LETTER TO EDITOR
Year : 2002 | Volume
: 13 | Issue : 4 | Page : 512--514
Does Dopamine Still Deserve to be Prescribed in "Renal Dose" to the Critically ill?
Anil K Saxena
Post-Graduate Department of Medicine, King Fahad Hospital, Hofuf, Al-Hasa-31982, Saudi Arabia
Anil K Saxena
Post-Graduate Department of Medicine, King Fahad Hospital, Hofuf, Al-Hasa-31982
|How to cite this article:|
Saxena AK. Does Dopamine Still Deserve to be Prescribed in "Renal Dose" to the Critically ill?.Saudi J Kidney Dis Transpl 2002;13:512-514
|How to cite this URL:|
Saxena AK. Does Dopamine Still Deserve to be Prescribed in "Renal Dose" to the Critically ill?. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2020 Dec 4 ];13:512-514
Available from: https://www.sjkdt.org/text.asp?2002/13/4/512/35803
To the Editor:
Despite persistent reservations expressed by various authors from time to time, particularly during the past ten years, dopamine "renal dose" continues to be administered very frequently to critically ill patients. The use of dopamine is not only for improving the state of circulatory distribution in imminent cadiogenic shock, but also for the prevention of declining and/or improvement of renal perfusion in diverse medical and surgical conditions and in high-risk procedures, in the hope of avoiding the menacing development of acute renal failure (ARF). The far-reaching global use of dopamine as a "renal protective" agent in critically ill patients is based on physiology suggesting selective renal vasodilatation in animal models and human subjects when it is infused at low-dose, the "renal-dose". , Earlier studies , involving small patient populations had reported consistent apparent increases in fractional excretion of sodium (FeNa), and urine output following "lowdose" dopamine administration with or without co-administration of diuretics. Since urine output is an erroneous marker of glomerular filtration rate (GFR), and simultaneous administration of diuretics may have a confounding influence on FeNa, these studies offer only meager data to support the use of dopamine in the management of ARF. Denton et al (1996) concluded that renal-dose of dopamine should not be used for its selective renal vasodilatory effect in patients with ARF until its effectiveness is established decisively. 
Dopamine exerts its action on the cardiovascular and renal neuro-humoral system by acting on a number of different receptors that have diverse actions making its effects extremely complicated. Dopamine stimulates beta-adrenoreceptors and increases the cardiac index.  High-dose dopamine interacts with peripheral alpha-one-adrenoreceptors causing systemic vasoconstriction.  In addition, it acts on peripheral receptors with their subgroups, DAi and DA2. DAi receptors have been recognized on renal, mesenteric, coronary and cerebral arteries while DA2 receptors, on autonomic ganglia and sympathetic nerve endings where they inhibit noradrenaline release.  DAi receptor-related vasodilatation and inhibition of electrolyte transport is mediated by cAMP. DA2 receptors inhibit aldosterone production in the adrenal gland.  In the inner medulla, DA2 receptor is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2.  However, the precise role of DA2 receptors remains unclear. Dopamine directly stimulates sodium uptake in proximal tubular cells; this implies that the natriuretic effect of dopamine is due to alterations in hemodynamics and distal tubular effects. Dopamine has been hypothesized to act as intrarenal natriuretic hormone. In view of the complexity of dopamine's actions, it is not surprising that there is an overlap of doses at which a range of effects of dopamine are seen concurrently and no dose could actually be absolutely renal in action.
Low-dose dopamine (0.5-3.0 ug/kg/min) infusion in normal human subjects has been reported to enhance renal blood flow (RBF) and GFR by stimulation of DA] receptors.  Nonetheless, Vargo et al,  found no significant change in GFR in their recent randomized, controlled, crossover trials. For these reasons, the authenticated evidence of low-dose dopamine-induced alteration of GFR in man is inconsistent.
Moreover, randomized controlled trials have failed to demonstrate a better outcome of dopamine use with respect to prevention of ARF, requirement for dialysis and resultant mortality in various clinical settings. The Auriculin Anaritide Acute Renal Failure Study  Group USA, in 1997, conducted a randomized placebo controlled multicentre trial that included 250 patients with ARF to examine the relationship between low-dose dopamine administration and outcomes of ARF. There were 93 (36%) deaths documented; 52 (20%) required dialysis during 60 days study period despite being on renal dose dopamine. The relative risk (RR) of death associated with dopamine administration was 1.11 (95% Confidence Interval0.66 to 1.89) raising reservations concerning its safety and efficacy. Similarly, the NORASEPT II Study,  USA (1999), in their controlled, randomized multicenter trial concluded that dopamine "renal-dose" does not prevent ARF in patients with septic shock and oliguria.
More recently, Kellum et al,  performed a meta-analysis of 58 studies (n=1019) from 1966 to 2000 including 17 randomized clinical trials (n=854) and reported that renal-dose dopamine did not reduce mortality (RR, 0.90 [0.44-1.83]; p=0.92), onset of renal failure [RR, 0.81 (0.55-1.19)] or need for dialysis [RR, 0.83 (0.55-1.24]. They concluded that there was insufficient statistical evidence to support any large (>50%) effect of dopamine on risk of ARF or need for dialysis and so this drug ought to be eliminated from routine clinical use.
A recent randomized, double blind, placebo controlled, multicenter study was carried out by the Australian and New Zealand Intensive Care Society clinical trial group.  They studied 328 patients admitted to 23 participating intensive care unit (ICU), randomly assigned to continuous intravenous infusion of dopamine (2 jag/kg/min) or placebo, administered through a central venous catheter (CVC) while in the ICU. The patients' assigned to dopamine (n=161) and those assigned to placebo (n=163), were similar in terms of baseline characteristics, renal function and duration of trial infusion. No difference between the dopamine and placebo groups was found in peak serum creatinine concentration during the treatment, in the increase from baseline to highest value during treatment, or in numbers of patients whose serum creatinine concentration exceeded 300 jimol/L or who required renal replacement therapy. Sixty-nine patients in the dopamine group and 66 in the placebo group died. The authors concluded that administration of low-dose dopamine by continuous infusion does not confer any protection from renal dysfunction in ICU. The credence of evidence currently reachable goes compellingly against the very existence of "renal-dose dopamine and its role as "renal protective" agent. In addition, there is apprehension related to impending adverse effects " ranging from local tissue necrosis to suppression of anterior pituitary dependent hormones and decline in T-cell proliferation through cardio-respiratory dysfunction. These factors demand the exclusion of so called "renal dose" of dopamine from regular clinical use, especially amongst critically ill individuals, with endangered metabolic and immunologic homeostasis.
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