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Magnesium Sulphate Before
Aortic Cross-Clamping,
¿Useful For 'Myocardial Protection'?

Santos Gracia, José*;
Olivera Martínez, Armando**;
Morlans Hernández, Karel*;
Valdés Valdés, Francisco***

Instituto de Cardiología y Cirugía Cardiovascular (ICCCV)*;
Centro de Investigaciones Médico-Quirúrgicas (CIMEQ)**
y Hospital Universitario "Calixto García"***. La Habana, CUBA

SUMMARY
Background: There is evidence of a chronic deficit of Magnesium in the world population, attributable to poor nutritional intake. In patients with cardiac disease, use of diuretic drugs leading to a depletion of magnesium aggravates this common deficit and contribute to the appearance of malignant arrhythmias. Magnesium has been recommended as part of the treatment of acute myocardial infarction for its 'energy preserving' action in the ischaemic or reperfused cardiac cell. Its use in cardiac surgery, although quite widespread, is also controversial.
Objective: To evaluate the effects of magnesium sulphate before aortic cross-clamping on the appearance of malignant arrhythmias and the requirement for inotropic drugs in the post-cardiopulmonary bypass period (post-CPB)
Methods: Prospective, controlled, single blind study with patient consent involving 78 consecutive patients, divided into a treatment group (MG) and control group (C) of 39 patients each, for elective aortic valve replacement or CABPG surgery with cardiopulmonary bypass (CPB) and cold crystalloid cardioplegia (CCC) between July 1999 and December 2000. MG group received an infusion of magnesium sulphate (4 grams/16 mmol in 50 ml of Normal Saline at a rate of 60 ml/h) before cross-clamping.
Main Results: There was no significant difference between MG and C group regarding demographic and laboratory variables. Cardiac re-activation (sinus rhythm) was similar in both groups (MG 72% vs. C 67%). However, the requirements of cardio/vasoactive drugs shows a significant difference in favour of NOT-HAVING to use pharmacological support in the MG group (MG 10/39 patients -20%- vs. C group 19/39 -53%- p < 0.04.
Conclusions: The findings might be due to a potential cytoprotective effect of magnesium, preserving cardiac cellular energy levels during the period of anoxic cardiac arrest and possibly related to less calcium influx into the ischaemic cells. We recommend its use as a "routine" in these selected patients.

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INTRODUCTION
   Chronic deficiency of Magnesium -second intracellular cation- is a reality nowadays, particularly in cardiac disease patients (1). It happens because of several causes: diuretics, reduced dietary intake, associated diseases, drugs-induced (ACEi interaction), but not always catches the physician's attention (the forgotten ion) (2-4). Magnesium acts as co-factor in more than 300 enzymatic reactions, including nucleic acid synthesis and energy metabolism. Its beneficial action on ischaemic myocardial cells (post myocardial infarction or post reperfusion) is related to cellular protection shifting mitochondrial Calcium to sarcoplasmic reticulum and competing to Troponin C-Ca binding. Other well-known actions of Mg included: hormone receptor binding, gating of calcium channel, transmembrane ion flux and regulation of adenylate cyclase; acting on muscular contraction, neuronal activity, cardiac excitability and vascular tone; moreover, releases neurotransmitters and antagonizes NMDA receptors (4) This characteristics have an immediate potential effect preserving myocardial energy and avoiding malignant arrhythmias but long acting effects on cerebral circulation and easing pain.

   Mg has been recommended in the treatment of Acute Myocardial Infarction before thrombolysis because of already mentioned "energy preserver effects" on reperfused or ischaemic cardiac cells (5) it is still recommended (6). Horner reported its benefits (7) but LIMIT 2 and ISIS 4 controversial findings did not help to clarify when and how to use it (8)

   Mg has been studied for two decades in all kind of arrhythmias, mainly on "torsades de pointes" (9)

   In cardiac surgery the development of arrhythmias and low output syndrome are threatened complications. Mg has been used post aortic cross-clamping, included in cardioplegic solutions and in the postoperative period as electrolyte replacement but there is no consensus how to recommend its use -neither by the same author- (10-15)
With this bases we selected elective patients to be operated on Coronary Artery Bypass Grafting (CABG) or Aortic Valve Replacement (AVR) because of their similarities on pathophysiology, treatment and potential ischaemic events. This universe is the majority on our scheduled patients.

