Clinical Pearls: Pressor Selection
The foundation of critical care practice stands upon heart and lung support. As you know a multitude of problems lead to these downstream complications, but at its core what we do in the unit is handle worst case scenarios. Even for a new nurse practitioner with loads of years at the ICU bedside, pressor selection can be difficult at first. What I hear from students is “Levo, let’s just start Levo.” They say this because it has been their experience and it’s of course discussed everywhere. But when I ask them to defend the selection there can be a dearth of knowledge. Ultimately, they may be right, but I argue that as a competent provider one must have a good understanding of the pharmacodynamics of the drug AND the pathophysiology of the disorder you are treating. Why? Because while the physician/team you are practicing with currently may never question you, at some point you will need to explain your rationale. And on a baser level you need to accurately treat the problem or you could 1)chose something ineffective 2)make things worse or 3)harm the patient. Let’s talk vasopressors.
From: https://www.britannica.com/science/G-protein-coupled-receptor
Why the scienc-y pic Bree? Because mastering pressor choice boils down to understanding what receptors the drugs bind to and therefore what primary effects it will induce.
But first. Lets talk nomenclature.
What does the term “pressor” mean? The vernacular as stated by most people is referring to any drug which will raise blood pressure. But several classes of medications can achieve this effect. Vasopressors are one class. Vasopressors are medications which primarily induce vasoconstriction thereby increasing Systemic Vascular Resistance (squeezing the pipes). Inotropes on the other hand exert their effect by augmenting Contractility (pumping the heart); thereby improving cardiac output. Remember the equation for MAP = CO (HR x SV) X SVR, aka MAP = Pump X Pipe squeezing.
Ok, easy enough. Let’s complicate things a bit by acknowledging that most “pressors” have dual effects. Some meds we use are primarily one or the other, but most of them have effects in both arenas with differing affinities. Critical care guru Scott Weingart has dubbed these “ino-pressors.” This is why understanding pharmacodynamics is crucial. If you know the targets and the affinities of the drugs you have a better grasp on anticipating the effects they will achieve. If you know the problem your patient has (what type of shock) you can choose a more selective drug.
So back to receptor sites.
ADRENERGIC RECEPTORS
Catecholamines target these and once bound stimulate a chain of effects leading to sympathetic nervous system stimulation.
Alpha 1(𝛼): Think pipe squeezers. Located in vascular smooth muscles, the primary effect when stimulated (agonized) is peripheral vasoconstriction. There is no cardiac stimulation. Therefore when active you will get increased SVR with no augmentation of contractility or heart rate. Agonizing this receptor alone will create an “unopposed alpha” effect. For a patient with a sick heart (HF, MI, cardiomoypathy) or someone with already blocked pipes (pulmonary embolus) you are forcing a weak heart to work exponentially harder against squeezed pipes. You can make this type of patient much sicker by doing so. The ideal pt for unopposed alpha is the transient hypotension in the setting of anesthesia or the pt with tachycardia.
Beta 1 (β1): Think heart pumper. Located in the heart, kidney, and fat cells. The primary effect is cardiac stimulation (increased heart rate, contractility, conduction velocity, relaxation) and systemic vasodilation. It is logical then that the main adverse effect will be tachycardia and arrhythmia. Ideal in cardiogenic shock (make the heart pump better and offload the heart by dilating the pipes). Because there is increased cardiac activity there is also increased myocardial oxygen consumption. So for a patient with ischemic heart failure this may not be ideal. Also, in a mixed shock state if you augment cardiac function you’ve addressed your cardiogenic state however you’ve worsened an already vasodilated (septic) patient. In that instance you would want to avoid a pure beta 1 agonist and opt for a more balanced agent like an inopressor (levo, epi).
VASOPRESSIN RECEPTORS 1-3
Located throughout the body, primarily in smooth muscle cells and have a primary effect of vasoconstriction.
In sepsis there is initial uptick in endogenous vasopressin release followed quickly by rapid depletion.
Less cardiac effects.
Decreases mesenteric (splanchnic) blood flow.
DOPAMINE RECEPTORS 1-5
Located in CNS (primarily), kidneys, and vasculature.
Basically all five receptors play a role in blood pressure management. Because this receptor is prevalent in so many body functions there is wide variability of effect when adding exogenous Dopamine as an agent to treat shock.
Less utility in current times given that there are “cleaner,” more predictable and reliable agents. However, some institutions still use and the primary instance I see it utilized is for bradycardia. I would argue Isuprel is the preferred agent in that setting.
ANGIOTENSIN II RECEPTORS
Amongst other places these are located in the heart and vascular smooth muscle.
Angiotensin II has multiple effects including increased vasoconstriction, inotropy, chronotropy, stimulation of norepi and vasopressin release, and increases aldosterone levels (these effects are why HF patients are placed on ACEi/ARB’s to prevent cardiac remodeling).
Numerous side effects: thromboembolic events including DVT, thrombocytopenia, tachycardia, fungal infection, acidosis, delirium, hyperglycemia, peripheral ischemia. I’ve seen dead bowel as a result (totally anectdotal I know).
