EDITORIAL COMMENTS
How Best to Determine Magnesium Status: A New Laboratory Test
Worth Trying
The article by Sacks, Brown, Dickerson and their
colleagues1 considers the limitations of tests that
determine magnesium status before and after magnesium therapy to
restore depleted levels of ten critically ill patients identified
as magnesium deficient on the basis of low serum values. Because
the added risk of complications from magnesium depletion in
patients already at high risk from their injuries has been cited,
the authors provided a continuous 24-h intravenous infusion
containing magnesium (0.5 or 0.75 mmol/kg as MgSO4). They
attempted to evaluate the efficacy of treatment, not only by
changes in serum values. but by white bloodcell.( mononuclear)
determinations, which is considered a better index of tissue
magnesium content. It was unanticipated that the mononuclear
blood cell magnesium would be less indicative of response to the
magnesium infusion than were the serum levels.
The authors considered several possible explanations for the
failure to demonstrate repletion by this blood cell test. They
suggested that variability in the assay, in conjunction with the
small number of patients in their study, and a possible
presumptive lowered renal threshold for magnesium reabsorption,
might account for failure to retain sufficient magnesium to
replete tissue levels. However, the elevation of serum magnesium
levels and correction of hypocalcemia ( a consequence of
magnesium depletion's impairment of parathyroid hormone
secretion, which the authors cited) indicate that the infusion
corrected those manifestations of magnesium deficiency. They also
consider it possible that the amount of magnesium infused was
insufficient to replete tissue stores in critically ill patients.
All these points are valid, but caution must be exercised in
increasing the magnesium load in a 24-h infusion to avoid levels
that might produce hypermagnesemia. Patients with decreased renal
reabsorption of magnesium would be at low risk of
hypermagnesemia. Patients with impaired renal clearance would be
at high risk of high circulating magnesium, which can cause
sufficient peripheral vasodilatation to trigger hypotension and
even shock, and might slow cardiac conduction, with risk of
bradycardia and even heart block.2,3 Abbott and
Rude4 have found lower infusion doses of parenteral
magnesium (12-24 mmol mg/d) given for 3-5 d, followed by
long-term repletion with orally administered magnesium (300-600
mg/d), to be effective in repairing magnesium deficiency, even
when characterized by acute signs, in critically ill
patients.
Whether the measurement of blood cell magnesium is necessarily
the best test to evaluate response to magnesium infusion is
uncertain. Arnold et al.5 evaluated the magnesium
status in erythrocytes and mononuclear blood cells in 15
critically ill patients whose magnesium depletion had been
diagnosed by the magnesium-load test. They found no significant
difference in plasma, red cell, and mononuclear blood cell
magnesium levels between magnesium depleted and nondepleted
groups, and concluded that a diagnosis of magnesium depletion
cannot be excluded despite normal values in plasma, erythrocytes,
or mononuclear blood cells.
In the serum magnesium test, the more indicative of those used
by Sacks et al.,1 serum magnesium comprises only 0.3%
of the body's magnesium (of about 24 g or 1 mol) and is made up
of protein-bound, complexed, and free ionic magnesium, which
constitutes 71 % of the amount in serum, and is the fraction that
is biologically active.6,7 There are now several
ion-selective electrode (ISE) instruments that are commercially
available.7-10 Which of the devices is best to use is
still controversial. The prototype of the NOVA Biomedical
instrument, used by Altura and colleagues,7,10,11 has
provided the most data. They have found that their ISE is
selective for Mg2+, and exhibits little or no
interference from pathophysiologic concentrations of ionic
calcium, sodium, potassium, hydrogen, ammonium, or heavy metals
(e.g., ionic iron, copper, zinc, cadmium, mercury, or lead) in
serum. Importantly, silicon (as found in vacutainer tubes) does
not interfere with measured levels — an important attribute
in collecting and transporting samples for analysis. Using this
device, Altura et al.7,11,12 have found
[Mg2+]o to be 71% of the total magnesium in serum, it
varies from subject to subject, but has been remarkably
consistent in sequential samples from an individual. Use of
specific ISEs for [Mg2+]o has disclosed that
Mg2+ levels often exhibit significant differences from
normality, despite no change in total serum magnesium in many
disorders (i.e., cardiac disease, hypertension, cardiopulmonary
bypass, abnormal pregnancy, renal and hepatic transplant,
migraine headaches, head injury, stroke, diabetes, asthma, and
other conditions).
