Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review.
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 = 54), PRO (n = 33), and PTB (n = 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 = 59), titration of treatment to EEG background suppression (n = 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.
Claassen
Jan
J
Department of Neurology, Division of Critical Care Neurology, and the Comprehensive Epilepsy Center, Neurological Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Hirsch
Lawrence J
LJ
Emerson
Ronald G
RG
Mayer
Stephan A
SA
D000927:Anticonvulsants / Q000627:therapeutic use*; D018757:GABA Modulators / Q000627:therapeutic use*; D006801:Humans; D008874:Midazolam / Q000627:therapeutic use*; D010424:Pentobarbital / Q000627:therapeutic use*; D015742:Propofol / Q000627:therapeutic use*; D013226:Status Epilepticus / Q000188:drug therapy*
D000927:Anticonvulsants; D018757:GABA Modulators; D010424:Pentobarbital; D008874:Midazolam; D015742:Propofol