Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature

Christoph Sponholz, Yasser Sakr, Konrad Reinhart, Frank Brunkhorst, Christoph Sponholz, Yasser Sakr, Konrad Reinhart, Frank Brunkhorst

Abstract

Introduction: Systemic inflammatory response syndrome is common after surgery, and it can be difficult to discriminate between infection and inflammation. We performed a review of the literature with the aims of describing the evolution of serum procalcitonin (PCT) levels after uncomplicated cardiac surgery, characterising the role of PCT as a tool in discriminating infection, identifying the relation between PCT, organ failure, and severity of sepsis syndromes, and assessing the possible role of PCT in detection of postoperative complications and mortality.

Methods: We performed a search on MEDLINE using the keyword 'procalcitonin' crossed with 'cardiac surgery,' 'heart,' 'postoperative,' and 'transplantation.' Our search was limited to human studies published between January 1990 and June 2006.

Results: Uncomplicated cardiac surgery induces a postoperative increase in serum PCT levels. Peak PCT levels are reached within 24 hours postoperatively and return to normal levels within the first week. This increase seems to be dependent on the surgical procedure and on intraoperative events. Although PCT values reported in infected patients are generally higher than in non-infected patients after cardiac surgery, the cutoff point for discriminating infection ranges from 1 to 5 ng/ml, and the dynamics of PCT levels over time may be more important than absolute values. PCT is superior to C-reactive protein in discriminating infections in this setting. PCT levels are higher with increased severity of sepsis and the presence of organ dysfunction/failure and in patients with a poor outcome or in those who develop postoperative complications. PCT levels typically remain unchanged after acute rejection but increase markedly after bacterial and fungal infections. Systemic infections are associated with greater PCT elevation than is local infection. Viral infections are difficult to identify based on PCT measurements.

Conclusion: The dynamics of PCT levels, rather than absolute values, could be important in identifying patients with infectious complications after cardiac surgery. PCT is useful in differentiating acute graft rejection after heart and/or lung transplantation from bacterial and fungal infections. Further studies are needed to define cutoff points and to incorporate PCT levels in useful prediction models.

Figures

Figure 1
Figure 1
Serum procalcitonin (PCT) concentrations in patients after cardiac surgery with no complications according to the type of surgery. Group 1, coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Group 2, CABG without CPB. Group 3, valvular surgery with CBP.© The Board of Management and Trustees of the British Journal of Anaesthesia. Reproduced from [36] by permission of Oxford University Press/British Journal of Anaesthesia.
Figure 2
Figure 2
Procalcitonin (PCT) or C-reactive protein (CRP) to predict infection. Receiver operating characteristic (ROC) curve for PCT and CRP values for prediction of infection. From [39] with permission.

