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  1. 1. ROLE OF MAGNESIUM, ITS DISORDER & MANAGEMENT. Dr. Arjun chhetri, Resident (NGMC)
  2. 2. magnesium  2nd abundant intracellular cation.  Serve as a cofactor >300 enzyme recn i.e. involve ATP.  Proper functioning of the Na+-K+ exchange pump that generates the electrical gradient across cell membranes.  regulates the movement of calcium into smooth muscle cells (maintenance of cardiac contractile strength and peripheral vascular tone)
  3. 3. Magnesium balance  The average-sized adult contains approximately 24 g of Mg. (over half is located in bone, < 1% is located in plasma).
  4. 4. Serum Magnesium  Serum is favored over plasma for magnesium assays. Ionized Magnesium  About 67% of the Mg in plasma is ionized, remaining 33% bound to plasma protein(19%), chelated (14%).  Spectrophotometry measures all three fractions.
  5. 5. Urinary Magnesium  Small quantities of magnesium are excreted in the urine.  When Mg intake is deficient, the kidneys conserve Mg and urinary Mg excretion falls to negligible levels.
  6. 6. Reference Ranges for Magnesium
  7. 7. MAGNESIUM DEFICIENCY  Hypomagnesemia is reported in as many as 65% of patients in ICU’s.  Mg depletion may not be accompanied by hypomagnesemia, incidence probably higher.  magnesium depletion has been described as : “the most underdiagnosed electrolyte abnormality in current medical practice”
  8. 8. Predisposing Conditions
  9. 9. Diuretic Therapy  Diuretics are the leading cause of Mg deficiency.  Urinary Mg excretion is most pronounced with the loop diuretics (furosemide and ethacrynic acid).  reported in 50% of patients receiving chronic therapy with furosemide.  thiazide diuretics show a similar tendency for magnesium depletion, but only in elderly patients .  Mg depletion does not occur with “potassium-sparing” diuretics
  10. 10. Antibiotic Therapy  Aminoglycosides, amphotericin and pentamidine.  The aminoglycosides block Mg reabsorption in the ascending loop of Henley.  Hypomagnesemia has been reported in 30% of patients receiving aminoglycosides therapy
  11. 11. Other Drugs  case reports- prolonged use of PPI (14 days to 13 years) can be associated with severe hypomagnesemia.  Other drugs digitalis, epinephrine, and the chemotherapeutic agents cisplatin and cyclosporine.
  12. 12. Alcohol  Hypomagnesemia is reported in 30% of hospital admissions for alcohol abuse, and in 85% of admissions for delirium tremens.  There is an association between magnesium deficiency and thiamine deficiency (required for the transformation of thiamine into thiamine pyrophosphate)
  13. 13. Secretory Diarrhea  Secretions from the lower GI tract are rich in magnesium (10–14 mEq/L).  Upper GI tract secretions are not rich in magnesium (1– 2 mEq/L).
  14. 14. Diabetes Mellitus  common in insulin-dependent diabetic patients, probably as a result of urinary Mg losses that accompany glycosuria.  reported in only 7% of admissions for diabetic ketoacidosis.  incidence increases to 50% over the first 12 hours after admission.
  15. 15. Acute Myocardial Infarction  Hypomagnesemia is reported in as many as 80% of patients with acute myocardial infarction.  The mechanism is unclear.
  16. 16. Clinical Manifestations  no specific clinical manifestations of magnesium deficiency  often accompanied by depletion of potassium, phosphate, and calcium. HYPOKALEMIA: Hypokalemia is reported in 40% of cases of magnesium depletion.  hypokalemia that accompanies magnesium depletion can be refractory to potassium replacement therapy.  magnesium replacement is often necessary before the hypokalemia can be corrected
  17. 17. CONTD… HYPOCALCEMIA: can cause hypocalcemia as a result of impaired parathormone release.  Hypocalcemia from magnesium depletion is difficult to correct unless magnesium deficits are corrected. HYPOPHOSPHATEMIA: Phosphate depletion is a cause rather than effect of magnesium depletion.  The mechanism is enhanced renal magnesium excretion.
