Shock is an acute, generalized state of inadequate perfusion of critical organs. It is defined as systolic blood pressure < 90 mm Hg or reduction of at least 40 mm Hg from baseline with perfusion abnormalities despite adequate fluid resuscitation.1 Mortality from shock ranges between 30 to 50%.2-5 While septic shock is associated with profound vasodilation leading to diminished systemic vascular resistance (SVR) and cardiogenic shock is caused by poor cardiac output, all shock states produce common physiologic derangements including impairment of myocardial contractility, alterations in adrenergic receptor activity, and hypoperfusion.2-5 Initial hemodynamic therapy of septic shock is the administration of intravenous fluid (20-40 mL/kg of crystalloid fluid), with the goal of attaining central venous pressure (CVP) of 8 to 12 mm Hg or 15 mm Hg in mechanically ventilated patients or patients with abdominal distension or preexisting ventricular dysfunction.4 Cardiogenic shock usually requires minimal fluid resuscitation.5
In septic shock patients not responding to fluid resuscitation, both dopamine and norepinephrine are considered agents of choice as the initial vasopressor.4 A recent survey of critical care pharmacists found that norepinephrine is the preferred initial agent (57%) followed by dopamine (28.6%).6 Inotropic support with dobutamine or dopamine is typically the initial pharmacologic therapy for patients with cardiogenic failure.5 Dosage titration and monitoring of vasopressor or inotropic support should be guided by the "best clinical response" as defined by hemodynamic stability (usually MAP ≥ 65 mm Hg), renal function (usually urine production ≥ 0.5 mL/kg/hour) and global perfusion parameters (usually venous oxygen saturation ≥ 70% or serum lactate concentration within normal range).4,5,7
Pharmacology of Dopamine and Norepinephrine
Dopamine possesses dose-related receptor activity at D1-, D2-, β1-, and α1-receptors.2,3 Dopamine stimulation at all dosages directly impedes gastric motility in critical illness and may aggravate gut ischemia in shock. At dosages of 5-10 mcg/kg/min, dopamine increases mean arterial pressure (MAP) by enhancing cardiac output (CO) through inotropic and chronotropic effects, primarily stimulating β1 receptors. The β-agonistic effects of dopamine may also explain the observations of some studies that showed dopamine is associated with pulmonary shunting, enhanced oxygen extraction by tissues relative to improved perfusion, and suppression of T-cell proliferation.2,3 At dosages > 10 mcg/kg/min, it increases MAP and SVR as a result of both increased CO and its α1 actions that induce vasoconstriction. Norepinephrine is a combined α- and β-agonist that produces vasoconstriction primarily via its more prominent α-effects on all vascular beds, thus increasing SVR.2,3 Norepinephrine administration generally produces either no change or minor increase in CO.2,3 It possesses minimal effects on tissue oxygen extraction or utilization.2,3
Comparative Studies of Dopamine and Norepinephrine
Few studies have compared these two agents for the purpose of hemodynamic resuscitation in shock. In a randomized study of 32 septic shock patients unresponsive to volume resuscitation, norepinephrine alone was superior to dopamine in achieving and maintaining preset hemodynamic (MAP of at least 80 mm Hg) and oxygen-transport variables for at ...