eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hypomagnesemia

Nona P Novello, MD, Associate Chair, Department of Emergency Medicine, Franklin Square Hospital
Howard A Blumstein, MD, FAAEM, Assistant Professor, Surgery; Medical Director, Department of Emergency Medicine, Wake Forest University School of Medicine

Updated: Aug 18, 2009

Introduction

Background

Magnesium, the fourth most common cation in the body, has been the recent focus of much clinical and scholarly interest. Previously underappreciated, this ion is now established as a central electrolyte in a large number of cellular metabolic reactions, including DNA and protein synthesis, neurotransmission, and hormone-receptor binding. It is a component of GTPase and a cofactor for Na⁺/K⁺ –ATPase, adenylate cyclase, and phosphofructokinase. Magnesium also is necessary for the production of parathyroid hormone. Accordingly, magnesium deficiency has an effect on multiple body functions.

Magnesium is present in greatest concentration within the cell and is the second most abundant intracellular cation after potassium. The total body content of magnesium is 2000 mEq. The intracellular concentration of magnesium is 40 mEq/L, while the serum concentration is 1.5-2 mEq/L. Most of the body's magnesium is found in bone. Only 1% of the total body magnesium is extracellular. Of this amount, one half is ionized, and 25-30% is protein bound.

Magnesium, a component of chlorophyll, is absorbed in the small bowel by active and passive transport mechanisms. Absorption of dietary magnesium takes place mainly in the ileum. It is excreted in stool and urine, but regulation of serum magnesium is under renal control. Most renal reabsorption of magnesium occurs in the proximal tubule and the thick ascending limb of the loop of Henle. In hypomagnesemic patients, the kidney may excrete as little as 1 mEq/L of magnesium. Additionally, magnesium may be removed from bone stores in times of deficiency.

A: Magnesium reabsorption in the thick ascending limb of the loop of Henle. The driving force for the reabsorption against a concentration gradient is a lumen-positive voltage gradient generated by the reabsorption of NaCl. Terms: FHHNC (familial hypomagnesemia with hypercalciuria and nephrocalcinosis); ADH (autosomal-dominant hypocalcemia); FHH/NSHPT (familial hypomagnesemia/neonatal severe hyperparathyroidism). B: Magnesium reabsorption in the distal convoluted tubule. Active transcellular transport is mediated by an apical entry through a magnesium channel and a basolateral exit, presumably via a Na+/Mg2+ exchange mechanism. Terms: HSH (hypomagnesemia with secondary hypocalcemia); GS (Gitelman syndrome); IDH (isolated dominant hypomagnesemia). Source: Konrad M, Schlingmann KP, Gudermann T: Insights into the molecular nature of magnesium homeostasis. Am J Physiol Renal Physiol 2004; 286: F599-F605.

Pathophysiology

Clinical effects of hypomagnesemia are greatest in the CNS, neuromuscular, GI, and cardiac systems.

Frequency

United States

Risk of incidence is as follows:

• 2% in the general population
• 10-20% in hospitalized patients
• 50-60% in ICU patients
• 30-80% in alcoholics
• 25% in diabetic outpatients

Sex

Incidence is equal in males and females.

Age

Magnesium deficiency may contribute to many age-related diseases.¹

Clinical

History

• Clues to the presence of hypomagnesemia can be found by obtaining a history of potential causes (see Causes).
  • Historical complaints related to hypomagnesemia are nonspecific.
  • Patients may report weakness, muscle cramping, or rapid heartbeats.
  • Altered mental status may be present in severe cases. Less severe cases may result in vertigo, ataxia, depression, and seizure activity.

Physical

The primary clinical findings are neuromuscular irritability, CNS hyperexcitability, and cardiac arrhythmias. The severity of symptoms is not related directly to the magnesium level. The reference range for serum magnesium level is 1.8-3 mEq/L. Usually, patients become symptomatic at 1.8 mEq/L. However, the physical findings may not be present in all cases. In one study of patients who were severely depleted of magnesium, abnormal physical findings were present in only 2 of 21 patients.