References

    1. Maruna P, Nedelnikova R, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res. 2000;49:S57–S61.
    1. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341:515–518. doi: 10.1016/0140-6736(93)90277-N.
    1. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, Bohuon C. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79:1605–1608. doi: 10.1210/jc.79.6.1605.
    1. Nijsten M, Olinga P, The TH, de Vries EG, Koops HS, Groothuis GM, Limburg PC, ten Duis HJ, Moshage H, Hoekstra HJ, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 2000;28:458–461. doi: 10.1097/00003246-200002000-00028.
    1. Oberhoffer M, Stonans I, Russwurm S, Stonane E, Vogelsang H, Junker U, Jager L, Reinhart K. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. J Lab Clin Med. 1999;134:49–55. doi: 10.1016/S0022-2143(99)90053-7.
    1. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39:206–217. doi: 10.1086/421997.
    1. Castelli GP, Pognani C, Meisner M, Stuani A, Bellomi D, Sgarbi L. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care. 2004;8:R234–R242. doi: 10.1186/cc2877.
    1. Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med. 2003;31:1737–1741. doi: 10.1097/01.CCM.0000063440.19188.ED.
    1. Brunkhorst FM, Wegscheider K, Forycki ZF, Brunkhorst R. Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock. Intensive Care Med. 2000;26:S148–S152. doi: 10.1007/s001340051134.
    1. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006;34:1996–2003. doi: 10.1097/01.CCM.0000226413.54364.36.
    1. Marc E, Menager C, Moulin F, Stos B, Chalumeau M, Guerin S, Lebon P, Brunet F, Raymond J, Gendrel D. [Procalcitonin measurement for reducing antibiotic treatments during outbreak of viral meningitis in children] Arch Pediatr. 2002;9:1–7. doi: 10.1016/S0929-693X(01)00793-X.
    1. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363:600–607. doi: 10.1016/S0140-6736(04)15591-8.
    1. Sandek A, Springer J, Habedank D, Brunkhorst FM, Anker SD. Procalcitonin-guided antibiotic treatment in heart failure. Lancet. 2004;363:1555–1556. doi: 10.1016/S0140-6736(04)16165-5.
    1. Oberhoffer M, Vogelsang H, Russwurm S, Hartung T, Reinhart K. Outcome prediction by traditional and new markers of inflammation in patients with sepsis. Clin Chem Lab Med. 1999;37:363–368. doi: 10.1515/CCLM.1999.060.
    1. Oczenski W, Fitzgerald RD, Schwarz S. Procalcitonin: a new parameter for the diagnosis of bacterial infection in the peri-operative period. Eur J Anaesthesiol. 1998;15:202–209. doi: 10.1111/j.0265-0215.1998.00280.x.
    1. Luyt CE, Guerin V, Combes A, Trouillet JL, Ben Ayed S, Bernard M, Gibert C, Chastre J. Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2005;171:48–53. doi: 10.1164/rccm.200406-746OC.
    1. Koszegi T. Immunoluminometric detection of human procalcitonin. J Biochem Biophys Methods. 2002;53:157–164. doi: 10.1016/S0165-022X(02)00104-5.
    1. Meisner M, Brunkhorst FM, Reith HB, Schmidt J, Lestin HG, Reinhart K. Clinical experiences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin. Clin Chem Lab Med. 2000;38:989–995. doi: 10.1515/CCLM.2000.147.
    1. Guerin S. [Evaluation of the detection of procalcitonin by an immuno-chromatography test: Brahms PCT-Q] Ann Biol Clin (Paris) 2000;58:613–614.
    1. Steinbach G, Rau B, Debard AL, Javourez JF, Bienvenu J, Ponzio A, Bonfa A, Hubl W, Demant T, Kulpmann WR, et al. Multicenter evaluation of a new immunoassay for procalcitonin measurement on the Kryptor System. Clin Chem Lab Med. 2004;42:440–449. doi: 10.1515/CCLM.2004.077.
    1. Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000;127:117–126. doi: 10.1067/msy.2000.101584.
