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Objectives: To assess the effects of low-dose dopamine on norepinephrine-induced renal and systemic vasoconstriction in normotensive healthy subjects. Design: On separate days, either a low-dose dopamine (4 micro signg/kg/min) or a placebo (5% glucose) infusion was added in a single, blinded, randomized order to incremental norepinephrine infusions of 40, 80, and 150 ng/kg/min over a 60-min period each. Setting: Outpatient clinic of a university-affillated hospital. Subjects: Normotensive healthy volunteers. Interventions: Infusions of norepinephrine and dopamine. Measurements and Main Results: Blood pressure and heart rate were measured with a semiautomated device, and glomerular filtration rate and effective renal plasma flow were determined with constant infusions of125 I-iothalamate and131 I-hippurate, respectively. Norepinephrine alone progressively increased mean arterial pressure to pressor levels, whereas this effect was attenuated by the addition of dopamine (p < .05 vs. norepinephrine alone). Glomerular filtration rate increased during lower norepinephrine doses and did not decrease at the highest norepinephrine dose. Addition of dopamine further increased glomerular filtration rate. Effective renal plasma flow decreased with each norepinephrine alone infusion step, but this decrease was completely prevented by concomitant dopamine infusion (p < .01 vs. norepinephrine). Sodium excretion tended to decrease with norepinephrine, but increased two- to three-fold after addition of dopamine (p < .01 vs. norepinephrine alone). Conclusions: In healthy man, norepinephrine causes a large decrease in renal plasma flow but not in glomerular filtration rate. Concomitant dopamine administration prevents this decrease in renal plasma flow, increases sodium excretion, and also attenuates the norepinephrine-induced systemic blood pressure increase. These findings warrant further clinical evaluation of the effect of concomitant low-dose dopamine and norepinephrine administration in critically ill patients. (Crit Care Med 1998; 26:260-265) Norepinephrine is increasingly recognized as a valuable agent in the treatment of septic shock 1-6. By eliciting a strong vasoconstrictive response, norepinephrine has been reported 1,4,6 to restore blood pressure and tissue perfusion more efficaciously than high-dose dopamine. However, the norepinephrine-induced reduction in renal blood flow 7-9 makes many clinicians reluctant to use this agent in hypotensive patients since an already compromised renal function may further deteriorate under these circumstances. Intravenous dopamine at dosages of 1 to 4 micro signg/kg/min augments renal blood flow in healthy man 10,11, as well as in mechanically ventilated patients 12. These low infusion rates of dopamine have been proposed to oppose the renal vasoconstrictive actions of norepinephrine 13,14. For this reason, low-dose dopamine is widely used as a renoprotective agent during norepinephrine therapy. However, the renal supportive action of dopamine to overcome norepinephrine-induced renal vasoconstriction has not been proven in these situations, and the hemodynamic effects of combined infusions have received little attention. In the dog, dopamine has been documented to increase in renal blood flow during norepinephrine infusions, but these observations cannot be easily extrapolated to humans since dogs have a different renal hemodynamic profile during norepinephrine infusion from man 15. In healthy subjects, recent results 16 suggested that dopamine may blunt the renal vasoconstrictive effect of norepinephrine that was given as a single pressor dose. In the present study, we evaluated whether dopamine could counteract norepinephrine's actions on renal hemodynamics by adding low-dose dopamine to stepwise incremental norepinephrine doses in normotensive healthy subjects.
Hoogenberg et al. (Sun,) studied this question.