Meet Nesitiride

[WAS967 97]

From http://www.jems.com/jems/exclus03/e1203b.html

Meet Nesitiride

By Howard Rodenberg, MD, MPH, Dip(FM)

Recently I've commented that there are a lot of acronyms in medicine. We use these conglomerations of unrelated letters to describe everything from patient demographics to diseases to patient care. I still recall an exercise we did in medical school to see if we could write out an entire history and physical exam using nothing but initials (75 y/o WF w/ COPD, CHF, r/o PE…you get the picture). And we all know that in EMS, we have certain "unauthorized" abbreviations. I will ask you to chuckle to yourself as you think of them, because if they're like the ones I know I can't write them down in public and still have a prayer of continuing to write this column. (I would, however, appreciate you e-mailing your favorites to me for my own particular amusement.)

Of course, this phenomenon is not unique to medicine. One of my favorite acronyms comes from the time I was working with NASA at the University of Florida. We would be on the flight line near the SLF ("Shuttle Landing Facility") amid signs warning us of FOD on the runway. It turns out that FOD stands for "Foreign Object Debris." That's so much better, and more bureaucratic, then just saying "trash."

I'm pleased to announce that the next acronym to come our way is BNP. BNP is short for B-type natriuretic peptide, an amino acid produced in the ventricles in response to myocardial wall stretching, volume expansion, and increased end-diastolic pressure. You'll recall that myocardial walls stretch when subjected to constant pressure or strain. The most common cause for this is chronic hypertension. The elevated afterload (systemic vascular resistance) places strain on the heart, and the walls of the ventricle expand in response to the strain of pumping against the contracted arterial vessels. To a point, the stretching helps the heart function more efficiently; but as the heart continues to expand, cardiac contraction becomes weaker and output falls. (You may recall this principle from physiology class as the Frank-Starling Law of the Heart). Congestive heart failure and pulmonary edema are the final results of this process.

Patients in CHF develop pulmonary edema as a result of the inability of the heart to pump effectively in the face of increased preload (intravascular fluid volume returning to the heart). The backup of fluids from ineffective cardiac contraction raises intravascular pressures. Fluid seeps from the smaller vessels into the interstitial space of the lungs, where it impedes effective gas exchange between the alveolar wall and the capillary beds.

BNP acts within the body to combat the excess fluid. Its major effect is on the kidney, where it acts to promote sodium excretion from the bloodstream into the renal tubules. Water follows the sodium (remember osmosis?) and is excreted in the urine, with a resultant loss of intravascular volume and pressure. Volume loss results in decreased preload, which improves cardiac function and allows the heart to begin clearing fluids from the pulmonary tissues.

BNP also causes peripheral vascular dilation by decreasing the secretion of renin, a hormone of the kidney that is converted in the body to the vasoconstrictor angiotensin. This decreases afterload, enhancing cardiac output. Finally, BNP decreases production of aldosterone, a hormone secreted by the adrenal glands to promote sodium and water retention (for those who follow such things, President Kennedy suffered from Addison's Disease, a lack of adrenal gland activity. There was also a lone gunman, but I'm sure somebody put him up to it).

It's of interest to note that BNP does not provoke inotropic or proarrhythmic effects. To best understand this difference, we need to jump back into the field. Inotropy refers to the pumping action of the heart, and an inotropic agent would enhance this effect. Inotropes used in EMS include dobutamine and epinephrine. These drugs are best classified as catecholamines. But while catecholamines enhance cardiac output, they do so while raising myocardial oxygen demand. This can be a problem when myocardial perfusion is tenuous, as in the patient with severe coronary artery disease. And the sympathomimetic effect of all catecholamines may produce tachydysrhythmias.

BNP is entering emergency care in two ways. The first is that BNP has been found to be an excellent marker to identify patients with CHF. A recent study of over 1,600 patients with confirmed CHF finds that a BNP level of > 100 pg/ml has a positive predictive value of 83.4%; at a level of < 50 pg/ml, the negative predictive value was 96% (the "normal" level of BNP is 9 pg/ml). Other works reflect that a BNP level of 100 pg/ml is 82% sensitive and 99% specific for CHF. (If you're not familiar with these terms, please consider reading the wonderful review by Greenhalgh in the British Medical Journal, 1997, 315:540-43. Or maybe I'll just milk the statistics for another column … )

The diagnostic use of BNP becomes of import to EMS when one considers the advent of on-scene, "point-of-care" testing. We've already discussed in a previous column my thoughts on this procedure. In a nutshell, I think it holds benefit for EMS only with long transports, and even then mainly as a means to speed up the patient's ED time upon arrival at the hospital. Given the 15-minute result time featured in most current "point-of-care" technologies, its impact on the majority of EMS care is probably minimal at this time. However, when transport times are prolonged, en-route BNP testing may be useful in establishing the presence of CHF and in guiding patient care if the origin of respiratory distress is unknown.

There are two other ways in which diagnostic testing for BNP may prove useful in prehospital care. The relatively short half-life of the molecule (20 minutes) makes it possible to use BNP as a monitoring tool to assess the efficacy of care or a worsening clinical condition. Other studies indicate that BNP may serve as a triage and risk stratification tool, as increased levels are associated with higher risks of myocardial infarction and heart failure in patients with acute coronary syndrome.

BNP has also been produced as a commercial product for use in the care of patients with severe congestive heart failure. Known as nesiritide (Natrecor), its use in the treatment of acute cardiogenic pulmonary edema has been subject to recent evaluation in a comparative trial with intravenous nitroglycerin (a potent vasodilator) and a placebo (an "inert" treatment, like a "sugar pill").