  18. 18. CONTD… Arrhythmias  Magnesium depletion will depolarize cardiac cells and promote tachyarrhythmia's.  magnesium deficiency will magnify the digitalis effect and promote digitalis cardio toxicity.  IV magnesium can suppress digitalis-toxic arrhythmias  IV magnesium can also abolish refractory arrhythmias (i.e., unresponsive to traditional antiarrhythmic agents) in the absence of hypomagnesemia.
  19. 19. CONTD…  One of the serious arrhythmias associated with magnesium depletion is torsade de pointes  Hypomagnesemia is associated with an increased incidence of atrial fibrillation.
  20. 20. CONTD… Neurologic Findings  Altered mentation, generalized seizures, tremors, and hyperreflexia. (All are uncommon, nonspecific, and have little diagnostic value).  The clinical presentation is characterized by ataxia, slurred speech, metabolic acidosis, excessive salivation, diffuse muscle spasms, generalized seizures.  The clinical features are often brought out by loud noises or bodily contact, and thus the term reactive CNS magnesium deficiency.
  21. 21. Diagnosis  serum Mg level is an insensitive marker of magnesium depletion.  When magnesium depletion is due to nonrenal factors (e.g., diarrhea), the urinary magnesium excretion is a more sensitive test for magnesium depletion.
  22. 22. CONTD… Renal Magnesium Retention Test
  23. 23. Magnesium Replacement  Oral and Parenteral Magnesium Preparations
  24. 24. CONTD…  The following magnesium replacement protocols are recommended for patients with normal renal function Mild, Asymptomatic Hypomagnesemia  The following guidelines can be used for a serum Mg of 1–1.4 mEq/L with no apparent complications : 1. Assume a total magnesium deficit of 1–2 mEq/kg. 2. Because 50% of the infused magnesium can be lost in the urine, assume that the total magnesium requirement is twice the magnesium deficit. 3. Replace 1 mEq/kg for the first 24 hours, and 0.5 mEq/kg daily for the next 3–5 days.
  25. 25. CONTD… Moderate Hypomagnesemia  The following protocol is recommended for a serum Mg <1 mEq/L, or for a low serum Mg that is accompanied by other electrolyte abnormalities: 1. Add 6 g MgSO4 (48 mEq of Mg) to 250 or 500 mL isotonic saline and infuse over 3 hours. 2. Follow with 5 g MgSO4 (40 mEq of Mg) in 250 or 500 mL isotonic saline infused over the next 6 hours. 3. Continue with 5 g MgSO4 every 12 hours (by continuous infusion) for the next 5 days.
  26. 26. CONTD… Life-Threatening Hypomagnesemia  The following is recommended for hypomagnesemia associated with serious cardiac arrhythmias (e.g., torsade de pointes) or generalized seizures: 1. Infuse 2 g MgSO4 (16 mEq of Mg) intravenously over 2– 5 minutes. 2. Follow with 5 g MgSO4 (40 mEq of Mg) in 250 or 500 mL isotonic saline infused over the next 6 hours. 3. Continue with 5 g MgSO4 every 12 hours (by continuous infusion) for the next 5 days.
  27. 27. Monitoring Replacement Therapy  Serum Mg levels will rise after the initial magnesium bolus, but will begin to fall after 15 minutes.  Serum Mg levels may normalize after 1 to 2 days, but it will take several days to replenish the total body magnesium stores.  The magnesium retention test can be valuable for identifying the end-point of potassium replacement therapy.
  28. 28. Anesthetic Considerations  no specific anesthetic Anesthetic Considerations  Isolated hypomagnesemia should be corrected prior to elective procedures because of its potential for causing cardiac arrhythmias.  magnesium appears to have intrinsic antiarrhythmic properties & cerebral protective effects (administered prior to cardiopulmonary bypass).
  29. 29. Eclampsia & magnesium Mild preeclampsia- Prophylactic use is controversial. Severe pre-eclampsia-  When prophylactically used 50% reduction in progression to eclampsia but with no neonatal or maternal mortality benefit.  25% of magnesium-treated women experienced side effects, mainly flushing
  30. 30. CONTD… Eclampsia-  Clear benefit on prevention of seizure recurrence as compared to diazepam and phenytoin.  Recommended dose being 4-6 gms IV over 20-30 mins f/b 1-2 gms/h or 4 gms in each buttock every 4 hr continued for at least 24 hrs after delivery.