Estimation of the [Mg2+]o level in serum or plasma
by analysis of ultrafiltrates (complexed Mg + Mg2+) is
somewhat unsatisfactory and time consuming. More importantly,
these methods do not distinguish the ionized or free form of Mg
from the Mg2+ bound to organic and inorganic
anions.11-13 Because the levels of these ligands
(e.g., lactate, bicarbonate, sulfate, citrate, phosphate,
acetate, etc.) can vary significantly in numerous pathologic
states, it is desirable to measure the levels of Mg2+
directly, in complex matrices such as whole blood, plasma, and
serum. Virtually no difference in [Mg2+]o was found
using the novel ISE, irrespective of whether whole blood, plasma,
or serum was sampled.7,10,13 These data demonstrate
that the mean concentration of [Mg2+]o in human blood
is about 600 µmol/L (0.54-0.65 mM/L, 95% CI), with 65-72%
total Mg being free or biologically active. Use of
3lP-nuclear magnetic resonance spectroscopy on human
red blood cells in samples taken from patients with disease
states to measure tissue intracellular free Mg
([Mg2+]i demonstrate a high correlaton (r =
0.5-0.8; P < 0.01) between [Mg2+]o and
[Mg2+]i, suggesting that a Mg2+ measurement
might be, quantitatively, a "true reflection" of soft tissue
levels.14,15
Difficulties in diagnosing magnesium deficiency and in
evaluating response to therapy are largely to blame for delays in
accepting low serum magnesium as an important contributor to
morbidity and mortality, and in attempting to correct it, a
particlarly important variable in the critically ill. Now that
clinically available means to determine ionic magnesium levels
are more widely available, the substantial knowledge of the
importance of diagnosing magnesium deficiency in patients,
determining the effects of drugs that affect its levels, and
ascertaining success in its repletion should be increasingly
applied to patient care.
MILDRED S. SEELIG,
PHD
Decatur, Georgia, USA
BURTON M. ALTURA,
PHD
Department of Physiology
SUNY Health Science Center at Brooklyn
Brooklyn, New York, USA
REFERENCES
1. Sacks GS. Brown RO. Dickerson RN. et al.. Mononuclear blood
cell magnesium content and serum magnesium concentration in
critically ill hypomagnesemic patients after replacement therapy.
Nutrition 1997; 13:303
2. Altura BM, Altura BT. Magnesium, electrolyte transport, and
coronary vascular tone. Drugs 1984;28 (suppl. 1):120
3. Seelig MS, Elin RJ, Antman EM. Magnesium in acute
myocardial infarction: still an open question. (submitted for
publication)
4. Abbott LG, Rude RK. Clinical manifestations of magnesium
deficiency. Miner Electrolyte Metab 1993; 19:314
5. Arnold A, Tovey J, Mangat P, Penny W, Jacobs S. Magnesium
deficiency in critically ill patients. Anaesthesia
1995;50:203
6. Elin RJ. Assessment of magnesium status. In: Itokawa Y,
Durlach J, eds. Magnesium in health and disease. London:
J. Libbey, 1989:137
7. Altura BT, Altura BM. Measurement of ionized magnesium in
whole blood, plasma and serum with a new ion-selective electrode
in healthy and diseased human subjects. Magnes Trace Elem
1991-1992;10:90
8. Lewenstam A, Blomqvist N, Ost J. Characterization,
standardization and experiences with KONE ISE for
Mg2+. Scand J Clin Lab Invest 1994;54(suppl.
217):37
9. Altura BM, Lewestam A. Unique magnesium-sensitive ion
selective electrodes. Scand J Clin Lab Invest 1994;54(Suppl.
217):1
10. Altura BT, Bertschat F, Jeremias A, Ising H, Altura BM.
Comparative findings on serum Mg2+ of normal and
diseased human subjects with rhe NOY A and KONE ISE's for
Mg2+. Scand J Clin Lab Invest 1994;54(suppl.
217):77
11. Altura BT, Altura BM. Role of magnesium in
pathophysiological processes and the clinical utility of
magnesium ion selective electrodes. Scand J Clin Lab Invest
1996;56(suppl. 224):211
12. Altura BT, Shirey TL, Young CC, et al. Characterization of
a new ion selective electrode for ionized magnesium in whole
blood, plasma, serum, and aqueous samples. Scand J Clin Lab
Invest 1994;54(suppl. 217):21
13. Altura BT, Altura BM. A method for distinguishing ionized,
complexed and protein-bound Mg in normal and diseased subjects.
Scand J Clin Lab Invest 1994;54(suppl. 217):83
14. Altura BT, Burack JL, Cracco RQ, et al. Clinical studies
wirh the NOVA ISE for IMg2+. Scand J Clin Lab Invest
1994; 54 (suppl. 217):53
15. Altura BM, Altura BT. Magnesium in cardiovascular biology.
Scientific Am Sci Med 1995:28-30.
PH S0899-9007(97)00073-7
Nutrition 13 (1997):376-377
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