Henk J. Huijgen

Magnesium in disease : a review with special emphasis on the serum ionized magnesium

Abstract This review deals with the six main clinical situations related to magnesium or one of its fractions, including ionized magnesium: renal disease, hypertension, preeclampsia, diabetes mellitus, cardiac disease, and the administration of therapeutic drugs. Issues addressed are the physiological role of magnesium, eventual changes in its levels, and how these best can be monitored. In renal disease mostly moderate hypermagnesemia is seen; measuring ionized magnesium offers minimal advantage. In hypertension magnesium might be lowered but its measurement does not seem relevant. In the prediction of severe pre-eclampsia, elevated ionized magnesium concentration may play a role, but no unequivocal picture emerges. Low magnesium in blood may be cause for, or consequence of, diabetes mellitus. No special fraction clearly indicates magnesium deficiency leading to insulin resistance. Cardiac diseases are related to diminished magnesium levels. During myocardial infarction, serum magnesium drops. Total magnesium concentration in cardiac cells can be predicted from levels in sublingual or skeletal muscle cells. Most therapeutic drugs (diuretics, chemotherapeutics, immunosuppressive agents, antibiotics) cause hypomagnesemia due to increased urinary loss. It is concluded that most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease. Keeping in mind that only 1% of the total body magnesium pool is extracellular, no simple measurement of the real intracellular situation has emerged; measuring ionized magnesium in serum has little added value at present.

Magnesium levels in critically ill patients. What should we measure

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.

Serum ionized magnesium: comparison of results obtained with three ion-selective analyzers.

Abstract In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg2+) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y = 0.972x−0.013; n = 138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p < 0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all < 4.0%. Coefficients of variation for the AVL and KONE were < 5% at normal and high iMg2+, but 10.7 and 9.4%, respectively, at iMg2+ ≈ 0.30 mmol/l. The reference intervals (mean ± standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55–0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43–0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators).

Intracellular and extracellular, ionized and total magnesium in pre-eclampsia and uncomplicated pregnancy.

Abstract Magnesium (Mg) and calcium (CA) concentrations in women with pre-eclampsia, women with an uncomplicated pregnancy and non-pregnant women were compared. Ionized serum magnesium and calcium concentrations and intracellular magnesium concentrations were measured in 15 pregnant women with severe pre-eclampsia, 34 uncomplicated pregnant women early, at midterm and preterm in their pregnancy and 24 non-pregnant women. The ionized calcium concentration did not chance during normal pregnancy or during pre-eclampsia relative to non-pregnant women. In contrast, elevated total and ionized magnesium serum concentrations were found in women with severe pre-eclampsia (total Mg = 0.85 ± 0.11 mM, ionized Mg = 0.61 ± 0.06 mM) relative to uncomplicated pregnant women (total Mg = 0.72 ± 0.06 mM, ionized Mg = 0.53 ± 0.03 mM). Total magnesium in pre-eclamptic women were similar to non-pregnant women. Intracellular ionized and total magnesium concentrations in mononuclear blood cells and erythrocytes were similar in pre-eclamptic women and women with uncomplicated pregnancy. Serum magnesium concentrations are elevated in severe pre-eclamptic women relative to women with uncomplicated pregnancy and are related to birth weight and gestational age at delivery. There may be a causal relationship since magnesium is involved in blood pressure regulation through an intracellular inhibition of NO synthase in endothelial cells.

Magnesium fractions in serum of healthy individuals and CAPD patients, measured by an ion-selective electrode and ultrafiltration

OBJECTIVES Validation and comparison of a magnesium ion-selective electrode (ISE) with a cation-exchange resin technique, followed by determination of all magnesium fractions in serum of healthy volunteers and continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN AND METHODS The analytical aspect has been studied by measuring the influence of complexing agents on the fraction ionized magnesium (friMg2+). A theoretical approximation of friMg2+, based on mass equilibria and complexation constants, was calculated and compared with the measurements. RESULTS ISE measurements showed good agreement with theory. Reference values of the ionized, protein-bound, and complexed magnesium fractions were (mean +/- SD) 0.65 +/- 0.04, 0.27 +/- 0.04, and 0.08 +/- 0.03, respectively. Fractions obtained in the CAPD group were 0.62 +/- 0.04, 0.22 +/- 0.05, and 0.16 +/- 0.05, respectively, and differed significantly from the values of the reference population. CONCLUSIONS All known serum magnesium parameters can be established by a combination of ultrafiltration, atomic absorption spectrometry, and ISE measurements. Unknown complexing compounds most probably account for the increased fraction of complexed magnesium in the serum of CAPD patients.

Precision of the Magnesium Determination in Mononuclear Blood Cells and Erythrocytes

OBJECTIVE Establishing the analytical variation and reproducibility of the intracellular magnesium (Mg) assay in mononuclear blood cells (MBC) and erythrocytes (RBC). DESIGN AND METHODS We assessed the analytical variation of the several determination steps, and the reproducibility for the complete intracellular Mg-assay (combination of preanalytical, analytical, and biological variation). The influence of platelets was determined by comparing Mg concentrations obtained from heparinized blood and defibrinated blood. RESULTS Coefficients of variation of the several determination steps used in the MBC- and RBC-assay were < or = 5.4%. The overall analytical variation was 5.0-6.8%, and reproducibility of the complete Mg-assay 11.6-14.0%. Mg measurements in MBC (expressed as fmol/cell) obtained from heparinized blood showed significantly higher values than those obtained from defibrinated blood. CONCLUSION This is the first study to describe in detail reproducibility data for the individual steps in the overall procedure to measure intracellular magnesium. It is shown that results obtained in daily practice should be interpreted with care. Moreover, the removal of platelets is essential in the determination of Mg in MBC.