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Critical Care Medicine:
doi: 10.1097/01.CCM.0000156293.35868.B2
Neurologic Critical Care

Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia*

McKee, J Andrew BSE; Brewer, Randall P. MD; Macy, Gary E. RN, MSN, CCNP; Phillips-Bute, Barbara PhD; Campbell, Kurt A. BS; Borel, Cecil O. MD; Reynolds, James D. PhD; Warner, David S. MD

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Abstract

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 Mg2+ into cerebrospinal fluid in patients with brain injury requiring ventricular drainage.

Design: A prospective evaluation of the cerebrospinal fluid total and ionized magnesium concentration, [Mg2+], during sustained hypermagnesemia was performed.

Setting: Neurosciences intensive care unit at a major teaching institution.

Patients: 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.

Interventions: Patients underwent 24 hrs of induced hypermagnesemia during which total and ionized cerebrospinal fluid [Mg2+] was measured. Serum [Mg2+] was adjusted to 2.1–2.5 mmol/L. Cerebrospinal fluid [Mg2+] was measured at baseline, at 12 and 24 hrs after onset of infusion, and at 12 hrs following infusion termination.

Measurements and Main Results: At baseline, total (1.25 ± 0.14 mmol/L) and ionized (0.80 ± 0.10 mmol/L) cerebrospinal fluid [Mg2+] was greater than serum total (0.92 ± 0.18 mmol/L) and ionized (0.63 ± 0.07 mmol/L) [Mg2+] (p < .05). Total (1.43 ± 0.13 mmol/L) and ionized (0.89 ± 0.12 mmol/L) cerebrospinal fluid [Mg2+] 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 [Mg2+]. Regulation of cerebrospinal fluid [Mg2+] is largely maintained following acute brain injury and limits the brain bioavailability of MgSO4.

© 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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