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Procalcitonin: improved biochemical severity stratification and postoperative monitoring in severe abdominal inflammation and sepsis

  • New Surgical Horizons
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Abstract

Background:

Infections and sepsis are among the most devastating complications in abdominal surgery and significantly contribute to morbidity and mortality. Early and reliable diagnosis of septic complications is notoriously difficult, and the search for novel approaches to overcome this problem is still a compelling issue for clinicians. Among a large array of inflammatory parameters, procalcitonin (PCT), the 116-amino-acid pro-peptide of calcitonin, has gained considerable importance in identifying patients at risk of developing infection and sepsis in clinical practice.

Methods:

Along with the latest insights into pathophysiological aspects of this pro-hormone, the literature as well as our own experience on the usefulness of PCT determinations in patients with severe inflammatory abdominal disorders was reviewed.

Results:

Although the term “sepsis” does not embrace the integral properties of PCT, a remarkable number of clinical studies have demonstrated the pivotal role of this parameter in the host response to microbial and fungal infections. In acute pancreatitis PCT allows early severity stratification and closely correlates with the development of subsequent pancreatic infections. In patients with peritonitis PCT reflects overall disease severity and is an early and reliable indicator of overall prognosis. Postoperative monitoring of PCT is a helpful tool to identify patients with evolving or persisting septic complications after elective and emergency abdominal surgery.

Conclusions:

Compared with established biochemical routine variables, PCT significantly contributes to earlier and better stratification of patients at risk of developing septic complications and provides excellent prognostic assessment in severe abdominal inflammation. The currently available test systems render PCT an applicable and readily available parameter under clinical routine and emergency conditions.

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References

  1. Wichmann MW, Inthorn D, Andress HJ, Schildberg FW (2000) Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med 26:167–172

    CAS  PubMed  Google Scholar 

  2. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256

    PubMed  Google Scholar 

  3. Marshall JC, Vincent JL, Fink MP, Cook DJ, Rubenfeld G, Foster D, Fisher CJ, Faist E, Reinhart K (2003) Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the fifth Toronto sepsis roundtable, Toronto, Ontario, Canada, October 25–26, 2000. Crit Care Med 31:1560–1567

    Article  PubMed  Google Scholar 

  4. Copp DH, Davidson AGP (1961) Evidence for a new parathyroid hormone which lowers blood calcium. Proc Soc Biol Med 107:342–344

    CAS  Google Scholar 

  5. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C (1993) High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 341:515–518

    CAS  PubMed  Google Scholar 

  6. Meisner M (2002) Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 232:17–29

    Article  Google Scholar 

  7. Carrol ED, Thomson APJ, Hart CA (2002) Procalcitonin as a marker of sepsis. Int J Antimicrob Agents 20:1–9

    Article  CAS  PubMed  Google Scholar 

  8. Müller B, Becker KL (2001) Procalcitonin: how a hormone became a marker and mediator of sepsis. Swiss Med Wkly 131:595–602

    PubMed  Google Scholar 

  9. Wimalawansa SJ (1997) Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily. Crit Rev Neurobiol 11:167–239

    CAS  PubMed  Google Scholar 

  10. Adema GJ, Baas PD (1992) A novel calcitonin-encoding mRNA is produced by alternative processing of calcitonin/calcitonin gene-related peptide. J Biol Chem 267:7943–7948

    CAS  PubMed  Google Scholar 

  11. Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304:129–135

    CAS  PubMed  Google Scholar 

  12. Russwurm S, Stonans I, Stonane E, Wiederhold M, Luber A, Zipfel PF, Deigner HP, Reinhart K (2001) Procalcitonin and CGRP-1 mRNA expression in various human tissues. Shock 16:109–112

    CAS  PubMed  Google Scholar 

  13. Müller B, White JC, Nylen ES, Snider RH, Becker KL, Habener JF (2001) Ubiquitous expression of the calcitonin-I gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 86:396–404

    PubMed  Google Scholar 

  14. Oberhoffer M, Stonans I, Russwurm S, Stonane E, Vogelsang H, Junker U, et al (1999) Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis related cytokines in vitro. J Lab Clin Med 134:49–55