  31. 31. HYPERMAGNESEMIA  serum Mg >2 mEq/L  Nearly always due to excessive intake (magnesium-containing antacids or laxatives) renal impairment (GFR < 30 mL/min).  Iatrogenic hypermagnesemia during magnesium sulfate therapy for gestational hypertension in the mother as well as the fetus.  Rear causes include adrenal insufficiency, hypothyroidism, rhabdomyolysis, and lithium administration.
  32. 32. Predisposing Conditions  Renal Insufficiency  Hemolysis: The Mg concentration in erythrocytes is approximately three times greater than in serum.  serum Mg is expected to rise by 0.1 mEq/L for every 250 mL of erythrocytes that lyse completely , so hypermagnesemia is expected only with massive hemolysis.
  33. 33. Clinical Features  The clinical consequences of progressive hypermagnesemia  Magnesium has been described as nature’s physiologic calcium blocker  Most of the cardiovascular depression is the result of cardiac conduction delays.
  34. 34. Contd…  Symptomatic hypermagnesemia typically presents with neurological, neuromuscular, or cardiac manifestations.  Hyporeflexia, sedation, and skeletal muscle weakness are characteristic features.  impair the release of acetylcholine and decreases motor end- plate sensitivity to acetylcholine in muscle.  Marked hypermagnesemia can lead to respiratory arrest.
  35. 35. Management  All sources of magnesium intake should be stopped.  Intravenous calcium (1 g calcium gluconate) can temporarily antagonize most of the effects of hypermagnesemia.  A loop diuretic along with an infusion of ½-NS in 5% dextrose enhances urinary magnesium excretion.  Hemodialysis is the treatment of choice for severe hypermagnesemia.
  36. 36. Anesthetic Considerations  Requires close monitoring of the ECG, blood pressure, and neuromuscular function.  Potentiation of the vasodilating and negative inotropic properties of anesthetics should be expected.  Dosages of NMBAs should be reduced by 25–50%.  Serial measurements of [Ca2+] and [Mg2+] may be useful.
  37. 37. Magnesium & Its others uses Preterm birth and fetal neuroprotection  used as a tocolytic agent, attenuates uterine contractility in vivo and in vitro.  Studies have shown Iv magnesium to reduce the risk of cerebral palsy in surviving preterm babies.  Antenatal administration may be considered because there is some evidence showing its neuroprotective effects in preterm neonates.
  38. 38. Contd… Magnesium and Pheochromocytoma  Care of patients during surgical removal of pheochromocytoma poses a significant anesthetic challenge.  Standard preoperative treatment includes pharmacologic stabilization by - and β-adrenergic antagonists.  Several case reports have described the successful use of magnesium during pheochromocytoma crisis.
  39. 39. Contd…  MOA: May stabilize hemodynamic by inhibition of catecholamine release from the adrenal medulla and peripheral adrenergic nerve endings  direct blockade of catecholamine receptors and vasodilation.  antiarrhythmic properties related to L-type calcium channel antagonism.
  40. 40. Contd… Magnesium and Asthma or Chronic Obstructive Pulmonary Disease magnesium-induced bronchodilation may be mediated by several pathways:  attenuation of calcium-induced muscle contractions,  inhibition of cholinergic neuromuscular transmission,  Anti-inflammatory activity.
  41. 41. Contd… Magnesium in tetanus  Use of magnesium reduce the need for mechanical ventilation, minimize sedation, minimize sympathetic overactivity associated with tetanus.  MgSO4 in the dose – 5gm iv loading dose f/b 2-3gm/hr via infusion. Therapy guided by patellar tendon reflex.
  42. 42. Magnesium and Side Effects  burning sensation or pain on injection  induce agitation  drowsiness  nausea  Headache  Dizziness  muscle weakness  hypotension and  bradycardia.  In eclampsia, approximately 25% of pts. flushing occurs.  Increases the risk of postpartum hemorrhage and respiratory depression.  neonatal lethargy, hypotension, and rarely respiratory depression after prolonged administration (more than 48 h).