The Role of Procalcitonin in Septic Patients A Brief Overview
Translational Medicine

Translational Medicine
Open Access

ISSN: 2161-1025

+44 1223 790975

Review Article - (2014) Volume 4, Issue 4

The Role of Procalcitonin in Septic Patients A Brief Overview

Dominik Hentschel, Christoph B Olivier, Christoph Bode and Philipp Diehl*
Heart Center, University of Freiburg, Dept. for Cardiology & Angiology I, Hugstetter Str. 55, 79100 Freiburg, Germany
*Corresponding Author: Philipp Diehl, Heart Center, University of Freiburg, Department For Cardiology & Angiology, Hugstetter Str. 55, 79100 Freiburg, Germany, Tel: 49 761 270 35600 Email:


Bacterial infections with consecutive sepsis have a high incidence in intensive care patients and are often associated with lethal complications. As early diagnosis followed by antibiotic therapy is vital for these patients, sensitive biomarkers indicating sepsis are of fundamental importance for the survival of septic patients. Procalcitonin, which is a protein produced by thyroidal c-cells, has been shown over 20 years to be increased in patients with sepsis. Since then, multiple studies have investigated the role of procalcitonin in patients with sepsis and systemic inflammation. However, the value of procalcitonin in patients with sepsis is still discussed controversial. This review aims to briefly summarize the current literature of procalcitonin and sepsis.


Keywords: Procalcitonin, Sepsis,Intensive care medicine


This review aims to summarize recent trials on procalcitonin (PCT) in septic patients. The discussed studies have been selected by the personal interest of the authors, with no claim of completeness.History of procalcitonin (PCT) begins with the discovery of the hormone calcitonin (CT) in the early 1960`s by Copp,et al. [1] being found in dogs as an adversary to parathormone.In 1975, Moyaet al. [2] described a precursor protein of calcitonin which was named procalcitonin.The molecular structure of procalcitoninwas firstdescribed in 1981, when it was shown that PCT is a glycoprotein consisting of 116 aminoacids with a weight of 13 kDathat is processed from its own precursor preprocalcitonin [3,4]. Being transcripted from the CALC-1-gene located on chromosome 11, PCT is under physiological conditions only produced by thyroidalc-cells, and in small amounts in neuroendocrine cells of the lung and small intestine respectively, where it is processed into its effective hormone calcitonin and stored in cellular vesicles until released in conditions of high serum calcium levels.Hence, PCT is nearly not detectable in serum of normocalcaemic patients [5].

Clinical Implication

Assicotet al. [6] were one of first describing increased PCT levels in the blood of patients with sepsis and systemic infection in 1993. Since then, several clinical studies have investigated the role of procalcitoninas biomarkers in patients with systemic infections and sepsis [7-9]. However, besides septic conditions, increased PCT levels have furthermore been described in several other pathological conditions, such cardiogenic shock, severe systemic-inflammatoryresponse- syndrom(SIRS), surgery and trauma [10-13]. Anyway, procalcitoninlevels > 10ng/ml are rarely seen in these diseases and its relevance remains mainly unknown [14].

Becoming an additional marker for sepsis, the superiority of PCT against other surrogate markers (e.g. C-reactive protein, CRP) was shown in several studies. Simon et al. [15] performed a meta?analysis of studies that evaluated PCT and CRP for the diagnosis of bacterial infections. They found that procalcitoninis more sensitive and more specific than CRP in discriminating bacterial from non?infective causes of systemic inflammation.Even though procalcitoninhas been found to be a promising diagnostic marker in sepsis, it does not play a major role in several international guidelines. Hence, as published in 2013, the American Society of Critical Care Medicine (SCCM, picks up PCT in a seemingly minor recommendation [16]. In a grade 2C recommendation it is suggest that low procalcitonin levels can aid stopping antibiotic therapy in patients with non-confirmed sepsis. However,due to a lack of evidence the SCCM does not recommend PCT measurements to discriminate between sepsis and non-infective systemic inflammation.Guidelines of other societies such as the German Sepsis Society (DSG, and German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI, recommend – within limitations - early measurement of procalcitoninin order to rule out severe sepsis and to stop antibiotic treatment in case of nonconfirmed sepsis [17]. For further studies that assessed the relevance of PCT for the guidance of antibiotic therapies, please see the already published work [18-20].

