Monitoring of serum ionized magnesium in neurosurgical intensive care unit: preliminary results.
ABSTRACT Our purpose was to determine the values for serum ionized magnesium (Mg) concentrations in traumatic brain injury and its effect on the prognostic scores of patients.
We prospectively measured serum ionized magnesium concentrations in 30 patients that were classified into three groups (severe, moderate, mild) by Glasgow Coma Scale Score. Serum ionized magnesium concentrations were measured during posttraumatic 5 days. Thirty patients with head trauma were followed in a neurosurgical intensive care unit with monitoring serum ionized magnesium concentrations. All patients were treated conservatively.
We found significant difference of serum ionized magnesium concentrations when we compared all groups with each other (p<0.001).
Based on this clinical preliminary study, traumatic brain injury is associated with graded deficit in serum ionized magnesium concentrations. Thus, measurement of serum ionized magnesium concentrations can be used as a clinical marker in traumatic brain injury.
- SourceAvailable from: Anil Gulati[Show abstract] [Hide abstract]
ABSTRACT: Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI.Journal of the American Society for Experimental NeuroTherapeutics 01/2010; 7(1):91-9. · 5.38 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) remains a serious health concern, and TBI is one of the leading causes of death and disability, especially among young adults. Although preventive education, increased usage of safety devices, and TBI management have dramatically increased the potential for surviving a brain injury, there is still a need to develop reliable methods to diagnose TBI, the secondary pathologies associated with TBI, and predicting the outcomes of TBI. Biomarkers (changes of amount or activity in a biomolecule that reflect injury or disease) have shown promise in the diagnosis of several conditions, including cancer, heart failure, infection, and genetic disorders. A variety of proteins, small molecules, and lipid products have been proposed as potential biomarkers of brain damage from TBI. Although some of these changes have been reported to correlate with mortality and outcome, further research is required to identify prognostic biomarkers. This need is punctuated in mild injuries that cannot be readily detected using current techniques, as well as in defining patient risk for developing TBI-associated secondary injuries.Journal of the American Society for Experimental NeuroTherapeutics 01/2010; 7(1):100-14. · 5.38 Impact Factor
- 01/2011: pages 167-179;
Monitoring of serum ionized magnesium in neurosurgical intensive
care unit: preliminary results
Serdar Kahramana,*, Taner Ozgurtasb, Hakan Kayalıa, Cem Atabeya,
Turker Kutluayb, Erdener Timurkaynaka
aDepartment of Neurosurgery, Gu ¨lhane Military Medical Academy, 06018 Etlik-Ankara, Turkey
bDepartment of Biochemistry, Gu ¨lhane Military Medical Academy, 06018 Etlik-Ankara, Turkey
Received 24 February 2003; received in revised form 7 May 2003; accepted 7 May 2003
Background: Our purpose was to determine the values for serum ionized magnesium (Mg) concentrations in traumatic brain
injury and its effect on the prognostic scores of patients. Methods: We prospectively measured serum ionized magnesium
concentrations in 30 patients that were classified into three groups (severe, moderate, mild) by Glasgow Coma Scale Score.
Serum ionized magnesium concentrations were measured during posttraumatic 5 days. Thirty patients with head trauma were
followed in a neurosurgical intensive care unit with monitoring serum ionized magnesium concentrations. All patients were
treated conservatively. Results: We found significant difference of serum ionized magnesium concentrations when we compared
all groups with each other (p<0.001). Conclusions: Based on this clinical preliminary study, traumatic brain injury is
associated with graded deficit in serum ionized magnesium concentrations. Thus, measurement of serum ionized magnesium
concentrations can be used as a clinical marker in traumatic brain injury.
D 2003 Elsevier B.V. All rights reserved.
Keywords: Head injury; Intensive care; Ionized magnesium; Neurotrauma
Blunt head injury is the most prevalent form of
brain injury . A number of studies to date have
demonstrated the importance of the magnesium
(Mg) ion in brain posttraumatic homeostasis [2,3].
Experimental evidences suggest that Mg plays an
important role in pathophysiology of neurotrauma
[4–6]. Using either phosphorus magnetic resonance
spectroscopy or atomic absorption spectrophotome-
try, studies have shown that intracellular free Mg
concentration declines following injury [3,7,8].
Moreover, the temporal profile of free Mg in the
brain changes after traumatic brain injury is
reflected in free Mg concentration in the blood
. The decline in Mg concentration affects a
number of secondary injury factors including neu-
rotransmitter release, ion changes, oxidative stress,
protein synthesis, and energy metabolism [10–12].
