Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia.
OBJECTIVE
Based on preclinical investigations, magnesium sulfate (MgSO4) has gained interest as a neuroprotective agent. However, the ability of peripherally administered MgSO4 to penetrate the blood-brain barrier is limited in normal brain. The current study measured the passage of intravenously administered Mg into cerebrospinal fluid in patients with brain injury requiring ventricular drainage.


METHODS
A prospective evaluation of the cerebrospinal fluid total and ionized magnesium concentration, [Mg], during sustained hypermagnesemia was performed.


METHODS
Neurosciences intensive care unit at a major teaching institution.


METHODS
Thirty patients with acute brain injury secondary to subarachnoid hemorrhage, traumatic brain injury, primary intracerebral hemorrhage, subdural hematoma, brain tumor, central nervous system infection, or ischemic stroke were studied.


METHODS
Patients underwent 24 hrs of induced hypermagnesemia during which total and ionized cerebrospinal fluid [Mg] was measured. Serum [Mg] was adjusted to 2.1-2.5 mmol/L. Cerebrospinal fluid [Mg] was measured at baseline, at 12 and 24 hrs after onset of infusion, and at 12 hrs following infusion termination.


RESULTS
At baseline, total (1.25 +/- 0.14 mmol/L) and ionized (0.80 +/- 0.10 mmol/L) cerebrospinal fluid [Mg] was greater than serum total (0.92 +/- 0.18 mmol/L) and ionized (0.63 +/- 0.07 mmol/L) [Mg] (p < .05). Total (1.43 +/- 0.13 mmol/L) and ionized (0.89 +/- 0.12 mmol/L) cerebrospinal fluid [Mg] was maximally increased by 15% and 11% relative to baseline, respectively, during induced hypermagnesemia (p < .05).


CONCLUSIONS
Hypermagnesemia produced only marginal increases in total and ionized cerebrospinal fluid [Mg]. Regulation of cerebrospinal fluid [Mg] is largely maintained following acute brain injury and limits the brain bioavailability of MgSO4.
McKee
J Andrew
JA
Neurosciences Intensive Care Unit, Duke University Medical Center, Durham, NC, USA.
Brewer
Randall P
RP
Macy
Gary E
GE
Phillips-Bute
Barbara
B
Campbell
Kurt A
KA
Borel
Cecil O
CO
Reynolds
James D
JD
Warner
David S
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008274:Magnesium / Q000134:cerebrospinal fluid*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate; D008274:Magnesium