    CAS  PubMed  Google Scholar 

  15. Oberhoffer M, Vogelsang H, Jaeger L, Reinhart K (1999) Katacalcin and calcitonin immunoreactivity in different types of leukocytes indicate intracellular procalcitonin content. J Crit Care 14:29–33

    CAS  Google Scholar 

  16. Balog A, Ocsovszki I, Mandi Y (2002) Flow cytometric analysis of procalcitonin expression in human monocytes and granulocytes. Immunol Lett 84:199–203

    Article  CAS  PubMed  Google Scholar 

  17. Monneret G, Laroche B, Bienvenu J (1999) Procalcitonin is not produced by circulating blood cells. Infection 27:34

    CAS  PubMed  Google Scholar 

  18. Svaldi M, Hirber J, Lanthaler AI, Mayr O, Faes S, Peer E, Mitterer M (2001) Procalcitonin-reduced sensitivity and specificity in heavily leukopenic and immunosuppressed patients. Br J Haematol 115:53–57

    Article  CAS  PubMed  Google Scholar 

  19. Silomon M, Bach F, Ecker D, Graeter T, Grundmann U, Larsen R (1999) Procalcitonin nach extrakorporaler Zirkulation. Anaesthesist 48:395–398

    CAS  PubMed  Google Scholar 

  20. Kretzschmar M, Krüger A, Schirrmeister W (2001) Procalcitonin following elective partial liver resection—origin from the liver? Acta Anaesthesiol Scand 45:1162–1167

    Article  CAS  PubMed  Google Scholar 

  21. Meisner M, Müller V, Khakpour Z, Toegel E, Redl H (2003) Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model. Shock 19:187–190

    Article  PubMed  Google Scholar 

  22. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, Bohuon C (1994) Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrine Metab 79:1605–608

    CAS  Google Scholar 

  23. Meisner M, Tschaikowsky K, Schnabel S, Schmidt J, Katalinic A, Schuttler J (1997) Procalcitonin—influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Eur J Clin Chem Clin Biochem 35:597–601

    CAS  PubMed  Google Scholar 

  24. Meisner M, Lohs T, Hüttemann E, Schmidt J, Hüller M, Reinhart K (2001) The plasma elimination rate and urinary secretion of procalcitonin in patients with normal and impaired renal function. Eur J Anaesthesiol 18:79–87

    CAS  PubMed  Google Scholar 

  25. Muller B, Becker KL, Kranzlin M, Schachinger H, Huber PR, Nylen ES, Snider RH, White JC, Schmidt-Gayk H, Zimmerli W, Ritz R (2000) Disordered calcium homeostasis of sepsis: association with calcitonin precursors. Eur J Clin Invest 30:823–831

    Article  CAS  PubMed  Google Scholar 

  26. Lind L, Carlstedt F, Rastad J, Stiernstrom H, Stridsberg M, Ljunggren O, Wide L, Larsson A, Hellman P, Ljunghall S (2000) Hypocalcemia and parathyroid hormone secretion in critically ill patients. Crit Care Med 28:93–99

    Article  CAS  PubMed  Google Scholar 

  27. Steinwald PM, Whang KT, Becker KL, Snider RH, Nylen ES, White JC (1999) Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. Crit Care 3:11–16

    Article  PubMed  Google Scholar 

  28. Claeys R, Vinken S, Spapen H, ver Elst K, Decochez K, Huyghens L, Gorus FK (2002) Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and biological correlates. Crit Care Med 30:757–762

    CAS  PubMed  Google Scholar 

  29. Monneret G, Pachot A, Laroche B, Picollet J, Bienvenue J (2000) Procalcitonin and calcitonin gene-related peptide decrease LPS-induced TNF production by human circulating blood cells. Cytokine 12:762–764

    Article  CAS  PubMed  Google Scholar 

  30. Preas HL, Nylen ES, Snider RH, Becker KL, White JC, Agosti JM, Suffredini AF (2001) Effects of anti-inflammatory agents on serum levels of procalcitonin precursors during human experimental endotoxemia. J Infect Dis 184:373–376

    Google Scholar 

  31. Monneret G, Arpin M, Venet F, Maghni K, Debard AL, Pachot A, Lepape A, Bienvenu J (2003) Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils. Intensive Care Med 29:923–928

