Diagnostic Efficacy and Prognostic Value of Serum Procalcitonin Concentration in Patients With...

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http://jic.sagepub.com/ Journal of Intensive Care Medicine http://jic.sagepub.com/content/24/1/63 The online version of this article can be found at: DOI: 10.1177/0885066608327095 2009 24: 63 originally published online 2 December 2008 J Intensive Care Med Daha and I. Arribas M.J. Ruiz-Alvarez, S. García-Valdecasas, R. De Pablo, M. Sanchez García, C. Coca, T.W. Groeneveld, A. Roos, M.R. Suspected Sepsis Diagnostic Efficacy and Prognostic Value of Serum Procalcitonin Concentration in Patients With Published by: http://www.sagepublications.com can be found at: Journal of Intensive Care Medicine Additional services and information for http://jic.sagepub.com/cgi/alerts Email Alerts: http://jic.sagepub.com/subscriptions Subscriptions: http://www.sagepub.com/journalsReprints.nav Reprints: http://www.sagepub.com/journalsPermissions.nav Permissions: http://jic.sagepub.com/content/24/1/63.refs.html Citations: What is This? - Dec 2, 2008 OnlineFirst Version of Record - Jan 14, 2009 Version of Record >> at BROWN UNIVERSITY on June 15, 2012 jic.sagepub.com Downloaded from

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Page 1: Diagnostic Efficacy and Prognostic Value of Serum Procalcitonin Concentration in Patients With Suspected Sepsis

http://jic.sagepub.com/Journal of Intensive Care Medicine

http://jic.sagepub.com/content/24/1/63The online version of this article can be found at:

 DOI: 10.1177/0885066608327095

2009 24: 63 originally published online 2 December 2008J Intensive Care MedDaha and I. Arribas

M.J. Ruiz-Alvarez, S. García-Valdecasas, R. De Pablo, M. Sanchez García, C. Coca, T.W. Groeneveld, A. Roos, M.R.Suspected Sepsis

Diagnostic Efficacy and Prognostic Value of Serum Procalcitonin Concentration in Patients With  

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Diagnostic Efficacy and PrognosticValue of Serum ProcalcitoninConcentration in Patients WithSuspected Sepsis

Ruiz-Alvarez M. J., PhD, Garcıa-Valdecasas S., PhD, De Pablo R., MD, PhD,Sanchez Garcıa M., MD, PhD, Coca C., MD, PhD, Groeneveld T. W., PhD,Roos A., PhD, Daha M. R., PhD, and Arribas I., MD, PhD

Background: Procalcitonin is released in response tobacterial infection and it is not released in Inflamma-tory and viral diseases.Objective: To show the diagnostic efficacy and prognos-tic value of procalcitonin for sepsis.Methods: A consecutive series of 103 patients withsuspected sepsis were admitted to the intensive careunit over a 2-year period. During the first 24 hours ofthe admission procalcitonin, C-reactive protein, andcomplement proteins were determined. The diagnosticefficacy was tested with predictive values, likelihoodratios, receiver operating characteristic curves, andmultiple logistic regression. The association of procal-citonin with mortality was assessed by the MultivariateCox proportional hazards model.Results: Procalcitonin had a better positive likelihoodratio than C-reactive protein –2.2 (95% confidenceinterval: 1.3-3.7) versus 1.1 (95% confidence interval:0.9-1.2). Sequential Organ Failure Assessment yieldedthe highest discriminative value, with an area under thecurve of 0.82 (95% confidence interval: 0.73-0.92),

followed by procalcitonin (0.81; 95% confidenceinterval: 0.72-0.89). Multivariate regression analysisshowed procalcitonin (adjusted odds ratio: 3.8;95% confidence interval: 1.2-11.8) and SequentialOrgan Failure Assessment score (adjusted odds ratio:5.3; 95% confidence interval: 1.4-19.9) as the onlyvariables independently associated with infection.Multivariate Cox regression analysis revealed thatprocalcitonin was not independently associated withmortality.Conclusions: The diagnostic accuracy of procalcitoninwas higher than C-reactive protein and complementproteins. Procalcitonin in combination with Sequen-tial Organ Failure Assessment was useful to diagnoseinfection. C-reactive protein, Sequential Organ FailureAssessment score, age, and gender showed to be helpfulto improve the prediction of mortality risk, but notprocalcitonin.

