A 2022 Delphi methodology study comprising 9 experts developed consensus-based recommendations for the management of adult and pediatric new-onset refractory status epilepticus (NORSE)/febrile infection‐related epilepsy syndrome (FIRES). A 9-point Likert scale was used to rate each statement. A median consensus score of ≥7 indicated appropriate statements, whereas inappropriate statements had a median consensus score of ≤3. A level of agreement (LA) was defined as the % of raters that gave a score of 7-9, and a level of disagreement (LD) as the % of raters that gave a score of 1-3 for each statement. [1]
There was a LA of 77.1% and LD of 4.2% to initiate ketogenic diets (KD) during the first week of treatment in NORSE/FIRES. A KD should be considered in prolonged and severe cases with a LA of 95.8% and LD of 0% due to its favorable outcomes in previous cases. There was a LA of 79.2% and LD of 0% for the parenteral option if the enteric option of the diet was not possible, based on local expertise and availability. A KD during the treatment of the post-acute phase (following the resolution of the epileptic seizure) was recommended with a LA of 87.5% and LD of 0% to continue for patients who initiated and benefited during the early stages. While an optimal duration of follow-up KD had yet to be established, continuation of follow-up diet for 3 months had a LA of 75%. Of note, these recommendations are limited to sparse evidence and subject to change with new evidence. Additionally, an expert panel made the recommendations based on expertise and experience; however, bias in the selection of focus points and questions could have influenced the integrity and validity of this international consensus. [1]
The preferred initial treatment for generalized convulsive status epilepticus is typically an intravenous (IV) benzodiazepine, followed by an IV infusion of a longer-acting anti-seizure drug (ASD) (i.e., phenytoin, fosphenytoin, phenobarbital, valproate, lacosamide, or levetiracetam). Refractory status epilepticus (RSE) occurs when status epilepticus (SE) persists despite treatment with an IV benzodiazepine and second, longer-acting IV ASD; treatment of RSE generally consists of “aggressive” therapy with a continuous IV infusion of midazolam, pentobarbital, or propofol. For super refractory status epilepticus (SRSE), alternatives may be considered when treatment for RSE is prolonged or with failure of a second attempt to withdraw highly sedating drugs. The KD, a high fat, low carbohydrate, adequate protein diet that is designed to mimic a fasting state and produce ketosis, can potentially be effective in patients with drug-resistant epilepsy. A retrospective review of 10 adults in intensive care units (ICUs) treated with KD for SRSE, finding ketosis was achieved in nine patients after a median of three days (see Table 1). However, the administration method of KD was not specified, and was likely enteral. In 3-5 days after KD initiation, about 2/3 of patients had resolution of SRSE, with subsequent withdrawal of the highly sedating medication. Adverse events included hypertriglyceridemia and transient acidosis in both studies, which resolved after cessation of KD. While KD appears to be safe and a potential treatment for patients with RSE and SRSE, potential limitations include difficult administration requiring professional dietician help, the need to avoid infusions that include carbohydrates (i.e., propylene glycol, which is used as a carrier in many IV ASDs), and late onset (2-3 days) to reach ketosis. [2]
Furthermore, the authors of a 2021 review note that enteral feeding is typically used for initiation and maintenance, however IV administration has been described in patients not tolerating enteral feeding secondary to ileus, or reduced gastrointestinal motility due to coma-inducing medications. Additionally, the review noted that the optimal timing for KD initiation remains unknown, as well as the effectiveness of KD compared to other treatment options or for specific etiologies. [3]