Refractory status epilepticus: frequency, risk factors, and impact on outcome

Arch Neurol. 2002 Feb;59(2):205-10. doi: 10.1001/archneur.59.2.205.


Background: Refractory status epilepticus (RSE) is a life-threatening condition in which seizures do not respond to first- and second-line anticonvulsant drug therapy. How often RSE occurs, risk factors that predispose to this condition, and the effect of failure to control seizures on clinical outcome are poorly defined.

Objective: To determine the frequency, risk factors, and impact on outcome of RSE.

Design: Retrospective cohort study.

Setting: Large academic teaching hospital.

Patients: Consecutive sample of 83 episodes of status epilepticus in 74 patients (mean age, 63 years).

Main outcome measures: Refractory status epilepticus was defined as seizures lasting longer than 60 minutes despite treatment with a benzodiazepine and an adequate loading dose of a standard intravenous anticonvulsant drug. Factors associated with RSE were identified using univariate and backward stepwiselogistic regression analyses.

Results: In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE (P=.03) and focal motor seizures at onset (P=.04) were identified as independent risk factors for RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line agent (usually phenobarbital). Although mortality was not increased (17% overall), RSE was associated with prolonged hospital length of stay (P<.001) and more frequent functional deterioration at discharge (P=.02).

Conclusions: Refractory status epilepticus occurs in approximately 30% of patients with SE and is associated with increased hospital length of stay and functional disability. Nonconvulsive SE and focal motor seizures at onset are risk factors for RSE. Randomized controlled trials are needed to define the optimal treatment of RSE.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / therapeutic use*
  • Benzodiazepines / therapeutic use*
  • Cohort Studies
  • Disabled Persons
  • Drug Resistance
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Status Epilepticus / epidemiology
  • Status Epilepticus / etiology
  • Status Epilepticus / pathology*


  • Anticonvulsants
  • Benzodiazepines