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Year : 2014  |  Volume : 8  |  Issue : 3  |  Page : 296-301  

Amalgamation of procalcitonin, C-reactive protein, and sequential organ failure scoring system in predicting sepsis survival

1 Department of Critical Care Medicine, Shikh Khalifa Medical City, Abu Dahbi, United Arab Emirates
2 Department of Critical Care Medicine, Faculty of Medicine, Beni-Suef University, Egypt
3 Department of Critical Care Medicine,Cairo University, Egypt
4 Department of Microbiology, Shikh Khalifa Medical City, Abu Dahbi, United Arab Emirates

Date of Web Publication17-Oct-2014

Correspondence Address:
Amr Salah Omar
Department of Critical Care Medicine, Faculty of Medicine, Beni Suef-University, P.O. Box 62511, Beni-Suef
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.143115

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Background: The clinical value of inflammatory biomarkers is still questionable.
Aim of the Work: The aim of this study is to compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentration in the early detection of sepsis, as well as relating these biomarkers to other scoring systems.
Patients and Methods: A total of 138 patients were enrolled in our study. All were subjected to PCT, CRP, and sequential organ failure assessment (SOFA) scores daily for 7 days (starting from admission day). Blood samples were collected before starting antibiotics, with 28 days follow-up and patients were assigned to three groups: Group I: SOFA 2-7, Group II: SOFA 8-10, and Group III: SOFA ≥11.
Results: Underlying clinical diagnosis revealed pneumonia in 72 patients, urinary tract infections in eight, bloodstream infection in four, and other infections in 23, while infection could not be traced in 25 patients. The mean PCT was 3 ng/ml (95% confidence interval [CI]: 1-4), 12 ng/ml (95% CI: 9.1-14), and 19 ng/ml (95% CI: 16.3-22.3) in Groups I, II, and III, respectively, with a statistically significant difference in the mean PCT level among the three groups (P < 0.0001). On the other hand, CRP mean level did not significantly differentiate between the groups (147.1 mg/L in Group II, which was even higher than the level of Group III, 138.4 mg/L).
Conclusion: PCT seems to do better than CRP in predicting the SOFA groups, giving its patronage display over a wide spectrum of insults.

Keywords: Acute physiology and chronic health evaluation II score, C-reactive protein, procalcitonin, sepsis, sequential organ failure assessment

How to cite this article:
Hegazy M A, Omar AS, Samir N, Moharram A, Weber S, Radwan W A. Amalgamation of procalcitonin, C-reactive protein, and sequential organ failure scoring system in predicting sepsis survival. Anesth Essays Res 2014;8:296-301

How to cite this URL:
Hegazy M A, Omar AS, Samir N, Moharram A, Weber S, Radwan W A. Amalgamation of procalcitonin, C-reactive protein, and sequential organ failure scoring system in predicting sepsis survival. Anesth Essays Res [serial online] 2014 [cited 2022 May 19];8:296-301. Available from:

   Introduction Top

Fever could be a prime event that may hit critically ill patients. The sensitivity of C-reactive protein (CRP) as inflammatory marker irrespective of the cause is well-identified, with the query about the specificity. Procalcitonin (PCT) has been widely studied as a marker for bacterial infection. The utility of this marker in severe sepsis is now widely acknowledged. Limper et al. described it as a differentiating biomarker among infections from noninfectious fever. [1]

Two or more of the following conditions characterize systemic inflammatory response syndrome (SIRS): Temperature >38.5°C or <35.0°C, heart rate of >90 beats/min, respiratory rate of >20 breaths/min or PaCo 2 of <32 mm Hg, and white blood cell count of >12,000 cells/ml, <4000 cells/ml, or >10% immature (band) forms. [2] Sepsis and its sequelae are common causes of mortality in intensive care units (ICUs), and delayed diagnosis and treatment are associated with increased mortality. [3]

