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A COMPARATIVE STUDY OF SERUM PROCALCITONIN (PCT) AND

C-REACTIVE PROTEIN (CRP)


AT VARIED SEVERITY OF ORGAN DYSFUNCTION IN SEPSIS IN A
TERTIARY CARE HOSPITAL IN KARNATAKA, INDIA

1 2 3
Dr Sumanth B V , Dr Sandeep S , Dr. Shivakumar N S

1
Assistant Professor, Department of Medicine AIMS, Bellur, Karnataka, India
2
Senior Resident, Sakra World Hospital, Bangalore, Karnataka, India
3
Professor, Dept of Medicine M.S.Ramaiah Medical college, Bangalore, Karnataka ,India

ADDRESS FOR CORRESPONDENCE ( CORRESPONDING AUTHOR) :


DR SUMANTH B V
ASSISTANT PROFESSOR, DEPARTMENT OF MEDICINE
AIMS, BG NAGARA
NAGAMANGALA - 571448
PERMANENT ADDRESS
NO 3979, 20TH MAIN HAMPI CIRCLE, VIJAYANAGAR 2ND STAGE
MYSORE - 570017
email : drsumanth.bv@gmail.com

ABSTRACT
Background and Objectives :
Sepsis is the leading cause of death in non-coronary ICU patients, and the tenth most common
cause of death overall according to data from the Center for Disease Control and Prevention.
Sequential organ failure assessment (SOFA) score was constructed using physiological measures
of dysfunction in six organ systems. Both C-reactive protein (CRP) and procalcitonin (PCT) are
accepted sepsis markers. But there is still some debate concerning the correlation between their
serum concentrations and sepsis severity. This study is aimed at analysis of serum concentrations
of CRP and PCT in varied severity of organ dysfunction in sepsis as assessed by SOFA scores.
Materials and Methods :
This is a prospective study conducted in M S Ramaiah hospitals. Study included 70 consecutive
patients admitted to medical ICU with a diagnosis of sepsis. Patients selected for study were
categorized into 4 groups with different severity of organ dysfunction in sepsis according to
SOFA score. Serum PCT [by Brahm’s PCT Kryptor Immunofluorescent assay
(Biomerieux,France)] and CRP[using SIEMENS] concentrations were estimated in all the
patients.
Results :
Mean SOFA score (organ dysfunction) was higher among patients who died(10.93±4.46) than
those who survived(6.21±3.49) & the difference is statistically significant(p<0.001).The mean
PCT(ng/ml) and CRP(mg/L) concentration in those who survived were 14.95 and 150.316
respectively and in those who died were 46.86(p value <0.001) and 184.684(p value 0.172)
respectively.
Conclusion :
SOFA score and serum PCT concentration show significant correlation with respect to the
severity of organ dysfunction and outcome in sepsis patients compared to serum CRP
concentration. The diagnostic capacity of PCT is superior to that of CRP due to the close
correlation between PCT levels and the severity of sepsis and outcome.
Key words : Sepsis, SOFA score, Serum PCT

INTRODUCTION :
1
American college of chest physicians(ACCP)/Society of critical care medicine (SCCM)criteria
2
define sepsis as presence of systemic inflammatory response syndrome (SIRS) with known or
suspected infection.
Sepsis is the leading cause of death in non-coronary ICU patients, and the tenth-most-common
cause of death overall according to data from the Center for Disease Control and Prevention (the
3
first being heart disease) . The worldwide incidence of sepsis is 1500 cases per million. The
incidence of severe sepsis and septic shock has increased over the past 30 years, and the annual
number of cases is now >700,000 (~3 per 1000 population).The average mortality of around 30%
4
can increase to 60% or more when multiple failure occurs in >3 organs for 3 or more days .
CRP is the prototypical acute phase protein in humans and is an important mediator of host
defense. Normal baseline levels of circulating CRP are low, but increase up to 10,000-fold within
hours of inflammation induced by infection or injury. CRP is a non specific indicator of
inflammation, its levels can be significantly influenced by a number of disease conditions as well
5
as other parameters .
6
PCT detected in blood during inflammation is not produced by C-cells of the thyroid .
Parenchymal cells (including liver, lung, kidney, adipocytes and muscle) provide the largest
tissue mass and principal source of circulating PCT in sepsis. Production of PCT during
inflammation is linked to bacterial endotoxins and inflammatory cytokines.
Sequential organ failure assessment (SOFA) score was constructed using physiological measures
7
of dysfunction in six organ systems (respiratory, cardiovascular, liver, coagulation, renal and
central nervous systems) each of which is graded from 0 to 4 with increasing severity of
dysfunction.
Hence this study is done to analyze serum concentrations of CRP and PCT in varied severity of
organ dysfunction in sepsis as assessed by SOFA scores.

