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A combination of ketamine and diazepam synergistically controls refractory status epilepticus induced by cholinergic stimulation
Author(s) -
Martin Brandon S.,
Kapur Jaideep
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01384.x
Subject(s) - diazepam , ketamine , status epilepticus , pharmacology , medicine , nmda receptor , anesthesia , stimulation , anticonvulsant , hippocampus , benzodiazepine , cholinergic , epilepsy , receptor , psychiatry
SummaryPurpose: New treatments are needed for status epilepticus (SE) that is refractory to drugs modulating GABA A receptors, and NMDA receptor antagonists are candidate drugs.Methods: Clinically available NMDA receptor antagonist ketamine was tested for effectiveness in terminating prolonged SE induced by a combination of lithium and pilocarpine. Animals were treated 10 min after first grade 5 behavioral seizure (Racine scoring scale) by intraperitoneal administration of ketamine, diazepam, or saline. Seizure termination was determined by electroencephalogram (EEG) recordings from the hippocampus and the cortex.Results: Animals treated with normal saline or either 20 mg/kg diazepam, or 50 mg/kg ketamine continued in SE for the next 300 min. However, combined treatment with diazepam and ketamine rapidly terminated prolonged cholinergic stimulation‐induced SE. Detailed study of dose response relationships demonstrated that diazepam enhanced efficacy and potency of ketamine in terminating SE.Discussion: This study demonstrated synergistic action of diazepam and ketamine in terminating SE. It suggests that a ketamine–diazepam combination might be a clinically useful therapeutic option for the treatment of refractory SE.