AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Background

Magnesium (Mg) is the second-most abundant intracellular cation and, overall, the fourth-most abundant cation. Almost all enzymatic processes using phosphorus as an energy source require magnesium for activation. Magnesium is involved in nearly every aspect of biochemical metabolism (eg, deoxyribonucleic acid [DNA] and protein synthesis, glycolysis, oxidative phosphorylation). Almost all enzymes involved in phosphorus reactions (eg, adenosine triphosphatase [ATPase]) require magnesium for activation. Magnesium serves as a molecular stabilizer of ribonucleic acid (RNA), DNA, and ribosomes. Because magnesium is bound to ATP inside the cell, shifts in intracellular magnesium concentration may help regulate cellular bioenergetics such as mitochondrial respiration.

Extracellularly, magnesium ions block neurosynaptic transmission by interfering with the release of acetylcholine. Magnesium ions also may interfere with the release of catecholamines from the adrenal medulla. Magnesium has been proposed as an endogenous endocrine modulator of the catecholamine component of the physiologic stress response.

Approximately 60% of total body magnesium is located in bone, and the remainder is in the soft tissues. This soft tissue intracellular compartment comprises about 38% of total body magnesium; relatively higher concentrations are found in skeletal muscle and liver. Because less than 2% is present in the extracellular fluid (ECF) compartment, serum levels do not necessarily reflect the status of total body stores.

Serum concentration typically ranges from 1.8-2.5 mEq/L. Approximately a third of this is protein-bound. Analogous to plasma calcium, the free (ie, unbound) fraction of magnesium is the active component. No accurate method exists to assess ionized serum magnesium.

Less than 40% of dietary magnesium is absorbed throughout the small intestine (predominantly in the ileum) and in the colon. A minimal daily intake of 0.3 mEq/kg of body weight has been suggested to prevent deficiency. Infants and children tend to have higher daily requirements.

Elimination is predominantly renal. The threshold for urinary excretion is near the normal serum concentration. Thus, when serum levels rise above 2.5 mEq/L, magnesium excretion increases dramatically. Conversely, the kidney retains a strong capacity to resorb magnesium, and the main site for reabsorption is the thick ascending loop of Henle. Several factors may impair renal reabsorption, such as volume expansion, ethanol ingestion, hypercalcemia, and diuretic administration (eg, osmotic, thiazide, loop). Of these 3 types of diuretics, loop diuretics have the greatest effect on renal magnesium wasting because of their site of action.

Pathophysiology

Hypomagnesemia is widespread among hospitalized patients. Hypomagnesemia has been reported in as many as 60% of ICU patients. Prolonged administration of magnesium-free parenteral fluids may be a contributing factor. Prolonged nasogastric suction, infectious diarrhea, steatorrhea, inflammatory bowel disease, and GI neoplasms may cause hypomagnesemia. A congenital defect in GI magnesium absorption also has been described.

Incidence of hypomagnesemia among people with alcohol dependence is approximately 25% and mainly is due to magnesium diuresis caused by alcohol.

Several drugs can cause increased urinary loss of magnesium. Magnesium deficiency is especially common in patients receiving furosemide diuretics, but all diuretics play a role. A congenital defect in tubular reabsorption of magnesium also has been described.

Severe hypomagnesemia may occur during the recovery phase of diabetic ketoacidosis. Patients with diabetes who have chronically poor glycemic control may have a total body magnesium deficit, possibly caused by ineffective insulin-mediated cellular uptake of magnesium.

Frequency

United States

Although the incidence of hypomagnesemia in the general population has been estimated at less than 2%, hospitalized patients are more prone to develop hypomagnesemia. Exact inpatient incidence is unknown. Recent studies of ICU patients have estimated frequencies in that setting as high as 60%.

Age

While no comprehensive studies have addressed the actual incidence of hypomagnesemia stratified by age group, neonates may be more predisposed to develop hypomagnesemia. The mechanism for this is unknown, although several studies suggest that neonates have an increased requirement for intracellular magnesium in growing tissues.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

History

Symptomatic hypomagnesemia may manifest clinically as CNS and neuromuscular hyperexcitability. Early manifestations may include painful muscle cramps, nausea, vomiting, and lethargy.

