Understanding prehospital vasopressors: Dopamine, epinephrine or norepinephrine?
Which vasopressor to use, when to use them and what to watch out for
Managing hypotension in the field can be tricky. While only about 1-2% of EMS patients (non-trauma) present with hypotension and shock, this small subset of patients carries an in-hospital mortality rate between 33-52% . This means that vasopressors are not used often, but they are used on the sickest of patients. A practical understanding of what common vasopressors do, both the good and the bad, is important in guiding clinical treatment decisions.
Vasopressors, sometimes called just “pressors,” refers to a group of medications that are used primarily for their ability to vaso-constrict blood vessels. The term inotrope refers to a group of medications used primarily for their ability to improve cardiac output by increasing the force of contraction of the heart. While these terms mean different things, they are often used interchangeably. This reflects the fact that many of these drugs can be both vasopressors and inotropes.
Not all vasopressors are the same
The three most common, first-line vasopressors are dopamine, epinephrine and norepinephrine. All three agents are catecholamines, which generally have the physiological effects described by their ability to stimulate sympathetic alpha and beta receptors.
Alpha stimulation primarily causes smooth muscle within the arteries and arterioles to contract, increasing afterload and systemic vascular resistance. Beta stimulation has a number of effects; Beta-1 is most significant for cardiac output. This increases contractility (inotropic effects) as well as heart rate (chronotropic effects). Additionally, dopamine has dopaminergic stimulation, which at low doses increases blood flow to the spleen and kidneys .
How norepinephrine, dopamine and epinephrine work
Norepinephrine increases blood pressure by vasoconstriction (alpha effects) and has very little effect on beta until it reaches the higher doses. In contrast, low and mid-range doses of dopamine and epinephrine increase blood pressure by increasing cardiac output through a combination of increased contractility and heart rate (beta effects).
At higher doses of dopamine and epinephrine, blood pressure continues to increase as alpha effects lead to vasoconstriction. The dopaminergic effects, or so-called renal dose of dopamine has not proved to be of any use clinically.
Which vasopressors work best?
Unfortunately, there are far more opinions than answers as to which vasopressors work best. A recent Cochrane review of six vasopressors, including dopamine, epinephrine and norepinephrine, determined that “evidence is insufficient to prove that any of the vasopressors at assessed doses are superior over others in terms of mortality” .
Several studies have discussed side effects specific to each vasopressor. One of the frequently cited papers that evaluated dopamine versus norepinephrine found that dopamine nearly doubled the risk of arrhythmia [4,5]. Research comparing epinephrine to norepinephrine noted that despite having no difference in mortality, epinephrine caused higher heart rates, higher lactate levels and higher incident of refractory shock .
Norepinephrine has been studied the most, so it has both the most and the strongest evidence for its use. This has led to it becoming the most common first-line vasopressor. It is important to remember that this has happened because norepinephrine has fewer side effects than epinephrine or dopamine, not because more patients survive when it’s administered.
Not all shock states are the same
Vasogenic shock states are easy to understand. Vasopressors cause vasoconstriction, so it makes sense that they are most useful in vasodilatory forms of shock. Norepinephrine in septic shock has the largest and strongest body of evidence supporting it and is the agent of choice when initial fluid fails, or – as is the case in sepsis-associated with COVID-19 – a conservative fluid strategy is recommended . Anaphylaxis, also a vasodilatory form of shock, is often found with wheezing and shortness of breath. Epinephrine is the only first-line vasopressor that also has beta-2 stimulation, leading to bronchodilation. This, combined with the alpha stimulated vasoconstriction for hypotension, means it is the recommended agent for anaphylactic shock .
Cardiogenic shock is more nuanced. Because the primary cause of the shock is a pump problem, drugs like dopamine and epinephrine would seem to make sense. However, norepinephrine is the first-line choice, because the evidence that is available suggests avoiding tachycardia in these patients is better . The exception involves bradycardia. AHA guidelines suggest beta adrenergic properties are reasonable, and specifically mentions a single study that found no difference in outcome for bradycardia between dopamine and transcutaneous pacing .
The use of vasopressors in hemorrhagic shock is controversial, especially as the evidence mounts against large volumes of crystalloid like normal saline. However, recent military studies specific to the prehospital environment reported lower survival in patients who received vasopressor therapy . Vasopressors should be reserved for patients who have failed traditional fluid and blood therapies .
Breaking down bradycardia
Clinically significant bradycardia: think about causes before you treat
Potential complications of vasopressors
Hospital standards like invasive BP monitoring and infusion pumps are not always realistic in the prehospital environment. Central lines are also not readily available, but peripheral IVs and IOs are generally considered safe, and any complications usually occur with prolonged use [11,12].
One important complication of vasopressors to be aware of is extravasation. When the drug leaks out of the vein into the interstitial space, the alpha effects of the vasopressors can constrict blood vessels, reducing blood flow enough to cause ischemia and necrosis. Tissue damage can be significant enough to require surgery, up to and including amputation.
Risk factors for extravasation 
If extravasation is suspected, stop the infusion immediately. Leave the IV in place; it may be possible to use it to aspirate some of the interstitial drug. Warm compresses and elevation may also be helpful. Injecting phentolamine, an alpha blocker, into the tissue may help to reverse vasoconstriction and restore blood flow. This may also be achieved with topical nitroglycerin paste .
Signs and symptoms extravasation 
Making an educated vasopressor drug choice
None of these drugs is clearly superior to the other and all three will likely improve hypotension, but BP isn’t everything! Understanding what each drug does, how it affects different shock states, as well as the risks involved allows a drug choice that can improve cardiac output and perfusion, not just increase the BP.
Finally, mechanisms of vasopressors are the same in pediatrics, however, frontline agent and evidence supporting their use varies widely from adults, but those details are for another article.
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This article was originally posted Jan. 12, 2021. It has been updated.