Serum ionized Mg is known to be the physiologi-
cally active fraction of total Mg. Despite many
researches on traumatic brain injury, few markers
0009-8981/03/$ - see front matter D 2003 Elsevier B.V. All rights reserved.
* Corresponding author. Tel.: +90-312-304-5302; fax: +90-312-
E-mail address: firstname.lastname@example.org (S. Kahraman).
Clinica Chimica Acta 334 (2003) 211–215
have been applicable to diagnose trauma at tissue
2. Material and methods
All procedures were performed in accordance
with the ethical standards of the Helsinki Declara-
tion revised in 1983. The serum ionized Mg con-
centrations of 30 patients with traumatic brain injury
submitted to Department of Neurosurgery, Gu ¨lhane
Military Medical Academy (GMMA) between
March 2001–June 2001 were examined. Thirty
patients with traumatic brain injury were classified
according to Glasgow Coma Scale score (GCS); 12
of them were in mild (GCS 13–15), 8 of them were
in moderate (GCS 8–12) and 10 of them were in
severe brain injury group (GCS 3–7). GCSs of the
patients did not change for 5 days in this study.
Only 6 of these patients were female and the mean
age of the whole group was 32.6 years. All of the
patients had no any acute or chronic systemic
problems, which required medication. Patients with
multiple injuries were not included in this study. All
patients were followed in neurosurgical intensive
care unit and no patients had blood transfusion.
The patients with severe and moderate groups had
taken standard anti-edema medication including diu-
retics. The control group consisted of 12 age-
matched healthy male volunteers.
Blood samples were obtained from all patients
within 3 h (before any medication) and during 5 days
following trauma. Five milliliters of blood sample was
taken from the patients into noncoated glass tubes
(RVacutainer system, Becton Dickinson, NJ) and it
was centrifuged at 2000?g for 10 min in GMMA
Biochemistry laboratory. Sera were extracted from the
samples and were stored at ?20 jC and analyzed
within 1 month after sampling. Ionized Mg was
measured with R988-4 Mg Analyzer from AVL
(Austria); analyzer with an ion-selective electrode
based on the ionophore ETH 7025.
Data are expressed as the meanFstandard devia-
tion (S.D.). Means were computed and compared by
nonparametric Kruskal–Wallis and Mann Whitney U
test using Statistical Programs for the Social Sciences
(SPSS). A p<0.05 was considered to be statistically
Serum ionized Mg concentrations in the posttrau-
matic period of 5 days in three groups are shown in
Fig. 1. When concentrations of serum ionized Mg are
compared, the decline was observed according to the
Fig. 1. The relationship between severity of trauma and serum
ionized magnesium concentrations. *Dot-lines are reference ranges.
Mean serum ionized magnesium concentrations in three groups
GroupsIonized magnesium concentration (mmol/l)
0 1st2nd 3rd4th 5th
Normal value: 0.40–0.65 mmol/l. *MeanFS.D.
S. Kahraman et al. / Clinica Chimica Acta 334 (2003) 211–215
intensity of trauma (p<0.05). The lowest concentra-
tions of serum ionized Mg were observed in severe
brain injury group. Mean serum ionized Mg concen-
trations and standard deviation of all groups are
shown in Table 1 and Fig. 1. The mean concentrations
of serum ionized Mg for 5 days in three groups were
compared and there were significant differences
among the all groups by using Kruskal Wallis test
(p<0.001) (Fig. 1).
