Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia.
OBJECTIVE
To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep.


METHODS
Randomised, controlled, experimental study.


METHODS
Animal research laboratory.


METHODS
12 adult instrumented, midazolam-sedated sheep.


METHODS
The animals were randomised to receive a 20-min continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10 microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25-30% increase in cardiac output by all three drugs during control conditions.


RESULTS
Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO2) and consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO2 and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO2 (especially in the coeliac trunk) observed during control conditions.


CONCLUSIONS
During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO2 and VO2.
Schwieger
I M
IM
Department of Anaesthesia, Pharmacology, and Surgical Intensive Care, University Hospital of Geneva, Genève, Switzerland.
Schiffer
E R
ER
Morel
D R
DR
D000818:Animals; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D018818:Fenoldopam / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011897:Random Allocation; D012756:Sheep; D013152:Splanchnic Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D018491:Dopamine Agonists; D014665:Vasodilator Agents; D018818:Fenoldopam; D004298:Dopamine; D009638:Norepinephrine