Definition

• Dogs-serum magnesium <1.89 mg/dL
• Cats-serum magnesium <1.8 mg/dL

Pathophysiology

• Magnesium is second only to potassium as the most abundant intracellular cation; is found primarily in bone (60%) and soft tissue (38%), with most soft tissue magnesium residing in skeletal muscle and liver; is required for many metabolic functions; is an activator or catalyst for more than 300 enzyme systems including phosphatases and enzymes that involve ATP.
• Serum magnesium is present in three forms: protein-bound form (approximately 25–30%) and chelated and ionized forms (together account for 70–75%).
• Because only 1–2% of total magnesium resides in the extracellular compartment, serum magnesium concentration does not always reflect the whole-body magnesium status.
• Magnesium absorption occurs primarily in the ileum. Absorption also occurs in the jejunum and colon.
• The kidneys maintain magnesium balance with 10–15% reabsorbed in the proximal tubule, 60–70% in the thick ascending limb of the loop of Henle, and 10–15% reabsorbed in the distal convoluted tubule. Reabsorption within the distal convoluted tubule is under hormonal and neurohormonal control and determines the final urine concentration of magnesium.
• Hypomagnesemia has many causes; incidence rates >50% have been reported in critically ill humans.
• Magnesium is an important cofactor in the sodium-potassium ATPase pump that maintains an electrical gradient across membranes. Magnesium is also important in the production and elimination of acetylcholine; a low concentration of magnesium in the extracellular fluid can increase concentrations of acetylcholine at motor endplates and cause tetany.
• Interference with the electrical gradient can change resting membrane potentials and repolarization disturbances, resulting in neuromuscular and cardiac abnormalities.
• Magnesium regulates calcium movement into smooth muscle cells and is important to contractile strength and peripheral vascular tone.
• Hypomagnesemia can alter the functions of the skeletal muscles, resulting in tetany and a variety of myopathies observed in patients receiving cisplatin and other nephrotoxic drugs.
• Magnesium regulates calcium movement into cardiac muscle cells and is important in cardiac conduction, excitability, and contraction.
• Magnesium depletion can affect the membrane pump on cardiac cell membranes, resulting in the depolarization of cardiac cells and tachyarrhythmias; cardiac arrhythmias associated with hypomagnesemia include ventricular arrhythmias, torsades de pointes, QT prolongation, ST segment shortening, and widening of T waves; hypomagnesemia increases the risk of digoxin toxicity because both inhibit the membrane pump.
• Hypomagnesemia causes resistance to the effects of PTH and can increase the uptake of calcium into bone.

Systems Affected

• Multiple organ systems
• Cardiovascular
• Endocrine
• Gastrointestinal
• Neuromuscular
• Renal

Signalment

Dog and cat

Incidence/Prevalence

Hypomagnesemia has been reported in 28–54% of critically ill dogs and cats.

Signs

• Hypomagnesemia occurs with a variety of diseases with diverse signs:
  • Weakness
  • Muscle fibrillation
  • Ataxia and depression
  • Hyperreflexia
  • Tetany
  • Behavior changes
  • Arrhythmias

Causes

• There are four general causes-gastrointestinal, renal, endocrine, and miscellaneous.
• Severe malnutrition or significant malabsorptive intestinal diseases can lead to hypomagnesemia; hypomagnesemia can occur after excessive loss of body fluids (e.g., severe, prolonged diarrhea); magnesium is found in high concentrations in the lower gastrointestinal tract, so secretory diarrhea in humans has been associated with profound hypomagnesemia; this has been reported in a dog with protein-losing enteropathy.
• Magnesium homeostasis is regulated by the kidney; renal control of tubular reabsorption takes place primarily in the ascending limb of the loop of Henle; renal magnesium loss can be due to nephrotoxic drugs, including cisplatin, aminoglycosides, and amphotericin B; magnesium reabsorption can also be impaired with osmotic diuresis (diabetes mellitus), loop diuretics, hypercalciuria, and tubular acidosis. Hypomagnesemia associated with diuretic administration is a significant problem in human heart failure patients and has been noted experimentally in mice.
• Hypomagnesemia develops during chronic thiazide diuretic therapy by downregulation of the epithelial Mg2⁺ channel transient receptor and accompanying Na⁺-Cl^– cotransporter inhibition or inactivation. Endocrine problems associated with hypomagnesemia include hypercalcemia, hyperthyroidism, and hyperparathyroidism.
• Lactation can cause excessive magnesium loss.
• Magnesium can be redistributed by refeeding after starvation, insulin therapy in diabetic patients, following parathyroidectomy, with the use of a total parenteral nutrition formulation with inadequate magnesium content, and in patients with acute pancreatitis or conditions of catecholamine excess.
• Causes of hypomagnesemia in the critically ill include decreased intake, lack of magnesium in parenteral fluids in patients receiving long-term fluid therapy or dialysis, excessive gastrointestinal loss, redistribution, and sequestration.
• Hypomagnesemia is associated with diabetes mellitus in humans, with nearly 25% of human diabetic outpatients having low serum magnesium.
• While one study showed no difference in presentation of ionized magnesium levels in dogs with diabetes when compared to controls, hypomagnesemia should still be considered in diabetic patients following aggressive insulin therapy for diabetic ketoacidosis.

