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A New Look at Dopamine and Norepinephrine for Hyperdynamic Septic Shock

1994; Elsevier BV; Volume: 105; Issue: 1 Linguagem: Inglês

10.1378/chest.105.1.7

1931-3543

Charles E. Lucas,

Sepsis Diagnosis and Treatment

In the June, 1993 issue of Chest, Martin and coworkers (103:1826) have addressed an important therapeutic challenge met daily by physicians caring for severely ill patients being treated for sepsis in a critical care setting. A significant percentage of patients with life-threatening sepsis will exhibit the hyperdynamic state as evidenced by a suboptimal blood pressure, a reduction in peripheral vascular resistance, and an increase in cardiac index. The current priorities of care in this setting include correction of red blood cell deficits to augment oxygen-carrying capacity and restoration of effective plasma volume to restore perfusion pressure and thus organ perfusion, especially renal circulation. When appropriate blood and fluid replacement provide inadequate restoration of perfusion, inotropic support is added. Most commonly, the inotropic agent first called for is dopamine, which is purported to increase perfusion pressure by enhancing cardiac contractility while protecting critical organs such as the kidney. The authors have challenged this routine practice. This well-planned and meticulously implemented prospective randomized study compares the effects of dopamine (2.5 to 25 pg/kg/min) with those of norepinephrine (0.5 to 5.0 µg/kg/min) in meeting reasonable predefined treatment goals. The definition of hyperdynamic septic shock used to permit entrance into the randomization process is well accepted. The predefined end points of restoring perfusion pressure and oxygen delivery are universally accepted. Within this framework, the authors have shown a clear-cut superiority of norepinephrine in meeting these end points compared with dopamine. Only 31 percent of the patients (5 of 16) reached these predefined treatment goals with dopamine (10 to 25 pg/kg/min), whereas 93 percent (15 of 16) reached the same end points with norepinephrine infusion (1.0 to 5.0 µg/kg/min). A more impressive finding in this study was the observation that 10 of the 11 patients who did not fully respond to dopamine infusion at a dosage of 25 µg/kg/min did reach the predefined end points when norepinephrine was added to the infusion as part of their crossover implementation design. In contrast, the single patient who did not reach predefined end points with epinephrine infusion also failed to reach these end points when dopamine infusion was added. One patient in each group died of refractory septic shock within hours of the study after being found not fully responsive to the combination of both dopamine and norepinephrine infusions; this reflects the severity of the septic insult in these patients. These findings should stimulate critical care physicians to re-examine at the role of routine dopamine infusion in such patients. Concomitantly, one must reassess the negative views on norepinephrine infusion that have developed. Prior bad experience likely reflected the combination of excessively high doses with inadequate effective plasma volume replacement. This combination led to a restoration of blood pressure but not perfusion in patients who were noted to have “cold, clammy skin” and oliguria that progressed to renal shutdown and death. Indeed, the practice of adding norepinephrine to the ongoing infusion was so feared that this treatment was dubbed a “lethalphed infusion.” A relook at the role of norepinephrine infusion in a setting where more accurate invasive monitoring allows for frequent assessment of cardiac index, peripheral vascular resistance, oxygen delivery, and central filling pressures is needed. Use of the Frank-Starling curve to identify when high central filling pressures are indicative of lung failure but not heart failure will facilitate these future studies. A frequent misconception is that the increased urine output observed in response to a low-dose dopamine infusion indicates a dopaminergic renal receptor which facilitates renal vasodilation and, thus, enhanced renal perfusion independent of cardiac index. The authors have demonstrated that this increase in urine output also occurs with norepinephrine infusion. Their data support the conclusion that the increase in urine output in response to a low-dose infusion of both agents results not from a renal receptor but from the traditional baroreceptor responses that shut off the release of antidiuretic hormone from the pituitary. No study in man using traditional methods for measuring renal blood flow has shown an increase in renal blood flow independent of an increase in cardiac output after low-dose dopamine or norepinephrine infusion. Unpublished studies from our laboratory show that renal blood flow is directly related to cardiac index after the addition of dopamine; thus, the increased urine output is explained totally by the antidiuretic hormone effect. The authors must be congratulated on this fine project, which should lead to many similar prospective assessments of these agents.