Keywords: procalcitonin; C-reactive protein; com-plement system; diagnosis sepsis; mortality; prognosis

Introduction

Sepsis is defined as a host response to infection andcan be difficult to distinguish from other noninfec-tious conditions in critically ill patients who areadmitted with clinical signs of systemic inflamma-tory response syndrome (SIRS).1

Early diagnosis and appropriate treatment ofsepsis are very important to reduce mortality.2,3

Accurate markers of the infectious disease are

From the Laboratorio de Analisis Clınicos (R-AMJ, G-VS, CC, AI)and Unidad de Cuidados Intensivos (DPR, SGM), HospitalUniversitario Prıncipe de Asturias, Alcala de Henares, Madrid,Spain; Department of Nephrology, Leiden University MedicalCenter, Leiden, The Netherlands (GTW, RA, DMR).

Address correspondence to: Ruiz-Alvarez, Marıa Jesus, Tv. DelCalvario 1, 2�B. CP 19200. Azuqueca de Henares. Guadalajara,Spain; e-mail: [email protected].

63

Journal of Intensive

Care Medicine

Volume 24 Number 1

January/February 2009 63-71

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needed to distinguish patients with sepsis from thosewith SIRS.4

Sepsis is characterized by an increase of whiteblood cells and humoral and cellular proinflamma-tory mediators5 such as C-reactive protein (CRP)and procalcitonin (PCT).6 These mediators can beused as markers of infection or its severity.7 Procal-citonin has been proposed as a potential specificmarker of infection,8,9 and it correlates with theseverity of infection.10-14 However, several investiga-tors have questioned the diagnostic accuracy of PCT,finding inconsistent and contradictory resultsdepending on the severity of the infection in thestudied population.15-17 The prognostic value ofPCT in patients with sepsis and septic shock is stillincompletely clarified.18-20

The host response to bacterial infection involvesthe activation of immune mechanisms as the com-plement through distinct pathways, as the classicaland alternative. The lectin pathway is initiatedby mannose-binding lectin (MBL) and ficolins.21

Clinical reports of small case series documentincreases in MBL levels during surgery and infec-tion.22-26 However, the relationship between serumlevels of MBL and the diagnosis of sepsis is poorlydocumented.27

The aim of this study is to evaluate the diagnosticand prognostic value of PCT as a marker of infectionin patients with clinically suspected sepsis admittedto the intensive care unit (ICU) and to compare itwith markers such as CRP and complement systemproteins.

Material and Methods

Design and Patients

A prospective observational study was carried out inthe ICU of our University Hospital. The study wasapproved by the local ethics committee. Informedconsent was obtained from all patients before enrol-ment in the study. In 93 cases, the consent wasobtained from next of kin.

Patients were considered to have suspected sep-sis/SIRS if 2 or more of the following conditionswere present: temperature >38�C or <36�C, a heartrate >90 beats/min, a respiratory rate >20 breaths/min or PaCO2 <32 mm Hg (4.26 kPa), a white bloodcell count >12 000 cells/mL or <4000 cells/mL, or>10% immature (band) forms.

Patients with chronic organ failure, or preg-nancy, who had received blood transfusion beforethe stay in ICU or those whose duration of stay wasunder 24 hours were excluded.

Clinical and Laboratory Measurements

The clinical data collected included the following:body temperature, heart and respiratory rates, bloodpressure, blood gases, lactate plasma concentrations,routine blood count, biochemistry and coagulationtests, the administration of vasopressor agents, andthe Acute Physiology and Chronic Health Evaluation(APACHE-II) and Sequential Organ Failure Assess-ment (SOFA) scores. Acute Physiology and ChronicHealth Evaluation II and SOFA scores were per-formed for each patient on the basis of the first24 hours in ICU.

