Top

Critical Care

Published in:

Open Access 01-10-2006 | Research

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

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

Published in: Critical Care | Issue 5/2006

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.

Available only for authorised users

Maruna P, Nedelnikova R, Gurlich R: Physiology and genetics of procalcitonin. Physiol Res 2000, 49: S57-S61.PubMed

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. 10.1016/0140-6736(93)90277-NCrossRefPubMed

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. 10.1210/jc.79.6.1605PubMed

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. 10.1097/00003246-200002000-00028CrossRefPubMed

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. 10.1016/S0022-2143(99)90053-7CrossRefPubMed

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. 10.1086/421997CrossRefPubMed

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. 10.1186/cc2877PubMedCentralCrossRefPubMed

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. 10.1097/01.CCM.0000063440.19188.EDCrossRefPubMed

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. 10.1007/s001340051134CrossRefPubMed

10.

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. 10.1097/01.CCM.0000226413.54364.36CrossRefPubMed

11.

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. 10.1016/S0929-693X(01)00793-XCrossRef

12.

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. 10.1016/S0140-6736(04)15591-8CrossRefPubMed

13.

Sandek A, Springer J, Habedank D, Brunkhorst FM, Anker SD: Procalcitonin-guided antibiotic treatment in heart failure. Lancet 2004, 363: 1555-1556. 10.1016/S0140-6736(04)16165-5CrossRefPubMed

14.

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. 10.1515/CCLM.1999.060CrossRefPubMed

15.

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. 10.1111/j.0265-0215.1998.00280.xCrossRefPubMed

16.

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. 10.1164/rccm.200406-746OCCrossRefPubMed

17.

Koszegi T: Immunoluminometric detection of human procalcitonin. J Biochem Biophys Methods 2002, 53: 157-164. 10.1016/S0165-022X(02)00104-5CrossRefPubMed

18.

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. 10.1515/CCLM.2000.147CrossRefPubMed

19.

Guerin S: [Evaluation of the detection of procalcitonin by an immuno-chromatography test: Brahms PCT-Q]. Ann Biol Clin (Paris) 2000, 58: 613-614.

20.

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. 10.1515/CCLM.2004.077CrossRefPubMed

21.

Lin E, Calvano SE, Lowry SF: Inflammatory cytokines and cell response in surgery. Surgery 2000, 127: 117-126. 10.1067/msy.2000.101584CrossRefPubMed

22.

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. 10.1007/s001340050644CrossRefPubMed

23.

Laffey JG, Boylan JF, Cheng DC: The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology 2002, 97: 215-252. 10.1097/00000542-200207000-00030CrossRefPubMed

24.

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. 10.1097/01.CCM.0000050454.01978.3BCrossRefPubMed

25.

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. 10.1097/01.CCM.0000117317.18092.E4CrossRefPubMed

26.

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.

27.

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. 10.1016/S0167-5273(03)00083-4CrossRefPubMed

28.

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. 10.1016/S1053-2498(00)00443-5CrossRefPubMed

29.

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.CrossRefPubMed

30.

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. 10.1007/s00134-006-0180-zCrossRefPubMed

31.

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. 10.1017/S1047951105002088CrossRefPubMed

32.

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. 10.1053/j.jvca.2004.01.021CrossRefPubMed

33.

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. 10.1191/0267659105pf800oaCrossRefPubMed

34.

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. 10.1016/j.ejcts.2005.07.007CrossRefPubMed

35.

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. 10.1515/CCLM.1999.048CrossRefPubMed

36.

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.CrossRefPubMed

37.

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. 10.1016/S0967-2109(00)00070-3CrossRefPubMed

38.

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.PubMed

39.

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. 10.1097/00003246-200009000-00008CrossRefPubMed

40.

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. 10.1007/s001340051143PubMed

41.

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. 10.1055/s-2001-17803CrossRefPubMed

42.

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. 10.1097/00003246-200102000-00019CrossRefPubMed

43.

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. 10.1034/j.1399-6576.2002.461010.xCrossRefPubMed

44.

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. 10.1053/jcan.2002.29672CrossRefPubMed

45.

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. 10.1007/s00134-002-1392-5CrossRefPubMed

46.

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. 10.1017/S1047951103000301CrossRefPubMed

47.

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. 10.1159/000072231CrossRefPubMed

48.

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. 10.2143/AC.59.6.2005245CrossRefPubMed

49.

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. 10.1055/s-2001-19011CrossRefPubMed

50.

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. 10.1016/S0003-4975(01)03391-4CrossRefPubMed

51.

Meisner M, Reinhart K: Is procalcitonin really a marker of sepsis? Int J Intensive Care 2001, 8: 15-25.

52.

Meisner M: Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2002, 323: 17-29. 10.1016/S0009-8981(02)00101-8CrossRefPubMed

53.

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. 10.1067/mtc.2003.323CrossRefPubMed

54.

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.CrossRefPubMed

55.

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.PubMed

56.

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. 10.1159/000067132CrossRefPubMed

57.

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. 10.1055/s-2003-45425CrossRefPubMed

58.

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. 10.1007/s001340051141CrossRefPubMed

59.

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.CrossRefPubMed

60.

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. 10.1007/s00134-002-1398-zCrossRefPubMed

61.

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. 10.1016/j.jcrc.2004.07.001CrossRefPubMed

62.

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. 10.1046/j.1399-6576.2003.00239.xCrossRefPubMed

63.

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. 10.1007/s001340000610CrossRefPubMed

64.

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.

65.

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. 10.1016/S0041-1345(00)02690-7CrossRefPubMed

66.

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. 10.1016/S0041-1345(96)00314-4CrossRefPubMed

67.

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. 10.1055/s-2002-32404CrossRefPubMed

68.

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. 10.1093/bja/aeh246CrossRefPubMed

Title: Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature
Authors: Christoph Sponholz
Yasser Sakr
Konrad Reinhart
Frank Brunkhorst
Publication date: 01-10-2006
Publisher: BioMed Central
Published in: Critical Care / Issue 5/2006
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc5067

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2006

Intravenous nitroglycerin does not preserve gastric microcirculation during gastric tube reconstruction: a randomized controlled trial

Risk factors for post-ICU red blood cell transfusion: a prospective study

Ethics roundtable debate: Patients and surrogates want 'everything done' – what does 'everything' mean?

Bench-to-bedside review: Potential strategies to protect or reverse mitochondrial dysfunction in sepsis-induced organ failure

Pro/con debate: Antifungal prophylaxis is important to prevent fungal infection in patients with acute necrotizing pancreatitis receiving broad-spectrum antibiotics

Accuracy and feasibility of point-of-care and continuous blood glucose analysis in critically ill ICU patients