    PubMed  Google Scholar 

  32. Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, Schobersberger W (2002) Migration of human monocytes in response to procalcitonin. Crit Care Med 30:1112–1117

    Google Scholar 

  33. Nylen ES, Whang KT, Snider RH Jr, Steinwald PM, White JC, Becker KL (1998) Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Crit Care Med 26:1001–1006

    CAS  PubMed  Google Scholar 

  34. Wagner KE, Martinez JM, Vath SD, Snider RH, Nylen ES, Becker KL, Muller B, White JC (2002) Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs. Crit Care Med 30:2313–2321

    Article  CAS  PubMed  Google Scholar 

  35. Martinez JM, Wagner KE, Snider RH, Nylen ES, Muller B, Sarani B, Becker KL, White JC (2001) Improved physiologic and metabolic parameters and increased survival with late procalcitonin immunoneutralization in septic pigs. Surg Infect 2:193–204

    Article  CAS  Google Scholar 

  36. Steinbach G, Rau B, Debard AL, Javourez JF, Bienvenu J, Ponzio A, Bonfa A, Hubl W, Demant T, Külpmann WR, Buchholz J, Schumann G (2004) Multicenter evaluation of a new immunoassay for PCT measurement on the Kryptor System. Clin Chem Lab Med (in press)

  37. Meisner M, Brunkhorst FM, Reith HB, Schmidt J, Lestin HG, Reinhart K (2000) Clinical experiences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin. Clin Chem Lab Methods 38:989–995

    CAS  Google Scholar 

  38. Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, Li Q, Tamarkin L, White JC (2000) Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock 14:73–78

    CAS  PubMed  Google Scholar 

  39. Ittner L, Born W, Rau B, Steinbach G, Fischer JA (2002) Circulating procalcitonin and cleavage products in septicaemia compared with medullary thyroid carcinoma. Eur J Endocrinol 147:727–731

    Google Scholar 

  40. Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG (1997) The potential role of procalcitonin and interleukin-8 in the prediction of infected necrosis in acute pancreatitis. Gut 41:832–840

    CAS  PubMed  Google Scholar 

  41. Benoist JF, Mimoz O, Assicot M, Edouard A (1998) Serum procalcitonin, but not C-reactive protein, identifies sepsis in trauma patients. Clin Chem 44:1778–1779

    CAS  PubMed  Google Scholar 

  42. Mimoz O, Benoist JF, Edouard AR, Assicot M, Bohuon C, Samii K (1998) Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome. Intensive Care Med 24:185–188

    Article  CAS  PubMed  Google Scholar 

  43. Wanner GA, Keel M, Steckholzer U, Beier W, Stocker R, Ertel W (2000) Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients. Crit Care Med 28:950–957

    CAS  PubMed  Google Scholar 

  44. Hensler T, Sauerland S, Lefering R, Nagelschmidt M, Bouillon B, Andermahr J, Neugebauer EA (2003) The clinical value of procalcitonin and neopterin in predicting sepsis and organ failure after major trauma. Shock 20:420–426

    Article  PubMed  Google Scholar 

  45. Sauerland S, Hensler T, Bouillon B, Rixen D, Raum MR, Andermahr J, Neugebauer EA (2003) Plasma levels of procalcitonin and neopterin in multiple trauma patients with or without brain injury. J Neurotrauma 20:953–960

    Article  PubMed  Google Scholar 

  46. Carsin H, Assicot M, Feger F, Roy O, Pennacino I, Le Bever H, Ainaud P, Bohuon C (1997) Evolution and significance of circulating procalcitonin levels compared with IL-6, TNF alpha and endotoxin levels early after thermal injury. Burns 23:218–224

    Article  CAS  PubMed  Google Scholar 

  47. von Heimburg D, Stieghorst W, Khorram-Sefat R, Pallua N (1998) Procalcitonin—a sepsis parameter in severe burn injuries. Burns 24:745–750

    PubMed  Google Scholar 

  48. Sachse C, Machens HG, Felmerer G, Berger A, Henkel E (1999) Procalcitonin as a marker for the early diagnosis of severe infection after thermal injury. J Burn Care Rehabil 20:354–360

