Should magnesium sulfate be used as first‑line seizure prophylaxis in patients with traumatic brain injury, or only after standard antiepileptic therapy fails?

Magnesium Sulfate Should NOT Be Used for Seizure Prophylaxis in Traumatic Brain Injury

Magnesium sulfate is not indicated for seizure prophylaxis in traumatic brain injury patients and should not be used as first-line or second-line therapy; levetiracetam or phenytoin are the recommended agents for high-risk patients requiring prophylaxis. 1

Evidence Against Magnesium Sulfate

The evidence definitively shows magnesium sulfate has no role in TBI seizure prophylaxis:

• A large randomized controlled trial of 499 TBI patients found magnesium sulfate was not neuroprotective and may have negative effects, with the lower-dose group performing significantly worse than placebo (p=0.007) and higher mortality observed in the higher-dose magnesium group. 2

• A systematic review and meta-analysis examining magnesium in severe TBI found no significant difference in all-cause mortality (RR 0.84,95% CI 0.54 to 1.33; P=0.46) and concluded there is a lack of evidence for magnesium pharmacotherapy in severe TBI. 3

• The only appropriate use of magnesium sulfate for seizures is specifically for eclampsia-related seizures, not traumatic brain injury. 4

Recommended First-Line Approach

For high-risk TBI patients requiring seizure prophylaxis, levetiracetam is the preferred first-line agent, not magnesium sulfate. 1

High-Risk Criteria Requiring Prophylaxis:

• Intracranial hemorrhage 1
• Depressed skull fracture 1
• Loss of consciousness or amnesia >24 hours 1, 5
• Age >65 years 1, 5
• Chronic subdural hematoma or past history of epilepsy 1

Dosing for Levetiracetam:

• Loading dose: 1000-1500 mg IV 1
• Maintenance: 500-1500 mg IV/PO twice daily 1
• Duration: Maximum 7 days unless actual seizures occur 1

Alternative Agent

• Phenytoin remains an acceptable alternative when rapid CSF penetration is prioritized, with loading dose of 18-20 mg/kg IV at maximum rate of 50 mg/min. 1

• Phenytoin has been the most extensively studied agent for post-traumatic seizure prophylaxis and is recommended by Brain Trauma Foundation guidelines. 6

Critical Management Pitfalls

• Avoid valproate due to increased mortality in TBI patients. 1

• Do not continue prophylactic antiepileptics beyond 7 days unless actual seizures occur, as prolonged use is not supported by evidence and may worsen neurological outcomes. 1

• Not all TBI patients require prophylaxis - overall prevention of post-traumatic seizures with antiepileptics cannot be broadly recommended based on analysis of over 2,700 patients across 11 clinical trials. 1, 7

Treatment of Active Seizures (Not Prophylaxis)

If actual seizures occur despite prophylaxis or in patients not receiving prophylaxis:

• Benzodiazepines (lorazepam) are first-line for active seizures. 1

• For refractory status epilepticus, levetiracetam, fosphenytoin, or valproate show equal efficacy (approximately 47% success rate). 1, 7