The clinical features of sepsis and noninfectious SIRS are very similar. The sensitivity and specificity of physiologic parameters such as criteria for SIRS is lacking. Microbiologic data are time consuming and may be nondiagnostic, as negative cultures do not exclude infection and the microbiologic diagnostic procedure requires at least 1-2 days for providing accurate quantitative results. Furthermore, viral infections are even more difficult to assess. [4]

Therefore, a rapidly obtainable marker that is capable of discriminating sepsis from noninfectious SIRS would be clinically useful. An ideal marker of infection would be highly specific, highly sensitive, and easy to measure, rapid, inexpensive, and correlated with the severity and prognosis of infection. In critically ill patients, confined information usually could be retrieved from a CRP measurement due to a relatively long clinical half-life, misleading assay in reinfection, and delayed response. [5] PCT plasma level increases in severe bacterial or fungal infections or sepsis and concentrations as high as 1000 ng/ml have been reported in sepsis and septic shock; however, localized bacterial infections, viral infections, and autoimmune and allergic disorders are not PCT inducers. [6]

Procalcitonin tend to be increased in bacterial sepsis, which seems to be related to the degree of microbial invasion, was first mentioned by Assicot et al. [7] The exact origin of PCT production is not known, but the liver seems to be the major location of production. A large amount of PCT had been produced after stimulation of human hepatocytes with tumor necrosis factor α and interleukin 6 (IL-6). [8] Under normal physiological conditions, the PCT serum level is extremely low, usually below 0.01 ng/ml, and in viral infection and inflammation concentrations is slightly increased, but rarely above 1 ng/ml. [9] However, levels up to 500 ng/ml or more have been described in bacterial infections. [10]

Critical care outcome predictors include clinical, diagnostic, and physiologic variables that are well-identified. The acute physiology and chronic health evaluation II (APACHE-II) scoring system is commonly used in intensive care populations for outcome prognostication, and comparison of medical care acuity in different ICUs, it was created for assessing disease severity in adult patients admitted to ICUs. [11],[12]

The relation between PCT concentrations and the severity of organ dysfunction indicated by a sepsis-related organ failure assessment (SOFA) score, [13] in patients with multiorgan dysfunction (MOD) secondary to systemic inflammation of infectious or noninfectious origin needs to be studied. We hypothesize that PCT is a better stigma for sepsis than CRP and may have a predictive rule in early or late sepsis-related mortality.

Aim of the work

The aim of the work is to compare the clinical informative value of PCT and CRP plasma concentration in the detection of infection/sepsis; to investigate the relation between both markers and the severity of organ dysfunction assessed by the SOFA score, and to study the mortality predictive power of PCT versus CRP.

   Patients and methods Top

During the period of the month between March 1, 2011 and March 31, 2012, after approval of the Ethical Committee, where informed consent was obtained from the patient or next of kin to be enrolled in the study, which was prospective with purposive sampling conducted over a period of 1 year, all consecutive adult patients aged ≥15 years admitted to the general ICU in tertiary health care institution in critical care medicine department with signs and symptoms of SIRS, sepsis, severe sepsis, or septic shock ( according to the American College of Chest Physicians/Society of Critical Care Medicine [ACCP/SCCM] definition), [14] were included in this prospective cohort study (138 patients total were included). The following patient categories were excluded: Age <15 years; chronic liver disease (Child-Pugh Class B or C); pancreatitis (serum lipase 3 times the upper limit); surgical patients (major thoracoabdominal surgery within 3 weeks); trauma patients; subjects with burns; and known immune suppressed state (corticosteroid causing immunosuppression, organ transplant recipient, leucopenia, or neutropenic and hematological malignancy).

Clinical and functional investigations

The APACHE-II score was used to determine the initial severity of illness. [12] PCT, CRP, and SOFA scores were determined daily for 7 days (from the time of admission). Blood samples were collected for analysis, depending on presenting symptoms, before starting antibiotics. All patients were followed-up for 28 days to be assigned to two groups: Survivors and nonsurvivors.

