PHILADELPHIA—The American Epilepsy Society has created a new guideline for the acute treatment of status epilepticus that will be published in Epilepsy Currents. In offering a treatment protocol based on a timeline that begins with patient presentation, the document follows the same format as that of the Epilepsy Foundation of America’s 1993 guideline on the same topic, said James Riviello, MD, Director of Pediatric Neurology at New York University Langone Medical Center in New York City. Dr. Riviello described the guideline at the 69th Annual Meeting of the American Epilepsy Society.
Initial Treatment Has Strongest Evidence
The first five minutes after presentation are a stabilization phase during which physicians should check the patient’s airway, assess his or her oxygenation, measure blood glucose, and begin EKG monitoring, according to the guideline. For adults, physicians should administer thiamine, attempt IV access, collect electrolytes, perform hematology testing, measure levels of anticonvulsant drugs, and screen for toxins if appropriate.
If the patient continues to have seizures after five minutes, Level I evidence indicates that a benzodiazepine is the preferred initial therapy, according to the guideline. A physician may administer 5 mg of intramuscular midazolam to a patient who weighs between 13 kg and 40 kg, and 10 mg to a patient who weighs more than 40 kg. Alternative choices include 0.1 mg/kg of IV lorazepam, with a maximum dose of 4 mg, or 0.15 to 0.2 mg/kg of IV diazepam. Repeating the dose once is permissible, but may slightly increase the risk for respiratory depression. If none of the first three options is available, physicians may administer IV phenobarbital.
If the patient continues to have seizures at 20 minutes, physicians should consider a second therapy. The guideline’s recommendations for second-line treatment are based on Level U evidence, however. One option is IV phosphenytoin, which is preferred over phenytoin. IV valproic acid or IV levetiracetam are alternatives. It is unclear how quickly levetiracetam reaches maximum concentration in the brain, and data suggest that valproic acid may stop seizures more effectively than levetiracetam, said Dr. Riviello. If none of these options is available, a physician may administer IV phenobarbital.
If the second medication fails to stop the seizure by 40 minutes after presentation, the patient is considered to have refractory status epilepticus. No clear evidence is available to guide the choice of a third therapy, and the guideline does not address the treatment of refractory status epilepticus.
If a patient returns to baseline at any point, physicians should provide symptomatic medical care. Most patients do not immediately return to the level of alertness they had before onset of status epilepticus, however. “They may be moving in the right direction,” said Dr. Riviello. “They may be responding to painful stimuli, but they may not be actually back to baseline.”
Class I Evidence Informed the Recommendations
The publication of several recent Class I studies contributed to the development of the new guideline, said Dr. Riviello. The first was the 1998 investigation by the Veterans Affairs Status Epilepticus Cooperative Study Group, which indicated that lorazepam was superior to phenytoin. The problem with phenytoin is that it takes 10 or 15 minutes to infuse, said Dr. Riviello.
The Prehospital Treatment of Status Epilepticus study in 2001 showed that diazepam and lorazepam were superior to placebo. The researchers also observed that respiratory events were more common in controls than in treated patients. The prolonged seizure itself, rather than benzodiazepines, may be the cause of respiratory depression, said Dr. Riviello.
In 2011, the results of the Rapid Anticonvulsant Medication Prior to Arrival Trial suggested that intramuscular midazolam was superior to IV lorazepam. Unlike other benzodiazepines, midazolam is water soluble. The researchers found no difference in efficacy between lorazepam and diazepam in children. Similarly, in 2014, the Pediatric Emergency Care Applied Research Network found no evidence that lorazepam was superior to diazepam for the treatment of status epilepticus. “If you give diazepam for seizures, the seizures may return, so you have to give a more chronic anticonvulsant,” said Dr. Riviello. “Lorazepam lasts longer, so it has a longer period of efficacy.”
In 2011, Rossetti et al investigated valproate, phenytoin, and levetiracetam as second-line therapies for status epilepticus. They found that valproic acid was superior to levetiracetam. Approximately 25% of patients failed treatment with valproate, compared with about 49% of patients who failed treatment with levetiracetam. Phenytoin’s efficacy was between that of the other two medicines. The trial was not randomized, said Dr. Riviello.
The current guideline also drew upon the Neurocritical Care Society’s 2012 guideline for the evaluation and management of status epilepticus. This document describes initial treatment and also discusses management of status epilepticus. The authors discuss the doses and the side effects of the various medicines, and also the treatment of refractory status epilepticus and status epilepticus in pregnancy.