Physical

• At serum magnesium levels less than 1.0 mEq/L, patients with hypomagnesemia may have tremor, hyperactive deep-tendon reflexes, hyperreactivity to sensory stimuli, muscular fibrillations, positive Chvostek and Trousseau signs, and carpopedal spasms progressing to tetany.
• Mental status changes may become evident and include irritability, disorientation, depression, and psychosis.
• Reversible respiratory muscle failure may occur in severe hypomagnesemia.
• In an analogous fashion to hypermagnesemia, the rate of development of hypomagnesemia may be more important than the absolute value in terms of symptom development.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Lab Studies

• Laboratory analysis by atomic absorption spectrophotometry (AAS) is the most specific technique available to measure total serum magnesium. Ion-selective electrodes for measurement of free magnesium have been developed; however, their use has not been rigorously tested, and they currently are not readily available for clinical use.

Other Tests

• Hypomagnesemia may be associated with nonspecific ECG changes, including ST-segment depression, altered T waves, or loss of voltage. Severe magnesium deficiency may cause PR prolongation or widened QRS complexes.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Medical Care

• When an underlying cause (eg, prolonged GI loss) exists, direct treatment toward correcting the problem. If hypomagnesemia is mild (ie, serum magnesium levels >1.2 mEq/L) and the patient is asymptomatic, PO replacement is appropriate. Little is understood about the uptake kinetics at the cell membrane level, so the optimal dosage to produce an effective intracellular uptake is unknown. Dosage also varies from patient to patient.
• In patients with normal renal function, if serum magnesium levels are less than 1 mEq/kg, the estimated total body replacement requirement is approximately 4 mEq/kg of body weight. With renal impairment, reduce these doses by at least half.
• In emergent cases (eg, refractory ventricular tachycardia) 16 mEq (2 mL of a 10% solution) of magnesium sulfate may be administered IV over 5-7 minutes.
• Base magnesium replacement in children on the child's weight. Administer 1 mEq/kg on the first day, then administer approximately half this amount daily during the next 3 days.
• Rapid IV administration can be life threatening. Risks involved with IV magnesium therapy include hypermagnesemia, hypocalcemia, and sudden hypotension. IV infusion rates should not exceed 67 mEq over 8 hours. Continuously monitor electrolytes and hemodynamic parameters during replacement under high infusion rates.

Diet

Magnesium is a component of chlorophyll and occurs in high concentrations in green leafy vegetables. Magnesium also is found in nuts, seeds, peas, beans, and cocoa. Do not discount the possibility of hypomagnesemia in patients with malnutrition. This may be particularly significant in patients with heavy alcohol consumption.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Treatment for hypomagnesemia depends on the degree of deficiency and the patient's clinical symptoms and signs. Therapy can be PO for patients with mild symptoms or IV for patients with severe symptoms.

Drug Category: Magnesium salts

Magnesium can be administered either PO in an oxide or gluconate form or parenterally as a sulfate salt.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Medical/Legal Pitfalls

• Although abnormally low levels of serum magnesium typically occur in adult patients hospitalized for prolonged periods, failure to include hypomagnesemia in the differential diagnosis for a similarly affected pediatric patient may be disastrous because hypomagnesemia is treated readily.
• Because hypomagnesemia can masquerade as other electrolyte imbalances, obtain magnesium levels with other electrolytes (eg, calcium, phosphorus) when ordering laboratory tests.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

• Knochel JP. Disorders of Magnesium Metabolism. Harrison's Principles of Internal. 1994;2:2187-2189. [Medline].
• Nadler JL, Rude RK. Disorders of Magnesium Metabolism. Clinical Disorders of Fluid and Electrolyte Metabolism. 1995;24:623-637. [Medline].
• Reinhart RA. Magnesium metabolism. Archives of Internal Medicine. 1988;148:2415-2420. [Medline].
• Rodriguez-Hernandez H, Gonzalez JL, Rodriguez-Moran M, Guerrero-Romero F. Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. Arch Med Res. Jul-Aug 2005;36(4):362-6. [Medline].
• Rude RK, Singer FR. Magnesium deficiency and excess. Ann Rev Med. 1981;32:245-259. [Medline].
• Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med. Jan-Feb 2005;20(1):3-17. [Medline].
• Topf JM, Murray PT. Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord. May 2003;4(2):195-206. [Medline].

Article Last Updated: May 25, 2006