BNP Levels: Useful in Separating ARDS from CPE?

Abstract & Commentary

By Andrew M. Luks, MD, Pulmonary and Critical Care Medicine, University of Washington, Seattle. Dr. Luks reports no financial relationship to this field of study.

This article originally appeared in the October 2007 issue of Critical Care Alert. It was edited by David J. Pierson, MD, and peer reviewed by William Thompson, MD. Dr. Pierson is Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, and Dr. Thompson is Staff Pulmonologist, VA Medical Center; Associate Professor of Medicine, University of Washington. Drs. Pierson and Thompson report no financial relationships relevant to this field of study.

Synopsis: When used in conjunction with clinical and radiographic data, brain natriuretic peptide levels may provide a non-invasive alternative for distinguishing between ARDS and cardiogenic pulmonary edema in patients with severe hypoxemic respiratory failure.

Source: Karmpaliotis D, et al. Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema. Chest. 2007;131:964-971.

Brain natriuretic peptide (BNP) levels have been shown to be useful in distinguishing between cardiac and non-cardiac causes of dyspnea in patients who present to the emergency department with an unclear clinical picture. Karmpaliotis and colleagues sought to determine whether this non-invasive test could also be used to distinguish between the acute respiratory distress syndrome (ARDS) and cardiogenic pulmonary edema (CPE) in ICU patients with severe hypoxemic respiratory failure. Karmapaliotis et al enrolled medical or surgical ICU patients with a PaO2/FIO2 ratio < 300 mm/Hg, with bilateral pulmonary infiltrates on chest radiograph, as well as diagnostic uncertainty requiring insertion of a pulmonary artery catheter to facilitate diagnosis. They excluded patients with acute or chronic renal failure, recent coronary artery bypass grafting, prior measurement of BNP during that admission, and known left heart failure with ejection fraction < 30%.

A single investigator performed all pulmonary capillary wedge pressure (PCWP) measurements, and BNP levels were measured using the Triage Biosite immunoassay. Ten days after study enrollment, 2 intensivists, who were blinded to the results of the BNP testing, reviewed all the diagnostic information and, using the American-European consensus conference definition of ARDS, categorized patients as having ARDS, CPE or a mixed picture (this last category was not defined by the authors). They created receiver operating characteristic (ROC) curves and determined the sensitivity, specificity, and positive- and negative predictive values of BNP for the diagnoses of ARDS and CPE. Multivariable logistic regression was used to assess for an association between BNP and the final diagnosis and to evaluate for a relationship between BNP and in-hospital mortality.

Eighty patients completed the study. While mean BNP levels were significantly lower in ARDS than in CPE (325 pg/mL vs 1260 pg/mL), BNP had a poor correlation (r = 0.27) with PCWP. The area under the ROC curve for BNP in the diagnosis of ARDS was 0.80. Using a cut-point of < 200 pg/mL, BNP had a specificity of 91%, and a positive predictive value of 91% for the diagnosis of ARDS, while a cut-point of > 1200 pg/mL had a specificity of 92% and a positive predictive value of 75% for the diagnosis of CPE. In multivariate analysis, higher concentrations of BNP were associated with a lower likelihood of the diagnosis of ARDS. Among the separate categories of ARDS and CPE patients, higher BNP levels were associated in multivariate analysis with increased mortality.


In the wake of many studies showing either no benefit or possible harm from the use of Swan-Ganz catheters, this study provides a potentially useful addition to the diagnostic armamentarium in the ICU. Given the mortality benefit associated with low-tidal volume ventilation in ARDS, making the correct diagnosis is of great importance and the BNP assay may provide a rapid, non-invasive means by which this objective can be achieved.

In considering the usefulness of the test, however, several points warrant emphasis. First, this trial examined only 80 patients and, as Karmpaliotis et al themselves state, further studies are necessary to validate these findings before instituting large changes in current practice. It is also important to note that the 200 pg/mL cut-point used for the diagnosis of ARDS in this study is higher than the cut points (80 pg/mL) used in the original emergency department studies that established the utility of the BNP assay in distinguishing between pulmonary and cardiac causes of dyspnea. Mistaken application of this lower threshold in the ICU could lead to inappropriate exclusion of ARDS and failure to institute low-tidal-volume ventilation in situations where it is actually warranted. Finally, the results of this trial make it clear that BNP levels correlate poorly with the PCWP and cannot be used as a surrogate marker for that variable. If accurate information about filling pressures is needed, invasive measurements may still be necessary.