In this study we have shown that control CRP levels can be used to predict the mortality of patients with respiratory failure due to sepsis and being treated by the sepsis protocol, as well as the initial APACHE II, and SOFA scores on the first and third day of ICU (well-known predictors of mortality).
Sepsis protocols proposed by the Sepsis Campaign have been successfully used and predicted mortality for sepsis patients with an initial ICU APACHE II was 32.2%, whereas actual mortality was 14.2%. It has been suggested that CRP levels could impact on the prognosis of ICU patients by some studies done in septic dogs and humans[5–7, 14]. Gebhardt et al. declared that the change in initial and third day control CRP levels was better for predicting mortality than initial CRP, and a fall in the third day CRP level demonstrated corrected survival with 94% accuracy in a study with septic dogs. In our study, we showed that initial and ∆ CRP levels were not as valuable for predicting ICU mortality in sepsis patients and 3rd day control CRP was better than initial CRP values and ∆ CRP values, respectively (3rd day CRP AUC: 0.72, CI: 0.63-0.80; initial CRP AUC: 0.57, CI: 0.48-0.66; ∆ CRP AUC: 0.41, CI: 0.30-0.50). These results differed from the study on dogs by Gebhardt et al.. Silvestre et al. recently studied the prognostic value of initial APACHE II, SAPS II, SOFA, CRP, fever, and leukocyte count in 158 sepsis patients. The AUC (CI 95%: lower-upper limit) was 0.75 (0.67-0.83), 0.82 (0.75-0.89), 0.80 (0.72-0.88), 0.55 (0.45-0.65), 0.48 (0.38-0.58), and 0.46 (0.35-0.56), respectively. They concluded that CRP was not an adequate test for the prognosis of sepsis patients. Initial CRP was not a good mortality predictor in our study, but control CRP was found to be as significant as the SOFA score for predicting response to sepsis treatment and prognosis. In another study which looked at the relationship between CRP levels and mortality in sepsis patients within the first 24 hours after discharge from ICU, the mean CRP for non-survivors and survivors was 174 mg/L and 85.6 mg/L, respectively. A high CRP level was indicated to be an independent risk factor of mortality. In our study, the CRP level at the time of discharge from the ICU was not recorded. In addition, we did not follow up on hospital mortality after ICU discharge. However, in the present study, after the 3rd-5th day of treatment, the median CRP values were higher in non-survivors than survivors (105 mg/L versus 44 mg/L, respectively). Instead of initial CRP values, CRP values measured a few days after admission may be more helpful for physicians to make judgments on treatment response and sepsis outcome in the ICU. Pro-calcitonin has also been highlighted as an indicator of inflammation due to infection and there are studies indicating the serum levels of pro-calcitonin may be a better indicator of sepsis severity than CRP[16, 17]. Pro-calcitonin is much more expensive than serum CRP and we did not use it in this study for financial reasons. It has been noted that using pro-calcitonin in sepsis management could increase the validity of the clinical decision since it yields results rapidly and it has a shorter half-life than CRP (by 19 hours).
SOFA scores on admission to ICU and on the third day were found to be good predictors of mortality risk (AUC for SOFA on the 1st day, 0.72 [CI: 0.64-0.81], SOFA on the 3rd day, 0.76 [CI: 0.67-0.86]). SOFA score is not as practical or as rapid a test as CRP to evaluate sepsis severity as it is calculated by adding platelet count, PaO2/FiO2 ratio, serum bilirubin, creatinine, and the Glasgow Coma Scale. In our study the 3rd day SOFA score and the 3rd day CRP value were shown to be risk indicators for sepsis related mortality when comparing severity scores. We believe that the 3rd day CRP value can be used in clinical practice in the ICU to reveal mortality risk and is comparable with the SOFA score when its level is high on third day after initiation of treatment for sepsis (> 100 mg/L).
Thus, in this study analyzing risk factors for overall mortality in sepsis and looking for parameters that influence mortality (indicated as significant in bivariate analysis, with logistical regression analysis) a higher SOFA score on the third day, hospital acquired sepsis, and a 3rd day CRP > 100mg/L were shown to be risk factors for mortality. The culture positivity for detecting an infectious agent in hospital acquired sepsis was only 20%. Pseudomonas spp was the most common agent in the culture results. The low culture positivity was assumed to be due to ongoing antibioticotherapy at the time of culture and the initiation of empirical therapy before collection of the culture specimen. In a previous study where CRP levels were checked every four days in critical patients with a 38% rate of culture positivity it was concluded that a ≥ 50 mg/L fall in CRP levels could be a good predictor of recovery. In our study there was a median fall of 18.3 mg/L in ∆ CRP in survivors.