Fig. 4

Caffeine by itself was not effective at reversing dexmedetomidine sedation. A group of 8 rats were exposed to 3 deep sedation sessions using bolus injections of dexmedetomidine, a week apart (protocol shown in supplementary material). At the end of each session the rats received a bolus injection of either saline or caffeine (25 mg/kg) or atipamezole (5 μg/kg) with 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 caffeine (middle group) or atipamezole with caffeine (rightmost group). Emergence from sedation was significantly different for saline (control) vs caffeine (repeated measures ANOVA, p = 0.0027, 95% C.I. = [230 to 793]); between saline (control) vs atipamezole with caffeine (p < 0.0001, 95% C.I. = [1539, 2044]); between caffeine vs atipamezole with caffeine (p < 0.0001, 95% C.I. = [968 to 1592]). RORR Times (in seconds): Saline (control): 1922, 1861, 1577, 208, 2109, 2105, 2162, 2610, Caffeine (25 mg/kg): 1787, 1092, 1237, 1401, 1646, 1202, 1944, 2027 Atipamezole (5 μg/ kg) with Caffeine (25 mg/kg): 403, 213, 130, 292, 114, 225, 276, 443