A randomized trial for the treatment of refractory status epilepticus.
BACKGROUND
Refractory status epilepticus (RSE) has a mortality of 16-39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to assess the effectiveness (RSE control, adverse events) of the first course of propofol versus barbiturates in the treatment of RSE.


METHODS
In this randomized, single blind, multi-center trial studying adults with RSE not due to cerebral anoxia, medications were titrated toward EEG burst-suppression for 36-48 h and then progressively weaned. The primary endpoint was the proportion of patients with RSE controlled after a first course of study medication; secondary endpoints included tolerability measures.


RESULTS
The trial was terminated after 3 years, with only 24 patients recruited of the 150 needed; 14 subjects received propofol, 9 barbiturates. The primary endpoint was reached in 43% in the propofol versus 22% in the barbiturates arm (P = 0.40). Mortality (43 vs. 34%; P = 1.00) and return to baseline clinical conditions at 3 months (36 vs. 44%; P = 1.00) were similar. While infections and arterial hypotension did not differ between groups, barbiturate use was associated with a significantly longer mechanical ventilation (P = 0.03). A non-fatal propofol infusion syndrome was detected in one patient, while one subject died of bowel ischemia after barbiturates.


CONCLUSIONS
Although undersampled, this trial shows significantly longer mechanical ventilation with barbiturates and the occurrence of severe treatment-related complications in both arms. We describe practical issues necessary for the success of future studies needed to improve the current unsatisfactory state of evidence.
Rossetti
Andrea O
AO
Department of Neurology, CHUV et Université de Lausanne, Lausanne, Switzerland. andrea.rossetti@chuv.ch
Milligan
Tracey A
TA
Vulliémoz
Serge
S
Michaelides
Costas
C
Bertschi
Manuel
M
Lee
Jong Woo
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001463:Barbiturates / Q000008:administration & dosage / Q000009:adverse effects; D003128:Coma / Q000139:chemically induced*; D003422:Critical Care / Q000379:methods*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects*; D011446:Prospective Studies; D013226:Status Epilepticus / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
D001463:Barbiturates; D006993:Hypnotics and Sedatives; D015742:Propofol