Abstracts

Rationale: Refractory status epilepticus (RSE), defined as continuous or recurrent seizure activity for one hour or more without recovery of baseline clinical state despite treatment, is a clinically and electrophysiologically heterogeneous entity whose management is often problematic. While there are data indicating that Levetiracetam (LEV) may have a role in the treatment of RSE, either in lieu of anesthetic antiepileptic medications (aAEDs, include midazolam, propofol and pentobarbital) or when attempting to taper them, there are few data that address the rapidity with which LEV may be safely titrated in this setting. We reviewed cases of RSE with the primary aim of assessing the tolerability of rapid titration of LEV in RSE. Methods: We identified 40 consecutive patients with RSE aged 18 or older treated between October 2006 and April of 2007 at Montefiore Medical Center. Patients were distinguished according to their LEV exposure as follows: Group 1: naive to LEV and received at least 2000 mg of LEV in the first 24 hours of exposure. Group 2: naive to LEV and received less than 2000 mg of LEV in the first 24 hours. Group 3: received LEV prior to and during treatment for RSE. Group 4: not exposed to LEV prior to or during treatment for RSE. Records were assessed from the time of onset of RSE through the calendar day after the endpoint was reached (resolution, death or cessation of attempts to treat RSE) to extract the etiology of RSE and identify adverse events (AEs) definitely or probably related to RSE treatment. Identification and attribution of AEs deferred to the clinician’s judgment when documented and was supplemented by clinical information contained in medical records and imaging, laboratory and EEG databases. Events were not classified as AEs if they may have been an intended effect of an AED or if its contribution was uncertain. Results: LEV was administered orally or by NG tube. The four treatment groups included 8, 19, 3 and 10 patients respectively. There were no significant differences in the duration of RSE, average number of concomitant AEDs, fraction of patients intubated and receiving aAEDs nor rates of reintroduction of aAEDs after attempted tapering nor reintubation amongst the four treatment groups. There were no significant differences between the rates of adverse events amongst the four groups (p>0.05, ANOVA). One case of psychosis was judged to have been probably associated with low initial dose LEV. No other AEs were associated with LEV. AEs attributed to particular AEDs are listed in Table 1. Hyponatremia has been reported with LEV administration and is frequent in hospitalized patients. Individually analyzed and pooled data did not demonstrate significant changes in sodium concentration with either LEV regime. Conclusions: Because of the retrospective nature of this study and the heterogeneity of the patients’ clinical characteristics and treatment regimens, it is not possible to compare the efficacy of particular AEDs in RSE from these data. These preliminary data do suggest that the introduction of LEV at doses of 2g or more in the first 24 hours may be fairly well tolerated in RSE patients.