Renal Protection:
All that Glitters is not Gold
This article is
a quick and useful compilation of clinical studies and case reports
of relevant fenoldopam use. Unfortunately, the volume of data regarding
applicability is sparse indeed.
Fenoldopam is a
dopaminergic receptor agonist [trade name: Corlopam® (fenoldopam
mesylate), Neurex Pharmaceuticals]. It selectively acts on DA1 (vasodilator)
and not DA2 (adrenergic effect) receptors. Primary studies have evaluated
fenoldopam against placebo (it's better!) and sodium nitroprusside [SNP]
(it's almost as good). SNP is somewhat quicker in effect, but fenoldopam,
with a half-life of 5-10 minutes, is much easier to titrate, and has
limited side effects (and no cyanide toxicity). [Editor's note: See
Dr.
Coursin's newest article for more information on drugs used for
renal protection]
The hypotensive
effects are accomplished via vasodilation, especially of key organs
such as the kidneys and GI tract. This causes a decrease in fractional
excretion of sodium and decreased specific gravity (i.e. more free water
excretion). SNP, in contrast, does not selectively dilate renal arteries
and does not have this same effect. The ejection fraction of the heart
is also aided as decreased afterload is accomplished (as with SNP),
but with less preload effects and possibly a better maintenance of cardiac
output.
Intraoperative use
of fenoldopam is rarely reported — it has been used in one patient
to augment SNP BP control during pheochromocytoma resection, and used
as a sole agent for that purpose in a patient who was well alpha- and
beta- blocked.
For post operative
HTN, effective infusion rates were 0.2 to 0.8 mcg/kg. Some individuals
required up to 1.6 mcg/kg/min.
Renal Protection
Due to the effects on renal vasculature, a role in perioperative protection
against renal failure has been postulated. The beneficial effects of
low dose "renal" dopamine infusions have been touted as a renal protectant,
but failed to demonstrate protective effects despite many years of use
and several clinical studies. Fenoldopam has never even been tested.
Having said that,
animal models have demonstrated a protective effect of fenoldopam on
toxic substance mediated renal failure. A couple of poor human study
abstracts (retrospective, no controls) are cited in this review paper
which give us at least some hope that this drug may be beneficial. A
real clinical study is needed however before committing to use this
drug for that purpose (e.g. during AAA surgery).
What actual data
is there? One studied compared use of SNP to induce hypotension vs.
fenoldopam. SNP lowered renal blood flow; fenoldopam increased it. In
another interesting study, with PEEP decreasing preload and causing
renal vasoconstriction, adding fenoldopam reversed the increased renal
vascular resistance and increased U.O.
Gastric effect
Just as dopamine receptors vasodilate the renal arteries, they similarly
affect the splanchnic circulation. Current thinking suggests that GI
ischemia may be a primary cause of postoperative complications and prolonged
length of stay, and may contribute to multi-organ system failure following
shock. Therefore, there is good reason to investigate whether this drug,
which has shown benefits maintaining GI mucosal pH (a sign of healthy
perfusion), will provide some degree of clinical protection. Again,
a real clinical study is in order before using fenoldopam for that purpose.
Adverse effects
Adverse effects are relatively infrequent and relate to vasodilation.
No rebound HTN has been reported after discontinuation. Of note, ICP
may be adversely affected by infusion. Rebound tachycardia should be
expected with decreased afterload. Other adverse effects can be found
in the package insert.
Conclusions
Fenoldopam has great promise but no proof of efficacy in our arena.
It is 100 times more expensive than SNP, and 20-50 times that of dopamine.
It is 4 times the cost of nicardipine. Therefore, before encouraging
routine use, there should be some study suggesting clinical utility.