• Neuromuscular irritability
  • Hyperactive deep tendon reflexes
  • Muscle cramps
  • Muscle fibrillation
  • Trousseau and Chvostek signs
  • Dysarthria and dysphagia from esophageal dysmotility
• CNS hyperexcitability
  • Irritability and combativeness
  • Disorientation
  • Psychosis
  • Ataxia, vertigo, nystagmus, and seizures (at levels <1 mEq/L)
• Cardiac arrhythmias that may be caused by hypomagnesemia alone or concomitant hypokalemia result from decreased activity of ATPase.
  • Paroxysmal atrial and ventricular dysrhythmias
  • Repolarization alternans
• Neonates
  • Apnea
  • Weakness
  • Seizures
  • Jitteriness

Causes

• GI losses
  • Malabsorption of magnesium in the ileum results in hypomagnesemia. Situations of decreased absorption include malabsorption syndromes (eg, celiac sprue), radiation injury to the bowel, bowel resection, or small bowel bypass.
  • GI secretions in large amounts may cause hypomagnesemia. Upper GI secretions contain 1 mEq/L of magnesium, while lower GI secretions contain 15 mEq/L of magnesium. Significant losses of magnesium that result in hypomagnesemia may result from chronic diarrhea, laxative abuse, inflammatory bowel disease, or neoplasm.
• Malnutrition leads to hypomagnesemia when dietary intake of magnesium is low. Dietary sources include green vegetables, fruits, fish, fresh meat, and cereal. Alcoholics are classically hypomagnesemic in part due to poor nutrition.² Diabetic patients who are not receiving magnesium supplements may have dietary deficiencies in magnesium.
• Renal losses from primary renal disorders or secondary causes (eg, drugs, hormones, osmotic load) may result in magnesium wasting and subsequent hypomagnesemia.
  • Primary renal disorders cause hypomagnesemia by decreased tubular reabsorption of magnesium by the damaged kidneys. This condition occurs in the diuretic phase of acute tubular necrosis, postobstructive diuresis, and renal tubular acidosis.
  • Drugs may cause magnesium wasting.
    • Diuretics (eg, thiazide, loop diuretics) decrease the renal threshold for magnesium reabsorption in addition to wasting of potassium and calcium.
    • Cisplatin causes dose-dependent kidney damage in 100% of patients receiving this drug.
    • Pentamidine and some antibiotics also cause renal magnesium wasting.
    • Fluoride poisoning similarly causes hypomagnesemia.
  • Endocrine disorders may cause hypomagnesemia.
    • Primary aldosteronism decreases magnesium levels by increasing renal flow.
    • Hypoparathyroidism and hyperthyroidism may cause renal wasting.
  • Osmotic diuresis results in magnesium loss in the kidney.
    • Diabetic patients, especially those with poor glucose control, develop hypomagnesemia from a glucose-induced osmotic diuresis.
    • Alcoholics become hypomagnesemic partially by an osmotic diuresis from alcohol. Urinary losses have been reported to be 2-3 times control values.
• Miscellaneous
  • Extracellular volume expansion, as in cirrhosis or intravenous (IV) fluid administration, may decrease magnesium levels.
  • Redistribution of magnesium into cells may cause lower magnesium levels. Insulin causes this effect.
  • Excessive lactation may create a significant amount of magnesium loss.
  • Hungry bone syndrome may lead to lower serum magnesium concentrations.
  • Pregnant women have been found to be magnesium depleted, especially those women who experience preterm labor.

Differential Diagnoses

Hypocalcemia
Hypokalemia

Workup

Laboratory Studies

• Serum magnesium, calcium, potassium, and phosphorus levels
  • The serum magnesium level is not a reliable way to determine total body magnesium depletion because only a small fraction of magnesium in the body is extracellular. Consider obtaining an ionized magnesium level.
  • Body stores of magnesium may be depleted markedly before the serum level drops.
  • Nevertheless, a deficiency of magnesium is clearly present if the serum level is low.
  • In one study, alcoholics were found to have total body magnesium depletion (via measurement of their 24-hour urinary magnesium excretion) despite having normal serum levels.
  • Because extracellular magnesium is protein bound, the patient's protein status is an important consideration in interpreting magnesium levels.
  • Hypomagnesemia contributes to hypokalemia. This condition may be due to defective membrane ATPase or urinary losses of potassium.
  • Hypocalcemia is caused by magnesium depletion, but the reason is not known.
    • Some studies link hypomagnesemia to decreased parathyroid hormone levels and end-organ resistance to parathyroid hormone.
    • Alterations in vitamin D metabolism contribute to hypocalcemia.
  • Hypophosphatemia has been found in patients with hypomagnesemia.
• BUN and creatinine levels
• Blood glucose level

Other Tests

• ECG and cardiac monitor
  • Findings in hypomagnesemia are nonspecific.
  • Findings include ST segment depression; tall, peaked T waves; flat T waves or depression in the precordium; U waves; loss of voltage; PR prolongation; and widened QRS.