Blood samples were collected within the first24 hours of admission, centrifuged at 3000g for8 minutes, and sera were stored at �30�C. Resultswere not made available to the attending clinicians.Blood cultures were performed on the admissionday and thereafter when a patient’s temperaturewas >38�C.

Procalcitonin was measured by Kryptor auto-mated immunofluorescent assay (Brahms Diagnos-tica, Germany). C-reactive protein was measured byimmunoturbidimetry (Olympus AU5420, Germany).Cutoff values for PCT and CRP were 0.5 ng/mL and10 mg/L, respectively, according to the manufactur-er’s protocol, and the coefficients of variation were3% and 2%, respectively.

The concentration of MBL was assessed byenzyme-linked immunosorbent assay (ELISA).28 Insummary, 96-well plates were coated with mAb3E7 (kind gift of Professor T. Fujita, Fukushima,Japan). Serum samples were diluted and incu-bated, followed by detection with digoxygenin(dig)-conjugated 3E7 and horseradish peroxi-dase–conjugated sheep Fab anti-dig antibodies(Roche Applied Science), respectively. Enzymeactivity was developed using ABTS 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid). C2 con-centrations were determined by ELISA usingthe same procedure and the rabbit anti-C2 wasprepared in our laboratory by immunization of arabbit with purified human C2. Cutoff values were400 ng/mL and 140 mg/mL, respectively. C3 andC4 were measured by radial immunodiffusion.

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Gold Standard and Definitions

The primary outcome was the infection status of thepatients. The American College of Chest Physicians/Society of Critical Care Medicine Consensus Con-ference (ACCP/SCCM) was used to identify patientsin one of the following categories: SIRS, sepsis,severe sepsis, and septic shock.29

Systemic inflammatory response syndrome wasconsidered if patients had 2 or more of the followingconditions: temperature >38�C or <36�C, heart rate>90 beats/min, respiratory rate >20 breaths/min orPaCO2 <32 mm Hg (4.3 kPa), white blood cell count>12 000 or <4000 cells/mL, or >10% band forms.Sepsis was defined as a systemic response includingthe criteria for SIRS plus microbiological evidenceof a focal infection and/or a positive blood culture.Severe sepsis, as the presence of sepsis and one of thefollowing manifestations: (a) hypoxemia (PaO2 < 10kPa [<75 mm Hg]); (b) metabolic acidosis (pH< 7.30); (c) oliguria (<30 mL/h); (d) lactic acidosis(plasma lactate > 2 mmol/L); or (e) acute alterationin mental status without sedation. Septic shock, asthe presence of sepsis accompanied by a sustaineddecrease in systolic blood pressure (<90 mm Hg)despite fluid resuscitation and the need for vasoac-tive amines to maintain adequate blood pressure.

Infection was confirmed by the presence ofmicrobiological documentation or radiological evi-dence (pneumonia cases) of the foci within 7 daysafter admission in ICU.

Statistical Analysis

Values were expressed as the mean + SD or as themedian and interquartile range in case of a nonnor-mal distribution. Statistical differences betweengroups were assessed by 1-way ANOVA followed byScheffe test for normal, and Kruskal-Wallis followedby Mann-Whitney U test and Bonferroni adjustmentfor nonnormally distributed variables. All tests wereperformed 2-tailed and considered significant atP < .05.

The diagnostic accuracy was evaluated with sen-sitivity, specificity, positive and negative predictivevalues (PPV, NPV), and positive and negative likeli-hood ratios (PLR, NLR) of each parameter. Thereceiver operating characteristic (ROC) curves andthe respective areas under the curves (AUCs) werealso calculated. Results are expressed with the 95%confidence intervals (95% CI).

