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C-Reactive Protein Levels an Early-Stage Biomarker for Sepsis Outcome: Presented at ISICEM

By Jenny Powers

BRUSSELS -- March 25, 2011 -- C-reactive protein (CRP) levels can be used as an early marker of sepsis resolution, according to results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study) reported at the 31st International Symposium on Intensive Care and Emergency Medicine (ISICEM).

CRP levels that failed to decrease by day 3 following antibiotic treatment indicated a poorer prognosis, while levels that showed a 10% decline daily associated significantly with decreased mortality risk, according to results from this large study of patients with sepsis who were admitted to hospital intensive care units (ICUs).

The diagnosis of severe sepsis and septic shock is currently made based on the presence of Systemic Inflammatory Response Syndrome (SIRS), organ dysfunction, and microbiological data. Although C-reactive protein, a marker of inflammation, has been proposed as a biomarker, its utility is still debated, and associations with outcome have not yet been demonstrated.

Researchers determined the usefulness of recording CRP levels following antibiotic treatment, and evaluated CRP level as a prognostic factor for resolution of community-acquired sepsis (CAS) in 891 consecutive patients admitted to 17 Portuguese ICUs over a 1-year period, stated lead investigator Pedro R. Povoa, MD, PhD, Hospital Sao Francisco Xavier, Lisbon, Portugal, speaking here on March 22

Data from this observational study were reported during the first 5 days in the ICU, on the day of ICU discharge or death, and at final discharge from hospital. C-reactive protein levels were compared between survivors and nonsurvivors.

The mean age of the study participants was 60 years (range 43-77 years), and there was 38% hospital mortality. The CRP levels on day 1 were not statistically different between the survivor and nonsurvivor groups: 19.8 ± 12.5 mg/dL versus 20.7 ± 12.8 mg/dL (P =.367), respectively.

Following comparisons made at the different time points between the groups, however, it was clear that elevated CRP levels from day 3 post treatment indicated a poorer prognosis; the CRP of nonsurvivors was significantly higher (P <.001, for days 3, 4, and 5).

After adjusting for Simplified Acute Physiology Score 2 (SAPS 2) and the severity of sepsis (sepsis, severe sepsis, and septic shock) in each patient, the initial CRP level did not significantly associate with hospital mortality (odds ratio [OR] initial = 1.01, 95% confidence interval [CI], 0.99-1.02, P =.297). Measurement of the relative change in each patient’s CRP levels over the 5 days in ICU, however, generated 2 variables: an intercept, which described the initial CRP value, and a slope, which described the CRP rate of change per day for a specific patient.

The slope significantly associated with hospital mortality (OR CPR-ratio = 1.03; 95% CI, 1.02-1.04, P <.001). Patients who displayed a downward slope reflecting an average 10% daily decrease of the CRP levels had a 32% less risk of death compared with patients with similar SAPS 2 scores and equivalent sepsis severity whose CRP levels remained elevated over time. The area under the receiver operating characteristic curve (AUROC) for the model -- including SAPS 2, severity of sepsis, initial CRP, and CRP course -- was 0.77.

No other significant differences between survivors and nonsurvivors were found upon daily monitoring of temperature and white cell count, both on day 1 (P =.799 and P =.496, respectively) and subsequent days (P =.360 and P =.594, respectively).

Daily CRP measurement following antibiotic treatment was useful to identify CAS patients with a poorer outcome, who could require additional intervention as early as day 3 in the ICU. A level slope of CRP was associated significantly with poorer outcome.

Dr. Povoa pointed out that this was the largest study carried out so far to demonstrate an association between CRP level and outcome, and that the rate of CRP decreases per day were associated significantly with a better prognosis and a lowered risk of sepsis-related death.

Funding for this study was primarily supported by unrestricted grants from the ASSUCIP and the GIS and also received support from Merck, Sharpe & Dohme, and Eli Lily Company.

[Presentation title: C-Reactive Protein as an Early Marker of Sepsis Resolution. Results From the Portuguese Community-Acquired Sepsis Study (SACiUCI Study). Abstract A182]

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