Dopamine is an inotropic agent that has vasodilatory effects at low doses. It is a common belief that low-dose dopamine may be helpful in the prevention and treatment of acute renal failure and is being widely used in these situations. Does dopamine have a beneficial effect in acute renal failure? Numerous studies in animals and a few in humans using low-dose dopamine have been reported. In this review, the authors summarize the literature and discuss the basis of this practice, which should be considered more of a myth than an ally for this purpose.
"Renal-dose" dopamine is widely used in clinical practice despite the controversial benefit in the prophylaxis and treatment of acute renal failure. Goldberg et al.[1] were the first to demonstrate the renal effects of low-dose dopamine in 1960. They found that dopamine at 100 µg/min caused increased natriuresis in patients with congestive heart failure. Still, more than 40 years since that report, low-dose dopamine for this indication remains controversial.
Infusion of dopamine in healthy animals and normal volunteers results in augmentation of renal blood flow and diuresis.[2-4] Dopamine at low doses augments renal blood flow by its action predominantly on the dopamine-1 receptors on the renal vasculature causing vasodilatation.[5] In intermediate doses it acts on the ß-adrenergic receptors and increases renal blood flow by increasing the cardiac output.[6,7] However, in higher doses dopamine acts predominantly as a vasoconstrictor by its action on α-andrenergic receptors. The distinctions between low, intermediate, and high doses are arbitrary and unclear in the literature. Generally, the low dose is considered to be <2.5 µg/kg/min, the intermediate dose is 2.5-5 µg/kg/min and the high dose is 5-20 µg/kg/min There may be significant overlapping between these doses. Also, there is a poor correlation between dopamine infusion and its plasma concentration.
Several animal studies using low-dose dopamine have been reported.[7-11] In these studies, acute renal failure was induced in the animals by clamping their renal arteries or aorta or by using nephrotoxic agents, and the effect of dopamine on renal blood flow and glomerular filtration rate (GFR) were studied. Doses of dopamine ranged from 0.4-6 µg/kg/min.[7-11] Animals receiving low-dose dopamine showed better preservation of GFR, improved renal perfusion, and natriuresis. However, it is not clear whether these effects have any influence on the long-term survival of the animal.
Numerous small case series and uncontrolled trials using low-dose dopamine have been reported in the literature. Most of these trials have several confounding variables -- i.e, serum creatinine, renal blood flow, and urine volume -- that limit the applicability of the results. Although low-dose dopamine has been shown to increase renal blood flow, as well as promote diuresis and natriuresis, its role in improving serum creatinine or creatinine clearance is not well established. Bellomo et al.,[12] in their multicenter randomized double-blind
study of 328 patients, demonstrated no difference between low-dose dopamine and placebo groups in the peak serum creatinine concentration. Baldwin et al.[13] studied 37 patients undergoing abdominal surgery and was unable to identify a favorable change in serum creatinine or creatinine clearance in the group of patients receiving low-dose dopamine. Additionally, Parks et al,[14] using low-dose dopamine on patients requiring surgery for obstructive jaundice, did not see any benefit in the GFR. A prospective study[15] on 52 patients undergoing coronary artery bypass grafting did not show any improvement in the urine output or serum creatinine with low-dose dopamine. Similarly, the prophylactic use of low-dose dopamine in patients undergoing liver transplantation has not been shown to be beneficial.[16,17]
Few other studies evaluated the effect of low-dose dopamine in patients with acute renal failure in the intensive care setting.[6] Flancbaum et al.[18] studied 19 postoperative oliguric patients and did not notice any difference in the mean creatinine or urine output in patients who received low-dose dopamine. Similarly, Paul et al.[19] observed no change in creatinine clearance or urine output with low-dose dopamine along with mannitol in their study involving 27 patients undergoing elective infrarenal aortic clamping. In a study by Davis et al.,[20] dopamine was infused at a dose of 100 µg/min for 4 hours in 15 patients with renal failure after cardiac surgery. In this study, the creatinine clearance, urine output, and the urine sodium excretion were improved in patients receiving low-dose dopamine. Similarly, Conte et al.[21] reported improvement in the renal blood flow, GFR, and urine output in the dopamine-treated patients in their study of eight subjects with cyclosporine-induced acute renal failure. However, in both these studies the benefits disappeared when the dopamine infusion was stopped. Patients may also develop tolerance to dopamine within 2-3 days.[22] Moreover, the effects of dopamine on the long-term renal outcome and survival of the patients is not known.[6]
Some clinicians use low-dose dopamine to prevent contrast-induced nephropathy in patients undergoing arteriography. There appears to be no benefit in the use of dopamine in this patient population. In a study by Gare et al.[7] a total of 66 patients with chronic renal failure and/or diabetes mellitus received low-dose dopamine (2 µg/kg/min) plus saline or saline alone for 48 hours. The authors reported no benefit of low-dose dopamine over saline in this high-risk patient population undergoing coronary angiography. In fact, a subset of patients with peripheral vascular disease treated with low-dose dopamine in this study showed worsening of their serum creatinine.
Low-dose dopamine is not without side effects. Dopamine can depress the respiratory drive, as well as increase the cardiac output and systemic vascular resistance.[23] There have been reports of low-dose dopamine causing tissue necrosis and digital gangrene.[24] Even small doses of dopamine can increase myocardial oxygen consumption and cause myocardial ischemia and cardiac arrhythmias.[25] Because of its natriuretic effects, dopamine can cause electrolytic imbalance, such as hypokalemia and hypophosphatemia, which can lead to serious problems in critically ill patients.[6] In addition, local extravasations of dopamine can cause a great deal of suffering, ischemia, and gangrene.
In conclusion, even though low-dose dopamine may facilitate urine output and natriuresis, the overall benefit of this effect in renal protection (prevention of a rise in the serum creatinine) is not established. Furthermore, there is no conclusive evidence to support using dopamine for the treatment or stabilization of acute renal failure. Moreover, even low-dose dopamine use can be associated with serious side effects. Therefore, based on the data presented here, we believe that it is a myth to consider low-dose dopamine use as a therapeutic option in the prevention or treatment of acute renal failure.
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