Besides its role as a diagnostic marker in bacterial infections, only few studies have investigated whether PCT itself triggers inflammation and sepsis progression. Promising results obtained in septic hamsters, in which PCT increased and anti-PCT antibodies reduced mortality, underline the role of procalcitoninas a mediator in sepsis [21,22]. However, these data have not been transferred on humans yet.

Recently Published Data

Since the second Surviving Sepsis Campaign was published in 2013, several studies have shown the valueof PCT as a diagnostic marker in septic patients [16]. However, there was no convincing evidence showing that PCTdiscriminates between ?bacterial sepsis and noninfective SIRSuntil Anandet al. [23] recently published a prospective observational single-centre trial in which they investigated whether procalcitoninand interleukin-6 (IL-6) can be used to distinguish between sepsis (cultural positive and negative) and non-infective SIRS. They found in 208 patients with either non-infectious SIRS, culturenegative or culture-positive sepsisthat PCT was significantly elevated in patients with culture-negative and culture-positive groups compared to patients with SIRS. If these findings can be confirmed in larger multicentre trials, they will likely change the role of PCT in future sepsis guidelines.

Current guidelines do not consider PCT as a marker predicting the clinical prognosis of septic patients.De Azevedo et al. [24] investigated whether PCT levels predict the outcome of sepsis patients.They used the so-called procalcitonin clearance (PCT-c), which was implemented by two Spanish studies in 2012and is calculated by the initial PCT value and those after 24 h and 48 h [25,26]. By correlating the PCT-c with the survival of 130 patients suffering from sepsis,De Azevedoet al. [24] found in patients with severe sepsis and septic shock that the PCT-c after 24 h/48 h was 10 %/35.5 % among survivors and -100 %/-170 % in non?survivors respectively. These data suggest that the PCT?c of 24 h and 48 h might be useful markers to assess the prognosis of patients with severe sepsis and are therefore in line with the aforementioned studies.

Multi organ failure with impaired hepatic or renal function is common in patients with severe sepsis. As it has been described that C reactive protein is increased during renal insufficiency, the question aroused whether a reduced glomerular filtration rate might be associated with increased procalcitoninlevels, too. In 2002, Sitter, et al. [27] investigated whether PCT allows to differ between chronic inflammation in kidney disease and bacterial invasion.They found that renal insufficiency is not associated with increased procalcitonin levels, or at least almost always below a cut-off <1,5ng/dl, and thus can be used as a parameter for early diagnosis of acute bacterial infection.These data are in line with recently published studies [28]. Besides impaired renal function, liver dysfunction has a high co incidence in septic patients. Hypothesizing that patients with decreased liver functions might have altered PCT levels, Rahimkhaniet al. [29] assessed PCT levels in 64 patients with cirrhotic liver diseases and compared the data to 32 control subjects. Theyfound that PCT levels are increased in patients with liver cirrhosis and particularly in those with a bacterial infection suggesting that an impaired hepatic function is related to increased PCT levels. This data was partly confirmed by Elefsiniotis, who found that patients with liver cirrhosis develop increased PCT levels under bacterial infection [30]. However, since studies in which PCT levels were assessed in cirrhotic patients show controversial results, procalcitoninlevels of these patients might need to be interpreted with caution.

In summary, as indicated in recently published studies PCT might have a higher diagnostic and prognostic value than reflected in current guidelines. Nevertheless, data from the above mentioned studies base on comparably small patient numbers and need to be confirmed in multicenter trials.


