Comparable increase of B-type natriuretic peptide and amino- terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure* Alain Rudiger, MD; Stefan Gasser, MD; Manuel Fischler, MD; Thorsten Hornemann, MD; Arnold von Eckardstein, MD; Marco Maggiorini, MD B -type natriuretic peptide (BNP) is a neurohormone that has been isolated first in the por- cine brain and later in human ventricular cardiomyocytes (1). It derives from a pre-prohormone, which is clipped into pro-BNP. After stimula- tion, pro-BNP is released from the cell into the circulation as the active 32- amino acid long polypeptide BNP and an inactive 77-amino acid long frag- ment N-terminal pro-BNP (2– 4). Be- cause of its longer plasma half-life time and higher stability, the measurement of N-terminal pro-BNP has been intro- duced into routine clinical diagnostics (5, 6). BNP and N-terminal pro-BNP are used for the early diagnosis of heart failure (HF) in patients presenting to the emergency room with dyspnea (7– 10). Additionally, in patients with chronic HF and acute and chronic cor- onary syndrome, both BNP and N- terminal pro-BNP are markers of unfa- vorable prognosis, being associated with increased mortality (11–14). Re- cently, elevated BNP levels have been measured in patients with septic shock and have been attributed to myocardial dysfunction due to sepsis (15–18). Be- cause BNP synthesis is also induced by endotoxin and inflammatory mediators (19 –21), the mechanisms leading to el- evated BNP levels in patients with sep- sis remain unclear. Little information is available concerning N-terminal pro- BNP levels in patients with critical ill- ness, especially with sepsis. To assess the clinical relevance of both BNP and N-terminal pro-BNP in inten- sive care unit (ICU) patients, we prospec- tively measured both markers in patients with severe sepsis and septic shock and compared them with natriuretic peptide levels obtained from patients admitted to our ICU with the diagnosis of acute con- gestive HF or low cardiac output syn- drome. *See also p. 2249. From the Bloomsbury Institute of Intensive Care Medicine, Wolfson Institute of Biomedical Research, University College London, London, UK (AR); Internal Medicine, Regional Hospital, Zofingen, Switzerland (SG); Intensive Care Unit, Department of Medicine, University Hospital, Zurich, Switzerland (MF, MM); and the Institute of Clinical Chemistry, University Hospital, Zurich, Switzerland (TH, AvE). Dr. Alain Rudiger was supported by the Stiefel Zangger Foundation, Zurich, and the Swiss National Science Foundations, Basel (Grant PBBSB-107757). Dr. von Eckardstein receives consultancy fees from Roche, but this does not specifically apply to BNP. The remaining authors have not disclosed any poten- tial conflicts of interest. Copyright © 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000229144.97624.90 Objective: B-type natriuretic peptide (BNP) and N-terminal pro-BNP measurements are used for the diagnosis of congestive heart failure (HF). However, the diagnostic value of these tests is unknown under septic conditions. We compared patients with severe sepsis or septic shock and patients with acute HF to unravel the influence of the underlying diagnosis on BNP and N-terminal pro-BNP levels. Design: Prospective, clinical study. Setting: Academic medical intensive care unit (ICU). Patients: A total of 249 consecutive patients were screened for the diagnosis of sepsis or HF. Sepsis was defined according to published guidelines. HF was diagnosed in the presence of an underlying heart disease and congestive HF, pulmonary edema, or cardiogenic shock. Interventions: BNP and N-terminal pro-BNP were measured from blood samples that were drawn daily for routine analysis. Measurements and Main Results: We identified 24 patients with severe sepsis or septic shock and 51 patients with acute HF. At admission, the median (range) BNP and N-terminal pro-BNP levels were 572 (13–1,300) and 6,526 (198 –70,000) ng/L in pa- tients with sepsis and 581 (6 –1,300) and 4,300 (126 –70,000) ng/L in patients with HF. The natriuretic peptide levels increased dur- ing the ICU stay, but the differences between the groups were not significant. Nine patients with sepsis and eight patients with HF were monitored with a pulmonary artery catheter. Mean (SD) pulmonary artery occlusion pressure were 16 (4.2) and 22 (5.3) mm Hg (p  .02), and cardiac indexes were 4.6 (2.8) and 2.2 (0.6) L/min/m 2 (p  .03) in patients with sepsis and HF, respectively. Despite these clear hemodynamic differences BNP and N-terminal pro-BNP levels were not statistically different between the two groups. Conclusion: In patients with severe sepsis or septic shock, BNP and N-terminal pro-BNP values are highly elevated and, despite significant hemodynamic differences, comparable with those found in acute HF patients. It remains to be determined how elevations of natriuretic peptide levels are linked to inflammation and sepsis-associated myocardial dysfunction. (Crit Care Med 2006; 34:2140–2144) KEY WORDS: natriuretic peptide; B-type natriuretic peptide; amino-terminal pro-B-type natriuretic peptide; sepsis; shock; myocardial dysfunction; heart failure; inflammation 2140 Crit Care Med 2006 Vol. 34, No. 8