Refractory Epilepsy
Conditions
Keywords
seizure, glutamate activation, N-Methyl D-Aspartate, gamma-aminobutyric acid receptor, Ketamine
Brief summary
The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.
Detailed description
The traditional treatment for refractory status epilepticus includes diazepam, midazolam, valproic acid, thiopental and propofol. These medications fail to control seizure activity in 20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity. Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce the epileptiform burst discharges and after potential. Therefore, targeting the N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the treatment of refractory status epilepticus. The specific aim is to determine whether continuous infusion of ketamine as a first line agent for refractory status epilepticus is effective in controlling seizures. The central hypothesis of our proposal is that early treatment with ketamine will be much more efficacious in controlling refractory status compared to the traditional treatment.
Interventions
DRUGTraditional Treatment (Group T)
Patients will receive traditional drug infusions
DRUGKetamine Infusion (Group K)
Patients will receive loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients more than 18 years of age with a diagnosis of status epilepticus * Considered for burst suppression therapy after failing 2 or 3 anti-epileptic medications
Exclusion criteria
* Post anoxic status epilepticus * Pregnant women, as confirmed by urine, or blood human chorionic gonadotropin, ultrasound or physical exam * Prisoners * Age less than 18 years * Allergy or sensitivity to the drug in question
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time taken for burst suppression | Baseline to 1 hr | Average time for burst suppression |
| Time taken for termination of seizures | Baseline to 24 hrs | Average time for seizures to terminate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of stay in ICU | Baseline to 72 hrs postoperatively | Total number of days in the ICU |
| Use of parenteral or enteral nutrition | Baseline to 72 hrs postoperatively | Nutrition provided through a feeding tube or catheter |
| Use of vasopressors | baseline to 72 hrs | The need of vasopressors |
| Mortality | baseline to post-op day 10 | death |
| Medical imaging results | Post-op Day 2 to Post-op day 10 | MRI scans 7 to 10 days after burst suppression |
| Number of days on ventilator | Baseline to 72 hrs | Total number of days patient is on the ventilator |
Countries
United States
Outcome results
None listed