  1. Copp DH, Cameron EC, Cheney BA, Davidson AG, Henze KG (1962) Evidence for calcitonin--a new hormone from the parathyroid that lowers blood calcium. Endocrinology 70: 638-649.
  2. Moya F, Nieto A, JL RC (1975) Calcitonin biosynthesis: evidence for a precursor. Eur J Biochem. [In Vitro]. 55:407-413.
  3. Jacobs JW, Lund PK, Potts JT, Bell NH, Habener JF (1981) Procalcitonin is a glycoprotein. J Biol Chem. 256:2803-2807.
  4. Vincent JL, Van Nuffelen M, Lelubre C(2015) Host response biomarkers in sepsis: the role of procalcitonin. Methods in molecular biology 1237:213-224.
  5. Muller B, White JC, Nylen ES, Snider RH, Becker KL, et al. (2001) Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 86:396-404.
  6. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, et al. (1993) High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 341: 515-518.
  7. Becker KL, Snider R, Nylen ES(2010) Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. British j pharmacol 159: 253-264.
  8. Sinha M, Desai S, Mantri S, Kulkarni A (2011) Procalcitonin as an adjunctive biomarker in sepsis. Ind J anaesthesia 55: 266-270.
  9. Vincent JL (2000) Procalcitonin: THE marker of sepsis?. Critical care medicine 28:1226-1228.
  10. Geppert A, Steiner A, Delle-Karth G, Heinz G, Huber K (2003) Usefulness of procalcitonin for diagnosing complicating sepsis in patients with cardiogenic shock. Inten care med. 29:1384-1389.
  11. Hausfater P, Hurtado M, Pease S, Juillien G, Lvovschi VE, et al. (2008) Is procalcitonin a marker of critical illness in heatstroke? Inten care med. 34: 1377-1783.
  12. Meisner M, Adina H, Schmidt J (2006) Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients. Critical care. 10: R1.
  13. Sorbera LA(2005) Procalcitonin as an effective biomarker for the diagnosis and prognosis of severe sepsis. Highlights from the 25th International Symposium on Intensive Care and Emergency Medicine. March 21-25, 2005, Brussels, Belgium. Drugs of today. 41:253-256.
  14. Meisner M (2014) Update on procalcitonin measurements. Ann Lab Med 34:263-273.
  15. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 39:206-217.
  16. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al. (2012) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: Critical care medicine. [Consensus Development Conference Practice Guideline Research Support, Non-U.S. Gov't]. 41: 580-637.
  17. Reinhart K, Brunkhorst FM, Bone HG, Bardutzky J, Dempfle CE, et al. (2010) Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinare Vereinigung fur Intensiv- und Notfallmedizin (DIVI)). Ger Med Sci. Practice Guideline. 8
  18. Prkno A, Wacker C, Brunkhorst FM, Schlattmann P (2013) Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock--a systematic review and meta-analysis. Crit Care. 17(6).
  19. Quenot JP, Luyt CE, Roche N, Chalumeau M, Charles PE, et al. (2013) Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy. Ann Intensive Care. 3:2110-5820.
  20. Schuetz P, Albrich W, Mueller B (2011) Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 9:1741-7015.
  21. Braithwaite SS (1998) Procalcitonin--marker, or mediator? Critical care medicine. [Comment Editorial]. 26:977-978.
  22. Nylen ES, Whang KT, Snider RH, Steinwald PM, White JC, et al. (1998) Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Critical care medicine. [Research Support, U.S. Gov't, Non-P.H.S.] 26:1001-1006.
  23. Anand D, Das S, Bhargava S, Srivastava LM, Garg A, et al. (2014) Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: A prospective, observational, cohort study. J critical care 30: 218.e7–218.e12.
  24. de Azevedo JR, Torres OJ, Beraldi RA, Ribas CA, Malafaia O (2014) Prognostic evaluation of severe sepsis and septic shock: Procalcitonin clearance vs Delta Sequential Organ Failure Assessment. J critical care.
  25. Suberviola B, Castellanos-Ortega A, Gonzalez-Castro A, Garcia-Astudillo LA, Fernandez-Miret B (2012) [Prognostic value of procalcitonin, C-reactive protein and leukocytes in septic shock]. Medicina intensiva / Sociedad Espanola de Medicina Intensiva y Unidades Coronarias. [Clinical Trial]. 36:177-184.
  26. Ruiz-Rodriguez JC, Caballero J, Ruiz-Sanmartin A, Ribas VJ, Perez M, Boveda JL, et al. (2012) Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock. A prospective pilot study. Medicina intensiva / Sociedad Espanola de Medicina Intensiva y Unidades Coronarias. 36:475-480.
  27. Sitter T, Schmidt M, Schneider S, Schiffl H (2012) Differential diagnosis of bacterial infection and inflammatory response in kidney diseases using procalcitonin. J Nephrol 15:297-301.
  28. Grace E, Turner RM (2014) Use of Procalcitonin in Patients With Various Degrees of Chronic Kidney Disease Including Renal Replacement Therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
  29. Rahimkhani M, Einollahi N, Khavari Daneshvar H, Dashti N (2013) Survey of serum procalcitonin in cirrhotic patients. Acta Med Iran 51:153-156.
  30. Elefsiniotis IS, Skounakis M, Vezali E, Pantazis KD, Petrocheilou A, et al. (2006) Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease. Eur J Gastroenterol Hepatol. 18: 525-530.
Citation: Hentschel D, Olivier CB, Bode C, Diehl P (2014) The Role of Procalcitonin in Septic Patients – A Brief Overview. Transl Med 4:144.

Copyright: © 2014 Hentschel D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.