Why ketamine

Abstract

We present the rationale for testing ketamine as an add-on therapy for treating benzodiazepine refractory (established) status epilepticus. In animal studies, ketamine terminates benzodiazepine refractory status epilepticus by interfering with the pathophysiological mechanisms and is a neuroprotectant. Ketamine does not suppress respiration when used for sedation and anesthesia. A Series of reports suggest that ketamine can help terminate refractory and super refractory status epilepticus. We propose to use 1 or 3 mg/Kg ketamine intravenously based on animal-to-human conversion and pharmacokinetic studies. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Keywords: Established status epilepticus; NMDA receptor; Neuroprotection; Pharmacokinetics.

Figure 1.

Pharmacokinetic simulations of ketamine 1 mg/kg IV (Panel A), 3 mg/kg IV (Panel B), and 4 mg/kg IM, a common dose for procedural sedation (Panel C). The lower red line is at 900 ng/mL and represents the minimum serum level associated with anti-seizure activity in rodents (Naidoo et al., 2019). PK simulations used PK parameters reported by Sherwin et al. (2015) for IV dosing and Hornik et al. (2018) for IM dosing and fixed dosing at 75 kg and greater. The upper red line at 2000 ng/mL represents serum levels associated with dissociative anesthesia.