Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus

Neurology. 2001 Sep 25;57(6):1036-42. doi: 10.1212/wnl.57.6.1036.


Background: Although cIV-MDZ has emerged as a popular alternative to barbiturate therapy for refractory status epilepticus (RSE), experience with its use for this indication is limited.

Objective: - To evaluate the efficacy of continuous intravenous midazolam (cIV-MDZ) for attaining sustained seizure control in patients with RSE.

Methods: The authors reviewed 33 episodes of RSE treated with cIV-MDZ in their neurologic intensive care unit over 6 years. All patients were monitored with continuous EEG (cEEG). MDZ infusion rates were titrated to eliminate clinical and EEG seizure activity; cIV-MDZ was discontinued once patients were seizure-free for 24 hours. Acute treatment failures (seizures 1 to 6 hours after starting cIV-MDZ), breakthrough seizures (after 6 hours of therapy), post-treatment seizures (within 48 hours of discontinuing therapy), and ultimate treatment failure (frequent seizures that led to treatment with pentobarbital or propofol) were identified.

Results: All patients were in nonconvulsive SE at the time cIV-MDZ was started; the mean duration of SE before treatment was 3.9 days (range 0 to 17 days). In addition to benzodiazepines, 94% of patients had received at least two antiepileptic drugs (AED) before starting cIV-MDZ. The mean loading dose was 0.19 mg/kg, the mean maximal infusion rate was 0.22 mg/kg/h, and the mean duration of cIV-MDZ therapy was 4.2 days (range 1 to 14 days). Acute treatment failure occurred in 18% (6/33) of episodes, breakthrough seizures in 56% (18/32), post-treatment seizures in 68% (19/28), and ultimate treatment failure in 18% (6/33). Breakthrough seizures were clinically subtle or purely electrographic in 89% (16/18) of cases and were associated with an increased risk of developing post-treatment seizures (p = 0.01).

Conclusions: Although most patients with RSE initially responded to cIV-MDZ, over half developed subsequent breakthrough seizures, which were predictive of post-treatment seizures and were often detectable only with cEEG. Titrating cIV-MDZ to burst suppression, more aggressive treatment with concurrent AED, or a longer period of initial treatment may reduce the high proportion of patients with RSE who relapse after cIV-MDZ is discontinued.

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Electroencephalography / drug effects*
  • Female
  • Humans
  • Infusions, Intravenous
  • Intensive Care Units
  • Male
  • Midazolam / administration & dosage*
  • Midazolam / adverse effects
  • Middle Aged
  • Monitoring, Physiologic*
  • Recurrence
  • Status Epilepticus / drug therapy*
  • Treatment Failure


  • Anticonvulsants
  • Midazolam