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Review
. 2023 Aug 3;7(1):15.
doi: 10.1186/s41512-023-00152-2.

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis

Daniel Molano-Franco  1 , Ingrid Arevalo-Rodriguez  2 , Alfonso Muriel  3   4 , Laura Del Campo-Albendea  3 , Silvia Fernández-García  5 , Ana Alvarez-Méndez  6 , Daniel Simancas-Racines  7 , Andres Viteri  7 , Guillermo Sanchez  8 , Borja Fernandez-Felix  3 , Jesus Lopez-Alcalde  3   9   10 , Ivan Solà  11 , Dimelza Osorio  12 , Khalid Saeed Khan  13 , Xavier Nuvials  14 , Ricard Ferrer  14 , Javier Zamora  3   15 ; SEPSIS-BIOMARKERS Collaborators
Collaborators, Affiliations
Review

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis

Daniel Molano-Franco et al. Diagn Progn Res. .

Abstract

Background: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation.

Methods: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates.

Results: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings.

Conclusion: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.

Trial registration: PROSPERO (CRD42019128790).

Keywords: Biomarkers; Mortality; Prognostic factors; Sepsis; Systematic review.

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Conflict of interest statement

Dr. Ferrer reports personal fees from Shionogi, personal fees from Pfizer, personal fees from MSD, personal fees from Gilead, personal fees from Menarini, personal fees from GSK during the conduct of the study. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of studies selection in the systematic review of prognostic value of biomarkers among critically ill adults with sepsis
Fig. 2
Fig. 2
Relation of baseline biomarkers measures with mortality at 28–30 days: selected biomarker performance assessments
See this image and copyright information in PMC

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