Figure 5 Comparisons of diazepam and ketamine dual therapy for SE at different time points. (A) Diazepam-ketamine dual therapy was injected when SE lasted over 40 min; the seizure-free rate decreased rapidly and significantly. SE was only controlled in 1 rat when SE was over 50 min; none of the rats were controlled in the 60-min group compared to all controlled in 10-min, 20-min, and 30-min groups (*** P<0.0001). ANOVA with Dunnett’s multiple comparisons. (B) The degree of seizures was assessed according to the Racine scale. SE in 10-min, 20-min, and 30-min groups were terminated successfully. The degree of behavioral seizure suddenly decreased to class 1 or disappeared completely in the 50-min and 60-min groups (*** P<0.0001). (C) Dual therapy was injected when SE was over 40 min, and it failed to decrease EEG power to reach twice the pre-seizure baseline, a pattern that indicates seizure termination. Dual therapy was administrated when SE lasted less than 30 min, and it drastically terminated SE. (*** P<0.0001), which suggests a temporal effect of diazepam-ketamine dual therapy. Values are means±SEM. ANOVA with Dunnett’s multiple comparisons. (D) Survival rates of animals that received placebo (n=5) or diazepam-ketamine 30 min (n=8) or diazepam-ketamine 60 min up to 7 days after SE treatment (* P=0.023, Log-rank test). Data are shown as the means±SEM (GraphPad Prism, Prism 8.0.2, GraphPad Software, Inc.). SE, status epilepticus; diazepam-ketamine, diazepam 10 mg/kg+ketamine 45 mg/kg.