Distinguishing pulmonary edema due to acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) from hydrostatic or cardiogenic edema is challenging in critically ill patients. B-type natriuretic peptide (BNP) can effectively identify congestive heart failure in the emergency room setting but, despite increasing use, its diagnostic utility has not been validated in the intensive care unit (ICU).
We performed a prospective, blinded cohort study in the medical and surgical ICUs at the University of Chicago Hospitals. Patients were eligible if they were admitted to the ICU with respiratory distress, bilateral pulmonary edema and a central venous catheter suggesting either high-pressure (cardiogenic) or low-pressure (ALI/ARDS) pulmonary edema. BNP levels were measured within 48 hours of ICU admission and development of pulmonary edema and onward up to three consecutive days. All levels were drawn simultaneously with the measurement of right atrial or pulmonary artery wedge pressure. The etiology of pulmonary edema ├óÔé¼ÔÇ£ cardiogenic or ALI/ARDS ├óÔé¼ÔÇ£ was determined by three intensivists blinded to BNP levels.
We enrolled a total of 54 patients (33 with ALI/ARDS and 21 with cardiogenic edema). BNP levels were lower in patients with ALI/ARDS than in those with cardiogenic edema (496 ├é┬▒ 439 versus 747 ├é┬▒ 476 pg/ml, P = 0.05). At an accepted cutoff of 100 pg/ml, specificity for the diagnosis of ALI/ARDS was high (95.2%) but sensitivity was poor (27.3%). Cutoffs at higher BNP levels improved sensitivity at considerable cost to specificity. Invasive measures of filling pressures correlated poorly with initial BNP levels and subsequent day BNP values fluctuated unpredictably and without correlation with hemodynamic changes and net fluid balance.
BNP levels drawn within 48 hours of admission to the ICU do not reliably distinguish ALI/ARDS from cardiogenic edema, do not correlate with invasive hemodynamic measurements, and do not track predictably with changes in volume status on consecutive daily measurements.
Early implementation of a lung protective ventilation strategy can improve survival from acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) . However, a recent survey of intensive care units (ICUs) found that a lack of physician recognition of ALI/ARDS was a major barrier to the initiation of lung-protective ventilation . Attributing pulmonary edema to volume overload or congestive heart failure may explain some of this underdiagnosis. The American├óÔé¼ÔÇ£European Consensus Conference definition of ALI/ARDS requires the exclusion of left atrial hypertension . However, advanced age and comorbidities can make this difficult in critically ill patients. Pulmonary artery catheters reliably measure left atrial pressure, but placement can be time-consuming and a recent multicenter randomized trial found no benefit with their routine use in ALI/ARDS . Echocardiography provides noninvasive assessment of left ventricular dysfunction but requires an experienced operator and is limited by lack of universal accessibility and added cost.
B-type natriuretic peptide (BNP), a rapidly-assayed, serum biomarker, has been found to be effective in distinguishing congestive heart failure (CHF) from other causes of dyspnea in the emergency or urgent care setting [5-7]. Ease, low cost, and objectivity have led to widespread incorporation of BNP into the clinical evaluation of CHF. Anecdotal experience also suggests an increasing use of BNP by physicians in the ICU; however, although extrapolation to other clinical settings is tempting, appropriate validation is lacking.
Jefic and colleagues found that levels of BNP correlated with severity of left ventricular dysfunction but did not reliably distinguish high from low pulmonary capillary wedge pressure (PCWP) causes of respiratory failure in critically ill patients . In addition, BNP levels can be markedly, but similarly, increased in both cardiogenic and septic shock despite significant differences in hemodynamic measures [9-11]. Conversely, Rana and colleagues found that a BNP level of less than 250 pg/ml had a high specificity for ALI/ARDS and was comparable to measuring PCWP and superior to troponin levels and echocardiography for distinguishing between ALI/ARDS and cardiogenic edema .
