(S)-Ketamine in Refractory and Super-Refractory Status Epilepticus: A Retrospective Study

Abstract

ObjectiveThe aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU).MethodsWe retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death.ResultsA total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %.ConclusionsTreatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.

Intravenous ketamine in status epilepticus

“…There are 26 studies on the use of KET in SE, including 18 single case reports (14 on adults and four on children) and eight case series (five on adults and three on children) available.…”

“…One pediatric case series included only one patient with KET; this study was therefore counted as a case report . Six case series were conducted in a single center, and one was a multicenter study . Except for two prospective pediatric studies, all others were retrospective.…”

Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

“…28 The case studies presented here provide further support for perampanel as a treatment for RSE. 34 A review of all published studies of ketamine treatment for SE found that 153 (73.9%) adult patients were responders. 33 Inaretrospectivestudy of (S)-ketamine treatment for RSE and SRSE, after a median of three failed AEDs, (S)-ketamine was the final drug administered before SEcessationin27(64.3%)patients;however,four(14.8%)ofthese were also receiving propofol concurrently.…”

“…33 Inaretrospectivestudy of (S)-ketamine treatment for RSE and SRSE, after a median of three failed AEDs, (S)-ketamine was the final drug administered before SEcessationin27(64.3%)patients;however,four(14.8%)ofthese were also receiving propofol concurrently. 34 A review of all published studies of ketamine treatment for SE found that 153 (73.9%) adult patients were responders. 33 InareportoffivepatientswithSRSE, stiripentol treatment after failure of 5-8 AEDs was followed by SE cessationinthree(60.0%)patientswithin4daysofadministration.…”

Brexanolone as adjunctive therapy in super‐refractory status epilepticus

“…Nevertheless, the high response rate in this study among patients with SRSE not previously responding to other treatments stands in comparison to previous observational studies. In a retrospective study of 42 patients with RSE and SRSE, (s)‐ketamine infusion for a median of 3 days resulted in a survival rate of 54.8% and resolution of SRSE in 64% of patients 48. Another retrospective case series demonstrated a 57% control rate and 57% survival rate when ketamine was administered in 58 subjects with 60 episodes, although no subject responded when ketamine was introduced 8 days beyond status epilepticus onset, compared to a large proportion of patients in our cohort responding after a 9.2‐day mean duration of status epilepticus before brexanolone administration 49.…”