Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus

Abstract

Objective: To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults.

Methods: We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes.

Results: Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died.

Conclusions: KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials.

Classification of evidence: This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis.

Figure. KD treatment algorithm for SRSE

ALT = alanine transaminase; AST = aspartate transaminase; CBC = complete blood count; CMP = comprehensive metabolic panel; HCG = human chorionic gonadotropin; KD = ketogenic diet; MAD = modified Atkins diet; MAP = mean arterial pressure; SRSE = superrefractory status epilepticus*Patients were excluded on the basis of a prior report of fatal propofol infusion syndrome in a patient who received concomitant KD therapy for status epilepticus.