The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial

Abstract

BackgroundThis study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis.MethodsThis is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity.Results1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0–45.9) and 43.1 (10.1–184.0)).ConclusionsMR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2001-5) contains supplementary material, which is available to authorized users.

Diagnosing and Managing Sepsis by Probing the Host Response to Infection: Advances, Opportunities, and Challenges

“…Proadrenomedullin and soluble urokinase plasminogen activator receptor (suPAR) are emerging prognostic biomarkers in patients with sepsis. Proadrenomedullin has shown superior prognostic accuracy for 28-day mortality in intensive care unit (ICU) patients with sepsis or septic shock compared to that of lactic acid, CRP, procalcitonin, and severity scores, including SOFA, simplified acute physiology score II (SAPS II), and acute physiology and chronic health evaluation II (APACHE II), but is not yet approved for clinical use (38). suPAR was shown to make no difference in outcomes in a large emergency department randomized control trial (TRIAGE III) (39).…”

Sepsis diagnosis and monitoring – procalcitonin as standard, but what next?

“…Elke et al [47] performed a randomized controlled trial analysis in patients with severe sepsis or septic shock across 33 German ICUs. Patients were stratified into low, intermediate, and high severity groups and 1089 patients with a 28-day mortality rate of 26.9% were analyzed.…”

“…The authors concluded that MR-proADM is a more accurate disease severity and mortality risk stratification biomarker than clinically established biomarkers and scores. Changes in MR-proADM kinetics may be used to identify patients at risk of treatment failure despite ongoing antimicrobial therapy [47].…”

Biomarkers and clinical scores to aid the identification of disease severity and intensive care requirement following activation of an in-hospital sepsis code

“…An early diagnosis of sepsis, irrespective of hospitalisation setting, is crucial in order to provide a rapid and appropriate therapeutic response. This, however, may be complicated by the complex and heterogeneous host response to infection, as well as the high level of patient heterogeneity between departments [1].…”