Hemodynamic effects of an intravenous bolus of epinephrine in healthy rats: A randomized, open-label, controlled pilot study

BACKGROUND: IV epinephrine is widely used in the treatment of shock to increase blood pressure (BP). However, whether it may also induce hypotension remains unknown. OBJECTIVE: The aim of this randomized, open-label, controlled pilot study was to observe hemodynamic changes after an IV bolus of epinephrine in healthy rats. METHODS: Healthy male Sprague-Dawley rats were randomized to 1 of 5 groups to receive IV epinephrine in doses of 0.5 μg/kg (group 1); 1 μg/kg (group 2); 2 μg/kg (group 3); 4 μg/kg (group 4); or 8 μg/kg (group 5). A sixth group received placebo (0.3 mL of normal saline) and served as the control. BP was monitored continuously. Mean arterial pressure (MAP) and heart rate (HR) were recorded at 0, 5, 15, and 30 seconds and 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and 20 minutes after administration. The highest mean (SD) systolic BP (SBP) and the lowest mean (SD) diastolic BP (DBP) during this period were also recorded. Hypertension and hypotension were defined as BP increased or decreased > 10% from baseline. RESULTS: Forty-two Sprague-Dawley rats were included in the study. The initial hypertension occurred at ~18 seconds in all epinephrine-treated groups (all, P < 0.01), and the subsequent hypotension occurred at mean (SD) 1.3 (0.5), 2.2 (0.4), 3.0 (0.6), and 3.4 (1.1) minutes in groups 2, 3, 4, and 5, respectively (all, P < 0.01). The highest mean (SD) SBP and the lowest mean (SD) DBP in groups 1, 2, 3, 4, 5, and the control group were 184 (12)/78 (11), 208 (14)/78 (10), 219 (18)/69 (14), 232 (17)/55 (11), 243 (16)/56 (15), and 148 (12)/91 (7) mm Hg, respectively, compared with baseline. HR decreased significantly at 15 seconds in groups 2 and 3, and at 5, 15, and 30 seconds in groups 4 and 5 (all, P < 0.01). One rat in group 4 and 1 rat in group 5 died due to treatment-related cerebral hemorrhage. The control group had no significant hemodynamic changes from baseline. Compared with the control group, MAP increased significantly at 5, 15, and 30 seconds and 1 minute in the epinephrine-treated groups and decreased significantly at 2, 3, and 4 minutes in group 3 and at 2, 3, 4, and 6 minutes in groups 4 and 5 (all, P < 0.05). CONCLUSIONS: An IV bolus of epinephrine > 1 μg/kg was associated with biphasic changes in BP, including initial hypertension and subsequent hypotension, in these healthy rats. Future blinded and larger studies using lower doses are needed.