Second-line status epilepticus treatment: Comparison of phenytoin, valproate, and levetiracetam

Abstract

SUMMARYPurpose: Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available. Methods: Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni-and multivariable statistical analyses were applied to compare the three agents. Key Findings: Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors. Significance: Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

“…Class III trials support efficacy and safety of valproic acid as first-line therapy (26,27), second-line therapy (31,32), and refractory therapy (66). Evidence for use of levetiracetam and lacosamide is limited to retrospective studies (67)(68)(69)(70)(71)(72). Given the favorable pharmacokinetic characteristics and adverse-effect profiles for these medications compared with fosphenytoin and phenobarbital, comparative trials of these medications as second-line therapy will provide vital evidence to improve future treatment of convulsive status epilepticus.…”

Intravenous levetiracetam of hospitalized patients in Srinagarind Hospital

“…The clinical data on efficacy and order of intravenous LEV in SE are still controversial. Alvarez et al (2011) reported that intravenous LEV was not as effective as sodium valproate for seizure control in SE after benzodiazepine treatment. In contrast, Gámez-Leyva et al (2009) showed that intravenous LEV had potential effectiveness for SE treatment.…”

The SAMUKeppra study in prehospital status epilepticus: lessons for future study

“…An analysis of publications until 2009 reported that 707 patients with various forms of SE had been safely treated with LEV, with a success rate was about 70% (3). In ESE, the efficacy of LEV was reported as 51.7% in one study (23) and 73.2% in another study (21). VPA has been used for the treatment of SE in prospective or retrospective series and two randomized open trials (12).…”

“…SE did not respond to 25.4% of cases treated with VPA, 41.4% treated with FOS, and 48.3% treated with LEV (23). Importantly, this was an open, nonrandomized trial, and the severity of SE in VPA treated patients may have been less than the other two groups, which may explain part of the apparent superiority of VPA in the study (23). Two ESE treatment studies were open, randomized, prospective studies.…”