Irreversible tissue injury following trauma to the
central nervous system (CNS) is caused by mechan-
ical, physiological, and biochemical events. Known
as secondary injury, this delayed injury process is
multifactorial. Many secondary injury factors have
been identified. Indeed, calcium (Ca) has been
reported to be central in the final common pathway
leading to cell death via intracellular accumulation
Interestingly, although Mg is known to be man-
datory for virtually all cell functions, an important
role has not been readily accepted for this ion,
despite a number of studies demonstrating a poten-
tial regulatory role for Mg in the expression of cell
metabolism. There has been a lot of interest in the
role and effects of Mg ion in brain injury because
Mg affects many cellular functions, including trans-
port of potassium and calcium ions, and modulates
signal transduction, energy metabolism, and cell
proliferation . Decline in brain intracellular free
Mg concentration following experimental traumatic
brain injury has been widely reported in a number of
studies [2,4–6,8]. Nevertheless, in this point there is
a problem, which is the inability to assess rapidly
and early the degree or progression of brain injury at
tissue concentration using simple biochemical anal-
ysis. Serum total Mg may also be measured in brain
injury but some authors reported the findings not to
be significant [3,13]. Recently, there are some tech-
nical developments about serum ionized Mg meas-
urements [16–18]. Some authors found a declined
serum ionized Mg concentration after traumatic
brain injury in experimental rat models [9,19]. In
addition, a number of clinical problems in intensive
care unit patients were observed to have lower
serum concentrations of some electrolytes such as
Mg . Yet, after the trauma, serum ionized Mg
concentrations of patients with brain injury were
studied in few clinical trials . Furthermore, it
has not been speculated sufficiently the causes of
decline in serum ionized Mg concentrations and the
association of declined serum ionized Mg concen-
trations with the pathophysiology of neurotrauma in
patient with traumatic brain injury. Not only the rate
of decline in serum ionized Mg has not been
correlated with the severity of trauma, but also the
duration of decline in the serum ionized Mg con-
centrations has not been determined. For this reason,
we measured serum ionized Mg concentrations in
patients with traumatic brain injury that were clas-
sified by GCS. Finally, we found low concentrations
of serum ionized Mg in our patients. Serum ionized
Mg concentrations showed decline on posttraumatic
first day and then proportional increase on subse-
quent days. The decline of serum ionized Mg con-
centrations was shown to persist for at least 4 days
following traumatic brain injury (Fig. 1). The results
of this study showed that there was a correlation
between the magnitude of decline and the grade of
traumatic brain injury (mild–moderate–severe).
Namely, there was a highest decline of serum
ionized Mg concentrations in severe brain injury
Mg is abundant intracellular ion. Only about 1% of
Mg is present in the blood plasma and red cell .
Under normal conditions only 3–5% of the filtered
Mg is excreted in the urine. The development of Mg
deficiency is usually linked to an increased renal Mg
excretion. Following the traumatic brain injury, post-
traumatic neurogenic polyurea already occurs and
serum ionized Mg is excreted with urine. Beside this,
sympathetic nervous system is activated by trauma
due to increased intracranial pressure (ICP) and brain
herniation syndromes, which lead to compression and
distortion of the pontomedullary junction. Some stud-
ies showed that hyperadrenergic activity including
both a-1 adrenergic agonists such as phenylephrine
and h-adrenergic agonists such as norepinephrine
or isoproterenol stimulate efflux of Mg from many
cells . Consequently, efflux Mg may be lost with
urine. Moreover, the hormones of sympathetic ner-
vous system also increase serum glucose concen-
tration after brain trauma. When posttraumatic
S. Kahraman et al. / Clinica Chimica Acta 334 (2003) 211–215
hyperglycemia occurs, hypomagnesemia is seen along
with this situation. Several studies have shown that
among patients with diabetes mellitus, the frequency
of hypomagnesemia is higher than expected, and
that it is correlated with the degree of severity of
hyperglycemia . Posttraumatic hyperglycemia was
observed routinely in all patients at same values in this
In addition, several drugs, particularly diuretics,
cause Mg loss into the urine by inhibiting Mg reab-
sorption in the kidney . On the other hand,
management with diuretics and osmotic agents in
neurosurgical intensive care unit, to lower increased
ICP, may cause decline in serum ionized Mg concen-
tration. Although we used diuretics in severe and
moderate trauma groups, significant hypomagnesemia
was observed only in severe trauma group.
Although we cannot determine the exact reason of
decline in serum ionized Mg, it may provide a
reasonable and early assessment of the degree or
progression of brain injury syndromes at a tissue
concentration. After the brain trauma, severity of
decline in serum ionized Mg concentrations may be
used to explain the state of patient. Thus, measure-
ment of serum ionized Mg could be a marker for
follow-up in neurosurgical intensive care unit.
Some studies showed that Mg therapies provide
beneficial effects on neurological outcome and in-
crease brain intracellular free Mg concentration fol-
lowing traumatic brain injury [24,25]. With this
point of view, the next step of this study will be
further and detailed investigation of a correlation
between the MgSO4treatment in patients with brain
injury in state of hypomagnesemia and improvement
 Bareyre FM, Saatman KE, Helfaer MA, Sinson G, Weisser
JD, Brown AL, et al. Alterations in ionized and total blood
magnesium after experimental traumatic brain injury: relation-
ship to neurobehavioral outcome and neuroprotective effi-
ciency of magnesium chloride. J Neurochem 1999 (Jul);73:
 Cernak I, Savic VJ, Kotur J, Prokic V, Velijovic M, Grbovic
D. Characterization of plasma magnesium concentration and
oxidative stress following graded traumatic brain injury in
humans. J Neurotrauma 2000 (Jan);17:53–68.
