Modified low ratio ketogenic therapy in the treatment of adults with super-refractory status epilepticus

Background: Induction of ketosis by manipulation of nutrition intake has been proposed as an adjunctive treatment for super-refractory status epilepticus (SRSE). However, the classical 4:1 ketogenic ratio may not meet the nutrition needs, specifically protein for critically ill adults. The aim of this study was to analyze the outcomes of adults with SRSE who received a lower ketogenic ratio of 2:1 grams of fat to non-fat grams, including 20%-30% of energy from medium chain triglycerides.

Methods: We reviewed patients aged ≥18 years with SRSE treated with ketogenic therapy between July 2015 and December 2020 at two quaternary teaching hospitals in Melbourne, Australia. Data collected from medical records included patient demographics, nutrition prescription, clinical outcomes, and ketogenic therapy-related complications. The primary outcome of the study was to assess tolerability of ketogenic therapy.

Results: Twelve patients (female = 7) were treated with ketogenic therapy for SRSE. Patients received between 4 and 8 antiseizure medications and 1-5 anesthetic agents prior to commencement of ketogenic therapy. Blood beta-hydroxybutyrate concentrations were variable (median = 0.5 mmol/L, range: 0.0-6.1 mmol/L). SRSE resolved in 10 cases (83%) after a median of 9 days (range: 2-21 days) following commencement of ketogenic therapy. Ketogenic therapy-associated complications were reported in five patients, leading to cessation in two patients.

Conclusion: Despite the challenge in maintaining ketosis during critical illness, low ratio 2:1 ketogenic therapy incorporating medium chain triglycerides is tolerable for adults with SRSE. Further studies are required to determine the optimal timing, nutrition prescription and duration of ketogenic therapy for SRSE treatment.