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. DESIGN:A prospective evaluation of the cerebrospinal fluid total and ionized magnesium concentration, [Mg], 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 [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. MEASUREMENTS AND MAIN 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.