Diagnostic And Prognostic Value Of CRP And Other Inflammatory Markers In ICU Patients:a Multicenter Observational Study

Background:It is not clear whether there is value in routine examination of markers reflecting inflammation for the prognosis judgment of intensive care unit(ICU)patients.We therefore conducted a multicenter,prospective,observational study to evaluate the effects of inflammatory markers in predicting mortality in general ICU populations.Meanwhile,the value of procalcitonin and other inflammatory markers in predicting early infection in ICU was evaluated.Methods:The clinical and laboratory data of patients at admission,including procalcitonin(PCT),white blood cell(WBC)count and C-reactive protein(CRP),were collected in four general ICUs from September 1,2018,to August 1,2019.Multivariate logistic regression was used to identify factors independently associated with nonsurvival.The area under the receiver operating characteristic curve(AUC-ROC),net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to evaluate the effect size of different factors in predicting mortality during ICU stay,hospital mortality,28 day mortality and 90 day mortality.Sensitivity analysis using a restricted cubic spline function with 3 knots was used to assess whether alternative cut points for these biomarkers were more appropriate.Multivariate logistic regression analysis was used to determine the independent risk factors associated with early ICU infection.The area under the receiver operating characteristic curve(auc-roc)was used to evaluate the influence of different factors on the prediction of early infection in ICU.Results:A total of 813 patients were recruited,among whom 121 patients(14.88%)died during the ICU stay.The serum concentrations of PCT and CRP were significantly higher in nonsurvivors than in survivors(PCT:0.97[0.23;5.51]vs.0.12[0;1.02]?g/L,P=0.000;CRP 66.70[12.80;140.00]vs.11.95[2.25;56.15]mg/L,P=0.000).The AUC-ROC values of PCT and CRP for discriminating ICU mortality were 0.696(95%confidence interval[CI],0.650-0.743)and 0.684(95%CI,0.633-0.735),respectively.In the multivariable analysis,only APACHE ? score(odds ratio,1.166;95%CI,1.129-1.203;P=0.000)and CRP concentration>62.8 mg/L(odds ratio,2.145;95%CI,1.343-3.427;P=0.001),but not PCT(P=0.444),were significantly associated with an increased risk of ICU mortality.Moreover,the combination of APACHE ? score and CRP>62.8 mg/L significantly improved risk reclassification over the APACHE ? score alone,with NRI(0.556)and IDI(0.013).Restricted cubic spline analysis confirmed that CRP concentration>62.8 mg/L was the optimal cut-off value for differentiating between surviving and nonsurviving patients.Among them,133 cases(16.36%)died during hospitalization,113 cases(13.90%)died within 28 days,and 145 cases(17.84%)died within 90 days.In multivariate analysis,only APACHE ? score and elevated CRP concentration were associated with increased in-hospital mortality,28 day mortality and 90 day mortality,while PCT was not associated with increased in-hospital mortality(P=0.051),28 day mortality(P=0.090)and 90 day mortality(P=0.068).Compared with APACHE ? score alone,combined APACHE ? score and CRP did not increase the area under the curve(AUROC)for predicting hospitalization(P=0.1083)and 28 day mortality(P=0.1403),but significantly increased the area under the curve(AUROC)for predicting 90 day mortality(P=0.035).470 patients were admitted to ICU without infection,and 115 of them had early infection.Multivariate analysis showed that CRP and PCT were independent risk factors for early infection.AUROC values of CRP and PCT in predicting early infection in ICU were 0.685(95%CI:0.641-0.727)and 0.733(95%CI:0.690-0.772)respectively.Combined PCT and CRP could not increase area under the curve(P=0.3469)(table 3-26,figure 3-12),and the sensitivity was 82.61%.Conclusion:Among the inflammatory biomarkers at ICU admission,CRP can be used as a predictor of ICU mortality,in-hospital mortality,28 day mortality and 90 day mortality.CRP combined with APACHE II score significantly improved the risk reclassification of prognosis prediction.PCT and CRP can be used as indicators to predict early infection in ICU,but the combination of PCT and CRP can not improve the prediction efficiency of early infection in ICU,but the sensitivity is improved.