Ketamine was first introduced for human use in 1965 and has been widely utilized as a general anesthetic with an excellent safety profile (Mion 2017, Dorandeu 2013). Ketamine works on several receptors, resulting in various actions such as anesthesia, analgesia, and antidepressant effects. While not widely studied, ketamine has been shown to have antiepileptic properties. In seizures, the excessive release of glutamate leads to the overactivation of N-methyl-D-aspartate (NMDA) receptors, thereby causing neuronal hyperexcitability and seizure-like activity. Ketamine works by regulating neuronal excitability and reducing excessive, synchronized neural activity through non-competitive inhibition of glutamatergic transmission, primarily via NMDA receptor antagonism. More specifically, blocking the NMDA receptor with ketamine decreases neuronal depolarization and excitotoxicity, potentially halting seizure propagation (Tan 2024).
The post Seizing the Evidence: Should We Consider Ketamine’s Place in Seizure Protocols? appeared first on REBEL EM – Emergency Medicine Blog.
The article discusses the potential role of ketamine in treating refractory and super-refractory status epilepticus.
Refractory status epilepticus occurs when seizures persist despite adequate doses of at least two antiepileptic drugs, typically including a benzodiazepine. Super-refractory status epilepticus is defined as seizures continuing or recurring 24 hours or more after starting anesthetic therapy, or after weaning from it.
Standard treatments for these conditions involve a progression of medications. First, benzodiazepines are used. If seizures continue, other antiepileptic drugs like phenytoin, fosphenytoin, levetiracetam, or valproic acid are added. For refractory cases, anesthetic agents such as midazolam, propofol, or pentobarbital are employed. These conventional anesthetic drugs primarily act on GABA-A receptors.
A significant issue with these standard anesthetic agents is their side effect profile, which includes hypotension, respiratory depression, and propofol infusion syndrome. Prolonged use can also lead to reduced effectiveness, requiring dose increases.
Ketamine offers a different approach due to its unique mechanism of action as an N-methyl-D-aspartate, or NMDA, receptor antagonist. During prolonged seizures, GABA-A receptors can become less responsive, while NMDA receptors may be upregulated, contributing to seizure activity and neuronal damage. By blocking NMDA receptors, ketamine can target a different pathway, potentially improving seizure control when GABAergic drugs fail.
Potential advantages of ketamine include its tendency to maintain hemodynamic stability, provide bronchodilation, and offer potential neuroprotection by reducing excitotoxicity.
Evidence for ketamine’s use mainly comes from observational studies, case series, and small prospective trials. These studies suggest that ketamine can achieve seizure control in 50 to 70 percent of patients with refractory or super-refractory status epilepticus, often when other treatments have failed. Pediatric studies also indicate similar rates of seizure control.
Ketamine dosing typically involves an intravenous loading dose, followed by a continuous infusion, titrated to achieve burst suppression on an electroencephalogram, or EEG.
Common side effects of ketamine include hypertension and tachycardia, which are usually mild and temporary. Concerns about increased intracranial pressure have not been consistently observed in ventilated patients, with some studies even suggesting it may decrease. Other rare side effects include laryngospasm and emergence reactions, which are less common in sedated intensive care unit patients. Increased salivation can occur but is manageable.
The article suggests considering ketamine, particularly in patients with super-refractory status epilepticus who have not responded to multiple GABAergic agents. It may be especially beneficial for patients with unstable blood pressure where propofol or pentobarbital could be risky. Ketamine can be added to existing anesthetic regimens or used as a sole anesthetic. There is a suggestion that earlier initiation in super-refractory cases might be more effective.
In summary, ketamine provides an alternative therapeutic option for severe, persistent seizures due to its distinct mechanism of action and a more favorable cardiovascular profile compared to other anesthetic agents, although further large-scale research is still needed to fully define its optimal use.
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