Duration not always definitive in convulsive status epilepticus

Timelines can help but shouldn't always be followed to the letter.

At the 2015 annual meeting of the American Epilepsy Society, held in Philadelphia last December, James J. Riviello Jr., MD, prefaced his review of an upcoming evidence-based guideline on treating convulsive status epilepticus with an important caveat.

The guideline, which appeared in the January/February Epilepsy Currents, provides a treatment algorithm based on seizure duration. But Dr. Riviello, a professor of neurology in the departments of epilepsy and neurology at Columbia University Medical Center in New York and one of the guideline's coauthors, cautioned attendees against following such timelines to the letter.

“Adhering to timelines kind of gives people a false sense of security. ‘If a seizure is going on, it's OK because the timeline says 10 to 20 minutes',” he said. “I really think that in a lot of situations you really need to think about what's the situation of the patient, what's the underlying disorder.”

With that proviso in mind, he walked attendees through the algorithm, which designates the first 0 to 5 minutes of seizure treatment as the stabilization phase. “This would be the phase in which the patient comes in and you're doing all the necessary things, the airway, the breathing, the circulation. You're assessing the oxygenation, you're starting EKG monitoring,” he said.

The stabilization phase is also the time to check blood glucose. Adults with a blood glucose level below 60 mg/dL should receive thiamine, 100 mg IV, followed by dextrose 50% in water, 50 mL IV. IV access should also be attempted to measure electrolytes, hematologic variables, toxicology if appropriate, and anticonvulsant drug levels, Dr. Riviello said.

After a seizure has lasted for 5 minutes, benzodiazepines are the initial therapy of choice, according to the guideline. There are level I indications for intramuscular midazolam dosed by weight (10 mg for patients >40 kg, 5 mg for patients 13 to 40 kg), IV lorazepam (0.1 mg/kg per dose to a maximum of 4 mg; the dose may be repeated once), and IV diazepam (0.15 to 0.2 mg/kg per dose; the dose may be repeated once), Dr. Riviello said.

“Now there really, with benzodiazepines, isn't really any maximum,” he noted. “If you're prepared to [monitor the steps of] airway, breathing, circulation, intubate, you can go up on these doses.”

If none of these drugs are available, IV phenobarbital can be used, although Dr. Riviello said that it takes a while for the drug to get into the brain. Rectal diazepam or intranasal midazolam is another option. “At least in our epilepsy patients, we've been using a lot of intranasal midazolam lately,” he noted, adding that in the United Kingdom, intranasal or buccal midazolam has become the rescue drug of choice as compared to the rectal form.

This initial therapy phase lasts for 5 to 20 minutes, according to the guideline. However, Dr. Riviello said, “I'm going to bring up my reservation again about timelines, because if you look at this, it sort of makes you think that 20 minutes is OK for somebody to have a seizure.”

During the second treatment phase, which the guideline defines as 20 to 40 minutes, there is no evidence-based therapy of choice, Dr. Riviello said. IV fosphenytoin is preferred, if it's available, over phenytoin, but if it isn't, phenytoin is acceptable, he said. IV valproic acid and IV levetiracetam are other options, although Dr. Riviello noted that a Swiss study found the latter to be less efficacious for seizures.

“We really don't know yet how fast the levetiracetam peaks in the brain,” he said. If none of these options are available, the guideline states that IV phenobarbital is again an acceptable alternative.

After 40 minutes, the treatment algorithm moves on to the third phase, in which there's no clear evidence to guide therapy, Dr. Riviello said. The guideline committee noted that clinicians may consider repeating second-line therapy or administering anesthetic doses of thiopental, midazolam, pentobarbital, or propofol, all with continuous EEG monitoring.

At each of these steps in the algorithm, Dr. Riviello said, the guideline recommends symptomatic medical care if the patient is back at baseline, but he considers this a problematic concept. “What I find difficult, especially when we consider the need for continuous EEG monitoring to rule out nonconvulsive status epilepticus, is what do we mean by back to baseline?” he said. “Most of these patients are not back to being awake and alert as they were pre-status. They may be moving in the right direction, they may be responding to painful stimuli, but they may not be actually back to baseline.”

Dr. Riviello also addressed the question of when a patient should be considered to have refractory status epilepticus. In the past, the condition was defined mainly by seizure duration, but now the transition phase should be thought of a moving line guided more by the underlying cause of the seizures, he stressed. “But having said that, people are now saying that the refractory status epilepticus is defined with failure of the second medication,” he said. “By that we mean initially we're going to give a benzodiazepine, if that fails we'll move on to second therapy...and then we move on to refractory status epilepticus.”

A trend toward earlier use of infusions has also developed, Dr. Riviello said. He discussed an international survey of experts done in 2012 that presented a case of epilepsy in an adult, a case of epilepsy in a child, and a refractory case of epilepsy in a child. The experts were polled on what they would use in each case as first-, second-, third-, fourth-, and fifth-line therapy; when they would move from standard therapy to IV therapy; how long they would continue continuous EEG monitoring; and when they would move to a continuous IV infusion. What they found, he said, was that for children, the experts were adhering strictly to stepwise protocols, whereas in adults, most experts moved to an infusion after the second medication rather than waiting.

“In the pediatric world, we were waiting more; in the adult world, they were going more after the failure of 2 drugs,” Dr. Riviello said. “I think that this would go along with how we're now defining refractory status epilepticus as failure of a first drug, a benzodiazepine, followed by the second medication. So the idea would be that then if your second med fails, and you're in the appropriate setting, well then, you start going to intravenous infusions.”

The survey also uncovered an interesting perspective regarding syndromic management of status epilepticus, he noted. For patients with convulsive status epilepticus, physicians will most likely treat first and ask questions about potential causes later.

“The person's having convulsive status epilepticus, and you're going to treat it,” Dr. Riviello said. “But if you get into things like...status epilepticus in someone with idiopathic generalized epilepsy, such as juvenile myoclonic epilepsy, then there might be more of a tailored approach to those patients. And that may be something that at some point people really want to focus on is the tailored management of status epilepticus for known patients with epilepsy.”