    1. Meisner M, Tschaikowsky K, Hutzler A, Schick C, Schuttler J. Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med. 1998;24:680–684. doi: 10.1007/s001340050644.
    1. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97:215–252. doi: 10.1097/00000542-200207000-00030.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31:1250–1256. doi: 10.1097/01.CCM.0000050454.01978.3B.
    1. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–873. doi: 10.1097/01.CCM.0000117317.18092.E4.
    1. Kiessling AH, Isgro F, Tran KH, Saggau W. Procalcitonin serum levels in the postoperative phase after cardiac surgery. 46th Annual Meeting Scand Ass For Thoracic Surgery (SATS) 1997.
    1. Potapov EV, Wagner FD, Loebe M, Ivanitskaia EA, Muller C, Sodian R, Jonitz B, Hetzer R. Elevated donor cardiac troponin T and procalcitonin indicate two independent mechanisms of early graft failure after heart transplantation. Int J Cardiol. 2003;92:163–167. doi: 10.1016/S0167-5273(03)00083-4.
    1. Wagner FD, Jonitz B, Potapov E, Qedra N, Wegscheider K, Weinmann E, Loebe M, Hetzer R. Procalcitonin: a donor-specific predictor of early graft failure and early graft failure mortality after heart transplantation. J Heart Lung Transplant. 2001;20:206. doi: 10.1016/S1053-2498(00)00443-5.
    1. Kilger E, Pichler B, Goetz AE, Rank N, Welte M, Morstedt K, Vetter HO, Godje O, Schmitz C, Lamm P, et al. Procalcitonin as a marker of systemic inflammation after conventional or minimally invasive coronary artery bypass grafting. Thorac Cardiovasc Surg. 1998;46:130–133.
    1. Celebi S, Koner O, Menda F, Balci H, Hatemi A, Korkut K, Esen F. Procalcitonin kinetics in pediatric patients with systemic inflammatory response after open heart surgery. Intensive Care Med. 2006;32:881–887. doi: 10.1007/s00134-006-0180-z.
    1. Michalik DE, Duncan BW, Mee RB, Worley S, Goldfarb J, Danziger-Isakov LA, Davis SJ, Harrison AM, Appachi E, Sabella C. Quantitative analysis of procalcitonin after pediatric cardiothoracic surgery. Cardiol Young. 2006;16:48–53. doi: 10.1017/S1047951105002088.
    1. Arkader R, Troster EJ, Abellan DM, Lopes MR, Junior RR, Carcillo JA, Okay TS. Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients. J Cardiothorac Vasc Anesth. 2004;18:160–165. doi: 10.1053/j.jvca.2004.01.021.
    1. Macrina F, Tritapepe L, Pompei F, Sciangula A, Evangelista E, Toscano F, Criniti A, Brancaccio G, Puddu PE. Procalcitonin is useful whereas C-reactive protein is not, to predict complications following coronary artery bypass surgery. Perfusion. 2005;20:169–175. doi: 10.1191/0267659105pf800oa.
    1. Franke A, Lante W, Fackeldey V, Becker HP, Kurig E, Zoller LG, Weinhold C, Markewitz A. Pro-inflammatory cytokines after different kinds of cardio-thoracic surgical procedures: is what we see what we know? Eur J Cardiothorac Surg. 2005;28:569–575. doi: 10.1016/j.ejcts.2005.07.007.
    1. Rothenburger M, Markewitz A, Lenz T, Kaulbach HG, Marohl K, Kuhlmann WD, Weinhold C. Detection of acute phase response and infection. The role of procalcitonin and C-reactive protein. Clin Chem Lab Med. 1999;37:275–279. doi: 10.1515/CCLM.1999.048.
    1. Aouifi A, Piriou V, Blanc P, Bouvier H, Bastien O, Chiari P, Rousson R, Evans R, Lehot JJ. Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations. Br J Anaesth. 1999;83:602–607.
    1. Boeken U, Feindt P, Micek M, Petzold T, Schulte HD, Gams E. Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX) Cardiovasc Surg. 2000;8:550–554. doi: 10.1016/S0967-2109(00)00070-3.
    1. Baykut D, Schulte-Herbrüggen J, Krian A. The value of procalcitonin as an infection marker in cardiac surgery. Eur J Med Res. 2000;5:530–536.