OBJECTIVES
   Define the Magnesium Sulphate "energy preserving" action according to:
1. post-aortic cross-clamping electrical activity and its actions on malignant arrhythmias (or not) or "pacing not-programmed" requirements.
2. Inotropic and vasodilators need to end cardiopulmonary bypass (CEC)

METHODS
   Previous oral consent, we planned a prospective single blind controlled study including 78 consecutives patients scheduled for elective open-heart surgery (CPBP/CEC). All eligible patients of Coronary Artery Bypass Surgery (CABG) or Aortic Valve Replacement (AVR) with aortic cross-clamping (PA) and cold crystalloid cardioplegia (CFC) between July 1999 to December 2000 were divided in two groups, 39 patients each (Magnesium -MG- vs. Control -C-) 4 g (16 mol) of Magnesium Sulphate in normal saline was infused at 60 ml/h in a deep jugular vein immediately after induction.

   Criteria of exclusion: Ejection Fraction <40% or creatinine >124 mg%.
"Balanced anesthesia" was achieved with inhaler agents, benzodiacepines, opioids and no depolarizing myorelaxants.

RESULTS
1. Both groups had similar age (54 years) (Fig. 1)


2. Aortic cross-clamping time (PA) was 46 minutes (p: ns) (Fig. 2)


3. Extra Corporeal Circulation time was 86 minutes (p: ns) (Fig. 3)


4. Malignant Arrhythmias or AV blocks weren't significant
5. Cardiac declamping activity was similar in both groups (sinus rhythm) (MG 28/39 patients -72%- vs. C 26/39 -67%-) (Fig. 4)


6. The use of vasodilator was no significant.
7. Inotropic/cardioactives drugs were highly significant, 10 patients of 39 in Mg -26%- vs. 19 of 39 -49%- Control Group (p< 0,04) (Fig. 5)

DISCUSSION
   Besides the main objectives we observed that Magnesium Sulphate provided excellent hemodynamic stability, "friendly" use and sympathicolysis being already reported by Puri et als (18).

  Demographic and laboratory parameters made no significant differences. The goal regarding lowering malignant arrhythmias could not be achieve as we expected from revisited data but those authors administered Mg after the end of extra corporeal support (15,16). We couldn't find higher energy requirements or increased number of electric shocks to defibrillate the heart as Hecker did (11)

   Anyway, the significant reduction of cardioactives drugs on Mg proved beyond doubt the cyto-protector effects of the ion. Hearse et als stated that the leak of Mg from cytosol favors the lack of energy available -ATP mediated- in post-reperfusion period (ischaemic cell permeability disorders). Higher levels of extra-cellular Mg contribute to reduce the leakage of Mg from cytosol allowing higher energy stocks (17). Patients suffering unstable angina scheduled for CABG showed a notorious myocardial recovery and less incidence of post-operative arrhythmias (19) and Storm highly recommended Mg to be used regardless refractory cardiogenic shock post CPBP (20).

   In an unpublished data from our group adding Mg to blood cardioplegia the incidence of ventricular fibrillation was nule.
The reduction of inotropes are not only related to the critical weaning period from CPBP but it is reducing complications derived from sustained adrenergic drugs in the postoperative period. In certain prone patients these powerful drugs predispose to multi-organ system failure syndrome (MOF). MOF is a main cause of morbid mortality everywhere.

CONCLUSION
   Magnesium Sulphate, safe and cheap, should be included as "routine" in elective/eligible patients submitted to CABG and AVR because of its beneficial energy protective myocardial effects fully demonstrated in our series and backed in part by the few available data. Other beneficial actions about neuroprotective effects (21) and controlling postoperative late pain (22) might draw attention to this ion that has been an orphan for the research.

