Critical Care (Mar 2018)

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

  • Gunnar Elke,
  • Frank Bloos,
  • Darius Cameron Wilson,
  • Frank Martin Brunkhorst,
  • Josef Briegel,
  • Konrad Reinhart,
  • Markus Loeffler,
  • Stefan Kluge,
  • Axel Nierhaus,
  • Ulrich Jaschinski,
  • Onnen Moerer,
  • Andreas Weyland,
  • Patrick Meybohm,
  • the SepNet Critical Care Trials Group

DOI
https://doi.org/10.1186/s13054-018-2001-5
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 12

Abstract

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Abstract Background This 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. Methods This 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. Results 1089 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)). Conclusions MR-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.

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