Blood sampling and biochemical assays

Electrochemiluminescence technology cobas e 411 analyzer for PCT was used, then it was measured by an immunoluminometric "LUMItest® PCT"- kit (B.R.A.H.M.S.-Diagnostica GmbH, Berlin, Germany) [15] and CRP by the Turbi-Quanti method (Behring, Marburg, Germany). [15] The test needs 2 ± 3 h and 20 ml of serum or plasma. Inter-assay and intra-assay variation at high and low concentrations is <8% and 7%, respectively. For PCT, the upper normal limit is 0.5 ng/ml. For CRP, the upper normal limit is 0.5 mg/dl. Retrospectively, after analysis of all diagnostic criteria, patients were categorized with the help of the criteria of the consensus conference of the ACCP/SCCM.

Statistical analysis

Statistical analysis was performed using SPSS statistical software (version 16.0, SPSS, Chicago, IL, USA). Taking into account that data were nonnormally distributed, a Mann-Whitney U-test was used to compare two independent samples. Patients were prospectively enrolled over the period of 1 year receiver operating characteristics curves (ROC) and the respective areas under the curve (AUC) were calculated. [16] ROC was used to compare daily PCT versus CRP in predicting the severity of the SOFA score. A P < 0.05 was considered as significant. We used the Chi-square test to find PCT and CRP cut-off values for the different SIRS groups. A Spearman correlation test was used to rank variables against each other positively or inversely.

   Results Top

A total of 138 patients were enrolled in our study (77 males and 61 females) with a mean age of 55.6 ± 19 years. The mean average APACHE-II score was 20.1, ranging from 2 to 45, while the mean SOFA score fluctuated between 7.9 and 6.8 by the 7 th day. The characteristic patient data at the time of enrollment are shown in [Table 1]. There was no significant difference for any of the variables between groups (P > 0.05, Mann-Whitney U-test) except for PCT, which was significantly higher on day 1 in nonsurvivors. By using the Spearman correlation test, a statistically significant positive correlation between CRP and SOFA scores occurred from days 4 to 7 [Table 2], while by using the same test, a statistically significant positive correlation between PCT and SOFA scores occurred from days 1 to 7 [Table 3]. When we correlated the PCT and CRP versus the APACHE-II score for day 1, we found a statistically significant positive correlation between the PCT and APACHE-II score by using the Spearman correlation test, but no significant correlation between CRP and APACHE-II [Table 4]. Serially, PCT is considered better when positive than when negative and more valid compared with CRP in days 1, 3, and 5 [Table 5] and [Table 6].{Table 1}{Table 2}{Table 3}{Table 4}{Table 5}{Table 6}

Patients were divided into three groups according to SOFA scores [Table 7] - Group I: SOFA 2-7, Group II: SOFA 8-10, and Group III: SOFA ≥11. There was a statistically significant difference in the mean CRP level between the three groups (P < 0.0001), with the mean CRP in Group I at 92.8 mg/L (95% confidence interval [CI]: 83.3-102.3 mg/L); the mean CRP in Group II at 147.1 mg/L (95% CI: 133-166.2 mg/L); and the mean CRP in Group III at 138.4 mg/L (95% CI: 123.9-153 mg/L). There was a statistically significant difference in the mean PCT level between the three groups (P < 0.0001) when the mean PCT in Group I was 3 ng/ml (95% CI: 1-4); the mean PCT in Group II was 12 ng/ml (95% CI: 9.1-14); and the mean PCT in Group III was 19 ng/ml (95% CI: 16.3-22.3). However, the mean value of the CRP level in Groups II and III was not significantly differentiated between the groups (the mean CRP level in Group II was 147.1 mg/L, which was even higher than the Group III level of 138.4 mg/L), where the mean PCT level in Group II was 12.0 ng/ml and in Group III was 19.3 ng/ml. This was proven again by ROC curves in which the AUC for the CRP for Group II was 0.64 and for Group III was 0.59, while the AUC for the PCT for Group II was 0.77 and for Group III was 0.75. PCT reflected better performance than CRP in predicting the SOFA groups.{Table 7}