We analyzed the associations between differentparameters and the presence of infection, aftertransforming the values of each marker into valuesover and under the median, and performing univari-ate analyses. The presence of confounders and inter-action was analyzed in a stratified analysis. Finally,a multiple logistic regression model was built toidentify variables independently associated with theoutcome. Odds ratio (OR) was calculated with the95% CI. The Hosmer-Lemeshow test was used tocheck the goodness of fit of the model.

To determine the prognostic value of the markers,we analyzed the patients’ survival from the admissionto ICU discharge. Kaplan-Meier survival analysisand the Breslow test were performed to asses the sig-nificance of the differences between groups. A multi-variate Cox proportional hazards model was built toidentify variables independently associated with mor-tality. Hazard’s ratio (HR) was calculated with the95% CI. Statistical calculations were performed withSPSS software (version 11.0; SPSS Inc, Chicago, Ill).

Results

A consecutive series of 103 patients (aged 17-84years, median 67; 75 men and 28 women; 22 surgicalpatients and 81 medical patients) with suspectedsepsis and staying for over 24 hours in the ICU werefinally included and classified into 4 diagnostic cate-gories according to the ACCP/SCCM between May2004 and January 2006. Characteristics of thepatients are presented in Table 1.

Two patients died 6 and 8 hours after admissionand were excluded. The reasons were multiorgan fail-ure and shock, respectively. The main diagnoses werepneumonia and abdominal sepsis. In the study, 22surgical and 81 medical patients were included.

The case ascertainment was done retrospectivelyby 2 independent investigators and concordance wasexcellent (� agreement ¼ 0.79, 95% CI, 0.71-0.88).Disagreement was settled by consensus involving athird physician.

Diagnostic Value of PCT

Serum PCT concentrations in the patients with sep-sis were significantly higher than in the noninfectedgroup (P < .001) and were able to differentiate thepatients with different degrees of infection (Table 1).

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Similar results were found for scores APACHE-IIand SOFA. C-reactive protein levels were not signif-icantly different among the groups. Neither the CRPconcentrations nor the concentrations of the com-plement proteins showed significant differencesbetween patients with sepsis and SIRS.

Table 2 summarizes the accuracy of the labora-tory variables for the specific diagnosis of infection.C-reactive protein was more sensitive than the othermarkers but showed lower specificity. The PPV wasbetter for PCT when compared with the other mar-kers. According to NPV, PCT and CRP showed sim-ilar results. The AUC for infection identification wasthe highest for PCT, followed by CRP and MBL, C2and C3, and C4 (data not shown). The best cutoff

value in the diagnosis of sepsis determined from theROC curves was 0.32 ng/mL for PCT and 96.5 mg/Lfor CRP. Procalcitonin had a higher PLR, and lowerNLR, than did CRP and complement proteins. TheNLR was better for CRP than that for PCT, but thisdifference was not statistically significant.

Table 3A shows that infection was significantlyand directly related to PCT, CRP, APACHE-II andSOFA scores, and age. Interaction effect was dis-carded and only PCT and SOFA score remained sig-nificant and both were independently associatedwith the diagnosis of infection in the multivariatelogistic regression model (Table 3B). The Hosmer-Lemeshow test was not significant (P ¼ .98) in vali-dating the multivariate model.

Table 2. Parameters of Diagnostic Validitya

Parameter PCT CRP MBL C2

Sensitivity 83 (73.1-90.6) 98 (92.1-99.9) 63 (51.5-74.2) 8 (3.3-17.2)Specificity 62 (40.7-80.4) 11 (3.0-31.2) 50 (27.8-72.2) 90 (66.9-98.2)NPV 54 (34.2-71.9) 75 (21.9-98.6) 27 (14.4-44.4) 21 (13-31)PPV 88 (77.9-94.0) 77 (67.6-84.7) 82 (69.6-90.8) 75 (35.6-95.5)NLR 0.3 (0.1-0.4) 0.1 (0.01-1.0) 0.7 (0.43-1.24) 1.0 (0.9-1.2)PLR 2.2 (1.3-3.7) 1.1 (0.9-1.2) 1.27 (0.8-2.03) 0.8 (0.2-3.7)AUC 0.8 (0.7-0.9) 0.7 (0.5-0.8) 0.6 (0.4-0.7) 0.5 (0.3-0.6)

