The effects of short-term infusion of fenoldopam on systemic haemodynamics and indices of renal function in the normotensive neonatal foal

The effects of fenoldopam mesylate, a dopamine-1 receptor agonist, are unknown in the foal, as is the distribution of dopamine1 receptors. The aim of this study was to document the effects of fenoldopam on the systemic circulation and renal function of the normotensive neonatal foal. Fenoldopam is licensed as an anti-hypertensive drug for humans in the USA. It decreases systolic and diastolic arterial pressure in hypertensive humans at doses of 0.04mcg/kg/min to 0.8mcg/kg/min (Taylor et al. 1999). However, no change in haemodynamics at a dose of 0.03mcg/kg/min were seen in normotensive humans, and a dose of 0.3mcg/kg/min caused a moderate decrease in diastolic pressure but no change in systolic pressure (Mathur et al. 1999). Both doses increased renal blood flow, but not creatinine clearance, in normotensive humans (Mathur et al. 1999). There are species differences in the renal response to fenoldopam. Dogs showed an increase in renal blood flow, but this effect could not be documented in the sheep (Lass et al. 1988) or in neonatal piglets (Pearson et al. 1996). Six Thoroughbred foals, 87-122 h in age, were studied. All were considered normal on the basis of clinical examination, haematology and baseline measurements of cardiac output and arterial pressure. The foals were sedated with 5-10mg intravenous diazepam, and instrumented with jugular venous, dorsal metatarsal arterial and urinary catheters for the study. The foals were allowed to stand and nurse from the dam, and given a recovery period of 1 h from the administration of diazepam. The foals were then restrained in lateral recumbency on a foal mat and given two doses of fenoldopam (low dose: 0.04mcg/kg/min and high dose: 0.4mcg/kg/min) and a control dose of saline, in a double blind, randomized study.The infusion was maintained for 30 min, and measurements were performed during the last 20 min of infusion. The washout period was 40 min between infusions. Heart rate, arterial blood pressure and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index and stroke volume index calculated. Renal function was estimated by urine output and endogenous creatinine clearance. Repeated measures and one-way ANOVA tests were used to compare these parameters between each drug and placebo. Compared with saline, high dose fenoldopam resulted in a significantly increased heart rate (from 104±14 bpm to 143±22bpm), and decreased mean (from 89±6mmHg to 72±7mmHg) systolic and diastolic arterial blood pressure. There were no changes in renal indices. Low dose fenoldopam had no significant effect on systemic haemodynamics, but increased urine output. There was a trend to increased creatinine clearance with low dose fenoldopam, which was significant when compared with high dose fenoldopam. These data suggest that, unlike in the normotensive human, high dose fenoldopam results in a significant decrease in arterial blood pressure in the neonatal foal. Low dose fenoldopam results in no significant changes in haemodynamics, with increased urine output. Low dose fenoldopam therefore has a potential clinical application in neonatal foals with acute renal failure, and this warrants further investigation. Lass N.A., Glock L.I. (1988). Circulation 78, 1310-1115. Mathur V.S., Swan S.K., Lambrecht L.J., Anjum S., Fellmann J., McGuire D., Epstein M., Murray M.D., Luther R.R. (1999). Crit Care Med 27(9), 1832-1837. Pearson R.J., Barrington K.J., Jirsch D.W., Cheung P-Y. (1996). Crit Care Med 24(10), 1706-1712.