Treatment of Refractory Status Epilepticus with Pentobarbital, Propofol, or Midazolam: A Systematic Review

Abstract

Summary:Background: New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients.Methods: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to "seizure suppression" versus "EEG background suppression").Results: Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n ‫ס‬ 54), PRO (n ‫ס‬ 33), and PTB (n ‫ס‬ 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n ‫ס‬ 59), titration of treatment to EEG background suppression (n ‫ס‬ 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001).Conclusions: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.

Short-term mortality and prognostic factors related to status epilepticus

“…The reported incidence of refractory SE is 9 to 38%, and mortality in that group is generally higher than in other SE patients, from 16 to 100% 24 . The incidence (36.2%) and mortality rate (57.9%) of refractory SE in our sample were similar to those in other studies.…”

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

“…EEG may also be used to gauge success at achieving electrographic suppression or burst suppression, which has been associated with decreased likelihood of relapsed status epilepticus following barbiturate therapy [95] with fewer breakthrough seizures [96].…”

An Emergency Medicine Perspective for Non-Convulsive Status Epilepticus Patients: Intravenous Midazolam

“…The studies conducted on the termination of seizures in NCSE patients at the emergency department are limited, whereas the medications used for standard SE patients are known to have benefits (10). In a review by Maganti et al (8) on NCSE, they reported that IV benzodiazepines could be given as first-line therapy followed by IV phenytoin, phenobarbital, or valproic acid.…”