Magnesium

Magnesium is the second most abundant intracellular cation, and is an essential element for the utilization of energy in the organic world. Unfortunately, the “tip of the iceberg” analogy used for potassium also applies to magnesium; i.e., only a minor fraction (0.3%) of total body magnesium is located in plasma (1,2,3), so monitoring the plasma magnesium provides little information about total body magnesium.

I. Basics

A. Distribution

The average-sized adult contains approximately 24 g (1 mole, or 2,000 mEq) of magnesium (Mg); a little over half is located in bone, whereas less than 1% is located in plasma (2).
The lack of representation in the plasma limits the value of the plasma Mg as an index of total body magnesium; e.g., plasma Mg levels can be normal in the face of total body Mg depletion (2,3).

B. Serum Magnesium

Serum is favored over plasma for Mg assays because the anticoagulant used for plasma samples can be contaminated with citrate or other anions that bind Mg (2).
The normal reference range for serum Mg (in healthy adults in the United States) is shown in Table 29.1 (4).

Table 29.1 Reference Ranges for Magnesium

Fluid	Traditional Units	SI Units
Serum Magnesium:
Total	1.7–2.4 mg/dL	0.7–1.0 mmol/L
	1.4–2.0 mEq/L
Ionized	0.8–1.1 mEq/L	0.4–0.6 mmol/L
Urinary Magnesium:	5–15 mEq/24 hr	2.5–7.5 mmol/24 hr
From Reference 4. Conversions: mEq/L = [(mg/dL × 10)/24] × 2; mEq/L = mmol/L × 2.

C. Ionized Magnesium

Only 67% of the Mg in plasma is in the ionized (active) form, and the remaining 33% is either bound to plasma proteins or chelated with divalent anions such as phosphate and sulfate (2).
The standard assay for Mg includes all plasma fractions. Therefore, when the serum Mg is abnormally low, it is not possible to determine whether the problem is a decrease in the ionized (active) fraction or a decrease in the bound fractions (e.g., hypoproteinemia).
Since the total amount of Mg in plasma is small, the difference between the ionized and bound Mg may not be large enough to be clinically relevant.

D. Urinary Magnesium

The normal range for urinary Mg excretion is shown in Table 29.1. Urinary Mg excretion is dependent on the Mg intake.

FIGURE 29.1 Urinary Mg excretion and plasma Mg levels in a healthy volunteer placed on a Mg-free diet. Solid bars on the vertical axes indicate the normal range for each variable. (Adapted from Shils ME. Medicine 1969; 48:61–82.)

When Mg intake is deficient, the kidneys conserve Mg, and urinary Mg excretion falls to negligible levels. This is shown in Figure 29.1. Note that after one week of a Mg-free diet, the plasma Mg remains in the normal range, while the urinary Mg excretion has decreased to negligible levels. This illustrates the relative value of urinary Mg excretion for monitoring Mg balance.

II. Magnesium Deficiency

Hypomagnesemia is reported in as many as 65% of ICU patients (1,6), and the incidence of Mg depletion is even higher (because the serum Mg level can be normal in patients with Mg deficiency) (2,3).

A. Predisposing Conditions

Several conditions promote Mg depletion, and these are listed in Table 29.2.

Table 29.2 Causes & Consequences of Mg Depletion

Predisposing Conditions	Clinical Findings
Drug Therapy: Furosemide (50%) Aminoglycosides (30%) Amphotericin, pentamidine Digitalis (20%) Cisplatin, cyclosporine	Electrolyte abnormalities: Hypokalemia (40%) Hypophosphatemia (30%) Hyponatremia (27%) Hypocalcemia (22%)
Diarrhea (secretory)	Cardiac manifestations:
Alcohol abuse (chronic)	Arrhythmias Digitalis toxicity
Diabetes mellitus
Acute MI	Reactive CNS Syndrome
Numbers in parentheses indicate incidence of associated hypomagnesemia.

1. Diuretic Therapy

Diuretics are the leading cause of Mg deficiency. Diuretic-induced inhibition of sodium reabsorption also interferes with Mg reabsorption, and the urinary Mg losses can parallel urinary sodium losses.

Urinary Mg excretion is most pronounced with loop diuretics like furosemide. Mg deficiency has been reported in 50% of patients receiving chronic therapy with furosemide (7).
The thiazide diuretics also promote Mg depletion, primarily in elderly patients (8).
Mg depletion is not a complication of “potassium-sparing” diuretics (9).

2. Antibiotic Therapy

The antibiotics that promote Mg depletion are the aminoglycosides, amphotericin and pentamidine (10,11). The aminoglycosides block Mg reabsorption in the ascending
loop of Henle, and hypomagnesemia has been reported in 30% of patients receiving aminoglycoside therapy (11).

3. Other Drugs

Prolonged use of proton pump inhibitors can be associated with severe hypomagnesemia (12). Other drugs associated with Mg depletion include digitalis and epinephrine (shift Mg into cells), and the chemotherapeutic agents cisplatin and cyclosporine (promote renal Mg excretion) (10,13).

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