Con: Magnesium should not be administered to all coronary artery bypass graft surgery patients undergoing cardiopulmonary bypass.

MAGNESIUM (Mg11) is the second most abundant intracellular cation and the fourth most abundant in the body. It plays an essential role in the regulation of cardiac excitability, vasomotor tone, neuronal activity, and neuromuscular transmission.1 Perioperative administration of intravenous Mg11 has received considerable attention in the cardiac surgical and anesthesiology literature. Hypomagnesemia occurs frequently not only in patients undergoing cardiac surgery, but also in many critically ill nonsurgical patients and has been associated with increased morbidity.2,3 Patients at risk for preoperative hypomagnesemia include those receiving diuretics or digoxin and those with type I diabetes mellitus.4 Mg11 administration during cardiac surgery has been reported to yield better myocardial protection as well as a reduction in the incidence of postoperative arrhythmias.5 Some investigators have also shown a potential neuroprotective and anti-inflammatory action of Mg11 in animal models.6,7 Although the authors support the recognition and treatment of perioperative Mg11 deficiency, the authors believe that the administration of Mg11 should be conducted cautiously and not in all patients undergoing coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). In plasma, Mg11 is found as a protein-bound and a free, ionized form. The ionized, free Mg11 (iMg11) is the most physiologically important fraction because it regulates electrolyte transport, the production of cellular energy, and the activity of membrane pumps. Most of the outcome studies done in cardiac patients undergoing CPB have based their conclusions on total plasma levels of Mg11.3-5,8,9 Although iMg11 represents 71% of total plasma Mg11 (TMg11), its concentration cannot be predicted from TMg11.10 Several studies done in healthy human subjects as well as in cardiac patients have shown that iMg11 displays a wide variation from normal values, whereas TMg11 remains unchanged.11,12 Brookes and Fry12 found a significant reduction of plasma iMg11 in cardiac patients at 24 hours after CPB, which was not associated with changes in TMg11. Other investigators have shown that iMg11 variations during the course of CABG surgery are not readily predictable.13 In the setting of acute acidosis, which often occurs in unstable, critically ill patients, the free iMg11 fraction is increased, while the protein-bound circulating Mg11 is reduced.14 Outcome studies using iMg11 are needed before administering Mg11 routinely to all CABG surgery patients undergoing CPB. Existing studies evaluating the role of TMg11 in preventing perioperative arrhythmias have yielded conflicting results. Several studies have shown that the administration of intravenous Mg11 reduces the incidence of supraventricular arrhythmias after coronary artery surgery.8,9,15 Other investigators, however, have shown that increasing serum Mg11 levels have been associated with a higher incidence of post-CABG surgery atrial fibrillation.16 Deceleration of the sinus rate by Mg11 was proposed as a potential mechanism for this increased incidence. In a double-blind, placebo-controlled study of 298 patients,17 no beneficial effect of Mg11 infusion on tachyarrhythmia was detected. Instead the investigators found a significantly increased incidence of atrioventricular conduction disturbances in the Mg11-treated group with no correlation between the serum Mg11 levels and the occurrence of conduction disturbances. With respect to ventricular arrhythmias, there is some evidence for a potential beneficial effect of Mg11.5 Small studies in patients with acute myocardial infarction (AMI) have shown a trend toward less ventricular ectopy in patients treated with Mg11.18 Patients with congestive heart failure and elevated plasma levels of Mg11, as the result of chronic renal insufficiency, had fewer ventricular arrhythmias when compared with patients with a decreased concentration of Mg11.19 Just as with supraventricular arrhythmias, however, other investigators have not found a statistically significant decrease in the rate of occurrence of ventricular arrhythmias after the administration of Mg11.8 In the Fourth International Study of Infarct Survival (ISIS-4) involving 58,050 patients with suspected AMI, no significant reduction in ventricular fibrillation was detected in patients treated with magnesium.20 Because the exact mechanism of the antiarrhythmic action of Mg11 has not been elucidated and because clinically relevant electric effects of hypomagnesemia seem to require the coexistence of other electrolyte abnormalities, it is likely that these conflicting findings result from small studies in which there are confounding variables, such as hypokalemia, hypocalcemia, and varying plasma levels of iMg11. Mg11 has been reported to afford myocardial contractile protection, particularly in patients with AMI.18,21 Potential mechanisms for this protection include a reduction in oxygen demand, an improvement of collateral blood supply, and membrane stabilization.22 In a double-blind, placebo-controlled, randomized trial (Leicester Intravenous Magnesium Intervention Trial [LIMIT-2]) in patients who sustained AMI, intravenous Mg11 was administered at the time of thrombolytic therapy. The investigators found a reduction in early mortality rate, which was comparable to but independent of thrombolytic or antiplatelet therapy.21 Most of the mortality rate reduction took place in the first week after myocardial infarction and was thought to be the result of a decrease in the incidence of congestive heart failure. However, there was neither a standardized assessment of left ventricular function, nor a comparison with previous left ventricular function. Morton et al,18 by looking at the size of infarction and its association with Mg11 administration, reported a reduction of infarct size only in patients with normal left ventricular function treated with intravenous Mg11. When heart failure was present, there was From the Department of Anesthesiology, Duke University Medical Center, Durham, NC. Address reprint requests to Joseph P. Mathew, MD, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710. Copyright r 2000 by W.B. Saunders Company 1053-0770/00/1403-0023$10.00 doi:10.1053/cr.2000.5836