    CAS  PubMed  Google Scholar 

  49. Dehne MG, Sablotzki A, Hoffmann A, Muhling J, Dietrich FE, Hempelmann G (2002) Alterations of acute phase reaction and cytokine production in patients following severe burn injury. Burns 28:535–542

    Article  PubMed  Google Scholar 

  50. Adamik B, Kubler-Kielb J, Golebiowska B, Gamian A, Kubler A (2000) Effect of sepsis and cardiac surgery with cardiopulmonary bypass on plasma level of nitric oxide metabolites, neopterin, and procalcitonin: correlation with mortality and postoperative complications. Intensive Care Med 26:1259–1267

    CAS  PubMed  Google Scholar 

  51. Baykut D, Schulte-Herbruggen J, Krian A (2000) The value of procalcitonin as an infection marker in cardiac surgery. Eur J Med Res 5:530–536

    CAS  PubMed  Google Scholar 

  52. Sablotzki A, Börgermann J, Baulig W, Friedrich I, Spillner J, Silber RE, Czeslik E (2001) Lipopolysaccharide-binding protein (LBP) and markers of acute phase response in patients with multiple organ dysfunction syndrome following open heart surgery. Thorac Cardiovasc Surg 49:273–278

    Article  CAS  PubMed  Google Scholar 

  53. Lecharny JB, Khater D, Bronchard R, Philip I, Durand G, Desmonts JM, Dehoux M (2001) Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery. Crit Care Med 29:323–325

    CAS  PubMed  Google Scholar 

  54. Aouifi A, Piriou V, Bastien O, Blanc P, Bouvier H, Evans R, Celard M, Vandenesch F, Rousson R, Lehot JJ (2000) Usefulness of procalcitonin for diagnosis of infection in cardiac surgical patients. Crit Care Med 28:3171–3176

    CAS  PubMed  Google Scholar 

  55. Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D, Tschaikowsky K (2002) Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications. Intensive Care Med 28:1094–1102

    Article  Google Scholar 

  56. Dörge H, Schöndube FA, Dörge P, Seipelt R, Voss M, Messmer BJ (2003) Procalcitonin is a valuable prognostic marker in cardiac surgery but not specific for infection. Thorac Cardiovasc Surg 51:322–326

    Article  PubMed  Google Scholar 

  57. Reith HB, Mittelkötter U, Debus ES, Küssner C, Thiede A (1998) Procalcitonin in early detection of postoperative complications. Dig Surg 15:260–265

    CAS  PubMed  Google Scholar 

  58. Meisner M, Tschaikowsky K, Hutzler A, Schick C, Schuttler J (1998) Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med 24:680–684

    Article  CAS  PubMed  Google Scholar 

  59. Di Filippo A, Lombardi A, Ognibene A, Messeri G, Tonelli F (2002) Procalcitonin as an early marker of postoperative infectious complications. Minerva Chir 57:59–62

    PubMed  Google Scholar 

  60. Beger HG, Bittner R, Block S, Büchler M (1986) Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 49:433–438

    Google Scholar 

  61. Rau B, Beger HG (1997) Surgical treatment of infected necrosis. World J Surg 21:155–161

    CAS  PubMed  Google Scholar 

  62. Bradley EL III, Allen K (1991) A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg 161:19–25

    PubMed  Google Scholar 

  63. Rau B, Pralle U, Uhl W, Schoenberg MH, Beger HG (1995) Management of sterile necrosis in instances of severe acute pancreatitis. J Am Coll Surg 181:279–288

    CAS  PubMed  Google Scholar 

  64. Rau B, Steinbach G, Baumgart K, Gansauge F, Grünert A, Beger HG (2000) The clinical value of procalcitonin in the prediction of infected necrosis in acute pancreatitis. Intensive Care Med 26:159–164

    Article  Google Scholar 

  65. Gerzof SG, Banks PA, Robbins AH, Johnson WC, Spechler SJ, Wetzner SM, Snider JM, Langevin RE, Jay ME (1987) Early diagnosis of pancreatic infection by computed tomography-guided aspiration. Gastroenterology 93:1315–1320

    CAS  PubMed  Google Scholar 

  66. Rau B, Pralle U, Mayer JM, Beger HG (1998) The role of ultrasonographically guided fine-needle aspiration cytology in the diagnosis of infected pancreatic necrosis. Br J Surg 85:179–184

