Magnesium Sulfate

Magnesium Sulfate

Indication

• the treatment of hypomagnesemia (the predominant clinical signs and symptoms of hypomagnesemia are neurological (neuromuscular excitability, clonic twitching and tremors)

Clinical Pharmacology

• After potassium, magnesium (Mg) is the second most abundant intracellular cation
• Magnesium is an important regulator of cell processes and has been identified as a cofactor in more than 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis
• total body content
  • 60% in the bone (a slow turnover pool)
  • 39% is distributed equally between muscle and non-muscular tissue in the intra-cellular space
  • 1 to 2 % is found extra-cellularly (1/3 protein bound; 2/3 free, ionized) in the circulation; it is this free, ionized fraction that is available for biochemical processes as well as filtration by the kidney
• Magnesium is necessary for both the secretion and function of parathyroid hormone (PTH); PTH is important in regulating the serum calcium concentration; thus, hypomagnesemia is frequently associated with hypocalcemia.
• Hypokalemia is also associated with hypomagnesemia (due to magnesium's effect on the renal tubules)
• normal (SJHC standard) serum concentrations of magnesium are 0.66 to 1.15 mmol/L
• the kidney is the primary regulator of extracellular magnesium concentration

Side Effects

• Effects are related to the serum magnesium level
  • >1.2 mmol/L: CNS depression, blocked peripheral neuromuscular transmission leading to anticonvulsant effect
  • >2 mmol/L: Depressed deep tendon reflexes, flushing, hypotension, sweating
  • >4.8 mmol/L: Respiratory paralysis, complete heart block, deep tendon reflexes may disappear
• Hypotension may develop with rapid IV administration and/or high doses
• Cardiac arrhythmias, respiratory/CNS depression are also possible during the infusion
• Flushing and sweating may occur with moderate doses ( a result of magnesium's peripherally acting vasodilatory effect)
• Diarrhea, abdominal cramps, muscle weakness and hypothermia may also occur
• Both the CNS depression and peripheral neuromuscular blockade produced by hypermagnesemia can be reversed with an infusion of calcium

Overdosage Treatment

• Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis
• Treat with IV calcium gluconate (same dose as for cardiac arrest)

Monitoring

• Continuously monitor heart rate, blood pressure and respiratory rate during the infusion
• monitor serum Mg levels to avoid overdosage
• Also monitor serum Ca levels which may become depressed following the administration of Mg
• renal function
• deep tendon reflexes

Contraindications

Precautions

• Use with caution in patients with impaired renal function (accumulation may lead to hypermagnesemia) and in patients who are receiving digoxin

Drug Interactions

• CNS depressants (eg morphine, phenobarbital, midazolam): additive effects
• Neuromuscular blocking agents (eg vecuronium): additive effects
• Cardiac glycosides (eg. digoxin): may alter cardiac conduction leading to heart block
• Aminoglycosides : increased risk of respiratory arrest

Dosage and Adminstration

• Conversion factor:
  • 500 mg MgSO4 = 2 mmol Mg = 4mEq Mg
    2 mmol/mL Mg = 50% MgSO4solution
• Hypomagnesemia:
  • 25 to 100 mg/kg MgSO4, (equivalent to 0.05 to 0.2 mL/kg of a 50% solution) slow IV over 2 to 4 hours (or IM)
  • in severe situations 1/2 of the dose may be infused over the first 15 to 20 minutes (see Side Effects)
  • reduce dose in renal impairment
  • maximum concentration for IV or IM dose is 200 mg/mL magnesium sulphate (therefore, solution from the vial must be diluted before administration)
  • may repeat q 6-12h for 2 to 4 doses (until symptoms resolve and serum Mg is within normal limits (0.66-1.15 mmol/L); monitor serum Mg levels and test knee jerk reflexes prior to each dose
• Seizures and Hypertension: (** Children's Dose **)
  • 25 to 100 mg/kg MgSO4 slow IV over 2 to 4 hours (or IM) (note that this is a child's dose)

Stability in IV Solutions:

• Stable in dextrose and saline solutions
• Compatible with both amino acid / dextrose component of TPN as well as with lipid component

Available

• 10 mL vial of magnesium sulphate 50%
• Each mL contains 500 mg magnesium sulphate (=2 mmol Mg=4mEq Mg)