Ketogenic Diet in the Treatment of Super-Refractory Status Epilepticus at a Pediatric Intensive Care Unit: A Single-Center Experience

Abstract

Background: To evaluate the use of the ketogenic diet (KD) for treatment of super-refractory status epilepticus (SRSE) at a pediatric intensive care unit (PICU). Design: A retrospective analysis of all pediatric patients treated for SRSE with the KD at our center was performed using patient data from our prospective longitudinal KD database. Setting: SRSE is defined as refractory SE that continues or recurs 24 h or more after initiation of anesthetic drugs. We describe the clinical and electroencephalographic (EEG) findings of all children treated with KD at our PICU. The KD was administered as add-on after failure of standard treatment. Response was defined as EEG seizure resolution (absence of seizures and suppression-burst ratio ≥50%). Patients: Eight consecutive SRSE patients (four females) treated with KD were included. Median age at onset of SRSE was 13.6 months (IQR 0.9-105), and median age at KD initiation was 13.7 months (IQR 1.9 months to 8.9 years). Etiology was known in 6/8 (75%): genetic in 4 (50%), structural in 1 (12.5%), and autoimmune/inflammatory in 1 (12.5%). Main Results: Time from onset of SRSE to initiation of KD was median 6 days (IQR 1.3-9). Time until clinically relevant ketosis (beta-hydroxybutyrate (BHB) >2 mmol/L in serum) was median 68.0 h (IQR 27.3-220.5). Higher ketosis was achieved when a higher proportion of enteral feeds was possible. Four (50%) patients responded to KD treatment within 7 days. During follow-up (median 4.2 months, IQR 1.6-12.3), 5/8 patients-three of them responders-died within 3-12 months after SRSE. Conclusions: In eight patients with SRSE due to severe etiologies including Alpers syndrome, we report an initial 50% response to KD. KD was used early in SRSE and sufficient levels of ketosis were reached early in most patients. Higher ketosis was achieved with combined enteral and parenteral feedings.

Keywords: beta-hydroxybutyrate; ketogenic diet; parenteral diet; pediatric; status epilepticus.

Figure 1

Ketosis after KD initiation. Ketone levels of beta-hydroxybutyrate (BHB) in serum as trajectories from day 1 to day 8. Relevant ketosis (>2 mmol/l) is marked above the red line. Detailed data on ketosis within the first days of KD were available in seven patients: while five patients reached relevant ketosis, the other two (patient 8 and patient 4) showed maximum levels of 0.7 and 0.2 mmol/l, respectively. In patient 8 (FIRES) corticosteroids were administered 3 days before KD start and overlapped for the first 3 days hence delaying ketosis.