Transition from intravenous to enteral ketamine for treatment of nonconvulsive status epilepticus

Abstract

BackgroundNonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date.Case presentationA 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment.ConclusionThis case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.

Potential Consequences of High-Dose Infusion of Ketamine for Refractory Status Epilepticus: Case Reports and Systematic Literature Review

“…The literature on ketamine treatment for RSE in adults includes eight case reports, seven retrospective case series and a single systematic review (Table 1) 15,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] . Of these 16 studies, nine (56%) report complete seizure control in all patients treated with ketamine.…”

“…In this case, ketamine was given within six hours of seizure onset and quickly resulted in complete suppression of seizure activity on EEG 45 . A 2017 case report also describes using ketamine within the first 24 hours of RSE with a similarly prompt treatment response 53 . In both of our cases, ketamine infusion was not introduced for several weeks (after trials of multiple AEDs), but after initiation, achieved burst suppression on EEG within 12 hours.…”

CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy

“…It is used either solely or in combination with opioids for the management of acute post-operative and chronic refractory pain (Laskowski et al, 2011 ). Its use in the management of status epilepticus, bipolar disorder, suicidal behavior, major depressive disorder and treatment resistant depression has been demonstrated (Yeh et al, 2011 ; Synowiec et al, 2013 ; Pizzi et al, 2017 ; Borsato et al, 2020 ). Ketamine acts as a non-competitive antagonist of the N-Methyl-D-aspartic acid receptor blocking its action, thereby preventing the development and chronification of pain (Noppers et al, 2010 ).…”

How close is ketamine to routine use in refractory status epilepticus?

“…Intravenous administration of ketamine is the conventional method, but enteral administration can also be effective. Pizzi et al [14] reported a patient with nonconvulsive status epilepticus (NCSE) in whom oral ketamine treatment was continued for 6 months, suggesting that enteral ketamine may be a potential adjunct to intravenous ketamine for the treatment of NCSE. Enteral ketamine can reduce the recurrence of SE, the duration of ICU stays, and intubation-related complications.…”