Skip to main content
Top
Published in: Critical Care 3/2013

Open Access 01-06-2013 | Research

Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients

Authors: Philipp Schuetz, Paula Maurer, Vikas Punjabi, Ami Desai, Devendra N Amin, Eric Gluck

Published in: Critical Care | Issue 3/2013

Login to get access

Abstract

Introduction

Close monitoring and repeated risk assessment of sepsis patients in the intensive care unit (ICU) is important for decisions regarding care intensification or early discharge to the ward. We studied whether considering plasma kinetics of procalcitonin, a biomarker of systemic bacterial infection, over the first 72 critical care hours improved mortality prognostication of septic patients from two US settings.

Methods

This retrospective analysis included consecutively treated eligible adults with a diagnosis of sepsis from critical care units in two independent institutions in Clearwater, FL and Chicago, IL. Cohorts were used for derivation or validation to study the association between procalcitonin change over the first 72 critical care hours and mortality.

Results

ICU/in-hospital mortality rates were 29.2%/31.8% in the derivation cohort (n = 154) and 17.6%/29.4% in the validation cohort (n = 102). In logistic regression analysis of both cohorts, procalcitonin change was strongly associated with ICU and in-hospital mortality independent of clinical risk scores (Acute Physiology, Age and Chronic Health Evaluation IV or Simplified Acute Physiology Score II), with area under the curve (AUC) from 0.67 to 0.71. When procalcitonin decreased by at least 80%, the negative predictive value for ICU/in-hospital mortality was 90%/90% in the derivation cohort, and 91%/79% in the validation cohort. When procalcitonin showed no decrease or increased, the respective positive predictive values were 48%/48% and 36%/52%.

