Efficacy of Low‐Dose Ketamine and Propofol in the Treatment of Experimental Refractory Status Epilepticus on Male Rats

Abstract

Refractory status epilepticus (RSE) is a condition with serious mortality and morbidity rate, resistant to benzodiazepine and second‐line antiepileptic drugs. This study aimed to electrophysiologically investigate the combination of NMDA receptor antagonist ketamine and GABAergic agent propofol in an RSE model induced by lithium‐pilocarpine in male Sprague–Dawley rats. Seventy‐two male Sprague–Dawley rats were divided into nine groups. The RSE model was induced by subcutaneous injection of lithium‐CI (5 mEq/kg) and intraperitoneal injection of pilocarpine‐HCl (320 mg/kg), after implanting tripolar EEG electrode. Ketamine (30, 60, and 90 mg/kg), propofol (20, 40, and 80 mg/kg), and combinations of both drugs (15 + 20 and 30 + 40 mg/kg) were administered intraperitoneally to animals with RSE. Video‐EEG recordings were taken after inducing model and 48 h later. The efficacy of drugs was statistically evaluated based on spike frequencies (spikes/min) and amplitudes (mV). Compared to RSE group, it was determined that 30 and 60 mg/kg doses of ketamine provided effective seizure control and prevented mortality (p < 0.001), while the 90 mg/kg showed toxic effects in all animals and caused mortality. The 80 mg/kg dose of propofol provided seizure control and reduced the mortality rate to 16.7% (p < 0.001), whereas the 20 mg/kg resulted in a 100% mortality rate. The low‐dose ketamine+propofol (15 + 20 mg/kg) combination provided early onset seizure control and were as effective as 80 mg/kg propofol (p < 0.05). The study concluded that in the experimental RSE model, seizure control could be achieved with low‐dose combination of ketamine and propofol without the need for high doses as in monotherapy, thus preventing dose‐related adverse effects.