(See also Overview of Disorders of Magnesium Concentration Overview of Disorders of Magnesium Concentration Magnesium is the 4th most plentiful cation in the body. A 70-kg adult has about 2000 mEq (1000 mmol) of magnesium. About 50% is sequestered in bone and is not readily exchangeable with magnesium... read more .)
Serum magnesium concentration, even when free magnesium ion is measured, may be normal even with decreased intracellular or bone magnesium stores.
Etiology of Hypomagnesemia
Magnesium depletion usually results from inadequate intake plus impairment of renal conservation or gastrointestinal absorption. There are numerous causes of clinically significant magnesium deficiency (see table Causes of Hypomagnesemia Causes of Hypomagnesemia ). Hypomagnesemia is common among hospitalized patients and frequently occurs with other electrolyte disorders, including hypokalemia Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more and hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more . Hypomagnesemia is related to decreased intake in patients with undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more or long-term alcohol use disorder Alcohol Use Disorder and Rehabilitation Alcohol use disorder involves a pattern of alcohol use that typically includes craving and manifestations of tolerance and/or withdrawal along with adverse psychosocial consequences. Alcoholism... read more . Decreased oral intake is frequently compounded by increased urinary excretion exacerbated by diuretic use, which increase urinary excretion of magnesium.
Drugs can cause hypomagnesemia. Examples include chronic (> 1 year) use of a proton pump inhibitor and concomitant use of diuretics. Amphotericin B can cause hypomagnesemia, hypokalemia, and acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more . The risk of each of these is increased with duration of therapy with amphotericin B and concomitant use of another nephrotoxic agent. Liposomal amphotericin B is less likely to cause either kidney injury or hypomagnesemia. Hypomagnesemia generally resolves with cessation of therapy.
Cisplatin can cause increased magnesium losses by the kidneys as well as generalized decrease in kidney function. Magnesium loses can be severe and persist despite discontinuation of cisplatin. Discontinuation of cisplatin is still recommended if signs of renal toxicity occur during therapy.
Symptoms and Signs of Hypomagnesemia
Some patients are asymptomatic. Clinical manifestations include anorexia, nausea, vomiting, lethargy, weakness, personality change, tetany (eg, positive Trousseau or Chvostek sign or spontaneous carpopedal spasm, hyperreflexia), and tremor and muscle fasciculations.
Trousseau sign is the precipitation of carpal spasm by reduction of the blood supply to the hand with a tourniquet or blood pressure cuff inflated to 20 mm Hg above systolic blood pressure applied to the forearm for 3 minutes.
Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just anterior to the exterior auditory meatus.
The neurologic signs, particularly tetany, correlate with development of concomitant hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more , hypokalemia Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more , or both. Myopathic potentials are found on electromyography but are also compatible with hypocalcemia or hypokalemia.
Severe hypomagnesemia may cause generalized tonic-clonic seizures, especially in children.
Diagnosis of Hypomagnesemia
Serum magnesium concentration < 1.8 mg/dL (< 0.70 mmol/L)
Hypomagnesemia is diagnosed by measurement of serum magnesium concentration. Severe hypomagnesemia usually results in concentrations of < 1.25 mg/dL (< 0.50 mmol/L). Associated hypocalcemia and hypocalciuria are common. Hypokalemia with increased urinary potassium excretion and metabolic alkalosis Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3−) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common... read more may be present.
Magnesium deficiency should be suspected even when serum magnesium concentration is normal in patients with unexplained hypocalcemia or refractory hypokalemia. Magnesium deficiency should also be suspected in patients with unexplained neurologic symptoms and alcohol use disorder, with chronic diarrhea, or after cyclosporine use, cisplatin-based chemotherapy, or prolonged therapy with amphotericin B or aminoglycosides.
Treatment of Hypomagnesemia
Oral magnesium salts
IV or IM magnesium sulfate for severe hypomagnesemia or inability to tolerate or adhere to oral therapy
Treatment with magnesium salts is indicated when magnesium deficiency is symptomatic or the magnesium concentration is persistently < 1.25 mg/dL (< 0.50 mmol/L). Patients with alcohol use disorder are treated empirically. In such patients, deficits approaching 12 to 24 mg/kg are possible.
About twice the amount of the estimated deficit should be given in patients with intact renal function because about 50% of the administered magnesium is excreted in urine. Oral magnesium salts (eg, magnesium gluconate 500 to 1000 mg orally 3 times a day) are given for 3 to 4 days. Oral treatment is limited by the onset of diarrhea.
Parenteral administration is reserved for patients with severe, symptomatic hypomagnesemia who cannot tolerate oral drugs. Sometimes a single injection is given in patients with alcohol use disorder who are unlikely to adhere to ongoing oral therapy. When magnesium must be replaced parenterally, a 10% magnesium sulfate solution (1 g/10 mL) is available for IV use and a 50% solution (1 g/2 mL) is available for IM use. The serum magnesium concentration should be monitored frequently during magnesium therapy, particularly when magnesium is given to patients with renal insufficiency or in repeated parenteral doses. In these patients, treatment is continued until a normal serum magnesium concentration is achieved.
In severe, symptomatic hypomagnesemia (eg, magnesium < 1.25 mg/dL [< 0.5 mmol/L] with seizures or other severe symptoms), 2 to 4 g of magnesium sulfate IV is given over 5 to 10 minutes. When seizures persist, the dose may be repeated up to a total of 10 g over the next 6 hours. In patients in whom seizures stop, 10 g in 1 L of 5% D/W (dextrose in water) can be infused over 24 hours, followed by up to 2.5 g every 12 hours to replace the deficit in total magnesium stores and prevent further drops in serum magnesium.
When serum magnesium is ≤ 1.25 mg/dL (< 0.5 mmol/L) but symptoms are less severe, magnesium sulfate may be given IV in 5% D/W at a rate of 1 g/hour as slow infusion for up to 10 hours. In less severe cases of hypomagnesemia, gradual repletion may be achieved by administration of smaller parenteral doses over 3 to 5 days until the serum magnesium concentration is normal.
Concurrent hypokalemia Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more or hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more should be specifically addressed in addition to hypomagnesemia. These electrolyte disturbances are difficult to correct until magnesium has been repleted. Additionally, hypocalcemia can be worsened by isolated treatment of hypomagnesemia with intravenous magnesium sulfate because sulfate binds ionized calcium.
Hypomagnesemia may occur in patients with alcohol use disorder, uncontrolled diabetes, or hypercalcemia or patients taking loop diuretics.
Symptoms include anorexia, nausea, vomiting, lethargy, weakness, personality change, tetany (eg, positive Trousseau or Chvostek sign, spontaneous carpopedal spasm, hyperreflexia), tremor, and muscle fasciculations.
Treat with magnesium salts when magnesium deficiency is symptomatic or persistently < 1.25 mg/dL (< 0.50 mmol/L).
Give oral magnesium salts unless patients have seizures or other severe symptoms, in which case, give 2 to 4 g of magnesium sulfate IV over 5 to 10 minutes.