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

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

Identification of developing multiple organ failure in sepsis patients with low or moderate SOFA scores

An early identification of sepsis patients likely to progress towards multiple organ failure is crucial in order to initiate targeted therapeutic strategies to decrease mortality. Our recent publication highlighted the greater accuracy of mid-regional proadrenomedullin (MR-proADM) compared with conventional biomarkers and clinical scores in predicting 28-day mortality in patients with initially low (≤7 points; N = 240) or moderate (8–13 points; N = 653) Sepsis-related Organ Failure Assessment (SOFA) scores, thus confirming results from smaller investigations. This additional post hoc analysis aimed to further describe the non-surviving patient population of both subgroups and identify those likely to progress towards sepsis-related multiple organ failure. ..

Predicting the requirement for renal replacement therapy in intensive care patients with sepsis

Sepsis is one of the most frequent causes of acute kidney injury (AKI) in critically ill patients, with initial organ impairment often followed by dysfunction in other systems. Renal dysfunction may therefore represent one facet in the evolution towards multiple organ dysfunction syndrome (MODS) or, alternatively, may be indicative of system-wide endothelial damage caused by hyperinflammation and a positive fluid balance. Whilst numerous biomarkers have been investigated to predict renal replacement therapy (RRT) requirement, including NGAL, TIMP-2 and IGFBP-7, mid-regional proadrenomedullin (MR-proADM) may also be of interest due to its involvement in capillary leakage, endothelial dysfunction and the initial stages of multiple organ failure development. ..

The prevalence of sepsis-induced coagulopathy in patients with sepsis – a secondary analysis of two German multicenter randomized controlled trials

Abstract Background Sepsis and septic shock are frequently accompanied by coagulopathy. Since the sepsis-induced coagulopathy (SIC) score was first described, subsequent studies from Asia revealed a SIC prevalence of 40–60%. In Europe, however, SIC prevalence in patients fulfilling sepsis criteria according to the third international consensus definition (SEPSIS-3) has not yet been evaluated. Methods The Critical Care Trials Group of the German Sepsis Competence Network (SepNet) conducted a secondary analysis of two randomized controlled trials. Only patients fulfilling sepsis criteria according SEPSIS-3 were included in this secondary analysis. In a two step approach, SIC prevalence was determined in 267 patients with sepsis but not septic shock (at the time of inclusion) from the “Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis” (HYPRESS) trial. Then, we estimated SIC prevalence in 1,018 patients from the “Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock” (SISPCT) trial using a simplified SIC score based on the platelet-SIC-subscore (PSSC). Study aims were to assess (i) the prevalence of SIC in patients with SEPSIS-3, (ii) the association of SIC with 90-day mortality and morbidity, (iii) the time when patients become SIC positive during the course of sepsis, and (iv) the value of the PSSC for predicting SIC. Results In the HYPRESS trial, SIC prevalence was 22.1% (95% confidence interval [CI] 17.5–27.5%). The estimated SIC prevalence in the SISPCT trial was 24.2% (95% CI 21.6–26.9%). In the HYPRESS trial, SIC was associated with significantly higher 90-day mortality (13.9% vs. 26.8%, p = 0.027) and morbidity. Logistic regression analysis adjusted for age, sex, treatment arm, and (SIC-adapted) SOFA score confirmed the negative association of SIC with survival (p = 0.011). In the SISPCT trial, increased PSSCs were associated with higher 90-day mortality (PSSC 0: 34.4%, PSSC 1: 40.5%, PSSC 2: 53.3%; p < 0.001). In both trials, SIC was already present at sepsis diagnosis or occurred during the following 4 days. Conclusions SIC is a clinically relevant complication of sepsis. Although it might be less frequent than previously reported, its occurrence is associated with higher morbidity and mortality and should be interpreted as an early warning sign