   Discussion Top

Finding a mediator that symbolizes mortality prediction and progress of infection in septic patients seems to be an ideal goal. In our study, we found a significantly higher PCT in nonsurvivors [Table 1], which was not the case in CRP. Acute-phase proteins are clinically the most widely used biomarkers. High levels of the acute-phase proteins CRP and PCT at the onset of sepsis have been described to be associated with a dismal outcome. [17] However, substantial overlaps between survivors and nonsurvivors in the initial plasma levels of those inflammation markers have also been reported. [18] Tschaikowsky et al., [19] prospectively evaluated PCT, IL-6, and CRP as a percentage of baseline (POB) to predict survival at day 28 after sepsis onset. In survivors, PCT and IL-6 significantly decreased from days 1 to 14, whereas CRP did not. However, no single cut-off value of PCT, IL-6, or CRP POB allowed survival prediction; moreover, they added that it might be used to guide duration of therapy in critically ill patients.

In our study, we found statistically significant positive correlation between CRP and SOFA scores from days 4 to 7 by using a Spearman correlation test [Table 2]. In their study Ferreira et al., [20] they found a similar relationship and reported that an increase in CRP and SOFA scores during the first 48 h in the ICU predicts a mortality rate of at least 50%, while a decreasing SOFA score is associated with a decrease in mortality rates from 50% to 27%, respectively. On the other hand [Table 3], there was a statistically significant positive correlation between PCT and SOFA scores from days 1 to 7 when using a Spearman correlation test. The changes with PCT were earlier than CRP. Su et al., [21] designed an elegant study that enrolled 144 ICUs. They found similar early changes in serum PCT that correlate with SOFA scores, and they added that the sepsis group had higher serum soluble triggering receptor expressed on myeloid cells 1, PCT, and CRP levels compared with the SIRS group, concluding that PCT concentrations are associated with the severity of MODs as assessed by the SOFA score.

We studied the correlation between PCT and CRP versus the APACHE-II score at day 1 [Table 4]. Our results found a statistically significant positive correlation between PCT and APACHE-II scores by using a Spearman correlation test, and they failed to find a statistically significant correlation between CRP and APACHE-II score by using a Spearman correlation test. Our results are similar to a study done by Wilhelm et al., [22] who compared the prognostic value of APACHE-II and SOFA scores, and the biomarkers CRP, PCT, and IL-6 at the time of admission to stratify patients at risk for ICU treatment. They found that all scores and biomarkers showed significant AUC values of ROC curve analysis for death within 30 days: 0.801 for APACHE-II, 0.693 for CRP, and 0.651 for PCT. For treatment in an ICU and ventilatory support demand, significant AUC value parameters were found; however, only APACHE-II, SOFA, and PCT showed significant AUC values for renal replacement therapy.

The ROC curves comparing the kinetics of both PCT and CRP relative to inflammation severity (as assessed by SOFA score) showed that the AUC on day 1 was 0.77 versus 0.52 for PCT and CRP, respectively, while on day 5, the AUC was 0.71 versus only 0.58 for PCT and CRP, respectively [Table 5] and [Table 6]. At the end of the study period, the median CRP remained significantly high (56.6 mg/L) while the PCT median level was approaching the normal value (0.53 ng/ml). This could be explained by improvement of infection with continuation of the inflammatory process. This observation was already described by several authors and thus is not focused on in this study. A study carried out by Silvestre et al., measuring the CRP in all patients at ICU discharge found that CRP values varied from 0.15 to 43.5 mg/L. Moreover, they concluded that serum CRP concentration was a poor indicator of post-ICU prognosis at discharge. Post-ICU death appears to be unrelated to the persistent inflammatory response. [23]

Monneret et al., [24] found that PCT was increased within 6 h after the initial stimulus, and CRP did not significantly increase before 12 h after the onset of induction. Furthermore, under clinical conditions, a speedy increase of PCT compared with CPR was described after the onset of severe inflammation. Moreover, the decline of PCT concentrations occurred more rapidly than that of CRP.