 Cormio M, Robertson CS, Narayan RK. Secondary insults to
the injured brain. J Clin Neurosci 1997;4:132–48.
 Heath DL, Vink R. Traumatic brain axonal injury produces
sustained decline in intracellular free magnesium concentra-
tion. Brain Res 1996;738:150–3.
 Heath DL, Vink R. Blood free magnesium concentration de-
clines following graded experimental traumatic brain injury.
Scand J Clin Lab Invest 1998 (Apr);58:161–6.
 Heath DL, Vink R. Delayed therapy with magnesium up to 24
h following traumatic brain injury improves motor outcome.
J Neurosurg 1999;90:504–9.
 Hristova EN, Cecco S, Niemela JE, Rehak NN, Elin RT.
Analyzer dependent difference in results for ionized calcium,
ionized magnesium, sodium and Ph. Clin Chem 1995;41:
 Huijgen HJ, Sanders R, Cecco SA, Rehak NN, Sanders GT,
Elin RJ. Serum ionized magnesium:comparison of results ob-
tained with three ion-selective analysers. Clin Chem Lab Med
 McIntosh TK. Neurochemical sequelae of traumatic brain in-
jury. Cereb Brain Metab Rev 1994;6:109–62.
 McIntosh TK, Vink R, Yamakami I, Faden AI. Magnesium
protects against neurological deficit after brain injury. Brain
 Menon ZI, Altura BT, Benjamin JL, Cracco RQ, Altura BM.
Predictive value of serum ionized but not total magnesium
concentrations in head injuries. Scand J Clin Lab Invest 1995
 Polderman KH, Bloemers FW, Peerdeman SM, Girbes AR.
Hypomagnesaemia and hypophosphatemia at admission in
patients with severe head injury. Crit Care Med 2000 (Jun);
 Quamme GA. Renal magnesium handling: new insights in
understanding old problems. Kidney Int 1997;52:1180–95.
 Romani A, Scarpa A. Regulation of cell magnesium. Arch
Biochem Biophys 1992;298:1–12.
 Saris NEL, Mervaala E, Karppanin H, Khawaja JA, Lewen-
stam A. Magnesium an update on physiological, clinical and
analytical aspects. Clin Chim Acta 2000;294:1–26.
 Shapira Y, Lam AM, Artru C, Soltow LE. Ketamine alters
calcium and magnesium in tissue following experimental head
trauma in rats. J Cereb Blood Flow Metab 1993;13:962–8.
 Siesjo BK. Calcium and ischemic brain damage. Eur Neurol
 Siesjo BK, Bengtsson F. Calcium fluex, calcium antagonists,
and calcium related pathology in brain ischemia, hypoglyce-
mia, and spreading depression:a unifying hypothesis. J Cereb
Blood Flow Metab 1990;9:127–40.
 Thurman DJ, Branche CM, Sniezek JE. The epidemiology of
sports related traumatic brain injuries in the United States:
recent developments. J Head Trauma Rehabil 1998;13:1–8.
 Van Ingen HE, Huijgen HJ, Kok WTH, Sanders GPT. Ana-
lytical evaluation of Kone Microlyte determination of ionized
magnesium. Clin Chem 1994;40:52–5.
 Vink R. Magnesium and brain trauma. Magnes Trace Elem
 Vink R, Cernak I. Regulation of intracellular free magnesium
S. Kahraman et al. / Clinica Chimica Acta 334 (2003) 211–215
central nervous system injury. Front Biosci 2000 (Aug);1:
 Vink R, McIntosh TK. Pharmacological and physiological
effects of magnesium on experimental traumatic brain injury.
Magnes Res 1990;3:163–9.
 Vink R, McIntosh TK, Demediuk P, Faden AI. Decrease in
total and free magnesium concentration following traumatic
brain injury in rats. Biochem Biophys Res Commun 1987;
 Vink R, McIntosh TK, Demediuk P, Weiner MW, Faden AI.
Decline in intracellular free magnesium concentration is asso-
ciated with irreversible tissue injury following brain trauma.
J Biol Chem 1988;263:757–61.
S. Kahraman et al. / Clinica Chimica Acta 334 (2003) 211–215