Discussion

In septic patients, procalcitonin kinetics over the first 72 critical care hours provide prognostic information beyond that available from clinical risk scores. If these observations are confirmed, procalcitonin monitoring may assist physician decision-making regarding care intensification or early transfer from the ICU to the floor.
Literature
1.
go back to reference Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Kumar A, Simon D, Peters C, Ahsan M, Chateau D, Cooperative Antimicrobial Therapy of Septic Shock Database Research Group: Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009, 136: 1237-1248. 10.1378/chest.09-0087PubMed Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Kumar A, Simon D, Peters C, Ahsan M, Chateau D, Cooperative Antimicrobial Therapy of Septic Shock Database Research Group: Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009, 136: 1237-1248. 10.1378/chest.09-0087PubMed
2.
go back to reference Ouanes I, Schwebel C, Francais A, Bruel C, Philippart F, Vesin A, Soufir L, Adrie C, Garrouste-Orgeas M, Timsit JF, Misset B, Outcomerea Study Group: A model to predict short-term death or readmission after intensive care unit discharge. J Crit Care 2012, 27: 422 e421-429.CrossRef Ouanes I, Schwebel C, Francais A, Bruel C, Philippart F, Vesin A, Soufir L, Adrie C, Garrouste-Orgeas M, Timsit JF, Misset B, Outcomerea Study Group: A model to predict short-term death or readmission after intensive care unit discharge. J Crit Care 2012, 27: 422 e421-429.CrossRef
3.
go back to reference Muller B, Becker KL, Schachinger H, Rickenbacher PR, Huber PR, Zimmerli W, Ritz R: Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000, 28: 977-983. 10.1097/00003246-200004000-00011CrossRefPubMed Muller B, Becker KL, Schachinger H, Rickenbacher PR, Huber PR, Zimmerli W, Ritz R: Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000, 28: 977-983. 10.1097/00003246-200004000-00011CrossRefPubMed
4.
go back to reference Linscheid P, Seboek D, Schaer DJ, Zulewski H, Keller U, Muller B: Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med 2004, 32: 1715-1721. 10.1097/01.CCM.0000134404.63292.71CrossRefPubMed Linscheid P, Seboek D, Schaer DJ, Zulewski H, Keller U, Muller B: Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med 2004, 32: 1715-1721. 10.1097/01.CCM.0000134404.63292.71CrossRefPubMed
5.
go back to reference Theodorou VP, Papaioannou VE, Tripsianis GA, Panopoulou MK, Christophoridis EK, Kouliatsis GA, Gioka TM, Maltezos ES, Ktenidou-Kartali SI, Pneumatikos IA: Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study. BMC Infect Dis 2012, 12: 247. 10.1186/1471-2334-12-247PubMedCentralCrossRefPubMed Theodorou VP, Papaioannou VE, Tripsianis GA, Panopoulou MK, Christophoridis EK, Kouliatsis GA, Gioka TM, Maltezos ES, Ktenidou-Kartali SI, Pneumatikos IA: Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study. BMC Infect Dis 2012, 12: 247. 10.1186/1471-2334-12-247PubMedCentralCrossRefPubMed
6.
go back to reference Coelho LM, Salluh JI, Soares M, Bozza FA, Verdeal JC, Castro-Faria-Neto HC, Lapa e Silva JR, Bozza PT, Povoa P: Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study. Crit Care 2012, 16: R53. 10.1186/cc11291PubMedCentralCrossRefPubMed Coelho LM, Salluh JI, Soares M, Bozza FA, Verdeal JC, Castro-Faria-Neto HC, Lapa e Silva JR, Bozza PT, Povoa P: Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study. Crit Care 2012, 16: R53. 10.1186/cc11291PubMedCentralCrossRefPubMed
7.
go back to reference Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, von Spiegel T: Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg 2009, 394: 221-226. 10.1007/s00423-008-0432-1CrossRefPubMed Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, von Spiegel T: Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg 2009, 394: 221-226. 10.1007/s00423-008-0432-1CrossRefPubMed
8.
go back to reference Hochreiter M, Kohler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, Schroeder S: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009, 13: R83. 10.1186/cc7903PubMedCentralCrossRefPubMed Hochreiter M, Kohler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, Schroeder S: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009, 13: R83. 10.1186/cc7903PubMedCentralCrossRefPubMed
9.
go back to reference Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177: 498-505. 10.1164/rccm.200708-1238OCCrossRefPubMed Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177: 498-505. 10.1164/rccm.200708-1238OCCrossRefPubMed
10.
go back to reference Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Regnier B, Brun-Buisson C, Chastre J, Wolff M, PRORATA trial group: Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010, 375: 463-474. 10.1016/S0140-6736(09)61879-1CrossRefPubMed Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Regnier B, Brun-Buisson C, Chastre J, Wolff M, PRORATA trial group: Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010, 375: 463-474. 10.1016/S0140-6736(09)61879-1CrossRefPubMed
11.
go back to reference Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Kristoffersen KB, Wei L, Burkhardt O, Welte T, Schroeder S, Nobre V, Tamm M, Bhatnagar N, Bucher HC, Mueller B: Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis 2012, 55: 651-662. 10.1093/cid/cis464PubMedCentralCrossRefPubMed Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Kristoffersen KB, Wei L, Burkhardt O, Welte T, Schroeder S, Nobre V, Tamm M, Bhatnagar N, Bucher HC, Mueller B: Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis 2012, 55: 651-662. 10.1093/cid/cis464PubMedCentralCrossRefPubMed
12.
go back to reference Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Soe-Jensen P, Lauritsen AO, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjaer J, Grarup J, Lundgren JD, Procalcitonin And Survival Study (PASS) Group: Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011, 39: 2048-2058. 10.1097/CCM.0b013e31821e8791CrossRefPubMed Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Soe-Jensen P, Lauritsen AO, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjaer J, Grarup J, Lundgren JD, Procalcitonin And Survival Study (PASS) Group: Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011, 39: 2048-2058. 10.1097/CCM.0b013e31821e8791CrossRefPubMed
13.