With increasing categories of the SOFA score, denoting the severity of MODs, higher PCT concentrations were monitored, and our results show that PCT concentrations are associated with the severity of MODs as assessed by the SOFA score as shown in [Table 5], where both CRP and PCT plasma levels increase with an increased SOFA score. However, the PCT level correlated better than the CRP level in assessing the severity of SOFA as shown by AUC, and the CRP level was elevated irrespective of the scores observed. Moreover, it has been shown that PCT levels correlate with the severity of sepsis and organ failure [Table 5] and [Table 6]. Castelli et al., [25] hypothesized that PCT and CRP concentrations are different in patients with infection and no infection at a similar severity of organ dysfunction or systemic inflammatory response. Enrolling 138 adult ICU patients and observing them consecutively over a period of 10 days, then comparing PCT, CRP, and infectious parameters in the studied groups, Castelli et al., found that PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction, although the correlation with the SOFA score was weak and the CRP levels were already near their maximum at lower SOFA scores, whereas the highest PCT concentrations correlated with higher score levels. They concluded that PCT and CRP levels are related to the severity of organ dysfunction, with infection related to higher values. [25]

We divided our patients according to sepsis syndrome into three groups [Table 7]. PCT has several advantages in severely ill patients compared with CRP. The most striking one, demonstrated in this study, is the enormous range of PCT reactivity resulting in a marked increase in PCT plasma levels, especially during severe stages of MODs and systemic inflammation. On the other hand, PCT concentrations are too low when only a mild organ dysfunction is present. Our results agreed with Miro et al., (2011), who retrospectively studied the predictive value of PCT for survival in 64 adult patients with severe sepsis and septic shock treated in intensive care. [26] Highlighting the acuity of PCT blood levels can predict the severity of sepsis in peritonitis patients as measured by a SOFA score in the first 48 h after surgery.

   Conclusion Top

Procalcitonin seems to do better than CRP in predicting the SOFA groups, giving its patronage display over a wide spectrum of insults.

Study limitation

A limited number (138) of patients was included in our study, but it seems that it could be added to if we had different microbiological culture groups and if it were a single-center study.

   References Top

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Tschaikowsky K, Hedwig-Geissing M, Schmidt J, Braun GG. Lipopolysaccharide-binding protein for monitoring of postoperative sepsis: Complemental to C-reactive protein or redundant? PLoS One 2011;6:e23615.  Back to cited text no. 19
Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001;286:1754-8.  Back to cited text no. 20
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Monneret G, Labaune JM, Isaac C, Bienvenu F, Putet G, Bienvenu J. Procalcitonin and C-reactive protein levels in neonatal infections. Acta Paediatr 1997;86:209-12.  Back to cited text no. 24
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:R234-42.  Back to cited text no. 25
Miro M, del Valle García S, Agámez G, García Pimentel P, Martínez Hurtado E, Olivas E. Correlation between SOFA score and procalcitonin blood levels in peritonitis patients. Eur J Anaesthesiol 2011;28:173.  Back to cited text no. 26


  [Table 1]AnesthEssaysRes_2014_8_3_296_143115_t1.jpg, [Table 2]AnesthEssaysRes_2014_8_3_296_143115_t2.jpg, [Table 3]AnesthEssaysRes_2014_8_3_296_143115_t3.jpg, [Table 4]AnesthEssaysRes_2014_8_3_296_143115_t4.jpg, [Table 5]AnesthEssaysRes_2014_8_3_296_143115_t5.jpg, [Table 6]AnesthEssaysRes_2014_8_3_296_143115_t6.jpg, [Table 7]AnesthEssaysRes_2014_8_3_296_143115_t7.jpg

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