Abstracts

Rationale: The treatment of refractory status epilepticus (RSE) is notoriously difficult. Glutamate antagonists might be more efficient than GABA agonists in the late stage of status epilepticus. Ketamine is an NMDA receptor antagonist with an attractive safety profile because it does not cause hypotension. It is occasionally used for this indication although current evidence to support its use is weak. We reviewed the safety and efficacy of ketamine for RSE. Methods: We conducted a retrospective multicenter study involving 6 academic centers. Medical records and EEG reports were reviewed of all patients receiving IV ketamine for RSE from 2004 to 2012. We included children and adults. Continuous EEG was used in all but one case. Results: We identified 22 patients and 23 episodes of RSE treated with ketamine. Mean age was 28+/- 4 years (7 months-74 years). The most common etiologies were CNS infection (5), autoimmune disease (4), malformation of cortical development (4) and genetic disorder (3). Five cases had purely electrographic status epilepticus while the remaining patients had associated clinical manifestations, including generalized (4), partial (3) and subtle (7) motor activity. In most cases, ketamine was introduced at least 1 week after the onset of SE (median time: 12 days; range: 1-44 days). An initial loading dose was commonly used (1.5-2.5 mg/kg), followed by continuous infusion (usual initial rate of 0 .1-0.5 mg/kg/h). The maximal infusion rate was typically 1-2mg/kg/h, although in 4 patients it was greater than 5mg/kg/h. The duration of ketamine treatment ranged from 2 to 24 days. Vasopressors were increased in 8 patients but only one developed new onset hypotension. Three patients developed severe acidosis that was attributed to shock and acute kidney injury in 2 cases and a syndrome similar to propofol infusion syndrome (PRIS) in the third patient. SE was permanently controlled within 72h of ketamine initiation in 7 patients. However, ketamine was the last drug to be used in only 1 of these patients; the others received at least one additional drug, most commonly benzodiazepine (7) and phenytoin/fosphenytoin (6). Overall, status epilepticus was temporarily controlled in 14 cases and permanently controlled in 10 cases. Conclusions: Assessing the efficacy of ketamine in RSE is difficult as it is used in the late stage of refractory SE and with a wide range of doses. This study indicates that ketamine is associated with a low incidence of identifiable serious adverse events, although we describe for the first time its association with a syndrome similar to PRIS. It is often transiently effective, and can be associated with permanent cessation of RSE in some patients. Further study is needed before recommendation can be made to extend its usage, but its hemodynamic profile, mechanism of action and preliminary results are promising. It should be included in future studies on RSE.