Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

 

Settings:

• 57 US hospitals: 26 sites for adults only, 18 sites enrolling only children, 13 sites enroll both.

Patients:

• 384 patients whose ages were 2 years and older. 
• Patients who continued to have generalized seizure for at least 5 minutes after “accepted” cumulative dose of benzodiazepines.

Intervention:

• levetiracetam at a dose of 60 mg per kilogram (maximum, 4500 mg),
• Fosphenytoin at a dose of 20 mg PE per kilogram (maximum, 1500 mg PE),
• valproate at a dose of 40 mg per kilogram (maximum 3000 mg)

Comparison:

• Patients > 32 kg total body weight:  diazepam of 10 mg; Lorazepam 4mg Intravenously; midazolam 10 mg intravenously or intramuscularly.
• Patients < 32 kg total body weight: diazepam at a dose of 0.3 mg per kilogram (administered intravenously or rectally), lorazepam at a dose of 0.1 mg per kilogram (administered intravenously), or midazolam at a dose of 0.3 mg of per kilogram (administered intramuscularly) or 0.2 mg per kilogram (administered intravenously)

Outcome: absence of clinical seizure at 60 minutes after infusion of medication.

Study Results:

• Rates of cessation of status epilepticus were similar in all 3 groups: 47% of levetiracetam vs. 45% Fosphenytoin vs. 46% for valproate.
• Fosphenytoin was associated with non-significantly higher rate of hypotension (3.2%) vs other drugs.
• Levetiracetam was associated with non-significantly higher rate of death (4.7%) vs. other drugs.
• All three medication was associated with similar rate of intubation within 60 minutes of drug infusion.

Discussion:

• The median time interval from start to cessation of status epilepticus appeared to be shorter for valproate but there was no formal analysis yet,
• Valproate (7.0 minutes) vs. levetiracetam (11.7 minutes) vs. Fosphenytoin (11.7 minutes)

Conclusion:

• Three medications, Fosphenytoin, levetiracetam, valproate were equally effective.

References

Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators.

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795.