Fig. 2

The combination of atipamezole with caffeine dramatically accelerated emergence from dexmedetomidine sedation compared to that produced by saline or atipamezole by itself. A group of 8 female rats were exposed to 3 deep sedation sessions using bolus injections of dexmedetomidine (10 µg/kg), a week apart. The protocol used is described in Fig. 1. At the end of each session the rats received a bolus injection of either saline or atipamezole (5 μg/kg) or atipamezole (5 μg/kg) & caffeine (25 mg/kg). The order of the drug injections was randomized. Rats were placed on their backs in a waking box, and the time for the rats to recover their righting reflex was recorded. This time is plotted in the figure as the emergence time. The figure plots the time to emerge from sedation for rats receiving saline (leftmost group) or atipamezole (middle group) or atipamezole with caffeine (rightmost group). A one-way repeated measures ANOVA revealed that there was a statistically significant difference in emergence times between at least two groups (F(2,14)) = 63.9, p < 0.0001. Tukey’s HSD Test for multiple comparisons found that the mean value for emergence from sedation was different for saline (control) vs atipamezole (p = 0.0009, 95% C.I. = [522 to 1401]); for saline (control) vs atipamezole with caffeine (p < 0.0001, 95% C.I. = [1129, 2057]); for atipamezole vs atipamezole with caffeine (p = 0.0023, 95% C.I. = [292 to 972]).RORR Times (in seconds): Female rats shown in Fig. 2: Saline (control): 1210, 1869, 1828, 1390, 1973, 1679, 2679, 1565, Atipamezole (5 μg/kg): 510, 446, 1332, 950, 1037, 795, 1078, 356, Atipamezole (5 μg/kg) with Caffeine (25 mg/kg): 142, 87, 232, 137, 276, 210, 149, 217. Male rats—Data presented in the Results Section: Saline (control): 2305, 2941, 5045, 2200, 1355, 2012, 1921, 3862; Atipamezole (5 µg/kg) & Caffeine (25 mg/kg): 79, 100, 151, 30, 25, 55, 163, 347