NOTES: AUC ¼ area under the receiver operating characteristic curve; CRP ¼ C-reactive protein; MBL ¼ mannose-binding lectin;NPV ¼ negative predictive value; NLR ¼ negative likelihood ratio; PCT ¼ procalcitonin; PLR ¼ positive likelihood ratio;PPV ¼ positive predictive value.a n ¼ 103 Patients; 95% confidence interval in parentheses; cutoff recommended by the manufacturer.

Table 1. Baseline Demographics of Study Population

InfectedNoninfected,

SIRS (I),n ¼ 25

Sepsis (II),n ¼ 20

Severe Sepsis(III), n ¼ 11

Septic Shock(IV), n ¼ 47 P Post hoc

Age (years)a 49 (17-77) 61 (28-77) 77 (26-83) 70 (29-84) .002 (I-IV), (I-III), (II-III)Gender, n (%)

Male 19 (25) 17 (23) 6 (8) 33 (44) .307 NSFemale 6 (21) 3 (11) 5 (18) 14 (50)

Days in ICUa 6 (2-45) 8 (1-72) 13 (6-34) 13 (1-120) .08 NSPCTa 0.3 (0.1-14.7) 1.1 (0.1-183.9) 1.9 (0.03-68.29) 9.1 (0.1-358.5) <.001 (I-IV), (I-III), (II-IV)CRPb 158 + 121 193 + 109 221 + 111 220 + 132 .2 NSAPACHE-IIb 14 + 6 15 + 4 16 + 7 21 + 6 <.001 (I-IV), (II-IV), (I-III)SOFAb 4 + 2 5 + 2 8 + 5 8 + 2 <.001 (I-IV), (II-IV)Outcomea

Nonsurvival 2 (6) 3 (9) 4 (12.9) 22 (71) <.003 (I-III), (I-IV), (II-IV)Survival 23 (32) 17 (23) 7 (9.7) 25 (35)

NOTES: APACHE-II ¼ Acute Physiology and Chronic Health II; CRP ¼ C-reactive protein; ICU ¼ intensive care unit;NS ¼ nonsignificant; PCT ¼ procalcitonin; SIRS ¼ systemic inflammatory response syndrome; SOFA ¼ Sequential Organ FailureAssessment.a Kruskal-Wallis test: results are shown as median and interquartile range.b ANOVA test: results are presented as means + SD.

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Prognostic Value of PCT

Procalcitonin levels showed no difference betweensurvivors and nonsurvivors (P¼ .23; Figure 1). How-ever, the patients who presented CRP levels higherthan the median had longer survival periods thanthose with lower concentration (P ¼ .02). Similarresults were observed for C2 (P < .001) and age(P ¼ .01). Furthermore, the patients with SOFAscore higher than the median had shorter survivalthan those with lower SOFA score (survival curvesnot shown). The median of stay in ICU was of 9 days.

Multivariate Cox regression analysis results areshown in Table 4. Procalcitonin was not related tomortality (P ¼ .48). C-reactive protein, SOFA score,age, and male sex were the variables associated, in anindependent way, with mortality.

Discussion

Our data show that PCT might be used as a markerof infection. Serum PCT concentrations in thepatients with sepsis were significantly higher than inthe noninfected group and were able to differentiatethe patients with different degrees of infection. Sim-ilar results were found for the scores APACHE-II

and SOFA. C-reactive protein was not significantlydifferent between the groups, neither were the com-plement proteins. Furthermore, the AUC for infec-tion identification was greater for PCT, followed byCRP and MBL. These data agree with the recentlyreported articles.30-32

Trying to apply these findings to clinical prac-tice, we calculated the likelihood ratios. By conven-tion, marked changes in prior disease probabilitycan be assumed in PLR exceeding 10.0 and NLRbelow 0.1.33 Procalcitonin had a higher PLR andlower NLR than did CRP and complement proteins.The likelihood ratios found for PCT, nevertheless,offer a modest contribution to the overall diagnosticvalue of sepsis. These results are in agreement withthose of Clec’h et al,34 who found positive and nega-tive ratios of 2.79 and 0.33, respectively, in medicalpatients with septic shock.

