there was significant fall in serum Mg 2+ levels in both the groups and this fall persisted for 24 hours.However patients in the study group (Group I) had a significantly higher mean serum magnesium level postoperatively than patients in the control group (1.71±0.121 vs. 1.49±0.146mg dl -1 , p<0.001).This higher mean serum magnesium level in group I persisted for 24 hours postoperatively (1.65±0.114 vs. 1.45±0.134mg dl -1 , p<0.001).

Groups
Our results are similar to the study of Shakerinea et al who observed that patients in whom Mg 2+ was supplemented in cardioplegic solutions had a significantly higher mean serum magnesium level postoperatively than patients in whom cardioplegic solution without magnesium was given (1.02±0.41 vs. 0.78±0.12mmolL -1 ) but the decline in serum magnesium levels was comparable in both the groups.23 It has been postulated that hypomagnesemia may be one of the many contributory factors that predisposes towards the development of postoperative arrhythmias.The intraoperative administration of magnesium may reduce the incidence of potentially serious arrhythmias following CPB.

11, 12
In our study incidence of preoperative arrhythmias was comparable in both the groups but ventricular arrhythmic events occurred more frequently in Group II than in group I (12 vs. 7).The relative risk for the increase in the incidence of arrhythmias was less in the study group as compared to the control group (2.75 vs. 3.2).Cook et al who studied administration of prophylactic intravenous magnesium sulphate in addition to oral β-blockade reported that it does not reduce the incidence of atrial arrhythmias after coronary artery or valvular heart surgery. 24In a similar study conducted by Shakerinea et al observed that ventricular arrhythmias occur significantly more frequently in patients in whom cardioplegic solution was not supplemented with Mg

4 , 5
Aglio et al. reported hypomagnesemia in almost 70% of patients following the cessation of CPB.

- 1 . 1 and subsequent doses were 5ml kg - 1 .
Standard cardioplegic solution consisted of 20mEq of potassium chloride, 50mEq of sodium bicarbonate and 8mg of dexamethasone per litre of ringer's solution.For study group I 16mmol L -1 of magnesium sulfate was added to cardioplegic solution.Cardioplegia was delivered after every 20 minutes or the return of electrical activity whichever was earlier.First dose was 10ml kg -Supplemental potassium was added to the pump if required to maintain a serum potassium level greater than 3.5 meq L -1 .

Table - 7 Distribution of postoperative arrhythmic events in the two groups
We observed delayed extubation in one patient in Group I. Increased energy for defibrillation was required in two patients, one was in the non magnesium group.Adverse effects related to magnesium intoxication usually appear at serum magnesium levels above 9 mg/dl