MATERIALS AND METHODS :


It was a prospective study conducted in 70 patients admitted to intensive care units at M S.
Ramaiah hospitals with sepsis over a period of one year. Patients with post-operative and post-
traumatic sepsis were excluded from the study.
The following investigations were done : Total WBC count, Platelet count, Serum bilirubin,
Serum creatinine, Arterial blood gas analysis, Serum Procalcitonin, Serum C-Reactive
Protein(CRP). Patients selected for study are categorized into 4 groups with different severity of
organ dysfunction in sepsis according to SOFA score as
SOFA score
Group 1 0-6
Group 2 7-12
Group 3 13-18
Group 4 19-24
STATISTICAL ANALYSIS
The descriptive statistics of SOFA score, PCT concentration, CRP concentration and would be
analyzed and expressed in mean and standard deviation(SD) /OR median and quartile deviation
whichever is applicable
Correlation coefficient between SOFA score and PCT concentration., CRP concentration. would
be analyzed and tested for significance with t-test.
• Sample size = 68
• Estimated using nMaster software based on this theory:
Comparision of PCT and CRP plasma concentrations at different SOFA scores during the
course of sepsis and MODS Michael M,Klaus T et.al,Critical care 1999, 3:45-50
• Considering the correlation coefficient of SOFA score and PCT r = 0.20
• The precision considered was 5% as α error,20% as β error and expecting the population
correlation coefficient as r = 0.5
RESULTS:
Out of 70 patients studied 39 (55.7 %) were males, 31(44.3%) were females. Most of the patients
(47.1 %) were in age group of 50-69 years. Type 2 DM(42.9%) & HTN(24.3%) were most
common comorbidites (Fig no 1). Fever, chills/rigors, cough & expectoration were most
common presenting symptoms (Fig no 2). Pneumonia(44.2% ) & UTI(28.5%) were most
common infections followed by diarrhoea and pyogenic meningitis. (Fig no 3). Urine culture
showed growth in 13 people ESBL E.Coli and Klebsiella were common organisms. Sputum
culture was positive among 10 people, Klebsiella and Pseudomonas were the commonest
organisms isolated.
85.7% of the patients were in SOFA 1 & 2 group (Table no 1). There were 15 deaths (21.4%) of
which 9 were females (60%) and 6 were males (40%). Pneumonia & UTI were the most
common causes of death (Table no 2).
Patients who were categorized in SOFA group 1 had a mean PCT of 7.832 ng/ml & mean CRP of
160 mg/L, As compared to group 4 who had 86.93 ng/ml & 40.86 mg/L respectively (Fig no 4).
Mean PCT was higher among people who died 46.86 ng/ml as compared to 14.95 ng/ml in who
survived. CRP was 150.36 mg/L among who survived and 184.684 mg/L among who died
(Fig 5). On comparison of study variables according to organ dysfunction GCS, platelet count,
SOFA score & serum PCT were statistically significant with p value < 0.001 (Table no 3).
DISCUSSION:
In our study, SOFA score & mean serum PCT concentration were higher among patients with
severe organ dysfunction(SOFA group 3&4) than those with mild organ dysfunction(SOFA
group 1&2) (p <0.001).Mean serum CRP concentration did not show any statistically significant
difference with SOFA groups(organ dysfunction)(p 0.238). Mean SOFA score (organ
dysfunction) was higher among patients who died(10.93±4.46 ) than those who survived
(6.21±3.49) & the difference is statistically significant(p <0.001). Mean serum PCT
concentration(ng/ml) was higher among patients who died (46.86±36.90) than those who
survived(14.95±19.48) & the difference is statistically significant (p <0.001). Mean serum CRP
concentration(mg/L) did not show a statistically significant difference with respect to the
outcome.
There was a statistically significant positive correlation between SOFA score & mean serum PCT
concentration (r value 0.535 & p value <0.001).
Our study results indicate that PCT concentration had a positive correlation with the severity of
organ dysfunction in sepsis as assessed by SOFA score. The results of our study are in general
agreement with studies in which PCT levels were compared with the severity of sepsis by sepsis-
related score systems. Previous studies have observed high concentrations of PCT during septic
shock, and comparable low concentrations during SIRS or less severe systemic inflammation.
8 9
Increasing PCT concentrations were previously reported by Oberhoffer et al and Zeni et al
during more severe stages of sepsis (severe sepsis and septic shock) as defined by the
10
ACCP/SCCM criteria. In a study by Al-Nawas et al , very low PCT concentrations were
measured during SIRS, but high concentrations when septic shock was diagnosed. Similar results
11 12
were published by Gramm et.al and de Werra et.al .These studies did not analyze the severity
of multiple organ dysfunction, instead they analyzed the severity of sepsis and systemic
inflammation.
Studies which focused on the extent of multi organ dysfunction rather than the severity or type of
inflammatory response or infection by use of SOFA score or other severity scales approach
closer to severity of clinical condition in sepsis. When serum PCT and CRP levels are to be
compared between different groups of patients, assessment of the severity of the disease and of
systemic inflammation, including the severity of MODS, is compulsory. In our study we
stratified patients with sepsis into four groups based on total SOFA score on day 1 of admission
to assess the severity of MODS. By stratification imbalances between groups as to severity of
inflammation or MODS can be minimized.
13
In a prospective observational study done by Castelli GP, Pognani C et.al , PCT and SOFA were
higher in septic shock than in severe sepsis and sepsis. They concluded that PCT and SOFA
closer correlate with the infection severity. The results of our study are consistent with this
conclusion.
14
In a prospective study done by Luzzani, Aldo MD et.al , the linear correlation between PCT
plasma concentrations and the four categories of patients(sepsis negative, SIRS , localized
infection, and sepsis group)was much stronger than in the case of CRP. A rise in sepsis-related
organ failure assessment score was related to a higher median value of PCT but not CRP. They
concluded that PCT is a better marker of sepsis than CRP & course of PCT shows a closer
correlation than that of CRP with the severity of infection and organ dysfunction. Results of our
study matches with these findings.
15
In a prospective study done by Michael Meisner, Klaus Tschaikowsky et.al , PCT, CRP, SOFA
score, APACHE II score and survival were evaluated in 40 patients with SIRS and consecutive
MODS over a period of 15 days. Higher SOFA score levels were associated with significantly
higher PCT plasma concentrations (SOFA 7–12: PCT 2.62 ng/ml, SOFA 19–24: PCT 15.22
ng/ml) (median), whereas CRP was elevated irrespective of the scores observed (SOFA 7–12:
CRP 131 mg/l, SOFA 19–24: CRP 135 mg/l). Measurement of PCT concentrations during
MODS provides more information about the severity and the course of the disease than that of
CRP. Our study results also highlight the above conclusion.
PCT has several advantages in severely ill sepsis patients compared with CRP. PCT
concentrations are quite low in case of mild organ dysfunction or a weak systemic inflammatory
response. In contrast, CRP levels are often elevated in patients with low SOFA scores. Thus
compared to PCT,CRP does not provide information on severity of organ dysfunction since it is
already increased to its maximum values during a less severe stage of disease. High PCT levels
were observed in patients with poor prognosis ie., those with severe organ dysfunction(high
SOFA score) and those who died of sepsis.
Unlike PCT, patients with a lethal outcome were not distinguished by CRP at any time in our
16
study. A recently conducted animal study by Nylen et al suggests that PCT might be a
significant lethal factor during sepsis.
The main limitation of our study is the small sample size in categories of patients with severe
organ dysfunction(SOFA groups 3 and 4).Also the course of organ dysfunction was not taken
into consideration for analyzing the correlation between serum PCT and CRP concentrations.
The number of patients in our study is too small and too heterogeneous for a general conclusion
regarding the absolute height of PCT concentrations and estimating the prognosis of the disease
by PCT.

