Vascular and extravascular volume expansion of dobutamine and norepinephrine in normovolemic sheep

• Published in: Shock (Augusta, Ga.) Ga.), 2011-09, Vol.36 (3), p.303-311
• Main Authors: Stephens, Christopher T, Uwaydah, Nabeel, Kramer, George C, Prough, Donald S, Salter, Michael, Kinsky, Michael P
• Format: Article
• Language: English
• Subjects: Adrenergic Agonists - therapeutic use; Adrenergic alpha-Agonists - therapeutic use; Adrenergic beta-Agonists - therapeutic use; Animals; Dobutamine - pharmacokinetics; Dobutamine - therapeutic use; Female; Fluid Therapy; Hemodynamics - drug effects; Norepinephrine - pharmacokinetics; Norepinephrine - therapeutic use; Plasma Volume - drug effects; Sheep
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0b013e318225b031

In low-flow states, such as circulatory shock, both fluids and catecholamines are often coadministered. We have previously found that adrenergic agents alter volume expansion after a fluid bolus. The present study tested the volume expansion properties of dobutamine and norepinephrine in sheep treated with (series 1) and without (series 2) a fluid bolus. Series 1 (n = 6 per group): no drug (control), dobutamine (10 μg x kg(-1) x min), or norepinephrine (1.0 μg x kg(-1) x min(-1)) was begun 30 min before a 24-mL x kg(-1), 20-min, 0.9% NaCl bolus. The effect of drug and fluid on plasma volume (ΔPV), urinary output (UOP), and extravascular volume (ΔEVV) was determined. Series 2: Identical protocol but no fluid bolus. Series 1: the fluid bolus resulted in a peak and sustained ΔPV expansion. Norepinephrine (7.5 ± 0.9 mL x kg(-1)) and dobutamine (9.5 ± 1.1 mL x kg(-1)) significantly increased ΔPV compared with control (3.8 ± 1.1 mL x kg(-1)). Cumulative UOP was reduced by dobutamine (3.8 ± 1.4 mL x kg) compared with norepinephrine (25.1 ± 3.9 mL x kg(-1)) and control (16.9 ± 4.0 mL x kg(-1)). Norepinephrine increased ΔPV, while reducing ΔEVV after bolus. Series 2: ΔPV was unchanged in the control group. Dobutamine and norepinephrine increased ΔPV over time, 5.1 ± 0.5 and 4.0 ± 0.5 mL x kg(-1), respectively. At study end, UOP was lowest in dobutamine. Norepinephrine resulted in loss of ΔEVV fluid. data suggest a novel role for adrenergic receptors in regulating vascular and EVV expansion. β-Adrenergic agonists enhance vascular volume expansion, whereas α-adrenergic agonists eliminate extravascular fluid.