ICU Registrar: "That new fever is a pain. I suppose we'll have to send a septic screen and start some broad spectrum antibiotics. I bet it's just his pancreas though. We'll probably have to arrange a CT to look for necrotic areas for the radiologist to do a needle aspirate."
ICU Resident: "What about sending one of those PCT thingies? That'll tell us what to do, won't it?"
Can't you just hear the "Critically appraise the role of PCT" question yelling out to you? Well, read on for the low-down on that PCT thingy.
PCT = Procalcitonin
Where does it come from?
What does it mean?
What are its limitations?
How is it used?
Matthew Hoffman's PulmCCM.org site recently examined an 2012 article from Chest (Schuetz P et al. Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections. Schuetz P etal. Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections.Chest 2012;141:1063-1073.) that reviewed the use of Procalcitonin (PCT) in acute illness. His blog gives a nice overview of many of the issues that have dogged the use of PCT, with some good links, and finishes off with a helpful summary of the Chest article's main points. To read more, follow this link.
Calcitonin production is traditionally ascribed to the C-cells of the thyroid gland. However, Pro-Calcitonin is produced by the parenchymal cells of the majority of solid organs; eg lung, liver, kidney, muscle, adipose tissue (2). There is negligible production of PCT by WBCs and leucocytes do not contribute to the rise in PCT levels seen during bacterial sepsis or other PCT elevated states.
While cytokines produced during bacterial infections upregulate the expression of PCT producing genes, viral infections result in interferon-y (IFN-y) which inhibits PCT production in most cases.
A higher PCT level is associated with a more severe bacterial infection and a daily fall in PCT level by > or = 50% is associated with resolution of that infection. PCT has a reported sensitivity of 85% (95% CI, 76–91%) and specificity of 83% (95% CI,
68–92%)) for differentiating bacterial from noninfectious causes (3).
However, there are other causes of a raised PCT level (4):
PCT > 0.5ng/ml is considered to be elevated. A PCT > 2ng/ml has a stronger association with systemic bacterial infection, but this is not absolute. A PCT between 0.5 and 2ng/ml is likely to be associated with a bacterial infection, but other differentials may be relevant depending upon the clinical context (4). A PCT < 0.1ng/ml is associated with a low liklihood of bacterial infection (5). These values may vary between labs.
The lack of a reliable gold standard for diagnosing bacterial causes of illness has caused problems in determining the true ability of PCT levels to predict the presence of a bacterial infection. So in recent years, the focus has shifted from using PCT to diagnose the presence of a bacterial infection, to using a falling PCT levels to guide the duration of antibiotic therapy, in an attempt to limit patient adverse drug effects and the emergence of antibiotic resistance (6).
There are flaws with the trials assessing the use of PCT to limit antibiotic duration of therapy and therefore the meta-anlayses are also flawed. However the trend of these trials suggests that a PCT-guided algorithm reliably reduces the duration of antibiotic exposure without significant adverse consequence. For more information on this aspect of PCT testing, read the PulmCCM blog and the 2012 Chest article.
I've just found another Scheutz study in Clin Infect Dis (http://cid.oxfordjournals.org/content/55/5/651.full.pdf) where he and his colleagues reviewed 14 PCT trials, covering about 4000 patients with respiratory tract infections (Did not look at other infection types). The paper highlights some interesting findings and makes some practice recommendations.
Overall, using a PCT algorithm in RTIs:
1) did not have a benefit on 30 day mortality (OR CI crosses unity)but was associated with:
2) lower rates of treatment failure for CAP and RTIs treated in primary care settings including ED, but not ICU (where there were much lower rates of adherence to the trial PCT algoritm) and not for VAP,
3) shorter duration of antibiotic therapy by 3.5 days without adverse morbidity, and this was seen across all RTI types and care settings, including ED and ICU,
4) no difference in ICU length of stay or duration of ventilation (Again, lowest rates of PCT algorithm adherence was seen in ICUs - I guess we prefer our clinical gestalt to biomarkers for some diseases)
Scheutz et al recommend that PCT be used like other biomarkers, to nudge pre-test probability. If the PTP is low and the PCT is <0.25ng/ml, they recommend not starting an antibiotic. However, they do not suggest a course of action for low PTP but raised PCT?
When the PTP is high, Scheutz et al recommend switching tack and now using the PCT level to determine the duration of antibiotic therapy, rather than whether or not to start it. They suggest that a fall in PCT to less than 90% of the peak allows safe cessation of the antibiotic(s).
It's a reasonable analysis and the conclusions seem fair, so it is probably also a useful way to think about how PCT can be best used based on current evidence, if you are not already doing so. Now we just need the cost of the test to come down a bit. That I'm aware of, no one has performed a cost-benefit analysis of serial PCT versus cost of antibiotic associated morbidity and duration of therapy.
Scheutz's paper it titled: Procalcitonin to Guide Initiation and Duration of Antibiotic Treatment in Acute Respiratory Infections: An Individual Patient Data Meta- Analysis. (http://cid.oxfordjournals.org/content/55/5/651.full.pdf)
1) Schuetz P et al. Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Schuetz P et al. Role of Procalcitonin in Managing Adult Patients With Respiratory TractInfections. Chest 2012;141:1063-1073.PMID: 22474148
2) Mirjam Christ-Crain, Beat Müller. Procalcitonin in bacterial infections – hype, hope, more or less? SWISS MED WKLY 2005;135:451–460.
3) Simon L, Gauvin F, Amre DK, Saint-Louis P, et al. Serum procalcitonin and C-Reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis. CID 2004;39:206–217. Erratum in: Clin Infect Dis. 2005 May 1;40(9):1386-8. PMID: 15307030.
4) Kristopher A. McGee, MD and Nikola A. Baumann, PhD. Clinical Laboratory News: Procalcitonin - Clinical Utility in Diagnosing Sepsis. American Association for Clinical Chemistry. July 2009: Volume 35, Number 7.
5) Christ-Crain M, Muller B. Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J 2007;30:556–573. PMID: 17766633
6) Briel M, Schuetz P, Mueller B, Young J, et al. Procalcitonin-guided antibiotic use vs. a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 2008;168(18):2000–2007. PMID:18852401