Role of Magnesium in Critical Care

1. Role of Magnesium in Critical Care Dr.MayMostafaDarwish Assistant lecturer of Anesthesia and ICU Ain Shams University

2. Introduction • Magnesium is essential for human life: • It plays a fundamental role in many cellular functions, such as storage, metabolism, and energy utilization. • Mg ions are involved as a cofactor in : • many enzymatic reactions • hormone receptor binding • protein synthesis • neuromuscular function • and nucleic acid stability

3. 4th most common mineral salt (P/Ca/K/Mg.) • 2nd intracellular cation after potassium • 4th plasma cation (Na/K/Ca/Mg…) • 53% in bone, 27% in muscle, 19% in soft tissues, 0.5% in erythrocytes, 0.3% in serum

4. In serum: • Ionized (active form): 60% • Protein-bound: 33% • In anion complexes (phosphates and citrates): 7%

5. Normal plasma Mg2+ concentration : 1.7 to 2.4 mEq/L (0.70 to 1.0 mmol/L) • Daily recommended requirement: 250-350 mg (10.4–14.6 mmol) in adults • Cocoa powder, chocolate, nuts, leafy green vegetables, cereals, seafood are rich sources for Mg2+

6. The maintenance of plasma Magnesium concentration through: • dietary intake . • effective renal and intestinal conservation.

7. Renal excretion is the primary route of elimination • 25% is reabsorbed in the PCT. • 50-60% is reabsorbed in the thick ascending limb of the loop of Henle.

8. Mg absorption and cellular uptake: PTH: intestinal absorption↑ Vitamin D: intestinal absorption↑ Insulin: cellular uptake↑ Glucagon: renal reabsorption ↑

9. Actions of Magnesium • Endogenous calcium antagonist by affecting its uptake and distribution. • Modulator of Na+ and K+ currents, thus influencing membrane potential. • Depressant effects in CNS : • antagonist of the (NMDA) receptor • inhibitor of catecholamine release.

10. What is the role of magnesium in ICU??

11. Magnesium and Cardioprotection

12. Acute myocardial infarction. • Coronary and systemic VD : • improve metabolism of cardiomyocytes • attenuate ischemia–reperfusion injury of myocardial tissue. • Decreases myocardial membrane excitability: • Na+/K+ATPase and Ca2+ATPase are important regulators of myocardial membrane stability. • Attenuates the incidence of infarction-related arrythmias: • prolongs the ARP and shortens the RRP

14. II. Cardiac Arrythmias : • slows electrical activity of the SAN. • prolongs AV conductance. • increases the refractory period of the AVN.

15. Types : • AF and ventricular arrhythmias after cardiac and thoracic surgery • digoxin induced supraventricular and ventricular arrhythmias • multifocal atrial tachycardia • polymorphic ventricular tachycardia (Torsade de points) • VF from drug overdoses.

16. III.Pulmonary Hypertension: • PH is defined as a mean PA pressure greater than 25 mmHg at rest and > 30 mmHg during exercise. • Magnesium is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures associated with persistent pulmonary hypertension (PPHN)

17. Magnesium and Preeclampsia

18. Eclampsia and Preeclampsia • Systemic, cerebral, and uterine vasodilation by: • Increase concentrations of the two endogenous potent vasodilators • endothelium-derived relaxing factor and • calcitonin gene-related peptide 2) It attenuates the circulating concentrations of endothelin-1 (an endogenous vasoconstrictor)

19. Dose : loading 4–6 g /20–30 min & maintenance of 1–2 g/h. • The infusion should be continued for at least 24 h after delivery. • To avoid serious adverse effects, respiration, the presence of tendon reflexes, and urine output should be closely monitored. • antenatal administration may be considered because of its neuroprotective effects in preterm neonates.

20. Magnesium and Asthma

21. MgSO4 has been administered to patients to treat acute severe asthma when conventional therapy with oxygen, corticosteroids and continuous aerosol beta agonists fail to provide adequate relief • Magnesium-induced bronchodilation may be mediated by several pathways: • attenuation of calcium-induced muscle contractions • inhibition of cholinergic neuromuscular transmission • antiinflammatory activity • potentiation of β-agonists on adenylylcyclase • reversal of magnesium depletion after β-adrenergic treatment

22. IV MgSO4 provides additional benefit in moderate to severe acute asthma in patients treated with bronchodilators and steroids. • Nebulised inhaled MgSO4 in addition to beta2- agonist used in ttt of acute asthma exacerbation improves pulmonary function. • Mg also possesses mild sedative effects valuable to achieving anxiolysis and relaxation in acute bronchospasm.

