From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
- 1 Mechanism of Action Ketamine hydrochloride, a racemic mixture of ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor.
The mechanism by which ketamine is effective is through its action as a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. However, the provided drug labels do not directly address the management of status epilepticus.
The FDA drug label does not answer the question.
From the Research
Ketamine is effective in managing status seizures due to its unique mechanism of action as an NMDA receptor antagonist, and it should be considered as a rescue therapy in refractory status epilepticus, as evidenced by the most recent study 1.
Mechanism of Action
Ketamine works by blocking glutamate-mediated excitatory neurotransmission, which becomes increasingly important as status epilepticus progresses and GABA-mediated inhibition (the target of benzodiazepines) becomes less effective. This is supported by the study published in 2022, which highlights the potential role of ketamine in treating status epilepticus 1.
Clinical Use
When traditional first-line anticonvulsants like benzodiazepines, phenytoin, or valproate fail to control seizure activity, ketamine may be considered as a rescue therapy, particularly in refractory status epilepticus. Typical dosing begins with a loading dose of 1-2 mg/kg IV, followed by a continuous infusion of 1-5 mg/kg/hour, titrated to clinical response.
Key Considerations
- The duration of therapy varies based on seizure control, typically ranging from hours to several days with gradual weaning once seizure activity has ceased for 24-48 hours.
- Ketamine has neuroprotective properties that may limit excitotoxicity during prolonged seizures.
- Side effects to monitor include tachycardia, hypertension, increased intracranial pressure, and emergence phenomena, though these concerns are often outweighed by the need for seizure control in status epilepticus.
- Continuous EEG monitoring is recommended during ketamine administration to assess treatment efficacy, as supported by the study published in 2018 2.
Evidence Summary
The use of ketamine in status epilepticus is supported by several studies, including a systematic review published in 2018, which analyzed 25 studies on the use of ketamine in status epilepticus and found an overall success rate of 74% in adults and 73% in children 2. However, the most recent and highest-quality study, published in 2022, provides the strongest evidence for the use of ketamine in refractory status epilepticus 1.