    1. Aouifi A, Piriou V, Bastien O, Blanc P, Bouvier H, Evans R, Celard M, Vandenesch F, Rousson R, Lehot JJ. Usefulness of procalcitonin for diagnosis of infection in cardiac surgical patients. Crit Care Med. 2000;28:3171–3176. doi: 10.1097/00003246-200009000-00008.
    1. Loebe M, Locziewski S, Brunkhorst FM, Harke C, Hetzer R. Procalcitonin in patients undergoing cardiopulmonary bypass in open heart surgery – first results of the procalcitonin in heart surgery study (ProHearts) Intensive Care Med. 2000;26:S193–S198. doi: 10.1007/s001340051143.
    1. Sablotzki A, Borgermann J, Baulig W, Friedrich I, Spillner J, Silber RE, Czeslick E. Lipopolysaccharide-binding protein (LBP) and markers of acute-phase response in patients with multiple organ dysfunction syndrome (MODS) following open heart surgery. Thorac Cardiovasc Surg. 2001;49:273–278. doi: 10.1055/s-2001-17803.
    1. Lecharny JB, Khater D, Bronchard B, Philip I, Durand G, Desmonts JM, Dehoux M. Hyperprocalcitoninemia in patients with perioperative myocardial infarction after cardiac surgery. Crit Care Med. 2001;29:323–325. doi: 10.1097/00003246-200102000-00019.
    1. Bach F, Grundmann U, Bauer M, Buchinger H, Soltesz S, Graeter T, Larsen R, Silomon M. Modulation of the inflammatory response to cardiopulmonary bypass by dopexamine and epidural anaesthesia. Acta Anaesthesiol Scand. 2002;46:1227–1235. doi: 10.1034/j.1399-6576.2002.461010.x.
    1. Kerbaul F, Guidon C, Lejeune PJ, Mollo M, Mesana T, Gouin F. Hyperprocalcitoninemia is related to noninfectious postoperative systemic inflammatory distress syndrome associated with cardiovascular dysfunction after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2002;16:47–53. doi: 10.1053/jcan.2002.29672.
    1. Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R. Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications. Intensive Care Med. 2002;28:1094–1102. doi: 10.1007/s00134-002-1392-5.
    1. Beghetti M, Rimensberger PC, Kalangos A, Habre W, Gervaix A. Kinetics of procalcitonin, interleukin 6 and C-reactive protein after cardiopulmonary-bypass in children. Cardiol Young. 2003;13:161–167. doi: 10.1017/S1047951103000301.
    1. Kin H, Kawazoe K, Nakajima T, Niinuma H, Kataoka T, Endo S, Inada K. Perioperative serum procalcitonin concentrations in patients with acute aortic dissection. Eur Surg Res. 2003;35:451–454. doi: 10.1159/000072231.
    1. Hammer S, Fuchs AT, Rinker C, Daebritz S, Kozlik-Feldmann R, Netz H. Interleukin-6 and procalcitonin in serum of children undergoing cardiac surgery with cardiopulmonary bypass. Acta Cardiol. 2004;59:624–629. doi: 10.2143/AC.59.6.2005245.
    1. Hammer S, Loeff M, Reichenspurner H, Daebritz S, Tiete A, Kozlik-Feldmann R, Reichart B, Netz H. Effect of cardiopulmonary bypass on myocardial function, damage and inflammation after cardiac surgery in newborns and children. Thorac Cardiovasc Surg. 2001;49:349–354. doi: 10.1055/s-2001-19011.
    1. Hovels-Gurich HH, Schumacher K, Vazquez-Jiminez JF, Qing M, Huffmeier U, Buding B, Messmer BJ, von Bernuth G, Seghaye MC. Cytokine balance in infants undergoing cardiac operation. Ann Thorac Surg. 2002;73:601–609. doi: 10.1016/S0003-4975(01)03391-4.
    1. Meisner M, Reinhart K. Is procalcitonin really a marker of sepsis? Int J Intensive Care. 2001;8:15–25.
    1. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta. 2002;323:17–29. doi: 10.1016/S0009-8981(02)00101-8.
    1. Aydin NB, Gercekoglu H, Aksu B, Ozkul V, Sener T, Kiygil I, Turkoglu T, Cimen S, Babacan F, Demirtas M. Endotoxemia in coronary artery bypass surgery: a comparison of the off-pump technique and conventional cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2003;125:843–848. doi: 10.1067/mtc.2003.323.
