A retrospective observational study of current treatment for generalized convulsive status epilepticus
Introduction
Status epilepticus (SE) is a common medical and neurological emergency. The Richmond-based population study projected an estimated 126,000–195,000 cases of SE per year in the United States with annual mortality of 22% despite aggressive medical treatment [1]. Along with high mortality, SE is associated with significant morbidity, including cognitive dysfunction and risk of subsequent epilepsy [2].
Benzodiazepines (BZDs) are considered first-line treatment based on randomized controlled trials. The VA Cooperative Study, a large multicenter randomized controlled trial, compared 4 treatments for SE and found that, in patients with overt SE, 0.1 mg/kg lorazepam was the most successful, terminating episodes in 65% of the patients which was statistically significantly greater compared with phenytoin (PHT) and numerically greater compared with the other treatments [3]. Two other randomized controlled trials also suggest superiority of lorazepam [4], [5]. Although a recent double-blind placebo controlled trial found superiority of intramuscular midazolam over intravenous lorazepam for out-of-hospital initial treatment for status epilepticus, it is likely that many emergency physicians still use lorazepam [6]. It is probable that BZDs are used almost uniformly for patients with SE, but it is unclear what types or doses are being used in current clinical practice.
While there are excellent data to support the use of BZDs for first-line treatment, there are no large prospective randomized controlled trials to guide second-line treatment. The majority of data come from case reports or case series of individual drugs. There have been two single center randomized controlled trials that found equivalent efficacy of VPA and PHT [7], [8] and one which found VPA to be statistically significantly more effective than PHT (66% vs 42%, p = 0.046) [9]. Alvarez et al. recently reported a retrospective analysis of patients in a clinical protocol who received a standardized dose of benzodiazepine followed by a choice of PHT = 20 mg/kg, VPA = 20 mg/kg, or LEV = 20 mg/kg and found that VPA failed to control SE in 25.4% of the patients, PHT in 41.4%, and LEV in 48.3% [10].
There have been no observational studies to determine what the current state of clinical practice is for the treatment for GCSE. A 2003 survey of members of the critical care or epilepsy sections of the American Academy of Neurology reported that 95% of participants would use fosphenytoin or PHT as a second-line agent [11]; however, this study was based on a response to a clinical vignette and may not reflect true clinical practice. More recently, a 2012 survey of the American Critical Care Society also came to a similar conclusion [12].
The lack of rigorous systematic data to support decision-making beyond BZDs, especially the lack of data about second-line therapy, prompted us to study how GCSE is actually treated in routine emergency room practice. We hypothesize that treatment is likely to be highly variable, especially benzodiazepine use, and that some routinely used treatments may be more effective than others.
Section snippets
Methods
We retrospectively reviewed the ICD9 coding database for visits to the University of Virginia Medical Center from 1/1/2006 to 12/31/2010 for the primary codes of 345.3 “grand mal status”, 345.2 “petit mal status”, and 345.7 “epilepsia partialis continua” and reviewed the medical records from each case to determine if they met criteria for acute GCSE originally presenting to an emergency department during that admission. The remaining primary epilepsy codes from the same database, 345.0–345.9,
Statistical analysis
Comparisons among the treatment groups were performed using two-tailed Fisher's exact test. The significance level for all tests was p < 0.05. Ninety-five percent confidence levels surrounding mean antiepileptic doses and antiepileptic levels were calculated when available.
Results
We identified 177 episodes of acute GCSE occurring in 170 patients. Of these episodes, 121 (68%) first presented to the University of Virginia Emergency Department, while 56 (32%) were seen initially in a community hospital. Demographic data and other characteristics of the population are presented in Table 1.
All patients except for one received BZDs as first-line treatment either in the prehospital or emergency room setting. The single patient who did not receive benzodiazepine was described
Discussion
To our knowledge, this is the first observational study of the current practice of acute emergency room treatment for GCSE in which emergency physicians were free to choose any treatment. There is currently a paucity of good quality evidence to guide second-line treatment for GCSE. As a result, treatment decisions are often guided by small nonrandomized studies, past experience, side effect profiles of medications, consensus opinion, or institutional or organizational treatment protocols.
Disclosures
Dr. Langer has no disclosures to report. Dr. Fountain has not received any personal funding but is the principal investigator on research grants awarded to the University of Virginia from UCB, SK Life Sciences, Medtonic, Neuropace, and NIH.
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