Hypomagnesemia

Definition, Etiology, PathogenesisTop

Hypomagnesemia is defined as a total serum [Mg2+] <0.65 mmol/L.

Causes:

1) Inadequate intake due to a low-magnesium diet or long-term parenteral nutrition using products with inadequate magnesium content.

2) Impaired magnesium absorption in the gastrointestinal (GI) tract due to chronic malabsorption syndromes (particularly involving the small intestine) or long-term proton pump inhibitor (PPI) use.

3) Increased magnesium loss:

a) Through the kidneys due to tubulopathies, which may be congenital (Gitelman syndrome; Bartter syndrome; isolated hypomagnesemia with hypocalciuria or normal urinary calcium excretion; familial hypomagnesemia with hypercalciuria, nephrocalcinosis, or both; hypomagnesemia with secondary hypocalcemia; activating mutation of the gene encoding the calcium receptor) or acquired (primary aldosteronism, chronic alcohol abuse, hypercalcemia, hypokalemia, diuretics, aminoglycosides, cisplatin, amphotericin B, cyclosporine [INN cyclosporin], polyuria in the course of acute tubular necrosis or after relief of urinary tract obstruction).

b) With body fluids (fistulas).

4) A magnesium shift from the extracellular compartment during intensive treatment of diabetic ketoacidosis, in so-called hungry bone syndrome after surgical treatment of hyperparathyroidism, in refeeding syndrome, during sympathetic stimulation, in chronic alcohol misuse, or in acute pancreatitis (saponification at the sites of fat necrosis).

Although hypomagnesemia is most frequently associated with reduced total body magnesium content, it may occur in patients with normal or even increased magnesium stores. Normal magnesium levels do not exclude magnesium deficiency.

Clinical FeaturesTop

Clinical features of hypomagnesemia are nonspecific. The most frequent manifestations are metabolic disturbances (hypocalcemia and hypokalemia resistant to supplementation, hypophosphatemia), arrhythmia (premature supraventricular and ventricular beats, tachycardia, atrial fibrillation, ventricular fibrillation), neuromuscular symptoms (hand and tongue tremor; symptomatic or latent tetany; muscle weakness, especially affecting respiratory muscles). Electrocardiography (ECG) may reveal a long QT interval, flat T waves, and the presence of U waves. Chronic mild hypomagnesemia is more frequent in patients with hypertension and ischemic heart disease.

DiagnosisTop

The diagnosis of hypomagnesemia is based on measurement of serum [Mg2+] (<0.65 mmol/L). In severe hypoalbuminemia, the value should be corrected by adding 0.05 mmol/L for each 1 g/dL (10 g/L) of reduction in the plasma albumin level below 4 g/dL (40 g/L). In all patients measure serum levels of other ions and creatinine. Blood gas analysis may be of use in more complex situations.

A baseline daily urinary magnesium excretion >1 mmol in a patient with hypomagnesemia is suggestive of renal magnesium loss, while values <1 mmol suggest other causes.

In the case of suspected magnesium deficiency in a patient with normal serum [Mg2+], you may perform a magnesium loading test that involves IV administration of 4 g of MgSO4 dissolved in 500 mL of a 5% glucose (dextrose) solution over 8 hours. A urinary magnesium excretion <15 mmol/d on the day of administration of the loading dose indicates magnesium deficiency.

TreatmentTop

1. Try to control the cause of hypomagnesemia.

2. Correct magnesium deficiency (suggested doses):

1) In patients with symptomatic hypomagnesemia (arrhythmia, tetany, seizures), administer IV magnesium sulfate 1 to 2 g over 10 to 15 minutes (to achieve a serum increase in [Mg2+] by ≥0.4 mmol/L as quickly as possible) followed by 5 g in 500 mL of 5% glucose over 5 hours as a slow IV infusion (≤2 g/h); in patients with torsades de pointes, administer the initial dose over 30 to 60 seconds and repeat if necessary after 5 to 15 minutes. If serum [Mg2+] is <0.25 mmol/L, magnesium deficiency is estimated to be 0.5 to 1.0 mmol/kg. The rate of correction follows local patterns and may include a rapid IV infusion (over a few hours) of MgSO4 1 to 4 g in 250 to 1000 mL of 5% glucose followed by more doses as needed.

2) In patients with asymptomatic hypomagnesemia, administer oral magnesium such as magnesium oxide (in patients with normal GI magnesium absorption). All oral magnesium formulations cause diarrhea (extended-release formulations least commonly), which may worsen magnesium deficiency.

3. Simultaneously correct coexisting hypokalemia, hypocalcemia, and hypophosphatemia, as these cause treatment-resistant hypomagnesemia.

4. Perform frequent serum magnesium measurements, depending on the severity of deficiency and doses used, and monitor the patient’s clinical status to avoid hypermagnesemia caused by magnesium overdose.