Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia.
Level 4 - case-series / case-control
Prospective single-arm interventional study (case series) without a control group
PubMed 15753761 · doi:10.1097/01.ccm.0000156293.35868.b2
What was done
Researchers evaluated total and ionized magnesium concentrations in the cerebrospinal fluid (CSF) and serum of 30 neuro-ICU patients with acute brain injury (subarachnoid hemorrhage, traumatic brain injury, intracerebral hemorrhage, subdural hematoma, brain tumor, CNS infection, or ischemic stroke) who required external ventricular drainage. Patients received continuous intravenous magnesium sulfate for 24 hours to target a serum magnesium level of 2.1–2.5 mmol/L. Total and ionized CSF magnesium levels were measured at baseline, 12 and 24 hours during infusion, and 12 hours post-infusion.
What was found
At baseline, total CSF magnesium (1.25 ± 0.14 mmol/L) and ionized CSF magnesium (0.80 ± 0.10 mmol/L) were significantly higher than total serum magnesium (0.92 ± 0.18 mmol/L) and ionized serum magnesium (0.63 ± 0.07 mmol/L) (p < .05). During induced hypermagnesemia, total CSF magnesium peaked at 1.43 ± 0.13 mmol/L (a 15% increase relative to baseline, p < .05) and ionized CSF magnesium peaked at 0.89 ± 0.12 mmol/L (an 11% increase relative to baseline, p < .05).
Why it matters
Even in acute brain injury, central regulation of magnesium is largely preserved, meaning high-dose peripheral magnesium sulfate produces only marginal increases in CSF magnesium. This limited penetration provides a pharmacokinetic explanation for why magnesium sulfate may fail to show clinical neuroprotection in brain injury trials.
Limits
The study had a small sample size (n = 30) with a heterogeneous mix of acute brain injury etiologies. It lacked a non-treated control group. Measurements were confined to ventricular CSF, which may not directly reflect brain parenchymal or intracellular magnesium concentrations, and clinical neurological outcomes were not assessed.
Cited by
- supports In humans, an increase of up to 300% in blood magnesium results in less than a 19% change in cerebrospinal fluid magnesium content.