Newsworthy: Veterinarians Find Infections Faster by Monitoring Nt-pCNP

"Stinger", a dog with sepsis from a bite wound. Image from Valley Center Veterinary Clinic, Valley Center, CA.

N-terminal portion of pro C-type natriuretic peptide. Try to say that one three times fast. ScienceDaily has a cool article detailing a couple new studies showing that this peptide (Nt-pCNP) could be a solid indicator of sepsis as opposed to a generalized inflammatory response. It could potentially be added to current serum chemistry analysis, or packaged as an ELISA snap for quick, in-house diagnostics for pertinent cases.

Overuse of antibiotics has been a long term problem that is being well addressed in human medicine, however they are used much more broadly and liberally in animals due to their non-prescription access (especially in large animal work), and their use as a diagnostic tool for patients who can’t speak and often can’t afford thorough diagnostics. A veterinarian who’s client is unwilling to pay for a culture will often send broad spectrum antibiotics home anyway as a less expensive option in the hopes that they will take care of the problem.

I was unable to find a chemistry profile of Nt-pCNP, but the journal article itself talks a bit about C-type natriuretic peptide. CNP is produced by vascular endothelial cells and immune system macrophages. It “inhibits microbial growth and modifies pathogenicity of microorganisms” (DeClue, 2011). The problem with looking for just CNP as an indicator of sepsis is that it has a very short half life, and tends to degrade even faster in removed serum. Therefore, the researchers decided to use Nt-pCNP as their target molecule.  Nt-pCNP is created in a 1:1 ratio with CNP as a byproduct, and is much more durable and long-lived in both the bloodstream and collected serum.

The results of the study support the hypothesis  that CNP is a good indicator of sepsis, however like anything else, it’s not ideal. CNP was shown to be a poor indicator of sepsis when the infection was peritoneal. This includes gastrointestinal perforations or other possible infections found within the peritoneum (the authors mention that using peritoneal fluid as opposed to serum from a distal point may yield better sensitivity). Taking these false negatives into account, the test had a 65.5% sensitivity, for all other origins of sepsis in the study, sensitivity was 92%. Unfortunately, there appears to be a large potential for ambiguous negatives when peritoneal infection is suspected, but it’s always important to remember to educate clients that medicine is rarely black and white. It’s nice that House is able to identify exactly what’s wrong with each of his patients every week, but most of the time, we’re just going to give them supportive care based on the most likely result. Some of the limitations of the study that the authors mentioned were the small sample size and uncontrolled natures of the ailments that may have influenced the blood chemistry (samples taken from bacterial vs. viral infections, condition as of admission, underlying secondary infection or ailment, etc.).

In the case of this test and many other lab tests, positives are very definitive and help us out, while negatives are ambiguous. This is true whether it’s a heartworm test, fine needle aspirate, fecal flotation, radiology, or any number of other diagnostic tests. Every one is a tool, and hopefully looking at Nt-pCNP levels will give us another way to confirm sepsis while our cultures are growing at the lab, or perhaps offering another faster or less expensive option that the situation necessitates.
This post was chosen as an Editor's Selection for ResearchBlogging.org
DeClue AE, Osterbur K, Bigio A, & Sharp CR (2011). Evaluation of serum NT-pCNP as a diagnostic and prognostic biomarker for sepsis in dogs. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, 25 (3), 453-9 PMID: 21457321

Article Review: Effects of intravenous administration of Lactated Ringer’s solution on hematologic, serum biochemical, rheological, hemodynamic, and renal measurements in healthy isoflurane-anesthetized dogs

Well, it’s about time I mentioned an article I didn’t particularly enjoy on here. It’s not like I think it’s a waste of paper, it’s an important topic, but it does nothing creative and does little to contribute to the understanding of the subject. The article looks at the effects of different rates of Lactated Ringers Solution administered while under isoflurane anesthesia. It uses healthy animals, discusses well documented effects in humans, and just reinforces common practice.

Lactated Ringers is the most frequently prescribed fluid for maintenance of homeostasis in surgery and pretty much any other health stress event. I know when any patient wasn’t feeling well from any situation at my clinic, we always administered LRS either through a catheter or subcutaneously for outpatients, the dosage based on weight and severity of condition. We know how to use it, and it’s gotten a proven history of effectiveness in both humans and animals. The article justifies itself by saying that fluid therapy in dogs is largely based on human evidence, and that the formulas we use to determine rates have not been thoroughly investigated. Yet throughout the article they repeatedly compare their results to similar studies, and make no conclusions that aren’t already accepted in human and animal medicine. Additionally, the gaps in the literature they identify can’t even be answered using the methods and results of this study, so you can’t use them to justify its existence.

So the big conclusions they determined were that providing LRS increased plasma volume and cardiac output, didn’t increase urine production, and appears to leave the blood volume and remain in extracellular space. These are important points, but they were accepted unanimously without the presence of this study. Further, if their goal was to confirm these assumptions, their results are pretty much irrelevant with a sample size of only 8 animals, all in perfect health, similar size (26-41 lbs isn’t a lot of variance in the world of dogs), and undergoing no medical stress other than common anesthesia and mechanical ventilation.

My impression after finishing the paper was that the people at QTest labs (associated with Ohio State University College of Veterinary Medicine) needed a study to do, needed to get a grant proposal ready, and did enough research on the subject to sell this trial. It’s well written and the authors do a great job of placing their results in context of the literature, mostly because it all agrees. But it can’t hide the fact that it does nothing revolutionary other than providing history on the subject, and giving an excellent account of the methods used in the study. With such great, specific, and controlled procedures, this facility could be solidifying other theories that have conflicting data, if they’d use a sample size large enough.  I’m sure that they don’t always do milk run trials such as this one, and I look forward to seeing their name again in future articles.

ResearchBlogging.orgWilliam W. Muir III, Anusak Kijtawornrat, Yukie Ueyama, Steven V. Radecki, & Robert L. Hamlin (2011). Effects of intravenous administration of lactated Ringer’s solution on hematologic, serum biochemical, rheological, hemodynamic, and renal measurements in healthy isoflurane-anesthetized dogs JAVMA, 239 (5), 630-637