Ketamine for Refractory Status Epilepticus: A Systematic Review

Background Ketamine is an emerging third-line medication for refractory status epilepticus, a medical and neurological emergency requiring prompt and appropriate treatment. Owing to its pharmacological properties, ketamine represents a practical alternative to conventional anaesthetics. Objective The objective of this study was to assess the efficacy and safety of ketamine to treat refractory status epilepticus in paediatric and adult populations. Methods We conducted a literature search using the PubMed database, Cochrane Database of Systematic Reviews and ClinicalTrials.gov website. Results We found no results from randomised controlled trials. The literature included 27 case reports accounting for 30 individuals and 14 case series, six of which included children. Overall, 248 individuals (29 children) with a median age of 43.5 years (range 2 months to 67 years) were treated in 12 case series whose sample size ranged from 5 to 67 patients (median 11). Regardless of the status epilepticus type, ketamine was twice as effective if administered early, with an efficacy rate as high as 64% in refractory status epilepticus lasting 3 days and dropping to 32% when the mean refractory status epilepticus duration was 26.5 days. Ketamine doses were extremely heterogeneous and did not appear to be an independent prognostic factor. Endotracheal intubation, a negative prognostic factor for status epilepticus, was unnecessary in 12 individuals (10 children), seven of whom were treated with oral ketamine for non-convulsive status epilepticus. Conclusions Although ketamine has proven to be effective in treating refractory status epilepticus, available studies are hampered by methodological limitations that prevent any firm conclusion. Results from two ongoing studies (ClinicalTrials.gov identification number: NCT02431663 and NCT03115489) and further clinical trials will hopefully confirm the better efficacy and safety profile of ketamine compared with conventional anaesthetics as third-line therapy in refractory status epilepticus, both in paediatric and adult populations.