“The important thing is not to stop questioning.”
Albert Einstein
C-Reactive Protein as a
Prognosis Factor for
Septic Patients
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SEPSIS
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SEPSIS
Sepsis is the body’s exacerbated
response to infection that threatens
patients of all ages.
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SEPSIS
1
leading cause of death in
noncoronary intensive care
units
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SEPSIS
It is defined as a complex syndrome
characterized by simultaneous
activation of inflammation and
coagulation in response to
infectious stimuli.
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SEPSIS
systemic inflammatory response
syndrome (SIRS)
inflammation
body’s normal antiinflammatory
response
=
sepsis
severe sepsis
septic shock
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
SIRS manifests itself
through the release
of, among other
molecular agents,
proinflammatory
cytokines
CRP (C-Reactive
Protein) – plasma
protein released by the
liver in response to
proinflammatory
cytokines: is an
indicator of
inflammation.
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
CRP = Biomarker of
sepsis
Is CRP a good
prognosis factor
for septic patients?
Prof. Doutor Armando Teixeira- Pinto
Prof. Doutor Altamiro Costa-Pereira
Introduction to Medicine 08/09
Class nr. 4
im4fmup@gmail.com
Problem / Research Question
Is C-reactive protein a good prognosis
factor for septic patients?
- “Are the levels of this protein related to the degree of
severity of sepsis?”
- “How can these values influence a good prognosis?”
- “Can it predict the mortality among patients?”
Systematic Review
C-Reactive Protein: a Prognosis Factor
for Septic Patients
C-Reactive Protein: a Prognosis Factor for Septic Patients
Key-Words
C-reactive
protein
Sepsis
Prognosis
C-Reactive Protein: a Prognosis Factor for Septic Patients
Aims
- Verify if C-reactive protein is a good prognosis factor of septic
patients;
- Analyze clinical data:
-Which are the values of C-reactive protein that can
predict each degree of sepsis?
-What kind of therapeutic can be applied based on Creactive protein’s values?
C-Reactive Protein: a Prognosis Factor for Septic Patients
Methods
C-Reactive Protein: a Prognosis Factor for Septic Patients
Query
The search terms include the following, their synonymous and, when
applicable, equivalent MeSH terms:
"C-reactive protein” AND (“prognosis” OR
“prognostic factor” OR “prognostic studies”) AND
("sepsis” OR “infection” OR “cross infection” OR
“hospital acquired infection” OR “multiple organ
dysfunction syndrome” OR “MODS” OR
“septicemia” OR “septic shock” OR “systematic
inflammatory response syndrome” OR “SIRS”) AND
(“hospital” OR “critical care” OR “intensive care”)
C-Reactive Protein: a Prognosis Factor for Septic Patients
Criteria
Inclusion Criteria
Exclusion Criteria
- Articles written in Portuguese, Spanish or - Articles whose full-text can´t be achieved for
English;
free;
- Articles about studies realized among - Articles about studies that not include samples
hospitalized patients in ICU (Intensive Care of patients with a septic diagnosis;
Unit) with a septic diagnosis;
- Articles about studies that not mention CRP as
- Articles about studies that mention CRP as a a biomarker/prognosis factor of sepsis;
prognosis factor of sepsis (alone or conjugated - Articles about studies with insufficient or
with other biomarkers);
- Articles about studies that include consistent
and organized data about CRP’s values in
different samples of patients and references to
outcomes in terms of morbidity and mortality.
inconclusive data.
C-Reactive Protein: a Prognosis Factor for Septic Patients
Research
We’ve searched the following database using the query referred
previously:
• Pubmed (221 articles – until 13/03/2009)
C-Reactive Protein: a Prognosis Factor for Septic Patients
Data Synthesis
Quantitative
Analysis
Descriptive
Analysis
performing
Meta-Analysis
Variables Extracted
organizing
work in
using
Microsoft Visio
SPSS 16.0
Microsoft Project
C-Reactive Protein: a Prognosis Factor for Septic Patients
Selection of Studies
The decision of inclusion or exclusion of
each article was taken according to the
inclusion or exclusion criteria determined.
C-Reactive Protein: a Prognosis Factor for Septic Patients
Articles included were divided
into 2 groups:
- Those with a positive association
between prognostic value of CRP
and sepsis (4 articles);
- Those with a negative association
between prognostic value of CRP
and sepsis (9 articles).
C-Reactive Protein: a Prognosis Factor for Septic Patients
- We created two Databases in order to organize data and make articles’ analysis
easier.
- To do this we used SPSS 16.0 ®
C-Reactive Protein: a Prognosis Factor for Septic Patients
Quality Test
Newcastle –Ottawa Scale (NOS)
(“The Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses”; GA Wells, B Shea, D O’Connell, J Peterson, V Welch, M Losos, P
Tugwell)
Test’s scale goes from 0* (minimum) to 9* (maximum).
Articles with negative association achieved a mean value of scores of
4,55* [(3-6); min. – max.] and the positive ones had a 4* mean score
[(2-6); min. – max.].
C-Reactive Protein: a Prognosis Factor for Septic Patients
- Studies compare different cutoffs and groups:
- survivors vs. non survivors;
- others consider groups according to the severity of sepsis (sepsis,
severe sepsis, septic shock);
- The summary measures presented are means±SD, medians (IR) and
medians (percentiles 5 – 95);
- Some studies present OR and RR values, ROC curves and diagrams.
C-Reactive Protein: a Prognosis Factor for Septic Patients
- Articles presented a group of different variables, various measurement
methods, different cutoff values of CRP and several ways of results’
presentation such as means associated with standard deviations, medians
and interquartile range, ROC curves, odds ration and relative risks =
Difficult to analyze the articles by quantitative means!
- We opted to perform a systematic review and to classify the articles
qualitatively through the NOS assessment method.
Meta-Analysis
Systematic Review
C-Reactive Protein: a Prognosis Factor for Septic Patients
Discussion
C-Reactive Protein: a Prognosis Factor for Septic Patients
- All studies concerning CRP, sepsis, and prognosis are relatively recent;
- Studies that consider no association are, generally, older than those that
state a positive association (except the study published by Silvestre J et
al. in 2008);
This can be explained by different parameters of evaluation of CRP
levels and its relation with prognosis; different methods, cutoffs and
scales used.
C-Reactive Protein: a Prognosis Factor for Septic Patients
- CRP as a factor of prognosis of sepsis is not largely studied, and its prognostic
power has to be proved consistently by further investigation in this area.
- It seems to be an important single marker of inflammatory activation and one of
the most suitable for use in clinical practice. However, its applicability in every day
clinical practice as a prognosis factor is not yet established.
- Many difficulty persists concerning the investigation’s methods and results’
interpretation regarding CRP.
- Although promising, the clinical relevance of prognostic assessment based in
CRP levels needs a deeper work in order to define the best cutoff, methodology
and analysis procedures in each clinical setting and whether CRP is or isn’t a good
factor of prognosis among septic patients.
C-Reactive Protein: a Prognosis Factor for Septic Patients
- In summary, despite the large amount of evidence linking CRP with
sepsis’ prognosis, current practice guidelines give no recommendations
regarding when CRP should be measured and how to proceed with a
patient with determined values of CRP.
- We propose a standardization with additional studies, which need to be
conducted in order to select the best methodology and to determined the
appropriate measurements of CRP and how to valorize the result
obtained.
Presenters:
Margarita Yakubovich
Sara Rodrigues
Class 4
2008 / 2009