1. C-Reactive Protein: a Prognosis Factor for Septic Patients Systematic Review and Meta-analysis Introduction to Medicine – 1 st Semester Class 4, First Year Prof. Doutor Armando Teixeira-Pinto Prof. Doutor Altamiro Costa-Pereira

2. Summary 1) Introduction 2) Studies 3) Problem / Research Question 4) Key-Words 5) Aims C-Reactive Protein: a Prognosis Factor for Septic Patients 6) Methods 6.1) Query 6.2) Criteria 6.3) Research 6.4)Selection of Studies 7) Expected Results 8) Balance

3. Introduction C-Reactive Protein: a Prognosis Factor for Septic Patients – Sepsis (systematic inflammatory response syndrome with a proven or suspected infectious etiology) is a very serious disease, so we found interesting to investigate if C-reactive protein (a plasma protein that circulates in increased amounts during inflammation and after tissue damage) can really predict the evolution of the disease and if its levels help to decide which therapy should be applied to patients.

4. Introduction C-Reactive Protein: a Prognosis Factor for Septic Patients – Among the studies we found there are some controversy about the relevance of C-reactive protein as a good prognosis factor for sepsis. – Study 1: The Time Course of Blood C-reactive Protein Concentrations in Relation to the Response to Initial Antimicrobial Therapy in Patients with Sepsis; – Study 2: High C-reactive Protein and Low Cholesterol Levels are Prognostic Markers of Survival in Severe Sepsis; – Study 3: Procalcitonin for Early Prediction of Survival Outcome in Postoperative Critically ill Patients with Severe Sepsis.

5. Studies C-Reactive Protein: a Prognosis Factor for Septic Patients

6. Studies Study 1: The Time Course of Blood C-reactive Protein Concentrations in Relation to the Response to Initial Antimicrobial Therapy in Patients with Sepsis C-Reactive Protein: a Prognosis Factor for Septic Patients Aim: Measure changes to look for the response treatment based on C-reactive protein blood levels in septic patients. Details 5 months (from 11/2005 to 04/2006); 2 hospitals in Brussels, Belgium. 50 patients were included since the day of septic diagnosis until time of administration of first antibiotic dose (D0); they were observed daily until death, transfer to the general floor or seventh day (D7). Table 1:Clinical characteristics of study patients during their ICU stay. Number of patients 50 Male76% Age (years)63 Sepsis20% Severe sepsis46% Septic shock34% Duration of ICU stay, days (range) 4-7 days

7. Studies C-Reactive Protein: a Prognosis Factor for Septic Patients Methods and Results : Patients were divided into three groups: - Blood CRP concentrations were determined by immunoturbidimetry. Group 1Patients with a favorable response to initial antibiotic therapy Group 2Patients who required a change in antibiotic Group 3Patients for whom additional information led to an intervention to control the infection 50 Patients 24 Group 1 18 Group 2 8 Group 3

8. Studies C-Reactive Protein: a Prognosis Factor for Septic Patients Conclusions: - Increases in CRP concentrations are associated with organ failure, prolonged ICU stay and high mortality; - CRP concentrations decrease are faster and more significant in patients with a good response to the initial treatment than in those who required a change in antibiotic therapy; - However, CRP concentrations in patients at the “septic shock” phase are conclusive that C-reactive protein isn’t helpful in predicting mortality. Schmit, X. et al., The Time Course of Blood C-reactive Protein Concentrations in Relation to the Response to Initial Antimicrobial Therapy in Patients with Sepsis, Infection 36 Æ 2008 Æ No. 3

9. Studies Study 2: High C-reactive Protein and Low Cholesterol Levels are Prognostic Markers of Survival in Severe Sepsis C-Reactive Protein: a Prognosis Factor for Septic Patients Aim: Evaluate the predictive value of cholesterol and C-reactive protein levels on the mortality and morbidity of severe sepsis. Details Prospective study; 96 patients (age range, 18-75 years; median, 56 years; men/women ratio, 40:56) diagnosed with severe sepsis. Methods: Patients' serum levels of C-reactive protein and cholesterol were measured thrice: upon admission to an intensive care unit, two days later, and on the day of discharge from the intensive care unit or on the day of death.

10. Studies C-Reactive Protein: a Prognosis Factor for Septic Patients Results: Conclusions: Table constructed based on the results of the study: Memiş D et al. High C-reactive protein and low cholesterol levels are prognostic markers of survival in severe sepsis. 2007 May;19(3):186-91.

11. Studies Study 3: Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis. C-Reactive Protein: a Prognosis Factor for Septic Patients Aim: Assess the utility of procalcitonin (PCT), C-reactive protein and other readily available parameters, as useful early (days 1–3) predictors of mortality in postoperative patients diagnosed with severe sepsis. Details: Period of 2 years; In ICU, were admitted 69 postoperative patients with severe sepsis and 890 non-septic. Methods: PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay.

12. Studies C-Reactive Protein: a Prognosis Factor for Septic Patients Results: Area under ROC (receiver operating characteristic) curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay. Conclusion: According to this study, C-reactive protein isn’t a good factor of prognosis among septic patients. Dahaba, A. A. et al. Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis. 2006 June 14

13. Problem / Research Question C-Reactive Protein: a Prognosis Factor for Septic Patients “Is C-reactive protein a good factor of prognosis for septic patients?” - “ Are the levels of this protein related to the degree of severity of sepsis?” - “How can those values influence a good prognosis?” - “Can it predict the mortality among those patients?”

14. Key-Words C-Reactive Protein: a Prognosis Factor for Septic Patients C-reactive protein Prognosis Sepsis

15. Aims C-Reactive Protein: a Prognosis Factor for Septic Patients

16. Methods C-Reactive Protein: a Prognosis Factor for Septic Patients

17. Query – The search terms will include the following, their synonymous and, when applicable, equivalent MeSH terms: ["C-reactive protein”] AND [“prognosis”] 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”] Query may also include [“hospital” OR “critical care” OR “intensive care”]. C-Reactive Protein: a Prognosis Factor for Septic Patients

18. Criteria C-Reactive Protein: a Prognosis Factor for Septic Patients

19. Research – In order to find the articles we need, we’ve searched in the following databases by inserting the key-words referred previously: Pubmed (154 articles); SCOPUS (search in course); Google Scholar ( 9520 results – analysis in process). C-Reactive Protein: a Prognosis Factor for Septic Patients

20. Data Synthesis C-Reactive Protein: a Prognosis Factor for Septic Patients

21. 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

22. Expected Results Different levels of C - Reactive Protein in blood at different stages of sepsis will be related to its progression or regression. Therefore, this will assess the chances of survival of patients. If this relation is confirmed, a most precise therapy could be chosen for each patient, according to the prognosis. Internment time would be reduced, economical expenses would be fewer, since useless medication wouldn’t be used. C-Reactive Protein: a Prognosis Factor for Septic Patients

23. Balance C-Reactive Protein: a Prognosis Factor for Septic Patients Presently We have made some meetings to manage tasks; We are improving our research work by reading and selecting studies; We are finishing the article’s protocol. Future Research, select and process more information; Organize the general structure of the rest of the article (besides protocol) and write it’s final text.

24. THE END Presenter: Sara Rodrigues Class 4 2008 / 2009