The Systemic and Regional Hemodynamic Effects of Phenylephrine in Sheep Under Normal Conditions and During Early Hyperdynamic Sepsis

Abstract

Phenylephrine treatment of hypotension in sepsis raises concern because it may decrease vital organ bloodflow. Accordingly, we investigated the effects of phenylephrine on systemic and regional bloodflow in normal and septic sheep. Responses to phenylephrine or vehicle infusion for 6 hours were determined in conscious normal sheep and sheep with early sepsis induced by administration of live Escherichia coli. Cardiac output and coronary, mesenteric, and renal bloodflow were measured with implanted flow probes. In normal sheep, phenylephrine decreased cardiac output and heart rate (HR) but increased stroke volume and mean arterial blood pressure (MAP) (84 ± 6 to 108 ± 6 mm Hg, magnitude of mean difference [diff.] 19 [22.6%]; 95% confidence intervals [CI], 17-21). There were significant decreases in regional conductance values with a transient decrease in mesenteric bloodflow, no change in coronary bloodflow, and increased renal bloodflow (222 ± 53 to 271 ± 55 mL/min; diff. 31 [13.9%]; 95% CI, 26-36). During hyperdynamic sepsis, vasodilatation and increased bloodflow occurred in all vascular beds. Phenylephrine restored MAP and stroke volume to baseline values, but HR, cardiac output, and total peripheral conductance progressively decreased. Phenylephrine decreased mesenteric and coronary conductance, with no sustained reduction in flows, but renal conductance was significantly decreased and overall renal bloodflow increased (293 ± 22 vs 347 ± 100 mL/min; diff. 55 [18.8%]; 95% CI, 47-65). In sheep with early hyperdynamic sepsis, phenylephrine, at a dose that restored MAP, increased stroke volume and renal bloodflow while decreasing HR and coronary bloodflow but not mesenteric bloodflow. Similar responses were seen in normal animals.