Treatment

Prehospital Care

Be attentive to the ABCs. At this point, the diagnosis usually is not known; therefore, advanced cardiac life support (ACLS) protocol should be followed. Seizures should be treated with benzodiazepines.

Emergency Department Care

• Treat life-threatening dysrhythmias according to ACLS protocol or as outlined below if hypomagnesemia is known.
• Treat seizures with benzodiazepines.
• Perform history, physical examination, and appropriate laboratory tests.
• Treat hypomagnesemia appropriately.

Medication

Treatment of hypomagnesemia depends on the degree of deficiency and the clinical effects. Oral replacement is appropriate for mild symptoms, while IV replacement is indicated for severe clinical effects.

Electrolyte supplement

These agents are used to replace an existing magnesium deficit.

Magnesium gluconate (Almora)

Oral supplementation should be given when patient is mildly depleted of magnesium (ie, magnesium level >1 mEq/L and patient is asymptomatic).
Other oral supplements (eg, magnesium oxide, magnesium hydroxide) may be used.

Dosing

Adult

500 mg/d (27 mg elemental magnesium) PO

Pediatric

3-6 mg elemental magnesium/kg/d PO divided tid/qid; not to exceed 400 mg in 24 h

Interactions

Concurrent nifedipine may cause hypotension and neuromuscular blockade; may worsen neuromuscular blockade seen with aminoglycosides, tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and ritodrine

Contraindications

Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Impaired renal function may increase toxicity; diarrhea is most common adverse effect

Magnesium sulfate

Supplementation via IV infusion should be given to patients with moderately severe to severe depletion.

Dosing

Adult

2-4 g of 50% magnesium sulfate (16.6-33.3 mEq) diluted in saline or dextrose IV over 30-60 min
In cases of life-threatening arrhythmias, give same amount IV push

Pediatric

1 mEq/kg IV on day 1; 0.5 mEq/kg/d over next 3 d

Interactions

Concurrent nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone and cardiotoxicity of ritodrine

Contraindications

Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

May alter cardiac conduction, leading to heart block in digitalized patients; respiratory rate, deep tendon reflexes, and renal function should be monitored when administered parenterally; caution when administering magnesium dose since may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL of 10% solution IV, can be given as antidote for clinically significant hypermagnesemia

Follow-up

Further Inpatient Care

• Urine should be collected and sent for measurement of 24-hour excretion of magnesium. In a hypomagnesemic patient with healthy kidneys, the excretion of magnesium should be less than 1 mEq/L.
• Continue IV therapy.

Inpatient & Outpatient Medications

• Oral supplementation should be considered in patients who do not have a correctable cause for their hypomagnesemia.

Deterrence/Prevention

• Education of high-risk populations may decrease recurrence.

Prognosis

• Patients have an excellent prognosis once the deficiency is corrected. For the most part, the symptoms are reversible with treatment.

Patient Education

• Patients should be counseled regarding modification of risks of hypomagnesemia.
• This modification may include maintaining a proper diet, ceasing alcohol consumption, improving diabetic controls, and taking supplements if the cause is still present.
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center; Esophagus, Stomach, and Intestine Center; Substance Abuse Center; and Endocrine System Center. Also, see eMedicine's patient education articles Chronic Kidney Disease, Celiac Sprue, Alcoholism, and Thyroid Problems.

Miscellaneous

Special Concerns

• Much research has been performed recently on the role of magnesium in various disease processes.
  • The attempt to establish a connection between magnesium and ischemic heart disease is most notable. This topic receives significant debate. Some studies have identified hypomagnesemia in patients who have had an acute myocardial infarction, even those who did not use diuretics. Small studies have shown a benefit for patients treated empirically with magnesium, but the large ISIS IV trial has demonstrated no significant benefit of magnesium therapy. Interest is focused on improving hemodynamic status in congestive heart failure patients using magnesium; however, more studies are needed.³
  • Magnesium has been associated with the development of alcohol withdrawal symptoms. The exact connection is not known.
  • Some studies have suggested a link between hypomagnesemia and diabetic complications. Again, more investigation of this topic is needed.

