PHILADELPHIA -- Continuous infusions for refractory status epilepticus may be more harmful than intermittent doses of drugs, researchers reported here.
In a prospective cohort study, children who continued to seize for more than 30 minutes took longer to control with continuous infusions than those who were given intermittent doses of drugs, , of Children's Hospital Colorado, reported during a press briefing at the American Epilepsy Society meeting.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- In a prospective nonrandomized study of 111 pediatric patients presenting with status epilepticus, continuous infusions of anticonvulsants were found to be less effective at stopping seizures than intermittent boluses of anticonvulsants, with an average time to seizure cessation of 155 minutes vs 110.5 minutes (P<0.01), respectively.
- Continuous infusions were also associated with more adverse outcomes such as hypotension and need for vasopressors compared to intermittent boluses, with three patients receiving continuous infusions dying compared to none in the intermittent group.
They also had worse outcomes in terms of greater need for blood pressure medications and a longer stay in the intensive care unit, Chapman said.
"To me, the take-home point is that maybe we don't need to put everyone in suppression, maybe we don't have to go to ketamine as the third drug," Chapman said. "Maybe it's better to continue to do intermittent doses of medications like fosphenytoin."
First- and second-line treatments for status epilepticus are well established. Protocols generally recommend a benzodiazepine as a first step followed by an anticonvulsant if that doesn't work. If those options fail, the third step is a little less clear, and part of that debate is whether clinicians should give intermittent boluses or continuous infusions of drugs, Chapman explained.
Recent research, however, has suggested that continuous therapy may do more harm than good, especially for certain seizure etiologies, whether it be head injury, stroke, or meningitis, Chapman said.
To assess the optimal third step, the researchers assessed 111 patients treated for status epilepticus at nine tertiary pediatric hospitals in the U.S. from June 2011 to June 2013. About half had continuous infusions and the other half had intermittent boluses.
They found no differences in overall seizure duration between groups. About 85% of patients seized for longer than 30 minutes in the hospital, and among these patients, time to seizure cessation was significantly longer in those who had continuous infusions (155 minutes versus 110.5 minutes, P<0.01), Chapman reported.
It's unclear why that is, Chapman said, but it could have something to do with the greater morbidity associated with continuous infusions. Those who had continuous infusions had more hypotension and a greater use of vasopressors than those who had bolus dosing, and these patients also had a longer stay in the pediatric ICU (10 days versus 2 days, P<0.001).
All three of the patients who died were in the continuous therapy arm, he added.
When asked whether patients given continuous therapy are worse off to begin with compared with those on intermittent dosing, Chapman said it was hard to distinguish since all patients who are continuously seizing appear to be in bad shape.
"That was hard for us to distinguish, but when we looked to see whether the patient was continuously seizing, we found that didn't predict who went into each arm," he said.
He concluded that continuous infusions may not be appropriate for all patients with resistant status epilepticus, but that further research needs to be done on what exactly this "third-step" should be.
"We want to stop seizures because they're detrimental to the child, so we tend to be quite aggressive at doing that," he said. "With continuous infusions, you can dial it up and make the brain flat real quick, sometimes at the expense of blood pressure, longer length or stay, added costs, or infection."
Disclosures
Chapman disclosed no financial relationships with industry.
Primary Source
American Epilepsy Society
Chapman K, et al "Continuous intravenous therapy versus intermittent bolus therapy for pediatric refractory status epilepticus" AES 2015; Abstract 1.123.