A critical look at dopamine

As I was perusing through the online medical education offerings a couple of months ago, an article in the New England Journal of Medicine caught my eye; a comparison of dopamine and norepinephrine in patients with shock:

http://www.nejm.org/doi/full/10.1056/NEJMoa0907118

Since it was a free download, I saved it to my computer and resolved to look at it once things settled down a little bit.  Now that the school semester is drawing to a close, I decided to take a look at it, and was immediately drawn in.  As it turns out, the authors discovered that there were no randomized, controlled trials comparing dopamine with other vasopressor/inotropes.  So they went ahead and did one; enrolling about 1600 patients with shock of all types, they gave either dopamine or norepinephrine and monitored for adverse events, 28-day mortality, and a few other parameters like days spent in the ICU, days spent on mechanical ventilation, and some other stuff that has great relevance in the ICU, but not in the back of the ambulance.

Overall, what they found was, you might say, interesting:

(Image source is the article linked above)

Overall, the choice of vasopressor didn't seem to matter with regards to adverse events, except for arrhythmias.  There, the dopamine group had a statistically significant incease in nasty arrhythmias like ventricular tachycardia and ventricular fibrillation.  The 28-day mortality findings were similar;

(Source: article linked above)
When they measured for 28-day mortality, the survival rates were about equal, except for patients with cardiogenic shock.  Then things changed; if you had cadiogenic shock and were given dopamine, you were more likely to die than if you were given norepinephrine.  This begs the question:

Why does norepinephrine seem to be equal, or better, than dopamine in treating shock?

Well, to start answering that question, we need to go back to the pharmacology book and review what the drugs do.

(Source: www.medscape.com)

Just referencing the chart above, norepinephrine seems to balance between inotropic and vasopressor actions a little better than dopamine, which strongly favors inotropy over vasopressor duties.

In most types of shock, this is not a big deal; the primary problem is not located in the heart, and the heart may be relatively normal.  In cardiogenic shock, however, the heart is dysfunctional and weakened; increasing the sympathetic stimulation and inotropy to it is probably analagous to running your automobile out of oil, transmission fluid, and radiator fluid and then taking it to the drag strip for a night of racing.  Or, it could be the opposite; norepinephrine increases sympathetic tone in the blood vessels, which would result in an increased diastolic blood pressure.  Diastole happens to be the phase during the cardiac cycle when the coronary arteries are perfused.  This could mean that the weakened heart is given its best chance at close-to-normal function with norepinephrine compared with dopamine.

No definitive answer; but then, that's the way that physiology goes.

Which inotrope/vasopressor should be on our ambulances?

Another good question.

Dopamine was a mainstay on the truck by the time that I first ventured into EMS; why that is, I don't know.  It might have been the prototype drug, but I have no information to support this (feel free to comment if you know the answer!).  When I learned about dopamine in paramedic school, it seemed like a neat idea; it could be an inotrope at lower dosages, or it could magically turn into a vasopressor at higher doses.  Truth is, dopamine's a fairly dirty drug (like amiodarone, but that's a whole other rant), without any evidence to support its' superiority in today's formulary.  It may have been the only drug of its' class when EMS began, but it isn't anymore.  And the only RCT comparing it to other agents shows that norepinephrine is just as good, or better in cardiogenic shock (and be honest....how many times have you hung dopamine in a patient who WASN'T in cardiogenic shock?).

Is it time for dopamine to get replaced by "Leave 'Em Dead"?  I'd really like to get your opinions on it....or even better, contrarian research :)