Intravenous ketamine in status epilepticus

Abstract

Status epilepticus (SE) is among the most common neurological emergencies. In refractory SE, due to subcellular maladaptive changes, γ-aminobutyric acidergic drugs are no longer effective, and there is an increase in synaptic N-methyl-d-aspartate (NMDA) receptors. Ketamine (KET) is a noncompetitive N-methyl-d-aspartate receptor antagonist that could be of value in the treatment of refractory SE. The aim was to analyze all published studies on KET in the treatment of SE. A systematic search (PubMed) of the literature identified 25 studies (from December 1996 to March 2017); with the exception of two prospective studies, all studies were retrospective in nature and published as a full paper. To date, PubMed lists a total number of 244 episodes of SE treated with KET (13 case reports and five case series in adults; four case reports and three case series in children); the overall success rate was 74% (153/207) in adults and 73% (27/37) in children. Adverse events were rare. Current evidence on the use of KET in acute seizures and SE is mostly restricted to retrospective case reports and case series, except for two prospective case series without control (class IV). Further prospective studies to inform clinicians are necessary.

Epilepsy in nonhuman primates

“…Inhibition of the negative feedback influencing glutamatergic activity via antagonism of presynaptic glutamate receptor activity results in a proconvulsive effect, while at higher ketamine doses, the glutamatergic effects may be suppressed by saturation of the postsynaptic glutamate receptors . Of interest, ketamine is currently recommended for treatment of refractory status epilepticus in humans . Proconvulsants, such as allyl‐glycine, which inhibits GABA synthesis, or the GABA‐receptor antagonist bicuculline, were routinely used in previous decades to reliably provoke photoconvulsive responses in NHP studies…”

“…24 Of interest, ketamine is currently recommended for treatment of refractory status epilepticus in humans. 25 Proconvulsants, such as allyl-glycine, which inhibits GABA synthesis, or the GABA-receptor antagonist bicuculline, were routinely used in previous decades to reliably provoke photoconvulsive responses in NHP studies. 6,11,12…”

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

“…21 Additionally, a case study documented perampanel administration for treatment of Lance-Adams syndrome, resulting in myoclonic seizure suppression. 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. Across three retrospective reviews, off-label ketamine use resulted in terminationof22.0%ofRSEcases(N=82).…”

“…Across three retrospective reviews, off-label ketamine use resulted in terminationof22.0%ofRSEcases(N=82). 33 InareportoffivepatientswithSRSE, stiripentol treatment after failure of 5-8 AEDs was followed by SE cessationinthree(60.0%)patientswithin4daysofadministration. 34 A review of all published studies of ketamine treatment for SE found that 153 (73.9%) adult patients were responders.…”

“…32 Across three retrospective reviews, off-label ketamine use resulted in terminationof22.0%ofRSEcases(N=82). 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.…”