Effects of fenoldopam on intracranial pressure and hemodynamic variables at normal and elevated intracranial pressure in anesthetized pigs.
Fenoldopam (FE), a dopamine DA1-receptor agonist, has been introduced for treatment of arterial hypertension and heart failure and for preservation of renal function. Vasodilators are generally assumed to affect all vascular beds including the cerebral circulation. We have evaluated effects of FE-induced (4 micrograms.kg-1.min-1) arterial hypotension on intracranial pressure (ICP) and intraocular pressure (IOP) under conditions of normal and increased intracranial elastance. ICP and IOP responses to hypertension were tested by infusion of angiotensin II (15 micrograms.kg-1.min-1), and the response to hypercapnia was tested by elimination and reintegration of soda lime canisters in the breathing circuit. Intracranial elastance was increased by infusing mock cerebrospinal fluid (CSF) into the lateral ventricle (20 +/- 3 ml.h-1). Arterial hypotension induced with FE did not increase ICP. With increased intracranial elastance, the infusion rate of mock CSF had to be reduced while administering FE to avoid a rise in ICP (p < 0.05 compared with preinfusion value); this indicates a shift on the volume-pressure curve to the right. There were no indicators that cerebral autoregulation or CO2 reactivity of the cerebral vasculature were affected by FE in this anesthetized porcine model, as speculated from analysis of the time course of delta ICP. There are, however, indicators of increased intracranial elastance, most likely caused by vasodilation. Caution should hence be exercised when FE is administered to patients with increased intracranial elastance.
Hennes
H J
HJ
Department of Anesthesiology, Johannes Gutenberg-University Medical School, Mainz, Germany.
Jantzen
J P
JP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000768:Anesthesia, General; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018818:Fenoldopam; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects*; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009798:Ocular Hypertension / Q000503:physiopathology; D011559:Pseudotumor Cerebri / Q000503:physiopathology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D015259:Dopamine Agents; D000804:Angiotensin II; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam