Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

Mirjam Christ-Crain, Nils G Morgenthaler, Joachim Struck, Stephan Harbarth, Andreas Bergmann, Beat Müller, Mirjam Christ-Crain, Nils G Morgenthaler, Joachim Struck, Stephan Harbarth, Andreas Bergmann, Beat Müller

Abstract

Introduction: Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores.

Method: We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay.

Results: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3-3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4-5.8) in those with sepsis, 2.3 (1.0-17.6) in those with severe sepsis and 4.5 (0.9-21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21-0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8-21.0]; P < 0.001) than in survivors (1.7 [0.4-17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used.

Conclusion: MR-proADM may be helpful in individual risk assessment in septic patients.

Figures

Figure 1
Figure 1
Admission levels of MR-proADM. (a) MR-proADM in patients with sepsis versus healthy control individuals. (b) MR-proADM in patients without infection (for example SIRS), and in patients with sepsis, severe sepsis and septic shock. (c) MR-proADM grouped according to PCT values. Lines denote median values, boxes represent 25–75th percentiles and whiskers indicate the range. The numbers of samples are indicated in parentheses. MR-proADM, mid-regional pro-adrenomedullin; PCT, procalcitonin; SIRS, systemic inflammatory response syndrome.
Figure 2
Figure 2
MR-proADM and PCT levels in surviving versus nonsurviving patients. Data from patients on admission are shown. Patients are grouped into (a) those with a clinical diagnosis of sepsis based on international guidelines and (b) those with circulating PCT levels above 1 ng/ml. Lines denote median values, boxes represent 25–75th percentiles and whiskers indicate the range. MR-proADM, mid-regional pro-adrenomedullin; PCT, procalcitonin.
Figure 3
Figure 3
Sensitivity and specificity of various biomarkers and scoring systems in predicting ICU mortality. Shown are ROC plot analyses of the abilities of various biomarkers to predict outcome (for example ICU mortality) in sepsis. Patients are grouped into (a) those with a clinical diagnosis of sepsis based on international guidelines and (b) those with circulating PCT levels above 1 ng/ml. Sensitivity was calculated with patients who died during their ICU stay and specificity was calculated with ICU survivors. The areas under the ROC curve are given with 95% confidence intervals. ICU, intensive care unit; PCT, procalcitonin; ROC, receiver operating characteristic.

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