Introduction Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone. Methods We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin). Results There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated. Conclusions Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.
References
[1]
Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348: 1546–1554.
[2]
Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, et al. (2005) C-reactive protein as a marker of ventilator-associated pneumonia resolution: a pilot study. Eur Respir J 25: 804–812.
[3]
Sakr Y, Vincent JL, Ruokonen E, Pizzamiglio M, Installe E, et al. (2008) Sepsis and organ system failure are major determinants of post-intensive care unit mortality. J Crit Care 23: 475–483.
[4]
Yende S, D'Angelo G, Mayr F, Kellum JA, Weissfeld L, et al. (2011) Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths. PLoS One 6: e22847.
[5]
Hedlund JU, Ortqvist AB, Kalin ME, Granath F (1993) Factors of importance for the long term prognosis after hospital treated pneumonia. Thorax 48: 785–789.
[6]
Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, et al. (2010) Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 38: 1276–1283.
[7]
Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, et al. (2006) Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax 61: 10–16.
[8]
Povoa P (2002) C-reactive protein: a valuable marker of sepsis. Intensive Care Med 28: 235–243.
[9]
Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, et al. (2006) Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study. Crit Care 10: R63.
[10]
Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, et al. (2005) Pilot study evaluating C-reactive protein levels in the assessment of response to treatment of severe bloodstream infection. Clin Infect Dis 40: 1855–1857.
[11]
Ranzani OT, Prada LF, Zampieri FG, Battaini LC, Pinaffi JV, et al. (2012) Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study. J Crit Care 27: 525.e9–525.e15.
[12]
Rey C, Los Arcos M, Concha A, Medina A, Prieto S, et al. (2007) Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children. Intensive Care Med 33: 477–484.
[13]
Grander W, Dunser M, Stollenwerk B, Siebert U, Dengg C, et al. (2010) C-reactive protein levels and post-ICU mortality in nonsurgical intensive care patients. Chest 138: 856–862.
[14]
Ho KM, Lee KY, Dobb GJ, Webb SA (2008) C-reactive protein concentration as a predictor of in-hospital mortality after ICU discharge: a prospective cohort study. Intensive Care Med 34: 481–487.
[15]
Al-Subaie N, Reynolds T, Myers A, Sunderland R, Rhodes A, et al. (2010) C-reactive protein as a predictor of outcome after discharge from the intensive care: a prospective observational study. Br J Anaesth 105: 318–325.
[16]
Ho KM, Dobb GJ, Lee KY, Towler SC, Webb SA (2006) C-reactive protein concentration as a predictor of intensive care unit readmission: a nested case-control study. J Crit Care 21: 259–265.
[17]
Kaben A, Correa F, Reinhart K, Settmacher U, Gummert J, et al. (2008) Readmission to a surgical intensive care unit: incidence, outcome and risk factors. Crit Care 12: R123.
[18]
Artero A, Zaragoza R, Camarena JJ, Sancho S, Gonzalez R, et al. (2010) Prognostic factors of mortality in patients with community-acquired bloodstream infection with severe sepsis and septic shock. J Crit Care 25: 276–281.
[19]
Dominguez de Villota E, Mosquera JM, Rubio JJ, Galdos P, Diez Balda V, et al. (1980) Association of a low serum albumin with infection and increased mortality in critically ill patients. Intensive Care Med 7: 19–22.
[20]
Carriere I, Dupuy AM, Lacroux A, Cristol JP, Delcourt C, et al. (2008) Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people. J Am Geriatr Soc 56: 840–846.
[21]
Fairclough E, Cairns E, Hamilton J, Kelly C (2009) Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med 9: 30–33.
[22]
Ranzani OT, Battaini LC, Moraes CE, Prada LF, Pinaffi JV, et al. (2011) Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases. Braz J Med Biol Res 44: 1184–1193.
[23]
Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56: 1129–1135.
[24]
Hosmer DW LS (2000) Applied Logistic Regression: Wiley.
[25]
Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148: 839–843.
[26]
Casalino E, Mendoza-Sassi G, Wolff M, Bedos JP, Gaudebout C, et al. (1998) Predictors of short- and long-term survival in HIV-infected patients admitted to the ICU. Chest 113: 421–429.
[27]
Silvestre J, Coelho L, Povoa P (2010) Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 10: 17.
[28]
Lee JH, Kim J, Kim K, Jo YH, Rhee J, et al. (2011) Albumin and C-reactive protein have prognostic significance in patients with community-acquired pneumonia. J Crit Care 26: 287–294.
[29]
Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM (2003) Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg 237: 319–334.
[30]
Bortz WM 2nd (2002) A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci 57: M283–288.
[31]
Van Hemelrijck M, Harari D, Garmo H, Hammar N, Walldius G, et al. (2012) Biomarker-based score to predict mortality in persons aged 50 years and older: a new approach in the Swedish AMORIS study. Int J Mol Epidemiol Genet 3: 66–76.
[32]
Pinilla JC, Hayes P, Laverty W, Arnold C, Laxdal V (1998) The C-reactive protein to prealbumin ratio correlates with the severity of multiple organ dysfunction. Surgery 124: 799–805; discussion 805–796.
[33]
Xie Q, Zhou Y, Xu Z, Yang Y, Kuang D, et al. (2011) The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury. BMC Nephrol 12: 30.
[34]
Cook NR, Buring JE, Ridker PM (2006) The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 145: 21–29.
[35]
Cook NR (2007) Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation 115: 928–935.
[36]
Araújo I, Gon?alves-Pereira J, Teixeira S, Nazareth R, Silvestre J, et al. (2012) Assessment of risk factors for in-hospital mortality after intensive care unit discharge. Biomarkers 17: 180–185.
[37]
Taori G, Ho KM, George C, Bellomo R, Webb SA, et al. (2009) Landmark survival as an end-point for trials in critically ill patients--comparison of alternative durations of follow-up: an exploratory analysis. Crit Care 13: R128.
[38]
Quartin AA, Schein RM, Kett DH, Peduzzi PN (1997) Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA 277: 1058–1063.
[39]
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, et al. (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34: 344–353.
[40]
Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40: 373–383.