23. Magnesium and Neuroprotection

24. Mg was shown to protect neurons and glia cells by: • inhibiting ischemia-induced glutamate release • inhibiting calcium-dependent enzymes • Therefore Mg exertesantiexcitotoxic properties and preventes cellular apoptosis.

25. Stroke: • The most promising time frame to facilitate maximal Neuroprotection is assumed to cover the first 3 h after onset of ischemia. II. Subarachnoid Hemorrhage: • Delayed cerebral ischemia is one of the main causes of death and disability after SAH and usually occurs 4–10 days after the initial bleeding event. • IV MgSO4 as an adjuvant to nimodipine may reduce delayed cerebral ischemia by 34%

26. III.Carotid Surgery: • Patients undergoing carotid endarterectomy are at particular risk for postoperative cognitive deficits caused by cortical ischemia after intraoperative hypotension or embolic events. • Mg is known to improve neurocognitive function on 1st postoperative day

27. IV. Spinal Cord Injury: • Once 1ry injury to the spinal cord has occurred, reduction of 2ry injury and ongoing ischemia by stabilizing hemodynamics and spinal perfusion pressure is most important. • Mg has proven its neuroprotective potential in spinal cord injury.

28. Magnesium and Pheochromocytoma

29. Pheochromocytoma is a CA producing and secreting neoplasm arising 1ry from the adrenal medulla. • Surgical removal of Pheochromocytoma possesses significant challenge dt the hemodynamic disturbances occurring when a tumor is manipulated and finally resected. • Standard preoperative treatment includes pharmacologic stabilization by  and β adrenergic antagonists.

30. Magnesium may stabilize hemodynamics : • inhibition of CA release from the adrenal medulla and peripheral adrenergic nerve endings. • direct blockade of CA receptors. • antiarrhythmic properties related to calcium channel antagonism. • An initial bolus dose of 40-60mg/kg IV followed by 2g/hr has been a suggested regimen

31. Pheochromocytoma Crisis • Mg was shown to improve severe hypertension and hypertensive encephalopathy in patients with pheochromocytoma crisis. • Based on arteriolar -dilating properties, its use might be advantageous to that of sodium nitroprusside, which dilates both arterioles and venules and may thus worsen hemodynamics, especially in hypovolemic patients. • Because Mg was shown to inhibit CA receptors, it may be superior to other competitive adrenergic antagonists, such as phentolamine because excessive CA concentrations may be present.

32. Magnesium and Tetanus

33. Mg reduces spasms and autonomic instability in tetanus. • A proposed regimen for management of • tetanus is 5g MgSO4 IV over 20mins followed by 2g/hour IV infusion. • This can be increased by 0.5g/hour until there is relief of spasms or loss of patellar reflexes.

34. Magnesium and Analgesia

35. Several studies report antinociceptive effects of Mg when administered IV or intrathecally. • Suggested mechanisms include the inhibition of calcium influx (CCB augment morphine-induced analgesia and decrease total opioid consumption ) and antagonism of NMDA receptors • In addition, Mg seems to attenuate or even prevent central sensitization after peripheral tissue injury or inflammation because of inhibition of dorsal horn NMDA receptors.

36. Magnesium and Shivering

37. Hypothermia may be an effective ttt for stroke or acute MI ; however, it provokes vigorous shivering, which causes potentially dangerous hemodynamic responses and prevents further hypothermia. • Mg is an attractive anti-shivering agent because it reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness.

38. Magnesium andLaryngoscopic Intubation Response

39. The role of Mg in blunting the intubation response is evolving: • It has direct VD properties on coronary arteries and inhibiting CA release, thus attenuating the hemodynamic effects during endotracheal intubation. • Beside its rolein blunting the pressor response to intubation ,it also produces less ST changes in coronary artery disease pts. • It was also concluded that pretreatment with different doses of Mg is more effective than pretreatment with Lidocaine.

40. Magnesium and Insulin Resistance

41. Clinical situations in which glycemia remains elevated despite increased insulin doses are frequent in ICU. • Mg regulates cellular glucose metabolism directly because it serves as an important cofactor for various enzymes and acts as a 2nd messenger for insulin. • Furthermore, hypomagnesaemia may induce : • altered cellular glucose transport • reduced pancreatic insulin secretion • defective post-receptor insulin signalling • altered insulin– insulin receptor interactions and thus aggravate insulin resistance

42. In a Nutshell

43. Mg is a cost effective, widely used drug with multidisciplinary applications. • Majority of its physiological effects are attributed to its calcium channel blocking properties. It is used as : • Vasdilator (antihypertensive) • Bronchodilator • Antiarrythmic • Antiseizures • Analgesic