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  • Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.

Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.

Critical care (London, England) (2014-06-03)
Deborah Pugin, Brandon Foreman, Gian Marco De Marchis, Andres Fernandez, J Michael Schmidt, Barry M Czeisler, Stephan A Mayer, Sachin Agarwal, Christine Lesch, Hector Lantigua, Jan Claassen
ABSTRACT

Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables. cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.

MATERIALS
Product Number
Brand
Product Description

Phenytoin, European Pharmacopoeia (EP) Reference Standard
Phenytoin for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Phenytoin, United States Pharmacopeia (USP) Reference Standard
Supelco
Phenytoin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
5,5-Diphenylhydantoin, ≥98%