ROLE OF MAGNESIUM, ITS DISORDER & MANAGEMENT.Dr. Arjun chhetri, Resident (NGMC)

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)

Magnesium balance The average-sized adult contains approximately

24 g of Mg. (over half is located in bone, < 1% is located in plasma).

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.

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.

Reference Ranges for Magnesium

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”

Predisposing Conditions

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

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

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.

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)

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).

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.

Acute Myocardial Infarction Hypomagnesemia is reported in as many as 80%

of patients with acute myocardial infarction.

The mechanism is unclear.

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

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.

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.

CONTD… One of the serious arrhythmias associated with

magnesium depletion is torsade de pointes

Hypomagnesemia is associated with an increased incidence of atrial fibrillation.

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.

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.

CONTD…Renal Magnesium Retention Test

Magnesium Replacement Oral and Parenteral Magnesium

Preparations

CONTD… The following magnesium replacement protocols are

recommended for patients with normal renal functionMild, 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.

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.

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.

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.

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).

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Contd…Magnesium and Asthma or Chronic Obstructive

Pulmonary Diseasemagnesium-induced bronchodilation may be mediated

by several pathways:

attenuation of calcium-induced muscle contractions,

inhibition of cholinergic neuromuscular transmission,

Anti-inflammatory activity.

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.

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).

THANK YOU REFERENCES PAUL MORINO ICU MORGAN CLINICAL ANESTHESIOLOGY