Abstracts

Rationale: There has been a growing interest in the use of midazolam in the treatment of neonatal status epilepticus (NSE). As a first line treatment, phenobarbital has only 50% efficacy, with many patients continuing to have refractory seizures for several days. Treatment has become focused on electrographic, rather than clinical, cessation of seizures, in an attempt to improve clinical outcomes. We recently described five infants with electrographic NSE refractory to phenobarbital, with resolution of NSE demonstrated by continuous video EEG upon initiation of midazolam infusion. Through continued use over the past two years, further insight has been garnered regarding the potential role of midazolam in treatment of these critically ill infants. Methods: All high-risk infants admitted to the Neonatal Intensive Care Unit with clinical seizures or moderate to severe hypoxic-ischemic injury were monitored on continuous video EEG. At time of seizure recognition, all infants initially received a loading dose of phenobarbital, which was repeated to total of 30-60 mg/kg. NSE was defined as seizure activity occupying greater than 50% of an hour of EEG recording. All patients who were identified as being in electrographic NSE despite phenobarbital received continuous midazolam infusion, which was titrated as necessary until seizures ceased, or to a maximum of 0.3 mg/kg/hr. Midazolam was continued until patients were seizure-free for 24 hours, and weaned on an individualized basis. All infants remained on continuous video EEG for the duration of midazolam treatment. Infants meeting criteria also underwent 72 hours of whole body cooling per protocol. Results: Ten patients were identified in a 15-month period as being in electrographic NSE despite treatment with phenobarbital at therapeutic doses (levels of 35-60). Seizures started between 1 hour of life and 6 weeks of age, and were secondary to various etiologies including stroke, trauma, and hypoxic-ischemic encephalopathy (table 1). Midazolam was started within 24 hours of electrographic status onset in all patients. Electrographic resolution of NSE was noted within 2 hours in six of ten patients, with complete cessation of seizures occurring within 4 hours in these patients. Of the four remaining infants, two patients had temporary resolution of NSE, which then recurred a few hours later and was controlled with an increase in midazolam dose. The other two patients were dying and seizure control was never obtained. Four patients received whole body cooling.Conclusions: Successful development and implementation of a NSE protocol in our institution s NICU has led to earlier EEG recognition, more rapid initiation of treatment, and sooner resolution of NSE. More rapid recognition and treatment initiation may also lead to lower maximal and total exposure to midazolam, minimizing potential side effects from the treatment. Intravenous midazolam should be considered in the management of neonatal status epilepticus.