Dopamine Infusion in Healthy Subjects and Critically Ill Patients

Ratge, D.; Steegmüller, U; Mikus, Gerd; Kohse, Klaus P.; Wisser, H.

doi:10.1111/j.1440-1681.1990.tb01332.x

“…Thus, although or metabolic products of noradrenaline [47]. In accordance with other studies [45, 46,48], the present plasma clearance a functional role of the high density of D 1 -receptors in the proximal tubule has been suggested by in vitro studies [13], of dopamine greatly exceeded hepatic blood flow and GFR. These data support the hypothesis of a peripheral metabolism the present results confirm that the natriuretic effect of D 1 -receptor agonists in humans and intact animals may occur of exogenous dopamine.…”

Section: Excretion Of Sodium and Water ( Figure 2)supporting

confidence: 89%

Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response study

Olsen¹,

Olsen

²

,

Bonde³

et al. 1997

Br J Clin Pharmacol

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AimsThe purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 mg kg −1 min −1 in normal volunteers. Methods While undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 mg of dopamine kg −1 min −1 over 2 h in a randomized and double-blind fashion. On each study day, renal clearance studies were performed during a 1 h baseline period and subsequently during the second 1 h infusion period. Lithium clearance (CL Li ) was used to estimate proximal tubular outflow.Results Cardiac output increased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dosedependent increase from the 7.5 mg kg Conclusions In conclusion, the renal vasodilating effect of dopamine was maximal with 3 mg kg −1 min −1 . The dose-dependent attenuation seen with higher doses is consistent with an increased a-adrenergic stimulation opposing the effect on dopaminergic receptors. The present CL Li studies confirm that dopamine increases proximal tubular outflow. The results suggest that the natriuretic effect of depressor doses of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Pressor doses further increased sodium excretion, indicating the presence of pressure natriuresis at these high doses.Keywords: renal haemodynamics, kidney function, natriuresis, dopamine, dose-response, tubular function, lithium clearance, sodium hydronephrotic kidney of the rat [4], thus supporting the Introduction concept of a vasodilating effect of specific dopaminergic D 1 -receptor activation, which at higher doses is opposed by In anaesthetized dogs [1] and rats [2], low doses of dopamine decreased renal vascular resistance, whereas higher doses an action of a-adrenergic receptors [5,6]. Another important effect of dopamine, which does not occur with other caused vasoconstriction. a-adrenergic receptor blockade abolished the vasoconstriction so that vasodilation was catecholamines, is the increase in sodium excretion [5][6][7]. Stimulation of D 1 -receptors in proximal tubular brushobserved with all doses of dopamine [2]. These dosedependent effects have been confirmed in studies using border membranes inhibits the Na

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“…Thus, although or metabolic products of noradrenaline [47]. In accordance with other studies [45, 46,48], the present plasma clearance a functional role of the high density of D 1 -receptors in the proximal tubule has been suggested by in vitro studies [13], of dopamine greatly exceeded hepatic blood flow and GFR. These data support the hypothesis of a peripheral metabolism the present results confirm that the natriuretic effect of D 1receptor agonists in humans and intact animals may occur of exogenous dopamine.…”

Section: Renal Haemodynamics ( Figure 1)supporting

confidence: 89%

Dopamine natriuresis in salt‐repleted, water‐loaded humans: a dose‐response study

Olsen¹,

Olsen

²

,

Bonde³

et al. 1997

Brit J Clinical Pharma

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AimsThe purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 mg kg −1 min −1 in normal volunteers. Methods While undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 mg of dopamine kg −1 min −1 over 2 h in a randomized and double-blind fashion. On each study day, renal clearance studies were performed during a 1 h baseline period and subsequently during the second 1 h infusion period. Lithium clearance (CL Li ) was used to estimate proximal tubular outflow.Results Cardiac output increased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dosedependent increase from the 7.5 mg kg Conclusions In conclusion, the renal vasodilating effect of dopamine was maximal with 3 mg kg −1 min −1 . The dose-dependent attenuation seen with higher doses is consistent with an increased a-adrenergic stimulation opposing the effect on dopaminergic receptors. The present CL Li studies confirm that dopamine increases proximal tubular outflow. The results suggest that the natriuretic effect of depressor doses of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Pressor doses further increased sodium excretion, indicating the presence of pressure natriuresis at these high doses.Keywords: renal haemodynamics, kidney function, natriuresis, dopamine, dose-response, tubular function, lithium clearance, sodium hydronephrotic kidney of the rat [4], thus supporting the Introduction concept of a vasodilating effect of specific dopaminergic D 1 -receptor activation, which at higher doses is opposed by In anaesthetized dogs [1] and rats [2], low doses of dopamine decreased renal vascular resistance, whereas higher doses an action of a-adrenergic receptors [5,6]. Another important effect of dopamine, which does not occur with other caused vasoconstriction. a-adrenergic receptor blockade abolished the vasoconstriction so that vasodilation was catecholamines, is the increase in sodium excretion [5][6][7]. Stimulation of D 1 -receptors in proximal tubular brushobserved with all doses of dopamine [2]. These dosedependent effects have been confirmed in studies using border membranes inhibits the Na

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“…One of the reasons for the failure of low‐dose dopamine in the clinical setting is due to its highly variable and unpredictable pharmacokinetics. In a study measuring levels of both free and sulfoconjugated dopamine (13), in healthy volunteers and critically ill patients, receiving an infusion of dopamine at 5 μg/kg/min, there was wide range of steady‐state concentrations (12.4–73.4 μ g/l). The volume of distribution also varied considerably (19.8–75 l/kg).…”

Section: Unpredictable Pharmacokineticsmentioning

confidence: 99%

CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Low‐dose Dopamine in the Intensive Care Unit

Karthik

¹

,

Lisbon

²

2006

Seminars in Dialysis

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For much of the last four decades, low-dose dopamine has been considered the drug of choice to treat and prevent renal failure in the intensive care unit (ICU). The multifactorial etiology of renal failure in the ICU and the presence of coexisting multisystem organ dysfunction make the design and execution of clinical trials to study this problem difficult. However, in the last decade, several meta-analyses and one large randomized trial have all shown a lack of benefit of low-dose dopamine in improving renal function. There are multiple reasons for this lack of efficacy. While dopamine does cause a diuretic effect, it does very little to improve mortality, creatinine clearance, or the incidence of dialysis. Evidence is also growing of its adverse effects on the immune, endocrine, and respiratory systems. It may also potentially increase mortality in sepsis. It is the opinion of the authors that the practice of using low-dose dopamine should be abandoned. Other drugs and treatment modalities need to be explored to address the serious issue of renal failure in the ICU.

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Dopamine Infusion in Healthy Subjects and Critically Ill Patients

Cited by 23 publications

References 15 publications

Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response study

Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response study

Dopamine natriuresis in salt‐repleted, water‐loaded humans: a dose‐response study

CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Low‐dose Dopamine in the Intensive Care Unit

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