Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission

• Published in: Critical care (London, England) Vol. 23; no. 1; p. 335
• Main Authors: Gonzalez Del Castillo, Juan, Wilson, Darius Cameron, Clemente-Callejo, Carlota, Román, Francisco, Bardés-Robles, Ignasi, Jiménez, Inmaculada, Orviz, Eva, Dastis-Arias, Macarena, Espinosa, Begoña, Tornero-Romero, Fernando, Giol-Amich, Jordi, González, Veronica, Llopis-Roca, Ferran
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.10.2019; BioMed Central; BMC
• Subjects: Adrenomedullin - analysis; Adrenomedullin - blood; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; Area Under Curve; Biological markers; Biomarkers - analysis; Biomarkers - blood; C-reactive protein; C-Reactive Protein - analysis; Critical care medicine; Disease progression; Emergency medicine; Emergency Service, Hospital - organization & administration; Emergency Service, Hospital - statistics & numerical data; Female; Health aspects; Hospitalization - statistics & numerical data; Humans; Identification and classification; Infection; Intensive Care Units - organization & administration; Intensive Care Units - statistics & numerical data; Lactates; Male; Middle Aged; Mortality; MR-proADM; NEWS; Organ Dysfunction Scores; Patient outcomes; Peptide Fragments - analysis; Peptide Fragments - blood; Procalcitonin - analysis; Procalcitonin - blood; Proportional Hazards Models; Prospective Studies; Protein Precursors - analysis; Protein Precursors - blood; qSOFA; Retrospective Studies; Risk Factors; ROC Curve; Sepsis; Sepsis - drug therapy; Sepsis - psychology; Severity of Illness Index; Social aspects; Statistics, Nonparametric; Time-to-Treatment; Spain; Infection; Emergency department; MR-proADM; Disease progression; NEWS; qSOFA; Sepsis; Intensive care unit
• ISSN: 1364-8535; 1466-609X; 1364-8535
• DOI: 10.1186/s13054-019-2613-4

The performance of blood biomarkers (mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate) and clinical scores (Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS), and quick SOFA) was compared to identify patient populations at risk of delayed treatment initiation and disease progression after presenting to the emergency department (ED) with a suspected infection. A prospective observational study across three EDs. Biomarker and clinical score values were calculated upon presentation and 72 h, and logistic and Cox regression used to assess the strength of association. Primary outcomes comprised of 28-day mortality prediction and delayed antibiotic administration or intensive care (ICU) admission, whilst secondary outcomes identified subsequent disease progression. Six hundred eighty-four patients were enrolled with hospitalisation, ICU admission, and infection-related 28-day mortality rates of 72.8%, 3.4%, and 4.4%, respectively. MR-proADM and NEWS had the strongest association with hospitalisation and the requirement for antibiotic administration, whereas MR-proADM alone had the strongest association with ICU admission (OR [95% CI]: 5.8 [3.1 - 10.8]) and mortality (HR [95% CI]: 3.8 [2.2 - 6.5]). Patient subgroups with high MR-proADM concentrations (≥ 1.77 nmol/L) and low NEWS (< 5 points) values had significantly higher rates of ICU admission (8.1% vs 1.6%; p < 0.001), hospital readmission (18.9% vs. 5.9%; p < 0.001), infection-related mortality (13.5% vs. 0.2%; p < 0.001), and disease progression (29.7% vs. 4.9%; p < 0.001) than corresponding patients with low MR-proADM concentrations. ICU admission was delayed by 1.5 [0.25 - 5.0] days in patients with high MR-proADM and low NEWS values compared to corresponding patients with high NEWS values, despite similar 28-day mortality rates (13.5% vs. 16.5%). Antibiotics were withheld in 17.4% of patients with high MR-proADM and low NEWS values, with higher subsequent rates of ICU admission (27.3% vs. 4.8%) and infection-related hospital readmission (54.5% vs. 14.3%) compared to those administered antibiotics during ED treatment. Patients with low severity signs of infection but high MR-proADM concentrations had an increased likelihood of subsequent disease progression, delayed antibiotic administration or ICU admission. Appropriate triage decisions and the rapid use of antibiotics in patients with high MR-proADM concentrations may constitute initial steps in escalating or intensifying early treatment strategies.