Risk Factors

• Total parenteral nutrition
• Polyuric renal disease
• Diuretic administration
• Peritoneal dialysis
• Diabetes mellitus and diabetic ketoacidosis
• Lactation
• Gastrointestinal malabsorption syndromes

Differential Diagnosis

• Signs of hypomagnesemia are vague and multisystemic; therefore, other causes of neuromuscular abnormalities, especially other electrolyte abnormalities, must be investigated.
• Consider cardiac abnormalities, intoxications, and renal diseases.

Laboratory Findings

Note: 12 mg of magnesium = 1 mEq of magnesium; to convert from mg/dL to mEq/L, divide by 1.2.

CBC/Biochemistry/Urinalysis

• Low serum magnesium.
• If patient is azotemic, consider renal causes.
• Tubular casts in urinary sediment might indicate nephrotoxicity.
• Hypokalemia, hyponatremia, and hypocalcemia are common findings with hypomagnesemia and should alert the clinician to the possibility of hypomagnesemia.

Other Laboratory Tests

• Diagnosis of magnesium depletion can be difficult since <1% of total body magnesium is located in serum; only 55% of the magnesium in plasma is in the active (ionized) form; 33% is bound to plasma proteins and 12% is chelated with divalent anions such as phosphate and sulfate; magnesium assays (spectrophotometry) measure all three fractions.
• Ionized magnesium can be measured with an ion-selective electrode or by ultrafiltration of plasma; alternative methods of evaluating magnesium status include measurement of mononuclear blood cell magnesium levels or quantifying retention from a loading dose.
• Urinary magnesium determination might help differentiate conditions associated with high urinary magnesium loss from conditions of low intake or absorption.
• Human studies suggest that retention of >40–50% of an administered magnesium load indicates magnesium depletion, while retention of <20% indicates adequate magnesium stores.

Diagnostic Procedures

Electrodiagnostics (e.g., electromyelography and electrocardiography) might reveal effects of hypomagnesemia but will not differentiate the cause.

Appropriate Health Care

• Treatment depends on the underlying cause and severity of hypomagnesemia.
• Management includes treatment of the underlying condition(s) and magnesium replacement.
• Mild hypomagnesemia might resolve with treatment of the underlying disorder; however, if hypomagnesemia is severe, intensive care and magnesium replacement are needed.

Nursing Care

Hypomagnesemia is a common finding in critically ill, hospitalized veterinary patients. Nursing should focus on the underlying disorder(s).

Activity

Activity restrictions should be based on concurrent conditions.

Diet

There are no dietary recommendations for hypomagnesemia other than meeting the patient's caloric requirements with a balanced, appropriate diet that takes into account all concurrent problems.

Drug(s) Of Choice

• Magnesium sulfate can be diluted in 5% dextrose in water.
• Emergency loading is accomplished with 0.15–0.3 mEq/kg of magnesium sulfate or magnesium chloride over 5–60 minutes.
• Rapid replacement can be accomplished by administering 0.75–1 mEq/kg/day (0.03 mEq/kg/h) of magnesium sulfate or magnesium chloride as a constant-rate intravenous infusion; the solution of magnesium salts should be <20%; the magnesium infusion should use a separate intravenous line to minimize interactions with other minerals.
• Administer 0.3–0.5 mEq/kg/day (0.013–0.02 mEq/kg/h) of magnesium sulfate or magnesium chloride for slow replacement.

Contraindications

• Do not use aminoglycosides; hypomagnesemia potentiates their nephrotoxicity.
• Do not use cisplatin chemotherapy.

Precautions

• Discontinue digoxin if possible.
• Use diuretics with caution.
• Hypermagnesemia is possible with overzealous treatment of hypomagnesemia.
• Azotemic patients requiring magnesium therapy should receive a lower dose and more frequent monitoring than patients with normal kidney function to prevent iatrogenic hypermagnesemia.

Possible Interactions

• Magnesium sulfate is incompatible with sodium bicarbonate, hydrocortisone, and dobutamine HCl; avoid mixing other drugs with magnesium sulfate solution.
• Avoid calcium-containing compounds; they lower the serum magnesium concentration.
• Additive CNS depression can occur when parenteral magnesium sulfate is used with CNS depressant sedatives, neuromuscular blocking agents, and anesthetics.
• Combined use of parenteral magnesium sulfate and non-depolarizing neuromuscular blocking agents has resulted in excessive neuromuscular blockade.
• Use magnesium supplementation cautiously with digitalis compounds to avoid serious conduction disturbances.
• Calcium supplements might negate the effects of parenteral magnesium.

Patient Monitoring

• Measurement of serum magnesium and calcium concentrations daily
• Continuous ECG monitoring, especially during magnesium infusion

Possible Complications

Severe hypomagnesemia can be fatal.

Expected Course and Prognosis

Outcome is dependent on resolution of the underlying disease(s).

Associated Conditions

• Hyperthyroidism
• Hypocalcemia
• Hypokalemia
• Hyponatremia
• Hypoparathyroidism
• Hypophosphatemia

Pregnancy/Fertility/Breeding

Effects on the fetus are identical to effects on the dam.

See Also

Hypocalcemia

Abbreviations

• ATP = adenosine triphosphate
• CNS = central nervous system
• Cl = chloride
• EDTA = ethylene diamine tetraacetic acid
• Mg = magnesium
• Na = sodium
• PTH = parathyroid hormone

Internet Resources

http://www.merck.com/mmpe/sec12/ch156/ch156i.html.