Prophylactic magnesium sulphate vs. lidocaine during off-pump coronary artery bypass grafting

EDITOR: The treatment of coronary artery bypass grafting (CABG) has evolved rapidly over the last three decades. The introduction of off-pump coronary artery bypass grafting (OP-CABG) has revolutionized the surgical approach for the treatment of coronary artery disease [1], not only by reducing the cost of surgery but also by eliminating the morbidity associated with cardiopulmonary bypass (CPB). Dysrhythmia is a common feature during OP-CABG for a variety of reasons: mechanical stimulation of the heart, myocardial ischaemia caused by snares/flow arresters used to control arteriotomy bleeding and electrolyte abnormalities including hypomagnesaemia. Malignant ventricular dysrhythmias, especially ventricular fibrillation, may pose a grave danger during OP-CABG. Hence, prophylactic administration of anti-dysrhythmic agents is recommended during distal coronary anastomosis. In this prospective randomized study, the anti-dysrhythmic efficacy of magnesium sulphate was compared to that of lidocaine and the possible anti-ischaemic effects of magnesium were explored. With approval of the institutional review committee and patient's written consent, 60 patients undergoing OP-CABG were included in the study. Exclusion criteria were as follows: poor left ventricular function (ejection fraction <40%), pre-operative dysrhythmia, previous pacemaker implantation, current treatment with anti-dysrhythmic drugs, left ventricular aneurysm and pre-existing renal disease. All patients had similar anaesthetic and surgical protocols. All anti-anginal and anti-hypertensive medications were continued up to the morning of surgery. Premedication consisted of oral diazepam 10 mg and atenolol 50 mg 1.5 h before anaesthesia. Pulse oximetry and end-tidal CO2 were monitored throughout the procedure. Anaesthesia was induced with morphine 0.1 mg kg−1, midazolam 0.1 mg kg−1 and thiopentone 1-2 mg kg−1. Endotracheal intubation was performed after muscle relaxation with pancuronium bromide 0.12 mg kg−1. The lungs were ventilated with intermittent positive pressure ventilation. Anaesthesia was maintained with oxygen, isoflurane and morphine. Glyceryl trinitrate and dopamine infusions were initiated at 0.5 and 2 μg kg−1 min−1, respectively, and titrated to a mean arterial pressure within 20% of the basal values. Phenylephrine was used in 50 μg boluses during coronary anastomosis in order to maintain the mean arterial pressure ≥70 mmHg. The patients were randomly divided into three groups as follows: Group L patients received a lidocaine bolus of 1.5 mg kg−1 followed by 2 mg kg−1 h−1 as an infusion. Group M patients received a 1 g bolus of magnesium sulphate followed by an infusion at a rate of 2 g h−1. The boluses of lidocaine and magnesium sulphate, respectively, were administered after sternotomy but prior to coronary anastomosis. Group C patients received an infusion of normal saline. The infusions were run during the period of anastomosis and terminated at the end of grafting. All patients had surgery through a median sternotomy. Normothermia was maintained. Patients received heparin 200 units kg−1. The target activated coagulation time was 300 s. Proximal anastomosis was undertaken with partial clamping of the ascending aorta and the distal grafting was performed using the Octopus II tissue stabilizer. OP-CABG was converted to conventional surgery with CPB at any point if the patient did not tolerate the period of ischaemia required to complete bypass grafting or for surgical reasons. Haemodynamic criteria to convert to CPB were a systolic arterial pressure of <70 mmHg for >5 min, heart rate (HR) <45 beats min−1, ventricular dysrhythmia unresponsive to lidocaine and visible cardiac distension. Electro cardiography (ECG) leads I, II and V5 were monitored with continuous ST segment analysis during the entire procedure. ST segment depression or elevation of >1.0 mm was considered as clinically significant ischaemia. The time interval during distal coronary artery anastomosis was divided into 5-min periods. During each such period any episode of dysrhythmia or ischaemia was designated as an 'adverse event'. For each patient, the number of periods with dysrhythmia or ischaemia, respectively, was added to give the total number of adverse events for that particular patient. Numerical data were expressed as mean ± SD and analysed statistically using the t-test and ANOVA. There were no significant differences in patient age (control: 52 ± 10 yr; lidocaine: 57 ± 10 yr; magnesium: 56 ± 9 yr) or pre-operative left ventricular ejection fraction (control: 47 ± 6%; lidocaine: 50 ± 5%; magnesium: 48 ± 5%). The incidence of dysrhythmias is shown in Table 1. Episodes of ischaemia are shown in Table 2. There were significantly fewer episodes of dysrhythmia and ischaemia in the magnesium group compared to the other two groups (P < 0.05). There were no significant differences between the control and lidocaine groups.Table 1: Episodes of rhythm disturbances during distal grafting.Table 2: Episodes of ischaemia during distal grafting.Magnesium has been shown to exert a cardioprotective effect when administered before an ischaemic period [2]. The cardioprotective effects of Mg2+ have been attributed to decreased Ca2+ influx during ischaemia, prevention and relief of coronary spasm, reduction of myocardial oxygen consumption, decreased afterload and hence improved cardiac index, anti-catecholamine effects, decreased platelet aggregation and decreased severity of myocardial stunning. Postulated anti-dysrhythmic mechanisms of Mg2+ are decreased cellular ischaemia-reperfusion injury, prolongation of atrioventricular (A-V) conduction time, Class IV and a weak Class I anti-dysrhythmic effect, suppression of conduction in accessory pathway and decreased irritability of the ischaemic myocardium. Perioperative hypomagnesaemia during OP-CABG can be caused by hyperventilation-induced reductions in ionized Mg2+ concentrations, catecholamine-induced lipolysis with chelation of magnesium by free fatty acids, pre-operative hypomagnesaemia secondary to use of diuretics and haemodilution secondary to intravenous (i.v.) fluid replacement [3]. Based on our findings, we conclude that prophylactic magnesium administration in patients under-going OP-CABG is associated with a significantly decreased incidence of dysrhythmias and ischaemic episodes compared to lidocaine or placebo infusions. M. Kanchi N. Prasad D. Garg S. K.