Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

Abstract

Introduction: Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores.

Methods: Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay.

Results: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score.

Conclusion: Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

Figure 1

Pro-atrial natriuretic peptide (ANP) according to severity of disease and circulating procalcitonin (PCT) levels. All patient data were grouped according to (a) the severity of the disease following consensus criteria ('no SIRS',' SIRS', 'sepsis', 'severe sepsis' and 'septic shock') or (b) circulating PCT concentrations. Data from all time points (i.e. on admission, day 2, day of discharge and death) are displayed. Solid lines denote median values, boxes represent 25th to 75th percentiles and whiskers indicate the range. ANOVA, analysis of variance.

Figure 2

Pro-atrial natriuretic peptide (ANP) and procalcitonin (PCT) levels in surviving as compared with nonsurviving patients. Data from the patients on admission are shown. Patients were grouped (a, c) by clinical diagnosis of sepsis according to international guidelines or (b, d) by circulating PCT levels in excess of 1 ng/ml. Solid lines denote median values, boxes represent 25th to 75th percentiles and whiskers indicate the range.

Figure 3

Receiver operating characteristic plot analysis of different biomarkers with respect to outcome prediction of sepsis. Patient data on admission were grouped by (a) clinical diagnosis of sepsis according to international guidelines or by (b) circulating procalcitonin (PCT) levels in excess of 1 ng/ml. Sensitivity was calculated in nonsurvivors, and specificity in survivors. APACHE, Acute Physiology and Chronic Health Evaluation; CRP, C-reactive protein; PCT, procalcitonin.