There are many possible explanations for these discrepancies. Coexisting cardiac and other organ dysfunction, rapid changes in volume status, variable bioavailability  and burst synthesis of BNP [14,15] may all confound interpretation of BNP levels in critically ill patients. Given the potential for confounding by coexisting or overlapping conditions of lung injury and hydrostatic pulmonary edema, we performed a prospective clinical trial of the diagnostic utility of BNP in selected patients with convincing evidence of either ALI/ARDS or cardiogenic pulmonary edema.
- The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000, 342:1301-1308.
- Rubenfeld GD, Cooper C, Carter G, Thompson BT, Hudson LD: Barriers to providing lung-protective ventilation to patients with acute lung injury. Crit Care Med 2004, 32:1289-1293.
- Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American├óÔé¼ÔÇ£European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149:818-824.
- Wheeler AP, Bernard GR, Thompson BT, Schoenfeld D, Wiedemann HP, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL: Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006, 354:2213-2224.
- Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA: Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002, 347:161-167.
- Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A: Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol 2002, 39:202-209.
- Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P, Pfisterer M, Perruchoud AP: Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med 2004, 350:647-654.
- Jefic D, Lee JW, Savoy-Moore RT, Rosman HS: Utility of B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in evaluation of respiratory failure in critically ill patients. Chest 2005, 128:288-295.
- Januzzi JL, Morss A, Tung R, Pino R, Fifer MA, Thompson BT, Lee-Lewandrowski E: Natriuretic peptide testing for the evaluation of critically ill patients with shock in the intensive care unit: a prospective cohort study. Crit Care 2006, 10:R37.
- Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein A, Maggiorini M: 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. Crit Care Med 2006, 34:2140-2144.
- Tung RH, Garcia C, Morss AM, Pino RM, Fifer MA, Thompson BT, Lewandrowski K, Lee-Lewandrowski E, Januzzi JL: Utility of B-type natriuretic peptide for the evaluation of intensive care unit shock. Crit Care Med 2004, 32:1643-1647.
- Rana R, Vlahakis NE, Daniels CE, Jaffe AS, Klee GG, Hubmayr RD, Gajic O: B-type natriuretic peptide in the assessment of acute lung injury and cardiogenic pulmonary edema. Crit Care Med 2006, 34:1941-1946.
- Wu AH, Smith A, Apple FS: Optimum blood collection intervals for B-type natriuretic peptide testing in patients with heart failure. Am J Cardiol 2004, 93:1562-1563.
- Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H: Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide. Biochem Biophys Res Commun 1989, 159:1427-1434.
- Kojima M, Minamino N, Kangawa K, Matsuo H: Cloning and sequence analysis of cDNA encoding a precursor for rat brain natriuretic peptide. Biochem Biophys Res Commun 1989, 159:1420-1426.
- Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13:818-829.
- Murray JF, Matthay MA, Luce JM, Flick MR: An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988, 138:720-723.
- S Konstantinides, A Geibel, G Heusel, F Heinrich, W Kasper: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002, 347:1143-1150.
- Charpentier J, Luyt CE, Fulla Y, Vinsonneau C, Cariou A, Grabar S, Dhainaut JF, Mira JP, Chiche JD: Brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis. Crit Care Med 2004, 32:660-665.
- Rudiger A, Fischler M, Harpes P, Gasser S, Hornemann T, von Eckardstein A, Maggiorini M: In critically ill patients, B-type natriuretic peptide (BNP) and N-terminal pro-BNP levels correlate with C-reactive protein values and leukocyte counts. Int J Cardiol 2007.
- Vieillard-Baron A, Schmitt JM, Augarde R, Fellahi JL, Prin S, Page B, Beauchet A, Jardin F: Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med 2001, 29:1551-1555.
- Nagaya N, Nishikimi T, Okano Y, Uematsu M, Satoh T, Kyotani S, Kuribayashi S, Hamada S, Kakishita M, Nakanishi N, Takamiya M, Kunieda T, Matsuo H, Kangawa K: Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol 1998, 31:202-208.
- Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL: Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006, 354:2564-2575.
- Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR: A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005, 33:1681-1687.