Abstracts

RATIONALE: Topiramate (TPM) is an antiepileptic drug (AED) proven effective for partial seizures (CPS) and generalized tonic-clonic seizures (GTC). It is suggested that TPM dosing be slowly titrated (over 8 weeks) as too rapid titration has been associated with dose-related cognitive dysfunction. This dosing regimen is not practical in critically ill patients requiring rapid seizure cessation. The rationale of this prescribing practice was: 1) to provide an adjunct to refractory seizures (in an effort to spare the use of high-dose barbiturate therapy) and 2) to provide an alternative to critically ill patients experiencing adverse events to other AED used for seizure prophylaxis. The purpose of this report is to describe patient tolerability to rapid TPM initiation for seizures in critically ill patients.
METHODS: After human investigation committee approval, a search of our hospital database flagged charts in which TPM was prescribed in the intensive care unit.
RESULTS: The median age was 62 (34-92) years with 5 females and 2 males. Admission diagnosis included: traumatic brain injury (2), hemorrhagic stroke (2), ischemic stroke (1), and status epilepticus (2). Only 2 patients had a history of a premorbid seizure disorder. TPM was initiated a median of 3.5 (2-11) days after acute seizure onset. All patients were receiving at least 1 other AED (median 2; range 1-3) prior to TPM initiation, primarily phenytoin and valproic acid. Two patients received a TPM bolus dose of 1200mg and 1 patient received 800mg per gastric tube. The median TPM maintenance dose was 1000 (400-1200) mg/day per gastric tube and this was achieved 1.5 (1-4) days after initiation. All patients expressed clinical seizure activity (3 CPS, 3 GTC, 1 CPS with secondary GTC) and 6/7displayed epileptiform discharges (EDC) on EEG prior to TPM initiation. Clinical seizure activity had dissipated in 6/7 patients 2 (1-5) days following TPM administration; in one patient clinical seizures did not stop with adjunctive TPM but there was no EEG evidence of seizure activity. All patients showed no EDC on EEG within 2-5 days of TPM initiation. Approximately 50% of patients required supplemental administration of either lorazepam, midazolam, or propofol after TPM was started. None of the patients required high-dose barbiturates. One patient experienced hallucinations after TPM was started but TPM therapy was continued. At discharge, 3 patients went to a rehabilitation facility, 1 went home, 1 went to a nursing home, and 2 expired. All patients discharged to home, rehab, or nursing home continued on TPM therapy either alone or with other AED. For one of these patients TPM was stopped as an outpatient due to acral paresthesias.
CONCLUSIONS: In this report, rapid TPM dose escalation was found to be well tolerated in critically ill patients. Rapid TPM administration appears to result in rapid cessation of both clinical and EEG seizure activity in combination with other AED. Further safety, efficacy, and pharmacokinetic studies of TPM rapid dose initiation are warranted in a controlled intensive care unit setting. This information should provide practictioners with initial experience with the use of rapidly administering TPM in critically ill patients.
(Disclosure: Salary - Kellie Murry is an emplyoee of Ortho McNeil Pharmaceutical, Inc., Grant - Dr. Coplin support in part by NIH/NINDS NS 38905, Stock - Kellie Murry holds stock option in Ortho McNeil Pharmaceutical, Inc., Other - Denise Rhoney - Educational grant from Ortho McNeil Pharmaceutical, Inc. William Coplin - Educational grant from Ortho McNeil Pharmaceutical Inc.)