Multimedia

Media file 1: A: Magnesium reabsorption in the thick ascending limb of the loop of Henle. The driving force for the reabsorption against a concentration gradient is a lumen-positive voltage gradient generated by the reabsorption of NaCl. Terms: FHHNC (familial hypomagnesemia with hypercalciuria and nephrocalcinosis); ADH (autosomal-dominant hypocalcemia); FHH/NSHPT (familial hypomagnesemia/neonatal severe hyperparathyroidism). B: Magnesium reabsorption in the distal convoluted tubule. Active transcellular transport is mediated by an apical entry through a magnesium channel and a basolateral exit, presumably via a Na+/Mg2+ exchange mechanism. Terms: HSH (hypomagnesemia with secondary hypocalcemia); GS (Gitelman syndrome); IDH (isolated dominant hypomagnesemia). Source: Konrad M, Schlingmann KP, Gudermann T: Insights into the molecular nature of magnesium homeostasis. Am J Physiol Renal Physiol 2004; 286: F599-F605.

References

1. Torii S, Kobayashi K, Takahashi M, Katahira K, Goryo K, Matsushita N, et al. Magnesium deficiency causes loss of response to intermittent hypoxia in paraganglion cells. J Biol Chem. Jul 10 2009;284(28):19077-89. [Medline].

2. Bohmer T, Mathiesen B. Magnesium deficiency in chronic alcoholic patients uncovered by an intravenous loading test. Scand J Clin Lab Invest. Dec 1982;42(8):633-6. [Medline].

3. Douban S, Brodsky MA, Whang DD, Whang R. Significance of magnesium in congestive heart failure. Am Heart J. Sep 1996;132(3):664-71. [Medline].

4. Agus ZS, Wasserstein A, Goldfarb S. Disorders of calcium and magnesium homeostasis. Am J Med. Mar 1982;72(3):473-88. [Medline].

5. Gibb MA, Wolfson AB, Tayal VS. Electrolyte disturbances. In: Emergency Medicine Concepts and Clinical Practice. Vol 3. 1998:2445-6.

6. Knochel JP. Disorders of magnesium metabolism. In: Harrison's Principles of Internal Medicine. Vol 2. 1994:2187-9.

7. Londner M, Hammer D, Kelen G D. Fluid and electrolyte problems. In: Emergency Medicine Comprehensive Study. 2004:177.

8. Matz R. Magnesium: deficiencies and therapeutic uses. Hosp Pract (Off Ed). Apr 30 1993;28(4A):79-82, 85-7, 91-2. [Medline].

9. Moe SM. Disorders of calcium, phosphorus, and magnesium. Am J Kidney Dis. Jan 2005;45(1):213-8. [Medline].

10. Monico EP, Bachman D, Anthony RG. Hypomagnesemia. Am J Emerg Med. Jul 1997;15(4):441-2. [Medline].

11. Nadler JL, Rude RK. Disorders of magnesium metabolism. In: Clinical Disorders of Fluid and Electrolyte Metabolism. Vol 24. 1995:623-36.

12. Stalnikowicz R. The significance of routine serum magnesium determination in the ED. Am J Emerg Med. Sep 2003;21(5):444-7. [Medline].

13. Tosiello L. Hypomagnesemia and diabetes mellitus. A review of clinical implications. Arch Intern Med. Jun 10 1996;156(11):1143-8. [Medline].

14. Wilson RF, Barton C. Fluid and electrolyte problems. In: Emergency Medicine Comprehensive Study Guide. 1996:135-6.

Keywords

hypomagnesemia, low magnesium level, magnesium, electrolytes, parathyroid hormone, magnesium deficiency, magnesium malabsorption, celiac sprue, radiation injury to the bowel, bowel resection, small bowel bypass, chronic diarrhea, laxative abuse, inflammatory bowel disease, neoplasm, malnutrition, diabetes, primary renal disorders, acute tubular necrosis, postobstructive diuresis, renal tubular acidosis, diuretics, cisplatin, pentamidine, fluoride poisoning, primary aldosteronism, hypoparathyroidism, hyperthyroidism, osmotic diuresis, alcoholism, insulin, excessive lactation, hungry bone syndrome, hypokalemia, hypocalcemia, hypophosphatemia, magnesium supplements, ischemic heart disease

Contributor Information and Disclosures

Author

Nona P Novello, MD, Associate Chair, Department of Emergency Medicine, Franklin Square Hospital
Nona P Novello, MD is a member of the following medical societies: American College of Emergency Physicians and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Howard A Blumstein, MD, FAAEM, Assistant Professor, Surgery; Medical Director, Department of Emergency Medicine, Wake Forest University School of Medicine
Howard A Blumstein, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robin R Hemphill, MD, MPH, Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University
Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Disclosure: Nothing to disclose.

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