go back to reference Karlsson S, Heikkinen M, Pettila V, Alila S, Vaisanen S, Pulkki K, Kolho E, Ruokonen E, Finnsepsis Study Group: Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study. Crit Care 2010, 14: R205. 10.1186/cc9327PubMedCentralCrossRefPubMed Karlsson S, Heikkinen M, Pettila V, Alila S, Vaisanen S, Pulkki K, Kolho E, Ruokonen E, Finnsepsis Study Group: Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study. Crit Care 2010, 14: R205. 10.1186/cc9327PubMedCentralCrossRefPubMed
14.
go back to reference Schuetz P, Amin DN, Greenwald JL: Role of procalcitonin in managing adult patients with respiratory tract infections. Chest 2012, 141: 1063-1073. 10.1378/chest.11-2430CrossRefPubMed Schuetz P, Amin DN, Greenwald JL: Role of procalcitonin in managing adult patients with respiratory tract infections. Chest 2012, 141: 1063-1073. 10.1378/chest.11-2430CrossRefPubMed
15.
go back to reference 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 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
16.
go back to reference Schuetz P, Christ-Crain M, Huber AR, Muller B: Long-term stability of procalcitonin in frozen samples and comparison of Kryptor and VIDAS automated immunoassays. Clin Biochem 2010, 43: 341-344. 10.1016/j.clinbiochem.2009.08.029CrossRefPubMed Schuetz P, Christ-Crain M, Huber AR, Muller B: Long-term stability of procalcitonin in frozen samples and comparison of Kryptor and VIDAS automated immunoassays. Clin Biochem 2010, 43: 341-344. 10.1016/j.clinbiochem.2009.08.029CrossRefPubMed
17.
go back to reference Cook NR: Statistical evaluation of prognostic versus diagnostic models: beyond the ROC curve. Clin Chem 2008, 54: 17-23.CrossRefPubMed Cook NR: Statistical evaluation of prognostic versus diagnostic models: beyond the ROC curve. Clin Chem 2008, 54: 17-23.CrossRefPubMed
18.
go back to reference Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign Management Guidelines C: 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 Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign Management Guidelines C: 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
19.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee, American Association of Critical-Care Nurses, American College of Chest Physicians, American College of Emergency Physicians, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases, European Society of Intensive Care Medicine, European Respiratory Society, International Sepsis Forum, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine, Society of Hospital Medicine, Surgical Infection Society, World Federation of Societies of Intensive and Critical Care Medicine: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41CrossRefPubMed Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee, American Association of Critical-Care Nurses, American College of Chest Physicians, American College of Emergency Physicians, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases, European Society of Intensive Care Medicine, European Respiratory Society, International Sepsis Forum, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine, Society of Hospital Medicine, Surgical Infection Society, World Federation of Societies of Intensive and Critical Care Medicine: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41CrossRefPubMed
20.
go back to reference Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Morgenthaler NG, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B, ProHOSP Study Group: Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care 2010, 14: R106. 10.1186/cc9055PubMedCentralCrossRefPubMed Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Morgenthaler NG, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B, ProHOSP Study Group: Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care 2010, 14: R106. 10.1186/cc9055PubMedCentralCrossRefPubMed
21.
go back to reference Schuetz P, Chiappa V, Briel M, Greenwald JL: Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med 2011, 171: 1322-1331. 10.1001/archinternmed.2011.318CrossRefPubMed Schuetz P, Chiappa V, Briel M, Greenwald JL: Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med 2011, 171: 1322-1331. 10.1001/archinternmed.2011.318CrossRefPubMed
22.
go back to reference Schuetz P, Briel M, Mueller B: Clinical outcomes associated with procalcitonin algorithms to guide antibiotic therapy in respiratory tract infections. JAMA 2013, 309: 717-718. 10.1001/jama.2013.697CrossRefPubMed Schuetz P, Briel M, Mueller B: Clinical outcomes associated with procalcitonin algorithms to guide antibiotic therapy in respiratory tract infections. JAMA 2013, 309: 717-718. 10.1001/jama.2013.697CrossRefPubMed
23.
go back to reference Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bhatnagar N, Bucher HC, Briel M: Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012, 9: CD007498.PubMed Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bhatnagar N, Bucher HC, Briel M: Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012, 9: CD007498.PubMed
24.
go back to reference Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M: Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006, 34: 2596-2602. 10.1097/01.CCM.0000239116.01855.61CrossRefPubMed Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M: Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006, 34: 2596-2602. 10.1097/01.CCM.0000239116.01855.61CrossRefPubMed
25.
go back to reference Johansen ME, Jensen JU, Lundgren JD: Antibiotics in intensive care: too little or too much? Crit Care Med 2011, 39: 1849-1851. 10.1097/CCM.0b013e318215c0e2CrossRefPubMed Johansen ME, Jensen JU, Lundgren JD: Antibiotics in intensive care: too little or too much? Crit Care Med 2011, 39: 1849-1851. 10.1097/CCM.0b013e318215c0e2CrossRefPubMed
26.
go back to reference Schuetz P, Mueller B: To escalate or to de-escalte--that is the question. Crit Care Med 2011, 39: 2590. author reply 2591 10.1097/CCM.0b013e31822a5ddfCrossRefPubMed Schuetz P, Mueller B: To escalate or to de-escalte--that is the question. Crit Care Med 2011, 39: 2590. author reply 2591 10.1097/CCM.0b013e31822a5ddfCrossRefPubMed
Metadata
Title
Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients
Authors
Philipp Schuetz
Paula Maurer
Vikas Punjabi
Ami Desai
Devendra N Amin
Eric Gluck
Publication date
01-06-2013
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2013
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc12787

Other articles of this Issue 3/2013

Critical Care 3/2013 Go to the issue