Our results also revealed that higher PCT plasmaconcentrations and SOFA score were associatedwith the presence of infection. These findings aresimilar to those reported by Harbarth et al,31 whopublished the only study that uses a logistic regres-sion analysis to assess the diagnostic value of PCTin patients with similar characteristics to that ofours, but with a lower sample size. Chan et al35 ina prospective study in patients admitted through theemergency department found the APACHE-II scoreand PCT level independently associated with thedevelopment of septic shock.

Some recently published prospective studies pre-sented doubtful conclusions about the relevance ofPCT determination in the assessment of sepsis andits superiority in comparison with CRP in sep-sis.7,14,31,36-38 In particular, Ugarte et al concludedthat PCT was not a better marker of infection thanCRP in critically ill patients, but a useful adjunctiveparameter to identify infection and a useful markerof the severity of infection. Suprin et al39 performeda study on 77 infected patients and 24 patientswith SIRS and reported that both markers had poorsensitivity and specificity for the diagnosis of infec-tion. C-reactive protein has been widely used as adiagnostic tool for infection,2,40 and some authorseven advocate using CRP as one of the criteria ofsepsis.41 In our study, all patients presented abnor-mally high CRP levels, in agreement with previousstudies.30 Hence, CRP is not useful for distinguish-ing both conditions.

The prognostic value of plasma PCT is stillcontroversial for predicting survival in adult with

Table 3. Association Between Different Markersand Diagnosis of Infection

(A) Univariate Analysis

Parameters OR 95% CI

PCT 5.30 1.79-15.63CRP 5.38 1.28-22.59MBL 1.63 0.59-4.43C2 0.97 0.36-2.61APACHE-II 4.31 1.46-12.69SOFA 7.18 1.98-26.02Age 3.07 1.17-8.10Gender 0.86 0.30-2.46

(B) Multivariate Logistic Regression Analysis

Parameters Coef. b P 95% CI

PCT 1.34 .02 1.24-11.82SOFA 1.67 .01 1.41-19.92

NOTES: APACHE-II ¼ Acute Physiology and Chronic Health II;CI ¼ confidence interval; Coef. ¼ coefficient; CRP ¼ C-reactiveprotein; MBL ¼ mannose-binding lectin; OR ¼ odds ratio;PCT ¼ procalcitonin; SOFA ¼ Sequential Organ FailureAssessment.

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suspected sepsis. Our results revealed that PCT wasnot related to mortality (HR ¼ 0.57, 95% CI: 0.14-2.25). The variables C-reactive protein, SOFA score,age, and male sex were the independent predictors ofmortality.

Claeys et al42 suggested that baseline valuesof PCT and CRP failed to predict outcome inpatients with septic shock because of a considerableoverlapped ranges in survivors and nonsurvivors.However, the monitoring of PCT levels predictsoutcome better than a single measurement. Acohort study including all critically ill patients wasconducted by Jensen et al,43 and they found that ahigh maximum PCT level and a PCT increase for1 day are the early independent predictors of mortal-ity in a 90-day follow-up period. Mortality riskincreases for every day that PCT increases. Never-theless, the initial PCT level did not predict mortalityin agreement with our results. C-reactive protein didnot predict mortality. Nonetheless, there are

available data indicating that PCT is correlated withthe patients’ prognosis.13,44 Clec’h et al34 found thatPCT was a reliable early prognostic marker in medi-cal patients with septic shock. A cutoff value of 6.0ng/mL had 76% sensitivity and 72.7% specificity forseparating patients who died in the ICU from thosewho were alive at ICU discharge. Remarkably, thepatients included in this study had sepsis diagnosedat the moment of inclusion, and this fact overesti-mated the prognostic value of PCT.