REFERENCES

1. McLean RN. Magnesium and its therapeutic uses: a review. Am J Med 1994; 96 (1): 63-70.

2. Gómez MN. Magnesium and cardiovascular disease. Anesthesiology 1998; 89: 222-40

3. Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth 1999; 83: 302-20

4. James MFM. Editorial II. Magnesium: quo vadis? Br J Anaesth 1999; 83: 202-3

5. Dyckner T. Serum magnesium in acute myocardial infarction; relation to arrhythmias. Acta Med Scand 1980; 207: 59-66

6. Shechter M, Hod H, Chouraqui P, Kaplinsky E, Rabinowics B. Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy. Am J Cardiol 1995; 75: 321-3

7. Horner SM. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992; 86 (3): 774-9. 10.

8. Baxter C, Sumeray M, Walker J. Infarct size and magnesium; insights into LIMIT 2 and 1S1S-4 from experimental studies. Lancet 1996 348: 1424-6

9. Roden DM. A practical approach to torsade de pointes. Clin Cardiol 1997; 20: 285-90

10. Scheinman V, Sullivan R, Hyatt K. Magnesium metabolism in patients undergoing cardiopulmonary bypass. Circulation I969; 34: 1235-41

11. Hecker B, Lake C, Kran I. et al. Influence of magnesium ion on human ventricular defibrillation after aortocoronary bypass surgery. Am J Cardiol 1985; 55: 61-4

12. Harris MNE, Crowther A, Jupp RA, Apps C. Magnesium and Coronary Revascularization. Br J Anaesth 1988; 60: 779-83

13. Aglio LS, Stanford GG, Maddi R, Boyd JL, Nussbaum S, Chernow B. Hypomagnesaemia is common following cardiac surgery J Cardiothorac Vasc Anesth 1991 5: 201-B

14. Satur C, Anderson J, Jennings A. et al. Magnesium flux caused by coronary artery bypass operation: three patterns of deficiency. Ann Thorac Surg 1994; 58: 1674-8

15. Jensen BM, Alstrup P, Klitgard NA. Magnesium substitution and postoperative arrhythmias in patient undergoing coronary artery bypass grafting. Scand Cardiovasc J 1997; 31: 265-9

16. Parikka H, Toivonen L, Pellinene T, Verkkala K. Jarvinen A, Nieminen M. The influence of intravenous magnesium sulphate on the occurrence of atrial fibrillation after coronary artery bypass operation. Eur Heart J I993; 14; 25 -8

17. Hearse D. Stewart D, Braimbridge M. Myocardial protection during ischaemic arrest. J Thorac Cardiovasc Surg 1978; 75: 877-85

18. Puri GD, Marudhachalam KS, Cari P, Suri RK. The effect of Magnesium Sulphate on Hemodynamics and Its Efficacy in Attenuating the Response to Endotracheal Intubation in Patients with Coronary Artery Disease. Anesth Analg 1998; 87:808-11

19. Caspi J, Rudis E, Bar I, Sadafi T, Saute M. Effects of Magnesium on myocardial function after coronary artery bypass surgery. Ann Thorac Surg 1995; 59(4):942-7

20. Storm W, Zimmerman JJ. Magnesium deficiency and cardiogenic shock after cardiopulmonary bypass. Ann Thorac Surg I997; 64: 572-7

21. Marinov MB, Harbaugh KS, Hoopes PJ, Pikus HJ, Harbaugh RE. Neuroprotective effects of preischaemia intraarterial magnesium sulfate in reversible focal cerebral ischaemia. J Neurosurg 1996; 85: 117-24

22. Wilder-Smith CH, Knopfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand 1997; 41: 1023-7

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
Scientific Committee
President
Dr. Armando Pacher
Technical Committee - CETIFAC
President
fgaro@fac.org.ar
fgaro@satlink.com
rbretal@fac.org.ar
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