Levophed, also known as norepinephrine, is another stress hormone, and the topic for today. We’ve mentioned norepinephrine in the posts on dopamine and epinephrine, but now we’re going a little deeper.
“Levophed will leave ’em dead,” I was taught as a new nurse in the ICU, and definitely it can. Norepinephrine is a powerful alpha-1-agonist, producing intense vascular vasoconstriction. High doses of this medication will clamp the vascular system, both arterial and venous, to the extent no perfusion occurs in the capillary beds.
In other words, it increases afterload. In fact, it can increase afterload so much that it causes metabolic acidosis. Because of its venous activity it diminishes preload. At the same time, cardiac output drops as the heart rate falls. This mechanism makes it a poor choice as an inotrope.
Wait a minute…heart rate falls?
Let’s look at this. Norepinephrine has beta-1 agonist activity comparable to epinephrine, but it has NO effect on beta-2 receptor sites. But didn’t I say that beta-1 agonists increase contractility and heart rate? Yes, I did.
The increase in mean arterial pressure levophed induces will cause baroreceptor-mediated drop in heart rate, which the beta-1 stimulation of norepinephrine is often too weak to overcome. Not always, though.
We use levophed as a first-line vasoactive agent, directly behind or in conjunction with crystalloid, for hypotensive patients in the presence of infection. This state is what we refer to as “septic shock,” and I’m not going into SIRS criteria in this post. In these patients it’s unlikely to see the drop in heart rate, as the pathophysiology of sepsis results in tachycardia.
Norepinephrine doesn’t affect the alpha-2 receptor sites, which are found in the cerebral circulation. Since it lacks beta-2 activity, it also will not dilate the bronchioles, making it less than ideal in anaphylaxis or status asthmaticus. Incidentally, it’s also a poor choice in cardiogenic shock or advanced heart failure patients since it increases afterload.
The higher the dose of levophed, the more profound the effect on systemic vascular resistance. A pet peeve of mine? Receiving a patient on levophed with a MAP greater than 75. Unless of course you are a neuro nurse, in which case you are titrating for an appropriate CPP (cerebral perfusion pressure) and you should ABSOLUTELY continue, please and thank you, carry on.
PRIMARY CONSIDERATIONS: The development of tachycardia (worse in septic patients, which is our primary use of levophed), dysrhythmias (as all beta-1 agonists do), myocardial ischemia, colitis, and other effects of decreased organ perfusion.
It doesn’t really contribute to hyperglycemia like epinephrine does.
Here’s an interesting tip about norepinephrine: it must be mixed in D5W in order to provide enough acidity to prevent oxidation. Oxidation makes levophed ineffective by inactivating it.
The lungs are responsible for clearing endogenous catecholamines, and can extract about 25% of circulating norepinephrine in a single go. This clearance is diminished by halothane & nitrous oxide in animal studies, so it may be that anesthetic agents interfere with the process in our patients, too.