The host response to infection involves theactivation of complement, and some complementproteins could be used for diagnosis. Levels of theC2, C3, C4, and MBL in serum samples from allpatients were measured. We did not find the associ-ation between the complement system and infectionsuggesting that serum levels of complement couldnot serve as the markers of sepsis. Furthermore, thecomplement system did not correlate with thepatients’ prognosis.

PCT

0 20 40 60 80 100–0.2

0.0

0.2

0.4

0.6

0.8

1.0

CRP

Survival in days

Percent

survival

0 20 40 60 80 100–0.2

0.0

0.2

0.4

0.6

0.8

1.0

Survival in days

Percent

survival

Figure 1. Kaplan-Meier survival curves. Survival curves of PCT and CRP. Solid line: values over the median (1.64 ng/mL and 189mg/L, respectively), dash line: values under the median. CRP, C-reactive protein; PCT, procalcitonin.

Table 4. Multivariate Cox Proportional Hazards Model

Parameters Coef. b P HR 95% CI

CRP �2.00 .003 0.13 0.04-0.51SOFA 1.54 .03 4.68 1.14-19.30Age 1.26 .036 3.53 1.08-11.52Gender �1.50 .039 0.22 0.05-0.92

NOTES: CI ¼ confidence interval; Coef. ¼ coefficient; CRP ¼ C-reactive protein; HR ¼ hazards ratio; SOFA ¼ Sequential OrganFailure Assessment.

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There are few studies showing the role of CRP asa prognosis tool in infections. Mirete et al45

described that CRP can be useful in the predic-tion of pleural complications in patients withcommunity-acquired pneumonia, and Yentis andcolleagues46 demonstrated that a decrease in CRPby 25% or more from the previous day’s level corre-lated with resolution of sepsis. It is noteworthy theprotective effect found in our study for baselineCRP on mortality. Recent hypotheses to explain thepoor prognosis observed in septic shock are basedon an immunosuppressive response47 leading tosecondary infections and death. C-reactive proteinconcentrations under 184 mg/dL were associatedwith a particularly high mortality. Increasing or per-sistently high levels, suggesting ongoing inflamma-tory activity, indicated a better prognosis, whereasdecreasing values were associated with a poorerprognosis. Hence, trends in CRP concentrationsduring the first 24 hours of ICU admission can beimportant in helping to decide whether more inva-sive diagnostic procedures are needed or not andwhether therapeutic interventions should be main-tained or modified.

Our results of SOFA score were similar to thoseof Vincent and colleagues,48 who showed that multi-ple organ dysfunction and high SOFA scores wereassociated with increased mortality. However, otherstudies35,49 revealed that in patients with suspectedsepsis, only the APACHE-III score was indepen-dently associated with hospital mortality, whereasCRP concentrations and other blood markers andSOFA did not differ between hospital survivors andnonsurvivors.50

A limitation of the current study is that it wasperformed in a single PCT level on admission to theICU. Thus, due to the rapid kinetic of PCT, the mes-sage of the study should be taken with some reserva-tion because the correlation with the outcomes maybe suboptimal. In addition, the multivariate logisticregression model needs validation in a differentstudy group.

Conclusions

In summary, PCT appeared to be a more accuratediagnostic parameter than CRP and complementproteins for differentiating between patients suffer-ing from SIRS and those with sepsis. The combina-tion of PCT concentrations and SOFA score

allowed an excellent discrimination of patientsbelonging to the sepsis or the SIRS group, and CRP,SOFA score, age and gender, but not PCT, showedto be helpful to improve the prediction of mortalityrisk in patients with suspected sepsis.

Acknowledgments

This work was supported by Ministerio de Sanidad yConsumo, Instituto de Salud Carlos III, Fondo deInvestigacion Sanitaria—FIS-PI052201. R-AMJ wassupported by the Post-formacion sanitaria especiali-zada programof the Ministerio de Sanidad y Consumo.

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