DOPAMINE 1910-2010 R.I.P.

Dopamine has had a rough couple of years. First, renal sparing low dose dopamine was disproven. Then, two big studies published in 2010 pushed it further into darkness: The SOAP II study had 1600 patients and another one printed in Shock had 250 patients. Both studies randomised patients in shock and in need of vasopressors to either dopamine or noradrenaline. Both made the same conclusion. There was no significant overall difference in 28-day mortality, but the dopamine group had significantly higher incidence of arrhythmias.

And as a kick in the nuts to the cardiologists, the dopamine sub-group with cardiogenic shock actually did show a higher mortality compared to noradrenaline. Cardiogenic shock is exactly the group where dopamine was recommended by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.

And all this after the magical kidney protecting low dose dopamine theory was debunked some years earlier.

So on its 100th anniversary, dopamine suffered a huge blow. This might not be the end of dopamine in critical care, but for the time being, it’s mostly sitting in a dark corner of the medical storage, and noradrenaline seems like the safest vasopressor choice in shock patients. Also – or even especially – in cardiogenic shock.


Comparison of dopamine and norepinephrine in the treatment of shock.
De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. N Engl J Med. 2010 Mar 4;362(9):779-89:

Background: Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other.

Methods: In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 μg per kilogram of body weight per minute for dopamine or a dose of 0.19 μg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events.

Results:The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P

Conclusions: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. ( number, NCT00314704.)

Additional letters to the Editor and the authors’ answer can be found here

Efficacy and safety of dopamine versus norepinephrine in the management of septic shock.
Patel GP, Grahe JS, Sperry M, Singla S, Elpern E, Lateef O, Balk RA. Shock. 2010 Apr;33(4):375-80:

Background: The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine (NE) and dopamine (DA) as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol.

Methods: A prospective, randomized, open-label, clinical trial was used in a medical intensive care unit comparing DA with NE as the initial vasopressor in fluid-resuscitated 252 adult patients with septic shock. If the maximum dose of the initial vasopressor was unable to maintain the hemodynamic goal, then fixed-dose vasopressin was added to each regimen. If additional vasopressor support was needed to achieve the hemodynamic goal, then phenylephrine was added. The primary efficacy end point was all-cause 28-day mortality. Secondary end points included organ dysfunction, hospital and intensive care unit length of stay, and safety (primarily occurrence of arrhythmias).

Results: The 28-day mortality rate was 50% (67/134) with DA as the initial vasopressor compared with 43% (51/118) for NE treatment (P = 0.282). There was a significantly greater incidence of sinus tachycardia with DA (24.6%; 33/134) than NE (5.9%; 7/118) and arrhythmias noted with DA treatment (19.4%; 26/134) compared with NE treatment (3.4%; 4/118; P < 0.0001), respectively. Logistic regression analysis identified Acute Physiologic and Chronic Health Evaluation II score (P < 0.0001) and arrhythmia (P < 0.015) as significant predictors of outcome.

Conclusion: In this protocol-directed vasopressor support strategy for septic shock, DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, there were significantly more cardiac arrhythmias with DA treatment. Patients receiving DA should be monitored for the development of cardiac arrhythmias.

Update 27. feb. 2012:
This just out meta-analysis, that includes the above-mentioned studies and more, just strengthens the case against dopamine as a first line treatment in shock:
Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis, Crit Care Med, 2012

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