Dopamine Versus Norepinephrine for the Treatment of Vasopressor Dependent Septic Shock

Research Question/Hypothesis: The initial selection of the vasopressor norepinephrine in comparison to dopamine will result in a decrease in mortality for patients in septic shock.

Study Design/Source Population:

This trial is a single-center, prospective, randomized, open-label comparison of dopamine versus norepinephrine as initial vasopressor for patients presenting with septic shock. The study takes place at Rush University Medical Center, a 600 bed facility. Patients are transferred to our medical intensive care unit from the emergency room (ER), general medical floors, and from outside hospitals. Patients were eligible if they were greater than 18 years of age, and presented with a diagnosis of SIRS plus a suspected or documented source of infection. Patients were not eligible if they were found to have hypovolemic and/or hemorrhagic etiologies of their vasodilatory shock or another etiology of their SIRS.

Patients in the medical intensive care unit presenting with septic shock were randomized to receive either dopamine or norepinephrine as the first-line vasopressors for septic shock. Randomization was based upon whether the patient presented on an odd or even day of the week. For example, if the patient had presented on the third then they would be randomized to dopamine and if they had presented to the ICU on the fourth then they would be randomized to the norepinephrine treatment arm. The study investigators accept that the randomization scheme is not truly randomized, however a patient presenting with sepsis is not dependent on the day of the week. For example, the timeline for a patient to present with sepsis is unpredictable and the therapy for septic shock is started immediately upon their diagnosis, therefore the selection of a vasoactive agent (norepinephrine or dopamine) is really determined by the date of the patient's presentation, rather than the investigator.

All patients were treated according to recommendations by the Surviving Sepsis Campaign (early-goal directed therapy including fluid resuscitation, early and appropriate antimicrobial therapy, strict glycemic control, and consideration of steroid replacement for patients with relative adrenal insufficiency). Patients presenting with hemodynamic instability are first treated with initial fluid resuscitation which encompasses either 500ml to 1000ml of crystalloid or 300ml to 500ml of colloid, depending on a clinician's preference. The administration and titration of vasopressors was directed to achieve a mean arterial pressure ≥ 60 mmHg or a systolic pressure ≥ 90 mmHg. If the predetermined maximum dose was reached for the initial vasopressor, then an addition of vasopressin at a continuous dose of 0.04 units/min was initiated. Patients who still required hemodynamic support were then started on an infusion of phenylephrine.