Antiepileptic Dose Delays Associated with Worse Outcomes

January 24, 2019
Kenneth Bender, PharmD, MA

A delay in giving the first dose of an antiepileptic for pediatric status epilepticus is common and associated with increased seizure duration.

Nathan Cohen, MD

A delay in administering the first dose of an antiepileptic drug (AED) for pediatric status epileptics (SE) was found to occur frequently and was associated with increased seizure duration and morbidity, in a recently published assessment of records from a major, metropolitan children’s treatment center.

"We found that there was significant delay to first dose of anti-seizure medication and sometimes inappropriate medication selection in patients presenting to our emergency department with status epilepticus," said study author Nathan Cohen, MD, Child Neurology Fellow, Children's National Health System, Washington, DC, in an interview with MD Magazine®.

Cohen and colleagues sought to ascertain the timing of first antiepileptic dose for SE at their institution relative to guidelines and the related outcomes, with recognition that delays pose a significant barrier to successful treatment.

"The timing of administration of anti-seizure medications is considered an important variable in preventing seizure-related brain injury from excitotoxicity and neuronal cell death," the investigators wrote.

"Status epilepticus is an emergency which may cause patient harm," Cohen told MD Mag. "Well-accepted treatment guidelines exist for the management of status epilepticus including dosing and timing of medication escalation."

Cohen and colleagues identified 247 patients, median age 45 months, presenting to the emergency department between 2009 and 2015 and having discharge diagnosis of seizure or SE and concomitant discharge prescription for AED. Of these, 141 had sufficient documentation in the medical record for the retrospective review to determine medication dosing and timing related to seizure onset.

The investigators reported that the median time to first dose of an AED, whether given by parent, EMT or in the ED, was 25 minutes (interquartile range [IQR] 7-56 minutes). The median duration of seizure was 59.5 minutes in the 12 patients who received the first dose in under 5 minutes, and 151.5 minutes in the 34 patients receiving the first dose at 60 minutes or more after seizure onset. Further, they found that a longer time to first dose was associated with increased risk of intubation and requirement for admission to the intensive care unit.

There were paradoxes in the data, however. Patients treated at less than 60 minutes were more likely to have shorter duration of SE, but also more likely to have received more doses; while others responded to the first dose despite a longer time before receiving it.

Cohen and colleagues suggested several possible explanations for these paradoxical findings, including a more rapid recognition and escalation in patients with a known diagnosis of epilepsy who were assumed to be presenting with refractory disease. They note, however, that such factors were not discernable from their data.

"The design of our study did not allow us to pinpoint areas causing variability in treatment," Cohen commented. "However, it would be important from a systems perspective to encourage institutional adherence to the established status epilepticus treatment guidelines."

"Hospitals should work to educate families, caregivers, and providers about the need for rapid and appropriate recognition and treatment of status epilepticus, " he recommended, "as many families do not use rescue medications prescribed to them for home use.

The study, “Timing and Selection of First Antiseizure Medication in Patients with Pediatric Status Epilepticus,” was published in Epilepsy Research.

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