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

Abstract

Background: Norepinephrine is a potent vasopressor that increases arterial blood pressure but may have adverse effects on renal blood flow. The combination of norepinephrine and dobutamine may lead to improved renal perfusion compared to an infusion of norepinephrine alone. The effects of these drugs in the normotensive neonatal foal have not been reported.Hypothesis: Norepinephrine increases arterial blood pressure. Adding dobutamine to a norepinephrine infusion will change the renal profile during the infusions without changing the arterial blood pressure.Animals: Eight conscious Thoroughbred foals were used in this study. Methods: Each foal received norepinephrine (0.1 mg/kg/min), combined norepinephrine (0.1 mg/kg/min) and dobutamine (5 mg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate, arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index, and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of sodium, potassium, and chloride were measured.Results: Norepinephrine and a combined norepinephrine and dobutamine infusion increased arterial blood pressure and systemic vascular resistance and decreased heart rate and cardiac index as compared to saline. The combination resulted in higher arterial pressure than norepinephrine alone. There was no significant difference in urine output, creatinine clearance, or fractional excretion of electrolytes with either infusion as compared to saline.Conclusions and Clinical Importance: These data suggest that norepinephrine and a combined norepinephrine and dobutamine infusion cause unique hemodynamic effects without affecting indices of renal function, and this effect warrants further investigation.

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

“…In this group of healthy foals, norepinephrine at 0.3 μg/kg/min increased urine output and creatinine clearance. This finding is in contrast to that observed in foals receiving a lower dosage rate of norepinephrine (0.1 μg/kg/min), where no change in urine output or creatinine clearance was seen 8 . The reason for this difference is unclear.…”

“…Norepinephrine caused a decrease in CO in the foals in this study. This confirms previous data obtained after norepinephrine administration in normal foals 8 and in 1 study of anesthetized foals, 22 but differs from data in other species and a study of hypotensive anesthetized foals, in which the administration of norepinephrine increased CO 6,7,24,25 . The reasons for these differences are unclear.…”

“…The reasons for these differences are unclear. It has been hypothesized that norepinephrine has minimal β‐effects in the normal neonatal foal, 8 which is supported by data from 1 study of anesthetized foals 22 but is not supported by data from anesthetized, hypotensive foals 25 . Different effects of norepinephrine may predominate during times of physiologic stress, as seen in the hypotensive anesthetized foals, compared with normal animals or anesthetized foals that are not hypotensive.…”

“…The 40‐minute washout period was based on previously conducted experiments with norepinephrine 8 and fenoldopam 16 in the neonatal foal and on the half life of fenoldopam (10 minutes) 27 and norepinephrine (2–2.5 minutes) in humans. This approach could have led to very low drug concentrations after the norepinephrine or norepinephrine plus fenoldopam infusions.…”

“…There are concerns about the possibility of norepinephrine adversely affecting renal hemodynamics, because it has been shown to decrease renal blood flow, urine output, or both in healthy humans 3,4 and dogs 5 . In normotensive sheep, however, norepinephrine increased urine output and renal blood flow, 6,7 and at 0.1 μg/kg/min had no effect on urine output or creatinine clearance in normotensive foals, despite changing systemic hemodynamics 8 . Norepinephrine‐induced renal vasoconstriction appears to be less problematic in states of hyperdynamic shock, in which the addition of norepinephrine to the treatment protocol improved mean arterial blood pressure and urine output in septic humans, 9–13 sheep, 14 dogs, 5 and foals 15 …”