FIGURE NO 1 : Comorbidities seen in study population

FIGURE NO 2 : Presenting symptoms in study population

FIGURE NO 3 : Infections seen in study population

FIGURE NO 4 : Comparison of mean serum PCT & mean serum CRP at various SOFA score

FIGURE NO 5 : Comparison between PCT & CRP

TOTAL SOFA SOFA GROUP Number of patients %


SCORE ON DAY 1 (N=70)

0-6 1 31 44.3

9-12 2 29 41.4

13-18 3 9 12.9

19-24 4 1 1.4

TABLE NO 1 : Classification of patients according to SOFA score on day 1

CAUSE NO. OF DEATHS (TOTAL = %


15)

PNEUMONIA 6 40

UTI 5 33.3

PNEUMONIA+UTI 1 6.6

DIARRHOEA 1 6.6

DENGUE SHOCK 1 6.6


SYNDROME (DSS)

SBP 1 6.6

TABLE NO 2 : Cause of death in patients

Variables SOFA group 1 SOFA group 2 SOFA group 3 SOFA group 4 P value
(Score 0-6) (Score 7-12) (Score 13-18) (Score 19-24)

GCS 14.87±0.34 14.34±1.85 10.33±4.12 7.00 <0.001**

Creatinine 1.89±1.67 2.58±1.25 2.96±0.95 2.33 0.147


(mg/dl)

Total bilirubin 1.45±1.57 4.35±8.19 2.44±0.66 2.10 0.241


(mg/dl)

Platelet count 241275.16 114242.06 83142.22 46000.00 <0.001**


(per mm3) ±115305.64 ±56221.54 ±35655.82

SOFA score 3.48±1.72 8.75±1.50 13.88±1.05 19.00 <0.001**

S.PCT (ng/ml) 7.83±7.90 28.14±29.01 42.14±37.00 86.93 <0.001**

S.CRP (mg/L) 160.59±52.04 156.20±64.08 147.12±57.22 40.86 0.238

TABLE NO 3 : Comparison of SOFA score groups with variables of SOFA score


Conflict of Interest : None
Ethical Clearance : Obtained
Source of Funding : Self
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