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 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.