Intravenous Magnesium Sulfate Does Not Increase Ventricular CSF Ionized Magnesium Concentration of Patients with Intracranial Hypertension Randall P. Brewer, Augusto Parra, Cecil O. Borel, Michael B. Hopkins, and James D. Reynolds Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA Summary: Magnesium sulfate has attracted interest as a potential neuroprotectant but passage of magnesium ion into the central nervous system has not been well docu- mented. For this study, we quantified plasma and cerebrospinal fluid (CSF) ionized magnesium concentration after systemic magnesium sulfate infusion in patients with intracranial hypertension. Patients (N = 9) received an intravenous infusion of 5 g/20 mmol magnesium sulfate (125 mL of a 4% wt/vol solution) over 30 minutes. Before and after dosing, CSF (from an indwelling ventricular catheter) and blood samples were collected at hourly intervals. Ionized magnesium concentration in all samples was de- termined using an electrolyte analyzer. Baseline plasma and CSF ionized magnesium concentrations were 0.58 ± 0.05 and 0.82 ± 0.06 mmol/L, respectively. Intravenous magnesium sulfate infusion significantly increased plasma ionized magnesium concen- tration (peak, 0.89 ± 0.11 mmol/L), but CSF magnesium levels did not change during the 4-hour study. Systemic administration of magnesium sulfate failed to increase CSF ion- ized magnesium concentration in patients with intracranial hypertension despite increas- ing plasma magnesium levels by >50%. Key Words: Cerebrospinal fluid—Intracranial hypertension—Magnesium Magnesium ion (Mg) is an essential cofactor for many enzymatic reactions and an important regulator of excitatory neurotransmission in the central nervous system (CNS). It is the latter role that has produced considerable interest in the use of Mg as a pharmaco- logic neuroprotective agent (1). To that end, assessing the human therapeutic potential of Mg in cases of stroke and traumatic brain injury is the primary goal of several randomized clinical trials (e.g., [2]). One of the key tenets for an effective neuroprotectant is the ability to enter the CNS. Despite this necessity, few studies have been conducted to determine whether central Mg levels actually increase after dosing. After systemic administration, usually in the form of magne- sium sulfate (MgSO 4 ), blood Mg is present in three forms: 27%–34% is protein-bound; 8%–12% is com- plexed to small anions; and the remainder is in the free, hydrated ion form, Mg 2+ (3). While clinical laborato- ries generally measure total Mg concentration, it is im- portant to realize that only the ionized or “free” fraction of Mg in the blood is physiologically active (4). By ex- tension, only the ionized form of Mg has the potential to enter the CNS. However, its divalent state does sug- gest that such passage could be hindered. Previous investigations that quantitated central Mg concentration after systemic administration of a Mg salt have yielded equivocal results. Hallak et al. (5) re- ported increased Mg in both rat cerebrospinal fluid (CSF) and brain 2 hours after MgSO 4 injection, whereas Kim et al. (6) reported no change in rat brain parenchymal Mg concentration after 5 days of MgSO 4 infusion, this despite observing almost a threefold in- crease in plasma Mg. In humans, preeclamptic patients receiving MgSO 4 therapy had higher CSF total Mg lev- els compared to control parturients (7), although infu- sion of MgSO 4 during craniotomy, which increased plasma Mg concentration by 380%, only produced a 15% increase in CSF Mg (8). Address correspondence and reprint requests to James D. Reynolds, Division of Women’s Anesthesia, Departments of Anesthesiology and Surgery, Box 3094, Duke University Medical Center, Durham, NC 27710, USA. Clinical Neuropharmacology Vol. 24, No. 6, pp. 341–345 © 2001 Lippincott Williams & Wilkins, Inc., Philadelphia 341