Save me! I’m deep in the forest of hemodynamics, struggling through the preload underbrush. Send whiskey. Post to follow soon, I promise.
SBT–spontaneous breathing trial–is a term used in the ICU for weaning from mechanical ventilation.
Today’s tip: spontaneous breathing is exercise. It’s essentially a cardiac stress test. That’s why evaluation of hemodynamic status is fundamental to the questions of “should we SBT” and “should we extubate.”
Today’s #CCRN, #CMC, #CSC education tip: VASOPRESSIN.
Today we’re going to talk about vasopressin.
Those of you who have been nursing a bit will remember when vasopressin, 40 units, IV as a bolus dose was the ACLS recommendation for the second medication to give during a cardiac arrest. The first? Epinephrine, as always. “All dead people get epi,” at least if we’re following the recommendation of the AHA. As I said before, there’s some controversy.
But we aren’t here to talk about epinephrine. Let’s look at vasopressin. The chart I posted over catecholamines is useful, but vasopressin wasn’t on it. That’s because vasopressin isn’t an alpha-1/beta-1/beta-2 drug. Nor does it metabolize into a drug that accesses those receptor sites.
Vasopressin is anti-diuretic hormone. It is necessary for life in humans and animals, and it works on the V1 and V2 receptor sites. The first is located on the membrane of a vascular smooth muscle cell and mediates vasoconstriction in much the same way as angiotensin II. The second receptor regulates water excretion by increasing water reabsorption.
Vasopressin is used to restore vascular tone in vasodilatory shock. We usually use it in sepsis, but also in vasoplegic syndromes and advanced heart failure. It’s the drug we reach for when shock is resistant to catecholamines.
There are several ways vasopressin performs its magic. We mentioned vasoconstriction and increasing water reabsorption. Other effects include modulating endrogenous nitric oxide and potentiating adrenergic agents to promote vasoconstriction.
Platelets are affected by stimulation of the V1 receptor site to provoke an increase in intracellular calcium levels. This facilitates thrombosis, but the amount of variability in aggregation response is so large it’s not possible to point to vasopressin as a cause of coagulopathy.
V1 receptor agonism doesn’t affect every part of the kidney in the same way, but selectively affects the inner (but not the outer) medulla blood flow rate, and contracts the efferent arterioles but not the afferent arterioles.
DDAVP is a selective form of vasopressin which affects only the V2 receptors, causing a release of von Willebrand factor and vasodilation in the kidney alone. Although V2 receptors are found elsewhere, for reasons most mysterious it doesn’t seems to have effects outside the renal circulation.
The vasopressin receptors are relatively resistant to downregulation. The interaction of vasopressin with arrestins, when combined with this resistance, allows vasopressin to (purportedly) bypass the downregulated myocardial adrenergic receptors.
Vasopressin is dosed in 0.01-0.04 units per minute or 0.1-0.4 units per hour. Either way, it’s particularly helpful in hypoxic/acidotic states, as well as those resistant to sympathomimetics. It’s not generally titrated–for sepsis or vasoplegic syndromes, we generally place it at 0.03 units/min and leave it. It increases MAP without affecting inotropy, as a general rule.
Although the cardiac effects of vasopressin are complex and conflicting, a few common uses have emerged over the last ten years. One is the pairing of milrinone and vasopressin. In cases of severe advanced heart failure requiring the use of inotropic agents, plus the necessity to bypass downregulated receptor sites, added to the need for diuresis in the presence of relative hypotension, vasopressin has emerged as a superior agent for maintaining vascular tone and perfusion.
It’s also an excellent choice for blood pressure support in PAH, as it avoids vasoconstriction in pulmonary circulation.
Consider adding vasopressin to levophed in refractory hypotension, particularly in septic shock. In those patients the levophed dose can get so high it blocks perfusion of the capillary beds. Starting vasopressin in these patients can allow you to reduce the rate of levophed infusions to much more reasonable levels.
Another use is in post-operative cardiac surgery patients. Maintenance on bypass circuitry for surgery has multiple effects on a patient’s physiology, which can evidence themselves in a vasoplegic scenario post-operatively. Vasopressin can prevent cardiovascular collapse in this patient population without adversely affecting inotropy.
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.
Epinephrine. #CCRN #CMC #CSC in today’s education post.
This drug, produced by the adrenal medulla in times of stress, is referred to as adrenaline. It’s a neurotransmitter that acts on the beta and alpha receptor sites much like the other inotropic medications we’ve discussed so far.
Epinephrine has ACLS-level fame, and is used for the treatment of cardiac arrest. It increases perfusion pressure to the coronary and cerebral blood vessels, as well as increasing blood flow to the skeletal muscle beds.
(Data supporting its use in resuscitation is limited–read about the controversy here.)
Epinephrine has beta-1 and beta-2 adrenergic effects, causing an increase in cardiac output and heart rate, as well as bronchodilation. This makes the medication particularly useful in the treatment of anaphylaxis.
We’ve talked about the beta-2 receptor site, and its vasodilatory properties. So how is epinephrine a treatment for shock states if it activates beta-2 receptors? It also has profound alpha-1 agonist activity, which causes vasoconstriction.
But, wait…doesn’t that mean epi works against itself?
Actually, no, because the concentration (dose) of the catecholamine at the level of the receptor site controls activation. At low doses, say, 2-10 mcg/min (0.02 mcg/kg/min-0.05 mcg/kg/min for weight-based dosing), beta stimulation predominates. At higher doses, the beta-2 stimulation is gradually overwhelmed by alpha-1 agonist activity.
What about the max on epi? Well, there is no true maximum dose of this catecholamine, but at 30 mcgs/min every receptor site accessible to epi is fully covered, so if your patient remains hypotensive adding norepinephrine or phenylephrine (targeting the same alpha-1s) is a futile endeavor. A much better alternative? Vasopressin.
PRIMARY CONSIDERATIONS: Epinephrine is proarrhythmogenic.
Renal flow is greatly reduced even if blood pressure doesn’t change…estimated 2-10 times greater effect on renal circulation when compared to norepinephrine. It also increases renin secretion.
Epinephrine has greater effects on metabolism than any of the other catecholamines we’ve mentioned. It increases blood glucose via glycogenolysis in the liver, lipolysis in adipose tissue, and inhibits insulin secretion. Lactate rises on epinephrine drips, probably due to glycogenolysis in skeletal muscles.
Effects on the gastrointestinal tract include smooth muscle relaxation. In other words, it decreases motility, which can result in nausea, particularly in post-operative patients.
Interestingly, epinephrine increases blood coagulation, possibly due to increased activity of factor V.
We measure all hemodynamic variables (CVP, PAs, PAWP, CO/CI) at end-expiration, because exhalation is usually the longest period of the respiratory cycle. Inhalation increases systemic venous return, but also decreases pulmonary venous return, which in turn decreases flow to the left side of the heart.
Here is that mechanism at work with bolus thermodilution:
This image demonstrates the high degree of variability from respiratory artifact. Trials 1, 3, 5 were performed at end-exhalation. Trials 2, 4, 6 were performed during inhalation.