    Article  CAS  PubMed  Google Scholar 

  67. Mandi Y, Farkas G, Takacs T, Boda K, Lonovics J (2000) Diagnostic relevance of procalcitonin, IL-6, and sICAM-1 in the prediction of infected necrosis in acute pancreatitis. Int J Pancreatol 28:41–49

    CAS  PubMed  Google Scholar 

  68. Riche FC, Cholley BP, Laisne MJ, Vicaut E, Panis YH, Lajeunie EJ, Boudiaf M, Valleur PD (2003) Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis. Surgery 133:257–262

    Article  PubMed  Google Scholar 

  69. Makay R, Issekutz A, Banga P, Belagyi T, Olah A (2003) Role of procalcitonin rapid test in the differential diagnosis of uninfected and infected forms of acute pancreatitis. Magy Seb 56:31–33

    Google Scholar 

  70. Ammori BJ, Becker KL, Kite P, Snider RH, Nylen ES, White JC, Barclay GR, Larvin M, McMahon MJ (2003) Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis. Pancreas 27:239–243

    Article  CAS  PubMed  Google Scholar 

  71. Kylänpää-Bäck ML, Takala A, Kemppainen E, Puolakkainen P, Haapiainen R, Repo H (2001) Procalcitonin strip test in the early detection of severe acute pancreatitis. Br J Surg 88:222–227

    Article  PubMed  Google Scholar 

  72. Kylänpää-Bäck ML, Takala A, Kemppainen EA, Puolakkainen PA, Leppäniemi AK, Karonen SL, Orpana A, Haapiainen RK, Repo H (2001) Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin in predicting the severity of acute pancreatitis. Crit Care Med 29:63–69

    Google Scholar 

  73. Müller CA, Uhl W, Printzen G, Gloor B, Bischofberger H, Tcholakov O, Büchler MW (2000) Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis. Gut 46:233–238

    Article  CAS  PubMed  Google Scholar 

  74. Pezzilli R, D’Eril GVM, Morselli-Labate AM, Merlini G, Barakat B, Bosoni T (2000) Serum amyloid A, procalcitonin, and C-reactive protein in early assessment of severity of acute pancreatitis. Dig Dis Sci 45:1072–1078

    Article  CAS  PubMed  Google Scholar 

  75. Frasquet J, Saez J, Trigo C, Martinez J, Such J, Perez-Maeto M (2003) Early measurement of procalcitonin does not predict severity in patients with acute pancreatitis. Br J Surg 90:1129–1130

    Article  CAS  PubMed  Google Scholar 

  76. Reith HB, Mittelkötter U, Wagner R, Thiede A (2000) Procalcitonin (PCT) in patients with abdominal sepsis. Intensive Care Med 26:165–169

    Article  Google Scholar 

  77. Schroder J, Staubach KH, Zabel P, Stuber F, Kremer B (1999) Procalcitonin as a marker of severity in septic shock. Langenbecks Arch Surg 384:33–38

    PubMed  Google Scholar 

  78. Lindberg M, Hole A, Johnsen H, Asberg A, Rydning A, Myrvold HE, Bjerve KS (2002) Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery. Scand J Clin Lab Invest 62:189–194

    Article  CAS  PubMed  Google Scholar 

  79. Molter GP, Soltez S, Kottke R, Wilhelm W, Biedler A, Silomon M (2003) Procalcitoninplasmakonzentration und systemische inflammatorische Antwort nach verschiedenen operativen Eingriffen. Anaesthesist 52:210–217

    Article  CAS  PubMed  Google Scholar 

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  1. Department of General, Visceral, and Vascular Surgery, University of the Saarland, Kirrberger Strasse, 66421, Homburg/Saar, Germany

    B. Rau, C. M. Krüger & M. K. Schilling

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  1. B. Rau
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Rau, B., Krüger, C.M. & Schilling, M.K. Procalcitonin: improved biochemical severity stratification and postoperative monitoring in severe abdominal inflammation and sepsis. Langenbecks Arch Surg 389, 134–144 (2004). https://doi.org/10.1007/s00423-004-0463-1

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