Effects of Norepinephrine and Combined Norepinephrine and Fenoldopam Infusion on Systemic Hemodynamics and Indices of Renal Function in Normotensive Neonatal Foals

Abstract

Background: Norepinephrine increases arterial blood pressure but may have adverse effects on renal blood flow. Fenoldopam, a dopamine-1 receptor agonist, increases urine output in normotensive foals. The combination of norepinephrine and fenoldopam may lead to improved renal perfusion compared with an infusion of norepinephrine alone. The combined effects of these drugs have not been reported in the horse.Hypothesis: Norepinephrine will alter the hemodynamic profile of foals without affecting renal function. Addition of fenoldopam will change the renal profile during the infusions without changing the hemodynamic profile.Animals: Five conscious pony foals. Methods: Each foal received norepinephrine (0.3 mg/kg/min), combined norepinephrine (0.3 mg/kg/min) and fenoldopam (0.04 mg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate (HR), arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance (SVR), stroke volume, cardiac index (CI), and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of electrolytes were measured.Results: Norepinephrine and a combined norepinephrine and fenoldopam infusion increased arterial blood pressure, SVR, urine output, and creatinine clearance and decreased HR and CI compared with saline. The combination resulted in higher HR and lower arterial blood pressure than norepinephrine alone.Conclusions and Clinical Importance: Norepinephrine might be useful for hypotensive foals, because in normal foals, this infusion rate increases SVR without negatively affecting renal function (creatinine clearance increased). Fenoldopam does not provide additional benefit to renal function. These findings warrant further investigation.

Renal Replacement Therapy in Healthy Adult Horses

“…Other significant changes included modest decreases in heart and respiratory rates at variable times. These changes were not perceived as clinically important and were likely related to the CRI of detomidine, which is known to cause cardiovascular and respiratory depression . In addition, transient arrhythmias were noted during RRT.…”

“…Creatinine clearance based on body weight (CrCl; mL/kg/min) of the effluent fluid: …”

Cardiac Output Response to Norepinephrine in Postoperative Cardiac Surgery Patients

“…Still other studies demonstrated a NE-induced reduction in HR in healthy humans (30)(31)(32), normal and hypertensive subjects (33), and in several animal studies (14,(34)(35)(36). The HR reduction in all these studies was attributed to a baroreceptor-mediated central sympathetic withdrawal triggered by the NE-induced increased blood pressure (34,36). However, such baroreceptor-induced change in HR is accompanied by vasodilation of veins and arterioles (37).…”

Endocrine adaptations in the foal over the perinatal period

“…Noradrenaline and adrenaline are known to affect cardiovascular function in fetal and newborn foals (Hollis et al . 2006; O'Connor et al .…”

“…They raise blood pressure by increasing both systemic vascular resistance and heart rate at all ages studied from mid gestation to 14 days after birth, although they are more effective pressor agents after than before birth (O'Connor et al . 2005, 2006; Hollis et al . 2006).…”