Controversial and a subject for consideration given side effects when considering Ang 2 as an adjunct.
PDE 3 INHIBITORS
Not a receptor site, but a pathway which is blocked leading to increased levels of cAMP.
Creates an effect of systemic and coronary vasodilation and increased inotropy. So the heart pumps better and against less constriction.
Promotes coronary vasodilation so therefore this is the ideal pathway to target in a pt with ischemic heart failure.
Now lets talk drugs and indications.
The key here is knowing which effects are primary. Start by memorizing the purists first. Indications for use are underlined.
Phenylephrine (Neosynephrine)
Pure Alpha 1 adrenergic agonist, meaning this drug has almost no activity on other receptor sites. The ultimate effect is squeezed pipes with no squeeze added to the heart.
There will be no increase in heart rate or contractility. This is why for a shock patient with tachycardia this may be a great selection.
This is also why it seems to be the drug of choice for anesthesia induced hypotension and the preferred pressor of choice in our OR/PACU/procedural patients.
Other indications: hypotension associated with AS, HOCM, or transient vagal mediated hypotension.
Who it’s not ideal for:
Someone with a sick heart. For example, if you have reduced EF, cardiomyopathy, or acute MI you have a sick heart. Now we are going to make that sick heart work twice as hard by forcing it to squeeze through tight pipes without doing anything to help the heart pump better.
Someone with obstructed vessels, like a pulmonary embolus.
Someone with high pulmonary vascular resistance like pulmonary hypertension. You’ll make the right heart work harder and worsen.
Someone with high SVR states like cardiogenic shock (add an inotrope instead), heart failure (add an afterload reducer to open the pipes and offload the heart), hypovolemia (fill the tank instead).
Isoproterenol (Isuprel)
Pure Beta 1 adrenergic agonist.
Increases heart rate and is my initial choice in all heart block or bradycardia. (Until we can effectively pace)
Increases CO (by increasing HR and contractility).
Raises systolic BP (contractility) but lowers diastolic BP (SVR is reduced) and therefore can worsen some shock states (unless the shock is solely cause by bradycardia).
Norepinephrine (Levophed)
Can be considered an inopressor because it targets both Alpha 1 and Beta 1adrenergic receptors.
Alpha > Beta effects so you get more pipe squeezing over heart pumping but it’s pretty close.
Fairly balanced and this is why it’s the quarterback of the pressor world and first line for undifferentiated or septic shock.
At higher doses will probably see some tachycardia. If so add Vasopressin if septic and reduce Levophed as able.
Epinephrine (Adrenaline)
Also an inopressor as it hits both.
Beta > Alpha effects so this is high on the list for consideration in cardiogenic shock.
Second vs third line for septic shock. I default to Levo, then Vaso (in most cases), then Epi.
Likely to see tachyarrhythmias especially as you approach higher doses as beta agonist properties predominate.
Induces gluconeogenesis (watch your BG levels) and is an independent factor in non shock related lactate generation.
Vasopressin
Great adjunct for catecholamine resistant shock.
Ideal for the septic patient on Levo or Epi especially if they are having the pro-arrhythmic effects from levo/epi.
Decreases mesenteric blood flow so may be ideal for the hemorrhagic shock (needs blood first) 2/2 to GIB.
Because of the above effect it will be less ideal for the pt with concerns of mesenteric ischemia (the pt with a sky high lactate I would want to rule this out before using).
Giapreza (Angiotensin II)
Studies lacking demonstration of improved mortality + side effects make this controversial and a subject for consideration when considering Ang 2 as an adjunct in septic shock.
Milrinone (Primacor)
PDE 3 inhibitor and as such ideal for cardiogenic shock in a pt with ischemic HF as coronary blood vessels will be dilated so although you have augmented contractility you will provide improved flow to the heart itself mitigating the increased myocardial oxygen demand.
Not ideal for the person with vasodilatory shock as this will be worsened by the systemic vasodilation effect. This is why septic or hypovolemic patients become hypotensive with Milrinone.
Dobutamine (Dobutrex)
Beta >>> Alpha effect. While there is some alpha adrenergic activity it is partial and less pronounced than the beta effect.
Technically could be considered an inopressor but given the strong imbalance this is utilized as an inotrope.
Most common agent seen in practice for cardiogenic shock.
Because there is some alpha effect, the augmentation in SVR is enough to offset the reduction in SVR caused by beta agonism. Therefore, Dobutamine will have less reduction in BP than a pure beta agonist like Isuprel.
As opposed to Milrinone there is no augmentation to coronary perfusion, and therefore cardiologists prefer Milrinone for ischemic HF patients. However, Dobutamine induces far less hypotension than Milrinone.
Dopamine
Well this one is the great debate and I put it at the bottom for a reason. It is well documented that Dopamine poses more risk of harm than benefit in patients with septic shock in particular. Increased mortality compared to Levophed and increased tachyarrhythmias.
Nonetheless, it is used still. Primary indications: bradycardia with shock and cardiogenic shock.
Make your own call. Attaching studies for reference.
https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-03960-y
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