    1. Bitkover K, Hansson LO, Valen G, Vaage J. Effects of cardiac surgery on some clinically used inflammation markers and procalcitonin. Scand Cardiovasc J. 2000;34:307–314.
    1. Sablotzki A, Dehne MG, Friedrich I, Grond S, Zickmann B, Muhling J, Silber RE, Czeslick EG. Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery. Eur J Med Res. 2003;8:71–76.
    1. Holzheimer RG. Oral antibiotic prophylaxis can influence the inflammatory response in aortic aneurism repair: results of a randomised clinical study. J Chemother. 2003;15:157–164. doi: 10.1159/000067132.
    1. Dörge H, Schondube FA, Dorge P, Seipelt R, Voss M, Messmer BJ. Procalcitonin is a valuable prognostic marker in cardiac surgery but not specific for infection. Thorac Cardiovasc Surg. 2003;51:322–326. doi: 10.1055/s-2003-45425.
    1. Hammer S, Meisner F, Dirschedl P, Fraunberger P, Meiser B, Reichart B, Hammer C. Procalcitonin for differential diagnosis of graft rejection and infection in patients with heart and/or lung grafts. Intensive Care Med. 2000;26:S182–186. doi: 10.1007/s001340051141.
    1. Boeken U, Feindt P, Petzold T, Klein M, Micek M, Seyfert UT, Mohan E, Schulte HD, Gams E. Diagnostic value of procalcitonin: the influence of cardiopulmonary bypass, aprotinin, SIRS, and sepsis. Thorac Cardiovasc Surg. 1998;46:348–351.
    1. Giamarellos-Bourboulis EJ, Mega A, Grecka P, Scarpa N, Koratzanis G, Thomopoulos G, Giamarellou H. Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med. 2002;28:1351–1356. doi: 10.1007/s00134-002-1398-z.
    1. Giamarellos-Bourboulis EJ, Giannopoulou P, Grecka P, Voros D, Mandragos K, Giamarellou H. Should procalcitonin be introduced in the diagnostic criteria for the systemic inflammatory response syndrome and sepsis? J Crit Care. 2004;19:152–157. doi: 10.1016/j.jcrc.2004.07.001.
    1. Fritz HG, Brandes H, Bredle DL, Bitterlich A, Vollandt R, Specht M, Franke UF, Wahlers T, Meier-Hellmann A. Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery. Acta Anaesthesiol Scand. 2003;47:1276–1283. doi: 10.1046/j.1399-6576.2003.00239.x.
    1. Adamik B, Kubler-Kielb J, Golebiowska B, Gamian A, Kubler A. 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. 2000;26:1259–1267. doi: 10.1007/s001340000610.
    1. Hammer S, Meisnera F, Beiras F, Meiser B, Fraunberger P, Hammer C. Procalcitonin: a new marker for the diagnosis of organ rejection and bacterial infections in patients receiving heart and lung transplants. Transplantes. 1999;5:26–32.
    1. Cooper D, Sharples L, Cornelissen J, Wallwork J, Alexander G, Trull A. Comparison between procalcitonin, serum amyloid A, and C-reactive protein as markers of serious bacterial and fungal infections after solid organ transplantation. Transplant Proc. 2001;33:1808–1810. doi: 10.1016/S0041-1345(00)02690-7.
    1. Staehler MH, Mer C, Meiser B, Reichart B. Procalcitonin: a new marker of differential diagnosis of acute rejection and bacterial infection in heart transplantation. Transplant Proc. 1997;29:584–585. doi: 10.1016/S0041-1345(96)00314-4.
    1. Boeken U, Feindt P, Schulte HD, Gams E. Elastase release following myocardial ischemia during extracorporeal circulation (ECC). Marker of ongoing systemic inflammation? Thorac Cardiovasc Surg. 2002;50:136–140. doi: 10.1055/s-2002-32404.
    1. Kerbaul F, Giorgi R, Oddoze C, Collart F, Guidon C, Lejeune PJ, Villacorta J, Gouin F. High concentrations of N-BNP are related to non-infectious severe SIRS associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery. Br J Anaesth. 2004;93:639–644. doi: 10.1093/bja/aeh246.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