Abstracts

RATIONALE: To understand the EEG changes associated with ketamine treatment for status epilepticus which was refractory to conventional anticonvulsants. Experimental studies suggest that after an hour or more of seizure activity, GABA agonists may lose efficacy while NMDA receptor activation becomes more prominent. Ketamine is the only clinically useful NMDA antagonist. In anesthetic doses, ketamine alone produces enhanced [beta] activity and some background slowing, but not suppression-burst (S-B) in normal humans. When added to GABAergic agents such as propofol, it may enhance the appearance of S-B in head-injured patients. The EEG effects of ketamine in refractory status epilepticus (RSE) patients have not been well described.
METHODS: After IRB approval, we searched for all cases of RSE treated with ketamine and reviewed the available EEG records. The response to ketamine with regard to seizures was judged by the available EEG records; other effects were extracted from the patients[ssquote] medical records.
RESULTS: We obtained the records of seven patients treated with ketamine for RSE. In all cases, only segments of the continuous EEG records had been archived. In all cases, ketamine was introduced because other agents had failed or could not be tolerated hemodynamically. The average duration of seizures prior to ketamine therapy was 60 hours (range 5 - 192 hrs). All of the patients were critically ill before ketamine was introduced (mean APACHE II score 23), and were receiving at least two other anticonvulsants, one of which was usually propofol or pentobarbital. Most patients received a loading dose (range 0.9 - 3.0 mg/kg); in two patients, the loading dose terminated RSE at least briefly. In the other five patients, infusion rates ranged from 0.3 - 5.8 mg/kg/hr; seizures stopped in two of these patients. Adding ketamine to other anticonvulsants induced a suppression-burst pattern in three patients without a pre-existing suppression-burst pattern. All patients eventually died during the index hospitalization. Ketamine had minimal effects on blood pressure.
CONCLUSIONS: Ketamine produced electrographic seizure control in over half of the RSE patients without inducing more hemodynamic instability. The response rate as judged by bedside clinicians was greater, but this was not the criterion used in this study. None of the deaths was unexpected or appeared related to the use of ketamine. The loading doses used were probably too small. We conclude that ketamine is a potentially important agent for the control of RSE and should be the subject of a prospective clinical trial.
[Supported by: University of Virginia Department of Neurology]