(I need to say a word about nitroglycerin in heart failure. I am an unabashed nitroglycerin fan. It's cheap, it's efficacious, and it does the job. And if you get in trouble while using the drug, you simply discontinue the infusion, add a bit of fluid and raise the patient's legs, and the problem goes away in a few minutes . I think nitroglycerin should be used liberally and often, without an artificial restriction to a specific quantity or dose. If it works, use it until it works no more. Needless to say, I am also a proponent of IV nitroglycerin for intractable cardiac chest pain and heart failure in EMS systems with prolonged transport times. It does require titration, but so do other EMS drugs such as dopamine. Please use it.)

In the trial mentioned above, both nitroglycerin and nesitiride proved to be more effective at relieving the clinical symptoms of CHF than placebo (like that's a surprise?). Differences between nitroglycerin and nesitiride were subtle. At three- and 24 hour endpoints, nesitiride significantly improved pulmonary capillary wedge pressure (PCWP, a measure of preload) more than did nitroglycerin. However, measures of overall clinical status were essentially the same. In a nutshell, the numbers looked better, but the patients were the same.

Based on this early study, I'm not sure exactly where this drug will fall into our pharmacologic quiver of therapeutic arrows. For now, its fairly costly at nearly $ 400.00 per dose (by way of contrast, IV nitroglycerin costs our hospital pharmacy less than $10.00), and seems to offer no distinct clinical advantage over IV nitroglycerin. But as more studies are done with this drug, it may well find a place in prehospital care, either in lieu of or as a complement to IV nitro. The best work to evaluate the efficacy of prehospital nesiritide should look at short term (minutes to hours) changes in patient status reflective of our limited patient contact times, and correlate outcome parameters to these short-term results. And upon that note, it's time to say AMF YOYO.

(Adios, my friend, you're on your own).

About the Author

Howard Rodenberg, MD, MPH, Dip(FM), is director of the Volusia County (Fla.) Health Department. He has previously served as medical director for Alachua County EMS and the ShandsCair Flight Program at the University of Florida and as consultant in emergency services for Medical Rescue International in Johannesburg, South Africa. He has edited or contributed to six texts, is the author of multiple articles and speaks frequently to national and international audiences on prehospital and air medical care. Contact him via e-mail at AMDEMS@aol.com.

[WAS967 97]

I posted the previous article because I thought it was very informative both about CHF and BNP. A few comments first: I too am a big proponent of Tridil (IV NTG) and would love to see it used in the field. As Doctor Rodenburg mentioned, it does require titration and most in hospital workers would scoff at using it without a medication pump. But we shall see. My organization has been contemplating putting IV pumps on the flycars for a while. Perhaps this would be a good reason to do just that. Also, it will be interesting to see how Natrcor (Nesitiride) pans out. Don't be surprised if it ends up in our drug bags in a few years. You may poo-poo the idea now, but contemplate this. I said the same thing about Cardizem 5 years ago. ;->

Anyways, on to the meat and potatoes. BNP (b-type Natriuretic Peptides) are something that most advanced prehospital providers should be at least aware of, if not for your own knowledge, for the sake of your patient. Why you say? Well, many hospitals are working towards using BNP as a marker for CHF patients. Hudson Valley Hospital just recently started using it. Northern Westchester has been using it for about 8 months. Why do you care? Well, if you don't typically draw prehospital labs when you start an IV, then you shouldn't. But if you are like me, and a lot of other advanced providers who DO draw bloods when starting a line, you might want to take heed. BNP levels typically require an extra purple (lavender) top blood tube. Next time you have a CHF patient, keep the second blood tube in mind. It will potentially save the patient from another stick later on. The BNP level from the field can also be used to gauge the effecacy of your tratment for the ADCHF (Acutely Decompensated Congestive Heart Failure) patients. I personally have gotten into the habit of including two purple top tubes in my IV start sets just so it is there as a reminder. If I don't need it, I don't draw it. Your milage my vary.)

Comments?

[Guest x901]

do you know if any of the hospitals in the south county area are checking the BNP?

[WAS967 97]

I do not unfortunatly. I only regularly work with HVHC and NWHC and occasionally Putnam (I have no idea if they have the ability). Best way to check is to talk to the ER doctor at your local ER and ask. If they have the capability to the BNP assay, they would know or would be able to tell you when they plan to deploy it. It's a really easy test and results can be had in about 15 minutes. It's not as quick as a Blood Glucose, but for the value of the results, it's worth a litle wait.

[x635 4,066]

I actually used this drug today (Natrcor-Nesitiride)

I found it interesting that upon arrival at WMC, they did not carry the drug and the patients theraputic course would have to be discontinued, although it was found to be very effective on the patient. Also, I learned later that WMC had a clinic for this drug, but, along with many other things, was cut and closed.

In regards to drawing bloods, I see 5-10 years down the line, with the advances in technology in the lab field, EMS being able to run some basic pertinent labs in the field and getting the results prior to hospital arrival.

[WAS967 97]

Oh most definatly. Look at blood sugars. Years ago you used paper that turned colors to get an idea of the person's blood sugar. Now you get a nice readout in a device smaller than your palm. Blood gases would be a good thing too. Blood gas machines return results within seconds. Why not have that capability in the field? One day, and with much more money than we have now.

As for the Natricor issue at the med. They are short on a lot of drugs for obvious reasons. I've taken several patients to thier L&D and had to bring medications with me from the sending hospital because WMC doesn't carry it. I can only hope that they fix the problems soon or people are going to die. (And some would argue, that several already have.)